Jeffrey Dach's Blog, page 21

Clostridia Difficile Enterocolitis Causes Prevention and Treatment

Clostridia Difficile Enterocolitis Causes Prevention and Treatment

by Jeffrey Dach MD

If you are unlucky enough to spend the night in a hospital bed this year, you might want to know if the previous occupant received antibiotics.  If so, then  you have increased risk of dying from  C. Diff, a common hospital acquired infection, according to a study in JAMA.(1) Left image Clostridia Difficile Electron Microscope Image courtesy of the CDC.

IV Antibiotics Anyone?

Of course, antecedent antibiotic use is now recognized as the single most important risk factor for contracting clostridia difficile enterocolitis in the hospital setting.(5)  The antibiotics obliterate the friendly bacteria in the gut, setting the backdrop for overgrowth of pathogenic Clostridia Difficile.  More virulent strains of the organism have been making headway.

The Chemotherapy Patient and C. Diff

Chemotherapy drugs such as methotrexate may also act as antibiotics disturbing the gut flora, and disrupting the mucus barrier function of the gut, predisposing to C. Diff entercolitis and gram negative septicemia .  This is a greater problem after hematopoetic stem cell transplant, a procedure commonly done for leukemia and lymphoma. (11)  These patients are commonly heavily treated with antibiotics, and probiotics are helpful in this setting in reducing non-relapse mortality, a euphemism meaning death caused by the procedure.  See my article on probiotics reduce mortality for the stem cell transplant patient.

Significant Mortality Rate Goes Up with Recurrence

The common hospital acquired infection, Clostridia Difficile has a mortality rate of about 8-9%, with half a million infections and 29,000 deaths in 2011.(2)  The incidence has been increasing rapidly. Pathogenic C. Diff produces two toxins which cause watery diarrhea, and electrolyte disturbance.  In severe cases there may be pseudo-membranous colitis and toxic megacolon requiring heroic measures such as total colectomy.

The C Diff infection usually responds to antibiotics such as Vancomycin and metronidazole (Flagyl).  However, antibiotics produce further disturbance in the gut microbiota, and fail to eradicate the spore form of C Diff, explaining the 30%-50% recurrence rate, an outcome associated with increased mortality. (3-4)

In-house hospital prevention of C Diff relies on standard infectious disease techniques such as microbial isolation, and hand washing before and after donning masks, gloves and gowns etc.  Clearly, there is a need for improved prevention and treatment of C Diff enteritis in the hospital setting.

Preventing C Diff with Probiotics

Donna L. Parker RN, director of nursing for a nursing residence experienced a high rate of C Diff among her patients treated with antibiotics.  After instituting a policy of giving a probiotic tablet along with the antibiotics, she reports no cases over two years. She writes about her experience using probiotics to prevent C Diff in her October 2016 article, “Preventing C. diff infections with probiotics”.  (10)

Others have studied the use of probiotics such as Lactobacillus GG and Sacchromyces Boulardi, and have found them effective in preventing C Diff.(7-13)

“L. rhamnosus GG has been shown to increase gut mucin production [Mack et al. 1999], which improves the barrier defences of the epithelium, and increases colonic water absorption [Madsen et al. 2001], which directly reduces diarrhoea.” (13) (Mary Hickson)

Recommended Probiotics

VSL#3 Medicinal Food Sachets

Renew Life 200 Billion Packets

Lactobacillus Rhamnosus GG Culturelle 10B

Miyarisan Clostridium Butyricum Nontoxigenic strain

Kefir as Probiotic

Kefir, containing multiple lactobacillus strains of probiotic grown in a milk substrate is a popular item at the grocery store, and available as a home starter kit.  A number of studies show health benefits from Kefir consumption.(14-15) Surprisingly, kefir was found to have significant anti-cancer activity in a mouse cancer xenograft model. (15)

Preventing Recurrence with Berberine

The botanical, berberine, also known  as the Orgegon Grape, has been used for thousands of years effective for watery diarhea.  Studies show that berberine capsules taken together with vancomycin prevent recurrence of Clostridia Difficile.  (6)  See my previous article on Berberine as an antidote to a modern epidemic .

Preventing Recurrent C Diff With Fecal Transplant

As mentioned in my previous article on Fecal Transplantation, this procedure is actually FDA approved for the treatment of recurrent C Diff. in over 100 US hospitals. (16)  After all, one might regard fecal transplantation as simply another way to administer a massive dose of probiotics.

Preventing Recurrent C Diff with Niclosamide

The anti-parasitic drug Niclosamide is FDA approved in the US for treatment of tapeworm, and has been repurposed for treatment of C Diff. (17-18)  The added advantage of Niclosamide is this drug will eradicate the spore form of C Diff resistant to conventional antibiotics. In addition, unlike conventional antibiotics which disturb the normal flora, Niclosamide leaves the normal flora relatively unharmed.  An added bonus for cancer patients, Niclosamide has potent anti-cancer activity at conventional dosing schedules. (19)

Conclusion:

Although mainstream medicine may be slow to adopt new ideas, improved strategies to prevent and treat C Diff are already available.  The only thing left to do is use them.

Jeffrey Dach MD

7450 Griffin Road Suite 190

Davie, Fl 33314

954 792 4663

Articles with Related Interest:

Probiotics for the Stem Cell Transplant Patient

Berberine Antidote to an Epidemic

Fecal Transplantation, The Sweet Smell of Success

1)  JAMA Less Is More October 10, 2016

Receipt of Antibiotics in Hospitalized Patients and Risk for Clostridium difficile Infection in Subsequent Patients Who Occupy the Same Bed

Daniel E. Freedberg, MD, MS1; Hojjat Salmasian, MD, PhD2; Bevin Cohen, MPH3; et al Julian A. Abrams, MD, MS1; Elaine L. Larson, RN, PhD3

1Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York

2Department of Biomedical Informatics, New York-Presbyterian Hospital, New York, New York

3Department of Epidemiology, Mailman School of Public Health, School of Nursing, Columbia University, New York, New York

Objective To assess whether receipt of antibiotics by prior hospital bed occupants is associated with increased risk for CDI in subsequent patients who occupy the same bed.

Design, Setting, and Participants This is a retrospective cohort study of adult patients hospitalized in any 1 of 4 facilities between 2010 and 2015. Patients were excluded if they had recent CDI, developed CDI within 48 hours of admission, had inadequate follow-up time, or if their prior bed occupant was in the bed for less than 24 hours.

Main Outcomes and Measures The primary exposure was receipt of non-CDI antibiotics by the prior bed occupant and the primary outcome was incident CDI in the subsequent patient to occupy the same bed. Incident CDI was defined as a positive result from a stool polymerase chain reaction for the C difficile toxin B gene followed by treatment for CDI. Demographics, comorbidities, laboratory data, and medication exposures are reported.

Results Among 100 615 pairs of patients who sequentially occupied a given hospital bed, there were 576 pairs (0.57%) in which subsequent patients developed CDI. Receipt of antibiotics in prior patients was significantly associated with incident CDI in subsequent patients (log-rank P 

Conclusions and Relevance Receipt of antibiotics by prior bed occupants was associated with increased risk for CDI in subsequent patients. Antibiotics can directly affect risk for CDI in patients who do not themselves receive antibiotics.

2)  Burden of Clostridium difficile Infection in the United States  Fernanda C. Lessa, M.D., M.P.H., et al. N Engl J Med 2015; 372:825-834 February 26, 2015

C. difficile was responsible for almost half a million infections and was associated with approximately 29,000 deaths in 2011

3) Olsen, Margaret A., et al. “Recurrent Clostridium difficile infection is associated with increased mortality.” Clinical Microbiology and Infection 21.2 (2015): 164-170.  Clostridium difficile infections (CDI) are associated with decreased survival, and up to 30% of CDI patients may experience a recurrence. Data on the impact of recurrent CDI on mortality are scarce. The purpose of this study was to determine whether recurrent CDI was independently associated with decreased 6-month survival compared with patients with CDI who did not develop a recurrence. We performed a retrospective cohort study at an academic, urban, tertiary care hospital. Data were collected from the electronic medical record and chart review. CDI patients were followed for 180 days from the end of their index hospital discharge or end of index CDI antibiotic treatment, whichever was later, to determine mortality. Kaplan–Meier analysis was used to compare patient mortality by recurrent CDI status. Cox proportional hazards models were used to determine independent risk factors for death within 180 days. In all, 3958 patients aged ≥ 18 years who developed an initial CDI episode from 2003 to 2009, including 421 patients with recurrent CDI, were included in the study. Thirty-six per cent of persons with recurrent CDI died within 180 days, compared with 26% of persons without CDI recurrence (log-rank p Recurrent CDI is associated with significantly increased risk of death within 6 months after completion of their initial CDI treatment compared with CDI patients who do not develop a recurrence.

4) Deshpande, Abhishek, et al. “Risk factors for recurrent Clostridium difficile infection: a systematic review and meta-analysis.” infection control & hospital epidemiology 36.04 (2015): 452-460.

5) Pépin, Jacques, et al. “Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile–associated diarrhea: a cohort study during an epidemic in Quebec.” Clinical Infectious Diseases 41.9 (2005): 1254-1260.

Since 2002, an epidemic of Clostridium difficile–associated-diarrhea (CDAD) associated with a high case-fatality rate has involved >30 hospitals in the province of Quebec, Canada. In 2003, a total of 55% of patients with CDAD at our hospital had received fluoroquinolones in the preceding 2 months. It has been suggested that massive use of proton pump inhibitors might have facilitated this epidemic.

Methods. To delineate the risk of CDAD associated with specific classes of antibiotics and whether this is modulated by concomitant use of proton pump inhibitors and other drugs altering gastric acidity or gastrointestinal motility, we conducted a retrospective cohort study of patients hospitalized in a teaching hospital in Sherbrooke, Canada, during the period of January 2003 through June 2004. We obtained data on 7421 episodes of care corresponding to 5619 individuals. Patients were observed until they either developed CDAD or died or for 60 days after discharge from the hospital. Adjusted hazard ratios (AHRs) were calculated using Cox regression.

Results. CDAD occurred in 293 patients. Fluoroquinolones were the antibiotics most strongly associated with CDAD (AHR, 3.44; 95% confidence interval [CI], 2.65–4.47). Almost one-fourth of all inpatients received quinolones, for which the population-attributable fraction of CDAD was 35.9%. All 3 generations of cephalosporins, macrolides, clindamycin, and intravenous β-lactam/β-lactamase inhibitors were intermediate-risk antibiotics, with similar AHRs (1.56–1.89). Proton pump inhibitors (AHR, 1.00, 95% CI, 0.79–1.28) were not associated with CDAD.

Conclusions. Administration of fluoroquinolones emerged as the most important risk factor for CDAD in Quebec during an epidemic caused by a hypervirulent strain of C. difficile.

Berberine

6) Antimicrob Agents Chemother. 2015 Jul;59(7):3726-35.

Berberine blocks the relapse of Clostridium difficile infection in C57BL/6 mice after standard vancomycin treatment.

Lv Z1, Peng G2, Liu W3, Xu H4, Su J5.

Vancomycin is a preferred antibiotic for treating Clostridium difficile infection (CDI) and has been associated with a rate of recurrence of CDI of as high as 20% in treated patients. Recent studies have suggested that berberine, an alternative medical therapy for gastroenteritis and diarrhea, exhibits several beneficial effects, including induction of anti-inflammatory responses and restoration of the intestinal barrier function. This study investigated the therapeutic effects of berberine on preventing CDI relapse and restoring the gut microbiota in a mouse model. Berberine was administered through gavage to C57BL/6 mice with established CDI-induced intestinal injury and colitis. The disease activity index (DAI), mean relative weight, histopathology scores, and levels of toxins A and B in fecal samples were measured. An Illumina sequencing-based analysis of 16S rRNA genes was used to determine the overall structural change in the microbiota in the mouse ileocecum. Berberine administration significantly promoted the restoration of the intestinal microbiota by inhibiting the expansion of members of the family Enterobacteriaceae and counteracting the side effects of vancomycin treatment. Therapy consisting of vancomycin and berberine combined prevented weight loss, improved the DAI and the histopathology scores, and effectively decreased the mortality rate. Berberine prevented CDIs from relapsing and significantly improved survival in the mouse model of CDI. Our data indicate that a combination of berberine and vancomycin is more effective than vancomycin alone for treating CDI. One of the possible mechanisms by which berberine prevents a CDI relapse is through modulation of the gut microbiota. Although this conclusion was generated in the case of the mouse model, use of the combination of vancomycin and berberine and represent a novel therapeutic approach targeting CDI.

7)   Nat Rev Gastroenterol Hepatol. 2016 Mar;13(3):150-60. doi: 10.1038/nrgastro.2015.220. Epub 2016 Feb 10.

Breakthroughs in the treatment and prevention of Clostridium difficile infection.  Kociolek LK1, Gerding DN2.

This Review summarizes the latest advances in the treatment and prevention of Clostridium difficile infection (CDI), which is now the most common health-care-associated infection in the USA. As traditional, standard CDI antibiotic therapies (metronidazole and vancomycin) are limited by their broad spectrum and further perturbation of the intestinal microbiota, which result in unacceptably high recurrence rates, novel therapeutic strategies for CDI are needed. Emerging CDI therapies are focused on limiting further perturbation of the intestinal microbiota and/or restoring the microbiota to its pre-morbid state, reducing colonization of the intestinal tract by toxigenic strains of C. difficile and bolstering the host immune response against C. difficile toxins. Fidaxomicin is associated with reduced CDI recurrences, and other emerging narrow-spectrum CDI antibiotic therapies might eventually demonstrate a similar benefit. Prevention of intestinal colonization of toxigenic strains of C. difficile can be achieved through restoration of the intestinal microbiota with faecal microbiota transplantation, as well as by colonizing the gut with nontoxigenic C. difficile strains. Finally, emerging immunological therapies, including monoclonal antibodies and vaccines against C. difficile toxins, might protect against CDI and subsequent CDI recurrences. The available clinical data for these emerging therapies, and their relative advantages and disadvantages, are described.

8) Int J Gen Med. 2016; 9: 27–37.

Probiotics are effective at preventing Clostridium difficile-associated diarrhea: a systematic review and meta-analysis

Christine SM Lau1,2 and Ronald S Chamberlain1,2,3 Probiotic supplementation is associated with a significant reduction in the risk of developing CDAD in patients receiving antibiotics.

9)  Evans, Charlesnika T., and Stuart Johnson. “Prevention of Clostridium difficile infection with probiotics.” Clinical Infectious Diseases 60.suppl 2 (2015): S122-S128.

10)   Donna L. Parker, RN October 06, 2016 Preventing C. diff infections with probiotics

Chemotherapy:

11)  Clostridium difficile Infection Associated with Antineoplastic Chemotherapy: A Review.  Ajay Anand and Aaron E. Glatt From the Department of Medicine, Nassau County Medical Center, East Meadow; the Division of Infectious Diseases, Department of Medicine, Catholic Medical Center, Jamaica; and SUNY Health Sciences Center at Stony Brook, Stony Brook, New York

Colitis and infection due to Clostridium difficile have been reported in patients receiving antineoplastic chemotherapy for cancer without prior antibiotic treatment. Chemotherapeutic agents can alter the normal bowel flora and cause extensive intestinal inflammatory changes, potentiating both the growth of C. difficile and its production of toxin. This review includes all 23 known reported cases of C. difficile infection associated with antineoplastic chemotherapy and examines the pathogenesis, clinical features, and management of this condition. Chemotherapy-associated C. difficile colitis has been documented in association with a variety of neoplasms. Various classes of antineoplastic agents have been incriminated, methotrexate most commonly. A spectrum of illness ranging from mild to fulminant has been reported. Symptoms, management, and outcome have appeared to be no different than for antibiotic-associated cases, but the available data are limited. Chemotherapy-associated infection with C. difficile may be underreported because it is not suspected and/or because frequent concomitant use of antibiotics masks its true incidence. C. difficile infection should be kept in mind whenever a patient undergoing antineoplastic chemotherapy develops diarrhea. Prompt, appropriate diagnostic testing and early treatment may avert morbidity and death.

Saccharomyces boulardii:

12)   Prevention of Clostridium difficile infection with Saccharomyces boulardii: A systematic review

Jennifer M Tung, BSc,1 Lisa R Dolovich, BSc MSc,1 and Christine H Lee, MD FRCPC1,2

Clostridium difficile is a major cause of antibiotic associated diarrhea within the hospital setting. The yeast Saccharomyces boulardii has been found to have some effect in reducing the risk of C difficile infection (CDI); however, its role in preventive therapy has yet to be firmly established.

OBJECTIVE:To review the effectiveness of S boulardii in the prevention of primary and recurrent CDI. Benefit was defined as a reduction of diarrhea associated with C difficile. Risk was defined as any adverse effects of S boulardii.

METHODS:A literature search in MEDLINE, EMBASE, CINAHL and the Cochrane Library was performed. Included studies were English language, randomized, double-blind placebo controlled trials evaluating S boulardii in CDI prevention.

RESULTS:Four studies were reviewed. Two studies investigated the prevention of recurrence in populations that were experiencing CDI at baseline. One trial showed a reduction of relapses in patients experiencing recurrent CDI (RR=0.53; P

CONCLUSION:S boulardii seems to be well tolerated and may be effective for secondary prevention in some specific patient populations with particular concurrent antibiotic treatment. Its role in primary prevention is poorly defined and more research is required before changes in practice are recommended.

13)  Therap Adv Gastroenterol. 2011 May; 4(3): 185–197.

Probiotics in the prevention of antibiotic-associated diarrhoea and Clostridium difficile infection   Mary Hickson

Diarrhoea, as a common side effect of antibiotics, increases treatment costs and length of stay in acute healthcare facilities. One potential strategy to prevent this side effect is the concurrent use of probiotic bacteria or yeast. This review discusses the evidence for the efficacy of probiotics in the prevention of antibiotic-associated diarrhoea and Clostridium difficile infection; the potential mechanisms by which probiotics may work; their safety; what future research is required; and recommendations for use in clinical practice.

L. rhamnosus GG has been shown to increase gut mucin production [Mack et al. 1999], which improves the barrier defences of the epithelium, and increases colonic water absorption [Madsen et al. 2001], which directly reduces diarrhoea.

Kefir- Probiotic Foods

14)  Lett Appl Microbiol. 2002;35(2):136-40.

Dietary influence of kefir on microbial activities in the mouse bowel.

Marquina D1, Santos A, Corpas I, Muñoz J, Zazo J, Peinado JM.

In this work the microflora present in kefir, a fermented milk product, was studied together with the effect of kefir administration on different groups of indigenous bacteria of mouse bowel.

METHODS AND RESULTS: Kefir microflora was composed of lactic acid bacteria, acetic acid bacteria and yeasts. Yeast population was composed of Saccharomyces cerevisiae, S. unisporus, Candida kefir, Kluyveromyces marxianus and K. lactis. The streptococci levels in kefir treated mice increased by 10-fold and the levels of sulfite-reducing clostridia decreased by 100-fold. The number of lactic acid bacteria increased significantly.

CONCLUSIONS: The administration of kefir significantly increased the lactic acid bacteria counts in the mucosa of the bowel. Ingestion of kefir specifically lowered microbial populations of Enterobacteriaceae and clostridia.

SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first long-term study about the effects of the kefir administration on the intestinal microflora of mice.

15) Antitumor Activity of Milk Kefir and Soy Milk Kefir in Tumor-Bearing Mice  Je-Ruei Liu , Sheng-Yao Wang , Yuh-Yih Lin & Chin-Wen Lin

Pages 183-187 | Published online: 18 Nov 2009

Abstract: The effects of oral administration of milk and soy milk kefirs on tumor growth in tumor-bearing mice and the mucosal immunoglobulin A response in mice were studied. Oral administration of milk and soy milk kefirs to mice inoculated with sarcoma 180 tumor cells resulted in 64.8% and 70.9% inhibition of tumor growth, respectively, compared with controls. In addition, oral administration of the two kefir types induced apoptotic tumor cell lysis. Total immunoglobulin A levels for tissue extracts from the wall of the small intestine were also significantly higher for mice fed a milk kefir or a soy milk kefir regimen for 30 days. These results suggest that milk and soy milk kefirs may be considered among the more promising food components in terms of cancer prevention and enhancement of mucosal resistance to gastrointestinal infection.

Fecal Transplant

16)

Drekonja, Dimitri, et al. “Fecal microbiota transplantation for Clostridium difficile infection: a systematic review.” Annals of internal medicine 162.9 (2015): 630-638.

Niclosamide

17)  Reprofiled anthelmintics abate hypervirulent stationary-phase Clostridium difficile .  Major Gooyit & Kim D. Janda Scientific Reports 6, Article number: 33642 (2016)

Prolonged use of broad-spectrum antibiotics disrupts the indigenous gut microbiota, which consequently enables toxigenic Clostridium difficile species to proliferate and cause infection. The burden of C. difficile infections was exacerbated with the outbreak of hypervirulent strains that produce copious amounts of enterotoxins and spores. In recent past, membrane-active agents have generated a surge of interest due to their bactericidal property with a low propensity for resistance. In this study, we capitalized on the antimicrobial property and low oral bioavailability of salicylanilide anthelmintics (closantel, rafoxanide, niclosamide, oxyclozanide) to target the gut pathogen. By broth microdilution techniques, we determined the MIC values of the anthelmintics against 16 C. difficile isolates of defined PCR-ribotype. The anthelmintics broadly inhibited C. difficile growth in vitro via a membrane depolarization mechanism. Interestingly, the salicylanilides were bactericidal against logarithmic- and stationary-phase cultures of the BI/NAP1/027 strain 4118. The salicylanilides were poorly active against select gut commensals (Bacteroides, Bifidobacterium and Lactobacillus species), and were non-hemolytic and non-toxic to mammalian cell lines HepG2 and HEK 293T/17 within the range of their in vitro MICs and MBCs. The salicylanilide anthelmintics exhibit desirable properties for repositioning as anti-C. difficile agents.

18)  Clostridium difficile Drug Pipeline: Challenges in Discovery and Development of New Agents.  Angie M. Jarrad†, Tomislav Karoli†, Mark A. T. Blaskovich†, Dena Lyras‡, and Matthew A. Cooper*†

† The Institute for Molecular Bioscience, University of Queensland, St. Lucia, Queensland 4072, Australia

‡ School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.  J. Med. Chem., 2015, 58 (13), pp 5164–5185

In the past decade Clostridium difficile has become a bacterial pathogen of global significance. Epidemic strains have spread throughout hospitals, while community acquired infections and other sources ensure a constant inoculation of spores into hospitals. In response to the increasing medical burden, a new C. difficile antibiotic, fidaxomicin, was approved in 2011 for the treatment of C. difficile-associated diarrhea. Rudimentary fecal transplants are also being trialed as effective treatments. Despite these advances, therapies that are more effective against C. difficile spores and less damaging to the resident gastrointestinal microbiome and that reduce recurrent disease are still desperately needed. However, bringing a new treatment for C. difficile infection to market involves particular challenges. This review covers the current drug discovery pipeline, including both small molecule and biologic therapies, and highlights the challenges associated with in vitro and in vivo models of C. difficile infection for drug screening and lead optimization.

19)  Cancer Lett. 2014 Jul 10; 349(1): 8–14.

Multi-targeted therapy of cancer by niclosamide: a new application for an old drug  Yonghe Li,1,* Pui Kai Li,2 Michael J. Roberts,3 Rebecca Arend,4 Rajeev S. Samant,5 and Donald J. Buchsbaum6

The rapid development of new anticancer drugs that are safe and effective is a common goal shared by basic scientists, clinicians and patients. The current review discusses one such agent, namely niclosamide, which has been used in the clinic for the treatment of intestinal parasite infections. Recent studies repeatedly identified niclosamide as a potential anticancer agent by various high-throughput screening campaigns. Niclosamide not only inhibits the Wnt/β-catenin, mTORC1, STAT3, NF-κB and Notch signaling pathways, but also targets mitochondria in cancer cells to induce cell cycle arrest, growth inhibition and apoptosis. A number of studies have established the anticancer activities of niclosamide in both in vitro and in vivo models. Moreover, the inhibitory effects of niclosamide on cancer stem cells provide further evidence for its consideration as a promising drug for cancer therapy. This article reviews various aspects of niclosamide as they relate to its efficacy against cancer and associated molecular mechanisms.

20)  Hospitals struggling against ‘C. diff’ bacteria  Philly.com

October 7, 2016

21)

PHIL ID #9999 Photo Credit: Janice Haney Carr, Centers for Disease Control and Prevention.  Download High Resolution. Description: This micrograph depicts gram-positive Clostridium difficile bacteria from a stool sample culture obtained using a .1µm filter.

The post Clostridia Difficile Enterocolitis Causes Prevention and Treatment appeared first on Jeffrey Dach MD .

Antonio Bianco TSH Inadequate for Levothyroxine Dosing

Antonio Bianco MD: TSH is Inadequate for Monitoring Levothyroxine Treatment

Is a Normal TSH Synonymous with “Euthyroidism” in Levothyroxine Monotherapy?

Dr Antonio Bianco endocrinologist and past president of the American Thyroid Association (ATA) from Rush Medical School in Chicago writes in Oct 2016 Journal of Clinical Endocrinology and Metabolism:  Is a Normal TSH Synonymous with “Euthyroidism” in Levothyroxine Monotherapy?  Left image Dr Antonio Bianco Courtesy of the NIH.

Dr Antonio Bianco studied 469 patients treated with levothyroxine (T4 only) for hypothyroidism, and compared to normal controls.  He found:

1) Levothyroxine treated patients ” had higher serum free T4 and lower serum free T3 than healthy or matched controls.” 

2) Levothyroxine treated patients were more likely to be overweight despite consuming less calories,

3) Levothyroxine patients were “more likely to be taking anti-depressants, and anti-cholesterol (statin) drugs compared to matched controls.”  

Clearly, Dr Antonio Bianco is reporting that levothyroxine dosage which manipulates the TSH lab test down into the normal range does NOT necessarily provide symptom relief for many patients.(15-17)

The Low Thyroid Condition – Case Report

Mary is a 57 year old female with chronic fatigue, dry, brittle hair, dry skin, muscle aches and pains, and depression, all obvious symptoms of a low thyroid condition. Mary has been to a number of endocrinologists, primary care doctors and even sought advice from her hair stylist. Her latest doctor prescribed a thyroid pill called Levothyroxine (50 mcg) which has done little to relieve her symptoms. In addition, she has depression, and her psychiatrist prescribed an SSRI antidepressant, called Zoloft. She also takes Xanax for bouts of anxiety and insomnia. Mary came into the office frustrated with her conventional medical treatment which was not helping her.

Routine Thyroid Panel

Our routine evaluation includes a full medical history, physical examination and lab panel. Mary’s baseline lab panel showed a TSH of 5.2, a Free T3 of 260 and a Free T4 of 1.4. TPO antibodies were very elevated (1,100) indicating Hashimoto’s Thyroiditis. Her spot urinary Iodine level was 47 mg/dl indicating iodine deficiency (based on World Health Organization Guidelines).

Switching from Levothyroxine to Natural Thyroid

Mary was switched from Levothyroxine to Naturethroid from RLC labs and within a week reported improvement in clinical symptoms. Six weeks later Mary’s Naturethroid dosage was gradually increased to Two and a Half Tablets every day (Using one grain tablets of 65 mg each) . Mary reports improvement. She has tapered off her antidepressants, as she no longer needs them.

Going to the OB/Gyne

Ten weeks later, Mary goes to see her OB Gyne doctor for her annual Pap smear and pelvic exam which included a TSH blood test, with a low result (0.1 which is below the reference range RR).

Her OB/Gyne doctor looks at the TSH test result and tells Mary she is taking too much thyroid medicine and needs to cut back. Mary then calls me at my office to relay this information. Two doctors are telling her different things and Mary doesn’t know who to believe. This scenario plays out in my office with a different patient each week.

The reality is that Mary is on the proper dosage of thyroid medication, and we expect to see a low or suppressed TSH result when this occurs.

In Part One of this series, we discussed how treatment of the low thyroid condition with natural thyroid is superior to Levo-thyroxine (also called Synthroid a T4 only medication).

In our office we use Nature-throid from RLC labs. (Disclosure: NONE, I have no financial relationship with RLC labs, the manufacturer of Nature-Throid NDT – natural dessicated thyroid pills) .

Natural Thyroid which contains both T3 and T4 is a more robust and safer thyroid medication when compared to T4 only medications such as levothyroxine and Synthroid. This is my assessment, based on 10 years of clinical experience prescribing Naturethroid. In addition, we have found that patients who have converted from Synthroid to Natural Thyroid are much happier with their treatment program. The mainstream medical literature is also in agreement.

In part one of this series, we also discussed how the TSH test is not a reliable indicator of adequacy of treatment.(2) In other words, when the patient is taking the proper dosage of natural thyroid medication with complete relief of symptoms, the TSH will typically fall below the lab reference range, also called a suppressed TSH.

In other words, the TSH will be quite low, and this will disturb the mainstream clinician who mistakenly believes the patient is taking too much thyroid medication. The issue can be settled simply by running a Free T3 test which will show that the Free T3 in the normal range, thus excluding any possibility of a “hyperthyroid state”. Unfortunately, most conventional docs do not have the knowledge to order a free T3 test, and have limited understanding of the thyroid patient.

Suppressive Dose Needed –

The TSH Test is Not a Reliable Monitor

Many patients do quite well on Synthroid. However about 20% (one fifth) of patients on T4 only medications like Synthroid do not do well, and have continued symptoms of a low thyroid condition.(3) Why is that? A miniscule amount of T4 medication such as 50-88 mcg of Levothyroxine may be sufficient to drive down the TSH, and the endocrinologist will then consider treatment dosage adequate. It is not adequate. This is explained by Dr D.S. Oreilly in his articles (4-5), and by Dr. Henry Lindner in his detailed article highlighting why TSH suppression below the lab reference range is needed for adequate treatment for the low thyroid condition. (6)

Japan in Agreement

In agreement is another article, this time from the Center for Excellence in Thyroid Care, Kuma Hospital, Japan in which the authors state that :

“TSH-suppressive doses of levothyroxine are required to achieve preoperative native serum triiodothyronine levels in patients who have undergone total thyroidectomy “(9),

Again, knowledgeable physicians are finding that TSH suppression below the lab reference range is required for adequate treatment of the low thyroid condition. In this Kuma Hospital study, doctors found TSH-suppressive doses of Synthroid were needed in post-thyroidectomy patients to achieve the same normal Serum T3 levels which were present on pre-operative labs.

Natural Thyroid

When Natural thyroid medication is used, and the dosage gradually adjusted upwards from 1/2 tab daily to the maintainance dose of two to three of the One Grain (65mg) Tabs daily (usually done over 6 weeks), the lab panel at this time will typically show a TSH which is below the normal reference range, and a free T3 which is in the upper end of the normal range 350-420. The low TSH is to be expected, is not disturbing, and is not indicative of a hyperthyroid state.

Why Has Endocrinology Mismanaged

the Low Thyroid Condition for Fifty Years?

The answer is obvious. Follow the money trail. Synthroid is the fourth most prescribed drug in America with 70 million prescriptions. Abbot labs, the makers of Synthroid, uses the massive profits to finance and fund Endocrinology Groups and Societies, their meetings, and clinical research grants. They also fund the key opinion leaders to give lectures at meetings in support of Synthroid and the TSH test. This is all done in spite of the obvious clinical inferiority of T4 only medications such as levothyroxine, and the unreliability of the TSH test to monitor adequacy of treatment. For many decades now, mainstream endocrinology has been completely corrupted by huge cash infusions from Big Pharma. Welcome to America. It’s a great country.

Articles With Related Interest

TSH Suppression Benefits and Adverse Effects

New Study Shows Natural Thyroid Better than Synthetic

Ann Nicole Smith and Hypothyroidism

Why Natural Thyroid is Better than Synthetic Part One

Why Natural Thyroid is Better Part Two

The TSH Reference Range Wars – Part One

TSH Wars, Part Two

Jeffrey Dach MD

7450 Griffin Road, Suite 190

Davie, Fl 33314

954-792-4663

www.jeffreydach.com

www.drdach.com

www.naturalmedicine101.com

www.bioidenticalhormones101.com

www.truemedmd.com

Links and References

1) http://www.scielosp.org/scielo.php?pid=S0042-96862002000800007&script=sci_arttext

Bulletin of the World Health Organization

Bull World Health Organ vol.80 no.8 Genebra Aug. 2002

dx.doi.org/10.1590/S0042-96862002000800007

Determining median urinary iodine concentration that indicates adequate iodine intake at population level by François Delange,1 Bruno de Benoist,2 Hans Bürgi,1 & the ICCIDD Working Group3

2) www.ncbi.nlm.nih.gov/pubmed/16416346

TSH may not be a good marker for adequate thyroid hormone replacement therapy. Wien Klin Wochenschr. 2005 Sep;117(18):636-40. Alevizaki M, Mantzou E, Cimponeriu AT, Alevizaki CC, Koutras DA. Endocrine Unit, Dept Medical Therapeutics, Alexandra Hospital, Athens University School of Medicine, Athens, Greece.

The objective of this study was to evaluate parameters of thyroid function and indices of peripheral thyroid hormone action (such as SHBG) in patients whose hypothyroidism was considered well controlled under current criteria. 85 – Eighty-five patients with T4-treated hypothyroidism, 28 of whom had athyria, were compared with 114 normal individuals with the same TSH levels. T3 levels were significantly lower in hypothyroidism although mean T4 and fT4 levels were significantly higher. Furthermore, mean SHBG levels were significantly lower in hypothyroidism independently of age. The difference remained when stricter criteria for adequate treatment were applied (TSH < 2.5 microgU/ml). Significant negative correlations were found between logTSH and T3. The slopes of the regression lines of T3 to TSH were significantly different in the control group and the hypothyroid group: thus, for the same TSH levels, T3 levels were lower in the hypothyroid group. “We conclude that patients with T4-treated hypothyroidism have lower T3 levels, lower T3/T4 ratio and lower SHBG than normal individuals with the same TSH, perhaps indicating relative tissue hypothyroidism in the liver. TSH levels used to monitor substitution, mostly regulated by intracellular T3 in the pituitary, may not be such a good indicator of adequate thyroid hormone action in all tissues. The co-administration of T3 may prove more effective in this respect,“ provided novel suitable preparations are developed. Until this is accomplished, substitution in hypothyroidism should aim at low normal TSH, to ensure normal T3 levels.

2011

3) www.ncbi.nlm.nih.gov/pmc/articles/PMC3148220/ .free full text ….

www.ncbi.nlm.nih.gov/pubmed/21829633

Levothyroxine Monotherapy Cannot Guarantee Euthyroidism in All Athyreotic Patients (normal TSH). Dr Damiano Gullo MD – Endocrine Unit, University of Catania Medical School, Catania, Italy PLoS ONE 6(8): Published: August 1, 2011

20% of patient on Synthroid (T4) will have abnormal T3/T4 ratios because they are unable to convert T4 to T3. I say: They need a more physiologic treatment such as natural dessicated thyroid. “More than 20% of these patients, despite normal TSH levels, do not maintain FT3 or FT4 values in the reference range, reflecting the inadequacy of peripheral deiodination to compensate for the absent T3 secretion.”

Context- Levothyroxine monotherapy is the treatment of choice for hypothyroid patients because peripheral T4 to T3 conversion is believed to account for the overall tissue requirement for thyroid hormones. However, there are indirect evidences that this may not be the case in all patients.

Objective – To evaluate in a large series of athyreotic patients whether levothyroxine monotherapy can normalize serum thyroid hormones and thyroid-pituitary feedback. Setting – Academic hospital.Patients- 1,811 patients with normal TSH levels under levothyroxine monotherapy and 3,875 euthyroid controls.

Measurements – TSH, FT4 and FT3 concentrations by immunoassays.

Results- FT4 levels were significantly higher and FT3 levels were significantly lower (p

The correlation between thyroid hormones and serum TSH levels indicated an abnormal feedback mechanism in levothyroxine-treated patients.

Conclusions- Athyreotic patients have a highly heterogeneous T3 production capacity from orally administered levothyroxine. More than 20% of these patients, despite normal TSH levels, do not maintain FT3 or FT4 values in the reference range, reflecting the inadequacy of peripheral deiodination to compensate for the absent T3 secretion. The long-term effects of chronic tissue exposure to abnormal T3/T4 ratio are unknown but a sensitive marker of target organ response to thyroid hormones (serum TSH) suggests that this condition causes an abnormal pituitary response. A more physiological treatment than levothyroxine monotherapy may be required in some hypothyroid patients.

2010

4) www.ncbi.nlm.nih.gov/pubmed/20584231

Thyroid hormone replacement: an iatrogenic problem.

Int J Clin Pract. 2010 Jun;64(7):991-4. Dr O’Reilly DS. Department of Clinical Biochemistry, Royal Infirmary, Glasgow, UK.

Abstract Thyroid hormone replacement is one of the very few medical treatments devised in the 19th century that still survive. It is safe, very effective and hailed as a major success by patients and clinicians. Currently, it is arguably the most contentious issue in clinical endocrinology. The current controversy and patient disquiet began in the early 1970s, when on theoretical grounds and without proper assessment, the serum thyrotropin (TSH) concentration was adopted as the means of assessing the adequacy of thyroxine replacement. The published literature shows that the serum TSH concentration is a poor indicator of clinical status in patients on thyroxine. The adequacy of thyroxine replacement should be assessed clinically with the serum T3 being measured, when required, to detect over-replacement.

1986

5) www.ncbi.nlm.nih.gov/pmc/articles/PMC1341585/

Br Med J (Clin Res Ed). 1986 September 27; 293(6550) full text

Are biochemical tests of thyroid function of any value in monitoring patients receiving thyroxine replacement? W D Fraser, E M Biggart, D S O’Reilly, H W Gray, J H McKillop, and J A Thomson

To establish their role in monitoring patients receiving thyroxine replacement biochemical tests of thyroid function were performed in 148 hypothyroid patients studied prospectively. Measurements of serum concentrations of total thyroxine, analogue free thyroxine, total triiodothyronine, analogue free triiodothyronine, and TSH thyroid stimulating hormone, made with a sensitive immunoradiometric assay, did not, except in patients with gross abnormalities, distinguish euthyroid patients from those who were receiving inadequate or excessive replacement. These measurements are therefore of little, if any, value in monitoring patients receiving thyroxine replacement. To stop doing thyroid function tests in these cases would result in considerable savings nationally in the cost of reagents in laboratories using commercial kits.

Article By Henry Lindner MD

6) hormonerestoration.com/files/TSHWrongtree.pdf

Against TSH-T4 Reference Range Thyroidology: The Case for Clinical Thyroidology Henry H. Lindner MD1

The current reliance upon the TSH to both detect hypothyroidism and direct its treatment is illogical and ineffective. Hypothalamic-pituitary function is modified by many known and unknown factors, and is known to deteriorate with age. Even if one could know that a person’s hypothalamic-pituitary response is perfect, one cannot assume that the TSH response to once-daily oral thyroid replacement is identical to the response to continual thyroidal hormone production. The TSH level is only a measure of the hypothalamic-pituitary response to thyroid hormones. It is neither a test of free thyroid hormone levels nor of thyroid hormone effects throughout the body. It is useful for determining the cause of hypothyroidism; not for diagnosing or treating it. The most reliable serum tests of thyroid hormone sufficiency are free T4 and free T3, but their broad laboratory reference ranges are neither optimal nor treatment ranges, and there are marked individual variations. Ultimately, both the diagnosis and treatment of hypothyroidism must be clinical.

7) www.ncbi.nlm.nih.gov/pubmed/11201857

Thyroid. 2000 Dec;10(12):1107-11. Is excessive weight gain after ablative treatment of hyperthyroidism due to inadequate thyroid hormone therapy?

Tigas S, Idiculla J, Beckett G, Toft A. Source Endocrine Unit, Royal Infirmary, Edinburgh, Scotland.

Abstract There is controversy about the correct dose and form of thyroid hormone therapy for patients with hypothyroidism. Despite restoration of serum thyrotropin (TSH) concentrations to normal, many patients complain of excessive weight gain. We have compared weight at diagnosis of hyperthyroidism with that when euthyroid, evidenced by a stable, normal serum TSH concentration, with or without thyroxine (T4) replacement therapy, in patients treated with an 18-month course of antithyroid drugs (43 patients), surgery (56 patients), or 13I (34 patients) for Graves’ disease. In addition, weights were recorded before and after treatment of 25 patients with differentiated thyroid carcinoma by total thyroidectomy, 131I, and long-term T4 suppressive therapy, resulting in undetectable serum TSH concentrations. Mean weight gain in patients with Graves’ disease who required T4 replacement therapy following surgery was significantly greater than in those of the same age, sex, and severity of hyperthyroidism rendered euthyroid by surgery (3.9 kg) (p < 0.001) or at the end of a course of antithyroid drugs (4.1 kg) (p < 0.001). Weight gain was similar in those requiring T4 replacement following surgery or 131T therapy (10.4 versus 10.1 kg). In contrast, ablative therapy combined with suppression of TSH secretion by T4 in patients with differentiated thyroid carcinoma did not result in weight gain. The excessive weight gain in patients becoming hypothyroid after destructive therapy for Graves’ disease suggests that restoration of serum TSH to the reference range by T4 alone may constitute inadequate hormone replacement.

8) www.ncbi.nlm.nih.gov/pmc/articles/PMC143526/

BMJ. 2003 February 8; 326(7384): 311–312. PMCID: PMC143526 full text free

Serum thyroid stimulating hormone in assessment of severity of tissue hypothyroidism in patients with overt primary thyroid failure: cross sectional survey Christian Meier, senior registrar in endocrinology, Peter Trittibach, clinical research fellow, Merih Guglielmetti, statistician, Jean-Jacques Staub, emeritus professor of endocrinology, and Beat Müller, head of division Division of Endocrinology, Department of Medicine, University Hospital, CH-4031 Basle, Switzerland

We found no correlations between the different parameters of target tissues and serum TSH. Our findings are in accordance with a cross sectional study showing only a modest correlation between TSH and the percentage of positive hypothyroid symptoms4 and data showing discordant responses between the pituitary and peripheral target tissues in patients treated with l-triiodothyronine.5 We assume that secretion of TSH is driven by maximal stimulation, with no further increase occurring with greater severity of hypothyroidism. Therefore, the biological effects of thyroid hormones at the peripheral tissues—and not TSH concentrations—reflect the clinical severity of hypothyroidism. A judicious initiation of thyroxine treatment should be guided by clinical and metabolic presentation and thyroid hormone concentrations (free thyroxine) and not by serum TSH concentrations.

TSH suppression required to achieve good result with Synthroid

9) http://www.eje-online.org/content/167/3/373.abstract

TSH-suppressive doses of levothyroxine are required to achieve preoperative native serum triiodothyronine levels in patients who have undergone total thyroidectomy by Mitsuru Ito,Akira Miyauchi,Shinji Morita,Takumi Kudo,Eijun Nishihara, Minoru Kihara,Yuuki Takamura,Yasuhiro Ito, Kaoru Kobayashi, Akihiro Miya, Sumihisa Kubota and Nobuyuki Amino from the Center for Excellence in Thyroid Care, Kuma Hospital, 8-2-35, Shimoyamate-Dori, Chuo-Ku, Kobe-City, Hyogo 650-0011, Japan

Objective Thyroidal production of triiodothyronine (T3) is absent in patients who have undergone total thyroidectomy. Therefore, relative T3 deficiency may occur during postoperative levothyroxine (l-T4) therapy. The objective of this study was to evaluate how the individual serum T3 level changes between preoperative native thyroid function and postoperative l-T4 therapy.

Methods We retrospectively studied 135 consecutive patients with papillary thyroid carcinoma, who underwent total thyroidectomy. Serum free T4 (FT4), free T3 (FT3), and TSH levels measured preoperatively were compared with those levels measured on postoperative l-T4 therapy.

Results Serum TSH levels during postoperative l-T4 therapy were significantly decreased compared with native TSH levels (P

Conclusions Serum FT3 levels during postoperative l-T4 therapy were equivalent to the preoperative levels in patients with moderately suppressed TSH levels. Our study indicated that a moderately TSH-suppressive dose of l-T4 is required to achieve the preoperative native serum T3 levels in postoperative l-T4 therapy.

10) full text

http://content.karger.com/ProdukteDB/produkte.asp?Doi=339447

Translational Thyroidology / Review

Thyroid Hormone Replacement Therapy: Three ‘Simple’ Questions, Complex Answers

Antonio C. Bianco, Sabina Casula from the Division of Endocrinology, Diabetes and Metabolism, University of Miami Miller School of Medicine, Miami, Fla., USA

Eur Thyroid J 2012;1:88-98

11) http://www.ncbi.nlm.nih.gov/pubmed/22593590

http://jcem.endojournals.org/content/97/7/2256.short

J Clin Endocrinol Metab. 2012 Jul;97(7):2256-71. doi: 10.1210/jc.2011-3399. Epub 2012 May 16.

Combination treatment with T4 and T3: toward personalized replacement therapy in hypothyroidism? Biondi B, Wartofsky L. Department of Clinical and Molecular Endocrinology and Oncology, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.

Levothyroxine therapy is the traditional lifelong replacement therapy for hypothyroid patients. Over the last several years, new evidence has led clinicians to evaluate the option of combined T(3) and T(4) treatment to improve the quality of life, cognition, and peripheral parameters of thyroid hormone action in hypothyroidism. The aim of this review is to assess the physiological basis and the results of current studies on this topic.

We searched Medline for reports published with the following search terms: hypothyroidism, levothyroxine, triiodothyronine, thyroid, guidelines, treatment, deiodinases, clinical symptoms, quality of life, cognition, mood, depression, body weight, heart rate, cholesterol, bone markers, SHBG, and patient preference for combined therapy. The search was restricted to reports published in English since 1970, but some reports published before 1970 were also incorporated. We supplemented the search with records from personal files and references of relevant articles and textbooks. Parameters analyzed included the rationale for combination treatment, the type of patients to be selected, the optimal T(4)/T(3) ratio, and the potential benefits of this therapy on symptoms of hypothyroidism, quality of life, mood, cognition, and peripheral parameters of thyroid hormone action.

The outcome of our analysis suggests that it may be time to consider a personalized regimen of thyroid hormone replacement therapy in hypothyroid patients.Further prospective randomized controlled studies are needed to clarify this important issue. Innovative formulations of the thyroid hormones will be required to mimic a more perfect thyroid hormone replacement therapy than is currently available.

12) http://www.eje-online.org/content/early/2012/11/26/EJE-12-0819.short

Is Pituitary Thyrotropin an Adequate Measure Of Thyroid Hormone-Controlled Homeostasis During Thyroxine Treatment? by Rudolf Hoermann, John E M Midgley, Rolf Larisch and Johannes W Dietrich

Objective. In recognition of its primary role in pituitary-thyroid feedback, thyrotropin (TSH) determination has become a key parameter for clinical decision-making. The present study evaluates the value of TSH as a measure of thyroid hormone homeostasis under T4 therapy.

Design,

Methods. We have examined the interrelationships between free triiodothyronine (FT3), free thyroxine (FT4) and pituitary TSH by means of 1) a retrospective analysis of a large clinical sample comprising 1994 patients either untreated or on varying doses of L-T4 and 2) independent mathematical simulation applying a model of thyroid homeostasis, together with a sensitivity analysis.

Results. Over a euthyroid to mildly hyperthyroid functional range, we found markedly different correlation slopes of log TSH versus FT3 and FT4 between untreated patients and L-T4 groups. Total deiodinase activity (GD) was positively correlated with TSH in untreated subjects. However, GD was significantly altered and the correlation lost under increasing L-T4 doses. 95% confidence intervals for FT3 and FT4, when assessed in defined TSH concentration bands, differed significantly for L-T4-treated, compared to untreated patients. Higher doses were often needed to restore FT3 levels within its reference range. Sensitivity analysis revealed the influence of various structural parameters on pituitary TSH secretion including a preeminent role of pituitary deiodinase type 2.

Conclusion. The data reveal disjoints between FT4-TSH feedback and T3 production that persist even when sufficient T4 apparently restores euthyroidism. T4 treatment displays a compensatory adaptation, but does not completely re-enact normal euthyroid physiology. This invites a study of the clinical consequences of this disparity.

13) Low Thyroid function associated with heart disease risk

HUNT study

14) http://www.ncbi.nlm.nih.gov/pubmed/18443261

Thyrotropin TSH Levels and Risk of Fatal Coronary Heart Disease- The HUNT Study . Norway Arch Intern Med. 2008;168(8):855-860. Bjørn O. Åsvold, MD; Trine Bjøro, MD, PhD; Tom Ivar L. Nilsen, PhD; David Gunnell, MD, PhD; Lars J. Vatten, MD, PhD (Norway) —

70% increased mortality from Heart Disease in higher TSH range (2.5-3.5) In a Norwegian population TSH Levels measured and pts followed over 8 years for death from heart attack 17, 311 women and 8,002 men (without known thyroid or cardiovascular disease or diabetes mellitus at baseline.) Results: In women the hazard ratios for coronary death were 1.41 (95% confidence interval [CI], 1.02-1.96) and 1.69 (95% CI, 1.14-2.52) for women in the intermediate (thyrotropin level, 1.5-2.4 mIU/L) and higher (thyrotropin level, 2.5-3.5 mIU/L) categories, respectively. Conclusions: (TSH) Thyrotropin levels within the reference range were positively and linearly associated with CHD mortality in women. The results indicate that relatively low but clinically normal thyroid function may increase the risk of fatal CHD by 70% .

Antonio C. Bianco M.D.

15) Is a Normal TSH Synonymous with “Euthyroidism” in Levothyroxine Monotherapy? Sarah J. Peterson Ph.D., Elizabeth A. McAninch M.D., and Antonio C. Bianco M.D. Division of Endocrinology and Metabolism, Rush University Medical Center, 1735 W Harrison St; Cohn Building Rm 212; Chicago, IL 60612, USA

Context: Levothyroxine (LT4) monotherapy is the standard of care for hypothyroidism.

Objective: To determine whether LT4 at doses that normalize the serum TSH is associated with normal markers of thyroid status.

Design: Cross-sectional data from the US National Health and Nutrition Examination Survey (2001–2012) was used to evaluate 52 clinical parameters. LT4-users were compared to healthy controls and controls matched for age, sex, race, and serum TSH. Regression was used to evaluate for correlation with serum thyroxine (T4) and triiodothyronine (T3) levels.

Participants: 9,981 participants with normal serum TSH were identified; 469 were LT4-treated.

Results: Participants using LT4 had higher serum total and free T4 and lower serum total and free T3 than healthy or matched controls. This translated to ∽15–20% lower serum T3:T4 ratios in LT4 treatment, as has been shown in other cohorts. In comparison to matched controls, LT4-treated participants: had higher BMI despite report of consuming less calories/day/kg; were more likely to be taking beta-blockers, statins, and anti-depressants; and reported lower total metabolic equivalents. A serum TSH level below the mean in LT4-treated participants was associated with a higher serum free T4 but similar free and total T3; yet those with lower serum TSH levels exhibited higher serum HDL and lower serum LDL, triglycerides, and CRP. Age was associated with serum free T3:free T4 ratio in all participants; caloric intake was associated in LT4-treated individuals.

Conclusions: In a large population study, participants using LT4 exhibited lower serum T3:T4 ratios and differed in 12/52 objective and subjective measures.

16) Hypothyroidism Symptoms Linger Despite Medication Use, Normal Blood Tests. Study questions value of TSH levels as indicator that disease is under control. Released: 12-Oct-2016 12:05 PM EDT

Source Newsroom: Rush University Medical Center

17) Hypothyroidism symptoms linger despite medication use, normal blood tests October 12, 2016 Rush University Medical Center

New research gives hypothyroidism patients—who often feel dismissed and forgotten—evidence that their persistent symptoms are not just in their heads.

Jeffrey Dach MD

7450 Griffin Road, Suite 190

Davie, Fl 33314

954-792-4663

www.jeffreydach.com

www.drdach.com

www.naturalmedicine101.com

www.bioidenticalhormones101.com

www.truemedmd.com

Click Here for: Dr Dach’s Online Store for Pure Encapsulations Supplements

Click Here for: Dr Dach’s Online Store for Nature’s Sunshine Supplements

Web Site and Discussion Board Links:

jdach1.typepad.com/blog/

disc.yourwebapps.com/Indices/244124.html

disc.yourwebapps.com/Indices/244066.html

disc.yourwebapps.com/Indices/244067.html

disc.yourwebapps.com/Indices/244161.html

disc.yourwebapps.com/Indices/244163.html

Disclaimer click here: www.drdach.com/wst_page20.html

The reader is advised to discuss the comments on these pages with his/her personal physicians and to only act upon the advice of his/her personal physician. Also note that concerning an answer which appears as an electronically posted question, I am NOT creating a physician — patient relationship. Although identities will remain confidential as much as possible, as I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur.

Link to this article: http://wp.me/p3gFbV-3RQ

Copyright (c) 2013 Jeffrey Dach MD All Rights Reserved. This article may be reproduced on the internet without permission, provided there is a link to this page and proper credit is given.

FAIR USE NOTICE: This site contains copyrighted material the use of which has not always been specifically authorized by the copyright owner. We are making such material available in our efforts to advance understanding of issues of significance. We believe this constitutes a ‘fair use’ of any such copyrighted material as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, the material on this site is distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes.

The post Antonio Bianco TSH Inadequate for Levothyroxine Dosing appeared first on Jeffrey Dach MD .

Fake Research on Heart Disease by Sugar Industry

Fake Research on Heart Disease by Sugar Industry

by Jeffrey Dach MD

Fraudulent research comes in many flavors.  Perhaps the most memorable scientific fraud was the 1974 case of Dr William Summerlin, a dermatologist at Sloan Kettering who claimed to solve transplant rejection by grafting black skin onto white mice.   However, one day the elevator operator noticed him using a black magic marker to draw the “black fur” dots on the mice.    The temptation to cheat is great, and there are many more examples.   Above left image courtesy of second opinion.

The Latest Science Fraud by the Sugar Industry

The latest scientific fraud that has come to light is the 1967 case of the Sugar Industry paying scientists to publish fake research in the New England Journal of Medicine claiming that heart disease is caused by eating fat, and not by eating sugar.(1-2) Left Image courtesy of People Who Fooled the World.

As a result of this deceit and fraud by the Sugar Industry,  we have had more than 50 years of incorrect dietary recommendations by the American Heart Association, and all cardiologists.

Dr Arthur Agatson Sees the Light

For example, Arthur Agatson’s best seller book, the South Beach Diet, makes a striking comment.  Immediately after finishing his cardiology training and starting his own cardiology practice ,  Dr Agatson placed all of his patients on a low fat diet based on guidelines of the American Heart Association.  He quickly discovered this diet did not work, and all his patients promptly died of heart disease.   This spurred him to come up with a new diet recommendation closer to the Atkin’s low sugar, low carbohydrate diet used by Diabetics.  Thus, the South Beach Diet book was born.  Left image mouse with dark spots courtesy of  Science Made Easy.

Dr WIlliam Davis Sees the Light

Another best seller book by a cardiologist, Wheat Belly by William Davis MD again tells a similar story of discovery that the low fat diet for prevention of heart disease doesn’t work .  Instead, Dr Davis discovered eliminating sugar and wheat products produced beneficial changes in health and lipid profiles in his patient population.

The Tip of the Iceberg

Revelations of the Sugar Industry Medical Research Fraud have taken more than 50 years to come to light.  Rest assured this is only the tip of the iceberg for corporate fraud in research science.   For decades, “Big Tobacco” used fraudulent science to hide the unpleasant fact that smoking cigarettes causes cancer and heart disease.

The chemical industry used hired goons and fraudulent science to fight Rachel Carson’s 1962 Silent Spring book which revealed the environmental impact of DDT and other pesticides.  DDT was finally banned in the US in 1972.

A more recent example of Industry sponsored fraud in science is Monsanto’s industry sponsored research claiming of safety for GMO food and the herbicide glyphosate.  There is nothing farther from the truth, as non-industry funded research shows GMO food and glyphosate herbicide usage pose the largest threat to human health in the history of civilization.

Conclusion: As physicians, it is our job to see through industry sponsored fraudulent research, and provide truthful advice to our patients.  The latest outrage of Sugar Industry sponsored research fraud dating back to 1967 is only the tip of the iceberg.  How many millions of patients have been harmed by these incorrect dietary recommendations perpetuated by the Sugar Industry ?  Your guess is as good as mine.

Jeffrey Dach MD

7450 Griffin Road Suite 190

Davie, FL 33314

954 792 4663

Links and references

1) Sugar Industry and Coronary Heart Disease Research A Historical Analysis of Internal Industry Documents JAMA Intern Med. 2016 Sep 12. Cristin E. Kearns, DDS, MBA1,2; Laura A. Schmidt, PhD, MSW, MPH1,3,4; Stanton A. Glantz, PhD1,5,6,7,8

1Philip R. Lee Institute for Health Policy Studies, San Francisco, California

By the 1960s, 2 prominent physiologists were championing divergent causal hypotheses of CHD2,3: John Yudkin identified added sugars as the primary agent, while Ancel Keys identified total fat, saturated fat, and dietary cholesterol. However, by the 1980s, few scientists believed that added sugars played a significant role in CHD, and the first 1980 Dietary Guidelines for Americans4 focused on reducing total fat, saturated fat, and dietary cholesterol for CHD prevention.

Link Between Sucrose and Elevated Serum Triglyceride Level

On July 1, 1965, the SRF’s Hickson visited D. Mark Hegsted, a faculty member of Stare’s department,24,25 after publication of articles in Annals of Internal Medicine in June 196526- 29 linking sucrose to CHD. The first 2 articles26,27 reported results from an epidemiological study suggesting that blood glucose levels were a better predictor of atherosclerosis than serum cholesterol level or hypertension. The third28(p210) demonstrated that sucrose, more than starches, aggravated carbohydrate-induced hypertriglyceridemia and hypothesized that “perhaps fructose, a constituent of sucrose but not of starch, [was] the agent mainly responsible.” An accompanying editorial29(p1330) argued that these findings corroborated Yudkin’s research and that if elevated serum triglyceride levels were a CHD risk factor, then “sucrose must be atherogenic.”

internal documents show that the SRF initiated CHD research in 1965 to protect market share and that its first project, a literature review, was published in NEJM in 1967 without disclosure of the sugar industry’s funding or role.  our findings suggest the industry sponsored a research program in the 1960s and 1970s that successfully cast doubt about the hazards of sucrose while promoting fat as the dietary culprit in CHD.

This study suggests that the sugar industry sponsored its first CHD research project in 1965 to downplay early warning signals that sucrose consumption was a risk factor in CHD. As of 2016, sugar control policies are being promulgated in international,61 federal,62,63 state, and local venues.64 Yet CHD risk is inconsistently cited as a health consequence of added sugars consumption. Because CHD is the leading cause of death globally, the health community should ensure that CHD risk is evaluated in future risk assessments of added sugars. Policymaking committees should consider giving less weight to food industry–funded studies, and include mechanistic and animal studies as well as studies appraising the effect of added sugars on multiple CHD biomarkers and disease development.65

2)  Food Industry Funding of Nutrition Research The Relevance of History for Current Debates ONLINE FIRST  Marion Nestle, PhD, MPH1

1Department of Nutrition and Food Studies, New York University, New York

JAMA Intern Med. Published online September 12, 2016.

3)   Research reveals role of sugar industry in heart disease studies

Harvard researchers were paid for writing a study suggesting sugar did not have a role in the development of heart disease, which the industry approved before publication. By Stephen Feller | Sept. 12, 2016 at 2:27 PM

4)  Sugar and heart disease: The sour side of industry-funded research

Written by Honor Whiteman Published: Wednesday 21 September 2016

The problem? The SRF funding was not disclosed – mandatory conflict of interest disclosure was not introduced until the 1980s – and there is evidence that the researchers of the 50-year-old study were paid to shift the focus away from the harms sugar intake poses for heart health.

The study in question was published in The New England Journal of Medicine on July 27, 1967.

Conducted by three former nutritionists at Harvard Medical School in Boston, MA – Dr. Frederick Stare, Dr. Mark Hegsted, and Dr. Robert B. McGandy, who are now deceased – the research claimed that consumption of dietary fats, rather than sugar, was the primary cause of coronary heart disease (CHD).

5) McGandy, Robert B., D. M. Hegsted, and F. J. Stare. “Dietary fats, carbohydrates and atherosclerotic vascular disease.” New England Journal of Medicine 277.4 (1967): 186-192.

6)  How Sweet: Sugar Industry Made Fat the Villain September 13, 2016 by Larry Husten  –Harvard researchers received sugar industry money to write a NEJM review.

7)  Sugar Papers Reveal Industry Role in Shifting National Heart Disease Focus to Saturated Fat  By Elizabeth Fernandez on September 12, 2016

8)  How the Sugar Lobby Skewed Health Research Alexandra Sifferlin  Sept. 12, 2016

9)  How the sugar industry sweetened research in its favor

By Jacqueline Howard, CNN Updated 12:26 PM ET, Mon September 12, 2016

10)  How the Sugar Industry Shifted Blame to Fat By ANAHAD O’CONNORSEPT. 12, 2016

11)   Sugar and Heart Disease: The Sour Side of Industry-Funded Research

09/21/2016 02:51 pm ET | Updated 1 day ago

12) Sweet deal? Sugar industry blamed fat in fake studies – study

Published time: 13 Sep, 2016

13) The Sugar Industry Financed Cardiac Health Research to Influence Public and Scientific Attitudes Toward Sugar Wednesday, September 21, 2016

14)  Sugar Industry Scandal: Sponsored Phony Harvard Research Blamed Fat for Heart Disease Dr Ax

15)  Sugar and hearts: how food industry still buys scientists

Posted in Heart Disease By Marika Sboros

16)  McGandy, Robert B., D. M. Hegsted, and F. J. Stare. “Dietary fats, carbohydrates and atherosclerotic vascular disease.” New England Journal of Medicine 277.4 (1967): 186-192.

17)  How Sweet: Sugar Industry Made Fat the Villain

September 13, 2016 by Larry Husten 3 Comments

–Harvard researchers received sugar industry money to write a NEJM review.

18)  The Summerlin Mouse Affair

Starting in 1970 as a young teaching and training fellow at Stanford, the young doctor claimed to be able to take skin transplants from one individual and make them “stick” to another genetically unrelated individual. He did this by allegedly culturing the skin in a special medium for four to six weeks. Doing so, the samples appeared to lose their natural ability to provoke an immune response.  The entire thing turned out to be a fraudulent hoax – Summerlin just painted the alleged transplants on the mice with a magic marker.

Jeffrey Dach MD

7450 Griffin Road, Suite 180

Davie, Fl 33314

954-972-4663

www.jeffreydach.com

www.drdach.com

www.naturalmedicine101.com

www.bioidenticalhormones101.com

www.truemedmd.com

Click Here for: Dr Dach’s Online Store for Pure Encapsulations Supplements

Click Here for: Dr Dach’s Online Store for Nature’s Sunshine Supplements

Web Site and Discussion Board Links:

jdach1.typepad.com/blog/

disc.yourwebapps.com/Indices/244124.html

disc.yourwebapps.com/Indices/244066.html

disc.yourwebapps.com/Indices/244067.html

disc.yourwebapps.com/Indices/244161.html

disc.yourwebapps.com/Indices/244163.html

Disclaimer click here: www.drdach.com/wst_page20.html

The reader is advised to discuss the comments on these pages with his/her personal physicians and to only act upon the advice of his/her personal physician. Also note that concerning an answer which appears as an electronically posted question, I am NOT creating a physician — patient relationship. Although identities will remain confidential as much as possible, as I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur.

Link to this article:http://wp.me/p3gFbV-3Qj

Copyright (c) 2016 Jeffrey Dach MD All Rights Reserved. This article may be reproduced on the internet without permission, provided there is a link to this page and proper credit is given.

FAIR USE NOTICE: This site contains copyrighted material the use of which has not always been specifically authorized by the copyright owner. We are making such material available in our efforts to advance understanding of issues of significance. We believe this constitutes a ‘fair use’ of any such copyrighted material as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, the material on this site is distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes.

The post Fake Research on Heart Disease by Sugar Industry appeared first on Jeffrey Dach MD .

Probiotics Decrease Mortality from Stem Cell Transplantation

Probiotics Decrease Mortality from Stem Cell Transplantation

by Jeffrey Dach MD

We are continually surprised by new studies showing the importance of the microbiome, or “friendly bacteria” colonizing the gut.  One such study was done  by Dr Ying Taur published in the hematology oncology journal, Blood, in 2014.(1)

Dr Ying Taur studied the “effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation.”  He obtained fecal specimens from 80 allogeneic transplant recipients, at time of engraftment.  He used bacterial 16S rRNA gene sequencing to characterize microbial diversity classified into high, intermediate, and low diversity.   Surprisingly, after three years, over all survival was only 36% for the patients with low diversity, compared to 67% over-all survival for patients with higher microbial diversity. Dr Taur’s conclusion:

In conclusion, the diversity of the intestinal microbiota at engraftment is an independent predictor of mortality in allo-HSCT recipients. These results indicate that the intestinal microbiota may be an important factor in the success or failure in allo-HSCT. (1) (note allo-HSCT =allogeneic stem cell transplant”

What is allogeneic hematopoetic stem cell transplantation?

This is a common treatment for leukemia or lymphoma in which the patient’s bone marrow stem cells are destroyed by an intensive chemotherapy regimen.  Bone marrow stem cells are essential for the immune system and  necessary for life. To restore them, stem cells from a matching sibling are drawn off. and then infused into the cancer patient, called engraftment, this  restores bone marrow cellularity.   The new bone marrow cells from the matched sibling mounts an immune response to the cancer cells, thus accounting for the curative effects of the allogeneic stem cell transplant procedure.

Conclusion:  Probiotics increase microbial diversity and reduce mortality associated with allogeneic stem cell transplantation.

This article is part two, for part one click here.

Articles with related interest:

Curing Autism with Antibiotics

Depression and Leaky Gut Michael Maes

NSAIDS Small Bowel and Leaky Gut

Links and References

header image human stem cell courtesy of  Microbiology Spring 2011

1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133489/

Taur, Ying, et al. “The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation.” Blood 124.7 (2014): 1174-1182.

Highly diverse bacterial populations inhabit the gastrointestinal tract and modulate host inflammation and promote immune tolerance. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), the gastrointestinal mucosa is damaged, and colonizing bacteria are impacted, leading to an impaired intestinal microbiota with reduced diversity. We examined the impact of intestinal diversity on subsequent mortality outcomes following transplantation. Fecal specimens were collected from 80 recipients of allo-HSCT at the time of stem cell engraftment. Bacterial 16S rRNA gene sequences were characterized, and microbial diversity was estimated using the inverse Simpson index. Subjects were classified into high, intermediate, and low diversity groups and assessed for differences in outcomes. Mortality outcomes were significantly worse in patients with lower intestinal diversity; overall survival at 3 years was 36%, 60%, and 67% for low, intermediate, and high diversity groups, respectively (P = .019, log-rank test). Low diversity showed a strong effect on mortality after multivariate adjustment for other clinical predictors (transplant related mortality: adjusted hazard ratio, 5.25; P = .014). In conclusion, the diversity of the intestinal microbiota at engraftment is an independent predictor of mortality in allo-HSCT recipients. These results indicate that the intestinal microbiota may be an important factor in the success or failure in allo-HSCT.

http://www.bloodjournal.org/content/126/14/1723.long?sso-checked=true

Blood. 2015 Oct 1;126(14):1723-8. doi: 10.1182/blood-2015-04-638858. Epub 2015 Jul 24.

Low urinary indoxyl sulfate levels early after transplantation reflect a disrupted microbiome and are associated with poor outcome.

Weber D1, Oefner PJ2, Hiergeist A3, Koestler J3, Gessner A3, Weber M4, Hahn J1, Wolff D1, Stämmler F5, Spang R5, Herr W1, Dettmer K2, Holler E1.

Indole, which is produced from l-tryptophan by commensal bacteria expressing tryptophanase, not only is an important intercellular signal in microbial communities, but also modulates mucosal barrier function and expression of pro- and anti-inflammatory genes by intestinal epithelial cells. Here, we hypothesized that decreased urinary excretion of 3-indoxyl sulfate (3-IS), the major conjugate of indole found in humans, may be a marker of gut microbiota disruption and increased risk of developing gastrointestinal (GI) graft-versus-host-disease. Using liquid chromatography/tandem mass spectrometry, 3-IS was determined in urine specimens collected weekly within the first 28 days after allogeneic stem cell transplantation (ASCT) in 131 patients. Low 3-IS levels within the first 10 days after ASCT were associated with significantly higher transplant-related mortality (P = .017) and worse overall survival (P = .05) 1 year after ASCT. Least absolute shrinkage and selection operator regression models trained on log-normalized counts of 763 operational taxonomic units derived from next-generation sequencing of the hypervariable V3 region of the 16S ribosomal RNA gene showed members of the families of Lachnospiraceae and Ruminococcaceae of the class of Clostridia to be associated with high urinary 3-IS levels, whereas members of the class of Bacilli were associated with low 3-IS levels. Risk factors of early suppression of 3-IS levels were the type of GI decontamination (P = .01), early onset of antibiotic treatment (P = .001), and recipient NOD2/CARD15 genotype (P = .04). In conclusion, our findings underscore the relevance of microbiota-derived indole and metabolites thereof in mucosal integrity and protection from inflammation.

A significantly higher transplant -related mortality (TRM) was observed in patients with low intestinal microbiome diversity, whereas patients with a microbiome dominated by commensal bacteria showed a better overall survival (OS) within 3 years after transplantation.8

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991773/

Sci Transl Med. 2016 May 18;8(339):339ra71. doi: 10.1126/scitranslmed.aaf2311.

Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice.

Shono Y1, Docampo MD2, Peled JU3, Perobelli SM2, Velardi E4, Tsai JJ2, Slingerland AE2, Smith OM2, Young LF2, Gupta J2, Lieberman SR2, Jay HV2, Ahr KF2, Porosnicu Rodriguez KA2, Xu K2, Calarfiore M2, Poeck H2, Caballero S2, Devlin SM5, Rapaport F6, Dudakov JA7, Hanash AM8, Gyurkocza B8, Murphy GF9, Gomes C9, Liu C10, Moss EL11, Falconer SB11, Bhatt AS11, Taur Y12, Pamer EG13, van den Brink MR14, Jenq RR15.

Intestinal bacteria may modulate the risk of infection and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT recipients often develop neutropenic fever, which is treated with antibiotics that may target anaerobic bacteria in the gut. We retrospectively examined 857 allo-HSCT recipients and found that treatment of neutropenic fever with imipenem-cilastatin and piperacillin-tazobactam antibiotics was associated with increased GVHD-related mortality at 5 years (21.5% for imipenem-cilastatin-treated patients versus 13.1% for untreated patients, P = 0.025; 19.8% for piperacillin-tazobactam-treated patients versus 11.9% for untreated patients, P = 0.007). However, two other antibiotics also used to treat neutropenic fever, aztreonam and cefepime, were not associated with GVHD-related mortality (P = 0.78 and P = 0.98, respectively). Analysis of stool specimens from allo-HSCT recipients showed that piperacillin-tazobactam administration was associated with perturbation of gut microbial composition. Studies in mice demonstrated aggravated GVHD mortality with imipenem-cilastatin or piperacillin-tazobactam compared to aztreonam (P < 0.01 and P < 0.05, respectively). We found pathological evidence for increased GVHD in the colon of imipenem-cilastatin-treated mice (P < 0.05), but no difference in the concentration of short-chain fatty acids or numbers of regulatory T cells. Notably, imipenem-cilastatin treatment of mice with GVHD led to loss of the protective mucus lining of the colon (P < 0.01) and the compromising of intestinal barrier function (P < 0.05). Sequencing of mouse stool specimens showed an increase in Akkermansia muciniphila (P < 0.001), a commensal bacterium with mucus-degrading capabilities, raising the possibility that mucus degradation may contribute to murine GVHD. We demonstrate an underappreciated risk for the treatment of allo-HSCT recipients with antibiotics that may exacerbate GVHD in the colon.

http://www.ncbi.nlm.nih.gov/pubmed/26900084

Biol Blood Marrow Transplant. 2016 Jun;22(6):1087-93. doi: 10.1016/j.bbmt.2016.02.009. Epub 2016 Feb 18.

Impact of Gut Colonization by Antibiotic-Resistant Bacteria on the Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective, Single-Center Study.

Bilinski J1, Robak K1, Peric Z2, Marchel H3, Karakulska-Prystupiuk E1, Halaburda K1, Rusicka P1, Swoboda-Kopec E3, Wroblewska M4, Wiktor-Jedrzejczak W1, Basak GW5.

Gut colonization by antibiotic-resistant bacteria may underlie hard-to-treat systemic infections. There is also accumulating evidence on the immunomodulatory function of gut microbiota after allogeneic stem cell transplantation (alloSCT) and its impact on graft-versus-host disease (GVHD). We investigated the epidemiology and clinical impact of gut colonization after alloSCT and retrospectively analyzed data on 107 alloSCTs performed at a single transplant center. Pretransplant microbiology screening identified colonization in 31% of cases. Colonization had a negative impact on overall survival after alloSCT in univariate (34% versus 74% at 24 months, P < .001) and multivariate (hazard ratio, 3.53; 95% confidence interval, 1.71 to 7.28; P < .001) analyses. Nonrelapse mortality was significantly higher in colonized than in noncolonized patients (42% versus 11% at 24 months, P = .001). Colonized patients more frequently experienced bacteremia (48% versus 24%, P = .01), and more deaths were attributable to infectious causes in the colonized group (42% versus 11% of patients and 67% versus 29% of deaths, P < .05). We observed a significantly higher incidence of grades II to IV acute GVHD in colonized than in noncolonized patients (42% versus 23%, P < .05), especially involving the gastrointestinal system (33% versus 13.5%, P = .07). In summary, we determined that gut colonization by antibiotic-resistant bacteria decreases the overall survival of patients undergoing alloSCT by increasing nonrelapse mortality and the incidences of systemic infection and acute GVHD.

Khoruts, Alexander, et al. “Toward revision of antimicrobial therapies in hematopoietic stem cell transplantation: target the pathogens, but protect the indigenous microbiota.” Translational Research (2016).

Host microbiota plays important roles in providing colonization resistance to pathogens and instructing development and function of the immune system. Antibiotic treatments intended to target pathogens further weaken the host defenses and may paradoxically increase the risk of systemic infections. This consequence is especially problematic in patients undergoing hematopoietic stem cell transplantation, where the mucosal defenses are already weakened by the conditioning regimens. This review discusses the roles that indigenous microbiota plays in protecting the host and maintaining immune homeostasis. In addition, we highlight possible strategies that are being developed to allow targeted antimicrobial therapy against pathogens, while minimizing the harm to indigenous microbiota.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996265/

Andermann, T. M., A. Rezvani, and A. S. Bhatt. “Microbiota Manipulation With Prebiotics and Probiotics in Patients Undergoing Stem Cell Transplantation.” Current hematologic malignancy reports 11.1 (2016): 19.

Hematopoietic stem cell transplantation (HSCT) is a potentially life-saving therapy that often comes at the cost of complications such as graft-versus-host disease and post-transplant infections. With improved technology to understand the ecosystem of microorganisms (viruses, bacteria, fungi, and microeukaryotes) that make up the gut microbiota, there is increasing evidence of the microbiota’s contribution to the development of post-transplant complications. Antibiotics have traditionally been the mainstay of microbiota-altering therapies available to physicians. Recently, interest is increasing in the use of prebiotics and probiotics to support the development and sustainability of a healthier microbiota. In this review, we will describe the evidence for the use of prebiotics and probiotics in combating microbiota dysbiosis and explore the ways in which they may be used in future research to potentially improve clinical outcomes and decrease rates of graft-versus-host disease (GVHD) and post-transplant infection.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0105706#abstract0

Vossen, Jaak M., et al. “Complete suppression of the gut microbiome prevents acute graft-versus-host disease following allogeneic bone marrow transplantation.” PloS one 9.9 (2014): e105706.

Complete Suppression of the Gut Microbiome Prevents Acute Graft-Versus-Host Disease following Allogeneic Bone Marrow Transplantation

The hypothesis that elimination of facultative and strict anaerobic microorganisms from the gastro-intestinal tract by antimicrobial drugs in the period of time around allogeneic bone marrow transplantation (BMT) prevents acute graft-versus-host disease (GVHD), was examined in a cohort of 112 children grafted between 1989 and 2002 for hematological malignancies. All patients received T-cell replete marrow from human leukocyte antigens (HLA) matched sibling donors under identical transplantation conditions. To eliminate microorganisms from the gastro-intestinal tract, total gastro-intestinal decontamination (GID) was applied by high doses of non-absorbable antimicrobial drugs while the graft recipient was maintained in strict protective isolation. About half of the children (51%) proved to be successfully decontaminated, and about half (49%) unsuccessfully. One recipient got acute GVHD in the first group and 8 in the second group (p = 0.013). The degree of success of total GID was decisive for the occurrence of acute GVHD, irrespective of the presence of other risk factors such as higher age of recipient and/or donor, female donor for male recipient and carriership or reactivation of herpesviruses. Our results demonstrate that successful total GID of the graft recipient prevents moderate to severe acute GVHD. We suppose that substantial translocation of gastro-intestinal microorganisms or parts of these, functioning as microbial-associated molecular patterns (MAMP’s), triggering macrophages/dendritic cells via pattern recognizing receptors (PRR’s) is prohibited. As a consequence the initiation and progression of an inflammatory process leading to acute GVHD is inhibited.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973578/

Biol Blood Marrow Transplant. 2014 May;20(5):640-5. doi: 10.1016/j.bbmt.2014.01.030. Epub 2014 Jan 31.

Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease.

Holler E1, Butzhammer P2, Schmid K3, Hundsrucker C2, Koestler J4, Peter K3, Zhu W2, Sporrer D3, Hehlgans T5, Kreutz M3, Holler B3, Wolff D3, Edinger M3, Andreesen R3, Levine JE6, Ferrara JL6, Gessner A4, Spang R2, Oefner PJ2.

next-generation sequencing of the hypervariable V3 region of the 16s rRNA gene isolated from serial stool specimens collected from 31 patients receiving allogeneic stem cell transplantation (SCT) was performed to elucidate variations in the composition of the intestinal microbiome in the course of allogeneic SCT. Metagenomic analysis was complemented by strain-specific enterococcal PCR and indirect assessment of bacterial load by liquid chromatography-tandem mass spectrometry of urinary indoxyl sulfate. At the time of admission, patients showed a predominance of commensal bacteria. After transplantation, a relative shift toward enterococci was observed, which was more pronounced under antibiotic prophylaxis and treatment of neutropenic infections. The shift was particularly prominent in patients that developed subsequently or suffered from active gastrointestinal (GI) graft-versus-host disease (GVHD). The mean proportion of enterococci in post-transplant stool specimens was 21% in patients who did not develop GI GVHD as compared with 46% in those that subsequently developed GI GVHD and 74% at the time of active GVHD. Enterococcal PCR confirmed predominance of Enterococcus faecium or both E. faecium and Enterococcus faecalis in these specimens. As a consequence of the loss of bacterial diversity, mean urinary indoxyl sulfate levels dropped from 42.5 ± 11 μmol/L to 11.8 ± 2.8 μmol/L in all post-transplant samples and to 3.5 ± 3 μmol/L in samples from patients with active GVHD. Our study reveals major microbiome shifts in the course of allogeneic SCT that occur in the period of antibiotic treatment but are more prominent in association with GI GVHD. Our data indicate early microbiome shifts and a loss of diversity of the intestinal microbiome that may affect intestinal inflammation in the setting of allogeneic SCT.

http://www.ncbi.nlm.nih.gov/pubmed/25708215

Biol Blood Marrow Transplant. 2015 Aug;21(8):1360-6. doi: 10.1016/j.bbmt.2015.02.016. Epub 2015 Feb 21.

Emerging Influence of the Intestinal Microbiota during Allogeneic Hematopoietic Cell Transplantation: Control the Gut and the Body Will Follow.

Docampo MD1, Auletta JJ2, Jenq RR3.

The intestinal microbiota has many critical roles in maintaining gastrointestinal epithelial and gastrointestinal systemic immune homeostasis. This review provides insight into how allogeneic hematopoietic cell transplantation (HCT) and its associated complications and supportive care therapies affect the microbiota. Additionally, the review discusses how preservation and restoration of the microbiota might be advantageous in decreasing HCT-related morbidity and mortality.

Jeffrey Dach MD

7450 Griffin Road, Suite 180

Davie, Fl 33314

954-972-4663

www.jeffreydach.com

www.drdach.com

www.naturalmedicine101.com

www.bioidenticalhormones101.com

www.truemedmd.com

Click Here for: Dr Dach’s Online Store for Pure Encapsulations Supplements

Click Here for: Dr Dach’s Online Store for Nature’s Sunshine Supplements

Web Site and Discussion Board Links:

jdach1.typepad.com/blog/

disc.yourwebapps.com/Indices/244124.html

disc.yourwebapps.com/Indices/244066.html

disc.yourwebapps.com/Indices/244067.html

disc.yourwebapps.com/Indices/244161.html

disc.yourwebapps.com/Indices/244163.html

Disclaimer click here: www.drdach.com/wst_page20.html

The reader is advised to discuss the comments on these pages with his/her personal physicians and to only act upon the advice of his/her personal physician. Also note that concerning an answer which appears as an electronically posted question, I am NOT creating a physician — patient relationship. Although identities will remain confidential as much as possible, as I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur.

Link to this article:http://wp.me/p3gFbV-3PQ

Copyright (c) 2016 Jeffrey Dach MD All Rights Reserved. This article may be reproduced on the internet without permission, provided there is a link to this page and proper credit is given.

FAIR USE NOTICE: This site contains copyrighted material the use of which has not always been specifically authorized by the copyright owner. We are making such material available in our efforts to advance understanding of issues of significance. We believe this constitutes a ‘fair use’ of any such copyrighted material as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, the material on this site is distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes.

The post Probiotics Decrease Mortality from Stem Cell Transplantation appeared first on Jeffrey Dach MD .

Alum Jax Cole Thyroid Cancer Epidemic of Overdiagnosis

Alum Jax Cole

Thyroid Cancer Epidemic of Overdiagnosis

The American Idol finalist Alum Jax Cole announced that she underwent thyroid surgery in April after discovering a “lump in her neck”.  She is now receiving radiation treatments, presumably radioactive iodine (I-131), after the finding of thyroid cancer at surgery.(1-3)

An Epidemic of Overdiagnosis of Thyroid Cancer  In Women

According to Dr Gilbert Welch in 2014 Otolaryngology, there is an epidemic of overdiagnosis of thyroid cancer in young women.(4)

Since 1975, the incidence of thyroid cancer in women has more than tripled from  6.5 to 21.4 per 100,000 women, mostly from papillary cancer.

However, the “mortality rate from thyroid cancer was stable between 1975 and 2009 (approximately 0.5 deaths per 100 000).” 

In other words, mortality from thyroid cancer did not increase, even though  the incidence tripled.  If this was real cancer, one would expect increase in mortality numbers.  There was none.

Dr Welch concludes:

“There is an ongoing epidemic of thyroid cancer in the United States. The epidemiology of the increased incidence, however, suggests that it is not an epidemic of disease but rather an epidemic of diagnosis. The problem is particularly acute for women, who have lower autopsy prevalence of thyroid cancer than men but higher cancer detection rates by a 3:1 ratio.”

Dr Nikiforov writes in JAMA Oncology 2016 that many thyroid cancers are really not cancer and should be reclassified.(6)  An example is the encapsulated follicular variant of papillary thyroid carcinoma.  These cases are treated as having conventional thyroid cancer, yet they are not really cancer,  Dr Nikiforov says this type of pathology does not require radioactive iodine after surgery.

Conclusion: Drs Welch and Nikiforov have come forward to alert the public to the “Epidemic of Overdiagnosis of Thyroid Cancer” in young women.  Is Alum Jax Cole just another example of this type of overdiagnosis? That is the obvious question, isn’t it?

Articles with Related Interest:

The Thyroid Nodule Epidemic

Links and References

1) ‘American Idol’ Alum Jax Is Battling Thyroid Cancer

August 9, 2016 @ 10:20 AM By Nicholas Hautman

She went to a local urgent-care center, where doctors discovered 18 tumors on her thyroid — 12 of which tested positive for cancer — and diagnosed her with Hashimoto’s disease, a type of hypothyroidism.

2)  ‘American Idol’ Alum Jax Cole Diagnosed with Thyroid Cancer

Former “American Idol” contestant Jackie “Jax” Cole is battling thyroid cancer.

Cole revealed she was diagnosed with cancer in April and has already undergone surgery to remove her thyroid and nearby lymph nodes.

Despite hearing the diagnosis, Cole tried to make light of the situation. She said, “The first thing I did when I found out about the cancer was crack a joke.

3)  ‘American Idol’ finalist Jax says she has thyroid cancer

Last Updated: Tuesday, August 09, 2016

MyCentralJersey.com reports (http://mycj.co/2aIoTjd ) Jax was diagnosed in the spring and underwent surgery to remove the thyroid and several lymph nodes. The 20-year-old singer and songwriter from East Brunswick became chronically ill with respiratory and exhaustion issues during her journey on “American Idol.”

The diagnosis came a week after a sold-out show in April. She says she felt something wasn’t right when she was recording on the West Coast. She went to an urgent care center, which found that she had 18 tumors on her thyroid.  She says she’s been undergoing radiation treatment in New York since her thyroid was removed.  Despite the diagnosis, Jax says she’s going to participate in the New York City Marathon on Nov. 6.

4)  JAMA Otolaryngol Head Neck Surg. 2014 Feb 20. doi: 10.1001/jamaoto.2014.1. [Epub ahead of print]

Current Thyroid Cancer Trends in the United States.

Davies L1, Welch HG2. IMPORTANCE We have previously reported on a doubling of thyroid cancer incidence-largely due to the detection of small papillary cancers. Because they are commonly found in people who have died of other causes, and because thyroid cancer mortality had been stable, we argued that the increased incidence represented overdiagnosis. OBJECTIVE To determine whether thyroid cancer incidence has stabilized. DESIGN Analysis of secular trends in patients diagnosed with thyroid cancer, 1975 to 2009, using the Surveillance, Epidemiology, and End Results (SEER) program and thyroid cancer mortality from the National Vital Statistics System. SETTING Nine SEER areas (SEER 9): Atlanta, Georgia; Connecticut; Detroit, Michigan; Hawaii; Iowa; New Mexico; San Francisco-Oakland, California; Seattle-Puget Sound, Washington; and Utah. PARTICIPANTS Men and women older than 18 years diagnosed as having a thyroid cancer between 1975 and 2009 who lived in the SEER 9 areas. INTERVENTIONS None. MAIN OUTCOMES AND MEASURES Thyroid cancer incidence, histologic type, tumor size, and patient mortality. RESULTS Since 1975, the incidence of thyroid cancer has now nearly tripled, from 4.9 to 14.3 per 100 000 individuals (absolute increase, 9.4 per 100 000; relative rate [RR], 2.9; 95% CI, 2.7-3.1). Virtually the entire increase was attributable to papillary thyroid cancer: from 3.4 to 12.5 per 100 000 (absolute increase, 9.1 per 100 000; RR, 3.7; 95% CI, 3.4-4.0). The absolute increase in thyroid cancer in women (from 6.5 to 21.4 = 14.9 per 100 000 women) was almost 4 times greater than that of men (from 3.1 to 6.9 = 3.8 per 100 000 men). The mortality rate from thyroid cancer was stable between 1975 and 2009 (approximately 0.5 deaths per 100 000). CONCLUSIONS AND RELEVANCE There is an ongoing epidemic of thyroid cancer in the United States. The epidemiology of the increased incidence, however, suggests that it is not an epidemic of disease but rather an epidemic of diagnosis. The problem is particularly acute for women, who have lower autopsy prevalence of thyroid cancer than men but higher cancer detection rates by a 3:1 ratio.

Feb 2014: Article by Welch in JAMA Otolaryngology .Since 1975, the incidence of thyroid cancer has now nearly tripled, from 5 to 15 per 100,000 population mostly from papillary thyroid cancer. The ongoing epidemic of thyroid cancer in the United States “is not an epidemic of disease but rather an epidemic of diagnosis. The problem is particularly acute for women,”

Thyroid cancer reclassified- Encapsulated given Benign Label

5) It’s Not Cancer: Doctors Reclassify a Thyroid Tumor The New York Times By GINA KOLATA APRIL 14, 2016,

6) Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma A Paradigm Shift to Reduce Overtreatment of Indolent Tumors Jama Oncology 2016   YE Nikiforov, RR Seethala, G Tallini

Importance Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer.

7) Editorials – Thyroid Nodules: Is It Time to Turn Off the US Machines? by John J. Cronan, MD June 2008 Radiology, 247, 602-604.

8)  Durante C, Costante G, Lucisano G, et al. The Natural History of Benign Thyroid Nodules. JAMA. 2015;313(9):926-935.

Conclusions and Relevance: Among patients with asymptomatic, sonographically or cytologically benign thyroid nodules, the majority of nodules exhibited no significant size increase during 5 years of follow-up and thyroid cancer was rare. These findings support consideration of revision of current guideline recommendations for follow-up of asymptomatic thyroid nodules.

9) Header Image Courtesy of MP3XYZ

Link to this article:http://wp.me/p3gFbV-3Mp

Jeffrey Dach MD

7450 Griffin Road Suite 190

Davie, Fl 33314

954-792-4663

www.jeffreydachmd.com

http://www.drdach.com

http://www.naturalmedicine101.com

http://www.bioidenticalhormones101.com

http://www.truemedmd.com

The reader is advised to discuss the comments on these pages with his/her personal physicians and to only act upon the advice of his/her personal physician. Also note that concerning an answer which appears as an electronically posted question, I am NOT creating a physician — patient relationship. Although identities will remain confidential as much as possible, as I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur.

Copyright (c) 2016 Jeffrey Dach MD All Rights Reserved. This article may be reproduced on the internet without permission, provided there is a link to this page and proper credit is given.

FAIR USE NOTICE: This site contains copyrighted material the use of which has not always been specifically authorized by the copyright owner. We are making such material available in our efforts to advance understanding of issues of significance. We believe this constitutes a ‘fair use’ of any such copyrighted material as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, the material on this site is distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes.

Serving Areas of: Hollywood, Aventura, Miami, Fort Lauderdale, Pembroke Pines, Miramar, Davie, Coral Springs, Cooper City, Sunshine Ranches, Hallandale, Surfside, Miami Beach, Sunny Isles, Normandy Isles, Coral Gables, Hialeah, Golden Beach ,Kendall,sunrise, coral springs, parkland,pompano, boca raton, palm beach, weston, dania beach, tamarac, oakland park, boynton beach, delray,lake worth,wellington,plantation.

The post Alum Jax Cole Thyroid Cancer Epidemic of Overdiagnosis appeared first on Jeffrey Dach MD .

Steven A Rosenberg and Cancer Immunotherapy

Steven A Rosenberg MD and

Cancer Immunotherapy

This article is part one

For part two, Click Here

The Mouse That Was Immune to Cancer by Jeffrey Dach MD

Laboring tediously for hours on end, medical students inject cancer cells into mice, producing many publications in prestigious journals. Left Image Steven A Rosenberg MD PhD courtesy of OncLive.

Expecting the Unexpected



As you might expect, all the cancer injected mice died promptly from cancer.  All except one.  The unexpected happened.  This one mouse survived, and was renamed, “the mouse that killed cancer.”  As Luis Pasteur once said, chance favors the prepared mind.

Spontaneous Regression of Cancer in the Mouse



Once identified as a “cancer killing” mouse, the little furry fellow was earmarked for study. These were exciting times and there were many questions.  Why didn’t this mouse die of cancer like all the others?   How was this mouse able to defeat the injected cancer cells?   What kind of  immune system protected this mouse? Left Image: Laboratory Mouse courtesy of wikimedia commons.

Immune to Cancer

Over the next 3 years, studies showed this strain of mice had an innate immunity to cancer, a genetic trait passed on to the offspring.  In this strain the immune system which consisted of the T-Cells, the white blood cells recognize and kill cancer cells, just as if cancer was any other invading microorganism.  These mice were called SR/CR mice, which stands for  for Spontaneous Regression/Complete Resistant to Cancer.(2)

Saving All the Other Mice From Cancer

What about the other regular mice with no immunity to cancer which quickly succumb to the injected cancer cells?   Could these regular mice be protected from cancer by transferring the immune system from a SR/CR mouse?  What if we infused the T-Cells, the immune cells from a SR/CR mouse into a regular mouse?  These immune cells are the T-Cells, the white blood cells called macrophages.

These experiments were done showing, yes, this is correct.  Protection from the injected cancer cells could be transferred to regular mice transfused with white blood cells (macrophages) from SR/CR mice.(3) In addition, the protective SR/CR white cells could be stockpiled in cold storage, infused weeks later, and still retain activity.(4)

Human Mice – Spontaneous Regression of Cancer



What about us humans? Do we have a similar immunity to cancer, with some humans protected from cancer? Yes, and this is called spontaneous regression (remission) of cancer, which has been reported many times in the medical literature. Spontaneous regression can be seen in neuroblastoma, renal cell carcinoma, malignant melanoma and lymphomas/leukemias (see Papac RJ and Chodorowski Z). (5)(6)

The Legend of Sir William Osler – Spontaneous Regression

In 1901, Dr William Osler, a legendary and revered doctor reported 14 cases of breast cancer spontaneous remission.  (reference: The Medical Aspects of Carcinoma of the Breast, with a Note on the Spontaneous Disappearance of Secondary Growths OSLER W., American Medicine: April 6 1901; 17-19; 63-66.)

A study by Dr Gilbert Welch concluded that small breast cancers may spontaneously regress. Gina Kolata wrote a New York Times piece about it.  Spontaneous regression in the cancer patient is a victory of the immune system over the malignant potential of the cancer mass.  Left Image Sir William Osler 1912 courtesy of wikimedia.

Adoptive Immunotherapy – Dr Steven A Rosenberg NIH

Inspired by this SR/CR Mouse model in which cancer protection may be transferred from one animal to another,  Steven A Rosenberg MD at the National Cancer Institute, developed a cancer treatment using T-Cells infused into cancer patients.   He called this “Adoptive Cell Transfer Immunotherapy”  with remarkable results have been remarkable.(7)  

Dr Rosenberg ‘s treatment involves pre-treating the patient’s T lymphocytes to increase the anti-tumor activity.  The patient’s blood is drawn, the lymphocytes isolated, and then activated and cloned in a test tube.  These activated lymphocytes are then re-infused into the patient. This method is very effective for metastatic melanoma, producing tumor regression in 50% of patients in clinical trials.

See Rosenberg’s case images showing tumor regression (7). See Figure 2 from his article showing examples of tumor regression in patients receiving immune cells, lymphocytes (white cells).(7)

What’s in the Future? the CAR or Chimeric Antigen Receptor

What if we could re-engineer the patients immune cells,  the T-Lymphocytes, to recognize and attack surface antigens on the cancer cell?  Using modern biotechnology techniques this can be done.  The technique is called CAR, which stands for Chimeric Antigen Receptor.(8-12)

The most promising initial efforts using CAR have been directed at hematologic malignancies.  These are cancer cells arising from white blood cells, such as Leukemia and Lymphoma.  These cancer cells have well known surface antigens, the small proteins protruding from the cell surface which can then be recognized by receptors on the Killer T-Cell.(8-12)   As of 2014,  there have been 13 publications of clinical trials using CAR T cells for  treatment of B-cell malignancies targeting the CD19 or CD20 surface antigen.  These have, showing dramatic remissions in a number of patients with refractory B-cell lymphoma. (10)(12)  The CAR technique has also been tried in neuroblastoma, and sarcoma patients. (11)

This article is part one, for part TWO, Click Here

Articles with Related Interest:

Cancer as a Parasitic Disease

Ivermectin Anti-Parasitic Anti-Cancer Wonder Drug

Cancer as a Metabolic Disease.

Natural Treatments for Skin Cancer.

How Does Cannabis Kill Cancer Cells?

Nicholas Gonzalez MD and the Trophoblastic Theory of Cancer

Jeffrey Dach MD

7450 Griffin Road

Suite 180/190

Davie, Florida 33314

954-792-4663

www.jeffreydachmd.com

Links and References

(1) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC164507/

Proc Natl Acad Sci U S A. 2003 May 27; 100(11): 6682–6687.

Spontaneous regression of advanced cancer: Identification of a unique genetically determined, age-dependent trait in mice. Zheng Cui, Mark C. Willingham, Amy M. Hicks, Martha A. Alexander-Miller et al.

We have established and studied a colony of mice with a unique trait of host resistance to both ascites and solid cancers induced by transplantable cells. One dramatic manifestation of this trait is age-dependent spontaneous regression of advanced cancers. This powerful resistance segregates as a single-locus dominant trait, is independent of tumor burden, and is effective against cell lines from multiple types of cancer. During spontaneous regression or immediately after exposure, cancer cells provoke a massive infiltration of host leukocytes, which form aggregates and rosettes with tumor cells. The cytolytic destruction of cancer cells by innate leukocytes is rapid and specific without apparent damage to normal cells. The mice are healthy and cancer-free and have a normal life span. These observations suggest a previously unrecognized mechanism of immune surveillance, which may have potential for therapy or prevention of cancer.

(2) http://www.cancerimmunity.org/v6p11/060911.htm

Cancer Immunity, Vol. 6, p. 11 (31 October 2006) Submitted: 28 March 2006. Resubmitted: 17 July 2006. Accepted: 28 September 2006. Effector mechanisms of the anti-cancer immune responses of macrophages in SR/CR mice.

Amy M. Hicks et al. The killing of cancer cells in SR/CR mice requires three distinct phases. First, the leukocytes must migrate to the site of cancer cells after sensing their presence. Second, they must recognize the unique properties of the cancer cell surface and make tight contact with it. Third, the effector mechanisms must finally be delivered to target cells. The difference between SR/CR and WT mice seems to lie in one of the first two phases. Upon challenge with cancer cells, WT mice lack leukocyte infiltration and rosette formation. Apparently, the mutation in SR/CR mice renders the leukocytes capable of sensing unique diffusible and surface signals from cancer cells, and of responding to the activation signals by migration and physical contact. Once the first two phases are accomplished, unleashing the pre-existing effector mechanisms for killing seems to ensue by default. Therefore, the mutated gene (or genes) likely determines whether leukocytes interpret the signals from cancer cells as inhibition, as in WT leukocytes, or as activation of migration and target recognition, as in SR/CR leukocytes. Identifying the mutated gene (or genes) will likely explain this unique resistance to cancer through immunity.

(3) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1458507/?tool=pubmed

Proc Natl Acad Sci U S A. 2006 May 16; 103(20): 7753–7758. Immunology Transferable anticancer innate immunity in spontaneous regression/complete resistance mice. Amy M. Hicks et al.

(4) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2749872/?tool=pubmed

BMC Cancer. 2009; 9: 328. Impact of sex, MHC, and age of recipients on the therapeutic effect of transferred leukocytes from cancer-resistant SR/CR mice

John R Stehle, Jr,1 Michael J Blanks,2 Gregory Riedlinger,1,3 Jung W Kim-Shapiro,1 Anne M Sanders,1 Jonathan M Adams,1 Mark C Willingham,1 and Zheng Cui1

1Department of Pathology, Wake Forest University School of Medicine Winston-Salem, North Carolina 27157, USA

Abstract Background

Spontaneous Regression/Complete Resistant (SR/CR) mice are resistant to cancer through a mechanism that is mediated entirely by leukocytes of innate immunity. Transfer of leukocytes from SR/CR mice can confer cancer resistance in wild-type (WT) recipients in both preventative and therapeutic settings. In the current studies, we investigated factors that may impact the efficacy and functionality of SR/CR donor leukocytes in recipients.

Spontaneous regression of cancer in Humans

(5)http://www.ncbi.nlm.nih.gov/pubmed/9891219

In Vivo. 1998 Nov-Dec;12(6):571-8.

Spontaneous regression of cancer: possible mechanisms. Papac RJ.

Section of Medical Oncology, Yale University School of Medicine, New Haven, CT 06520, USA.

Spontaneous regression of cancer is reported in virtually all types of human cancer, although the greatest number of cases are reported in patients with neuroblastoma, renal cell carcinoma, malignant melanoma and lymhomas/leukemias. Study of patients with these diseases has provided most of the data regarding mechanisms of spontaneous regression. Mechanisms proposed for spontaneous regression of human cancer include: immune mediation, tumor inhibition by growth factors and/or cytokines, induction of differentiation, hormonal mediation, elimination of a carcinogen, tumor necrosis and/or angiogenesis inhibition, psychologic factors, apoptosis and epigenetic mechanisms. Clinical observations and laboratory studies support these concepts to a variable extent. The induction of spontaneous regression may involve multiple mechanisms in some cases although the end result is likely to be either differentiation or cell death. Elucidation of the process of spontaneous regression offers the possibility of improved methods of treating and preventing cancer.

(6) http://www.ncbi.nlm.nih.gov/pubmed/17724923

Przegl Lek. 2007;64(4-5):380-2.

[Spontaneous regression of cancer–review of cases from 1988 to 2006]

Chodorowski Z, Anand JS, Wiśniewski M, Madaliński M, Wierzba K, Wiśniewski J.

Katedra i Klinika Chorób Wewnetrznych, Geriatrii i Toksykologii Klinicznej, Akademii Medycznej w Gdańsku.

Spontaneous regression of malignant tumours is a rare and enigmatic phenomenon. We reviewed the cases of spontaneous regression of cancer in medical literature according to MEDLINE database in the period 1988-2006 and compared them with similar reviews from 1900-1987 period. The number of reported cases of spontaneous regression increased steadily in XX century, probably due to a rising interest in this problem and new possibilities of radiological and biopsy examinations. Spontaneous regression of malignancy was reported in almost all types of human cancer, although the greatest number of cases in years 1988-2006 were reported in patients with nephroblastoma, renal cell carcinoma, malignant melanoma, lymphoma. Elucidation of the process of spontaneous regression offers the possibility of improved methods of preventing andlor treating cancer.

Adoptive Cell Therapy ACT

(7) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2553205/?tool=pubmed

Nat Rev Cancer. 2008 April; 8(4): 299–308.

Adoptive cell transfer: a clinical path to effective cancer immunotherapy

Steven A. Rosenberg, Nicholas P. Restifo, James C. Yang, Richard A. Morgan, and Mark E. Dudley. Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892, USA.

Adoptive cell therapy (ACT) using autologous tumour-infiltrating lymphocytes has emerged as the most effective treatment for patients with metastatic melanoma and can mediate objective cancer regression in approximately 50% of patients. The use of donor lymphocytes for ACT is an effective treatment for immunosuppressed patients who develop post-transplant lymphomas. The ability to genetically engineer human lymphocytes and use them to mediate cancer regression in patients, which has recently been demonstrated, has opened possibilities for the extension of ACT immunotherapy to patients with a wide variety of cancer types and is a promising new approach to cancer treatment.

Figure 2

Examples of objective tumour regressions in patients receiving adoptive cell transfer of autologous anti-tumour lymphocytes following a lymphodepleting preparative regimen

In each case the pretreatment scans and photos are shown on the left and the post-treatment on the right. a | A 45-year-old male with metastatic melanoma to the liver (upper) and right adrenal gland (middle) who was refractory to prior treatment with high dose α interferon as well as high-dose interleukin 2 (IL2). He underwent a rapid regression of metastases and developed vitiligo (lower). b | A 55-year-old male with rapid tumour growth in the axilla as well as multiple brain metastases from metastatic melanoma that was refractory to prior treatment with high dose IL2 who underwent rapid regression of nodal and brain metastases.

The future of ACT

In contrast to common epithelial cancers, melanoma appears to be a tumour that naturally gives rise to anti-tumour T cells. However, other cancers are equally susceptible as the targets of reactive T cells. The susceptibility of melanoma to ACT provides optimism for the application of ACT to common epithelial cancers using TCR gene-modified lymphocytes.

A major problem with the application of ACT is that it is a highly personalized treatment and does not easily fit into current modes of oncological practice. The treatment is labour-intensive and requires laboratory expertise. In essence, a new reagent is created for each patient and this patient-specific nature of the treatment makes it difficult to commercialize. Pharmaceutical and biotechnology companies seek off-the-shelf drugs, easy to produce, vial and administer. From a regulatory standpoint, ACT might be more appropriately delivered as a service rather than as a ‘drug’. Blood banks have been instrumental in providing CD34+ haematopoietic stem cells for clinical studies and might be the ideal location for the generation of the anti-tumour T cells needed for ACT.

As modern science increasingly provides the physician with sophisticated information about the unique aspects of an individual cancer, changes in the modes of care delivery need to accommodate this. The ability to use this patient-specific information can lead to a new era of personalized medicine in which individual treatments, such as ACT, are devised for each patient.Studies of ACT have clearly demonstrated that the administration of highly avid anti-tumour T cells directed against a suitable target can mediate the regression of large, vascularized, metastatic cancers in humans and provide guiding principles as well as encouragement for the further development of immunotherapy for the treatment of patients with cancer.

8) Setting the Body’s ‘Serial Killers’ Loose on Cancer By ANDREW POLLACK AUG. 1, 2016 New York Times Dr. Steven Rosenberg, who turns 76 on Tuesday, still works nearly every day. “I want to end this holocaust,” he said of cancer. Chimeric antigen receptor (CAR) T-cell therapy

Antibody-modified T cells: CARs

10)  Maus, Marcela V., et al. “Antibody-modified T cells: CARs take the front seat for hematologic malignancies.” Blood 123.17 (2014): 2625-2635.

There are 14 publications reporting clinical trials of CAR T cells in hematologic malignancies. All but one of these focused on B-cell malignancies by targeting CD19 or CD20; the other focused on acute myeloid leukemia (AML) by targeting Lewis-Y antigen.

11)  Dai, Hanren, et al. “Chimeric antigen receptors modified T-cells for cancer therapy.” Journal of the National Cancer Institute 108.7 (2016): djv439.  The genetic modification and characterization of T-cells with chimeric antigen receptors (CARs) allow functionally distinct T-cell subsets to recognize specific tumor cells. The incorporation of costimulatory molecules or cytokines can enable engineered T-cells to eliminate tumor cells. CARs are generated by fusing the antigen-binding region of a monoclonal antibody (mAb) or other ligand to membrane-spanning and intracellular-signaling domains. They have recently shown clinical benefit in patients treated with CD19-directed autologous T-cells. Recent successes suggest that the modification of T-cells with CARs could be a powerful approach for developing safe and effective cancer therapeutics.

Adoptive immunotherapy for cancer has a long and somewhat checkered history; the first observations that immune system engagement had antitumor effects are commonly attributed to William Coley, who observed the regression of sarcoma following severe bacterial infections in the 1890s (1). However, the seminal finding that hematopoietic stem cell transplantation (HSCT) using syngeneic donors (from identical twin) was less effective at preventing relapse of leukemia compared with sibling donors provided the founding rationale for adoptive T-cell therapy (2). Additionally, the direct isolation and ex vivo activation of the tumor-infiltrating lymphocytes (TILs) was tested in multiple early-phase studies and resulted in durable responses in melanoma (3).

Recently, laboratory studies of chimeric antigen receptor (CAR)–specific T-cells have been viewed with exceptional interest for clinical development at an array of academic institutions. The redirection of T-cells to tumor antigens by expressing transgenic chimeric antigen receptors takes advantage of potent cellular effector mechanisms via human leukocyte antigen (HLA)–independent recognition. The potential of this approach has recently been demonstrated in clinical trials, wherein T-cells expressing CAR were infused into adult and pediatric patients with B-cell malignancies, neuroblastoma, and sarcoma (4–12).

12) free pdf

Almåsbak, Hilde, Tanja Aarvak, and Mohan C. Vemuri. “CAR T Cell Therapy: A Game Changer in Cancer Treatment.” Journal of Immunology Research 2016 (2016). Almåsbak Hilde CAR T Cell Therapy Game Changer Cancer Immunology Research 2016

The development of novel targeted therapies with acceptable safety profiles is critical to successful cancer outcomes with better survival rates. Immunotherapy offers promising opportunities with the potential to induce sustained remissions in patients with refractory disease. Recent dramatic clinical responses in trials with gene modified T cells expressing chimeric antigen receptors (CARs) in B-cell malignancies have generated great enthusiasm. This therapy might pave the way for a potential paradigm shift

in the way we treat refractory or relapsed cancers. CARs are genetically engineered receptors that combine the specific binding domains from a tumor targeting antibody with T cell signaling domains to allow specifically targeted antibody redirected T cell activation. Despite current successes in hematological cancers, we are only in the beginning of exploring the powerful potential of CAR redirected T cells in the control and elimination of resistant, metastatic, or recurrent nonhematological cancers. This review

discusses the application of the CAR T cell therapy, its challenges, and  strategies for successful clinical and commercial translation.

Years of successive and significant innovations have finally culminated in clinical studies demonstrating the tremendous potential of second generation CAR expressing T cells (Figure 1). Genetic redirection of patient T cells with

CARs targeting the B lymphocyte antigen CD19 has met with exceptional success in various therapy-refractory hematologic diseases (reviewed in [9]). Given their remarkable activity, CAR T cells are expected to enter the mainstream of health care for refractory or relapsed B-cell malignancies within few years and become the game changer for similar approaches in treating other cancers, such as solid tumors.

Jeffrey Dach MD

http://www.drdach.com/

http://www.naturalmedicine101.com/

http://www.truemedmd.com/

Disclaimer click here: http://www.drdach.com/wst_page20.html

The reader is advised to discuss the comments on these pages with his/her personal physicians and to only act upon the advice of his/her personal physician. Also note that concerning an answer which appears as an electronically posted question, I am NOT creating a physician — patient relationship. Although identities will remain confidential as much as possible, as I can not control the media,

I can not take responsibility for any breaches of confidentiality that may occur.

Link to this article: http://wp.me/P3gFbV-s1

Copyright (c) 2009-2013 Jeffrey Dach MD All Rights Reserved. This article may be reproduced on the internet without permission, provided there is a link to this page and proper credit is given.

FAIR USE NOTICE: This site contains copyrighted material the use of which has not always been specifically authorized by the copyright owner. We are making such material available in our efforts to advance understanding of issues of significance. We believe this constitutes a ‘fair use’ of any such copyrighted material as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, the material on this site is distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes.

The post Steven A Rosenberg and Cancer Immunotherapy appeared first on Jeffrey Dach MD .

Menopause Accelerates Aging New Study

Two UCLA Studies Show Menopause Accelerates Aging

A new study by Dr Morgan E. Levine from UCLA in PNAS shows that  menopause accelerates aging. (1)  A second study by Dr Judith Carroll from UCLA reported in  Biological Psychiatry that “insomnia symptoms are implicated in accelerated aging”.(2)  Insomnia is a frequent menopausal symptom, along with other typical symptoms of hot flashes, night sweats,  vaginal dryness, and loss of libido, etc.(3)  Left Image Girl Before A Mirror courtesy of PabloPicasso.org

Menopause Accelerates Early Mortality

These two studies also show that menopause is associated with increased aging-related diseases and early mortality.(4,5,6)  Acceleration of mortality after menopause had been reported 20 years ago.   Dr Shiro Horiuchi reported in 1997 that “mortality data from seven industrialized countries have shown postmenopausal mortality acceleration clearly”. (6)

Menopause and Skin Aging

According to Dr Julie Thornton in her 2013 article,  menopause causes estrogen deficiency, and accelerated aging, or deterioration of the skin, all of which are delayed or prevented by estrogen administration.(14)  Many other doctors have reported similar opinions.(15-18)

Longer Telomere Length in Women on Estrogen HRT

The telomere theory of aging states that the telomeres on the ends of our chromosomes shorten as we age.  Aging can be prevented or reverse by lengthening telomeres.  Dr Lee reported in 2005 that “post-menopausal long-term estrogen therapy lengthened telomeres” thus slowing and reversing the aging process.(9) Left Image Aging Woman in mirror courtesy of Mirror UK.

Estrogen HRT Prevents Bone Loss

Dr David Felson reported in NEJM 1993, estrogen therapy prevents bone loss in post menopausal women.(10)  For this reason, estrogen therapy was recommended.(10)

Estrogen Prevents Coronary Artery Disease in Postmenopausal Women

Dr Grodstein et al reported in 2006 that estrogen hormone replacement, early after menopause prevented coronary artery disease.(11)

Estrogen HRT Prevents Menopausal Arthritis

Dr Russell Cecil reported in 1925 fifty cases of Arthritis after menopause (12)  In 2013 Dr Rowan Chlebowski confirmed these findings with his report on “Estrogen alone and joint symptoms in the Women’s Health Initiative randomized trial.”   Post menopausal women on estrogen replacement had significantly less joint pain than the placebo group.(13)

Estrogen Protects the Brain

A large body of studies show that estrogen is protective of the brain in the context of aging, cognitive function, cerebrovascular insult, and head trauma. (19-21)

Conclusion: Bioidentical Hormones Prevent Aging and Reduce Mortality:

Estrogen deficiency related to Menopause is associated with accelerated aging and early mortality, findings which can be prevented and reversed with bioidentical hormone therapy.  Our program includes a robust cocktail of all female hormones including  estrogen,  progesterone, testosterone, all with identical chemical structures to those that occur naturally in the female body.

Articles with Related Interest

Estrogen Prevents Menopausal Arthritis

Estrogen Prevents Heart Disease

Estrogen HRT Could Have Saved 50,000 Lives

Estrogen, Telomere Length and Aging

Jeffrey Dach MD

7450 Griffin Road Suite 190

Davie, Fl 33314

954-792-4663

References and Links

1) http://www.pnas.org/content/early/2016/07/20/1604558113.short

Morgan E. Levine, Ake T. Lu, Brian H. Chen, Dena G. Hernandez, Andrew B. Singleton, Luigi Ferrucci, Stefania Bandinelli, Elias Salfati, JoAnn E. Manson, Austin Quach, Cynthia D. J. Kusters, Diana Kuh, Andrew Wong, Andrew E. Teschendorff, Martin Widschwendter, Beate R. Ritz, Devin Absher, Themistocles L. Assimes, and Steve Horvath. Menopause accelerates biological aging. PNAS, July 2016 DOI: 10.1073/pnas.1604558113

Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the “epigenetic clock”), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women’s Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson’s disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further.

Insomnia and Menopause

2)  Carroll, Judith E., et al. “Epigenetic aging and immune senescence in women with insomnia symptoms: Findings from the Women’s Health Initiative Study.” Biological Psychiatry (2016).

In this large population based study of women in the United States, insomnia symptoms are implicated in accelerated aging.

3)

A prospective population-based study of menopausal symptoms.

Obstet Gynecol. 2000 Sep;96(3):351-8. Dennerstein L1, Dudley EC, Hopper JL, Guthrie JR, Burger HG.

To identify symptoms that change in prevalence and severity during midlife and evaluate their relationships to menopausal status, hormonal levels, and other factors.

METHODS: In a longitudinal, population-based study of 438 Australian-born women observed for 7 years with an 89% retention rate, 172 advanced from premenopause to perimenopause or postmenopause. Annual measures included a 33-item symptom check list; psychosocial, lifestyle, and health-related factors; menstrual status; hormone usage; and blood levels of follicle-stimulating hormone and estradiol (E2).

RESULTS: Increasing from early to late perimenopause were the number of women who reported five or more symptoms (+14%), hot flushes (+27%), night sweats (+17%) and vaginal dryness (+17%) (all P Trouble sleeping increased by +6%. The major change in prevalence was from early to late perimenopause, except for insomnia, which showed a gradual increase. Those variables most related to onset of hot flushes were number of symptoms at early perimenopause (P

CONCLUSION: Although middle-aged women are highly symptomatic, the symptoms that appear to be specifically related to hormonal changes of menopausal transition are vasomotor symptoms, vaginal dryness, and breast tenderness. Insomnia reflected bothersome hot flushes and psychosocial factors.

4) http://time.com/4422860/menopause-accelerates-aging/

Menopause Makes Your Body Age Faster by Alice Park  Time Magazine July 25, 2016 .   The hormone loss that accompanies years after menopause may accelerate aging in the body

5) http://newsroom.ucla.edu/releases/menopause-sleepless-nights-may-make-women-age-faster

Menopause, sleepless nights may make women age faster.

Two UCLA studies show menopause, insomnia could increase women’s risk for aging-related diseases by Elaine Schmidt and Mark Wheeler | July 25, 2016

In a pair of studies published today UCLA researchers report that menopause accelerates biological aging and that insomnia, which often accompanies menopause, also has a clear association with age acceleration.

The dual findings suggest both factors could increase women’s risk for aging-related diseases and earlier death. The two studies, published in separate journals, contribute to increasing evidence of the biological clock’s variability.

free full pdf

6) Horiuchi, Shiro. “Postmenopausal acceleration of age-related mortality increase.” The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 52.1 (1997): B78-B92.

It is thus expected that menopause should trigger an acceleration of age-related mortality increase in human females.  Life table aging rate patterns for selected industrialized countries generally support this hypothesis. A cause-of-death decomposition analysis indicates that the sex differential in mortality acceleration is mainly due to cardiovascular diseases.  Mortality data from seven industrialized countries have shown postmenopausal mortality acceleration clearly,

7) free pdf

Bromberger, Joyce T., et al. “Prospective study of the determinants of age at menopause.” American journal of epidemiology 145.2 (1997): 124-133.

8) Leidy, L. E. “Biological aspects of menopause: across the lifespan.” Annual Review of Anthropology (1994): 231-253.

Longer telomere length in women on HRT



9)  http://synapse.koreamed.org/DOIx.php?id=10.3349/ymj.2005.46.4.471

Lee, Duk-Chul, et al. “Effect of long-term hormone therapy on telomere length in postmenopausal women.” Yonsei medical journal 46.4 (2005): 471-479.

Telomeres undergo attrition with each cell division, and telomere length is associated with age-related diseases and mortality in the elderly. Estrogen can influence the attrition of telomeres by diverse mechanisms. This is a retrospective case control study that investigated the influence of long-term hormone therapy (HT) on telomere length in postmenopausal women. We recruited 130 postmenopausal women from 55 to 69 years of age for this study, and divided them into two groups. The first group included 65 women who had been on estrogen and progesterone therapy for more than five years (HT group). The other group was composed of 65 women matched in age to the HT group who had never had HT (non-HT group). The relative ratios of telomere length of study subjects to a reference DNA from a healthy young female were measured using quantitative PCR. Plasma levels of lipid profiles, total antioxidant status (TAS), C-reactive proteins (CRP), fasting glucose levels, and estradiol levels were measured. Age at menopause, vitamin use, and exercise, alcohol, and cigarette smoking histories were also assessed in a questionnaire. Mean duration (± SD) of HT was 8.4 ± 2.3 years. Prevalence of vitamin use and regular exercise were higher in the HT group than in the non-HT group (pLong-term HT in postmenopausal women may alleviate telomere attrition.

Bone Density after Menopause

10) http://www.nejm.org/doi/full/10.1056/NEJM199310143291601

Felson, David T., et al. “The effect of postmenopausal estrogen therapy on bone density in elderly women.” New England Journal of Medicine 329.16 (1993): 1141-1146.

Estrogen therapy prevents bone loss in postmenopausal women who take it early in the postmenopausal period. The risk of fracture is highest much later in life, however. We studied whether bone mass in elderly women was affected by earlier estrogen use and how long women needed to take estrogen for it to have a beneficial effect on bone density later in life.

METHODS:  In 1988 and 1989, we measured bone mineral density at the femur, spine, shaft of the radius, and ultradistal radius in 670 white women in the Framingham Study cohort (mean age, 76 years; range, 68 to 96). These women had been followed prospectively through menopause and had been asked repeatedly about estrogen therapy. After excluding women who began taking estrogen after a fracture, we investigated whether postmenopausal estrogen therapy affected bone density; in these analyses we adjusted for age, weight, height, cigarette smoking, physical activity, and age at menopause.

RESULTS:  A total of 212 women (31.6 percent) had received estrogen therapy (mean estimated duration of treatment, 5 years). Only women who had taken estrogen for 7 to 9 years or for 10 or more years had significantly higher bone mineral density than women who had not taken estrogen (7 to 9 years of treatment, P < 0.05 at sites in the femur and the spine; > or = 10 years, P < 0.05 at all sites except the spine). In the women less than 75 years of age who had taken estrogen for seven or more years, the bone density was, averaging all sites, 11.2 percent greater than in women who had never received estrogen. Among women 75 years of age and older in whom the duration of therapy was comparable, bone density was only 3.2 percent higher than in women who had never taken estrogen.

CONCLUSIONS:  For long-term preservation of bone mineral density, women should take estrogen for at least seven years after menopause. Even this duration of therapy may have little residual effect on bone density among women 75 years of age and older, who have the highest risk of fracture.

HRT prevents Heart Disease After Menopause

11) http://www.ncbi.nlm.nih.gov/pubmed/16417416

http://online.liebertpub.com/doi/abs/10.1089/jwh.2006.15.35

J Womens Health (Larchmt). 2006 Jan-Feb;15(1):35-44.

Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation.

Grodstein F1, Manson JE, Stampfer MJ.

Apparently discrepant findings have been reported by the Women’s Health Initiative (WHI) trial compared with observational studies of postmenopausal hormone therapy (HT) and coronary heart disease (CHD).

METHODS: We prospectively examined the relation of HT to CHD, according to timing of hormone initiation relative to age and time since menopause. Participants were postmenopausal women in the Nurses’ Health Study, with follow-up from 1976 to 2000. Information on hormone use was ascertained in biennial, mailed questionnaires. We used proportional hazards models to calculate multivariable adjusted relative risks (RR) and 95% confidence intervals (CI). We also conducted sensitivity analyses to determine the possible influence of incomplete capture of coronary events occurring shortly after initiation of HT.

RESULTS:  Women beginning HT near menopause had a significantly reduced risk of CHD (RR = 0.66, 95% CI 0.54-0.80 for estrogen alone; RR = 0.72, 95% CI 0.56-0.92 for estrogen with progestin). In the subgroup of women demographically similar to those in the WHI, we found no significant relation between HT and CHD among women who initiated therapy at least 10 years after menopause (RR = 0.87, 95% CI 0.69-1.10 for estrogen alone; RR = 0.90, 95% CI 0.62-1.29 for estrogen with progestin). Among women who began taking hormones at older ages, we also found no relation between current use of estrogen alone and CHD (for women aged 60+ years, RR = 1.07, 95% CI 0.65-1.78), although there was a suggestion of possible reduced risk for combined HT (RR = 0.65, 95% CI 0.31-1.38). In sensitivity analyses, we found that the incomplete capture of coronary events occurring shortly after initiation of HT could not explain our observation of a reduced risk of coronary disease for current users of HT.

CONCLUSIONS:  These data support the possibility that timing of HT initiation in relation to menopause onset or to age might influence coronary risk.

Arthritis After Menopause

12) http://jama.jamanetwork.com/article.aspx?articleid=1151859

CECIL, RUSSELL L., and Benjamin H. Archer. “Arthritis of the menopause: a study of fifty cases.” Journal of the American Medical Association 84.2 (1925): 75-79.

WHI Study

13) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855295/

Estrogen Alone and Joint Symptoms in the Women’s Health Initiative Randomized Trial

Chlebowski, Rowan T., et al. “Estrogen alone and joint symptoms in the Women’s Health Initiative randomized trial.” Menopause (New York, NY) 20.6 (2013).

While joint symptoms are commonly reported after menopause, observational studies examining exogenous estrogen influence on joint symptoms provide mixed results. Against this background, estrogen alone effects on joint symptoms were examined in post hoc analyses in the Women’s Health Initiative randomized, placebo-controlled clinical trial.

Methods  10,739 postmenopausal women with prior hysterectomy were randomized to receive daily oral conjugated equine estrogen (0.625 mg/d) or matching placebo. The frequency and severity of joint pain and joint swelling were assessed by questionnaire at entry and year 1 from all participants and in a random 9.9% subsample (n=1062) following years 3 and 6. Logistic regression models were used to compare frequency and severity of symptoms by randomization group. Sensitivity analyses evaluated adherence influence on symptoms.

Results   At baseline, joint pain and swelling were closely comparable in the randomization groups (about 77% with joint pain and 40% with joint swelling). After one year, joint pain frequency was significantly lower in the estrogen alone compared to the placebo group (76.3% vs 79.2%, P=0.001) as was joint pain severity and the difference in pain between randomization groups persisted through year 3. However, joint swelling frequency was higher in the estrogen alone group (42.1% vs 39.7%, P=0.02). Adherence adjusted analyses strengthen the estrogen association with reduced joint pain but attenuated the estrogen association with increased joint swelling.

Conclusions  The current findings suggest that estrogen alone use in postmenopausal women results in a modest but sustained reduction in the frequency of joint pain

skin aging estrogen

14)  Thornton, M. Julie. “Estrogens and aging skin.” Dermato-endocrinology 5.2 (2013): 264-270.

The menopause causes hypoestrogenism, accelerating age-related deterioration of the skin. Estrogen administration has positive effects on human skin by delaying or preventing skin aging manifestations,

15) Stevenson, Susan, and Julie Thornton. “Effect of estrogens on skin aging and the potential role of SERMs.” Clinical interventions in aging 2.3 (2007): 283.

Hormone replacement therapy (HRT) has been shown to increase epidermal hydration, skin elasticity, skin thickness (Sator et al 2001), and also reduces skin wrinkles

Post-menopausal skin has been shown to have increased dryness (Sator et al 2004), decreased elasticity (Henry et al 1997; Sumino et al 2004), and increased wrinkling (Dunn et al 1997).

16) Wend, Korinna, Peter Wend, and Susan A. Krum. “Tissue-specific effects of loss of estrogen during menopause and aging.” Frontiers in endocrinology 3 (2012): 19.

a number of studies have established an essential function of E2 in skin biology. Therefore, E2 may offer an appropriate treatment option to prevent or delay age-associated alterations of the skin by affecting dermal fibroblasts, epidermal keratinocytes, or hair follicles.

17) Emmerson, Elaine, and Matthew J. Hardman. “The role of estrogen deficiency in skin ageing and wound healing.” Biogerontology 13.1 (2012): 3-20.

18) Verdier‐Sévrain, Sylvie, Frederic Bonte, and Barbara Gilchrest. “Biology of estrogens in skin: implications for skin aging.” Experimental dermatology 15.2 (2006): 83-94.

Estrogen and Neuroprotection

19)  Engler-Chiurazzi, E. B., M. Singh, and J. W. Simpkins. “From the 90׳ s to now: A brief historical perspective on more than two decades of estrogen neuroprotection.” Brain research 1633 (2016): 96.

neuroprotective actions of estrogen, and specifically 17β-estradiol, identified by early investigations, remain well-documented.

Preliminary investigations suggested that estrogen-containing therapies typically given for the management of disruptive menopausal symptoms could reduce AD risk, attenuate disease-associated cognitive deficits, and modulate brain substrates known to be dysregulated by the condition, such as the cholingeric system.

20)  Engler-Chiurazzi, E. B., et al. “Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury.” Progress in neurobiology (2016).

Here we provide a summary of the biological actions of estrogen and estrogen-containing formulations in the context of aging, cognition, stroke, and traumatic brain injury.

21)  Chakrabarti, Mrinmay, et al. “Estrogen receptor agonists for attenuation of neuroinflammation and neurodegeneration.” Brain research bulletin 109 (2014): 22-31.

link to this article: http://wp.me/p3gFbV-3KS

Jeffrey Dach MD

7450 Griffin Road Suite 190

Davie, Fl 33314

954-792-4663

www.jeffreydachmd.com

http://www.drdach.com

http://www.naturalmedicine101.com

http://www.bioidenticalhormones101.com

http://www.truemedmd.com

The reader is advised to discuss the comments on these pages with his/her personal physicians and to only act upon the advice of his/her personal physician. Also note that concerning an answer which appears as an electronically posted question, I am NOT creating a physician — patient relationship. Although identities will remain confidential as much as possible, as I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur.

Copyright (c) 2016 Jeffrey Dach MD All Rights Reserved. This article may be reproduced on the internet without permission, provided there is a link to this page and proper credit is given.

FAIR USE NOTICE: This site contains copyrighted material the use of which has not always been specifically authorized by the copyright owner. We are making such material available in our efforts to advance understanding of issues of significance. We believe this constitutes a ‘fair use’ of any such copyrighted material as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, the material on this site is distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes.

Serving Areas of: Hollywood, Aventura, Miami, Fort Lauderdale, Pembroke Pines, Miramar, Davie, Coral Springs, Cooper City, Sunshine Ranches, Hallandale, Surfside, Miami Beach, Sunny Isles, Normandy Isles, Coral Gables, Hialeah, Golden Beach ,Kendall,sunrise, coral springs, parkland,pompano, boca raton, palm beach, weston, dania beach, tamarac, oakland park, boynton beach, delray,lake worth,wellington,plantation.

The post Menopause Accelerates Aging New Study appeared first on Jeffrey Dach MD .

Defending the Cholesterol Hypothesis in the Elderly

Defending the Cholesterol Hypothesis in the Elderly

by Jeffrey Dach MD

Med Page Today ran an article by cardiologist Larry Husten, defending the cholesterol theory of heart disease entitled “Cholesterol Skeptics Launch Another Attack”. (1)(10)  Left Image Medpage Today Logo courtesy of Medpage Today.

Dr Husten is responding to an article published in British Medical Journal by Dr Uffe Ravnskov (left image) in which a number of previously published studies contradict the cholesterol theory by showing an “Inverse association between low-density-lipoprotein (LDL) cholesterol and mortality in the elderly”.(2) 

In other words,  higher serum cholesterol in the elderly is associated with decreased mortality.   This directly contradicts the cholesterol theory which states that higher cholesterol should increase mortality from heart disease.  In the elderly, it doesn’t work this way.  Old people tend to live longer if they have a higher serum cholesterol.  Low serum cholesterol in the elderly is a marker for increased mortality.

Cholesterol Theory has Been Falsified

Current accepted dogma proposes cholesterol as the cause of  atherosclerotic plaque, and therefore, reduction of serum cholesterol with a statin drug (left image)  should prevent coronary artery disease. Quite to the contrary, the cholesterol theory has been falsified. According to Dr. William R Ware, there is no correlation between serum cholesterol and the amount of atherosclerotic plaque when reviewing either autopsy studies or coronary calcium score studies.(5)

The lack of relationship between serum cholesterol and calcium score was reported by Dr. Hecht who says:

”There were no significant differences in the calcium scores throughout the entire range of all lipid parameters; calcium percentiles were virtually identical within lipid value subgroups.”(6)

More than a dozen studies show low cholesterol in the elderly is a marker for increased mortality, not improved survival.  In women, cholesterol lowering drugs should not be used as they do not improve survival and do not improve health.

Also, in selected medical conditions such as congestive heart failure, haemodialysis, chronic obstructive pulmonary disease (COPD), as in the elderly, higher cholesterol is associated with improved survival, and lower cholesterol with increased mortality.(9) Left Image advertising for the cholesterol theory of heart disease, creating irrational fear .  This has been falsified.

Conclusion:  Med Page Today cardiologist Larry Husten’s misplaced enthusiasm defending the cholesterol theory of heart disease is a sad commentary on the state of cardiology today.  By now, the published data is overwhelming that the cholesterol theory of heart disease has been falsified.

Jeffrey Dach MD

Articles with related Interest:

Low Level Endotoxemia Coronary Artery Disease

Getting Off Statin Drug Stories

The Art of the Curbside Cholesterol Consult

Cholesterol Lowering Drugs in the Elderly, Bad Idea

Cholesterol Lowering Drugs For Women, Just Say No.

Links and References:

1) CardioBrief: Cholesterol Skeptics Launch Another Attack

But most experts say new study is highly flawed by Larry Husten Cardiologist

Michael Blaha, MD, MPH, also of Johns Hopkins, said that he agrees with the authors that LDL by itself is a poor marker of risk in the elderly

According to Blaha, the fact that the role of LDL diminishes with age “has been known for a long time — and in fact is baked into equations like the Framingham Risk Score and the Pooled Cohort Equations.” One reason is that “cumulative exposure to high cholesterol is likely what matters most, thus very high LDL matters more in younger patients, while late-life elevation matters very little.”

In addition, Blaha said, “one must also account for survival bias in these studies,” as the older patients with high LDL are a selected group.

2) BMJ Open 2016;6:e010401 doi:10.1136/bmjopen-2015-010401

Cardiovascular medicine

Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review

Uffe Ravnskov1, David M Diamond2, Rokura Hama3, Tomohito Hamazaki4, Björn Hammarskjöld5, Niamh Hynes6, Malcolm Kendrick7, Peter H Langsjoen8, Aseem Malhotra9, Luca Mascitelli10, Kilmer S McCully11, Yoichi Ogushi12, Harumi Okuyama13, Paul J Rosch14, Tore Schersten15, Sherif Sultan6, Ralf Sundberg16

Abstract

Objective It is well known that total cholesterol becomes less of a risk factor or not at all for all-cause and cardiovascular (CV) mortality with increasing age, but as little is known as to whether low-density lipoprotein cholesterol (LDL-C), one component of total cholesterol, is associated with mortality in the elderly, we decided to investigate this issue.

Setting, participants and outcome measures We sought PubMed for cohort studies, where LDL-C had been investigated as a risk factor for all-cause and/or CV mortality in individuals ≥60 years from the general population.

Results We identified 19 cohort studies including 30 cohorts with a total of 68 094 elderly people, where all-cause mortality was recorded in 28 cohorts and CV mortality in 9 cohorts. Inverse association between all-cause mortality and LDL-C was seen in 16 cohorts (in 14 with statistical significance) representing 92% of the number of participants, where this association was recorded. In the rest, no association was found. In two cohorts, CV mortality was highest in the lowest LDL-C quartile and with statistical significance; in seven cohorts, no association was found.

Conclusions High LDL-C is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.

3) Uffe Ravnskov The Cholesterol Myths by UffeRavnskov, MD, PhD

4) THINCS For decades, enormous human and financial resources have been wasted on the cholesterol campaign, more promising research areas have been neglected, producers and manufacturers of animal food all over the world have suffered economically, and millions of healthy people have been frightened and badgered into eating a tedious and flavorless diet or into taking potentially dangerous drugs for the rest of their lives. As the scientific evidence in support of the cholesterol campaign is non-existent, we consider it important to stop it as soon as possible.

The International Network of Cholesterol Skeptics (THINCS) is a steadily growing group of scientists, physicians, other academicians and science writers from various countries. Members of this group represent different views about the causation of atherosclerosis and cardiovascular disease, some of them are in conflict with others, but this is a normal part of science. What we all oppose is that animal fat and high cholesterol play a role. The aim with this website is to inform our colleagues and the public that this idea is not supported by scientific evidence; in fact, for many years a huge number of scientific studies have directly contradicted it.

5) Ware WR. The mainstream hypothesis that LDL cholesterol drives atherosclerosis may have been falsified by non-invasive imaging of coronary artery plaque burden and progression. Med Hypotheses. 2009;73(4):596-600.  cholesterol atherosclerosis falsified coronary artery plaque Ware Medical Hypotheses 2009

6) Hecht HS, Superko HR, Smith LK, McColgan BP. Relation of coronary artery calcium identified by electron beam tomography to serum lipoprotein levels and implications for treatment. Am J Cardiol. 2001;87(4):406-12.

7) Ravnskov U, McCully KS. Biofilms, lipoprotein aggregates, homocysteine, and arterial plaque rupture. MBio. 2014;5(5):e01717-14.Biofilms Arterial Plaque Rupture Ravnskov Uffe Kilmer McCully 2014

8) Ravnskov U, McCully KS. Infections may be causal in the pathogenesis of atherosclerosis. Am J Med Sci. 2012;344(5):391-4.  Infections May be Causal in the Pathogenesis of Atherosclerosis Ravnskov McCully 2012

9) Sandek A., Utchill S, Rauchhaus M. The endotoxin-lipoprotein hypothesis-an update. Arch Med Sci. 2007;3(4A):S81.   The endotoxin lipoprotein hypothesis Anja Sandek 2007

10)  CEBM response: “Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review” – a post publication peer review

Here we provide a post publication critical appraisal of the methodology and evidence used to support the findings from the Ravnskov et al paper.

Therefore their search strategy and reporting thereof presents a high risk of bias for missing important and relevant studies.

link to this article: http://wp.me/p3gFbV-3JT

Jeffrey Dach MD

7450 Griffin Road Suite 190

Davie, Fl 33314

954-792-4663

www.jeffreydachmd.com

http://www.drdach.com

http://www.naturalmedicine101.com

http://www.truemedmd.com

Disclaimer click here: http://www.drdach.com/wst_page20.html

The reader is advised to discuss the comments on these pages with his/her personal physicians and to only act upon the advice of his/her personal physician. Also note that concerning an answer which appears as an electronically posted question, I am NOT creating a physician — patient relationship. Although identities will remain confidential as much as possible, as I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur.

Copyright (c) 2016 Jeffrey Dach MD All Rights Reserved. This article may be reproduced on the internet without permission, provided there is a link to this page and proper credit is given.

FAIR USE NOTICE: This site contains copyrighted material the use of which has not always been specifically authorized by the copyright owner. We are making such material available in our efforts to advance understanding of issues of significance. We believe this constitutes a ‘fair use’ of any such copyrighted material as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, the material on this site is distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes.

Serving Areas of: Hollywood, Aventura, Miami, Fort Lauderdale, Pembroke Pines, Miramar, Davie, Coral Springs, Cooper City, Sunshine Ranches, Hallandale, Surfside, Miami Beach, Sunny Isles, Normandy Isles, Coral Gables, Hialeah, Golden Beach ,Kendall,sunrise, coral springs, parkland,pompano, boca raton, palm beach, weston, dania beach, tamarac, oakland park, boynton beach, delray,lake worth,wellington,plantation.

The post Defending the Cholesterol Hypothesis in the Elderly appeared first on Jeffrey Dach MD .

GMO Food Fight on Senate Floor

GMO Food Fight on Floor of Senate

Setting the Record Straight

When it comes to debate among members of the Senate, we think of the great orators of antiquity such as Ancient Greece and Rome.  These were the intellectual giants who inspired us to greatness and made possible great civilizations .  Left Image Sen, Heidi Heitkamp (D) official portrait courtesy of wikimedia.

However, in the matter of the recent GMO label Senate debate recorded on CSPAN, I was surprised to find a much different level of discourse.   I invite you to listen to the presentation by Senator Heidi Heitkamp, Democrat from North Dakota:

Senator Heitkamp urges the members to

“Stop denying science and accept the fact that GMO ingredients are just as healthy as any other ingredient.”

In all due respect, I have a few questions for Senator Heidi Heitkamp:

1) If GMO ingredients are so healthy, then why has Russia, Japan, China and 60 other countries banned or restricted GMO production in their countries.(16-19)  Why has Europe rejected GMO food, with no GMO products on store shelves in Europe?(26)

2) If GMO food is so healthy, why did the International Agency for Research on Cancer (IARC), the specialized cancer agency of the World Health Organization classify Glyphosate as a “probable carcinogen” on  March 2015?(37)   Glyphosate is Monsanto’s Round-Up Herbicide, applied in great quantities to GMO Corn and Soy.  Glyphosate is also copiously applied to wheat fields and other crops as a pre-harvest drying agent.

3) If GMO ingredients are so healthy for us, then why did the American Academy of Environmental Medicine (AAEM) release a position paper in 2009 on Genetically Modified foods stating that “GM foods pose a serious health risk” and calling for a moratorium on GM foods? (44)

4) If GMO ingredients are so healthy, why did the US courts rule in 2004 that GMO food is a “public nuisance” ?(39-41)  August 2004, Aventis settled a class-action lawsuit and paid farmers 110 million dollars for genetic contamination of farmers fields with the Aventis Starlink Corn. A separate settlement paid 9 million dollars to consumers who had heath problems from consuming the genetically modified Starlink corn. The courts considered the GMO Starlink Corn a “public nuisance”.(39-41)

Heidi Heitjkamp’s remarks continued:

“It’s critically important that we set the record straight on genetically modified ingredients, and we make sure everyone in our country understands the science of what we have been doing over centuries of work in growing more resilient and better yield crops. And we wouldn’t be able to do that in America today, or across the world without genetics, without looking at applying science to the work we do in agriculture. Agricultural Innovation has saved lives. I want to remind everyone about a great American Hero, Nobel peace prize laureate, Norman Borlaug,  He is thought of as the forefather of modern biotechnology.  Because of his innovation, he is known as the man who saved a billion lives.  His wheat breeding work created a wheat which enabled increased production and revolutionizing farming in America and across the world.  As he saved countless lives, he sparked the Green Revolution. And that is why we know that biotechnlogy isn’t just good for farmers.  It increases and stabilizes yields and fights against crop pests and disease.

With due respect, I have a few questions and clarifications about the good Senator’s reference to Normal Borlaug.

Yes, it is true that Norman Borlaug is a hero who saved a billion lives from starvation with his high yield semi-dwarf wheat which has revolutionized agriculture.   Left Image: Norman Borlaug in wheat field in Mexico cover of LIFE Magazine Nov 1970, courtesy of Time/Life Magazine. Borlaug received the Nobel Prize for his semi-dwarf high yield wheat which averted global famine, literally saving 3 billion lives.

However, since Borlaug’s work in the 1960’s came before the advent of biotechnology, Borlaug used existing hybridization techniques, and his wheat is not a GMO product.   Since Borlaug’s wheat is not a GMO product, using the Borlaug example to laud GMO Food is a deceptive and misleading tactic.  The other possibility is the speaker has a limited understanding of her subject matter.

The real problem we face with our wheat is not the wheat itself which is non-GMO, it is the massive amounts of the glyphosate herbicide applied as a pre-harvest drying agent which ends up in the final food which we all eat.  Glyphosate has been labeled a “probable carcinogen”  by the World Health Organization (WHO).(37)

Senator Heidi Heitkamp continues her remarks:

“Agricultural biotechnology is also great for consumers, not just in stabilizing or reducing prices, but it can literally save lives, like the Golden Rice can. Just last week, over 100 Nobel laureates wrote to dispute claims involving Golden Rice and to talk about how important those innovations were to saving populations from blindness and from disease.”  Left image Inventor of Golden Rice,  Ingo Potrykus on cover of Time Magazine July 2000.

In all due respect, I have a question about Senator Heitkamp’s remarks about Golden Rice.  The good Senator’s remarks gives the impression that Golden Rice has saved populations from blindness and disease.

There is nothing farther from the truth.  Golden Rice, which is rice genetically modified to contain Beta Carotene, a vitamin A precursor, was invented and donated to the public domain by Ingo Potrykus almost 20 years ago, and has yet to undergo basic toxicology testing in animals.  With lack of safety testing, Golden Rice has never been approved here in the US, or by any other government for human consumption.(46)  If found safe after extensive testing, and approved for human use, would Golden Rice provide Beta Carotene to poor starving children, thus preventing vitamin A deficiency diseases?  Maybe so.  We may never know.  A cheaper, more effective and certainly less risky approach to preventing vitamin A deficiency diseases is to hand out vitamin A capsules to the population at risk, or teach the population how to grow many of indigenous foods containing beta carotene such as mango, and sweet potato.   According to Robert Greer in,  We Don’t Need Golden Rice: (14)

Fruit and root crops rich in Vitamin A are plentiful in every heavily-populated bioregion in the world.  Mangoes, oranges, yams, squash, papaya, watermelons, and cantaloupes are all rich in Vitamin A, and these crops typically produce yields that rival or surpass GMO rice.(14)

Senator Heitkamp remarks continue:

“And so, if we really are concerned about science, let’s start talking about science, and lets start realizing that in no place has there ever been a study that said these ingredients, GMO inputs, are bad for consumers, or in any way injure our livelihood,  or our health.”   …”The bottom line is this technology is safe, and we have nothing to hide.” (This is a partial transcript of her talk)

Left Image: March Against Monsanto Vancouver  May 2013 Courtesy of Wikimedia

Again in all due respect to the good senator, I would offer a differing opinion on the scientific evidence for safety of GMO food   The reality is that there is NO Scientific Consensus that GMO Food is Safe. (4-6)

The reason for this is unlike drugs which require placebo controlled trials showing effectiveness and safety,  GMO Food was FDA approved in the US without any safety testing or labeling based on the theory of “substantial equivalence”.  This GMO regulation was written by Michael Taylor, a lawyer and Monsanto V.P. who was appointed to the FDA for the sole purpose of writing GMO regulations favorable to Monsanto.  For the next generation of GMO products, these rules will no doubt be changed, as safety testing will be necessary and mandatory according to David R Schubert, in his article, “The Problem with nutritionally enhanced plants in Journal Medicinal food 2008″

“Among the next generation of genetically modified (GM) plants are those that are engineered to produce elevated levels of nutritional molecules such as vitamins, omega-3 fatty acids, and amino acids. Based upon the U.S. current regulatory scheme, the plants and their products may enter our food supply without any required safety testing. The potential risks of this type of GM plant are discussed in the context of human health, and it is argued that there should be very careful safety testing of plants designed to produce biologically active molecules before they are commercially grown and consumed. This will require a mandatory, scientifically rigorous review process.”

There has been an exponential Increase in GastroIntestinal and other diseases since introduction of GMO Food and Glyphosate.  Just ask the CDC for ICD-10 coded hospital discharge data.  Nancy Swanson has provided these charts in her publications showing high correlation with  glyphosate and increasing incidence of 22 diseases.(29)   In all due respect, don’t you think it would be prudent to do epidemiologic studies to determine if this correlation was correct and indicated causation?  Below charts are only a few of 22 diseases that all look pretty much the same, courtesy of Nancy Swanson (29)  This is a public health issue, so why not allocate a few Billion dollars to various Departments of Public Health such as Yale, Harvard, Duke, Stanford, University of Chicago etc to study this issue ?  Are not these people the great minds who can solve this?

….Next listen to Senator Richard Blumenthal (D) from Connecticut:

One final comment: the issue of genetic contamination of the environment was not mentioned in Senator Heidi Heitkamp’s remarks.  This is a serious issue, because once Genetically Modified Organisms are released into the environment, they don’t gradually degrade and dissipate as does chemical pollution.  Unlike chemical pollution, GMO pollution multiplies throughout the eco-system like releasing a genie from a bottle.  You can’t get it back.   This results in contamination of neighboring fields and a “public nuisance” as described above.

In conclusion, this GMO labeling compromise bill is next going to the House of Representatives, so there is still time for the people to speak up.  I implore the reader to call or write their congressional representative to ask for a real mandatory GMO labeling bill, not this “Micky Mouse” compromise bill which Senator Richard Blumenthal so eloquently explained.

Articles with related interest:

Zika Virus or Glyphosate Causing Microcephaly in Brasil ?

Dont Ask For HIV Test, Ask For Glyphosate Test

Genetically Modified Food, GMO the Great Scandal

Jeffrey Dach MD

7450 Griffin Road Suite 180/190

Davie, Florida 33314

954-792-4663

Links and References:

Heidi Heitkamp north dakota senator gmo label

1) Senator Heidi Heitkamp Speaks In Favor Of S. 764

Coalition For Safe Affordable Food

2) http://thehill.com/regulation/legislation/286720-gmo-labeling-bill-advances-in-senate

The Hill  – GMO labeling bill advances in the Senate over Dem objections

3) Senator Blumenthal (Conn) Speaks Out Against Anti-GMO Labeling Measure

——–

No scientific concensus on safety of GMOS

4) http://www.ensser.org/increasing-public-information/no-scientific-consensus-on-gmo-safety/

10/21/13 Statement: No scientific consensus on GMO safety

European Network of SCientists for Social and Environmental Resposibility

“Decisions on the future of our food and agriculture should not be based on misleading and misrepresentative claims that a “scientific consensus” exists on GMO safety. ”

NO Scientific Consensus

5)  No scientific consensus on GMO safety. by Angelika Hilbeck, et al. “No scientific consensus on GMO safety.” Environmental Sciences Europe 27.1 (2015): 1.

Rigorous studies investigating the safety of GM crops and foods would normally involve, inter alia, animal feeding studies in which one group of animals is fed GM food and another group is fed an equivalent non-GM diet. Independent studies of this type are rare, but when such studies have been performed, some have revealed toxic effects or signs of toxicity in the GM-fed animals [2,8,11-13]. The concerns raised by these studies have not been followed up by targeted research that could confirm or refute the initial findings.

It is often claimed that ‘trillions of GM meals’ have been eaten in the US with no ill effects. However, no epidemiological studies in human populations have been carried out to establish whether there are any health effects associated with GM food consumption.

6) Illusory Consensus GMO Health Assessment Science Technology Human Values Sheldon Krimsky 2015

Krimsky, Sheldon. “An illusory consensus behind GMO health assessment.” Science, Technology & Human Values (2015): 0162243915598381.

I found twenty-six animal feeding studies that have shown adverse effects or animal health uncertainties.

This point was made by the 300 scientists who signed a joint statement that was published in Environmental Sciences Europe. The statement ‘‘does not assert that GMOs are unsafe or safe. Rather the statement concludes that the scarcity and contradictory nature of the scientific evidence published to date prevents conclusive claims of safety, or lack of safety, of GMOs’’ (Hilbeck et al. 2015, 1). David Schubert, professor at the Salk Institute, summarized the state of affairs of the GMO controversy as follows: ‘‘To me, the only reasonable solution is to require that all GM plant products be tested for long-term toxicity and carcinogenicity before being brought to market’’

(2002, 969).

I have argued that the putative consensus about the inherent safety of transgenic crops is premature.

pro gm rebuttal to Krimsky

7) https://foodscienceinstitute.com/2015/08/27/krimskys-illusory-consensus-is-itself-illusory/  Krimsky’s ‘Illusory Consensus’ is itself illusory

8) https://www.bostonglobe.com/lifestyle/health-wellness/2014/08/17/with-sheldon-krimsky/oR1rIk3yspnUcJvHKtrrbM/story.html

Q&A with Sheldon Krimsky     By Karen Weintraub Boston Globe Correspondent  August 18, 2014

Hybrid crops are in the same species. In genetically engineered crops, you’re taking a gene from a completely distant species, and putting it in a plant genome.

Professor Sheldon Krimsky, editor and author of  The GMO Deception: What You Need to Know About the Food, Corporations, and Government Agencies Putting Our Families and Our Environment at Risk.

The deception in this statement is that it mistakenly assumes that genetic engineering of plants is a precise technology for transplanting genes. The fact is that the insertion of foreign DNA is an imprecise and uncontrolled process. One of the common mistakes made by the pro-GMO advocates is that they treat the plant genome like a Lego construction where the insertion or deletion of a gene does not affect the other genes. They argue that adding new genes just adds new properties to the organism. This understanding of genetics was long ago proven obsolete in human biology where scientists have come to understand that most characteristics are influenced by complex interactions among multiple genes and the environment acting together.

The FDA’s approach to risk assessment of GMO crops is based on the concept of “substantial equivalence.” While the concept has never been well-defined, it is based on the idea that when a few components of the GMO crop such as certain nutrients and amino acids are similar in content to its non- GMO counterpart, the GMO crop is declared “substantially equivalent.”

The gap between what is being proposed by independent scientists and what is actually being done in hazard assessment of GMO crops is gargantuan. Nowhere is it greater than in the United States where the food safety requirements for GMO crops are similar to the chemical food additives designated as “generally regarded as safe” (or GRAS). In both cases the evaluation of health effects largely has been left to the manufacturers.

9) Book by Steven Druker : Altered Genes, Twisted Truth: How the Venture to Genetically Engineer Our Food Has Subverted Science, Corrupted Government, and Systematically Deceived the Public 1st Edition by (Author)

10) Book by Sheldon Krimsky,  The GMO Deception: What You Need to Know About the Food, Corporations, and Government Agencies Putting Our Families and Our Environment at Risk.

11)  full free pdf

Schubert, David R. “The problem with nutritionally enhanced plants.” Journal of medicinal food 11.4 (2008): 601-605. Problem with nutritionally enhanced plants Journal Medicinal food David Schubert 2008

ABSTRACT Among the next generation of genetically modified (GM) plants are those that are engineered to produce elevated levels of nutritional molecules such as vitamins, omega-3 fatty acids, and amino acids. Based upon the U.S. current regulatory scheme, the plants and their products may enter our food supply without any required safety testing. The potential risks of this type of GM plant are discussed in the context of human health, and it is argued that there should be very careful safety testing of plants designed to produce biologically active molecules before they are commercially grown and consumed. This will require a mandatory, scientifically rigorous review process.

12)  Ghostbusters, GMOs and the Feigned Expertise of Nobel Laureates  by Devon G. Peña  July 5, 2016

13)  William F Engdahl : Seeds of Destruction – The GMO Hidden Agenda

14) We Don’t Need Golden Rice  by Robert Greer Guest Authors / July 17, 2015    in The League

Fruit and root crops rich in Vitamin A are plentiful in every heavily-populated bioregion in the world.  Mangoes, oranges, yams, squash, papaya, watermelons, and cantaloupes are all rich in Vitamin A, and these crops typically produce yields that rival or surpass GMO rice.  Virtually every significant farming culture has had hundreds of years of experience with at least one of these crops.

the IRRI explained in 2014 that GMO golden rice had failed its field trials, hadn’t yet been safety tested, and wouldn’t be available for several years. Promoters of GMO golden rice seem to want an impoverished food model to continue by ensuring that all people will have to eat is rice, in this case an untested-for-long-term-safety GMO rice.  Increasingly people lack access to land on which to grow crops to feed themselves. This is a political and economic problem that will not be solved by offering GM crops.

15)  Monsanto ‘Biotechnology Book for Kids’ Caught Brainwashing Children

Anthony Gucciardi  Posted on March 22, 2012

=======================================================

GMO FOOD Rejected or Banned in 60 Countries

16) Keith Good: China’s Rejection of GMO Corn May Have Cost U.S. Ag $2.9B  By Mike Christensen April 17, 2014

17)  The Japanese reject American/Monsanto GMO wheat by turning to Russian wheat  Posted on May 6, 2016 by Bd-1 In Tokyo

Japan has rejected GMO-raised crops as a food source and that includes American produced wheat while America is alleged to be facing a crisis in exporting crops. Is it any wonder since more and more governments, including the Russian and Japanese governments, are becoming acutely aware the threat imposed by GMO crops? …. Russia has now declared that it would become the world’s largest producer on non-GMO foods and that is encouraging.

18) CNBC – Govt decides to ban GMO food production in Russia: Deputy PM Wednesday, 23 Sep 2015

A senior Russian government member told reporters the cabinet decided that any food production in the country will completely exclude any genetically-modified organisms or parts thereof.

“As far as genetically-modified organisms are concerned, we have made decision not to use any GMO in food productions,” Deputy PM Arkady Dvorkovich said at an international conference on biotechnology in the Russian city of Kirov.

19)  Russian president signs law banning GMO production July 05, 2016 TASS News.  MOSCOW, July 5. /TASS/. Russian President Vladimir Putin has signed the law banning genetically modified organisms (GMOs) and production in Russia, excluding examinations and scientific researches. The law was passed by the State Duma (lower house of parliament) on June 24 and approved by the Federation Council (upper house) on June 29, 2016.

The law bans imports of GMOs aimed for releasing to the environment and GMO products to the territory of the Russian Federation. The document obliges importers of GMO products to a compulsory public registration.

20)  GMO Facts Frequently Asked Questions NON GMO Project

Most developed nations do not consider GMOs to be safe. In more than 60 countries around the world, including Australia, Japan, and all of the countries in the European Union, there are significant restrictions or outright bans on the production and sale of GMOs.

Senator stastes GMO Food Labeling is a “Wrecking Ball”

21) https://www.congress.gov/congressional-record/2016/3/16/senate-section/article/s1516-1

What we face today is a handful of States that have chosen to enact

labeling requirements on information that has nothing to do with

health, safety, or nutrition.

Those labeling laws will ultimately impact consumers who will suffer from higher priced food. It will cost $1,050 per year for an average family of four.

The amendment before us today stops this wrecking ball before any more damage can be done.

22)  GMO Wars: The Global Battlefield  The case against GMOs has strengthened steadily over the last few years, even as the industry has expanded all over the world.  By Walden Bello, October 28, 2013

in Thailand for instance, one of the world’s leading producers of rice, those who grow rice – and would potentially grow Golden Rice – do so for the sole purpose of selling it. They do indeed consume part of their annual harvest – but the species they grow are determined by market demand.  Not only is there no demand for genetically modified rice species, nor will there ever be, Golden Rice contaminating the thousands of varieties of native, organic rice species Asia’s rice farmers do depend on for their livelihood would be an immeasurable catastrophe.

23)  What is the status of the Golden Rice project coordinated by IRRI?

Golden Rice will only be made available broadly to farmers and consumers if it is successfully developed into rice varieties suitable for Asia, approved by national regulators, and shown to improve vitamin A status in community conditions.

24)   Buiatti, M., P. Christou, and G. Pastore. “The application of GMOs in agriculture and in food production for a better nutrition: two different scientific points of view.” Genes & nutrition 8.3 (2012): 255.

25) Fitzpatrick, Teresa B., et al. “Vitamin deficiencies in humans: can plant science help?.” The Plant Cell 24.2 (2012): 395-414.

26) Lucht, Jan M. “Public acceptance of plant biotechnology and GM crops.” Viruses 7.8 (2015): 4254-4281.

Almost no GM food products are found on European grocery shelves,

Europeans, where labeled GM foods have been kept off the market.

==========================================================

27) Anthony Samsel blasts GMO-Technology and the one gene one enzyme hyphotheses  Tonu.org

28) Samsel A, Seneff S. Glyphosate, pathways to modern diseases II: Celiac sprue and gluten intolerance. Glyphosate pathways to modern diseases Celiac Gluten Two Seneff 2013

29) Swanson, Nancy L., et al. “Genetically engineered crops, glyphosate and the deterioration of health in the United States of America.” Journal of Organic Systems 9.2 (2014): 6-37. Genetically engineered crops glyphosate deterioration health United States Swanson J Organic Systems 2014

30)  The Possible Link between Autism and Glyphosate Acting as Glycine Mimetic – A Review of Evidence from the Literature with Analysis

Beecham JE and Stephanie Seneff   Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge MA 02139, USA

31) Is there a link between autism and glyphosate-formulated herbicides?

James E. Beecham1 and Stephanie Seneff  MIT Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, USA.

32) Glyphosate Suppression Cytochrome P450 amino acid biosynthesis by the gut microbiome Pathways Modern Diseases Entropy Seneff 2013

33) Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines_Seralini_Gasnier_Toxicology_2009

34) Glyphosate Roundup Human Placental Cells Aromatase Seralini Richard 2005 Env Health Persp

35) Glyphosate herbicides toxic endocrine disruptors human cell Gasnier Toxicology 2009

36) Human contamination by glyphosate Friends of the Earth Europe 2013

37)   IARC_Monograph_20_March_2015_Volume_112_Herbicide_Glyphosate_Cancer_Carcinogen_Dr_Oz

———————-

Golden Rice

38) Potentially Dangerous GMO ‘Golden Rice’ Fed to Children Without Warning by Elizabeth Renter Posted on October 20, 2013

Starlink Corn Public Nuisance

August 2004, Aventis settled a class-action lawsuit and paid farmers 110 million dollars for genetic contamination of farmers fields with the Aventis Starlink Corn. A separate settlement paid 9 million dollars to consumers who had heath problems from consuming the genetically modified Starlink corn. The courts considered the GMO Starlink Corn a “public nuisance”, and this ruling was enough to cause Aventis to abandon its next GMO product, the Liberty Link™ Soybean.  A similar class action suit was settled for LibertyLink rice.

39) Posted 8/23/2004 StarLink corn settlement also to include interest By Kevin O’Hanlon, Associated Press LINCOLN, Neb.

40) Engineering Legal Risk Management Into Agricultural Biotechnology Thomas P Redick 2004 Engineering Legal Risk Management Into Agricultural Biotechnology Thomas P Redick 2004

41)  February 25, 2015 Schlessinger, L., and A. B. Endres. “The Missing Link: Farmers’ Class Action Against Syngenta May Answer Legal Questions Left After the StarLink and LibertyLink Litigation.” farmdoc daily (5):35, Department of Agricultural and Consumer Economics, University of Illinois at Urbana-Champaign, February 25, 2015.

Professor Don Huber

42)  Scientist says flawed science of GMOs jeopardizing future generations

By Ken Roseboro   Published: March 1, 2012

Don Huber, emeritus professor of plant pathologiy at Purdue University, gave a two-and-a-half hour indictment of glyphosate herbicide and genetically modified crops at the Acres USA conference in December.

Mae Wan Ho and The Institute of Science In Society 

43) BANISHING GLYPHOSATE .pdf – The Institute of Science In Society BANISHING GLYPHOSATE The Institute of Science In Society Mae Wan Ho

44) The American Academy Of Environmental Medicine Calls For Immediate Moratorium On Genetically Modified Foods Press Advisory – May 19, 2009

Wichita, KS – The American Academy of Environmental Medicine (AAEM) today released its position paper on Genetically Modified foods stating that “GM foods pose a serious health risk” and calling for a moratorium on GM foods. Citing several animal studies, the AAEM concludes “there is more than a casual association between GM foods and adverse health effects” and that “GM foods pose a serious health risk in the areas of toxicology, allergy and immune function, reproductive health, and metabolic, physiologic and genetic health.”

“Multiple animal studies have shown that GM foods cause damage to various organ systems in the body. With this mounting evidence, it is imperative to have a moratorium on GM foods for the safety of our patients’ and the public’s health,” said Dr. Amy Dean, PR chair and Board Member of AAEM.

45)  GMO Myths and Truths      Jill Carnahan, MD

Golden Rice

46) full free pdf   GMO Myths and Truths John Fagan Michael Antoniou Claire Robinson Earth Open Source 2014  GMO Myths and Truths An evidence-based examination of the claims made for the safety and efficacy of genetically modified crops and foods 2014

John Fagan, PhD Michael Antoniou, PhD Claire Robinson, MPhil

2nd edition, Version 2.0 Earth Open Source

2nd Floor, 145–157 St John Street

London EC1V 4PY, Great Britain

www.earthopensource.org

The much-hyped GM golden rice, which is claimed to be able to alleviate vitamin A deficiency in developing countries, is still not ready for the market and at the time of writing had not yet undergone toxicological testing.

At the time of writing (2014), golden rice had not been subjected to basic toxicological testing in animals – testing that is required by the European regulatory system for all GMOs before they can be authorized for human consumption.10 Nevertheless this GM rice was fed to human subjects (adults11 and children12) in experiments conducted by researchers from Tufts University, Boston, MA.

The feeding of GM golden rice to human subjects, especially young children, in the absence of prior animal toxicological testing was condemned by international scientists as a breach of medical ethics and the Nuremberg Code, which was established after World War II to prevent a repeat of inhumane Nazi experiments on people.13

Inexpensive and effective methods of combating vitamin A deficiency have long been available. The World Health Organization’s (WHO) long-standing project to combat vitamin A deficiency uses supplements where necessary, but centres on education and development programmes. These programmes encourage mothers to breastfeed and teach people how to grow carrots and leafy vegetables in home gardens – two inexpensive, effective, and widely available solutions.

Beta-carotene is one of the commonest molecules in nature, being found in abundance in green leafy plants and fruits. There is no need to engineer beta-carotene into rice.

The WHO says its programme has “averted an estimated 1.25 million deaths since 1998 in 40 countries.”15 According to WHO malnutrition expert Francesco Branca, these approaches are, for now, more promising approaches to combating vitamin A deficiency than golden rice.6

Vitamin A supplementation enjoys broad support. A review published in the British Medical Journal assessed 43 studies involving 200,000 children and found deaths were cut by 24% if children were given the vitamin. The researchers estimated that giving vitamin A supplements to children under the age of five in developing countries could save 600,000 lives a year. They concluded, “Vitamin A supplements are highly effective and cheap to produce and administer.”16,17

47) GMO OMG Film director and concerned father Jeremy Seifert is in search of answers. How do GMOs affect our children, the health of our planet, and our freedom of choice? And perhaps the ultimate question, which Seifert tests himself: is it even possible to reject the food system currently in place, or have we lost something we can’t gain back? These and other questions take Seifert on a journey from his family’s table to Haiti, Paris, Norway, and the lobby of agra-giant Monsanto, from which he is unceremoniously ejected. Along the way we gain insight into a question that is of growing concern to citizens the world over: what’s on your plate?

link to this article:http://wp.me/p3gFbV-3I8

Jeffrey Dach MD

7450 Griffin Road Suite 190

Davie, Fl 33314

954-792-4663

www.jeffreydachmd.com

http://www.drdach.com

http://www.naturalmedicine101.com

http://www.bioidenticalhormones101.com

http://www.truemedmd.com

The reader is advised to discuss the comments on these pages with his/her personal physicians and to only act upon the advice of his/her personal physician. Also note that concerning an answer which appears as an electronically posted question, I am NOT creating a physician — patient relationship. Although identities will remain confidential as much as possible, as I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur.

Copyright (c) 2016 Jeffrey Dach MD All Rights Reserved. This article may be reproduced on the internet without permission, provided there is a link to this page and proper credit is given.

FAIR USE NOTICE: This site contains copyrighted material the use of which has not always been specifically authorized by the copyright owner. We are making such material available in our efforts to advance understanding of issues of significance. We believe this constitutes a ‘fair use’ of any such copyrighted material as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, the material on this site is distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes.

Serving Areas of: Hollywood, Aventura, Miami, Fort Lauderdale, Pembroke Pines, Miramar, Davie, Coral Springs, Cooper City, Sunshine Ranches, Hallandale, Surfside, Miami Beach, Sunny Isles, Normandy Isles, Coral Gables, Hialeah, Golden Beach ,Kendall,sunrise, coral springs, parkland,pompano, boca raton, palm beach, weston, dania beach, tamarac, oakland park, boynton beach, delray,lake worth,wellington,plantation.

 

The post GMO Food Fight on Senate Floor appeared first on Jeffrey Dach MD .

Vitamin B3 Niacinamide for Osteoarthritis

Vitamin B3 Niacinamide for Osteoarthritis

Jim is a 47 year old retired truck driver who came to see me because of severe knee pain which interferes with his favored sport, racquet ball.   Jim’s  Xrays and MRI scans show severe osteoarthritis with loss of cartilage and “bone on bone” appearance of both knees.  Jim has been to many doctors over the years who prescribed steroids, and NSAIDs type drugs giving short term relief.  However, these drugs accelerated the joint destruction.

Stem Cell Injections ?

Jim went to a doctor who specializes in stem cell injections and wanted to try it, but Jim couldn’t afford the exorbitant $10,000 cost per injection.

Next, Jim saw the top orthopedic surgeon in the area who recommended bilateral knee joint replacement as soon as possible.

Now Jim is asking me  if anything could be done to avoid knee replacement surgery.  Left Image: AP Xray of normal knee joint (left) and severe osteoarthritis (right) notice joint space narrowing and reactive sclerosis. Courtesy of Victoria Wellness.

“There is good news, Jim, we have an excellent program that can save your knees and get you back on the racquetball court.”

I then explain to Jim our program for osteoarthritis:

1) Avoid Nightshade Vegetables in the Diet (Tomatoes, Eggplant, Potatoes, Peppers)

2) Curcumin Phytosome or Lipospheric Curcumin

3) Glucosamine / Chondroitin Sulfate

4) DHA/EPA Fish Oil

5) Niacinamide 3 grams daily in divided doses.

Jim started on his program, and 6 weeks later called the office to report how amazed he was that his pain had decreased, and he is feeling better.  Maybe he wouldn’t need that knee operation after all. Left Image: Xray showing severe osteoarthritis of knee joint with irregular narrowing, reactive sclerosis, and spurring courtesy of  Duke Orthopedics.

Niacinamide for Osteoarthritis

Most orthopedic docs who see arthritis don’t know of the pioneering work by Dr Kaufman using niacinamide, vitamin B3,  for osteoarthritis.  It is quite effective at a dose of 500 mg six times a day.  Dr Kaufman reported patients had improved range of motion and reduction in pain after using Vitamin B3.(1-10)

Here is a Review on Amazon from a Vitamin B3 user:

“I have been taking this product for my cholesterol because my doctor told me to, but the nice side effect that I got with it was that it began to help the pain of arthritis in my thumb, shoulder and hip joints. I am almost pain free now and if I stop using it within three days the pain is back again. My daughter has bad arthritis in her knees and she has noticed the same thing…if she stops using niacinamide the pain returns. We both take 3,000mgs daily. Wonderful stuff Niacinamide. “

Left image Niacinamide chemical structure courtesy of  Skin lightening compositions Patent US 20060216254 A1

Articles with related interest:

Arthritiis and NightShades

Glucosamine and Chondroitin for Arthritis

Bioidentical Hormones Prevent Arthritis

Jeffrey Dach MD

Links and references

header image of Knee courtesy of Medical Xpress.

full free pdf

1) Prousky, Jonathan E. “The use of Niacinamide and Solanaceae (Nightshade) Elimination in the Treatment of Osteoarthritis.” JOM 30.1 (2015): 13.

Regarding the 455 patients treated with niacinamide, Kaufman discovered that long term therapy usually increased joint mobility (an increase in the JRI) and decreased subjective complaints of articular pain, stiffness or subjective limitation of joint movement, crepitus, articular discomfort attributed by the patient to changes in weather, articular swelling, and articular deformities.

Niacinamide repairs articular cartilage by inducing metabolic changes in articular cartilage cells (i.e., the chondrocytes) thus enhancing the ability of cartilage to repair itself.

The mechanism explaining the therapeutic effectiveness of the vitamin was related to the raising of coenzymes NAD and NADP in the synovial fluid and within the cartilage matrix itself. This would provide energy and nucleic acids through non-oxidative processes, which is vital for cartilage repair in the deeper layers of the matrix and might have the net effect of increasing cartilage repair rates.

ideal dose should be 250 mg in tablet form, taken anywhere from 3-16 times each day, depending on the severity of OA.

500 mg niacinamide tablets six times each day.

2) http://www.ncbi.nlm.nih.gov/pubmed/8841834

Inflamm Res. 1996 Jul;45(7):330-4.

The effect of niacinamide on osteoarthritis: a pilot study.

Jonas WB1, Rapoza CP, Blair WF.

To evaluate the effect of niacinamide, on selected parameters of osteoarthritis using a double-blind, placebo controlled study design.

METHODS:Seventy two patients with osteoarthritis were randomized for treatment with niacinamide or an identical placebo for 12 weeks. Outcome measures included global arthritis impact and pain, joint range of motion and flexibility, erythrocyte sedimentation rate, complete blood count, liver function tests, cholesterol, uric acid, and fasting blood sugar. Compliance was monitored with a pill record sheet and interview.

RESULTS:Global arthritis impact improved by 29% (95% confidence interval [CI] 6, 46) in subjects on niacinamide and worsened by 10% in placebo subjects (p = 0.04). Pain levels did not change but those on niacinamide reduced their anti-inflammatory medications by 13% (95% CI 9, 94; p = 0.01). Niacinamide reduced erythrocyte sedimentation rate by 22% (95% CI 6, 51; p < 0.005) and increased joint mobility by 4.5 degrees over controls (8 degrees vs 3.5 degrees; p = 0.04). Side effects were mild but higher in the niacinamide group (40% vs 27%, p = 0.003).

CONCLUSION:This study indicates that niacinamide may have a role in the treatment of osteoarthritis. Niacinamide improved the global impact of osteoarthritis, improved joint flexibility, reduced inflammation, and allowed for reduction in standard anti-inflammatory medications when compared to placebo. More extensive evaluation of niacinamide in arthritis is warranted.

3) http://www.ncbi.nlm.nih.gov/pubmed/10608273

Med Hypotheses. 1999 Oct;53(4):350-60.

Niacinamide therapy for osteoarthritis–does it inhibit nitric oxide synthase induction by interleukin 1 in chondrocytes?

McCarty MF1, Russell AL.

Fifty years ago, Kaufman reported that high-dose niacinamide was beneficial in osteoarthritis (OA) and rheumatoid arthritis. A recent double-blind study confirms the efficacy of niacinamide in OA. It may be feasible to interpret this finding in the context of evidence that synovium-generated interleukin-1 (IL-1), by inducing nitric oxide (NO) synthase and thereby inhibiting chondrocyte synthesis of aggrecan and type II collagen, is crucial to the pathogenesis of OA. Niacinamide and other inhibitors of ADP-ribosylation have been shown to suppress cytokine-mediated induction of NO synthase in a number of types of cells; it is therefore reasonable to speculate that niacinamide will have a comparable effect in IL-1-exposed chondrocytes, blunting the anti-anabolic impact of IL-1. The chondroprotective antibiotic doxycycline may have a similar mechanism of action. Other nutrients reported to be useful in OA may likewise intervene in the activity or synthesis of IL-1. Supplemental glucosamine can be expected to stimulate synovial synthesis of hyaluronic acid; hyaluronic acid suppresses the anti-catabolic effect of IL-1 in chondrocyte cell cultures, and has documented therapeutic efficacy when injected intra-articularly. S-adenosylmethionine (SAM), another proven therapy for OA, upregulates the proteoglycan synthesis of chondrocytes, perhaps because it functions physiologically as a signal of sulfur availability. IL-1 is likely to decrease SAM levels in chondrocytes; supplemental SAM may compensate for this deficit. Adequate selenium nutrition may down-regulate cytokine signaling, and ample intakes of fish oil can be expected to decrease synovial IL-1 production; these nutrients should receive further evaluation in OA. These considerations suggest that non-toxic nutritional regimens, by intervening at multiple points in the signal transduction pathways that promote the synthesis and mediate the activity of IL-1, may provide a substantially superior alternative to NSAIDs (merely palliative and often dangerously toxic) in the treatment and perhaps prevention of OA.

4) http://www.doctoryourself.com/kaufman.html

NIACINAMIDE AND ARTHRITIS

The authors of a 1996 study on niacinamide and osteoarthritis (Jonas WB, Rapoza CP, Blair WF. The effect of niacinamide in osteoarthritis: a pilot study. Inflammatory Research 45:330–334.) could have omitted the words “pilot study” from their title. Dr. William Kaufman had already published, 47 years earlier, his meticulous case notes for hundreds of patients, along with specific niacinamide dosage information applicable to both osteoarthritis and rheumatoid arthritis. In addition, the doctor added some remarkably prescient observations on the antidepressant-antipsychotic properties of B-3. Dr. Kaufman, whom his widow has described as a conservative physician, was nevertheless the first to prescribe as much as 5,000 mg niacinamide daily, in many divided doses, to improve range of joint motion.

5) free pdf

Hoffer, A. “Treatment of arthritis by nicotinic acid and nicotinamide.” Canadian Medical Association Journal 81.4 (1959): 235.

6) http://www.sciencedirect.com/science/article/pii/0006294469900465

Johnson, Willard J., and Lewis Kanics. “Stimulation of adrenocortical secretion by nicotinic acid and certain of its derivatives and analogues.” Biochemical Medicine 2.6 (1969): 438-447.

The effect of nicotinic acid, nicotinamide, and related substances on adrenocortical secretion has been investigated. Nicotinic acid and nicotinamide gave rise to a 2- to 3-fold elevation of plasma corticosterone in the intact rat. This effect was abolished by hypophysectomy. The plasma corticosterone response to nicotinamide injection was greatly delayed as compared with that of nicotinic acid, thus suggesting that the activity of nicotinamide is contingent upon prior conversion to nicotinic acid and possibly other active metabolites. 6-Amino-, 5-methyl-, and 5-fluoro-nicotinamide, nicotinylhydrazide, and isoniazid were also found to be potent stimulators of adrenocortical secretion. Our results indicate that these compounds exert their effect on adrenocortical secretion by a stimulatory effect on the pituitary output of ACTH.

Free pdf

7) Saul, Andrew W. “The pioneering work of William Kaufman: Arthritis and ADHD.” Journal of orthomolecular medicine 18.1 (2003).

8) https://youtu.be/NR2NTaYo7TQ

you tube video dr jonathon wright

Dr. Jonathan V. Wright ~ Osteoarthritis a Basic Vitamin Treatment

Dr. Wright shares his treatment for osteoarthritis. http://tahomaclinic.com/

9) full free pdf

Gaby, Alan R. “Natural treatments for osteoarthritis.” Alternative Medicine Review 4 (1999): 330-341.

10) http://www.vrp.com/single-vitamins/si....

Silencing the Aging Gene:Another Look at Clinical Uses for Niacinamide By Daniel J. Bourassa, D.C.

11) buy on Amazon

Nature’s Way Niacinamide 500 mg Capsules, 100 Count

http://amzn.to/29gkHlK

A User

I have been taking this product for my cholesterol because my doctor told me to, but the nice side effect that I got with it was that it began to help the pain of arthritis in my thumb, shoulder and hip joints. I am almost pain free now and if I stop using it within three days the pain is back again. My daughter has bad arthritis in her knees and she has noticed the same thing…if she stops using niacinamide the pain returns. We both take 3,000mgs daily. Wonderful stuff Niacinamide.

12) free pdf

Hoffer, Abram. The Vitamin Cure for Alcoholism: Orthomolecular Treatment of Addictions: Easy read Comfort Edition. ReadHowYouWant. com, 2009.

link to this article: http://wp.me/p3gFbV-3Hf

Jeffrey Dach MD

7450 Griffin Road Suite 190

Davie, Fl 33314

954-792-4663

www.jeffreydachmd.com

http://www.drdach.com

http://www.naturalmedicine101.com

http://www.bioidenticalhormones101.com

http://www.truemedmd.com

The reader is advised to discuss the comments on these pages with his/her personal physicians and to only act upon the advice of his/her personal physician. Also note that concerning an answer which appears as an electronically posted question, I am NOT creating a physician — patient relationship. Although identities will remain confidential as much as possible, as I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur.

Copyright (c) 2016 Jeffrey Dach MD All Rights Reserved. This article may be reproduced on the internet without permission, provided there is a link to this page and proper credit is given.

FAIR USE NOTICE: This site contains copyrighted material the use of which has not always been specifically authorized by the copyright owner. We are making such material available in our efforts to advance understanding of issues of significance. We believe this constitutes a ‘fair use’ of any such copyrighted material as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, the material on this site is distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes.

Serving Areas of: Hollywood, Aventura, Miami, Fort Lauderdale, Pembroke Pines, Miramar, Davie, Coral Springs, Cooper City, Sunshine Ranches, Hallandale, Surfside, Miami Beach, Sunny Isles, Normandy Isles, Coral Gables, Hialeah, Golden Beach ,Kendall,sunrise, coral springs, parkland,pompano, boca raton, palm beach, weston, dania beach, tamarac, oakland park, boynton beach, delray,lake worth,wellington,plantation.

The post Vitamin B3 Niacinamide for Osteoarthritis appeared first on Jeffrey Dach MD .