Jeffrey Dach's Blog, page 16

August 19, 2018

Financial Kickbacks to Pediatricians for Vaccination Harms Children

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Financial Kickbacks to Pediatricians for Vaccination Harms Children
Financial Kickbacks are Illegal in the Medical Field

When I worked in the hospital as a radiologist doing medical imaging, part of my job was to recommend additional imaging studies. For example, if I saw a mass on a chest Xray, I would recommend a chest CAT scan. If I saw blastic lesions in the rib on a chest Xray, I would recommend a radionuclide bone scan, etc. I always thought to myself, what if i owned a radiology imaging center. That would be great because I could really make a lot of money by referring all of these cases to myself. Above image courtesy of Bob the Pharmacist.

Stark Anti-Kickback Laws

However, there is a problem. Referring cases to my own imaging center is illegal, a form of fraud and abuse, a violation of the 1988 Stark Law “Ethics in Patient Referrals Act“.(4,5) These laws are summarized by the Office of Inspector General Report Department of Health and Human resources:(4)

“The five most important Federal fraud and abuse laws that apply to physicians are the False Claims Act (FCA), the Anti-Kickback Statute (AKS), the Physician Self-Referral Law (Stark law), the Exclusion Authorities, and the Civil Monetary Penalties Law (CMPL). Government agencies, including the Department of Justice, the Department of Health & Human Services Office of Inspector General (OIG), and the Centers for Medicare & Medicaid Services (CMS), are charged with enforcing these laws. As you begin your career, it is crucial to understand these laws not only because following them is the right thing to do, but also because violating them could result in criminal penalties, civil fines, exclusion from the Federal health care programs, or loss of your medical license from your State medical board.”(4)

Practice of Medicine is Not a Multi-Level Marketing Scheme

In other words, the practice of medicine is not a Multi-Level Marketing Scheme to make money by “gaming the system” by running large numbers of patients through tests or procedures for financial profit. Not only does this waste a huge amount of public money, it may cause considerable harm to the patient population. This is considered unethical behavior by the doctor, who is then subject to various civil and criminal penalties including loss of license.

Pediatricians Allowed to “Game the System”

This brings us to the financial incentives to pediatricians offered by insurance companies for vaccinating our children. The Blue Cross Blue Shield health insurance document explaining these financial incentives can be found Here . Pediatricians are raking in 40-80 thousand dollars a year from these kickback schemes.

Illegal Kickback Fraud and Abuse

I would argue this type of financial incentive to pediatricians is a form of illegal kickback prohibited by the anti-kickback laws. This type of financial arrangement gives a “green light” to the pediatricians to “game the system” to maximize financial gain by increasing the volume of a procedure. This is fraud and abuse which should be prosecuted by the Office of Inspector General.

Why Does the Health Insurance Company Offer Kickbacks for Vaccinations?

The health insurance company is offering this financial incentive, in reality a cash kickback, because the insurance company thinks vaccination makes a healthier population with fewer insurance claims.(10-11) The insurance company believes they will have fewer insurance claims in heavily vaccinated populations, and will make more money. The insurance company is happy to share their increased profit with the doctors in the form of a “kickback” cash incentive. This is clearly an unethical “kickback” scheme. Pediatricians should be providing health care as part of the routine practice of medicine, not on the basis of a financial kickback. Please contact your congressman and ask them to request the office of inspector general bring a halt this illegal kickback arrangement.

Are Vaccinated Populations Healthier and Utilize Less Health Care Resources?

Are vaccinated populations healthier and utilize less health care resources, thereby leading to greater profits for the health insurance industry? The answer is yes, according to this article in 2014 Pediatrics from authors employed by the CDC and the Bill and Melinda Gates Foundation. They concluded the cost savings are enormous. Health insurance company decisions to offer financial incentives to pediatricians for vaccinating children is based on this and similar studies.(11)

Analyses showed that routine childhood immunization among members of the 2009 US birth cohort will prevent 42,000 early deaths and 20 million cases of disease, with net savings of $13.5 billion in direct costs and $68.8 billion in total societal costs, respectively. The direct and societal benefit-cost ratios for routine childhood vaccination with these 9 vaccines were 3.0 and 10.1.(11)

Of course, the article is severely flawed because it is based on historical data and various assumptions and calculations which may turn out to be false. The only way to really know if a highly vaccinated population is healthier than an unvaccinated, and utilizes less health care, is to do a randomized prospective study. Such a study would follow a population of children over 5-10 years with the population randomized to vaccinated or unvaccinated. At the end of the observation period, the numbers can be tabulated for ER (emergency room) visits and hospitalizations, autoimmune disease, and neuro-developmental disorder in the vaccinated vs. unvaccinated groups, and get a real answer to the question. Of course, this study has never been done, and probably never will.

Are Vaccinated Healthier than Unvaccinated?

Quite opposite to what the health insurance industry believes, we have studies showing that vaccinated populations are NOT healthier than unvaccinated populations. A study by Neil Z. Miller in the 2016 Journal of Am Phys Surg 2016, reveals the children receiving greater numbers of vaccinations have more ER visits, more hospitalizations and increased mortality reported to the VAERS Database (VAERS= Vaccine Adverse Event Reporting System).(7) Neil Miller says that less healthcare is better than more healthcare. He examined the:

“VAERS database from 1990 through 2010. There were more than 325,000 VAERS reports. Our study showed that infants who receive several vaccines concurrently, as recommended by CDC, are significantly more likely to be hospitalized or die when compared with infants who receive fewer vaccines simultaneously”.(7)

CDC Says Receiving Multiple Vaccines Concurrently is Safe ?

The CDC says that receiving multiple vaccines concurrently is safe for children:(8)

“Scientific data show that getting several vaccines at the same time does not cause any chronic health problems. A number of studies have been done to look at the effects of giving various combinations of vaccines, and when every new vaccine is licensed, it has been tested along with the vaccines already recommended for a particular aged child. The recommended vaccines have been shown to be as effective in combination as they are individually. Sometimes, certain combinations of vaccines given together can cause fever, and occasionally febrile seizures; these are temporary and do not cause any lasting damage. Based on this information, both the Advisory Committee on Immunization Practices and the American Academy of Pediatrics recommend getting all routine childhood vaccines on time.”

However, Neil Miller says the CDC is lying to you. He says:”this combination of eight vaccines administered during a single physician visit was never tested for safety in clinical trials.”(7)

“Although CDC recommends polio, hepatitis B, diphtheria, tetanus, pertussis, rotavirus, Haemophilus influenzae type B, and pneumococcal vaccines for two-, four-, and six-month-old infants, this combination of eight vaccines administered during a single physician visit was never tested for safety in clinical trials….CDC urges infants to receive multiple vaccines concurrently without scientific evidence to confirm the safety of this practice. Administering six, seven, or eight vaccine doses to an infant during a single physician visit is certainly more convenient for parents, as opposed to making additional trips to the doctor’s office, and increases the likelihood that the infant will receive all the vaccines, but vaccine safety must remain the highest priority.”(7)

If someone could show me the clinical trials testing eight vaccines in combination at one time, showing them safe, then I would be happy to believe the CDC over Mr. Miller. So far I have been unable to find any of these studies.

Evidence of Harm from Vaccines

Another recent study from Dr. Mawson in Translational Medicine 2017 suggests that vaccinated populations are more prone to neurodevelopmental disorders defined as learning disability, Attention Deficient Hyperactivity Disorder, and Autism Spectrum Disorder. (12-14) The harm was greater if the infant was pre-term.(12-14)

Harming the Pediatric Population for Financial Gain

If these studies are true, this would suggest the Health Insurance program of financial incentives (ie kickbacks) to pediatricians for increasing vaccinations is harming our children. Not only is this unethical and illegal practice based on our existing anti-kickback law, this practice is causing immeasurable harm to the children, the families and our society. Print this article and send a copy to your friends and family. Call, email or write your congressman and ask them to request the Inspector General’s Office to bring a stop to this unethical and illegal kickback scheme.

Jeffrey Dach MD

7450 Griffin Road Suite 190

Davie,Florida 33314

954-792-4663

Articles with Related Interest:

Aluminum Adjuvants in Vaccines Cause Autism

The Failure of Global Polio Eradication

References:

1) Blue Cross Blue Shield 2016 Booklet Financial Incentives to Pediatricians to Vaccinate Children. Pediatricians Receive Financial Incentives Kickbacks to Vaccinate Children BCBS 2016 Booklet

2) Blue Cross Blue Shield Pays Your Doctor A $40,000 Bonus For Fully Vaccinating 100 Patients Under The Age of 2 By Paul Meizner

3) Are Physicians Given Financial Incentives to Vaccinate Our Children?

1 By Jonathan Wright on September 8, 2017

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

4) A Roadmap for New Physicians Fraud & Abuse Laws Office of Inspector General

The five most important Federal fraud and abuse laws that apply to physicians are the False Claims Act (FCA), the Anti-Kickback Statute (AKS), the Physician Self-Referral Law (Stark law), the Exclusion Authorities, and the Civil Monetary Penalties Law (CMPL). As you begin your career, it is crucial to understand these laws not only because following them is the right thing to do, but also because violating them could result in criminal penalties, civil fines, exclusion from the Federal health care programs, or loss of your medical license from your State medical board.

Taking money or gifts from a drug or device company or a durable medical equipment (DME) supplier is not justified by the argument that you would have prescribed that drug or ordered that wheelchair even without a kickback.

The Physician Self-Referral Law, commonly referred to as the Stark law, prohibits physicians from referring patients to receive “designated health services” payable by Medicare or Medicaid from entities with which the physician or an immediate family member has a financial relationship, unless an exception applies

5) Anti-kickback & Stark Compliance Information AAFP

What is the anti-kickback rule? The anti-kickback statute makes it illegal for providers (including physicians) to knowingly and willfully accept bribes or other forms of remuneration in return for generating Medicare, Medicaid or other federal health care program business.

—————————

document: General Accountability Office Report: MEDICARE Implementation of Financial Incentive Programs under Federal Fraud and Abuse Laws

However, there are no exceptions or safe harbors specifically for financial incentive programs intended to improve quality and efficiency, and legal experts reported that the constraints of existing exceptions and safe harbors make it difficult to design and implement a comprehensive program for all participating physicians and patient populations.

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

6) Cornell Law Review

h) Preventive screening tests, immunizations, and vaccines. Preventive screening tests, immunizations, and vaccines that meet the following conditions:

(1) The preventive screening tests, immunizations, and vaccines are subject to CMS-mandated frequency limits.

(2) The arrangement for the provision of the preventive screening tests, immunizations, and vaccines does not violate the anti-kickback statute (section 1128B(b) of the Act).

Does not violate the anti-kickback statute

Does not violate the anti-kickback statute, as used in this subpart only, means that the particular arrangement –

(1)

(i) Meets a safe harbor under the anti-kickback statute, as set forth at § 1001.952 of this title, “Exceptions”;

(ii) Has been specifically approved by the OIG in a favorable advisory opinion issued to a party to the particular arrangement (for example, the entity furnishing DHS) with respect to the particular arrangement (and not a similar arrangement), provided that the arrangement is conducted in accordance with the facts certified by the requesting party and the opinion is otherwise issued in accordance with part 1008 of this title, “Advisory Opinions by the OIG”; or

(iii) Does not violate the anti-kickback provisions in section 1128B(b) of the Act.

(2) For purposes of this definition, a favorable advisory opinion means an opinion in which the OIG opines that –

(i) The party’s specific arrangement does not implicate the anti-kickback statute, does not constitute prohibited remuneration, or fits in a safe harbor under § 1001.952 of this title; or

(ii) The party will not be subject to any OIG sanctions arising under the anti-kickback statute (for example, under sections 1128A(a)(7) and 1128(b)(7) of the Act) in connection with the party’s specific arrangement.

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

7) Combining Childhood Vaccines at One Visit Is Not Safe by Neil Z. Miller Journal of American Physicians and Surgeons, Volume 21, Number 2, Summer 2016

Combining Childhood Vaccines at One Visit Is Not Safe Neil Z Miller J Am Phys Surg 2016

Although CDC recommends polio, hepatitis B, diphtheria, tetanus, pertussis, rotavirus, Haemophilus influenzae type B, and pneumococcal vaccines for two-, four-, and six-month-old infants, this combination of eight vaccines administered during a single physician visit was never tested for safety in clinical trials.

CDC urges infants to receive multiple vaccines concurrently without scientific evidence to confirm the safety of this practice. Administering six, seven, or eight vaccine doses to an infant during a single physician visit is certainly more convenient for parents, as opposed to making additional trips to the doctor’s office, and increases the likelihood that the infant will receive all the vaccines, but vaccine safety must remain the highest priority.

Vaccine Adverse Event Reporting System (VAERS)

VAERS database from 1990 through 2010. There were more than 325,000 VAERS reports.

Our study showed that infants who receive several vaccines concurrently, as recommended by CDC, are significantly more likely to be hospitalized or die when compared with infants who receive fewer vaccines simultaneously.

8) Getting multiple vaccines at the same time has been shown to be safe. Centers for Disease Control and Prevention. CDC twenty four seven. Saving Lives, Protecting People

Scientific data show that getting several vaccines at the same time does not cause any chronic health problems. A number of studies have been done to look at the effects of giving various combinations of vaccines, and when every new vaccine is licensed, it has been tested along with the vaccines already recommended for a particular aged child. The recommended vaccines have been shown to be as effective in combination as they are individually. Sometimes, certain combinations of vaccines given together can cause fever, and occasionally febrile seizures; these are temporary and do not cause any lasting damage. Based on this information, both the Advisory Committee on Immunization Practices and the American Academy of Pediatrics recommend getting all routine childhood vaccines on time.

9) How Much Money Do Pediatricians Really Make From Vaccines?

10) Zhou, Fangjun, et al. “Economic evaluation of the 7-vaccine routine childhood immunization schedule in the United States, 2001.” Archives of pediatrics & adolescent medicine 159.12 (2005): 1136-1144.

Participants A hypothetical 2001 US birth cohort of 3 803 295 infants was followed up from birth through death.

Main Outcome Measures Net present value (net savings) and benefit-cost ratios of routine immunization.

Results Routine childhood immunization with the 7 vaccines was cost saving from the direct cost and societal perspectives, with net savings of $9.9 billion and $43.3 billion, respectively. Without routine vaccination, direct and societal costs of diphtheria, tetanus, pertussis, H influenzae type b, poliomyelitis, measles, mumps, rubella, congenital rubella syndrome, hepatitis B, and varicella would be $12.3 billion and $46.6 billion, respectively. Direct and societal costs for the vaccination program were an estimated $2.3 billion and $2.8 billion, respectively. Direct and societal benefit-cost ratios for routine childhood vaccination were 5.3 and 16.5, respectively.

Conclusion Regardless of the perspective, the current routine childhood immunization schedule results in substantial cost savings.

11) Zhou, Fangjun, et al. “Economic evaluation of the routine childhood immunization program in the United States, 2009.” Pediatrics (2014): peds-2013. Economic evaluation routine childhood immunization program United States 2009 Zhou Fangjun Pediatrics 2014

Analyses showed that routine childhood immunization among members of the 2009 US birth cohort will prevent 42 000 early deaths and 20 million cases of disease, with net savings of $13.5 billion in direct costs and $68.8 billion in total societal costs, respectively. The direct and societal benefit-cost ratios for routine childhood vaccination with these 9 vaccines were 3.0 and 10.1.

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

12) Mawson, Anthony R., et al. “Preterm birth, vaccination and neurodevelopmental disorders: a cross-sectional study of 6-to 12-year-old vaccinated and unvaccinated children.” J Transl Sci 3 (2017). Preterm birth vaccination and neurodevelopmental disorders vaccinated and unvaccinated children Mawson Anthony R J Transl Sci 2017

From about 8% to 27% of extremely preterm infants develop symptoms of autism spectrum disorder, but the causes are not well understood. Preterm infants receive the same doses of the recommended vaccines and on the same schedule as term infants. The possible role of vaccination in neurodevelopmental disorders (NDD) among premature infants is unknown, in part because pre-licensure clinical trials of pediatric vaccines have excluded ex-preterm infants. This paper explores the association between preterm birth, vaccination and NDD, based on a secondary analysis of data from an anonymous survey of mothers, comparing the birth history and health outcomes of vaccinated and unvaccinated homeschool children 6 to 12 years of age. A convenience sample of 666 children was obtained, of which 261 (39%) were unvaccinated, 7.5% had an NDD (defined as a learning disability, Attention Deficit Hyperactivity Disorder and/or Autism Spectrum Disorder), and 7.7% were born preterm. No association was found between preterm birth and NDD in the absence of vaccination, but vaccination was significantly associated with NDD in children born at term (OR 2.7, 95% CI: 1.2, 6.0). However, vaccination coupled with preterm birth was associated with increasing odds of NDD, ranging from 5.4 (95% CI: 2.5, 11.9) compared to vaccinated but non-preterm children, to 14.5 (95% CI: 5.4, 38.7) compared to children who were neither preterm nor vaccinated. The results of this pilot study suggest clues to the epidemiology and causation of NDD but question the safety of current vaccination practices for preterm infants. Further research is needed to validate and investigate these associations in order to optimize the impact of vaccines on children’s health.

13) Mawson, Anthony R., et al. “Pilot comparative study on the health of vaccinated and unvaccinated 6-to 12-year-old US children.” J. Transl. Sci 3.3 (2017): 1-12. Pilot comparative study on the health of vaccinated and unvaccinated 6-to 12-year-old US children Mawson Anthony Transl. Sci 2017

Vaccinations have prevented millions of infectious illnesses, hospitalizations and deaths among U.S. children, yet the long-term health outcomes of the vaccination schedule remain uncertain. Studies have been recommended by the U.S. Institute of Medicine to address this question. This study aimed

1) to compare vaccinated and unvaccinated children on a broad range of health outcomes, and

2) to determine whether an association found between vaccination and neurodevelopmental disorders (NDD), if any, remained significant after adjustment for other measured factors. A cross-sectional study of mothers of children educated at home was carried out in collaboration with homeschool organizations in four U.S. states: Florida, Louisiana, Mississippi and Oregon. Mothers were asked to complete an anonymous online questionnaire on their 6- to 12-year-old biological children with respect to pregnancy-related factors, birth history, vaccinations, physician-diagnosed illnesses, medications used, and health services. NDD, a derived diagnostic measure, was defined as having one or more of the following three closely-related diagnoses: a learning disability, Attention Deficient Hyperactivity Disorder, and Autism Spectrum Disorder. A convenience sample of 666 children was obtained, of which 261 (39%) were unvaccinated. The vaccinated were less likely than the unvaccinated to have been diagnosed with chickenpox and pertussis, but more likely to have been diagnosed with pneumonia, otitis media, allergies and NDD. After adjustment, vaccination, male gender, and preterm birth remained significantly associated with NDD. However, in a final adjusted model with interaction, vaccination but not preterm birth remained associated with NDD, while the interaction of preterm birth and vaccination was associated with a 6.6-fold increased odds of NDD (95% CI: 2.8, 15.5). In conclusion, vaccinated homeschool children were found to have a higher rate of allergies and NDD than unvaccinated homeschool children. While vaccination remained significantly associated with NDD after controlling for other factors, preterm birth coupled with vaccination was associated with an apparent synergistic increase in the odds of NDD. Further research involving larger, independent samples and stronger research designs is needed to verify and understand these unexpected findings in order to optimize the impact of vaccines on children’s health.

14) New Studies Reveal Vaccine Harm June 06, 2017 By Dr. Mercola

Jeffrey Dach MD

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Published on August 19, 2018 10:04

August 10, 2018

Italy Overturns Mandatory Vaccination Stands Up to Medical Fascism

[image error] Italy Overturns Mandatory Vaccination Stands Up to Medical Fascism

Italy is no stranger to Fascism having suffered under the dictatorship of Benito Mussolini who aligned Italy with Nazi Germany and deported 8,000 Jews to concentration camps. Ever since, Italy has experienced the back and forth, ebb and flow of fascism rearing its ugly head.(2)(12-14)

[image error]Just this week, in a striking rebuke to Medical Fascism, Italy’s new government overturned the Mandatory Vaccination Laws. Parents will now exercise their right to decide on timing and scheduling of vaccinations, or may choose to opt out entirely.(1)

Massive Rallies Not Covered By Media

Last year 2017, saw massive protest rallies and marches in Italy protesting mandatory vaccination laws. There was very little coverage from the US media. You can watch a video from the marches here and here.(16)

What is Medical Fascism ?

[image error]Government coercion which forces a citizen to undergo a medical procedure without their consent is the hallmark of medical fascism. (3-11) For example medical experimentation on concentration camp victims by Nazi doctors is medical fascism.(15)

Sterilization Laws of Indiana

Forcing people to undergo surgical procedure, sterilization, based on state law is a form of medical fascism. The state of Indiana passed a Eugenics inspired sterilization law in 1907. The law was struck down in 1921 by the Indiana Supreme Court after 2500 people had been involuntarily sterilized by the state. Sterilization of institutionalized patients continued to the mid-1970’s in 33 states. In all, about 60,000 Americans were involuntarily sterilized. Similarly forcing people or their children to undergo vaccination is medical fascism.

[image error]Conclusion: We must be vigilant and protect our freedom. We must stand with Italy against medical fascism of any kind, including mandatory vaccination and forced sterilization.

Link to this article:

Jeffrey Dach MD

Articles with related interest:

Aluminum in Vaccines Causes Autism

The Failure of Global Polio Eradication

Which is More Dangerous Measles of Measles Vaccine ?

Donald Trump, Kennedy, Vaccines and Autism

Links and References

1) https://www.cnn.com/2018/08/07/health...

Why Italy’s U-turn on mandatory vaccination shocks the scientific community

By Gianluca Mezzofiore, CNN Updated 1:59 PM ET, Tue August 7, 2018

League leader and Interior Minister Matteo Salvini said in June that the 10 obligatory vaccinations, which include measles, tetanus and polio, “are useless and in many cases dangerous, if not harmful,” according to ANSA news agency.

“I confirm the commitment to allow all children to go to school,” he added. “The priority is that they don’t get expelled from the classes.”

Health Minister Giulia Grillo, a Five Star member, said the government wants to “spur school inclusion and simplify rules for parents.”

2) https://www.bbc.com/news/world-europe...

Italy’s mixed feelings about Fascism By David Willey BBC News, Rome

Former Prime Minister Silvio Berlusconi, who is actively campaigning for re-election in next month’s general election, set off a chorus of outrage this week.

He suggested, while attending a Holocaust Memorial Day ceremony in Milan, that the Duce had not been as entirely bad as the history books made out. In fact he had done some “good things”.

Mr Berlusconi said that the racial laws, which led to 8,000 Italian Jews being herded off to death camps, were Mussolini’s “worst mistake”.

Mr Berlusconi was even rebuked by Italy’s head of state, President Giorgio Napolitano, who said that democratic Italy knew that Fascism was an “aberration”.

The canny media magnate was immediately accused of courting extreme right-wing support for his proposed new People of Freedom party coalition in the run-up to the election on 24-25 February.

3) https://www.newparadigm.ws/natural-he...

Medical Fascism Dealing With The Establishment’s Destructive Health Regime Paul A Philips

4) https://realfarmacy.com/vaccination-e...

Avoiding Vaccinations Under Medical Fascism by PAUL FASSA

5) http://freedom-articles.toolsforfreed...

Mandatory Vaccinations Afoot: Medical Fascism Approaching Fast by Makia Freeman

as California has just achieved the horrific distinction of becoming the first state in the US to introduce compulsory vaccinations for both children and adults (bills SB277 and SB792 respectively). This goes to show that the NWO (New World Order) agenda of collectivism and medical fascism is fast approaching.

7) http://www.thedailysheeple.com/the-va...

8) http://birdflu666.wordpress.com/2009/...

9) https://yournewswire.com/airlines-con...

10) http://www.ronpaulinstitute.org/archi...

11) http://www.anh-usa.org/when-does-cron...

When Does Crony Medicine Become Fascist Medicine?

By anh-usa on September 20, 2016 Stop Poisoning Ourselves

It’s when the attorney general of California tries to stop medical exemptions for vaccines.

12) https://www.tandfonline.com/doi/abs/1...

Italian fascism: organization, enthusiasm, opinion

Paul Corner Pages 378-389 | Published online: 27 May 2010

13) https://fascistitaly.wordpress.com/be...

Benito Mussolini & the Italian Fascism State

14) https://www.britannica.com/place/Ital...

The Fascist era The rise of Mussolini

15) https://www.ushmm.org/wlc/en/article....

Nazi Medical Experiments United States Holocaust Memorial Museum

During World War II, a number of German physicians conducted painful and often deadly experiments on thousands of concentration camp prisoners without their consent.

16) https://thevaccinereaction.org/2017/0...

Vaccine Freedom Marches Across Italy Highlight Global Vaccination Agenda

by Barbara Loe Fisher Published June 20, 2017

June 2017 saw the biggest public demonstrations against forced vaccination held in Europe since the Victorian era,1 as tens of thousands of Italians of all ages marched for vaccine freedom of choice in Rome, Florence, Milan, Bologna, Turin, Cagliani and other cities.2 They marched in opposition to a May 19 decree endorsed by the government’s Health Minister and President mandating that school children receive multiple doses of 12 vaccines or be prohibited from attending school with fines of up to $7500 euro (about $9,700) assessed to non-compliant parents.3 4 5

Jeffrey Dach MD

7450 Griffin Road, Suite 190

Davie, Fl 33314

954-792-4663

www.jeffreydachmd.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

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jdach1.typepad.com/blog/

disc.yourwebapps.com/Indices/244066.html

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http://sci.med.narkive.com/covV2Qo2/jeffrey-dach-book-announcment-natural-medicine-101

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Published on August 10, 2018 12:14

July 8, 2018

Aluminum in Vaccines Cause Autism

[image error]

Aluminum in Vaccines Cause Autism

by Jeffrey Dach MD

The most alarming public health issue is the relentless increasing autism epidemic. New Jersey reports 1 in 34 children, and about 5 percent of Eight-Year-Old boys affected as of 2014.(10) If this rate continues, half of all children born in 2025 will be autistic according to Stephanie Seneff PhD.(11) Above image vaccine courtesy of wikimedia commons.

What is Causing the Epidemic ?

Our government health agencies, academic medicine and public health institutions have been silent on this question of what is causing the autism epidemic. They merely shrug their shoulders and say “we don’t know “, quickly adding, “It is certainly not vaccines“.

[image error]

It IS The Vaccines – Aluminum Adjutants in Vaccines Cause Autism

We now have 5 years of medical research, mostly from outside the United States, incriminating aluminum adjuvants in vaccines as the SOLE cause of autism epidemic. JB Handley does a nice job laying out the argument and summarizing this research.(3) He uses the web site, Vaccine Papers, as a good source for the documentation.(4) Many others have raised the red flag on aluminum adjuvants.(1-2)

[image error]Very High Aluminum Levels in Autistic Brains

Revelations about aluminum neuro-toxicity have been made even more urgent by the findings of Dr Christpher Exley who found extremely high aluminum content in post mortem brains of autistic individuals. (5-8) Left Image Aluminum Foil courtesy of Wikimedia commons.

Plausible Mechanism Has Been Discovered

Aluminum at the vaccine injection site is taken up by macrophages which travel to the brain causing micro-glial activation, inflammation and immune activation with increased IL-6 cytokine levels, and impaired neuro development, leading to many of the symptoms of autism in animal models.(12-23)

Studies on Aluminum Adjuvant Safety – Using Aluminum in the Placebo

The “authorities” have told us repeatedly that vaccines are safe, and the science is settled. You might then ask the obvious question, ” Where is the data on studies showing the safety of vaccine aluminum adjuvants“? The correct answer is: “There are no suitable safety studies.” (16) The FDA merely ASSUMED aluminum adjuvants to be safe. It appears the FDA is very good at assuming things. Another outrageous gimmick is the use of aluminum adjuvants in the placebos used in trials for FDA approval. (24-25) In these studies, half the patients are injected with the vaccine and the other half are injected with placebo, and the number of adverse reactions are reported. A placebo should contain inert sugar water, not an immunotoxic aluminum adjuvant. This simple ploy allows the immunotoxicity of the aluminum adjuvant to be ignored.(24-25)

Conclusion: Recent medical research makes a strong case for neuro-toxicity of aluminum adjuvants as the cause of our autism epidemic. The din of silence in the media has been quite remarkable. Nothing will change unless you get involved and bring about change. Print out this article and send it to all your friends, congressmen, doctors, and family members. It is time for the din of silence to become a deafening roar that cannot be ignored.

Watch the Video JB Handley Del Big Tree Interview: Aluminum in Vaccines and Autism

Book on Amazon: How to End the Autism Epidemic – September 19, 2018 by J.B. Handley

Articles with Related Interest:

HPV Vaccine the Greatest Scandal of Our Time

The Failure of Global Polio Eradication

References and links:

video: Dr Christopher Exley Aluminum Adjuvants in Vaccines

Video in French w/English Subtitles: Prof. Romain Gherardi: Aluminum in vaccines ends up in the Brain

1) Aluminum in Vaccines: What Everyone Needs to Know May 7, 2018 By Kendall Nelson Weston Price.

2) Miller, N. “Aluminum in childhood vaccines is Unsafe.” Journal of American Physicians and Surgeons 21.4 (2016): 109-117. Aluminum in childhood vaccines is Unsafe Miller N J Amer Physicians Surgeons 2016

3) International scientists have found autism’s cause. What will Americans do?

BY J.B. HANDLEY April 2, 2018

“there’s an ongoing, permanent immune-system activation in the brains of autistic people.”

Discovery #1: “Maternal Immune Activation” can cause autism

Discovery #1: Immune Activation from the Cytokine Interleukin-6

While Dr. Pardo and colleagues were the first to find this “microglial activation” in the brain of children with autism, this finding has now been replicated many times, here’s a study from Japan in 2013 finding the same thing:

“Maternal infection during pregnancy is associated with an increased risk of schizophrenia and autism in the offspring. Supporting this correlation, experimentally activating the maternal immune system during pregnancy in rodents produces offspring with abnormal brain and behavioral development. We have developed a nonhuman primate model to bridge the gap between clinical populations and rodent models of maternal immune activation (MIA).”

“In summary, our study supports a critical role of IL-6 elevation in modulating autism-like behaviors through impairments on synapse formation, dendritic spine development, as well as on neuronal circuit balance. These findings suggest that manipulation of IL-6 may be a promising avenue for therapeutic interventions.”

Discovery #2: Aluminum Adjuvant causes immune activation and is far more neurotoxic than previously thought

“Concerns about its [aluminum adjuvant’s] safety emerged following recognition of its unexpectedly long-lasting biopersistence within immune cells in some individuals, and reports of chronic fatigue syndrome, cognitive dysfunction, myalgia, dysautonomia and autoimmune/inflammatory features temporally linked to multiple Al-containing vaccine administrations.”

Discovery #3: Aluminum can increase IL-6 in the brain

Discovery #4: Hepatitis B vaccine induces IL-6 in postnatal rats

The Hep B vaccine rats, however, showed the kind of immune activation event we are seeing in autism (high IL-6) This is biological proof of the link between a vaccine — given to a post-natal animal — inducing an immune activation event, including the cytokine marker for autism, IL-6. A scientific first.

Discovery #5: High levels of aluminum in autism brains

No vaccine containing aluminum adjuvant has ever been explored for its relationship to autism, despite a growing and clear body of evidence implicating aluminum adjuvant in causing “immune activation,” the central cause of autism.

Will we look back one day and say that aluminum adjuvant caused the autism epidemic the way we say that Thalidomide triggered birth defects? I think we will, but that’s just my opinion.

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

4) Vaccine Papers Is Anonymous

Aluminum Adjuvant Toxicity

It is now known that aluminum adjuvants are not safely eliminated from the body, as assumed by vaccine advocates. Rather, they are taken up by immune system cells (macrophages) and transported around the body, including into the brain. Aluminum adjuvant can cause brain injury and autoimmune diseases.

Immune Activation Brain Injury

Human brain development is controlled by immune-system signals (i.e. “cytokines”). Activation of the immune system during brain development causes disruptions in these signals, resulting in permanent brain injury. The injury manifests as autism, schizophrenia and other mental illnesses. Adverse vaccine reactions are proven to stimulate a cytokine (interleukin-6) proven to cause autism. There is a large amount of research on this, by many laboratories around the world, but the connection to vaccines is being overlooked.

Aluminum and Immune Activation

Aluminum and immune activation are connected, because aluminum triggers immune activation, and interleukin-6 specifically. Aluminum stimulates IL-6 in the brain. Aluminum also stimulates Th2 activation, a type of immune activation shown to impair brain development in animal studies. So the issues of aluminum adjuvant toxicity and immune activation are connected.

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

free pdf

5) Mold, Matthew, et al. “Aluminium in brain tissue in autism.” Journal of Trace Elements in Medicine and Biology 46 (2018): 76-82. Aluminium in brain tissue in autism Mold Matthew Christopher Exley Journal Trace Elements 2018

6) Professor Chris Exley | 30th November 2017 | Infection/Disease, Innovation, Mental Health, Neurology, Hippocratic Post

7) ‘Perhaps we now have the link between vaccination and autism’: Professor reveals aluminium in jabs may cause sufferers to have up 10 times more of the metal in their brains than is safe

Aluminium crosses the membrane that separates the brain from blood

The metal accumulates in cells that maintain a constant internal environment

Autism sufferers may have genetic changes that cause them to hold aluminium

Disgraced doctor Andrew Wakefield linked autism to the MMR vaccine in 1995

His views are widely discredited, but the WHO says vaccine fears put many off

By Professor Chris Exley For The Hippocratic Post and Alexandra Thompson Health Reporter For Mailonline

Published: 11:03 EDT, 30 November 2017 | Updated: 11:56 EDT, 3 December 2017

8) Autism and aluminium: The din of silence. Professor Chris Exley | 14th January 2018

—————————————————–

9) Lyons-Weiler, James, and Robert Ricketson. “Reconsideration of the immunotherapeutic pediatric safe dose levels of aluminum.” Journal of Trace Elements in Medicine and Biology 48 (2018): 67-73. Reconsideration of the immunotherapeutic pediatric safe dose levels of aluminum LyonsWeiler Ricketson J Trace Elem Med Biology 2018

While the effect of our proposed reduction on the final antigenicity of the vaccine is unknown, the full effects of the high injected doses of aluminum on the developing brain are also unknown. Indications of accumulation of aluminum associated with autism were recently published [42] in which the majority of tissue samples from post-mortem brains of patients diagnosed with autism spectrum disorder (ASD) were found to contain high concentrations of aluminum. Many samples contained extremely high concentrations, and the study also localized aluminum in glial cells in the brain, consistent with aluminum-induced gliosis models of neurodevelopmental disorders.

10) Autism rates in NJ are the highest in the US, have tripled recently Lindy Washburn, Staff Writer April 26, 2018

11) Stephanie Seneff Autism calculations

12) Wei, Hongen, et al. “Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors.” Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1822.6 (2012): 831-842

“Here we show that mice with elevated IL-6 in the brain display many autistic features, including impaired cognitive abilities, deficits in learning, abnormal anxiety traits and habituations, as well as decreased social interactions. IL-6 elevation caused alterations in excitatory and inhibitory synaptic formations and disrupted the balance of excitatory/inhibitory synaptic transmissions. IL-6 elevation also resulted in an abnormal change in the shape, length and distributing pattern of dendritic spines. These findings suggest that IL-6 elevation in the brain could mediate autistic-like behaviors, possibly through the imbalances of neural circuitry and impairments of synaptic plasticity.”

13) Tomljenovic, Lucija, and C. A. Shaw. “Mechanisms of aluminum adjuvant toxicity and autoimmunity in pediatric populations.” Lupus 21.2 (2012): 223-230.

14) Tomljenovic, Lucija, and Christopher A. Shaw. “Do aluminum vaccine adjuvants contribute to the rising prevalence of autism?.” Journal of inorganic biochemistry 105.11 (2011): 1489-1499.

15) Couette, Maryline, et al. “Long-term persistence of vaccine-derived aluminum hydroxide is associated with chronic cognitive dysfunction.” Journal of inorganic biochemistry 103.11 (2009): 1571-1578.

16) Tomljenovic, L., and C. A Shaw. “Aluminum vaccine adjuvants: are they safe?.” Current medicinal chemistry 18.17 (2011): 2630-2637. Aluminum vaccine adjuvants are they safe Tomljenovic Shaw Cur med chem 2011

17) Shaw, Christopher A., and Michael S. Petrik. “Aluminum hydroxide injections lead to motor deficits and motor neuron degeneration.” Journal of inorganic biochemistry 103.11 (2009): 1555-1562.

18) Exley, Christopher, et al. “A role for the body burden of aluminium in vaccine-associated macrophagic myofasciitis and chronic fatigue syndrome.” Medical hypotheses 72.2 (2009): 135-139.

19) Agmon-Levin, N., G. R. V. Hughes, and Y. Shoenfeld. “The spectrum of ASIA:‘Autoimmune (Auto-inflammatory) Syndrome induced by Adjuvants’.” (2012): 118-120.

20) Luján, Lluís, et al. “Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA syndrome) in commercial sheep.” Immunologic research 56.2-3 (2013): 317-324.

21) Shaw, C. A., Y. Li, and L. Tomljenovic. “Administration of aluminium to neonatal mice in vaccine-relevant amounts is associated with adverse long term neurological outcomes.” Journal of inorganic biochemistry 128 (2013): 237-244.

22) Shaw, C. A., and L. Tomljenovic. “Aluminum in the central nervous system (CNS): toxicity in humans and animals, vaccine adjuvants, and autoimmunity.” Immunologic research 56.2-3 (2013): 304-316.

23) Israeli, Eitan, et al. “Adjuvants and autoimmunity.” Lupus 18.13 (2009): 1217-1225.

24) Safety studies of aluminum in vaccines lack immunotoxicity analysis of this immunological adjuvant: Ignorance or deception? Safety studies of aluminum in vaccines lack immunotoxicity Vinu Dec 2017

25) Ignoring immunotoxicity of aluminum adjuvants in vaccines, won’t make it go away 05 April 2018 Vinu Arumugham BMJ 2018;360:k1378

26) Comprehensive Guide to Autism pp 1585-1609 | Cite as Autism Spectrum Disorders and Aluminum Vaccine Adjuvants Lucija Tomljenovic Russell L. Blaylock Christopher A. Shaw

27) Gherardi, Romain Kroum, et al. “Biopersistence and brain translocation of aluminum adjuvants of vaccines.” Frontiers in neurology 6 (2015): 4.

28) Crépeaux, Guillemette, et al. “Highly delayed systemic translocation of aluminum-based adjuvant in CD1 mice following intramuscular injections.” Journal of inorganic biochemistry 152 (2015): 199-205.

29) Gherardi, Romain K., Josette Cadusseau, and François‐Jérôme Authier. “Aluminum Particle Biopersistence, Systemic Transport, and Long‐Term Safety: Macrophagic Myofasciitis and Beyond.” Vaccines and Autoimmunity. Hoboken, NJ, USA: John Wiley & Sons, Inc, 2015. 261-270.

30) Shaw, C. A., Y. Li, and L. Tomljenovic. “Administration of aluminium to neonatal mice in vaccine-relevant amounts is associated with adverse long term neurological outcomes.” Journal of inorganic biochemistry 128 (2013): 237-244.

Jeffrey Dach MD

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Published on July 08, 2018 06:39

June 24, 2018

Fibrinolytic and Proteolytic Enzymes Medical Use

[image error] Fibrinolytic and Proteolytic Enzymes, Medical Use

by Jeffrey Dach MD

Sam is a 24 year old with a swollen painful ankle after an injury playing basketball. Xrays are negative for fracture, but Sam cannot walk and stays at home applying ice packs. Jim is a 62 year old who sees a Cardiologist for episodes of chest pain, and was diagnosed with “stable angina” and given nitro pills. Ralph sees a urologist for an enlarged prostate, and was given the diagnosis of BPH (Benign Prostatic Hyperplasia). Sue has chronic sinusitis and bronchitis with thick mucus. Neal had two episodes of a “mild” stroke with transient slurred speech.

What do all these patients have in common?

They could all benefit from proteolytic enzymes available at the health food store without a prescription. Since these are supplements, it is unlikely their doctor would mention it. Left image Scanning Electron Microscope of fibrin strands courtesy of CNN.

The three major enzymes are

1) Serrapeptidase,

2) Nattokinase and

3) Lumbrokinase.

Serrapeptidase is made by the silk worm, and used to digest the cocoon. Serrapeptidase has anti-inflammatory activity, and has been suggested as a replacement for NSAID anti-inflammatory drugs like Ibuprofen and Indomethacin. Serrapeptidase is just as effective without the adverse side effects of NSAIDS.

“Serratiopeptidase or serrapeptase is a protein (proteolytic) enzyme isolated from the non-pathogenic enterobacteria Serratia E15 found in silkworms. Serratiopeptidase often prescribed in various specialties like surgery, orthopedics, otorhinolaryngology, gynecology and dentistry for its anti-inflammatory, anti-endemic and analgesic effects . In the research in recent years, exploration illustrated enzyme also plays a vital role in the management of atherosclerosis as it does possess fibrinolytic and caseinolytic properties. ” quote (1)

Blood clots, cysts and arterial plaque are all gradually dissolved. Over 50 clinical trials from Europe and Asia attest to the ability of Serrapeptase to successfully treat conditions ranging from sprains, torn ligaments, post-operative swelling (edema), fibrocystic breast disease, deep vein thrombosis (DVT), carpal tunnel syndrome, ear, nose and throat infections and atherosclerosis. Serrapeptase literally digests inflammatory tissue.”Quote(8)

Serrapeptidase useful for Ankle Sprains

Dr Esch studied ankle sprains in 66 patients finding the use of Serrapeptidase significantly reduced pain and swelling after the injury.(2)

Nattokinase

Nattokinase comes from fermented soy products and a staple of the Japanese diet. Nattokinase has fibrinolytic effects and thought to be useful in prevention of cardiovascular disease, and is currently undergoing a clinical trial at University of Southern California, Dr Howard Hodis. (70):

“Various animal and human trials have demonstrated that NK improves blood circulation and helps decrease the risk of a variety of cardiovascular diseases without producing any adverse side effects.”quote (22)

[image error]Lumbrokinase

Lumbrokinase comes from earthworms and is the most potent fibrinolytic enzyme of the three. It was found effective in improving myocardial perfusion and reducing angina symptoms in patients with coronary artery disease.(1)

Left Image: Improvement in Myocardial Perfusion Scan in Angina Patient after Lumbrokinase. Courtesy of Kasim 2009. Left column before treatment. Right column alter treatment. Note perfusion defect between white arrows resolves after treatment.(26)

Lumbrokinase was useful in treatment of Ischemic Stroke, angina, myocardial ischemia, deep venous thrombosis, hypertension, vascular dementia and hypercoagulation-associated complications.(27)

“serrapeptase is not considered a strong fibrinolytic enzyme and should primarily be used for inflammation and pain association with oral/facial surgeries, sinus infection, arthritis, or chronic airway diseases. Respectively, nattokinase and lumbrokinase would be more suited for patients with mild and severe hypercoagulation or for patients with low and high cardiovascular risks.” Quote from (27)

Proteolytic Enzymes Dissolve Biofilms – Assist Antibiotics

A number of studies show that proteolytic enzymes enhance antibiotic effects by breaking up biofilms. The enzymes are useful add-ons for antibiotic treatment of infectious micro-organisms known to produce bio-films.

Find Lumbrokinase, Nattokinase and Serrapeptidase on Amazon

Jeffrey Dach MD

7450 Griffin Road, Suite 180/190

Davie, Fl 33314

954-792-4663

Links and References

https://www.sciencedirect.com/science...

1) Tiwari, Manju. “The role of serratiopeptidase in the resolution of inflammation.” Asian journal of pharmaceutical sciences 12.3 (2017): 209-215.

Serratiopeptidase or serrapeptase is a protein (proteolytic) enzyme isolated from the non-pathogenic enterobacteria Serratia E15 found in silkworms. Serratiopeptidase often prescribed in various specialties like surgery, orthopedics, otorhinolaryngology, gynecology and dentistry for its anti-inflammatory, anti-endemic and analgesic effects [42]. In the research in recent years, exploration illustrated enzyme also plays a vital role in the management of atherosclerosis as it does possess fibrinolytic and caseinolytic properties [43]. Like most enzymes, serratiopeptidase also possesses broad substrate affinity and has been to be reported therapeutically useful in the management of pain and inflammation.

Sprained Ankle

2) https://www.ncbi.nlm.nih.gov/pubmed/2...

Esch, P. M., H. Gerngross, and A. Fabian. “Reduction of postoperative swelling. Objective measurement of swelling of the upper ankle joint in treatment with serrapeptase–a prospective study.” Fortschritte der Medizin 107.4 (1989): 67.

Using a quantitative standardized procedure, the swelling of the ankle produced by supination trauma was measured. In the 66 patients with fresh rupture of the lateral ligament treated surgically at our Department between December 1986 and April 1987, a prospective study of the effect of serrapeptase (Aniflazym) on post-operative swelling and pain was carried out in 3 randomized groups of patients. In the group receiving the test substance, the swelling had decreased by 50% on the third post-operative day, while in the other two control groups (elevation of the leg, bed rest, with and without the application of ice) no reduction in swelling had occurred at that time. The difference is statistically significant (p = 0.013). Decreasing pain correlated for the most part with the reduction in swelling. Thus, the patients receiving the test substance more rapidly became pain-free than did the control groups. On the basis of these results, serrapeptase would appear to be an effective preparation for the post-operative reduction of swelling, in comparison with the classical conservative measures, for example, the application of ice.

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https://www.globalhealingcenter.com/n...

3) The Health Benefits of Serrapeptase Dr. Edward Group DC, NP, DACBN, DCBCN, DABFM Last Updated on June 5, 2017

Discovered in the early 1970’s, this proteolytic enzyme was isolated from the Serratia species of bacteria located in the intestines of silkworms.

references

4) Kee WH, Tan SL, Lee V, Salmon YM. The treatment of breast engorgement with Serrapeptase (Danzen): a randomised double-blind controlled trial. Singapore Med J. 1989 Feb;30(1):48-54.

5) Mazzone A, Catalani M, Costanzo M, Drusian A, Mandoli A, Russo S, Guarini E, Vesperini G. Evaluation of Serratia peptidase in acute or chronic inflammation of otorhinolaryngology pathology: a multicentre, double-blind, randomized trial versus placebo. J Int Med Res. 1990 Sep-Oct;18(5):379-88.

6) Kakinuma A, Moriya N, Kawahara K, Sugino H. Repression of fibrinolysis in scalded rats by administration of Serratia protease. Biochem Pharmacol. 1982 Sep 15;31(18):2861-6.

http://www.notjustnotes.ws/Serrapepta...

7) SERRAPEPTASE Studies and Technical Information Serrapeptase – Scientific Background of the Most Potent Proteolytic Enzyme

Dr. Michelle Kmiec

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https://highlevelwellness.ca/blogs/ne...

8) Conquer Inflammation with Serrapeptase By Zoltan P. Rona, M.D., M.Sc.

9) Mazzone A, Catalani M, Costanzo M, et al. Evaluation of Serratia peptidase in acute or chronic inflammation of otorhinolaryngology pathology: a multicentre, double-blind, randomized trial versus placebo. J Int Med Res 1990;18:379-88.

9) Nakamura S, Hashimoto Y, Mikami M, et al. Effect of the proteolytic enzyme serrapeptase in patients with chronic airway disease. Respirology 2003;8:316-20.

10) Tachibana M, Mizukoshi O, Harada Y, et al. A multi-centre, double-blind study of serrapeptase versus placebo in post-antrotomy buccal swelling. Pharmatherapeutica 1984;3:526-30.

11) Harris Interactive Over-The-Counter Pain Medication Study Sponsored by the National Consumers League. January 30, 2003. Chairman of Harris Poll, New York, NY: Humphrey Taylor. Contact: www.harrisinteractive.com and www.nclnet.org.

12) Tachibana M, et al. A muti-centre, double-blind study of serrapeptase versus placebo in post-antrotomy buccal swelling. Pharmatherapeutica; 1984; 3(8); 526-30.

13) Panagariya A, Sharma AK. A preliminary trial of serratiopeptidase in patients with carpal tunnel syndrome. J Assoc Physicians India; 1999; 47 (12); 1170-1172.

14) Kee WH, et al. The treatment of breast engorgement with Serrapeptase (Danzen): a randomized double-blind controlled trial. Singapore Med J.; 1989 30 (1); 48-54.

15) Sasaki S, et al. Serrapeptase-induced lung injury manifesting as acute eosiniphilic pneumonia. Nihon Kokyuki Gakkai Zasshi. 2000; 38 (7); 540-4.

16) Desser L, Rehberger A. Oncology. Induction of tumor necrosis factor in human peripheral-blood mononuclear cells by proteolytic enzymes. 1990;47(6):475-7.

17) Koyama A, Mori J, Tokuda H, Waku M, Anno H, Katayama T, Murakami K, Komatsu H, Hirata M, Arai T, et al. Augmentation by serrapeptase of tissue permeation by cefotiam]. Jpn J Antibiot. 1986 Mar;39(3):761-71.

18) Sivaramakrishnan G, Sridharan K. Role of Serratiopeptidase After Surgical Removal of Impacted Molar: A Systematic Review and Meta-analysis. J Maxillofac Oral Surg. 2018 Jun;17(2):122-128.

https://www.sciencedirect.com/science...

19) Gupte, Vandana, and Umesh Luthra. “Analytical techniques for serratiopeptidase: A review.” Journal of Pharmaceutical Analysis 7.4 (2017): 203-207.

free pdf

https://www.journal-surgery.net/artic...

20) Bhagat, Shivani, Monika Agarwal, and Vandana Roy. “Serratiopeptidase: a systematic review of the existing evidence.” International Journal of Surgery 11.3 (2013): 209-217.

CONCLUSION: Serratiopeptidase is being used in many clinical specialities for its anti-inflammatory, anti-edemic and analgesic effects. It is even being promoted as a health supplement to prevent cardiovascular morbidity.

21) https://www.ncbi.nlm.nih.gov/pubmed/1...

Respirology. 2003 Sep;8(3):316-20. Effect of the proteolytic enzyme serrapeptase in patients with chronic airway disease. Nakamura S1, Hashimoto Y, Mikami M, Yamanaka E, Soma T, Hino M, Azuma A, Kudoh S.

The proteolytic enzyme serrapeptase (SER) is widely used in clinical practice in Japan. We investigated the effect of SER on sputum properties and symptoms in patients with chronic airway diseases.

METHODS: This study was an open-labelled trial with a non-treatment control group. Patients were randomly assigned to oral treatment with (n = 15) and without (n = 14) SER 30 mg/day for 4 weeks. Patients collected sputum samples for about 4 h in the morning on the day the trial began and 4 weeks later. We measured the amount of sputum by weighing. Part of each sputum sample was weighed and then completely dried and reweighed. The percentage solid component, viscosity and elasticity of the sputum were measured. Mucociliary transportability index was measured using ciliated bovine trachea ex vivo. Sputum smears were also prepared to count sputum neutrophils. Patients’ symptoms were assessed by a questionnaire that used a visual analogue scale.

RESULTS: After 4 weeks of SER treatment, sputum weight in the morning, percentage solid component, viscosity and elasticity of sputum, sputum neutrophil count, frequency of coughing and frequency of expectoration significantly decreased. The mean mucociliary transportability index increased from 13.3 +/- 1.8 to 24.4 +/- 2.5 (P = 0.0103).

CONCLUSIONS: SER may exert a beneficial effect on mucus clearance by reducing neutrophil numbers and altering the viscoelasticity of sputum in patients with chronic airway diseases.

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

Nattokinase

https://www.ncbi.nlm.nih.gov/pmc/arti...

22) Weng, Yunqi, et al. “Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease.” International Journal of Molecular Sciences 18.3 (2017).

NK can break down blood clots by directly hydrolyzing fibrin and plasmin substrate, converts endogenous prourokinase to urokinase (uPA), degrades PAI-1 (plasminogen activator inhibitor-1), and increases tissue plasminogen activator (t-PA) which supports fibrinolytic activity (Figure 3: Mechanism of action) [2]. Unlike common fibrinolytic proteases, such as t-PA and uPA, which can produce various side effects such as bleeding, NK exhibits little to no side effects. Studies also indicate that an oral administration of NK can be absorbed by the intestinal tract [3,4]. NK exhibits strong fibrinolytic activity after intraduodenal absorption. These characteristics make NK a versatile and potent fibrinolytic enzyme that can be used to combat blood clots.

Nattokinase exhibits exceptionally potent fibrinolytic activity. Natto, a soybean product fermented by B. subtilis (natto) and rich in NK, has been served as a traditional food in Asia for hundreds of years and has recently garnered increased interest in Western medicine. Various animal and human trials have demonstrated that NK improves blood circulation and helps decrease the risk of a variety of cardiovascular diseases without producing any adverse side effects. The unpleasant odor and texture of natto limits its utilization as a dietary nutriment. Costly and complicated extraction and purification processes have inhibited the general use of NK as a nutraceutical. Currently, NK is sold as a dietary supplement in the United States, Canada, and Europe. It is available as a powder contained within a vegetable-based capsule.

https://www.sciencedirect.com/science...

23) Hsia, Chien-Hsun, et al. “Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects.” Nutrition research 29.3 (2009): 190-196.

pdf

24) Xu, Jianping, et al. “Thrombolytic effects in vivo of nattokinase in a carrageenan-induced rat model of thrombosis.” Acta haematologica 132.2 (2014): 247-253.

Nattokinase is a serine protease produced by Bacillus subtilis during the fermentation of the soybean product natto. The fibrinolytic activity and thrombolytic effects of nattokinase have been observed in vitro, but the effect in vivo has still to be researched. The objective of this study was to demonstrate the activity of nattokinase in vivo. Methods: To establish a rat model of thrombosis, κ-carrageenan was injected subcutaneously into the toes of Sprague-Dawley (SD) rats. Histological examination confirmed thrombosis. The rats were then treated with varying doses of nattokinase and the resulting thrombolysis was histologically assessed. ELISA was used to determine the levels of the fibrin/fibrinogen degradation products (FDPs) and D-dimer, which are sensitive indices of fibrinolytic activity. Vermis kinase, a known thrombolytic agent, was used as a positive control. Results: Biopsy results revealed partial thrombolysis in the tail vessels of the rats treated with nattokinase or vermis kinase. FDP and D-dimer levels were higher in rats treated with high-dose nattokinase than in those treated with saline. No difference in FDP or D-dimer levels was observed between rats treated with high-dose nattokinase and those treated with vermis kinase. Conclusions: Both the histological and physiological evidence from this study indicate that nattokinase exerts thrombolytic effects in vivo.

https://www.ncbi.nlm.nih.gov/pmc/arti...

25) Kurosawa, Yuko, et al. “A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles.”

Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p

+++++++++++++++++++++++++++++++++++++++++++++++

Lumbrokinase Boluoke® (lumbrokinase) Canada RNA Biochemical Inc.

26) Myocardial Perfusion Scan before and after Lumbrokinase

Kasim, Manoefris, et al. “Improved myocardial perfusion in stable angina pectoris by oral lumbrokinase: a pilot study.” The Journal of Alternative and Complementary Medicine 15.5 (2009): 539-544. Improved myocardial perfusion in stable angina pectoris by oral lumbrokinase. Kasim 2009

Recent clinical trials confirmed its clinical efficacyin the treatment of CAD and thrombotic cerebral infarct,8,9

albeit publication related to the former has been largely con-fined to the Chinese language literature.

Two (2) capsules of TrombolesÒ(The Institute of Biophy-sics, Chinese Academy of Sciences, Beijing), each containing

250 mg lumbrokinase extract equivalent to 300,000 U oflumbrokinase derived from an artificially culturedLumbricusstrain, were administered three times daily for 30 consecu-tive days.

Lumbrokinase effects a reduction in the degree and extent of inducible myocardial ischemia with amelioration of anginal symptoms in patients with CAD with stable angina.

http://www.townsendletter.com/May2018...

27) MAY 2018 Lumbrokinase – An Enzyme for More Than Just Circulatory Health! by Martin Kwok, BSc, MSAOM, ND

28) http://townsendletter.com/May2018/Lum...

REFERENCES

lumbrokinase is primarily a fibrinolytic enzyme and it possesses both direct and indirect fibrinolytic effects.

It can activate the innate plasminogen system and also can achieve direct fibrinolysis independent of the plasminogen system (see Diagram 1). In 2004, Zhang el al discovered that lumbrokinase also inhibits PAI-1 activity and enhances t-PA activity.4 In addition to being a strong fibrinolytic agent, lumbrokinase may indirectly achieve anticoagulation by inhibiting platelet functions.

Potential Clinical Applications

As an oral enzyme supplement, lumbrokinase is not allowed or approved to make any therapeutic claims in North America. However, by looking into available animal and human research, it is not too hard for anyone to see the following potential applications:

Ischemic Stroke. To further explore the traditional medical uses of earthworms in stroke, naturally one of the most intensely researched areas has been in the prevention and treatment of ischemic stroke patients. Lumbrokinase has been shown to be safe and effective for treating acute ischemic stroke by lowering blood viscosity, preventing re-perfusion damage, and reducing neural deficits.7-9 It was also shown to improve the efficacy of aspirin as a secondary prevention of stroke.10,11 In fact, for people who are resistant to aspirin (thus does not benefit from taking aspirin as a prevention), lumbrokinase appears to negate aspirin resistance and potentially help achieve the goal of cardiovascular disease prevention.12

On a milligram to milligram basis, the fibrinolytic strength of lumbrokinase is about 300-fold stronger than serrapeptase

On a milligram to milligram basis, the fibrinolytic strength of lumbrokinase is about 30-fold stronger than nattokinase

Therefore, serrapeptase is not considered a strong fibrinolytic enzyme and should primarily be used for inflammation and pain association with oral/facial surgeries, sinus infection, arthritis, or chronic airway diseases. Respectively, nattokinase and lumbrokinase would be more suited for patients with mild and severe hypercoagulation or for patients with low and high cardiovascular risks.

28) Mihara H, et al. A novel fibrinolytic enzyme extracted from the earthworm, Lumbricus rubellus.

Japanese Journal of Physiology. 1991;41(3):461–472.

29) Ma EL, et al. Effects of Rongshuan No 1 (F-1) on the antithrombotic and antiplatelet aggregation. Journal of Shenyang

Pharmaceutical University. 2001;18(5):370-372.

30) He ZZ, et al. Separation and purification of earthworm fibrinolytic enzyme and the study of anti-thrombosis activity. Chinese

Journal of Biochemical Pharmaceutics. 2001;22(6):284-286.

31) Zhang J, et al. Experimental study on the effect of lumbrokinase on fibrinolysis in rats.

Chinese Journal of Pathophysiology. 2004;20(5):891-892.

32) Jiang DS, et al. Inhibition of platelet aggregation in hamsters by lumbrokinase extracted from Eisenia fetida.

Journal of Capital Medical University . 1994;15(4):291-294.

33) Zhao J, et al.Eisenia fetida Protease-III-1 Functions in Both Fibrinolysis and Fibrogenesis. J Biomed Biotechnol 2007;2007(5):97654.

34) Yang M, et al. Eisenia fetida lumbrokinase research VI – thrombolytic effect in rabbits and protective effects in experimental stroke model in hamsters. Biotechnology . 1995;5(3):9-11.

35) Li WY, et al. Observation of treating twenty-seven cases of ischemic stroke patients with lumbrokinase. New Chinese Medicine. 2003;34(4):63-64.

36) Zhang HY. Observation of treating acute ischemic stroke with lumbrokinase. Capital Medicine . 2000;7(3):45-46.

37) Zhang DJ, et al. Prevention of ischemic stroke recurrence using lumbrokinase. Capital Medicine . 2003;5(10):47-48.

38) Cao YJ, et al. Oral fibrinogen-depleting agent lumbrokinase for secondary ischemic stroke prevention: results from a

multicenter, randomized, parallel-group and controlled clinical trial.

Chin Med J (Engl). 2013 Nov;126(21):4060-5.

39) Sun MY, et al. Clinical Observations of Lumbrokinase Intervention in 60 Coronary Heart Disease Patients with Aspirin Resistance.

Chinese Journal of Gerontology . 2009; 29: 760-761.

40) Liu HS. Clinical observation of treating 60 angina patients with lumbrokinase. Tianjin Pharmacy . 2002;14(2):45-46.

41) Yi XF, et al. Efficacy of treating unstable angina seniors with lumbrokinase.Capital Medicine. 2002;9(9):57-58.

42) Zhou HS, et al. Clinical observation of treating unstable angina seniors with lumbrokinase capsules. Central Plains Medical

Journal . 2001;28(9):2-3.

43) Kasim M, et al. Improved myocardial perfusion in stable angina pectoris by oral lumbrokinase: a pilot study. J Altern Complement Med

. 2009 May;15(5):539-44.

44) Song JS, et al. Clinical analysis of treating 17 cases of deep venous thrombosis with lumbrokinase. Occupation and Health 2001;17(4):111-115.

45) Ye SZ, et al. Observation of treating 51 cases of essential hypertension with lumbrokinase. Clinical Medicine . 2007;27(9):59.

46) Gao Y, et al. Efficacy of combining lumbrokinase with nimodipine in the treatment of vascular dementia. Journal of Liaoning University of Traditional Chinese Medicine . 2008;10(11):5-7.

47) De Cicco M. The prothrombotic state in cancer: pathogenic mechanisms. Crit Rev Oncol Hematol . 2004 Jun;50(3):187-96.

48). Molnar S, et al. Procoagulant factors in patients with cancer.

Hematology . 2007 Dec;12(6):555-9.

49). Falanga A, et al. Hypercoagulability and tissue factor gene upregulation in hematologic malignancies. Semin Thromb Hemost

.2008 Mar;34(2):204-10.

50) Francis JL, et al. Effect of antihemostatic agents on experimental

tumor dissemination. Thrombosis and Hemostasis . 2002; 28:

29-38.

51) Caine GJ, et al. The hypercoagulable state of malignancy: pathogenesis and current debate. Neoplasia . 2002

Nov-Dec;4(6):465-73.

52) Clerk CP, et al. The effect of low molecular weight heparin on survival in patients with advanced malignancy. J Clin Oncol 2005 Apr 1;23(10):2130-5.

53). Kakkar AK, et al. Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin

advanced malignancy outcome study (FAMOUS).

J Clin Oncol . 2004 May 15;22(10):1944-8.

54) DeFeo K, et al. Use of dabigatran et exilate to reduce breast cancer progression. Cancer Biol Ther . 2010 Nov15;10(10):1001-8.

55) Li HY, et al. Antitumor activity of earthworm fibrinolytic enzyme.

Chinese Pharmacological Bulletin . 2004;20(8):908-910.

56) Chen H, et al. Effect of earthworm fibrinolytic enzyme

on the inhibition of invasion and metastasis in hepatocellular

carcinoma cell. Jiangsu Medical Journal. 2008;34(4):383-385.

57) Chang CX, et al. Anti-metastatic activity of earthworm fibrinolytic enzyme on hepatoma cell in vivo. Traditional Chinese Drug Research & Clinical Pharmacology . 2009;20(6):520-524.

58) Levi M, et al. Infection and inflammation and the coagulation system.

Cardiovasc Res . 2003 Oct 15;60(1):26-39.

59). Kitchens CS. Concept of hypercoagulability: a review of it

s development, clinical application, and recent progress.Semin Thromb Hemost . 1985 Jul;11(3):293-315.

60) Song WG, et al. Clinical observation of Boluoke with Lotensin, a new therapy for early stage diabetic nephropathy. Jiangxi

Medical Journal . 2010 July; 45(7): 667-668.

61) Gu XL, et al. Observation of the effectiveness of treating diabetic peripheral neuropathy by lumbrokinase. Chinese Journal of

Primary Medicine and Pharmacy. 2003 July; 10(7): 665.

62) Liao HE, et al. Cardio Protective Effects of Lumbrokinase and Dilong on Second-Hand Smoke-Induced Apoptotic Signaling in the Heart of a Rat Model. Chin J Physiol. 2015 Jun 30;58(3):188-96.

63) Fu YT, et al. Porous gelatin/tricalcium phosphate/genipin composites containing lumbrokinase for bone repair. Bone . 2015 Sep;78:15-22.

64) Fu YT, et al. Earthworm (Pheretima aspergillum) extract stim

ulates osteoblast activity and inhibits osteoclast differentiation.

BMC Complement Altern Med . 2014 Nov 11;14:440.

65) Wang CL, et al. Progress in lumbrokinase. Progress in Veterinary Medicine . 2009;30(11):86-90.

66) Tang YJ, et al. Lumbrokinase: A review of domestic research literatures. Capital Medicine. 2011;18(6):39-42.

67) Serrapeptase Monograph, Natural Health Products Ingredients Database, Health Canada. 2014 February 7.

68) Weng YQ, et al. Nattokinase: An Oral Antithrombotic

Agent for the Prevention of Cardiovascular Disease. Int J Mol Sci

. 2017 Mar; 18(3): 523.

69) Wang KY, et al. Recombinant protein production of earthwo

rm lumbrokinase for potential antithrombotic application.

Evid Based Complement Alternat Med. 2013;2013:783971.

70) Nattokinase Atherothrombotic Prevention Study Howard N Hodis MD University of Southern California. At the conclusion of this trial, the investigators expect to have sufficient evidence as to whether reducing the propensity for thrombus formation and/or increasing fibrinolytic activity can prevent the progression of atherosclerosis and cognitive decline.

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Fan Q, Wu C, et al. Some features of intestinal absorption of intact fibrinolytic enzyme III-1 from Lumbricus rubellus. Biochem Biophys Acta, 2001; 1526(3): 286-92

Gao Y, Qin MZ. Lumbrokinase in treatment of patients with hyperfibrinogenemia of coronary atherogenesis disease. Journal of Capital University of Medical Sciences, 1999; 4(20)

Gong B, Wu XY. Observation of using Baiao lumbrokinase capsules to treat ischemic cerebrovascular accident with hyperlipidemia. Capital Medicine, 2000; 7(12): 39

Guo ZF, Liu XX. Observation of treating ischemic cerebrovascular accident with Baiao lumbrokinase capsules. Capital Medicine, 2000; 7(11): 45

Huang ZD, Li ZW, Zhang WX. Lumbrokinase in treating cerebral infarction. Chinese Journal of New Drugs and Clinical Remedies, 2000; 6(19): 453-455

Jie WH. Clinical observation of treating unstable angina in seniors with lumbrokinase. Capital Medicine, 2000; 7(10): 37

Jin L, Jin H, Zhang G, Xu G. Changes in coagulation and tissue plasminogen activator after the treatment of cerebral infarction with lumbrokinase. Chinese Journal of Microcirculation, 2000; 23: 213-218.

Jing LR, Xu GZ. Dynamics of fibrinolysis and hemostasis in ischemic stroke patients, and the effects of lumbrokinase on those dynamics. Chinses Journal of New Drugs and Clinical Remedies, 1999; 18(1): 48-49

Liao RH. Analytical report of treating 30 patients of ischemic cerebrovascular disease with Panford lumbrokinase and nimodipine. Strait Pharmaceutical Journal, 1997; 9(3): 25-26

Liu J, Zhou LM, Ren Y. Lumbrokinase capsule vs Salvia miltiorrhiza tablet in treating coronary disease with angina pectoris. Chinese Journal of New Drugs and Clinical Remedies, 1999; 1(18): 17-19

Mihara H, Sumi H, Mizumotoh, et el. Oral administration of earthworm powder as a possible thrombolytic therapy ed In: Tamkak, Recent advance in thrombosis and fibrinolysis. Hapan Academic Press, 1996, 287.

Mihara H, Sumi H, Yoneta T, Mizumoto H, et al. A novel fibrinolytic enzyme extracted from the earthworm, Lumbricus rubellus. Jpn J Physiol, 1991; 41: 461-72.

Mihara H. A possibility of Earthworm powder as therapeutic agent for thrombosis. Thromb Haemost, 1988; 50: 258.

Pan SY. Treating Blood-Stagnation type angina with Baiao lumbrokinase. Capital Medicine, 1998; 9(5):40-41

Pang SQ, Ding MC, Xie SP, et al. A clinical study of therapeutic effectiveness in treating ischemic cerebrovascular disease with Lumbrokinase (Boluoke). Chinese Journal of Neurology and Psychiatry, 1993; 26(4): 229.OOOOOPark S, Kye KC, Sumi H, et al. Fibrinolytic activity of the earthworm extract. Thromb Haemost, 1989; 62: 545.

Park Y, Ryu E, Kim H, Jeong J, et al. Characterization of antithrombotic activity of lumbrokinase-immobilized polyurethane valves in the total artificial heart. Artif Organs,1999; 23: 210-4.

Qi W, Yu XB, et al. Effects of lumbrokinase on blood rheology of seniors with coronary arterial diseases. Chinese Journal of Microcirculation, 2000; 1(10): 55

Ryu GH, Park S, Kim M, et al. Antighrombogenicity of lumbrokinase-immobilized polyurethane. J Biomed Mater Res, 1994; 28: 1069-77.

Tang Y, Liang D, et al. Crystal structure of earthworm fibrinolytic enzyme component a: revealing the structural determinants of its dual fibrinolytic activity. J Mol Biol, 2002; 32(1): 57-68

Wang LH, Yao W. Vermis kinase (Boluoke) therapeutic evaluation to cerebral infarction and influence to blood rheology. Journal of Practical Medical Technology, 1998; 5(2).

Wang R, Chen Q, Fang XQ, et al. Effects of Fleroxacin combined with urokinase or earthworm kinase on bacterial biofilm. Acta Pharmaceutica Sinica, 1999; 9(34):662-665

Wang XL, Yan DC. Clinical observation of using Baiao lumbrokinase capsules to treat patients with coronary artery disease secondary to diabetes mellitus. Capital Medicine, 2000; 7(8): 38

Wu XQ, Wu C, et al. Immobilized earthworm fibrinolytic enzyme III-1 with carbonyldiimidazole activated agarose. Protein and Peptide Letters, 2002: 9(1): 75-80

Yang GR. Treating unstable angina with Baiao lumbrokinase capsules. Capital Medicine. 1999; 3(6): 30

Zhang GP, Jin HM, Zhang M, et al. Anticoagulative and fibrinolytic effects of lumbrokinase and their relation to tissue plasminogen activator. Chinese Journal of Geriatrics, 1998; 6(17): 366-368

Zhang GP, Qian RZ, et al. Experimental observation of the inhibitory effects of lumbrokinase on platelets. National Medical Journal of China, 1998; 5(78): 394-95

Zhang HY. Clinical evaluation of treating acute ischemic cerebrovascular disease with lumbrokinase. Capital Medicine, 2000; 7(3): 45-46

Zhang JQ, Jing CH. Clinical evaluation of using Baiao lumbrokinase in the treatment of central retinal vein occlusion. Capital Medicine, 1999; 6(2): 51

Zhang LP, et al. Preventative effects of lumbrokinase on experimentally induced emboli. Chinese Journal of Hemorheology, 1995, 11(10): 679-680

Zhang NH. Blood rheological changes of coronary artery disease patients prior and after lumbrokinase treatment. Chinese Journal of Hemorheology, 1999; 1(9): 63

Zheng HJ, Xu JM, Huang ZH. Lumbrkinase capsule vs ticlopidine in treating coronary artery disease with angina pectoris. Chinses Journal of New Drugs and Clinical Remedies, 2000; 5(19): 406-408

Zheng Z, Lin JN, et al. Observation of 20 unstable angina patients treated with Baiao lumbrokinase capsules. Capital Medicine, 2000; 7(6): 38

Zhao J, Fan R, et al. Assay of lumbrokinase with a chromophoric substrate. Protein and Peptide Letters, 1997; 4(6): 409-14

Zhou M, Wang FQ. The effects of lumbrokinase on blood rheology in patients with sudden hearing loss. Journal of Chinese Microcirculation, 2000; 3(4): 177-178

Zhou XD, Zhao RX, Zheng XR, Zhang H. Observation of Boluoke (lumbrokinase) treatment in the recovery of motor function after cerebral infarction. Chinese Journal of Western and Chinese Medicine Cooperation, 1997; 12 (17).

Jeffrey Dach MD

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Published on June 24, 2018 09:37

June 17, 2018

Evolocumab Are You Joking Me?

[image error] Evolocumab, Are You Joking Me?

by Jeffrey Dach MD

Ralph is a 48 year old divorce lawyer who arrives in my office with a history of familial hypercholesterolemia. Every lab panel since he was a kid showed a cholesterol of 340. Other family members had the same genetic abnormality, and some even died of heart attack at early age. About six months ago Ralph switched primary care doctors. His new doctor was alarmed by his high cholesterol, and started him on a statin drug which reduced his LDL cholesterol down to 95. However, thinking this was insufficient, the doctor added Evolocumab, to drive the LDL cholesterol even lower. Header image courtesy of LongevityFacts.com

FDA Approved in Dec 2017

Amgen’s Evolocumab (Repatha), was recently FDA approved, and requires an injection every two weeks. At $14,000 a year, Evolocumab is the most expensive cholesterol drug on the market. A similar PCSK9 inhibitor drug, bococizumab, under development by Pfizer was discontinued after a failed study.(7)

Lowest LDL in History

After the Evolocumab drug was added to the statin drug, Ralph’s labs showed an LDL cholesterol of 30, the lowest in the history of Western Civilization in a human. I looked at Ralph and asked him if he was all right. Not exactly, he said. Ralph has trouble sleeping ever since starting the cholesterol lowering drugs. He has been experiencing troublesome tingling and burning sensations on his arms at night while trying to sleep. In a nutshell, Ralph is miserable, and wants to know if he can safely stop the cholesterol medication.

“A Lifesaving Miracle Drug”

Many newspapers and Cardiologists proclaim Evolocumab is a “lifesaving” miracle drug.(1)(27) Let us see the data showing the number of lives saved. Here is the data table (below) from Dr Marc Sabatine’s FOURIER study .(2) In this study, 27,500 patients on statin drugs for atherosclerotic heart disease were randomized to either drug (Evolocumab) or placebo. The drug reduced the LDL-cholesterol by 60%, from 90 to 30 mg/dl.

Below Image Table 2 FOURIER Study courtesy of Sabatine, Marc S., et al. “Evolocumab and clinical outcomes in patients with cardiovascular disease.” New England Journal of Medicine 376.18 (2017): 1713-1722.(2) Red arrow and circle=drug group. Green arrow and circle=placebo group.

[image error]

Cardiovascular Death- No Lives Saved

At the end of the 2.2 year study period there were eleven more deaths in the drug treated group. There were 251 cardiovascular deaths in the drug group (red arrow and circle), and only 240 in the placebo group (green arrow and circle). No lives saved.

Death from Any Cause – No Lives Saved

There were 444 deaths in the drug group (red arrow and circle), and only 426 in the placebo group (green arrow and circle). No lives saved. Eighteen more deaths in the drug treated group.

Hospitalization for Unstable Angina- No Difference

There were about the same number of hospitalizations for unstable angina in each group.

A Lifesaving Drug that Actually Kills More People Than Placebo ?

Perhaps someone can explain to me how this can be called a “lifesaving” miracle drug, when in fact, more people died in the drug group, and no lives were actually saved by the drug?

The Miraculous Benefit of Intensive Lowering of LDL Cholesterol

If one is coldly objective about the data coming in, one might say the PCSK9 drug trials have actually falsified the cholesterol theory of heart disease. Here we have the lowest LDL cholesterol ever achieved in the history of medicine, yet no lives are saved. Bryan Hubbard says in May 2017:

The PCSK9 drug trials are inadvertently challenging the cholesterol-heart disease theory. The drugs are bringing down ‘bad’ LDL cholesterol to unprecedented levels, and yet similar numbers of people are dying from heart attack and stroke whether taking the drug or a placebo.(20)

Concern for Adverse Neurocognitive Effects

The study reported no adverse effects of intensive lipid lowering. I find this difficult to believe in view of the FDA warning letter asking for a prospective study of neurocognitive adverse effects in the PCSK9 Inhibitor treated group.(29,30) Neurocognitive effect is a polite way to say loss of ability to focus, think and remember. In other words, drug induced dementia.

Dr Kristopher Swiger wrote an article in 2015 Drug Safety entitled: “PCSK9 Inhibitors and Neurocognitive Adverse Events: ” (31). He says:

On both theoretical and empirical grounds, concern for adverse neurocognitive effects currently extends to PCSK9 inhibitors.(31) These events included delirium, cognitive and attention disorders and disturbances, dementia, disturbances in thinking and perception, and mental impairment disorders.(32)

Adverse Psychiatric Reactions with Intensive Cholesterol Lowering

Lower cholesterol level is associated with a number of adverse psychiatric reactions, such as increased risk of suicidal and violent behavior, depression, aggression, and impulsivity . (35-37) Dr Eriksen wrote in Psychiatry Research 2017:

“low cholesterol is a risk marker for inpatient and post-discharge violence in acute psychiatry.”(39)

People with low cholesterol are more likely to commit violent crimes.(41) Dr Beatrice Golomb found that low cholesterol was associated with:

“severe irritability homicidal impulses, threats to others, road rage, generation of fear in family members, and damage to property.”(42)

Dr Michael Tatley writes about “Psychiatric adverse reactions with statins, fibrates and ezetimibe.” in Drug Safety 2007(43). He says:

“The reactions mentioned … include depression, memory loss, confusion and aggressive reactions….The observation that other lipid-lowering agents have similar adverse effects supports the hypothesis that decreased brain cell membrane cholesterol may be important in the aetiology of these psychiatric reactions.”

Dr Repo-Tiihonen investigated “associations between Total Cholesterol levels, violent and suicidal behavior, age of onset of the conduct disorder (CD) and the age of death among 250 Finnish male criminal offenders with ASPD (Antisocial Personality Disorder)”, finding lower cholesterol a prognostic marker for early unnatural death, and violent crimes. (44)

We Cannot Ignore the Massive Data of Negative Impact

In 2016 Drug Safety, Drs Cham, Koslik, and Golomb reoorted on “Mood, Personality, and Behavior Changes During Treatment with Statins: A Case Series.“ Adverse events related to cholesterol lowering drugs included violent ideation, irritability, depression, and suicide. These problems resolved when the drug was stopped and recurred when the drug restarted. (45)

Dr Alfonso Troisi says in Neuroscience & Biobehavioral Reviews 2009 :

“we cannot ignore the mass of data showing a negative impact of low cholesterol in some clinical populations or healthy subjects.”(38)

Conclusion: The lack of mortality benefit reported in the FOURIER study in spite of the lowest LDL levels in medical history actually falsifies the cholesterol theory of heart disease. Rather than call for more intensive cholesterol lowering with new drugs, cardiologists should wake up and admit this does more harm than good.

Articles with Related Interest

Familial Hypercholesterolemia and Statin Drugs

Jeffrey Dach MD

7450 Griffin Road

Suite 180/190

Davie, Florida 33314

954-792-4663

Links and References

Header image courtesy of LongevityFacts.com

Evolocumab and clinical outcomes in patients with cardiovascular disease.” New England Journal of Medicine

1) New wonder drug can ‘slash the risk of heart attack, stroke or death by a QUARTER’ compared with just statins. The Sun U.K. Prof Sir Nilesh Samani, of the British Heart Foundation, said: “Creating new treatments with this approach could prove life-saving for patients with high cholesterol and those who cannot tolerate statins.”

2) Sabatine, Marc S., et al. “Evolocumab and clinical outcomes in patients with cardiovascular disease.” New England Journal of Medicine 376.18 (2017): 1713-1722.

In terms of individual outcomes, evolocumab had no observed effect on cardiovascular mortality

……no observed effect on the rates of hospitalization for unstable angina, cardiovascular death or hospitalization for worsening heart failure, or death from any cause (Table 2).

3) Correspondence. Evolocumab in Patients with Cardiovascular Disease August 24, 2017 . N Engl J Med 2017; 377:785-788

The FOURIER trial showed no benefit of evolocumab on cardiovascular mortality after 26 months, and there was a nonsignificant increase in deaths from any cause among patients who received evolocumab as compared with those who received placebo (444 deaths vs. 426 deaths).

However, there was a 1.2-percentage-point absolute difference in the rate of myocardial infarction in the evolocumab group. One explanation is that most of the myocardial infarctions in the trial were not ST-segment elevation myocardial infarctions (STEMIs) but were related to elevated troponin levels of unclear clinical significance. These myocardial infarctions of lesser severity could be related to the fact that more patients underwent revascularization (which is associated with elevated troponin levels) in the placebo group than in the evolocumab group. Could the authors provide rates of STEMI, non-STEMI with a risk of a Thrombolysis in Myocardial Infarction (TIMI) risk score greater than 2, and non-STEMI with a TIMI risk score of 2 or less?

Rita F. Redberg, M.D.

University of California, San Francisco, San Francisco, CA

Under the assumption that the annual list price of evolocumab is $14,350,1 preventing one such event would cost approximately $861,000 in North America and $3,314,850 in Europe.

—————————————————————————–

4) Mar 22, 2017 Forbes Magazine. Not All Cardiologists Trust Amgen’s Cholesterol Drug Study John LaMattina , Contributor

Amgen did pay for this study–I would guess about $500 million or so.

5) Questioning the safety and benefits of evolocumab

Luca Mascitelli, Mark R Goldstein Published: January 2018

PCSK9 inhibitor treatment added to statins might be of little benefit.

6) Cholesterol lowering – proven or not? Repatha malcolm Kendrick. The downside is when you look at cardiovascular deaths. The total number of deaths from cardiovascular disease in the Repatha group was 251. The total number of deaths from cardiovascular disease in the placebo group was 240. So, 11 more people died of cardiovascular disease in the Repatha group.

The total number of, overall, deaths in the Repatha group was 444

The total number of, overall, deaths in the placebo group was 426

So, there were 18 more deaths in those taking Repatha.

7) Pfizer Ends Development Of Its PCSK9 Inhibitor ‘November 1, 2016 by Larry Husten CardioBrief

Immune issues and diminishing efficacy doomed the new drug.

Pfizer announced on Tuesday that it was discontinuing development of bococizumab, its cholesterol-lowering PCSK9 inhibitor under development.

———————————————-

8) Is the drug industry honest? Uffe Ravsnskov MD

You have probably heard or read about the recent trial named FOURIER where the drug company Amgen has tested a new cholesterol-lowering drug named Evolocumab (a so-called PCSK9-inhibitor) on almost 30,000 patients with heart disease. Half of them got the drug injected twice a month; the other half was injected with an innocent liquid (probably saltwater)., and both groups received statin treatment as well. The “bad” LDL-cholesterol was lowered by 59%; from 92 mg/dl (2.4 mmol/l) to 30 mg/dl (0.78 mmol/l). Very few cholesterol-lowering trials have succeeded with that before.

How do they explain that 444 died in the treatment group, but only 426 among the untreated? I mean, if the “bad” high LDL-cholesterol was the cause of atherosclerosis and heart disease, then we should expect that a 59% lowering of this “poisonous” molecule should lower mortality, not increase it.

9) Does the New Cholesterol Drug Repatha Save Lives?

Is evolocumab (Repatha) a breakthrough for treating high cholesterol? Or is it an expensive drug that won’t save any lives?

Joe GraedonMarch 27, 2017

10) The cholesterol and calorie hypotheses are both dead — it is time to focus on the real culprit: insulin resistance Clinical Pharmacist14 JUL 2017By Maryanne Demasi, Maryanne Demasi , Robert H Lustig , Aseem Malhotra

Similarly, the recent report of the efficacy of the latest ‘blockbuster’ drug evolocumab (Repatha, a PCSK-9 inhibitor) was underwhelming, despite the media hype. Published in The New England Journal of Medicine, the paper reported that evolocumab (together with a statin) lowered LDL-C by a whopping 60%, yet translated into only a 1.5% reduction in (non-fatal) CVD events[12]. Furthermore, evolocumab did not reduce total or cardiovascular mortality. Rather, there was a non-significant increase in mortality from CVD (n=251) compared with placebo (n=240), and a non-statistically significant increase in overall mortality in the experimental group (n=444) compared with placebo (n=426).

11) Dixon, Dave L., et al. “Clinical utility of evolocumab in the management of hyperlipidemia: patient selection and follow-up.” Drug design, development and therapy 11 (2017): 2121.

FOURIER trial. In March 2017, the FOURIER trial was published.9 This outcomes trial randomized 27,564 patients with ASCVD and LDL-C >70 mg/dL to receive evolocumab or placebo in addition to background statin therapy. Nearly 70% of patients were receiving high-intensity statins, and the median LDL-C was 92 mg/dL (IQR 80–109). The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization.

There were no significant differences in cardiovascular death, death from any cause, or hospitalization for unstable angina.

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

12) ACCP CARDIOLOGY PRN JOURNAL CLUB NEWSLETTER March 2017 |Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease (FOURIER) Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease

the lack of mortality benefit and the large price tag of evolocumab therapy propagate controversy regarding its clinical utility.

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

13) Evolocumab for High Cholesterol New Evidence Update ICER Sep 11 2017

As was reported in the meta-analysis of statin randomized trials, the reduction in MIs, strokes, and revascularization was greater in years 2+ than in the first year of therapy. However, the lack of reduction in CVD death overall and in years 2+ is concerning. Similar findings have been observed in other trials of intensification therapy. For instance, in the IMPROVE-IT trial, the addition of ezetimibe reduced cardiovascular disease event rates, but did not reduce CVD mortality (HR 1.00, 95% CI 0.89 -1.13).9

It is also concerning that there was no trend toward a reduction in death from cardiovascular disease and the increase in mortality was greater in years 2+ than it was in the first year of the trial. Studies of statin therapy for secondary prevention have consistently demonstrated a reduction in CVD and total mortality. Thus, we give evolocumab added to statin therapy an ICER rating of C+ (comparable or better) based on moderate certainty of a small net benefit compared to statin therapy alone . We considered a B+ rating (incremental or better), but the uncertainty introduced by the non -significant trend towards increased cardiovascular mortality in years 2+ of the trial (HR 1.12, 95% CI 0.88-1.42) led us to the more conservative assessment.

14) Will Evolocumab Help With Coronary Heart Disease?

By Naveed Saleh, MD, MS | Reviewed by Richard N. Fogoros, MD

Updated April 03, 2018

15) Amgen’s FOURIER cardiovascular outcomes trial. While the landmark study proved Repatha’s heart benefits, results showed the drug had no statistically significant effect on cardiovascular death.

16) Giugliano, Robert P., et al. “Clinical Efficacy and Safety of Evolocumab in High-Risk Patients Receiving a Statin: Secondary Analysis of Patients With Low LDL Cholesterol Levels and in Those Already Receiving a Maximal-Potency Statin in a Randomized Clinical Trial.” JAMA cardiology 2.12 (2017): 1385-1391.

Odyssey Praluent

17) Mar 10, 2018 The ODYSSEY Trial Ends Well — But Will It Be Enough? Larry Husten , Contributor Forbes

ODYSSEY compared alirocumab (Praluent, Sanofi/Regeneron) with placebo in 18,924 patients with a recent (1-12 months) heart attack (MI) or unstable angina.

The investigators also reported a significant reduction in overall mortality, from 4.1% in the placebo group to 3.5% in the alirocumab group (HR=0.85; CI: 0.73-0.98, p = 0.026). Because, in accordance with the predetermined statistical analysis plan, the reduction in CHD mortality did not achieve statistical significance, the reduction in overall mortality was considered an observational finding. As a result, this means the company will not be able to make a mortality reduction claim without qualification. Sanjay Kaul (Cedars-Sinai) commented that the mortality finding should not be considered robust.

CHD death: 2.2% for alirocumab versus 2.3%, p=0.38

(The drugs now have a list price of more than $14,000 per year but are usually discounted to about $9,000.)

18) Praluent Cuts Deaths by 29% for Those With Highest Cholesterol Levels, ODYSSEY Finds Mary Caffrey Coverage of the 67th Scientific Session of the American College of Cardiology.

A year ago, FOURIER showed evolocumab produced an overall reduction in cardiac events, especially heart attacks, and that benefit increased after the first year. But there was a slight, nonsignificant increase in all-cause death, and payers were not impressed with the results.

19) Dark arts pushing heart drugs Jerome Burne | 20th March 2016

20) The new pretender by Bryan Hubbard May 2017 (Vol. 28 Issue 2)

The PCSK9 drug trials are inadvertently challenging the cholesterol-heart disease theory. The drugs are bringing down ‘bad’ LDL cholesterol to unprecedented levels, and yet similar numbers of people are dying from heart attack and stroke whether taking the drug or a placebo (see main story).

21) How To Save Zero Lives For The Low, Low Cost Of Two Million Dollars And Change, Tom Naughton April 19, 2018

22) More cholesterol craziness 08/07/2017 DRUG BUST by Alan Cassels

23) Sick Pharma Commercial: Repatha – Pay or Die! Uncle Vince

24) https://vimeo.com/210502210 Repatha_Commercial

25) New Cholesterol Drugs Protect High Risk Heart Patients: MORE FAKE NEWS! Mar 17 2017 David Brownstein MD

26) Inflammatory and Cholesterol Risk in the FOURIER Trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) Erin A. Bohula, Robert P. Giugliano, Lawrence A. Leiter, Subodh Verma, Jeong-Gun Park, Peter S. Sever, Armando Lira Pineda, Narimon Honarpour, Huei Wang, Sabina A. Murphy, Anthony Keech, Terje R. Pedersen, Marc S. Sabatine

LDL-C reduction with evolocumab reduces cardiovascular events across hsCRP strata with greater absolute risk reductions in patients with higher-baseline hsCRP. Event rates were lowest in patients with the lowest hsCRP and LDL-C.

27) THE WALL STREET JOURNAL June 20 2017 Sumathi Reddy A Cholesterol Drug Tug-of-War Patients struggle for insurance approvals of PCSK9 inhibitors, powerful drugs that lowerbad cholesterol when statins don’t work

Some doctors believe PCSK9 inhibitors could be a lifesaving solution for millions of heart-disease patients.

odyssey

28) The ODYSSEY trial is first clinical trial to show a mortality benefit with a PCSK9 inhibitor—there was no such reduction observed in the FOURIER trial. TCTMD HeartBeat. ACC2018 By Michael O’Riordan March 10, 2018

For de Lemos, the mortality reduction is an important finding, but he pointed out the absolute difference between the placebo- and alirocumab-treated patients was just 0.6% over nearly 3 years. “It’s ‘lifesaving’ with a very small L,” he said.

Underberg, as well as Andrew Foy (Penn State Health, Hershey, PA), questioned the clinical applicability of the mortality benefit, with Foy somewhat underwhelmed by the absolute risk reduction.

Foy suggested post-ACS treatment would include high-intensity statin therapy followed by ezetimibe (Zetia, Merck/Schering-Plough), with use of a PCSK9 inhibitor reserved for patients with elevated LDL cholesterol levels.

ODYSSEY suggests that 64 patients need to be treated to prevent one MACE and 163 patients to prevent one death, said Steg. Among patients with LDL cholesterol levels ≥ 100 mg/dL, the number needed to treat to prevent one MACE is 29 and to prevent one death is 60.

29) This ‘miracle drug’ is really nothing but a dangerous dud

Health Sciences Institute 3/27/17.

Early on in the approval game, the FDA sent a letter to drugmakers who were tinkering with these PCSK9 meds (there’s another one on the market now called Praluent), warning about the very real potential of “neurocognitive adverse events” with them. Or, to say that more simply, dementia. These PCSK9 drugs can drop cholesterol levels to such unheard-of, dangerous lows that, as we’ve told you before, they are basically a prescription for losing your ability to focus, think and remember.

30) FDA CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER 125559Orig1s000 SUMMARY REVIEW

Applicant is seeking approval of alirocumab PRALUENT is indicated for long-term treatment of adult patients with primary hypercholesterolemia (non-familial and heterozygous familial)

Because the etiology of the rare post-marketing reports of cognitive impairment associated with statin use (class safety labeling change in 20 12) remains uncertain, the potential for PCSK9 inhibitors to have neurocognitive effects has been a focus of attention.

The table below from Dr. Roberts’s review summarizes the results. In the placebo -controlled trials, the preferred terms “confusional state” and “memory impairment” both occurred at a higher incidence in the alirocumab group (0.2% for each) than in the placebo group (

The reviewer recommended a randomized long term controlled trial that prespectively evaluates changes in neurocognitive function as a post marketing requirement

31) Swiger, Kristopher J., and Seth S. Martin. “PCSK9 Inhibitors and Neurocognitive Adverse Events: Exploring the FDA Directive and a Proposal for N-of-1 Trials.” Drug Saf 38 (2015): 519-526.

On both theoretical and empirical grounds, concern for adverse neurocognitive effects currently extends to PCSK9 inhibitors.

32) Early Evidence Linking PCSK9 Inhibitors to Neurocognitive Adverse Events: Does Correlation Imply Causation?Jun 01, 2015 | Kristopher Swiger, MD; Seth Shay Martin, MD, MHS, FACC Expert Analysis

two phase III efficacy and safety trials2,3 reported a greater incidence of CAEs in the PCSK9 treatment group.cognitive adverse events

The Open-Label Study of Long-Term Evaluation against LDL Cholesterol (OSLER) study4 was the first to report increased CAEs in the PCSK9 treatment group and likely prompted the FDA directive. The study enrolled 1,104 hypercholesterolemic patients, randomized them to receive 420 mg of evolocumab + standard of care or standard of care alone, and monitored the incidence of adverse events over one year. CAEs were more common in the evolocumab group with three reporting amnesia (

Earlier in 2015, the OSLER program released additional data2 from 4,465 participants with 11-month follow-up also that showed increased CAEs in the evolocumab group (0.9%) relative to the standard of care group (0.3%). These events were heterogeneous, including delirium, cognitive and attention disorders and disturbances, dementia, disturbances in thinking and perception, and mental impairment disorders.

33) New cholesterol-lowering blockbusters fast track to dementia

Researchers from Johns Hopkins crunched the clinical data and found that in one trial, patients were three times as likely to suffer serious cognitive problems – and in another, they were more than twice as likely. The problems included delirium, amnesia, difficulty in thinking and reasoning, and even dementia.

FDA did something shockingly out of character. It actually sent a letter to the companies developing the drugs warning them of “neurocognitive adverse events.”

34) Praluent: New Cholesterol Drugs Get Riskier By The Day Editor | January 15, 2015

Low cholesterol associated with Suicide

35) Kunugi, Hiroshi, et al. “Low serum cholesterol in suicide attempters.” Biological Psychiatry 41.2 (1997): 196-200.

Previous studies have shown an association between low serum cholesterol concentration and suicide; however, conflicting results have also been reported. To examine this potential association, cholesterol levels in 99 patients admitted to an emergency ward following an attempted suicide were compared with those in 74 nonsuicidal psychiatric inpatients, and those in 39 psychiatrically normal individuals with accidental injuries. Cholesterol concentrations in suicide attempters were found to be significantly lower compared with both psychiatric and normal controls, when sex, age, psychiatric diagnosis, and physical conditions (serum total protein and red blood cell count) were adjusted for. This significant relationship was observed in mood disorders and personality or neurotic disorders, but not in schizophrenia spectrum disorders. These results support the previous claim that lower cholesterol level is associated with an increased risk of suicidal behavior.

Suicide

36) Vevera, J., et al. “Cholesterol concentrations in violent and non-violent women suicide attempters.” European Psychiatry 18.1 (2003): 23-27. The aim of this study was to evaluate whether women with a history of violent suicide attempts have lower serum cholesterol concentrations than those who attempted suicide by non-violent methods. Our retrospective study used a case-control design to compare serum total cholesterol concentration, hematocrit, red blood cell count and body mass index (BMI) in women with a history of violent (n = 19) or non-violent (n = 51) suicide attempts and of non-suicidal controls (n = 70) matched by diagnosis and age. Analysis of covariance (ANCOVA) with age as the covariate was used to analyze differences in cholesterol levels in groups according to violence. Violence was found to be a significant factor (P = 0.016). Using the Scheffé test, a significant difference (P = 0.011) was revealed between the group of violent and non-violent suicide attempters and between the violent suicide attempters and the control group. Patients with a violent suicidal attempt have significantly lower cholesterol levels than patients with non-violent attempts and the control subjects. Our findings suggest that suicide attempts should not be considered a homogeneous group. They are consistent with the theory that low levels of cholesterol are associated with increased tendency for impulsive behavior and aggression and contribute to a more violent pattern of suicidal behavior.

37) Stevenson, R. J., and H. M. Francis. “The role of cholesterol in disorders of brain and behavior: human and animal perspectives.” Handbook of cholesterol. Wageningen Academic Publishers, 2016. 291-298..

Abnormal cholesterol metabolism is likely to have significant adverse impacts on the functioning of the brain and hence on behavior, given its key role in membrane function. In this chapter we examine the animal and human literature pertaining to links between abnormal cholesterol metabolism and impaired brain and behavioral function. In particular we focus on Alzheimer’s disease, suicide, depression, aggression, impulsivity, and autism. The literature indicates associations between all of these conditions and abnormalities in cholesterol metabolism, although the evidence base indicates substantial heterogeneity of outcome. An especially important line of evidence has come from lipid lowering medications, which have provided key causal data. This has suggested that abnormal cholesterol metabolism may have a more specialized role than was once first thought, affecting particular subgroups (e.g. violent suicides), rather than populations in general.

38) Troisi, Alfonso. “Cholesterol in coronary heart disease and psychiatric disorders: same or opposite effects on morbidity risk?.” Neuroscience & Biobehavioral Reviews 33.2 (2009): 125-132.Cholesterol in coronary heart disease psychiatric disorders effects on morbidity Troisi Alfonso Neuroscience Biobehavioral Reviews 2009

“we cannot ignore the mass of data showing a negative impact of low

cholesterol in some clinical populations or healthy subjects.”

39) Eriksen, Bjørn Magne S., et al. “Low cholesterol level as a risk marker of inpatient and post-discharge violence in acute psychiatry–A prospective study with a focus on gender differences.” Psychiatry research 255 (2017): 1-7.

Several studies indicate an association between low levels of serum cholesterol and aggressive behaviour, but prospective studies are scarce. In this naturalistic prospective inpatient and post-discharge study from an acute psychiatric ward, we investigated total cholesterol (TC) and high-density lipoprotein (HDL) as risk markers of violence. From March 21, 2012, to March 20, 2013, 158 men and 204 women were included. TC and HDL were measured at admission. Violence was recorded during hospital stay and for the first 3 months post-discharge. Univariate and multivariate binary logistic regression were used to estimate associations between low TC and low HDL and violence. Results showed that HDL level was significantly inversely associated with violence during hospital stay for all patients. For men, but not for women, HDL level was significantly inversely associated with violence the first 3 months post-discharge. Results indicate that low HDL is a risk marker for inpatient and post-discharge violence in acute psychiatry and also suggest gender differences in HDL as a risk marker for violence.

40) Banach, M., et al. “Intensive LDL-cholesterol lowering therapy and neurocognitive function.” Pharmacology & therapeutics 170 (2017): 181.

The key lipid-lowering target is to achieve guideline-recommended low-density lipoprotein cholesterol (LDL-C) levels, usually by using statins. The new treatment strategies for lipid-lowering therapy include using proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors as an exciting approach to reduce residual risk of cardiovascular diseases (CVD). However, concerns about possible adverse effects, including neurocognitive disorders, were issued by the Food and Drug Administration (FDA). The current disputable evidence does not allow definite conclusions as to whether statins contribute to, or cause, clinically meaningful cognitive impairment. Some evidence indicates a high rate of memory loss, while other evidence suggests a benefit in dementia prevention. This debate should not discourage appropriate statin and other lipid-lowering drug administration. However, prescribers should be aware of such potential drug-related side effects. Prospective controlled studies comparing the short- and long-term effects of different statins on cognitive function are warranted. The effects of intensive LDL-C lowering on neurocognition might be attributed to an off-target effect. It is also possible that pre-existing pathology and vascular risk may already be present outweighing any effect related to lipids. Gender, genetic, LDL-C-related genotypes and aging-related changes should also be considered. Some data indicate that carriers of apolipoprotein E (apoE) ε-4 allele, with low levels of apoA1 and high-density lipoprotein cholesterol have a distinct plasma lipid profile and may be more susceptible to neurocognitive dysfunction. Future research on lipid-lowering drugs and cognition is needed; careful study design and analysis will be critical.

Low Cholesterol Associated with Increased criminal violence

41) Golomb, Beatrice A., Håkan Stattin, and Sarnoff Mednick. “Low cholesterol and violent crime.” Journal of Psychiatric Research 34.4-5 (2000): 301-309.

BACKGROUND:Community cohort studies and meta-analyses of randomized trials have shown a relation between low or lowered cholesterol and death by violence (homicide, suicide, accident); in primates, cholesterol reduction has been linked to increased behavioral acts of aggression (Kaplan J, Manuck S. The effects of fat and cholesterol on aggressive behaviour in monkeys. Psychosom. Med 1990;52:226-7; Kaplan J, Shively C, Fontenot D, Morgan T, Howell S, Manuck S et al. Demonstration of an association among dietary cholesterol, central serotonergic activity, and social behaviour in monkeys. Psychosom. Med 1994;56:479-84.). In this study we test for the first time whether cholesterol level is related to commission of violent crimes against others in a large community cohort.

METHODS:We merged one-time cholesterol measurements on 79,777 subjects enrolled in a health screening project in Varmland, Sweden with subsequent police records for arrests for violent crimes in men and women aged 24-70 at enrollment; and with information on covariates. We performed a nested case control comparison of cholesterol in violent criminals – defined as those with two or more crimes of violence against others – to cholesterol in nonoffenders matched on age, enrollment year, sex, education and alcohol, using variable-ratio matching, with a nonparametric sign test.

RESULTS:One hundred individuals met criteria for criminal violence. Low cholesterol (below the median) was strongly associated with criminal violence in unadjusted analysis (Men: risk ratio 1.94, P=0.002; all subjects risk ratio 2.32, Pviolent criminals had significantly lower cholesterol than others identical in age, sex, alcohol indices and education, using a nonparametric sign test (P=0.012 all subjects; P=0.035 men).

CONCLUSIONS:Adjusting for other factors, low cholesterol is associated with increased subsequent criminal violence.

42) Golomb, Beatrice A., T. Kane, and Joel E. Dimsdale. “Severe irritability associated with statin cholesterol-lowering drugs.” Qjm 97.4 (2004): 229-235.

Methods: Six patients referred or self-referred with irritability and short temper on statin cholesterol-lowering drugs completed a survey providing information on character of behavioural effect, time-course of onset and recovery, and factors relevant to drug adverse effect causality.

Results: In each case the personality disruption, once evident, was sustained until statin use was discontinued; and resolved promptly with drug cessation. In four patients, re-challenge with statins occurred, and led to recrudescence of the problem. All patients experienced other recognized statin adverse effects while on the drug. Manifestations of severe irritability included homicidal impulses, threats to others, road rage, generation of fear in family members, and damage to property.

43) Tatley, Michael, and Ruth Savage. “Psychiatric adverse reactions with statins, fibrates and ezetimibe.” Drug Safety 30.3 (2007): 195-201.

The HMG-CoA reductase inhibitors (‘statins’) have come into widespread use internationally. There has been a long history of their use in New Zealand and this use has increased in recent years. There has also been an increase in the number of reports to the New Zealand Centre for Adverse Reactions Monitoring (CARM) of suspected psychiatric adverse reactions associated with statins. The reactions mentioned in these reports include depression, memory loss, confusion and aggressive reactions. Convincing reports to CARM of recurrence of these reactions upon rechallenge add weight to recent studies reporting serious psychiatric disturbances in association with statin treatment. Aggressive reactions associated with statins are poorly documented in the literature. These observations emphasise the need to be vigilant in looking for these reactions as they can have a significant personal impact on a patient. The observation that other lipid-lowering agents have similar adverse effects supports the hypothesis that decreased brain cell membrane cholesterol may be important in the aetiology of these psychiatric reactions.

44) Repo-Tiihonen, E., et al. “Total serum cholesterol level, violent criminal offences, suicidal behavior, mortality and the appearance of conduct disorder in Finnish male criminal offenders with antisocial personality disorder.” European archives of psychiatry and clinical neuroscience 252.1 (2002): 8.

Associations between low total serum cholesterol (TC) levels and antisocial personality disorder (ASPD), violent and suicidal behavior have been found. We investigated the associations between TC levels, violent and suicidal behavior, age of onset of the conduct disorder (CD) and the age of death among 250 Finnish male criminal offenders with ASPD. The CD had begun before the age of 10 two times more often in non-violent criminal offenders who had lower than median TC levels. The violent criminal offenders having lower than median TC levels were seven times more likely to die before the median age of death in the study material. The violent offenders having lower than median TC levels were eight times more likely to die of unnatural causes. The mean TC level of these male offenders with ASPD was lower than that of the general Finnish male population. Low TC levels are associated with childhood onset type of the CD, and premature and unnatural mortality among male offenders with ASPD. The TC level seems to be a peripheral marker with prognostic value among boys with conduct disorder and antisocial male offenders.

free pdf

45) Cham, Stephanie, Hayley J. Koslik, and Beatrice A. Golomb. “Mood, Personality, and Behavior Changes During Treatment with Statins: A Case Series.“ Drug safety-case reports 3.1 (2016): 1.

We sought to elicit history of central nervous system/behavioral changes in connection with statin and/or cholesterol-lowering drug use.

Participants (n = 12) reported mood/behavior change that commenced following statin initiation and persisted or progressed with continued use.

Reported problems included violent ideation, irritability, depression, and suicide. Problems resolved with drug discontinuation and recurred with rechallenge where attempted.

(1) Simvastatin 80 mg was followed in 5 days by irritability/depression culminating in suicide in a man in his 40s (Naranjo criteria: possible causality).

(2) Simvastatin 10 mg was followed within 2 weeks by depression in a woman in her 50s (probable causality).

(3) Atorvastatin 20 mg was followed in ~1 month by depression and irritability/aggression in a male in his 50s (probable causality).

(4) Atorvastatin 10 mg was followed in several months by aggression/irritability and depression culminating in suicide in a man in his 40s (possible causality).

(5) Fenofibrate + rosuvastatin (unknown dose), later combined with atorvastatin were followed in 1 month by aggression/irritability in a male in his 30s (probable causality).

(6) Lovastatin (unknown dose and time-course to reaction) was followed by depression, dyscontrol of bipolar disorder, and suicide attempts in a male in his 40s (possible causality).

(7) Atorvastatin 20 mg was followed within 2 weeks by cognitive compromise, and nightmares, depression, and anxiety culminating in suicide in a man in his teens (definite causality).

(8) Simvastatin 10 mg was followed (time-course not recalled) by depression, aggression/irritability culminating in suicide in a man in his 60s (possible causality).

(9) Simvastatin 20 mg then atorvastatin 10 mg were followed (time-course not provided) by irritability/aggression in a man in his 60s (definite causality).

(10) Atorvastatin 10 then 20 then 40 mg were followed shortly after the dose increase by violent ideation and anxiety in a man in his 30s (probable causality).

(11) Atorvastatin 20 mg and then simvastatin 20 mg were followed in 2 weeks by aggression/irritability in a man in his 50s (definite causality).

(12) Lovastatin, rosuvastatin, atorvastatin, and simvastatin at varying doses were followed as quickly as 1 day by aggression, irritability, and violent ideation in a man in his 40s (definite causality). ADRs had implications for marriages, careers, and safety of self and others. These observations support the potential for adverse mood and behavioral change in some individuals with statin use, extend the limited literature on such effects, and provide impetus for further investigation into these presumptive ADRs.

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Published on June 17, 2018 11:04

June 10, 2018

Alcohol and Testosterone Adverse Health Effects

[image error] Alcohol and Testosterone, Adverse Health Effects

Jim is a 57 year old wine collector who consumes a bottle of wine nightly. His wine cellar contains 800 bottles of vintage wines collected over 20 years. Jim has been to many doctors for low testosterone in spite of many treatments. Alcohol consumption causes low testosterone. This is the elephant in the room ignored by his previous doctors who failed to mention it. Above left image wine glass courtesy of wikimedia commons.

Alcohols Effect on the HPA (Hypothalamic Pituitary Axis)

The harmful effects of alcohol are summarized by Dr Nadia Rachdaoui’s excellent articles, required reading for anyone thinking about drinking alcohol. Alcohol not only reduces testosterone levels, it has far reaching deleterious effects on the endocrine system, and causes “Leaky Gut”.(1)(4) Dr Nadia Rachdaoui says:

“Alcohol-induced hormonal dysregulations affect the entire body and can result in various disorders such as stress abnormalities, reproductive deficits, body growth defect, thyroid problems, immune dysfunction, cancers, bone disease and psychological and behavioral disorders.”(4)

In alcohol abusers, the HPG (Hypothalamic-Pituitary-Gonadal) dysfunction was shown to be associated with a decrease in libido, infertility and gonadal atrophy. Several studies have clearly documented that alcohol has deleterious effects on all three components of the HPG axis, the hypothalamus, pituitary, and gonads.

“Alcohol abuse disorders are often associated with chronic systemic inflammation and high circulating proinflammatory cytokine levels as well as high circulating cortisol levels. …the gut microflora-derived lipopolisacharides (LPS) were suggested as key players in alcohol-mediated inflammation…… Alcoholics have been shown to have reduced brain mass, cortical neuronal loss and impaired cognitive functions“(4)

[image error]Alcohol consumption increases aromatase activity in the liver, with increased conversion of testosterone to estrogen. There is also reduced circulating IGF-1 levels (growth hormone).(1)(4) Dr. Cicero’s experiments showed that alcohol consumption decreases LH, FSH and Testosterone levels in male rats. (7-9) He also showed alcohol directly inhibits testicular production of testosterone.(7) Left image: Alcohol courtesy of NY Times.

Alcohol and Leaky Gut

Alcohol causes increases translocation of gram negative microbes (LPS) from the gut to the blood stream.(2-3) Dr Joe Wang in 2010 World journal of gastroenterology says.(2)

“Alcohol can significantly increase the translocation of LPS from the gut. …It has been well established in humans that heavy alcohol consumption is associated with an increase in gut permeability and LPS leakage, with or without liver disease. Abstinence for 2 wk or longer is necessary for increased gut permeability to return to a baseline level. Studies of animal models show that acute alcohol feeding in mice increases LPS in plasma approximately five-fold within 30-90 min. Daily binge feeding of alcohol in rats for 4 wk increases the plasma LPS level approximately 15-fold compared to control animals.”(2)

[image error]Alcohol Causes Thiamine Deficiency and Brain Damage

Alcohol consumption causes thiamine (vitamin B1) deficiency which, in turn, causes cerebellar degeneration and brain damage. (11-17) Alcohol consumption even in moderate amounts is a risk factor for dementia. Left Image : Alcohol causes brain atrophy. MRI Brain showing enlarged ventricles indicating atrophy (white arrows). Courtesy Washington U . Alcohol and the Brain.

Alcohol Causes Liver Disease (18)

Alcohol induced cirrhosis of the liver is a major cause of mortality globally. These patients develop portal hypertension with bleeding esophageal varices. (18)

Alcohol is an Addictive Psych Drug

Abrupt discontinuation of alcohol can cause severe withdrawal effects, “Delerium Tremors” . Slow gradual reduction is therefore recommended to avoid withdrawal effects.(19)

Conclusion: Alcohol consumption has profound effects on the endocrine system in males with reduction in testosterone, caused by inhibition at all three levels of the HPA. Alcohol also causes increased translocation of LPS from the gut (Leaky Gut), causing systemic inflammation. Alcohol causes brain and liver damage.

Jeffrey Dach MD

References

1) Rachdaoui, Nadia, and Dipak K. Sarkar. “Pathophysiology of the effects of alcohol abuse on the endocrine system.” Alcohol research: current reviews 38.2 (2017): 255.

Alcohol abuse disrupts all of these systems and causes hormonal disturbances that may result in various disorders, such as stress intolerance, reproductive dysfunction, thyroid problems, immune abnormalities, and psychological and behavioral disorders. Studies in both humans and animal models have helped shed light on alcohol’s effects on various components of the endocrine system and their consequences.

2) Wang, H. Joe, Samir Zakhari, and M. Katherine Jung. “Alcohol, inflammation, and gut-liver-brain interactions in tissue damage and disease development.” World journal of gastroenterology: WJG 16.11 (2010): 1304.

Chronic inflammation is often associated with alcohol-related medical conditions. The key inducer of such inflammation, and also the best understood, is gut microflora-derived lipopolysaccharide (LPS). Alcohol can significantly increase the translocation of LPS from the gut. In healthy individuals, the adverse effects of LPS are kept in check by the actions and interactions of multiple organs. The liver plays a central role in detoxifying LPS and producing a balanced cytokine milieu. The central nervous system contributes to anti-inflammatory regulation through neuroimmunoendocrine actions. Chronic alcohol use impairs not only gut and liver functions, but also multi-organ interactions, leading to persistent systemic inflammation and ultimately, to organ damage. The study of these interactions may provide potential new targets for therapeutic intervention.

Enhancement of LPS translocation by alcohol: It has been well established in humans that heavy alcohol consumption is associated with an increase in gut permeability and LPS leakage, with or without liver disease. Abstinence for 2 wk or longer is necessary for increased gut permeability to return to a baseline level[39]. Acute heavy alcohol consumption is associated with a transient appearance of LPS in the circulation in normal human subjects[40]. Individuals with alcoholic fatty liver but not severe liver disease also show an elevated LPS level in plasma[8]. Studies of animal models show that acute alcohol feeding in mice increases LPS in plasma approximately five-fold within 30-90 min[41,42]. Daily binge feeding of alcohol in rats for 4 wk increases the plasma LPS level approximately 15-fold compared to control animals[43].

3) Lancet. 1984 Jan 28;1(8370):179-82.

The leaky gut of alcoholism: possible route of entry for toxic compounds.

Bjarnason I, Peters TJ, Wise RJ.

Intestinal permeability was investigated with a chromium-51-EDTA (edetic acid) absorption test in 36 non-intoxicated alcoholic patients without liver cirrhosis or overt clinical evidence of malabsorption or malnutrition. Patients abstaining from alcohol for less than 4 days almost invariably had higher intestinal permeability than controls, and in many the abnormality persisted for up to 2 weeks after cessation of drinking. The presence of gastritis did not correlate with the presence of increased permeability. The site of altered intestinal permeability was shown by an in-vitro permeability test to be the small bowel. The increased intestinal permeability to toxic “non-absorbable” compounds of less than 5000 molecular weight may account for some of the extraintestinal tissue damage common in alcoholic patients.

First, the Zn2+ deficiency that is common in alcoholics also adversely affects gut epithelial integrity[48,49].

full free 2013

4) Rachdaoui, Nadia, and Dipak K. Sarkar. “Effects of alcohol on the endocrine system.” Endocrinology and Metabolism Clinics 42.3 (2013): 593-615.

Chronic consumption of a large amount of alcohol disrupts the communication between nervous, endocrine and immune system and causes hormonal disturbances that lead to profound and serious consequences at physiological and behavioral levels. These alcohol-induced hormonal dysregulations affect the entire body and can result in various disorders such as stress abnormalities, reproductive deficits, body growth defect, thyroid problems, immune dysfunction, cancers, bone disease and psychological and behavioral disorders. This review summarizes the findings from human and animal studies that provide consistent evidence on the various effects of alcohol abuse on the endocrine system.

In alcohol abusers, the HPG dysfunction was shown to be associated with a decrease in libido, infertility and gonadal atrophy. Several studies have clearly documented that alcohol has deleterious effects on all three components of the HPG axis, the hypothalamus, pituitary, and gonads.

Associations between both acute and chronic alcohol consumption and lower testosterone levels have been clearly demonstrated.

Muthusami and colleagues, in a study on 66 alcoholic and 30 non-alcoholic men, found that chronic alcohol consumption significantly increased FSH, LH, and estrogen levels, whereas testosterone and progesterone were significantly decreased and prolactin (PRL) unchanged.

Ethanol increases aromatase activity, an enzyme that converts androgens to estrogens, especially in the liver70.

Alcoholic individuals often show dysregulations of the hypothalamic-pituitary-thyroid axis. A significant reduction in T4 and T3 concentrations was observed in the alcoholic groups during withdrawal and early abstinence, compared to non-alcoholic healthy groups90.

Numerous studies in both humans and experimental animals have shown that acute and chronic alcohol exposure reduces circulating GH and IGF-I levels.

Alcohol abuse disorders are often associated with chronic systemic inflammation and high circulating proinflammatory cytokine levels as well as high circulating cortisol levels. Two mechanisms through which alcohol induces inflammation have been proposed; first, the gut microflora-derived lipopolisacharides (LPS) were suggested as key players in alcohol-mediated inflammation129 and second, alcohol metabolism through production of reactive-oxygen species (ROS) and cell damage triggers the production of pro-inflammatory cytokines such as TNF-α and IL-6130. An alcohol-induced systemic inflammation that persists, in the case of alcohol abuse, has far reaching damaging actions on every organ of the body. In the brain, alcohol has neurotoxic effects that result in neuronal death and neurodegeneration131, 132. Alcoholics have been shown to have reduced brain mass, cortical neuronal loss and impaired cognitive functions133, 134.

6) Emanuele, Mary Ann, and Emanuele Nicholas. “Alcohol and the male reproductive system.” Alcohol Research 25.4 (2001): 282.

Alcohol use affects all three parts of the hypothalamic-pituitary-gonadal (HPG) axis, a system of endocrine glands and hormones involved in male reproduction. Alcohol use is associated with low testosterone and altered levels of additional reproductive hormones. Researchers are investigating several potential mechanisms for alcohol’s damage. These mechanisms are related to alcohol metabolism, alcohol-related cell damage, and other hormonal reactions associated with alcohol consumption. Chronic alcohol use in male rats also has been shown to affect their reproductive ability and the health of their offspring.

7) Cicero, THEODORE J., et al. “Ethanol and acetaldehyde directly inhibit testicular steroidogenesis.” Journal of Pharmacology and Experimental Therapeutics 213.2 (1980): 228-233.

The effects of ethanol and acetaldehyde on testicular steroidogenesis were examined. We found that ethanol markedly inhibited the gonadotropin-stimulated production of testosterone in enzymatically dispersed cell preparations of the testes of adult rats. The effects of ethanol on testicular steroidogenesis appeared to be noncompetitive since testosterone production could not be restored to nondrug-treated levels even by extremely high concentrations of gonadotropin. Acetaldehyde also inhibited testicular steroidogenesis in vitro but was between 1000 and 4000 times more effective than ethanol. As little as 50 microM acetaldehyde was effective in suppressing testicular steroidogenesis, whereas much higher (200 mM) concentrations of ethanol were required. Our results further demonstrated that cell viability was unaffected by incubation with very high concentrations of ethanol and acetaldehyde, indicating that the two drugs did not simply irreversibly impair the ability of the dispersed cells to appropriately respond to stimulation by gonadotropins. These results suggest that ethanol directly inhibits testicular steroidogenesis, but that acetaldehyde is much more potent.

8) Cicero, THEODORE J., and Thomas M. Badger. “Effects of alcohol on the hypothalamic-pituitary-gonadal axis in the male rat.” Journal of Pharmacology and experimental Therapeutics 201.2 (1977): 427-433.Effects of alcohol on the hypothalamic-pituitary-gonadal axis in the male rat Cicero 1977

9) Cicero, T. J., E. R. Meyer, and R. D. Bell. “Effects of ethanol on the hypothalamic-pituitary-luteinizing hormone axis and testicular steroidogenesis.” The Journal of pharmacology and experimental therapeutics 208.2 (1979): 210

10) Alcohol Alcohol. 1987;22(3):241-9. Vitamin A at pharmacologic doses ameliorates the membrane lipid peroxidation injury and testicular atrophy that occurs with chronic alcohol feeding in rats.

Rosenblum ER, Gavaler JS, Van Thiel DH.

The interaction of ethanol (ETOH) with testicular subcellular membranes contributes, at least in part, to alcohol-induced gonadal dysfunction. Vitamin A reaches the testes via the circulation as the retinyl ester and is converted to the free alcohol (retinol) and then to the aldehyde (retinal); retinal is the form of the vitamin which is essential for normal spermato-genesis. Because retinol can function as a free radical scavenger, testicular mitochondria were evaluated for evidence of a protective role provided by supplemental dietary vitamin A on ETOH-induced alterations in testicular structure and function in rats. Lipid peroxidation was evaluated by measurement of malonaldehyde formation and glutathione content of the testes. Compared to isocalorically matched dextrimaltose-fed controls (ISO) receiving a modified vitamin A containing diet, rats fed the corresponding ETOH diet for 50 days had a reduced testes/body ratio (ETOH: 0.0114 +/- 0.0004 vs ISO: 0.0128 +/- 0.0004). Mitochondrial enriched extracts obtained from the testes of these ETOH-fed rats showed significant increases in malonaldehyde formation; moreover, glutathione levels were reduced in the testes of the alcohol-fed animals when compared to their isocaloric controls. In contrast, no evidence for testicular atrophy was present in ETOH-fed rats receiving a standard vitamin A enriched diet; moreover, such ETOH-fed rats had a reduced rate of malonaldehyde formation as compared to their respective controls. Similarly, glutathione levels were not depleted in the testes of the ETOH-fed rats receiving the vitamin A enriched diet. Taken together, these data suggest that lipid peroxidation is a consequence of ethanol metabolism which can be attenuated, at least in part, by vitamin A.

Alcohol and thiamine deficiency

11) Martin, Peter R., Charles K. Singleton, and Susanne Hiller-Sturmhöfel. “The role of thiamine deficiency in alcoholic brain disease.” Alcohol Research 27.2 (2003): 134.

12) Mulholland, P. J., et al. “Thiamine deficiency in the pathogenesis of chronic ethanol-associated cerebellar damage in vitro.” Neuroscience 135.4 (2005): 1129-1139. Thiamine deficiency in the pathogenesis of chronic ethanol-associated cerebellar damage in vitro Mulholland Neuroscience 2005

13) Topiwala, Anya, et al. “Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study.” bmj 357 (2017): j2353.

Alcohol consumption, even at moderate levels, is associated with adverse brain outcomes including hippocampal atrophy.

14) a bottle of wine is 750ml, or 25 ounces, there are around 5 glasses of wine in a bottle

15) Schwarzinger, Michaël, et al. “Contribution of alcohol use disorders to the burden of dementia in France 2008–13: a nationwide retrospective cohort study.” The Lancet Public Health 3.3 (2018): e124-e132.

Alcohol use disorders were a major risk factor for onset of all types of dementia, and especially early-onset dementia.

16) Braillon, Alain. “Alcohol consumption and cognitive decline: the elephant in the room?.” The Lancet Public Health 3.5 (2018): e216.

17) Ladouceur, Roger. “What if alcohol were harmful, even in moderation?.” (2017): 742-742.

18) Mann, Robert E., Reginald G. Smart, and Richard Govoni. “The epidemiology of alcoholic liver disease.” Alcohol research and health 27 (2003): 209-219.The epidemiology of alcoholic liver disease Mann Robert E Alcohol research and health 2003

19) Jesse, S., et al. “Alcohol withdrawal syndrome: mechanisms, manifestations, and management.” Acta Neurologica Scandinavica 135.1 (2017): 4-16.

Jeffrey Dach MD

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April 29, 2018

Is Your Drug From the Medical Museum?

[image error] Is Your Drug From the Medical Museum?

If you are a curious tourist, visit the Medical Museum where you will be shocked with the sight of glass specimen jars filled with tissue samples. There you will find relics of past medical treatments and machines, such as the Iron Lung machine. Left Image Brain in Jar at the Medical Museum courtesy of wikimedia commons.

Although some of museum artifacts are horrifying, you might be surprised to learn your doctor may be treating you with a drug or technique already relegated to the medical museum. They just don’t know it yet.

Five of Twenty in the Medical Museum

Of the top twenty drugs prescribed by mainstream medicine, five are clearly from the medical museum: statin anti-cholesterol drugs (number 2 and 12) , Levothyroxine thyroid pills (Number 4), and SSRI antidepressants (17 and 19).

Are You Taking A Statin Cholesterol Pill?

Firstly, we will discuss why the serum cholesterol test and statin cholesterol pills were relegated to the medical museum back in 2004 with the publication of the calcium score study by Paolo Raggi from Tulane University. Dr Raggi recruited 500 patients with known underlying heart disease all on statin drugs to reduce cholesterol, and followed for 6 years with annual calcium score and serum cholesterol levels. Of the 500 patients in the study, 41 of them suffered heart attacks. In this group, annual calcium score progression was greater than 15%. For the other 450 patients who were heart attack free, annual calcium score progression was less than 15%. Surprisingly, the serum cholesterol was the same for the two groups, those who had heart attacks and those heart attack free. Dr Raggi’s study was nothing less than a paradigm shift in the management of heart disease, relegating the serum cholesterol test to the medical museum, having been replaced by the annual calcium score. However, mainstream cardiology ignored and buried the Raggi study for the past 14 years.

The good news from the Raggi study for those with high calcium score, if you can alter diet and life style to reduce calcium score progression to less than 15% per year, then you have a good prognosis regardless of starting calcium score.

Why is calcium score so much better than cholesterol testing? Think about it. The serum cholesterol is a measurement of a blood substance distant from the wall of the artery where the disease is located. The calcium score measures the disease progression in the wall of the artery exactly where the disease is located.

What is the calcium score test?

The calcium score is a CAT Scan (Computerized Axial Tomography) without IV contrast (plain) limited to the heart with imaging of the coronary arteries. The computer adds up the calcium in the coronary arteries to yield a “calcium score” representing the amount of calcium in the coronary arteries. The calcium score correlates with future mortality from heart disease. The higher the calcium score, the higher the mortality.

How to reduce calcium score?

Dr Matt Budoff studied aged garlic showing excellent result for reducing progression of calcium score. The women’s health initiative study showed that the estrogen treated arm had reduced calcium score by 35%.

What About Statin Drugs for Calcium Score?

Multiple Statin Drug studies show no benefit for calcium score. Results with statin drugs were similar to placebo. Similarly, studies show no correlation between amount of calcification in the coronary arteries and serum cholesterol level.

Are you taking Levothyroxine Thyroid Pills ?

If you are taking a thyroid pill, you might be surprised to find out your thyroid pill might be taken from the medical museum. As of 2016, levothyroxine (also known as T4 monotherapy) has been relegated to the medical museum with the publication of Dr Antonio Bianco’s study of 469 Levothyroxine (T4) treated patients compared to controls. The Levothyroxine treated patients more likely to have lower serum T3/T4 ratios, higher BMI (Body Weight), more likely to be taking Beta-Blockers drugs, Statin drugs, and SSRI Anti-depressant drugs. And they were more likely to suffer from cognitive Impairment. (Peterson, Sarah J., Antonio C. Bianco. (2016).

Dr Antonio C. Bianco, MD, PhD, past president of the American Thyroid Association and professor of medicine at Rush Medical School says this:

Despite normal TSH tests, these patients still have many nagging symptoms of hypothyroidism. “Patients complain of being depressed, slow and having a foggy mind,” ….

“They have difficulty losing weight. They complain of feeling sluggish and have less energy. Yet we doctors keep telling them, ‘I’m giving you the right amount of medication and your TSH is normal. You should feel fine.’”

“Better medications (than Levo) are needed to treat hypothyroidism….Patients who continue to have symptoms on Levothyroxine monotherapy might try a pill that contains both T3 and T4. “ (Antonio Bianco MD 12-Oct-2016)(Peterson, Sarah J., Antonio C. Bianco. (2016)

Dr Bianco’s study showed that T4 only monotherapy has been relegated to the medical museum, having been replaced with a better formulation, the combined T3 and T4 thyroid pill such as Nature-Throid from RLC labs, a natural desiccated thyroid product.

[image error] Above image: Iron Lung Courtesy of Melnick Medical Museum

Are you taking an SSRI Antidepressant Pill ?

Are you taking an SSRI antidepressant to help control menopausal symptoms of hot flashes and night sweats? SSRI antidepressant pills have been relegated to the medical museum with the publication of the Irving Kirsch article,” “Antidepressants and the placebo effect.” In Zeitschrift für Psychologie (2015).

Your SSRI antidepressant pill may induce temporary neuro stimulation followed fairly rapidly by drug induced tolerance, after which the drug serves as “addictive placebo”. Getting off the drug requires a tapering schedule to avoid uncomfortable withdrawal effects. When the drug stops working, patients go back to the doctor asking for more powerful combinations of psychoactive drugs, leading to the tragedy of lives destroyed by brain damaging drug cocktails freely prescribed by the medical system. If your doctor has prescribed SSRI antidepressant pills for your menopausal symptoms of hot flashes and night sweats, then you are taking a treatment that belongs in the medical museum. Menopausal symptoms are caused by estrogen deficiency. There is no estrogen in SSRI antidepressants. So, this is blatant medical abuse of women by the medical system.

More Drugs in the Medical Museum- Synthetic Hormones

If your OB/Gyne doctor is not prescribing bioidentical hormones for your menopausal symptoms, then you may very well be taking synthetic hormones from the Medical Museum. There are many synthetic hormones such as Medroxyprogesterone commonly prescribed to women for various hormonal complaints. Medroxyprogesterone was shown carcinogenic, causing breast cancer in the Women’s Health Initiative Study. Cancer researchers use medroxyprogesterone to induce breast cancer in laboratory animals, the “Medroxyprogesterone model of breast cancer” in animals. Medroxy progesterone belongs in the Medical Museum, on the shelf beside DES (Diethylstilbestrol), banned when found to induce cervical cancer in the daughters of women who took the drug. Also on the same shelf is methyl-testosterone banned when found it induced liver cancer.

Banned Drugs in the Medical Museum

About 10% of all drugs approved for use by the FDA are later banned after they are found to be “bad drugs”. These are sent to the medical museum.

Discontinued or Banned Vaccines in the Medical Museum

Examples are the live Sabine polio vaccine discontinued in the US in 2000 because the vaccine itself was causing VAPP, vaccine associated paralytic polio. The Swine flu vaccine was banned in 1976 because of increased Guillan Barre syndrome after vaccination. etc. The whole cell pertussis vaccine was associated with increased mortality in children receiving the vaccine. In Sweden, whole cell pertussis vaccination was suspended in 1979, and was later replaced with a safer acellular Pertussis vaccine. In Japan, DTP vaccination was banned in 1993 due to safety concerns.(31)(46) A partial listing of discontinued vaccines in the Medical Museum .can be seen here: Discontinued_Vaccines

Banned Procedures Are Sent to the Medical Museum

A number of procedures such as Arthroscopy for Osteoarthritis, Bone Marrow Transplant for Breast Cancer, have been relegated to the medical museum.

Jeffrey Dach MD

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Davie, Fl 33314

954 792-4663

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Published on April 29, 2018 08:55

April 15, 2018

The Non-Mystery of Chronic Fatigue Syndrome

[image error]The Non-Mystery of Chronic Fatigue Syndrome

My wife gave me an article from Hadassah Magazine entitled “The Mystery of Chronic Fatigue Syndrome”, by Carol Saline, about the 2017 documentary on Jennifer Brea called “Unrest”. The film documents her experience with severe chronic fatigue.(1-3) Jennifer Brea was a previously healthy robust young women until the onset of immune dysfunction with six different infections, followed by debilitating fatigue and brain fog. The article goes on to state there is no known cause and no known cure for “chronic fatigue syndrome” also called “ME/CFS”. This has changed. The mystery has been unraveled by a group from Stanford. Above image courtesy of Jennifer Brea Unrest Movie.

[image error]Leaky Gut – Incriminating the GUT Microbiome

Dr Montoya’s group at Stanford found elevated pro-inflammatory cytokines in chronic fatigue patients, implicating chronic inflammatory up regulation. (4-5) In an accompanying editorial in PNAS, Dr Anthony Komaroff explains it nicely with this quote:(5)

“Another way of incriminating infection in CFS (Chronic Fatigue Syndrome) involves the gut microbiome. Several recent studies have reported dysbiosis accompanied by low-grade inflammation and increased permeability of the gut mucosa. This allows bacterial lipopolysaccharide to enter the circulation, possibly activating innate immunity both systemically and in the brain.”

[image error]Notice Jennifer Brea’s story includes six different infections, yet the story says nothing about the antibiotics used to treat these infections. Many of these patients have history of multiple long term antibiotic use implicating gut dysbiosis and leaky gut. The use of NSAIDS for fibromyalgia pain worsens the leaky gut pathology as discussed in my previous article.

Leaky gut causes low grade endotoxemia which then upregulates inflammatory cytokines which travel to the brain causing upregulated microglia, depression and HPA (hypothalamic pituitary axis) dysfunction, which then causes adrenal, thyroid and gonadal hormone dysfunction leading to severe fatigue and fibromyalgia. On top of this there is usually a variable element of mitochondrial dysfunction.

Pre-Existing Genetic Defects and Aggravating Conditions

Symptoms are worse in patients with pre-existing genetic defects in methylation pathways such as MTHFR, or COMT (catechol -o-methl-tranferase), or B12 transport protein defects (detected with elevated MMA levels) Symptoms are worse if there is an aggravating medical condition such as low thyroid, menopausal transition, gluten sensitivity, stressful workplace or home life etc.

The Mystery Becomes Unraveled

The reason why this disease is a mystery is because the mainstream conventional physician does not bother to test for any of these abnormalities. Nor do they treat them. We do, and most of our patients eventually get better. That is why Chronic Fatigue/Fibromyalgia is a non-mystery.

Jeffrey Dach MD

7450 Griffin Road Suite 180-190

Davie, Florida 33314

954-792-4663

Articles with Related Interest

Low Level Endotoxemia, Depression and Endocrinopathy

NSAIDS, Small Bowel Damage and Leaky GUT

Links and References

1) The Mystery of Chronic Fatigue Syndrome By Carol Saline February 2018

2) Jennifer Brea’s Sundance award-winning documentary, Unrest, is a personal journey from patient to advocate to storyteller. Jennifer is twenty-eight years-old, working on her PhD at Harvard, and months away from marrying the love of her life when a mysterious fever leaves her bedridden. When doctors tell her it’s “all in her head,” she picks up her camera as an act of defiance and brings us into a hidden world of millions that medicine abandoned.

In this story of love and loss, newlyweds Jennifer and Omar search for answers as they face unexpected obstacles with great heart. Often confined by her illness to the private space of her bed, Jennifer connects with others around the globe. Like a modern-day Odysseus, she travels by Skype into a forgotten community, crafting intimate portraits of four other families suffering similarly. Jennifer Brea’s wonderfully honest and humane portrayal asks us to rethink the stigma around an illness that affects millions. Unrest is a vulnerable and eloquent personal documentary that is sure to hit closer to home than many could imagine.

Myalgic Encephalomyelitis (ME), commonly known as Chronic Fatigue Syndrome (CFS) or ME/CFS, is a devastating multi-system disease that causes dysfunction of the neurological, immune, endocrine and energy metabolism systems.

It often follows an infection and leaves 75% of those affected unable to work and 25% homebound are bedridden. An estimated 15-30 million people worldwide have ME.

3) Psychology Today: Why is Chronic Fatigue Syndrome Still a Mystery?

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

4) Montoya, Jose G., et al. “Cytokine signature associated with disease severity in chronic fatigue syndrome patients.” Proceedings of the National Academy of Sciences (2017): 201710519.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) devastates the lives of millions of people and has remained a mystery illness despite decades of research. It has long been suspected that inflammation is central to its pathogenesis. Although only two cytokines were found to be different (TGF-β higher and resistin lower) in ME/CFS patients compared with controls, 17 cytokines correlated with ME/CFS severity. Thirteen of these cytokines are proinflammatory and may contribute to many of the symptoms these patients experience for several years. Only CXCL9 (MIG) inversely correlated with fatigue duration.

Although some signs of inflammation have been reported previously in patients with myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), the data are limited and contradictory. High-throughput methods now allow us to interrogate the human immune system for multiple markers of inflammation at a scale that was not previously possible. To determine whether a signature of serum cytokines could be associated with ME/CFS and correlated with disease severity and fatigue duration, cytokines of 192 ME/CFS patients and 392 healthy controls were measured using a 51-multiplex array on a Luminex system. Each cytokine’s preprocessed data were regressed on ME/CFS severity plus covariates for age, sex, race, and an assay property of newly discovered importance: nonspecific binding. On average, TGF-β was elevated (P = 0.0052) and resistin was lower (P = 0.0052) in patients compared with controls. Seventeen cytokines had a statistically significant upward linear trend that correlated with ME/CFS severity: CCL11 (Eotaxin-1), CXCL1 (GROα), CXCL10 (IP-10), IFN-γ, IL-4, IL-5, IL-7, IL-12p70, IL-13, IL-17F, leptin, G-CSF, GM-CSF, LIF, NGF, SCF, and TGF-α. Of the 17 cytokines that correlated with severity, 13 are proinflammatory, likely contributing to many of the symptoms experienced by patients and establishing a strong immune system component of the disease. Only CXCL9 (MIG) inversely correlated with fatigue duration.

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

Another way of incriminating infection in CFS involves the gut microbiome. Several recent studies have reported dysbiosis accompanied by low-grade inflammation and increased permeability of the gut mucosa. This allows bacterial lipopolysaccharide to enter the circulation, possibly activating innate immunity both systemically and in the brain (5, 16⇓–18).

5) Komaroff, Anthony L. “Inflammation correlates with symptoms in chronic fatigue syndrome.” Proceedings of the National Academy of Sciences 114.34 (2017): 8914-8916.

Neuroendocrine studies demonstrate abnormalities of the hypothalamic–pituitary–adrenal axis, of growth hormone secretion, and of adrenergic metabolism in CFS patients that are distinct from those seen in healthy control subjects and in patients with major depression.

Increased lactate levels in cerebrospinal fluid may indicate impaired oxidative phosphorylation, with a consequent shift to anaerobic metabolism. Possible causes of acquired mitochondrial dysfunction in the CNS include infection and cerebral hypoperfusion.

Many studies have found evidence of oxidative stress in CFS patients:

For 17 of the 51 cytokines there was a statistically significant upward linear correlation between the level of the molecule and the severity of the illness, suggesting that the cytokine levels are, indeed, causally associated with the symptoms.

Patients with severe symptoms and increased production of proinflammatory cytokines during the initial illness were the most likely to develop CFS.

Another way of incriminating infection in CFS involves the gut microbiome. Several recent studies have reported dysbiosis accompanied by low-grade inflammation and increased permeability of the gut mucosa. This allows bacterial lipopolysaccharide to enter the circulation, possibly activating innate immunity both systemically and in the brain (5, 16⇓–18).

6) Blomberg, Jonas, et al. “infection elicited autoimmunity and Myalgic encephalomyelitis/Chronic Fatigue syndrome: an explanatory Model.” Frontiers in Immunology 9 (2018): 229.

7) Researchers identify biomarkers associated with chronic fatigue syndrome severity

Stanford investigators used high-throughput analysis to link inflammation to chronic fatigue syndrome, a difficult-to-diagnose disease with no known cure. Jul 31 2017 Jose Montoya and his colleagues have found evidence inflammation may be the culprit behind chronic fatigue syndrome, a disease with no known cure. Steve Fisch

Researchers at the Stanford University School of Medicine have linked chronic fatigue syndrome to variations in 17 immune-system signaling proteins, or cytokines, whose concentrations in the blood correlate with the disease’s severity.

The findings provide evidence that inflammation is a powerful driver of this mysterious condition, whose underpinnings have eluded researchers for 35 years.

“Our findings show clearly that it’s an inflammatory disease and provide a solid basis for a diagnostic blood test.”

8) Scientists zoom closer towards understanding chronic fatigue

Last updated on August 1st, 2017 at 6:43 pm by Mihai Andrei E-mail author

Montoya and colleagues found levels of 17 cytokines dramatically higher than normal in patients suffering from CFS. Out of these 17, no less than 13 were associated with promoting inflammation.

Jeffrey Dach MD

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Published on April 15, 2018 14:39

March 28, 2018

Calcium Score Paradigm Shift in Cardiology

[image error]

Calcium Score Paradigm Shift in Cardiology

by Jeffrey Dach MD

A Cardiology “Paradigm Shift” occurred in 2004 with publication of the Raggi study on annual Calcium Score progression.(1)

This left chart shows the MAJOR FINDING: Less than 15% annual increase in calcium score is associated with a good prognosis.(upper line), regardless of high starting score. On the other hand, greater than 15% annual progression (lower line) shows poor prognosis with increasing Myocardial Infarction rate.

When you see this chart for calcium score, let me remind you, there are no similar data charts for LDL cholesterol. As a matter of fact, there was no difference in LDL levels for the 41 heart attack patients compared to 450 others free of heart attack. There was no difference !!! Dr Paoli Raggi says:

“Mean LDL level did not differ between groups (118 mg/dL versus 122 mg/dL, MI versus no MI).(Dr Raggi 2004 (28) (Note: MI = Myocardial Infarction)”(1)

Dr Paoli Raggi found that LDL cholesterol is a useless marker for predicting future heart attack. Above Left Chart Fig2 Courtesy of Dr Raggi 2004 (1)

Why is Calcium Score a Superior Predictor Over Cholesterol

Cholesterol and subfractions are substances we measure in the blood stream, distant from the wall of the artery where the pathology is located. With calcium score, we are measuring the pathology directly in the wall of the artery. Progression of calcium score indicates progression of pathological change in the wall of the artery.

Conclusion:

Dr Paoli Raggi’s study in 2004 showed superiority of calcium score over LDL cholesterol in predicting future heart attack. As a matter of fact, the cholesterol panel has been, (as of 2004), replaced by the calcium score for routine management of heart disease. This is the paradigm shift in Cardiology. However, more than a decade later, mainstream cardiology is still in denial, having buried and ignored Dr Raggi’s 2004 study. The financial stakes are too high to give up on the “Cholesterol Myth” and the billions from the cholesterol drugs. As Upton Sinclair once said: “You can’t get a Cardiologist to understand something if his salary depends on him not understanding it.”

Jeffrey Dach MD

7450 Griffin Road Suite 180/190

Davie, Fl 33314

954 -792-4663

Articles with Similar Content

LDL Cholesterol, What Gives ?

Reducing Calcium Score with Aged Garlic

References:

1) Raggi, Paolo, Tracy Q. Callister, and Leslee J. Shaw. “Progression of coronary artery calcium and risk of first myocardial infarction in patients receiving cholesterol-lowering therapy.” Arteriosclerosis, thrombosis, and vascular biology 24.7 (2004): 1272-1277.

Objective— Statins reduce cardiovascular risk and slow progression of coronary artery calcium (CAC). We investigated whether CAC progression and low-density lipoprotein (LDL) reduction have a complementary prognostic impact.

Methods and Results— We measured the change in CAC in 495 asymptomatic subjects submitted to sequential electron-beam tomography (EBT) scanning. Statins were started after the initial EBT scan. Myocardial infarction (MI) was recorded in 41 subjects during a follow-up of 3.2±0.7 years. Mean LDL level did not differ between groups (118±25 mg/dL versus 122±30 mg/dL, MI versus no MI).On average, MI subjects demonstrated a CAC change of 42%±23% yearly; event-free subjects showed a 17%±25% yearly change (P=0.0001). Relative risk of having an MI in the presence of CAC progression was 17.2-fold (95% CI: 4.1 to 71.2) higher than without CAC progression (P15% per year (P

Conclusions— Progression of CAC was significantly greater in patients receiving statins who had an MI compared with event-free subjects despite similar LDL control. Continued expansion of CAC may indicate failure of some patients to benefit from statin therapy and an increased risk of having cardiovascular events.

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Published on March 28, 2018 10:41

February 27, 2018

LDL Cholesterol Particle Size and Number What Gives ?

[image error] LDL Particle Size and Particle Number, What Gives?

Ron is a 72 year old retired engineer, and has a total cholesterol of 174 which hasn’t changed over the seven years we have been following him. This is quite low. Yet, Ron is concerned because his LDL particle number and LDL particle size are “outside of the lab range”. He is very worried about this and is concerned about his risk for future heart attack. I explained to Ron the lab range doesn’t apply to him. Ron’s Calcium Score is low, and his total cholesterol is 174, and he does not have metabolic syndrome or diabetes, so he doesn’t need to worry about the LDL particle size or particle number.

What does the mainstream cardiology say about the value of LDL particle size and number?

The Quebec Study – Small Dense LDL Associated with Increased Mortality from Coronary Artery Disease

[image error]You might say “wait just a minute here”, the Quebec study followed 2072 males over 13 years and found that small dense LDL was associated with increased mortality from cardiovascular disease above chart).(6) The above chart is very convincing, and the three lines for small dense LDL are nicely separated. (6) However, as pretty as the above chart looks, Correlation is not necessarily causation. If increased small dense LDL particle number causes coronary artery disease, then an intervention that reduces small dense LDL particles should be preventive. However we know that it is not. Above image courtesy of Medscape.

Houston, We Have a Problem, New Drug Reduces Small LDL,

However, No Benefit in Preventing Heart Disease

Treatment with the new cholesterol lowering drug, Evacetrapib, resulted in significant decreases in “total LDL particle number (LDL-P) (up to -54%), and small LDL particle (sLDL) (up to -95%) concentrations”.(5) Yet, according to Dr Lincoff in NEJM 2017,

“treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease.”(4)

As a matter of fact, Eli Lilly abandoned drug development after this failed study.(4) So we see that reducing total LDL particle number, or increasing LDL particle size had no benefit for preventing death from heart disease. The benefit was same as a placebo.

Dr Allaire agrees that LDL particle size is not very useful. Dr Allaire writes in 2017 Current Opinion in Lipidology:(1)

“LDL particle size….has not been independently associated with CVD risk after adjustment for other risk factors such as LDL cholesterol, triglycerides, and HDL-C and that routine use of information pertaining to particle size to determine and manage patients’ risk is not yet justified.”(1)

In other words, according to Dr Allaire, the LDL particle size is not a good predictor of cardiovascular risk.(1)

Predicting Risk: LDL Subfraction Vs. Calcium Score

The next question you might ask: “If LDL cholesterol is not helpful, then what other test is useful for predicting risk of cardiovascular disease?”

The answer is the Calcium Score which is an inexpensive test which uses a CAT scan to measure the amount of calcium in the coronary arteries. Studies show that the higher the number the greater the risk, the lower the number the smaller the risk. None of the cholesterol subfractions can provide this type of information, and in my opinion should be relegated to the medial museum, as a relic from the past.

Conclusion: When it comes down to a contest between LDL Cholesterol Subfractions and Calcium Score, there is no contest. The Calcium Score wins every time.

Jeffrey Dach MD

7450 Griffin Road Suite 190

Davie Florida 33314

954 792-4663

Articles with Related Interest

Aged Garlic for Calcium Score

Autopsy Studies Show No Correlation

Statin Denialism Internet cult

Links and References

Header Image LDL particle courtesy of Drs Wolfson

1) Curr Opin Lipidol. 2017 Jun;28(3):261-266. LDL particle number and size and cardiovascular risk: anything new under the sun? Allaire J1, Vors C, Couture P, Lamarche B.

LDL particle size, on the other hand, has not been independently associated with CVD risk after adjustment for other risk factors such as LDL cholesterol, triglycerides, and HDL-C and that routine use of information pertaining to particle size to determine and manage patients’ risk is not yet justified.

We provide here an up-to-date perspective on the potential use of LDL particle number and size as complementary risk factors to predict and manage cardiovascular disease (CVD) risk in the clinical realm.

RECENT FINDINGS: Studies show that a significant proportion of the population has discordant LDL particle number and cholesterol indices [non-HDL cholesterol (HDL-C)]. Data also show that risk prediction may be improved when using information on LDL particle number in patients with discordant particle number and cholesterol data. Yet, most of the current CVD guidelines conclude that LDL particle number is not superior to cholesterol indices, including non-HDL-C concentrations, in predicting CVD risk. LDL particle size, on the other hand, has not been independently associated with CVD risk after adjustment for other risk factors such as LDL cholesterol, triglycerides, and HDL-C and that routine use of information pertaining to particle size to determine and manage patients’ risk is not yet justified.

SUMMARY: Additional studies are required to settle the debate on which of cholesterol indices and LDL particle number is the best predictor of CVD risk, and if such measures should be integrated in clinical practice.

Women with discordant high particle concentration were more likely to have metabolic syndrome (MetS) and diabetes

2) Clin Chem. 2017 Apr;63(4):870-879. doi: 10.1373/clinchem.2016.264515. Epub 2017 Feb 7. Discordance between Circulating Atherogenic Cholesterol Mass and Lipoprotein Particle Concentration in Relation to Future Coronary Events in Women.

Lawler PR1,2,3,4, Akinkuolie AO1,3, Ridker PM2,3, Sniderman AD5, Buring JE3,4, Glynn RJ3,4, Chasman DI3, Mora S6,2,3.

It is uncertain whether measurement of circulating total atherogenic lipoprotein particle cholesterol mass [non-HDL cholesterol (nonHDLc)] or particle concentration [apolipoprotein B (apo B) and LDL particle concentration (LDLp)] more accurately reflects risk of incident coronary heart disease (CHD). We evaluated CHD risk among women in whom these markers where discordant.

METHODS:Among 27533 initially healthy women in the Women’s Health Study (NCT00000479), using residuals from linear regression models, we compared risk among women with higher or lower observed particle concentration relative to nonHDLc (highest and lowest residual quartiles, respectively) to individuals with agreement between markers (middle quartiles) using Cox proportional hazards models.

RESULTS:Although all 3 biomarkers were correlated (r ≥ 0.77), discordance occurred in up to 20.2% of women. Women with discordant high particle concentration were more likely to have metabolic syndrome (MetS) and diabetes (both P < 0.001). Over a median follow-up of 20.4 years, 1246 CHD events occurred (514725 person-years). Women with high particle concentration relative to nonHDLc had increased CHD risk: age-adjusted hazard ratio (95% CI) = 1.77 (1.56-2.00) for apo B and 1.70 (1.50-1.92) for LDLp. After adjustment for clinical risk factors including MetS, these risks attenuated to 1.22 (1.07-1.39) for apo B and 1.13 (0.99-1.29) for LDLp. Discordant low apo B or LDLp relative to nonHDLc was not associated with lower risk.

CONCLUSIONS:Discordance between atherogenic particle cholesterol mass and particle concentration occurs in a sizeable proportion of apparently healthy women and should be suspected clinically among women with cardiometabolic traits. In such women, direct measurement of lipoprotein particle concentration might better inform CHD risk assessment.

3) Curr Opin Endocrinol Diabetes Obes. 2018 Jan 10. Discordance between lipoprotein particle number and cholesterol content: an update.

Cantey EP1, Wilkins JT2.

The cholesterol content within atherogenic apolipoprotein-B (apoB) containing lipid particles is the center of consensus guidelines and clinicians’ focus whenever evaluating a patient’s risk for atherosclerotic cardiovascular disease. The pathobiology of atherosclerosis requires the retention of lipoprotein particles within the vascular intima over time followed by maladaptive inflammation resulting in plaque formation and rupture in some. The cholesterol content is widely variable within each particle creating either cholesterol-deplete or cholesterol-enriched particles. This variance in particle cholesterol content varies within and between individuals. Discordance analysis exploits this difference in cholesterol content of particles to demonstrate the differential significance of LDL-cholesterol (LDL-C) and non-HDL-C from measures of lipoprotein particle number in terms of assessing atherosclerotic cardiovascular disease risks.

RECENT FINDINGS:Three studies have added to the growing body of literature of discordance analysis. Despite wide variability of discordance cutoffs, baseline risk of atherosclerotic disease, and populations sampled, the conclusion remains the same: risk of atherosclerotic disease follows apoB lipid particle concentration rather than cholesterol content of lipid particles.

SUMMARY:In addition to traditional lipid fractions, assessments of atherogenic particle number should be strongly considered whenever assessing CVD risk in nontreated and treated individuals. There is a need for clinical trials that focus not only on the reduction in LDL-C but apoB, as well.

4) Lincoff, A. Michael, et al. “Evacetrapib and cardiovascular outcomes in high-risk vascular disease.” New England Journal of Medicine 376.20 (2017): 1933-1942.

Although treatment with evacetrapib has resulted in reductions of 60 to 70% in the levels of small dense LDL particles,29 effects on the total number of LDL particles and on apolipoprotein B levels (reductions of 22% and 20%, respectively) are considerably less pronounced.

CONCLUSIONS:Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease.

5) Nicholls SJ, Ruotolo G, Brewer HB, et al. Evacetrapib alone or in combination with statins lowers lipoprotein(a) and total and small LDL particle concentrations in mildly hypercholesterolemic patients. J Clin Lipidol 2016;10:519-527.e4

Potent CETP inhibitors reduce plasma concentrations of atherogenic lipoprotein biomarkers of cardiovascular risk.

OBJECTIVES:To evaluate the effects of the cholesteryl ester transfer protein (CETP) inhibitor evacetrapib, as monotherapy or with statins, on atherogenic apolipoprotein B (apoB)-containing lipoproteins in mildly hypercholesterolemic patients.

METHODS:VLDL and LDL particle concentrations and sizes (using nuclear magnetic resonance spectroscopy) and lipoprotein(a) concentration (using nephelometry) were measured at baseline and week 12 in a placebo-controlled trial of 393 patients treated with evacetrapib as monotherapy (30 mg/d, 100 mg/d, or 500 mg/d) or in combination with statins (100 mg plus simvastatin 40 mg/d, atorvastatin 20 mg/d, or rosuvastatin 10 mg/d; Clinicaltrials.gov Identifier: NCT01105975).

RESULTS:Evacetrapib monotherapy resulted in significant placebo-adjusted dose-dependent decreases from baseline in Lp(a) (up to -40% with evacetrapib 500 mg), total LDL particle (LDL-P) (up to -54%), and small LDL particle (sLDL) (up to -95%) concentrations. Compared to statin alone, coadministration of evacetrapib and statins also resulted in significant reduction from baseline in Lp(a) (-31%), LDL-P (-22%), and sLDL (-60%) concentrations. The percentage of patients with concentrations above optimal concentrations for LDL-P (>1000 nmol/L) and sLDL (>600 nmol/L) decreased from 88% and 55% at baseline, respectively, to 20% and 12% at week 12, for patients treated with evacetrapib plus statins. Evacetrapib, alone or with statins, significantly increased LDL-P size.

CONCLUSIONS:Evacetrapib, as monotherapy or with statins, significantly reduces the concentrations of atherogenic apoB-containing lipoproteins, including Lp(a), LDL-P, and sLDL.

6) St-Pierre, Annie C., et al. “Low-density lipoprotein subfractions and the long-term risk of ischemic heart disease in men: 13-year follow-up data from the Quebec Cardiovascular Study.” Arteriosclerosis, thrombosis, and vascular biology 25.3 (2005): 553-559.Low density lipoprotein Risk of ischemic heart disease Quebec St Pierre Annie Arterio thrombo vasc bio 2005

The objective of the present study was to investigate the association between large and small low-density lipoprotein (LDL) and long-term ischemic heart disease (IHD) risk in men of the Quebec Cardiovascular Study.

METHODS AND RESULTS:Cholesterol levels in the large and small LDL subfractions (termed LDL-C> or =260A and LDL-COur study confirmed the strong and independent association between LDL-C, particularly over the first 7 years of follow-up. However, elevated LDL-C> or =260A levels (third versus first tertile) were not associated with an increased risk of IHD over the 13-year follow-up (RR=0.76; P=0.07).

CONCLUSIONS:These results indicated that estimated cholesterol levels in the large LDL subfraction were not associated with an increased risk of IHD in men and that the cardiovascular risk attributable to variations in the LDL size phenotype was largely related to markers of a preferential accumulation of small dense LDL particles.

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Published on February 27, 2018 15:35