Mark Sisson's Blog, page 187

9 Trends of Primal Interest

I get a lot of industry news. I eat out a fair bit. I talk to people whose job it is to spot and track health trends. I’m privy to some of the greatest, most innovative minds in the alternative health community—my readers. And you guys are always sending me interesting links. Today, I’m going to discuss some trends of Primal interest. I might poke fun at some of them, and others might be relatively small-scale, but even the silly or minor ones point to interesting movements in the health and fitness zeitgeist.

So, what are the 9 I’m highlighting today?

Experiences over Things

In 2015, I wrote about the dichotomy of value between experiences and things, pointing to research suggesting that buying experiences brings more joy and meaning to a person’s life than buying material objects. I explained how our hunter-gatherer evolution probably wired us to get more out of experiences, and I dug a bit into my own opinion on the matter.

People appear to be agreeing with me. Millennials in particular are choosing things like travel and dining out over gear and gadgets. And the material objects people are consuming enable experiential living—smartphones, fitness trackers, and such. Even media consumption is shifting away from ownership of music and movies to on-demand services like Spotify and Netflix.

Eating Root-to-Leaf

Nose-to-tail eating has taken off. Previously arcane bits like sweetbreads, liver, tripe, marrow, and kidney are on menus everywhere, and few people bat an eye anymore. It’s normal.

Eating root-to-leaf means considering the edibility of the entire plant. More often than not, we’re throwing away a large amount of digestible, nutrient-dense flora.

Broccoli crowns are amazing, but did you know you can eat the leaves? Broccoli leaves are some of my favorite. This also works for Brussels sprouts, cauliflower, and celery.

It means eating roots and their greens, whether it’s a carrot, a beet, a rutabaga, or a turnip. When the guy at the farmer’s market asks if you want him to “twist off the leaves,” say “absolutely not.”

Even things like lemon, orange, or grapefruit rinds can be grated, pickled, or processed to extract the flavonoids.

Artisanal Wilderness Retreats

Outfits are taking young professionals on carefully curated excursions into the wild. Check out this video from Wilderness Collective documenting their maiden trip. Yes, it’s overwrought. Yes, it’s a bit silly and a little too perfect. But it’s satisfying a real need people have: spending unbroken days immersed in natural settings.

Walking the dog in the park before work is better than nothing. Putting up a Yosemite wallpaper on your laptop is nice (and may even have an effect). Actually spending 5 nights camping out and trekking through Yosemite is nicer and far more real, even if you’ve got a Michelin-starred chef flambéing flat iron steaks for you at dinnertime.

Movement, Not Just Exercise

There’s growing awareness of the importance and primacy of frequent—constant, if you can—low-level movement. Developments like fitness trackers, walking clubs at the workplace, the rise of standing workstations (pun intended), the bi-monthly article railing against the dangers of sitting too much, the concept of “exercise snacks,” (mini workouts done throughout the day) and the constant recommendations that people walk at least 10,000 steps a day suggest that the word has gotten out. Folks like Katy Bowman (of Don’t Just Sit There fame) have played a huge role in furthering, explicating, and refining the message.

Formal, dedicated training isn’t going anywhere. Nor should it. The stuff plain works. But it works better atop a foundation of constant low-level movement.

Health and Wellness Tourism

I’m not talking about jetting off to Costa Rica for dental work, or Thailand for a sex change operation. I’m talking about hiking the Pacific Coast Trail, or maybe the Appalachian Trail, or even flying to Spain to hike the Camino de Santiago, or to Turkey to do the Lycian Way. Kickboxing camps in Chiang Mai, Inca Trail maintenance at Machu Picchu, WWOOFing.

Nutrigenomics

Right now, we know a few things about the interactions between specific genetic variants and certain foods, activities, and environmental inputs. But biology is probably the most complex system in the universe. We’re missing a ton.

It’s also getting better. Scientists continue to unmask, identify, and catalogue new variants and their effects—and how what you eat and how you train affects them. A product I used and enjoyed, DNA Fit, and similar ones will only get better, more accurate, and more comprehensive.

Monetization of Recovery Days

With all the CrossFitting, Tough Muddering, Olympic lifting, and other training people are doing, they’re finally beginning to wise up to the role recovery days play in fitness. But rather than only rely on time off and sleep, they’re spending big bucks on the best recovery money can buy. Float tanks (rich in magnesium sulfate epsom salts; the sensory deprivation activates but ultimately helps you tame the monkey mind), cryotherapy chambers (ultra-cold therapy), mobility tools that help you stretch and perform self-myofascial release.

Yes, this can get expensive. This isn’t a bad thing. I’ve always argued for more rest and relaxation and recovery, and the consensual exchange of money for services indicates that consumers of cryotherapy, float tanks, mobility/self-myofascial-release products are clearly getting something out of the exchange.

The Rise of Purple Food

Used to be you could only get a big whack of the all-important purple anthocyanins from a cup of blueberries. That’s changing. There’s purple carrots, purple cauliflower, purple sweet potatoes, purple regular potato, purple asparagus, purple corn, black rice. These aren’t recent creations. Purple/black varieties of produce have been around for decades. They’re becoming more prominent though. All that purple doesn’t make up for the loss of Prince, but it’s probably good for our insulin sensitivity and cognitive function.

Cellular Agriculture

Tech companies’ recent forays into food haven’t gone very well, but cellular agriculture could be a game changer. To grow a piece of beef in the lab, they culture stem cells taken from a piece of beef off an actual living cow. Tender cuts (filets) are harvested earlier, tougher cuts (chuck) are harvested later.

The most prominent cellular agriculture company, Memphis Meats, hopes to have its stem cell-grown “clean” chicken and pork on store shelves by 2021. They’ve already got a working meatball for people to taste.

Will it save us?

That remains to be seen. The “cultured meat” evangelists who decry the climactic impact of ruminants always overlook the vital role holistically-grazed livestock play in maintaining soil health, re-greening land, and building carbon sinks. What other “alternative” benefits of eating and raising traditional will they miss? If they try to “optimize” the fatty acid content of a stem-cell ribeye by excising the saturated fat and bumping up the linoleic acid, I will be very upset (but not very surprised).

If the technology gets cheap enough, we’ll probably be able to grow our own at home to whichever specifications we like. Bump up the vitamin K2, omega-3, collagen, zinc, and so on. That could be cool. Whatever the supposed benefits, if it doesn’t taste and behave just like good meat I’m not interested.

That’s it for me, folks. What about you? What are the trends you’re watching for? Which are the trends you’ve adopted? Let me know down below, and thanks for reading!

The post 9 Trends of Primal Interest appeared first on Mark's Daily Apple.

Dear Mark: Raw Mushrooms, Tom Brady’s Diet, and Beta-Glucan Alternatives

For today’s edition of Dear Mark, I’m answering three questions. First, are raw mushrooms safe to eat? Are there toxins? Are there any other issues to consider? Second, what’s the deal with Tom Brady’s diet and lifestyle? It seems healthy enough, but there are some unanswered questions, too. And finally, are there any other ways to get beta-glucans without eating mushrooms, yeast, or oats?

Let’s go:

I love raw mushrooms, but I have also read that they should only be consumed cooked or they’re too harsh on the insides. Any truth to that?

Basic white mushrooms (agaricus bisporus) do contain a toxin called agaritine. In one study, researchers fed mice diets high in different types of mushrooms or synthetic agaritine to see how each option affected bladder cancer rates. Bladder cancer rates were as follows: mice eating fresh white mushroom, 30.8%; fresh shiitake, 23.5%; dried shiitake, 9.8%; pure agaritine, 50%; paraffin wax as control, 5.4%.

Yet storage, including in the fridge or freezer, and cooking all reduce agaritine to a considerable degree.

Recall that a couple years ago, I wrote about the extensive benefits of eating mushrooms. That stands. They are incredibly healthy and helpful when people actually eat them the way people actually eat them. Maybe don’t eat them raw in large amounts. I find them uninteresting raw, anyway, unless it’s on a salad. Nothing like a pan full of sautéd mushrooms in a reduced Worscestershire sauce/soy sauce/gelatin/butter sauce.

The second biggest knock against raw mushrooms—after controlling for the poisonous varieties—is that they contain chitin, a type of fiber that makes up the cellular walls of funguses (plus many insects). As the story goes, “lots of people” don’t produce enough chitinase, the enzyme that digests chitin, to handle large numbers of raw mushrooms.

Is it true? I doubt it. In 2007, stomach assays of 25 Italian adults found that 20 of them produced chitinase. And the widespread consumption of chitin-rich insects throughout human history never would have occurred if they gave you crippling stomach pain each time you ate one. Crickets aren’t that good.

In fact, chitin supplements have shown to provide major benefits.

Chitosan supplementation may reduce cartilage destruction in autoimmune arthritis.
In healthy men, pre-breakfast supplementation with 3 grams of chitosan increased fecal excretion of dioxins and PCBs, two prominent types of xenoestrogenic compounds found in most modern diets.
A chitin-glucan supplement (extracted from fungi) lowered oxidized LDL in humans. Oxidized LDL is likely causally related to atherosclerosis (as opposed to just plain ol’ LDL), so this could be a helpful supplement for people at risk.

A little off-topic, I would be interested in Mark’s take on Tom Brady’s diet, which I was reading about just yesterday. He is very much a health nut, but his diet, although okay for what it is, seems far too limited to me.

I mentioned this diet in Weekend Link Love a couple months ago. It is an interesting one:

“80% of what they eat is…the freshest vegetables. If it’s not organic, I don’t use it.” Not much to complain about here. 80% is a little high, of course. And is 80% a precise number, or is it shorthand for “a lot”? Does it refer to % of caloric energy or % of volume on the plate?

“And whole grains: brown rice, quinoa, millet, beans.” This is the mystery line. So much to unpack. Beans, for one, aren’t grains. And is this category included in the vegetable category? Whole grains aren’t vegetables, clearly. Yet the next line confirms that “the other 20 percent” is meat and fish, so there’s nothing left over for the grains. Unless… has Brady cracked 100 percent? Do his go up to eleven? Although it wasn’t specified, I’m guessing he’s gluten-free. No one eats millet if they don’t have to.

“The other 20 percent is lean meats: grass-fed steak, duck every now and then, and chicken. As for fish, I mostly cook wild salmon.” Good stuff here. All delicious and nutritious. Duck is a strange one to just toss in there every once in awhile. I love duck. But rarely do I think to myself, “I could really go for some duck breast.” Plus, it’s far from lean.

No nightshades. That means no peppers, tomatoes, potatoes. Some people report sensitivity to the alkaloids in nightshades, though I’ve never seen definitive evidence. The most common complain seems to be joint pain (PubMed search autofills “nightshade arthritis” but doesn’t produce any good results).

“No white sugar. No white flour. No MSG.” No arguments. I’m not too worried about MSG, but then again, I don’t eat foods that contain it.

“I’ll use raw olive oil, but I only cook with coconut oil.” Standard advice that I’m not sure is right. Olive oil—even, or especially EVOO—is quite stable in the presence of heat. The antioxidants protect it (which is why EVOO is so stable) and even prevent the formation of trans fats.

“Fats like canola oil turn into trans fats.” Yes and no. While making baked goods with canola oil has negligible effects on trans-fat formation, high-heat cooking and frying with vegetable oils significantly increases the trans-fat content of the oils.

Brady goes way beyond diet. He’s made an entire lifestyle shift, including going to bed by 9 PM and avoiding parties and alcohol. He shies away from heavy lifting for fear of excessive “shortening” of the muscle, opting instead for flexibility, which he says “softens” and “lengthens” the muscles.

Whatever he’s doing works. Not every individual piece of his diet and lifestyle approach is optimal. But the stuff that works is enough to push him over the edge.

Unfortunately, I’m allergic to mushrooms. Any options for getting beta-glucans other than via oats or yeasts?

Kelp has a fair bit of beta-glucans. You could gnaw on dried kombu or use it in your cooking. Other, tougher seaweeds likely have it as well.

You could try a supplement, though most are sourced from baker’s yeast. If that’s an issue.

Thanks for reading, everyone. Take care and be sure to chime in down below if you have anything to add.

The post Dear Mark: Raw Mushrooms, Tom Brady’s Diet, and Beta-Glucan Alternatives appeared first on Mark's Daily Apple.

Weekend Link Love – Edition 446

RESEARCH OF THE WEEK

Marathons are hard on the kidneys.

Chimps hear music but they don’t hear it, man.

Heart disease patients who were intolerant to statins had more cardiovascular events than those taking statins, but they also lived longer.

The house mouse is at least 15,000 years old.

Daily tea may protect against cognitive decline.

NEW PRIMAL BLUEPRINT PODCASTS

Episode 162: Dave Asprey: Host Elle Russ chats with The Bulletproof Exec himself, Dave Asprey, about his new book, Head Strong, which helps people boost cognitive function, optimize brain health, and eliminate the dietary and environmental triggers bringing us down.

INTERESTING BLOG POSTS

What’s unsafe for your pets to eat? Here’s the real list.

Genetic links between Indians and Latin Americans.

Suicide risk assessments might increase the risk of suicide.

MEDIA, SCHMEDIA

Here’s what happened when three people measured their individual glucose responses to different foods.

McDonald’s switches to fresh beef in their quarter pounders.

EVERYTHING ELSE

Next time you’re in Istanbul, you may be able to work off some of that doner kebab by trampolining and rope-swining your way through a city park.

A descent into India’s strange, beautiful step-wells.

How shame retards personal development, plus other notes on mindfulness and self-judgment.

Prince George is attending a nursery school where having a best friend—an essential aspect of human development—is banned.

Patients are increasingly opting to stay awake during surgery.

Ice skating, meet hiking.

THINGS I’M UP TO AND INTERESTED IN

True crime story I liked: How the Iceman was killed.

Study I found interesting: Physicians who spend more money on patient care do not produce better outcomes.

Article I’m pondering: Where Zika is most likely to hit the continental United States.

Product I want to try but probably shouldn’t: Black Insomnia Coffee, sporting the highest caffeine levels ever recorded.

Miscellaneous news I enjoyed: Dinosaur descendent attacks New Jersey family, plunging headfirst through the windshield.

RECIPE CORNER

Simple Greek-style meatballs are a breeze to make.
Got an Instant Pot? Make this hurried lamb curry.

TIME CAPSULE

One year ago (Apr 2– Apr 8)

How to Get Organized and Stay Focused in a Modern World – There’s a lot of chaff vying for your attention. How to avoid it and focus on what matters.
15 Reasons Not to Trust That Latest Nutritional Study – How to watch for spotty research.

COMMENT OF THE WEEK

“I have worked in pharmaceutical safety for six years, and am involved in clinical trials every day. The following is my personal opinion and does not necessarily reflect the opinion of my employer.

I’d just like to clarify the point about study discontinuation, since Mark points this out as a key smoking gun here. Many drugs are now tested for so called MACE (major adverse cardiac events) events – this is particularly true with diabetes drugs but is often seen with other classes including CV drugs. This really became more common after Avandia and the discovery of unintended CV events. Cardiovascular outcomes trials are almost always results-based and do not have well-defined timelines. That is, they go until they reach enough MACE events to draw statistical significance, then stop. Drug companies will have some idea of how long this should take, based on their knowledge of patients with this disease. Without seeing the protocol I don’t know about the timelines here, but I would expect that they reached their endpoints early. Clinical trials are massively expensive and companies aren’t going to keep running a trial once they get to a level where data is statistically significant.

Ending a study early doesn’t necessarily indicate poor outcomes related to study drug. It could mean that they have reached the designated number of endpoints in the control group. More importantly, it could actually indicate that their treatment is so effective that it’s unethical to keep giving patients a placebo or comparator. This happened with a cancer drug that I was working on – it was so clear that the drug was extending lives that FDA didn’t feel it was ethical to withhold the treatment from the other group. I doubt that’s what happened here, but it does happen and ending a study early isn’t damning on its own. In fact, Amgen is about to enroll on a long term, open label extension of this study to examine potential adverse events, so I highly doubt that this was stopped early due to safety concerns.

Otherwise, I agree with you that it didn’t improve mortality and therefore is not a huge deal. Wall Street also agreed, and Amgen stock took a hit, even with positive results.”

– Important insight from an insider. Thank, wildrover.

The post Weekend Link Love – Edition 446 appeared first on Mark's Daily Apple.

Green Tea Chicken Soup

A warm bowl of soup always tastes nourishing. Add green tea to the broth, and the soup is even more nourishing, offering anti-inflammatory and anti-oxidative properties that can have a positive effect on a wide range of health issues. If you’re not a bonafide green tea lover, this soup might turn into a favorite way to “drink” green tea. The flavor that green tea adds to soup is very subtle, a little herbal, with just a hint of the astringency that tea is known for. Otherwise, it’s still the familiar, savory bowl of soup you love.

You can steep green tea into your own favorite chicken soup recipe, or try this one. In this simple recipe, garlic and ginger are simmered in chicken broth, then the green tea is steeped in the broth for 5 minutes. Thinly sliced mushrooms and spinach are added at the very end (plus optional shredded chicken).

Loose-leaf green tea, which is often thought to be fresher, more flavorful and more healthful, is ideal when steeping green tea into soup. But if you already have a box of green tea bags in your pantry, or if buying tea bags is the most practical option for you, then do it. The soup will still be delicious and nutritious in every way.

Time in the Kitchen: 25 minutes

Servings: 2

Ingredients

6 cups chicken stock (1.4 L)
2 inches ginger, peeled and cut into thin coins (5 cm)
4 garlic cloves, smashed
3 green tea bags, or 3 tablespoons loose-leaf green tea leaves put in a tea ball or T-Sac (45 ml)
8 ounces mushrooms, shiitake or cremini, thinly sliced (230 g)
2 handfuls baby spinach or tatsoi (2 ounces/56 g)
Optional: 1 cooked chicken breast, shredded or cubed

Instructions

In a large pot, simmer the ginger and garlic in the chicken stock for 10 minutes.

Turn off heat. Add the green tea bags. Steep tea bags for 5 minutes.

Remove tea. Strain out garlic and ginger.

Bring broth back to a simmer. Add mushrooms and simmer 5 minutes. Add spinach or tatsoi and chicken (optional) to the broth. Simmer 1 minute more. Turn off heat and serve.

The post Green Tea Chicken Soup appeared first on Mark's Daily Apple.

My “Almost” Success Story

It’s Friday, everyone! And that means another Primal Blueprint Real Life Story from a Mark’s Daily Apple reader. If you have your own success story and would like to share it with me and the Mark’s Daily Apple community please contact me here. In fact, I have a contest going right now. So if you have a story to share, no matter how big or how small, you’ll be in the running to win a big prize. Read more here.

 I’ve entitled my story as an ‘Almost’ Success Story because my story is not yet complete. After having lost 50 kilos (just over 100 pounds), I still have about 10 or 15 kilos to go.

Can I say that while I don’t consider myself Paleo (mainly because I don’t believe in evolution, so I’m pretty sure that disqualifies me….lol), but I do appreciate the articles on all the individual foods that have helped me make healthful choices in what I eat and how many carbs I consume. They have been invaluable, and I am so very grateful for this community and especially for Mark and all he does to help people on their journey to good health. I have adopted the low-carb way of eating (between 50 and 150g daily), and I believe this has been the key to my success. I seldom eat anything refined or highly processed, and I eat all dairy.

For me, it all started after I got a blood test back on October 10, 2015. I was prediabetic at 47 Hba1C, had a slightly fatty liver, and my triglycerides were 2.9 mmol/L. I was also experiencing gout in my big toe (OUCH!), my hips would burn in pain after walking anywhere, I was barely able to move without feeling discomfort, and I had IBS which pretty much ruled my life (as any of you with that condition can attest to). When I got my blood tests back, I remember saying out loud (I was the only one in the room), “I am NOT going to get old and sick!” (I was 48). I had tried so many diets and failed. I, like many of you, had had some successes on the typical LF/HC diets commonly recommended, but I could never stick at it long term. Cravings were simply insatiable, and, let’s face it, who has the superhuman willpower needed to be able to apply it every single day for the rest of your life, which is what one needs to do if one is going to keep the weight off eating LF/HC.

I had already done quite a bit of reading on this website, and I knew controlling my carbs and eliminating highly refined/processed foods was going to be the key for me. So I began immediately. I’m an all-or-nothing girl, and I literally went through my pantry and all my cupboards and ditched everything that was now out of bounds. My darling husband, who is simply awesome, btw, was supportive from the start. After being together for 25 years, and not once with him telling me I needed to lose weight (Oh, and he is slim and 6’4″), I knew that he would eat whatever I put in front of him and never complain. Just as well, because at that stage I simply didn’t have the energy to cook two different meals every night. He has also adopted this way of eating fully, although I am stricter with my carb load than he is.

So off I went, full tilt. I remember sitting on the couch about 3 days after I started, and I said to my husband, “I feel funny….in a good way, but I can’t put my finger on it.” It took me 24 hours to realise what it was: I was no longer experiencing any cravings! Seriously, you’d think I would have recognised that instantly, but what can I tell you. I didn’t. Then, after about two weeks, I was sitting on the couch watching some telly at about 10 pm, and I said to DH, “Man, I feel so good that I could literally get up and go for a long walk!! This is so weird!!”….lol.

Can you believe that! I mean, why couldn’t my doctors have told me that? I’m very grateful for the medical profession when it comes to broken arms, surgeries, etc…but nutritionally…..forget it. Man, they are hopeless at dealing with health issues using food.

I had a blood test three months after I began. Predictably, my fatty liver disappeared, my cholesterol improved (even though I was eating way more saturated fat than I used to), and my BS had gone from 47 to 32 (barely on the start of the scale they measure with). A couple of blood tests later showed that my HDL had risen, my Triglycerides had dropped from 2.9 to 0.4!, and my BS had dropped to 26 (with a note on my tests from my doctor that you don’t get much lower than that!!). My gout has gone, as has the burning pain in my hips. The tiny skin tags all over my neck have disappeared, and, unexpectedly, but very happily, my skin really cleared up! At 48, I still had terrible skin from acne, and the colour and texture also improved.

My hobbies used to be: couch potato or anything else that involved sitting on my chuff. And my poor, enduring husband, who hunts and is as fit as the day is long, would ask if I would accompany him on the odd walk, to which I occasionally agreed out of guilt, but would struggle to complete even short walks. Now he calls me a machine as I hike with him up and down dale (and this coming from a guy who would hunt deer and pig, walking for anything up to 8 hours at a time, carrying a pack and then meat from any animal he was blessed enough to get). So I take his encouragement as a real compliment.

I also love to cycle. I don’t think I’m super fit, by any means, but I’m pretty fit. The first time we walked up Kaiti Hill together (a local landmark in my city which is a 1 kilometre hill climb), I thought I was going to have a heart attack at the top. I was heaving and sweating like the proverbial and honestly, I only shuffled up that flippen hill at a snail’s pace. But it almost killed me….lol. Now it’s like a walk in the park. Really. I love it. And we do much longer walks together.

My life has changed completely. I am, in the first, so grateful to God, and second, to the people who have encouraged me along the way, and to the people in this community who have shared their stories of encouragement, and of course, last but certainly not least, to Mark and his diligence in food research.

To anyone who is contemplating changing their eating to reduce carbs, eat whole foods, eliminate grains and sugars…..don’t wait one more day! Do it! I am turning 50 this year, but I feel like I have gotten younger!

Thank you, everyone.

The post My “Almost” Success Story appeared first on Mark's Daily Apple.

The Plight of the Modern Foot: Conditions that Plague Us—and How to Avoid Them

For all the focus on hearts and arteries, brain tissue and muscle mass, we tend to neglect one critical part of the body with dramatic influence over how we fare in later decades. It’s little surprise really. Feet don’t exactly garner much attention, let alone media time. Yet, the stakes are big.

For example, research shows that foot conditions like hallux vagus (HV, a common forefoot deformity in older people commonly referred to as “bunions”) was directly associated with marked decreases in quality of life. Foot pain, reduced foot function, lowered social capacity, and even degraded general health. That sort of thing.

But that’s just one foot condition, right? Yes…and no. The picture of averages looks rather bleak.

A clinical assessment of 166 Hong Kong hospital outpatients over the age of 65 found that 70% of those patients had some sort of foot condition. In the U.S., things aren’t much better. While surveys have shown extensive variability in reports of foot problems (anywhere between 30% and 95%), other research points to more dramatic prevalence of what I’d consider significant problems. Large-scale, random epidemiological studies aren’t available without confounding factors that muddy the waters. Still, one extensive European study found that 78% of people over 65 suffered from kind of diagnosed foot issue. Even at the most conservative of estimates, that means a minimum of one third of all Americans over 65 will have some form of debilitating foot disorder. And the worst part? Many of the studies discovered that only a small percentage of these people actually report or complain about their foot problems. Apparently, for them it’s just a fact of life.

But most of us here choose differently for ourselves. We prefer to challenge that fatalist “come what may” approach to aging. Feet shouldn’t be an exception. In fact, given the statistics, they might well be a smart priority.

Common Foot Conditions to Avoid

The human foot is an anatomical masterpiece. Each one is made up of 42 muscles, 26 bones, 33 joints, and over 50 ligaments and tendons. That’s more than a little impressive, but it also means that a lot that can go wrong…especially given their workload every day.

Gout

Gout targets the feet and particularly the big toe, causing intense pain and a whole lot of swelling. Unfortunately, many health care providers seem to take great pleasure in informing the Primal, paleo, or general whole food eater that their chances of gout have just skyrocketed on account of all those purines. Purines from organ meats, seafood and various other quintessentially Primal go-to’s.

I’ve talked about gout at length before, so there’s no need to delve back into it. Suffice to say that these kinds of “rich man’s” foods do elevate purines and therefore uric acid in the blood, but they’re also generally high in anti-inflammatory fatty acids. Research shows that systemic inflammation is a key catalyst for gout attacks, meaning high-quality Primal-friendly meats can actually reduce your risk of gout by lowering this causative inflammation. Hah!

I’d personally be more worried about fructose. In elevated doses from the likes of high fructose corn syrup and table sugar, fructose has been shown to promote excess uric acid production and prevent it’s excretion in urine. Alcoholic and smoking binges will have much the same effect.

Athlete’s Foot

As you’re probably well aware, athlete’s foot is the work of our good friend, fungus. Ideal conditions for this mildly repulsive affliction are the same as those for most fungi—warm, dark, moist environments. The same environment that you’re creating on your feet every time you slip on socks and shoes for the day… Look for signs of athlete’s foot between the toes or on the soles of the feet, indicated by inflamed skin or a white, scaly rash with a red undertone. Delicious.

And while most of us would file athlete’s foot under minor inconvenience, there’s sometimes more worth considering. The cause of athlete’s foot can morph from a fungal-derived condition at the early stages to a bacterial overgrowth-derived condition as the skin slowly but surely becomes more “macerated.” Athlete’s foot also has a strong association with cellulitis. Marathon runners have been identified as one of the most at-risk groups for developing athlete’s foot. (File it under obvious on account of having their feet shoved into hot, sweaty shoes for hours at a time.) Barefoot running, anyone?

Hammertoe

If your second, third, or fourth toe is crossed, bent in the middle of the toe joint, or just pointing at an odd angle, you may have a hammertoe. Hammertoes are the tip of the poor foot-health iceberg, and can pave the way for various other foot conditions. The number one cause of hammertoe? Ill-fitting shoes. This might seem straightforward, but, again, the picture gets more complicated than shoe design.

While adopting a Primal diet greatly diminishes your diabetes risk, it’s useful to know that people suffering from diabetes have a much higher likelihood of developing foot problems like hammertoe. In fact, of the 16 million or so Americans with diabetes, around a quarter of them will develop foot problems related to this disease. Pro-inflammatory cytokines, appear to play a role in the development of diabetic foot disorders like hammertoe. Diabetic neuropathy lowers one’s sensitivity to pain, meaning they’re more likely to develop foot-stressing gaits and wear ill-fitting shoes that can then lead to the development of hammertoe. Neurological conditions like Parkinson’s and Cerebral Palsy or any other health problem that distorts the gait can put you more at risk.

Bunions (Hallux vagus)

Got a weird-looking joint on your big toe that forces it to turn into your smaller toes? You’ve probably got a bunion. Research has time and again identified shoes as the leading cause of bunions. As one study observed, “hallux vagus (the condition I mentioned earlier) occurs almost exclusively in shoe-wearing societies.” (Grok is nodding here….)

The more constrained the shoe, like heels or pointed dress shoes, the higher the risk. Safety footwear has also been identified as a common harbinger of bunions.

Women and anyone who is flat-footed might take special notice.

Corns and calluses

An oddly visual yin and yang of the hardened skin world. Corns look slightly cone-shaped and point inwards, while calluses cover a larger area and are more convex in nature. If you’ve got hard areas of skin forming where certain foot pressure points are rubbing on your shoes, you’ve probably got a corn or callus forming.

Corns and calluses can be the result of stresses imposed by ill-fitting footwear, foot deformity (and the subsequent mechanical abnormalities), as well as high activity levels. Essentially, corns and calluses are your skin’s attempt to protect itself from excessive friction. And I think you know where that friction is coming from.

Plantar Fasciitis and Heel Spurs

Plantar fasciitis occurs when the connective tissue between the ball of your foot and the heel becomes inflamed. Coming from experience, it feels like a perpetual bruise on the bottom of your foot. Heel spurs are bony growths at the heel base that often develop after you’ve had plantar fasciitis.

I’ve actually had plantar fasciitis before, and I can confirm that it’s no fun at all. My theory is that it developed by repeated jumping and high-impact exercises performed on a hard surface with no shoes. It wasn’t the lack of shoes that was the problem, it was the hard surface – repeated slamming of the feet (and perhaps not enough landing on the balls of my feet) on that surface was bound to result in bruising, and hence plantar fasciitis, eventually. This didn’t go away until I ditched my nearly every shoe I owned and spent more time on grass and sand than hard surfaces.

Using Primal Approaches to Promote Foot Health

As much impact (oh, the puns…) as foot health can have on mobility and quality of life, it’s really rooted in the basics of Primal well-being. The more your feet can emulate those of Grok, the more robust they’ll likely end up being. As always, we modify for the necessities of our immediate environments. Wood chopping barefoot? Heavy weightlifting barefoot? Strolling the urban jungle barefoot? I’d be inclined to opt for the “shoed” option in those scenarios.

I’ve written at length about bare footing and minimalist shoes. In the past, I’ve highlighted research showing that societies that have largely forgone the whole shoe craze were completely free of all the modern foot conditions I discussed in the previous section. I’ve reflected on the ways shoes have become a part of our psyche, and why switching to a shoeless way of life can ensure continuing foot health into the future.

So what are you to do when faced with a compulsory shoe scenario? This is where our conventional practitioners’ advice may finally be of some use. Unsurprisingly, research shows that folks who switch to wider, higher, “box-toed” shoes reduce their risk. Research also indicates that those who wear constrained shoes like heels or pointed dress shoes are at the greatest risk of developing foot problems. The take-away from this is self explanatory, really – give your feet room to move within their compulsory housing. Avoid shoes that taper in towards the end, that have a low ceiling, and that don’t allow your toes some lateral and vertical wiggle room. Free range toes, as it were.

LIkewise, it’s important to keep feet both dry and supple. This might seem like a bit of a conundrum, but they don’t have to be mutually exclusive. As soon as you get home from work, ditch both the shoes and the socks. If you have access to sunshine, whether through an open window or (preferably) on a sun drenched lawn, get those feet in it!

The benefit of this will be two-fold: first, research has shown that light therapy, whereby concentrated UV irradiation is used to treat fungal infections of the skin and nails, is an effective form of treatment. That sunshine is essentially providing your own light therapy, albeit at lower concentrations than in the lab. Second, you’re re-activating the small muscles of your feet that have essentially been in hibernation since you donned your shoes that morning.

Once you’ve immersed your feet in some healing sunshine, or perhaps just thrust them out in the general direction of a fireplace or heater, you’ve essentially fulfilled the “dry” requirement. Next, lock in the moisture by applying a natural hydrating product like coconut or avocado oil. Both have the added benefit of being anti-fungal and antibacterial, killing two pathogenic birds with one stone. Moisturizing your feet in this way should help to prevent the development of hardened skin layers, which as we know can lead to nasties like bunions, corns and calluses.

And why not give your feet a little care and attention? Therapeutic massage can soften clenched muscles in the feet, reduce inflammation, and remove adhesions between muscles and fascia tissue. All of which means the likelihood of developing muscular or bone-related disorders of the foot are further reduced. Consider it justification for frequent indulgence. It’s just possible that massage therapy may also alleviate the symptoms of diabetic neuropathy, which can contribute to foot problems down the line. Post-oil application, use your knuckles and thumbs to knead the sole, arch and toe joints as you would a lump of (Primal) bread-dough. Mmmmm, dough.

On a side note, I know most people these days rip up any remaining carpet in their house and install hardwood floors, tiles, or even polished concrete. It may look sleek, but our feet weren’t designed to spend their days pounding perfectly flat, unforgiving surfaces. From an evolutionary perspective, this is a relatively recent development. Even post-Agricultural Revolution, most people would have lived in houses with either dirt floors or dirt floors covered in straw. I like the cleanliness of hard floors, but I keep plenty of rugs in the living areas and gel mats in the kitchen and workout room. If you have a standing workstation, consider it for there, too.

Beyond these simple daily steps, there are plenty of other pro-foot changes you can make:

Gut dysbiosis has often been linked to a greater risk of toenail fungus and athlete’s foot. Ditch the antibiotics, up the probiotics, and ease up (big time) on the sugar intake.
Up the anti-inflammatory ante. As I discussed earlier, foods that are high in omega-3s and low in omega-6s can help to reduce your risk of gout, but they can also reduce your risk of developing the likes of plantar fasciitis and any number of other arthritis-derived foot conditions.
Stretch those feet! Studies have shown that stretching is one of the most effective forms of both prevention and treatment for many muscular and tissue-based foot conditions.
Ample low level, low impact activity (e.g. biking, walking, swimming) can keep foot muscles and tendons in good shape, too.
If you’re suffering from recurrent fungal foot attacks, consider investing in a strong topical anti-microbial like tea tree oil. And apparently marigold therapy shows some promise for natural treatment of bunions, warts, and even plantar fasciitis. It’s not a sure thing, but it might be worth considering.

Thanks for reading, everybody. Have you dealt with any of the above issues? Have you found any particular Primal-friendly steps to be effective? Share your solutions (or questions) in the comment section. Take care.

The post The Plight of the Modern Foot: Conditions that Plague Us—and How to Avoid Them appeared first on Mark's Daily Apple.

5 Obscure Nutrients: Why We Need Them and How Grok Got Them

Everyone reading this knows about the macronutrients. You’re all eating enough protein, fat, carbs, and the various sub-categories, like fiber, omega-3s, MUFAs, SFAs, linoleic acid, and so on. You know the major micronutrients, like magnesium, calcium, vitamin B12, and most of the minor (but still vital) ones, like plant polyphenols, iodine, and vitamin K2. Today I’ll be talking about the truly obscure nutrients. The ones health food hipsters were super into like, five years ago (“I’m taking beta-1,3-glucan, you probably haven’t heard of it, there’s only one group at Hokkaido University doing any research, you can only get it off the DarkNet using bitcoins”). The ones Grok was super into like, 50,000 years ago.

What are they, what do they do for us, and, if they’re so great, how did Grok obtain them?

Beta-glucans

Beta-glucans are fibrous carbohydrates that make up the cell walls of certain organisms. They’re found in oats, yeasts, and—most relevant to you—mushrooms. Rather than just provide colonic bulk or prebiotic substrate, what makes beta-glucans so uniquely attractive is their ability to modulate the immune system.

Given to critically-ill patients on enteral feeding, they reduced CRP and improved immune function.

They may improve the immune system’s ability to fight tumors.

According to a recent survey of wild and cultivated mushrooms, both types contain appreciable levels of beta-glucans. Were our hunter-gatherer ancestors eating mushrooms? Almost certainly. Recent research into dental residues found that Neanderthals living in Spain ate gray shag mushrooms. They may even have used mushrooms for their medicinal properties, as gray shag contains an antimicrobial protein.

Phosphatidylserine

One of the hardest words in the English language to type, phosphatidylserine is probably my favorite stress-fighter. The body doesn’t make much of it and stress depletes what little we have. PS works on both mental and physical stress, improving mood and blunting cortisol after physical exercise. (And, yes, it’s why I include PS in Primal Calm.) Older folks in particular seem to benefit from PS, enjoying boosts to memory and cognitive function. Kids with ADHD show better attention when given PS, especially paired with fish oil.

After refined soy lecithin, an industrial product Grok never would have had access to, the best source of PS is ruminant brain. If that sounds like an arcane, unrealistic food source, guess again. Before we were top hunters, we scavenged. We ate the stuff the top carnivores couldn’t, like load-bearing bones and heads, both of which we’d shatter with rocks to obtain the marrow and brains inside. After brain, which is no longer available due to Mad Cow disease worries, the best sources are cold water mackerel, herring, and chicken hearts. A 100 gram (3.5 oz) serving of any of them will give you between 400-700 mg of PS, which matches or exceeds the dosages used in the studies.

Inositol

To give you an idea of inositol’s importance, it used to be called vitamin B8. To give you explicit details of insoitol’s importance, I’ll discuss some research.

High dose inositol can reduce anxiety, even comparing favorably with some pharmaceuticals. It can also reduce insulin resistance and improve fertility in women with PCOS.

If you’ve got the right gut bacteria—and since Grok spent his entire life immersed in a decidedly un-sterile world of dirt and bugs and animal guts, he likely did—you can even convert phytic acid into inositol. Or, rather, they can. That means nuts and seeds effectively become good sources of inositol, provided you train your gut bacteria to make the conversion.

Beta-alanine/Carnosine

Carnosine is woefully underrated. Found abundantly in meat, it’s a combo of the amino acids beta-alanine and histidine. We can synthesize it in our bodies, but in-house synthesis isn’t always up to par. And if it is, adequate isn’t always optimal.

High levels of carnosine are linked to muscle endurance and it acts as an antioxidant in the brain. There’s something called chicken extract that can enhance mood and reduce anxiety, and speed up recovery from stress-related fatigue, and it’s basically a carnosine supplement.

There’s some evidence that taking beta-alanine as a precursor is more effective at increasing muscle carnosine content than taking carnosine itself. We can absorb carnosine, but it doesn’t seem to increase serum levels. Beta-alanine is one of the fitness supplements with the most support in the literature. If you can get past the pins and needles feeling it provokes, beta-alanine can provide:

Improved muscle endurance.
More anaerobic (sprints, high intensity output) capacity.
More lean mass (perhaps by increasing the amount of work you’re able to complete).

Either way, you could just eat meat, the ultimate source of both beta-alanine and pre-formed carnosine. People with a history of athletics have higher muscle carnosine levels than non athletes, and researchers suspect this might be due to the former’s higher meat intakes.

Alpha-Lipoic Acid (ALA)

ALA is created in the mitochondria (especially liver mitochondria) to assist in the creation of various mitochondrial enzymes and Acetyl-COA, which we need to metabolize fats, protein, and carbohydrates. In short, we use ALA to produce cellular energy and maintain cellular function. It’s extremely important.

Yes, we make it. We can still use some extra, some of us more than others.

Diabetics: ALA has also been shown to prevent the descent from glucose intolerance into full-blown type 2 diabetes and increase insulin sensitivity in type 2 diabetics. It may even reduce diabetic neuropathic pain.

Oxidative stress: In patients with metabolic syndrome and endothelial dysfunction, 300 mg/day reduced several markers of inflammation and improved vasodilation. In healthy exercising men, it reduced lipid peroxidation and increased glutathione.

Kidney has between 3-4 mcg of ALA for every gram. Liver, around 1-2 mcg/g and beef heart, about 1 mcg/g. Spinach, tomato, and broccoli are the best sources of ALA in the vegetable kingdom. If you try to get ALA through food, you’re looking at a dose far smaller than you’d get through supplementation, and far smaller than the doses used in research. Then again, the amount of oxidative stress we face as modern humans is unprecedented, whether it’s from the diets we eat, the psychological stress we undergo, the exercise we don’t get, the lack of sleep, the absence of meaning, the loneliness, the disjointed manner in which so many of us lead our lives. Hunter-gatherers by and large didn’t have these problems. They had other problems, more immediate ones. But they weren’t bogged down by the chronic oxidative stress that requires supplementation.

You’ve probably noticed that the research I cite to support the importance of these obscure nutrients almost always uses supplemental doses unachievable through natural sources. Does this mean we can’t benefit from taking them?

Our hunter-gatherer ancestors ate a wider variety of plants, all wild. Wild plants are exposed to more environmental stressors than domesticated plants. To stay robust and survive, the wild plants produce higher levels of polyphenols. They were effectively consuming superfoods in every bite. Supplements can play that role.

Our ancestors lived lives punctuated by short bouts of extreme stress. If they survived, they were more resistant to future stressors, with less inflammation. We don’t have that. We have chronic stress that breaks us down, makes us more vulnerable to future stressors, with more inflammation. If we want similar stress resistance, we must manufacture it and then make sure we get ample recovery time, all while getting a handle on the chronic stress. Supplements can help with that.

Our ancestors likely didn’t deal with the kind of existential crises and psychosocial stress we embroil ourselves in. They break us down and deplete reserves of critical nutrients required for stress resistance. Supplements can replenish them.

If I’ve done my job, you’ll be rushing out in the next few hours to grab chicken hearts, kidneys, almonds and Brazil nuts from the grocery store and forage for mushrooms out in the woods. Right?

Thanks for reading, everyone.

What are your favorite nutrients that few people know about (or ones you’d like me to write about in the future)? What vitamin, mineral, or phytonutrient were you taking before it was cool? Take care.

The post 5 Obscure Nutrients: Why We Need Them and How Grok Got Them appeared first on Mark's Daily Apple.

The Empathy Effect: How Befriending Your Future Self Can Impact Your Health Today

You are not the person you were fifteen years ago. The cells that compose your tissues and deliver oxygen have been recycled many times over. Your face has changed. You move differently. You’re probably slower and weaker, or, depending on your daily habits, faster and stronger. As it becomes available, you incorporate new information into your belief system. Even the neat narrative we imagine we’re orchestrating unbroken in our heads has nightly intermissions lasting hours during which we have no real clue what happens.

Is this all just philosophical navel-gazing better suited for 2 AM in a dorm room covered with Bob Marley posters? Not exactly. Accepting the idea that past and future selves are different people can have real benefits today—and tomorrow.

A study from late last year found that disrupting the temporo-parietal junction—a part of the brain that studies reveal is consistently involved in empathy, essentially our ability to overcome self-centeredness and put ourselves in another’s shoes—led human subjects to choose smaller, immediate rewards over larger, long-term rewards. It had no effect on people’s ability to perceive time, space, or numbers. They understood that the reward would be bigger if they just waited. They just didn’t care. In other words, when people were no longer able to empathize with their future selves, they made choices that benefited their present selves while shortchanging their future ones.

We already subconsciously envision our future selves as different people. Today I’m going to argue that we should be doing it consciously, too, and that doing so can help improve our lives in the present and future.

As I go back through my time as a coach and, now, a health author privy to the trials and tribulations of people trying to get healthier, happier, and more productive, I’m realizing that the biggest successes almost always included some reckoning of the future self. They’d “write 5 year plans.” They’d see how their parents ended up and resolve not to do the same. In almost every instance, they were imagining some version of themselves in the future. Now that I’ve come across this “empathy for future self” research, I’m convinced that these people were inadvertently treating the person they’d eventually become as another person worthy of empathy.

I’m wondering if we can make this work on a conscious level. How can we leverage this “future self as being worthy of empathy” phenomenon?

I’ve got a few ideas.

Write a back blurb for the novelization of your dystopian future.

Dystopian futures are huge these days. From zombie wastelands and father-and-son duos trudging through ruined Americas to shiny high-tech societies where every whim is satisfied but the soul’s, popular culture assumes the future is bleak and horrifying. Imagine, for the purposes of this exercise, that your future is also bleak and horrifying, that someone’s writing a book about it, and that you have to write the back blurb that lays out the basics: the setting, the protagonist, the main conflict.

We all have fears about our future. We all wonder about the worst case scenario. Just how bad could it get? It’s frightening to think about the subject with any sort of depth, so we end up pulling back before it gets too visceral and realistic. With your blurb, get visceral. Imagine in excruciating detail what you don’t want to happen, and write it down. Paint the most miserable—yet conceivable—future for yourself.

Make it so bad that you feel deep empathy for that miserable wretch. And, hopefully, do everything in your power to avoid becoming them.

If you’ve got it in you, write a full-page synopsis.

Write a letter.

A common exercise among life coaches is to have the client write a letter from their future selves telling the present self how awesome their life will be. It’s supposed to help folks believe in the power of change and to see beyond their present circumstances to the glory that lies just around the bend. I’ve put a spin on it: Have your future self write you a letter requesting help with specific tasks.

It could be a positive or negative future. If it’s a positive one, your future self will make requests that ensure things go well and turn out right. If it’s a negative one, the requests will help you avoid the mistakes “you” made.

Daydream with focus.

People often think of daydreaming as reverie: a conscious float through the subconscious. And most of the time, you really do drift from thought to thought to fantasy to thought to imagery. It’s a pleasant way to de-stress, relax your racing mind, and potentially stumble upon an interesting revelation or insight.

To increase empathy for your future self, go into your daydream session with a purpose. Imagine yourself a year, two years, ten years in the future. Imagine you’re living the best life possible. What kind of shape are you in in the future? What’s in your refrigerator? How much can you squat? Don’t steer things too much in one direction or another. Just see what “you” are up to in the future, investigate the details, ask questions, and then return to waking life. Debrief yourself. How’d it look? Did you like what you saw? How do you feel about your future self? What can you do differently today to realize (or avoid) the future you witnessed?

Think of it as a mini vision quest that occurs entirely inside your head. Hallucinogenic toad secretions and 5-day-long fast in the desert are optional.

Ask “How does this affect my future self?”

I don’t suggest you ask this question before every action. You’d end up paralyzed if you had to figure out the long term ramifications of wearing the jeans or the slacks. But the ones with clear impact? The “should I get up and go to the gym or squander another hour staring at my phone in bed?” The “oh man, the salt and vinegar kettle chips are on sale” moment? Ask the question.

We probably already kinda do this on some level. And I bet those who ponder this question on a subconscious level most often are the ones who have the most success and make the right decisions. Some people might never consider doing so on their own but will after reading this. So consider this post a nudge. Ask the question.

Oh, and be sure to answer it to the best of your ability.

Try “Self-Authoring.”

I heard Jordan Peterson on Joe Rogan’s podcast a few months back, and he really resonated with me. A clinical psychiatrist and psychology professor at the University of Toronto, Peterson studies myth, meaning, truth, personality, and self-improvement. His lectures, which he posts to Youtube, get rave reviews. He’s got an extremely unique take on religion, tradition, and how it all relates to scientific facts. Peterson also has a product called the Self-Authoring Suite.

It has three components—Past, Present, and Future. For each, you complete a series of writing exercises designed to help you identify, understand, and eventually realize what you want out of life. There appears to be a good deal on the whole shebang right now, but you can also buy the components separately.

It seems to work. Ethnic minority students in Holland who tried the self-authoring program ended up erasing the academic gap that usually separates minority students from native Dutch students. Think about how it might help you push beyond current obstacles or old stories.

Try a guided meditation to meet your future self.

You probably know that I’m not big on sitting meditation. It just doesn’t work for me. So I do other things that get me into similar mind states. One of them is the guided meditation. Although I don’t listen to guided meditations very often, I’ve really enjoyed the ones I have. They seem to “do the trick” and allow me to reach that place fans of sitting meditation are always gushing over.

Turns out they have guided meditations designed to help you meet your future self. You can go long—this one clocks in around an hour long. You can go shorter—this one from Tara Brach is just over 7 minutes long. If you’re a fan of meditation and find you’re able to achieve those mind states, using a meditation to meet your future self could be extremely convincing.

When you do these exercises, do them for real. Fully inhabit the future self. Take them seriously. If you just half-ass your way through it, your temporo-parietal junction will know it. If this is going to work, you have to commit. You have to really meet and extend empathy for the future self.

That’s it for today, folks. I urge you to give some or all of these exercises a try and report back. Did it help? Do you have any other tips for achieving the same effect?

Thanks for reading and take care!

 

The post The Empathy Effect: How Befriending Your Future Self Can Impact Your Health Today appeared first on Mark's Daily Apple.

Want to Join the Primal Kitchen Team? Become a Brand Ambassador!

Calling all Primal Kitchen enthusiasts! Do you love our products? Does the idea of educating others on the benefits of wholesome, healthy, delicious ingredients pique your interest? Looking for some fun, flexible, part-time work? Then today is your lucky day! We’re expanding our Brand Ambassador teams in multiple cities across the United States. If you (or someone you know) meet the requirements from the list below, and you’re looking for work with lots of control over your schedule, please apply by filling out the application and emailing your resume to brittany.young@primalkitchen.com.

Go over our Brand Ambassador checklist and see if you’re a match. If you are, then you might be snagging one of the hottest positions in town.

Requirements:

You love hanging out in Whole Foods or your local natural grocery store.
You have an outgoing personality and can talk with anyone.
You live a Primal lifestyle.
You love to share your passion for health and nutrition with others.
You live in or near Austin, Los Angeles, Miami, Maui, Missoula, Oahu, New Jersey, NYC, San Francisco, Sacramento, Seattle (or another major metro area).
You have reliable transportation and a smartphone.

Click here to submit your application to become a Primal Kitchen® Brand Ambassador today!

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Dear Mark: That New Cholesterol-Lowering Drug Study

For today’s edition of Dear Mark, I’m answering one question. It’s a good one. A reader (many, actually) wrote in to get my opinion on the latest blockbuster cholesterol-lowering drug. A new study appears to show that the drug in question—Repatha—reduced LDL to unprecedented levels and protected patients against the primary cardiovascular disease endpoints they were measuring. What does it all mean? Should we all start taking Repatha?

Let’s dig into it:

Hi Mark,

What’s your take on this study of a new heart disease drug called Repatha? Apparently it was able to reduce LDL levels to an unprecedented degree, and the lower the LDL the lower the heart attack risk.

Yeah, I saw this. Here’s an article about it in the NY Times. Here’s the actual study. The Times article is positively gushing, recounting that the drug “significantly reduced the chance” of a “heart attack or stroke” in “men and women who had exhausted all other options.”

What’d they take? Repatha is an PCSK9 inhibitor. PCSK9 binds to LDL receptors and prevents them from taking up LDL particles. More PCSK9 activity, fewer available LDL receptors, more LDL particles in the blood.

Given that I’ve spoken about the importance of having good LDL receptor availability and the likely causative role of oxidized LDL particles in heart disease, this doesn’t sound too bad. After all, all else being equal, shouldn’t we want fewer LDL particles? At least Repatha isn’t cutting off a major enzymatic pathway with multiple downstream effects, which is what statins do.

Who took it? High-risk patients with heart disease, about 27.5k of them split into two groups. One got Repatha. One got placebo. Everyone was on statins, so there was no true placebo.

What happened? As the NY Times mentions, the drug did lower the chance of the primary endpoint.

Except the endpoint wasn’t just one event. The endpoint was a composite endpoint. That is, they grouped different events together. The endpoint wasn’t just “did the person have a stroke?” It was “did the person have a stroke, heart attack, hospitalization due to unstable angina or coronary revascularization, or cardiovascular death?”

There’s a big problem with composite endpoints: they assume the constituent events are of equal signifiance. Everyone can agree that death deserves “primary endpoint status.” I’d rather not die of a heart attack (or anything). I imagine most people feel the same way. Not everyone would put “ended up in the hospital because of chest pain” on equal footing as “died from a heart attack”—particularly the people taking the drug. But the success of the Repatha study depends on the two being equally undesirable.

Other “benefits” included reducing LDL levels to an average of 30. A quarter of subjects taking Repatha got their LDL levels down to 19! You’d think with LDL that low they’d be totally impervious to heart attacks and fast approaching demi-god status if not outright immortality.

They weren’t. When you shatter the composite endpoints and examine the individual events, you notice that Repatha didn’t actually help people avoid fatal heart attacks or death from other causes. In fact, the Repatha group had slightly higher death rates from heart attacks (251 vs 240) and other causes (444 vs 426), though it didn’t reach statistical significance.

Furthermore, this study was supposed to last 4 years. They ended it after a little more than 2 years. Drug companies don’t cut studies short if they’re going great. They cut studies short when things start trending south. Were the deaths piling up? Were the initial gains in primary endpoints showing signs of reversal? We just don’t know. But it looks bad if you ask me.

What’s the purpose of PCSK9, though? It can’t be “to give us heart disease.” It’s got to be there for some reason or another, even if that reason is an “outdated relic” of our ancestral past.

It probably evolved as an anti-infectious disease adaptation. LDL is anti-microbial; it can protect against viruses, bacteria, and parasites. In environments with high parasite loads or rampant infectious disease, high PCSK9 activity could enable protective levels of LDL to circulate. 

Another role of LDL is to “soak up” oxidants and other inflammatory agents in the blood. Sure enough, inflammation also increases PCSK9 activity.

Are there any other ways to inhibit PCSK9 that don’t involve spending thousands a month on a potentially-risky drug?

Berberine inhibits PCSK9. It even performs favorably against cholesterol-lowering drugs.

Fasting inhibits PCSK9. In one study, fasting humans achieved the lowest levels of PCSK9 at the 36 hour mark.

Those appear to be safer options. They at least have more history than Repatha.

Overall, I’m not sure what to say. Clearly, the gushing media coverage is misleading. The drug helped reduce non-fatal cardiovascular events, but failed to reduce fatal ones (and even slightly increased them). Furthermore, they cut the study short, which suggests the possibility of worsening mortality and/or other undesirable trends.

I’m not writing it off completely. PCSK9 inhibition might help certain people with confirmed heart disease at high risk of having another attack, like those with familial hypercholesterolemia. Maybe they work better if you’re not taking a statin. Maybe PCSK9-inhibitor+statin is just too much LDL reduction. And maybe there are other, safer ways to inhibit the enzyme.

With the massively positive response from the industry, I’m sure we’ll be getting more research in the coming years. Hopefully, it pans out. But don’t be too surprised if it doesn’t.

That’s it for today, folks. Did you hear about the study? What do you think about the results?

Take care.

The post Dear Mark: That New Cholesterol-Lowering Drug Study appeared first on Mark's Daily Apple.