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The Longevity Paradox: How to Die Young at a Ripe Old Age

Posted by on August 12, 2019 in Health, Longevity & Life Extension with 0 Comments

By Dr. Joseph Mercola |


  • Certain plant lectins are highly inflammatory and interfere with nutrient absorption across your intestinal wall. Evidence suggests avoiding these lectins could help boost longevity by protecting gut health
  • Many of those 95 or older who are still in excellent health have an IGF-1 level between 70 and 80. Restricting animal protein has been shown to consistently lower IGF-1 levels to a significant degree
  • IGF-1 activates the mTOR pathway, which inhibits autophagy, the breakdown and repair of damaged subcellular parts. Keeping IGF-1 low will allow you to properly cycle through autophagy activation
  • Metabolic inflexibility also inhibits autophagy, which is a necessary process for optimal health and longevity. A ketogenic diet and cyclical fasting are both effective ways to regain the metabolic flexibility to burn both sugar and fat for fuel
  • Polyphenols such as quercetin, fisetin, EGCG or resveratrol can be used to activate and augment autophagy

In this interview, Dr. Steven Gundry, medical director for International Heart & Lung Institute and director for Center for Restorative Medicine, reviews some of the concepts covered in his book “The Longevity Paradox: How to Die Young at a Ripe Old Age.”

While trained as a cardiothoracic surgeon, Gundry now specializes in treating patients holistically, focusing on food. I’ve previously interviewed him about plant lectins — the topic of his book “The Plant Paradox” — and the damage they can wreak on your health. Considering their potential influence, it’s not surprising to find plant lectins covered in his book on longevity as well.

What are plant lectins?

As noted by Gundry, certain plant lectins are potent inflammatories, and inflammation is a foundational contributor to most disease. Some lectins — including wheat germ agglutinin found in wheat — bind to receptor sites on your intestinal mucosal cells and interfere with the absorption of nutrients across your intestinal wall.

At the 2019 American Heart Association’s vascular biology meeting, Gundry presented evidence showing dietary lectins can cause an autoimmune attack on the surface of blood vessels.

You can tell this by measuring a cytokine called IL-16, which pulls inflammatory cells to a site. “I showed that removing dietary lectins would dramatically reverse a score that’s been validated for risk of an acute coronary syndrome in the next five years, called the pulse score,” Gundry says. “And it did so by lessening IL-16 production.”

In summary, plant lectins are proteins used by the plant as a self-defense mechanism. “The plants use lectins to defend themselves against being eaten,” Gundry says, admitting the concept that plants don’t want to be eaten is a tough nut for most people to swallow.

“On the other hand, it’s a way of distributing seeds,” he says. “That’s how plants, once again, manipulate their predators to get what they want … Lectins are sticky proteins designed to bond to particular sugar molecules that line our gut … the spaces in our joints … between nerves [and] … our blood vessels.

I and definitely others are convinced that lectins can contribute or are a major cause of what we associate with the diseases of aging, such as arthritis, heart disease [and] neuropathy. There is pretty good increasing information that Parkinson’s may be a lectin problem.

We know that several of the insecticides and herbicides can use lectins to climb the vagus nerve to the brain and go directly to the substantia nigra. My humble opinion is that lectins should be looked at seriously.”

Should everyone avoid plant lectins?

Avoiding certain inflammatory plant lectins is one of the foundational recommendations in “The Longevity Paradox,” and while lectins may be particularly hazardous to specific groups of people, especially those with autoimmune diseases, Gundry believes lectin avoidance is a core longevity strategy for anyone with a damaged gut, which would include most people.

“There are differences in how people react to lectins. Let me say that first off. I can tell you absolutely positively, when we get the major dietary lectins out and we simultaneously seal their gut wall and rebuild their gut microbiome, then over 90% of these people go into remission for their autoimmune disease,” Gundry says.

“On the other hand, is everybody sensitive to them? I think if you have a decent diverse gut microbiome and an incredibly thick mucus layer on your gut, then you’re going to be able to withstand the onslaught or the dietary lectins.

I think what’s happened [is] … our microbiome has been devastated. Our gut wall permeability has been devastated by nonsteroidal anti-inflammatory drugs, glyphosate, and Roundup. Our proton pump inhibitor is changing.”

Does animal protein have a place in a longevity diet?

While Gundry’s book makes many excellent points, one of the positions I disagree with is his stance against animal protein — a position largely based on Blue Zone observations. So-called Blue Zones are areas in the world where people tend to be unusually long-lived. Gundry explains his position:

“I spent most of my career as a professor at Loma Linda University, which is a Blue Zone — Loma Linda, California. I’ve become convinced, looking at the diet of most of the Blue Zones … I think the unifying factor of all the Blue Zones is not that they eat grains and beans, but [that] they have limited amounts of animal protein.

None of them completely avoid animal protein, except the vegans' study by Dr. Gary Fraser. The vegans have the longest long life of all the Adventists studied.

Recently, he’s introduced a paper showing that any addition of animal protein starts skewing them towards more heart disease. Now, this is a study that’s been ongoing in the Seventh-day Adventist community for a very long time.

I am not a vegan. I tend to eat mostly vegan during the week, but my wife and I eat fish and shellfish on the weekends. I consider myself a vegaquarian. I take care of a great number of vegans and vegetarians because of my experience at Loma Linda.

Some of the vegans and vegetarians who come to see me are some of the sickest people I deal with, because in general, they’re pasta and ‘grainarians,’ as I call them. When we get these major lectin-containing foods away from them, they do better.”

Beef alone is not an ideal carnivore diet

The idea that animal protein promotes disease is a position shared by many, so Gundry is certainly not a minority in that perspective. However, I would counter this view by pointing out there are specific variables that typically are not addressed when people promote a meatless diet. In my view, the problems associated with meat consumption are a side effect of:

The observational studies cited by Gundry and others do not take these factors into account. For longevity, in particular, methionine excess appears problematic. Methionine is an amino acid found in meat, fish, and dairy.

However, when you add in connective tissue, one-third of which is glycine, the methionine-to-glycine ratio dramatically improves, thereby diminishing many of the pernicious effects of elevated methionine.

My belief is that when these variables are factored in, animal protein is likely to support optimal health and longevity. The keys, though, are to eat “nose to tail” and some form of cyclical fasting. Gundry replies:

“I don’t disagree with that at all. One of the big points of ‘The Longevity Paradox’ … [is that] we have to have periods of restricted calories at timed intervals, whether we call it intermittent fasting or that we call it time-restricted fasting, whether we call it pure water fasting.

You and I both agree that prolonged water fasting, unless you have a system for getting rid of those heavy metals … is not the best way to go, currently. I do agree with you. The case is very strong that glycine supplementation can make up for methionine restriction.

Glycine, in addition to a normal diet, will act almost as if you’re methionine-restrictive. I take glycine several times a day. [The herbicide] glyphosate is almost identical to glycine … I think the other reason to flood ourselves with glycine is to hopefully occupy those places that glyphosate could occupy.”

Glycine also helps increase nicotinamide adenine dinucleotide phosphate (NADPH), which can be likened to the battery of the cell that recharges your antioxidants. This is yet another reason for taking glycine.

Carnivorous societies tend to live shorter lives

One of Gundry’s main arguments against a carnivore diet is that no carnivorous societies are particularly long-lived. Personally, Gundry gets most of his animal protein from shellfish and mollusks, as well as fats from krill oil.

Krill oil is an excellent source of beneficial phosphatidylcholine (a phospholipid and a major component of biological membranes), serine (an amino acid required for many proteins) and important fats such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are essential cellular components.

Gundry also supports his stance against animal protein through blood testing. He still sees patients and has the benefits of having observed certain patterns within the testing of those patients. He explains:

“Probably for 10 years now, I’ve been tracking insulin-like growth factor (IGF-1) in my patients. I was impressed by the St. Louis University study looking at their IGF-1s and also with a group of vegetarians that they follow.

The Calorie-Restriction Society (CR) does quite well with IGF-1, which you would expect. But they were surprised that they weren’t lower. They asked some of the CR Society members to switch to a vegan diet with the same number of calories. Their IGF-1 factors fell quite dramatically, sometimes 50 points.

I’ve asked some of my patients to let us get an IGF-1 baseline … and then dramatically limit animal protein. I haven’t written the paper yet, because I don’t think I have enough data to get good statistics, but invariably, their IGF-1s fall as much as 50 points from their baseline.

Just this morning, I saw a woman who’s 70 years old. I asked her purposely for the next test to diminish her animal protein. Her IGF-1 fell 30 points down to 160. She was impressed. I was impressed. Does that make a paper? No. That’s just an anecdote. But I think there’s something here …

She skips breakfast and … was doing a shortened feeding period … I think that if you have restricted feeding, it almost always means you’re restricting calories [so] you can get away with a higher protein diet simply because compared to a normal human being [you’re eating fewer calories].

On the other hand, in my practice, most people are not going to do that. They will tell me, ‘I have a life. I’m going out for dinner. I’m going to socialize with friends. Come on. Let’s be serious here.’

We’ve had the occasion of interviewing guests who are doing the carnivore diet. But that carnivore diet is a ketogenic carnivore diet with intermittent fasting, with periods of true fasting, supplementation [and] nose-to-tail eating, so we’ll see.”

Hallmarks of the ‘super old’

Gundry defines “super old” as 95 and older; people who are still thriving, are active and not confined to a nursing home. In general, these patients have an IGF-1 level between 70 and 80.

“The other thing that’s fascinating about these folks is they run low temperatures. Their temperatures are usually 95.5 to 96 [degrees Fahrenheit]. They’re never normal. They tend to run on the hypothyroid side of things. Particularly, they tend to run low free T3s. I think that maybe one of the secrets.

Certainly, we see in fasting — at least in myself and certainly, some of my other patients who I’ve asked to do this — their free T3s are low, but their thyroid-stimulating hormones (TSHs) are absolutely normal. In fact, on the perfect side of normal.”

Longevity requires metabolic flexibility

One of the reasons Gundry is so concerned about IGF-1 is that it tends to activate the mTOR pathway, which inhibits autophagy — one of the most important metabolic processes we have. Autophagy, the breakdown, and repair of damaged subcellular parts is inhibited in the vast majority of the population.

Keeping IGF-1 low will allow you to properly cycle through autophagy activation and mTOR activation. The leading edge of nutritional science right now is really focused on fine-tuning the timing of this cycling. I suspect it has a lot to do with the timing of meals and not just the foods you eat or the ones you avoid. Gundry weighs in:

“Certainly, circadian rhythms are probably lost on most of us in the modern world because of our sources for light, sources of food and availability of food. Up until 100 years ago, we had only light from oil or gas lamps, which is nicely full of red light. It doesn’t have any blue light. We went through seasons of bright blue light in the summer and none in the winter.

Food availability usually corresponded with light. The idea that we, 365 days a year, should be eating in the same pattern doesn’t make evolutionary sense. I’m convinced, looking at our modern hunter-gatherers who still exist, that even their microbiome shifts on a seasonal basis as their food shifts.

I think this diversity and shifting of the microbiome that I talk about in ‘The Longevity Paradox’ may be one of those factors that have been lost in our modern diet. It’s fine to eat organic, grass-finished beef, but we didn’t eat these things every day, continuously for 365 days a year.

That’s part of what’s been lost in all this argument. Most of us have no metabolic flexibility anymore. No ability to switch from glucose … to ketones as our [metabolic fuel]. That’s one of our biggest problems.”

Again, the repercussion of this metabolic inflexibility is the inhibition of autophagy, which is a necessary process for optimal health and longevity. If your body cannot properly clean out damaged cellular components, they end up clogging the proverbial machinery, leading to increased damage. The result is a decline in functionality and frailty.

How to incorporate autophagy boosting supplements

One strategy employed by many is the use of polyphenols, such as quercetin or resveratrol, to activate and augment autophagy. Gundry recommends them for this reason as well.

“These plant compounds we would have eaten on a seasonal basis, not every day probably. I’ve written several papers on the effect, for instance, of grapeseed extract, pycnogenol, which is French maritime tree bark, on vascular flexibility and on phospholipase A2 (PLA2) activity which, for lack of a better word, is how sticky the insides of our blood vessels are to attracting oxidized cholesterol.

Adding these polyphenols actually improves vascular flexibility and stops stickiness. Removing these polyphenols stiffens blood vessels and makes blood vessels stickier. In my own research, polyphenols do some amazing things. They should be in everyone’s diet … [but] I think we should be eating fruit that’s growing locally only during the summer and fall.

I think, for most of us, that we should limit our fruit intake during the winter and early spring … Great apes only gain weight once a year. That’s during fruit season. Normal fruit does not ripen year-round, even in the jungle. Most of our fruit has also been hybridized for sugar content …

How long should you pulse them? Well, I tend to use a lot more polyphenols in the summer and fall, then I tend to back off in the winter. But having said that, I will track my PLA2s, my vascular flexibility markers. If I see them slipping, I’ll add some of these back in. That’s what I do. That’s what I usually do with my patients and watch where we go from there.”

I’ve reached similar conclusions. After taking autophagy-boosting polyphenols daily, year-round, I finally concluded that this probably is not a wise idea. Nowadays, I use a far more targeted approach, taking them only when fasting, as this is when autophagy is triggered.

I typically exercise while still in a fasted state, and then include higher amounts of protein — which will activate mTOR, the rebuilding process, and deactivate autophagy — when I break my fast and eat that day.

All of that said, none of these supplements will do you any good unless you also have sufficient amounts of nicotinamide adenine dinucleotide (NAD) — a coenzyme found in living cells of all types.

NAD is necessary to activate SIRT1, one of the longevity proteins. Based on my review of the scientific literature, I believe optimizing NAD is essential to optimize your health, but typically only becomes a problem after the age of 50 or 60.

A healthy gut might lower your protein requirement

I used to be mTOR-phobic — overly concerned with limiting protein and overly focused on autophagy. I’ve grown wiser as I’ve grown older and disagree with that position now. That’s why I’m more in favor of protein, especially animal protein if you’re exercising extensively.

There are a number of experts who consistently agree that your protein requirements increase with age and when you’re engaged in strenuous exercise, especially strength-training exercise. Either of these will increase your protein requirement by about 25%. Those are two good reasons to include animal protein in your diet. Plant protein just doesn’t seem to work as well in my experience.

Interestingly, as noted by Gundry, most older people who are hospitalized will have low serum albumin, which is a marker for low protein intake. Albumin is a pretty good marker for longevity too. However, in his patients, he’s noticed that once their diet is changed and their gut wall is healed, their albumin levels rise back to normal even though they’re restricting animal protein.

“This is part of the longevity paradox,” he says. “I think our diet has been destroying the absorptive surface of our gut … We can rebuild those microvilli by taking away, among other things, lectins …

The other thing I will argue is we’ll never have the muscle mass of a gorilla or a horse, and all they eat are leaves and grass … To say we have to have animal protein to make muscle mass does not jive with the animal kingdom.”

On the pro-protein side is the argument that protein is a component of your immune system, and you need it to fight infections. The older you get, the more important that becomes, because elderly people tend to die from infections. On the other hand, Gundry argues, you might not require protein per se to optimize immune function. The real key might actually be periodic fasting, as this is one of the most effective ways to regenerate your immune system and stem cells.

Centenarians have healthy gut microbiomes

A key to longevity, Gundry believes, is optimizing your gut microbiome. “There are a number of people 105 years of age around the world who have vibrant health,” he says. “Their gut microbiome, No. 1, is very diverse.” Diet is, of course, a primary contributor to a healthy gut, but an absence of food also plays an important role. Gundry explains:

“Evidence … shows that C. elegans ages and dies because of the breakdown in the intestinal barrier, even its little bacteria, eventually break down that barrier. The thicker you can make your mucus layer, the happier you can make Akkermansia muciniphila, the better. Fasting is one great way to do it.”

Gundry’s longevity plan

Gundry, now 69, is like me — interested in life extension, and more importantly, the extension of health. When asked about his personal strategy to live to 100 or beyond, he says:

“My strategy is, No. 1., I absolutely, positively think time-restricted feeding is going to be one of the big ways I can get there. For the last 13 years, from January through June … I eat no breakfast. I eat lunch. I eat all my calories between a two-hour window, between 6 and 8 o’clock at night.

Why did I choose that two-hour window? Well, if I was really smart, that would not be my two-hour window. But that’s when my wife and I both get home from work. That works for both of us. If I was going to do it and had total control, I would probably have lunch as my two-hour window.

On the weekends, I don’t eat breakfast. I eat a salad for lunch and then usually shellfish for dinner. I do that for six months. Why six months? Because that, I think, and evidence would suggest that that would have been the time period for limited access to food … I do think that polyphenols at the appropriate time [will be required] to get me to 150.”

As Gundry admits, eating that close to bedtime is far from ideal, as you’re feeding your body with calories at a time when calorie expenditure is at its lowest. When your body cannot burn those calories as fuel, they’re stored as energy instead.

In the process of storing it as energy, fatty acids are created, which are the biggest consumer of NADPH. As a result, late-night eating lowers your NADPH level, which is the last thing you want to do, as reducing NADPH creates oxidative stress. Increased oxidative stress, in turn, is a major contributor to aging.

More information

Overall, I believe Gundry’s book, “The Longevity Paradox: How to Die Young at a Ripe Old Age,” is a helpful addition to anyone’s library, as it provides many valuable viewpoints on how to maintain health well into old age.

“I think all of us want to live healthily to at least 100. But what we see in our future doesn’t look very good. We have to make changes. Our entire health care system will crumble if we don’t make some fundamental changes soon,” Gundry says.

Indeed, the U.S. has the most expensive health care system in the world, yet Americans struggle with exceptionally high rates of chronic illness. Our life expectancy is also on the decline while soaring in many other parts of the world. Clearly, the U.S. health care system leaves much to be desired when it comes to addressing chronic illness, and the lack of focus on real food and disease prevention through nutrition is likely a huge component of that.

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