Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

Over a century ago, fasting was hailed not only as a means of combating “cerebral lassitude,” but also for the prolongation of healthy longevity. If that turns out to be true, FGF21 might be a missing link. FGF21 is characterized as a systemic enhancer of longevity. It can be boosted through prolonged fasting, but thankfully there are other, less drastic measures, such as more carbs or less protein.

Give people lots of starchy foods, and you can shoot up FGF21 levels. The healthiest sources would likely be whole grains and beans, since butyrate appears to boost FGF21, too, and we get that from fiber. That’s one of the things our good gut bugs make from fiber-rich foods.

Circulating FGF21 levels are also increased dramatically when you eat a lower protein diet. Over 150% increase within four weeks. And when I say protein restriction, it can just be restricting protein intake, down from the typical excess that most Americans get, down to the recommended amount.

The recommended daily allowance of protein for most men is 56 grams of protein a day, though most American men are getting over 100. So, if you take men getting the typical excess of about 112 grams a day and reduce them down to 64, which again is still more than the recommended 56—so the protein “restricted” group was still getting more than enough protein—you can essentially double FGF21 levels in the blood. That may help explain why despite them getting significantly more calories, they lost more body fat. How can you eat 300 more calories a day and still lose two more pounds of straight body fat? By just bringing your protein levels down to normal levels. Who hasn’t fantasized about a diet that allows ingestion of excess calories that are burned off effortlessly by ramping up fat burning? So, maybe we should play down protein to play up metabolism, thanks to FGF21.

Even just a quite modest protein restriction regimen down to recommended levels may have significant clinical benefits. Now, this was after a month and a half. A similar study found that even less protein restriction, taking men down to just 73 grams a day, resulted in a six-fold increase in FGF21 within a single week, accompanied by a significant increase in insulin sensitivity. They conclude that “dietary protein dilution” promotes metabolic health in humans.

Evidence suggesting that a lower protein intake is positively associated with increased health, survival, and insulin sensitivity has continued to mount, but we weren’t sure exactly how. Maybe FGF21 provides an explanation. Interestingly, the studies were feeding people nine percent of calories from protein, which is what the Okinawans were getting when they were one of the healthiest, longest-living populations in the world.

You may remember my videos on methionine restriction to both fight cancer and as a life-extension strategy. Methionine is an amino acid found predominantly in animal proteins, and so one could achieve methionine restriction by cutting down on animal foods. That may actually be an FGF21 effect. Methionine restriction boosts levels so much so, it’s been called the most important mediator of the metabolic reprogramming in methionine restriction. So, some proteins may be more important to restrict than others. The highest methionine levels are in meat. Legumes (which are beans, split peas, chickpeas, and lentils) have about three times less methionine than meat.

FGF21 has been proposed as a potential mediator of the protection from cancer, autoimmune diseases, obesity, and diabetes afforded by strictly plant-based diets. Maybe that’s one of the reasons whole food plant-based diets have been shown to have such extraordinary results. Take Dr. Esselstyn’s work, for example, showing that the number one killer of men and women can be largely halted or reversed, and risk of heart attack almost eliminated, with the help of a whole food, low-fat vegan diet. This benefit cannot be attributed solely to cholesterol reduction, as we have these new powerful cholesterol-lowering drugs now that can force cholesterol levels as low as healthy eaters but appear to have less effect. So, the marked benefits reported by Esselstyn evidently reflect a variety of protective mechanisms associated with whole food plant-based diets, and FGF21 may be one of those mechanisms. So, it’s not just the fat and cholesterol, but the quantity and quality of protein may also be playing a role. But there’s never been a study to see whether vegans do indeed have higher levels of FGF21…until now.

I’m glad I didn’t just pass on this study based on the title. In addition to studying New Zealand obese mice, they investigated the circulating FGF21 levels among those eating plant-based, and then put it to the test by removing meat from other people’s diets to see if FGF21 would go up. And…FGF21 levels were markedly higher in vegan humans compared with omnivores, and they went up when the omnivores were switched to vegetarian diets after just four days. And not just a little. FGF21 levels increased by 232 percent after just four days free of meat.

The bottom line is that “the various fasting approaches are likely to have limited efficacy, particularly on aging and conditions other than obesity, unless combined with high-nourishment diets such as the moderate calorie intake and mostly plant-based Mediterranean or Okinawa low-protein diets,” by which they mean the recommended amount of protein.

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