Fasting and exercise can boost the longevity hormone FGF21, but what can we eat—or avoid eating—to get similar effects?
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 their FGF21 levels shoot up. 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 also increase dramatically after eating a lower-protein diet—more than a 150% increase within four weeks. By the way, “lower protein” simply means reducing intake from the typical excess consumed by most Americans 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 more than 100 grams. When researchers studied men who had been getting the typical excess of about 112 grams a day and reduced them down to 64, which is still more than the recommended 56 grams, so the protein “restricted” group was still getting more than enough protein—they found that FGF21 levels in the blood essentially doubled. That may help explain why they lost more body fat, despite getting significantly more calories. 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 eating excess calories that are effortlessly burned off by ramping up fat-burning? So, maybe we should “play down protein to play up metabolism,” thanks to FGF21.
Even just a modest protein restriction regimen down to recommended levels might 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 sixfold increase in FGF21 within a single week, accompanied by a significant increase in insulin sensitivity, as you can see below and at 2:46 in my video How to Boost FGF21 with Diet for Longevity.
Researchers concluded that dietary protein dilution promotes our metabolic health.
Evidence suggesting that lower protein intake has positive associations with better health, survival, and insulin sensitivity has continued to grow, but we weren’t sure exactly how. Maybe FGF21 provides an explanation. Interestingly, the studies were feeding people 9 percent of calories from protein, which is about what the Okinawans were getting when they were one of the healthiest, longest-living populations in the world.
I’ve talked previously about methionine restriction to fight cancer and as a life-extension strategy. Methionine is an amino acid found predominantly in animal proteins, so one could achieve methionine restriction by cutting back on animal foods. That may actually be an FGF21 effect. Methionine restriction boosts levels, so much so that it’s been called “the most important mediator of metabolic reprogramming in methionine restriction.” Some proteins may be more important to restrict than others. The highest methionine levels are in meat. Legumes (beans, split peas, chickpeas, and lentils) have about three times less methionine than meat, as you can see below and at 3:55 in my video.
FGF21 has been proposed as a potential mediator of the protection from cancer, autoimmune diseases, diabetes, and obesity, 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 coronary disease—the number one killer of men and women—can be largely halted or reversed, and the risk of heart attack almost eliminated, with the help of a whole food, low-fat vegan diet. This benefit can’t be attributed solely to cholesterol reduction, as we have powerful cholesterol-lowering drugs now that can force cholesterol levels as low as those of healthy eaters but appear to have less effect. So, the marked benefits Esselstyn reported seem to 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—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.
In addition to studying New Zealand obese mice, researchers investigated the circulating FGF21 levels among those eating plant-based diets, and then put it to the test by removing meat from other people’s diets to see if FGF21 levels would go up. They found that FGF21 levels were markedly higher in vegan people compared to omnivores, and the levels went up when the omnivores were switched to vegetarian diets after just four days. And not just by a small amount—FGF21 levels increased by 232% after just four meat-free days.
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.
Doctor’s Note
I introduced FGF21 in the first video. If you missed it, check out Life Extension with FGF21.
The methionine videos I mentioned are Methionine Restriction as a Life-Extension Strategy and Starving Cancer with Methionine Restriction.
So, how do you get the benefits without the starvation? Might a ketogenic diet be able to 
