 Let's say you really need to find reliable information about the best diet for high blood pressure or heart disease or diabetes. Where do you go? Do you go to a website sponsored by Big Pharma that wants to sell you pills to fix your problem? Or do you want to treat the cause? Welcome to the Nutrition Facts Podcast. Most of us want to live longer. And if we could locate that fountain of youth, we would probably take a sip or two. However, there is a hormone already in our body that does something very similar. It's a longevity hormone called FGF21. Here's our first story. In the year 2000, a new human hormone was discovered. It was the 21st documented fibroblast growth factor, so they called it FGF21. Since this discovery, FGF21 has emerged as a key agent for promotion of metabolic and artery health, leanness, and longevity. Injected into fat monkeys and they lose body weight without reducing food intake. And not just a little, a 27% drop in body fat eating the same amount. In mice, it increases their lifespan 30 to 40% comparable to a lifelong caloric restriction, but again was achieved without decreasing food intake. The researchers conclude that FGF21 could potentially be used as a hormone therapy to extend lifespan in mammals, which has gotten big pharma salivating, raising the question, can aging be drugged? And that's not all it can do, the idea that one drug can treat obesity, diabetes, dyslipidemia like high cholesterol, and hypertension, all at once might have seemed impossible a few years ago, but is now a tantalizing and exciting prospect. The reason you can't just give people straight FGF21 is that it gets rapidly broken down in the body, so you'd have to get injections like every hour or two around the clock. So drug companies try to patent a variety of longer acting FGF21 look-alikes, and indeed give people little PF050 to 31023 and they can lose about 10 pounds in 25 days along with dramatic drops in triglycerides and cholesterol. But then the side effects of these newfangled drugs started cropping up. OK, so hey, what about this? We package the FGF21 gene into a virus and then inject the virus and have it like stitch extra FGF21 genes into our DNA, or you can just lace on your running shoes. Exercise boosts FGF21 levels, which may in fact be one of the reasons exercise is so good for us. Which works better, though. Aerobic exercise, eight weeks of running, training, or resistance exercise, eight weeks of weights? The answer is both, but their resistance exercise edged out the running, a 42% increase in FGF21 versus a 25% increase in the aerobic exercise group. OK, but what can we do with food? Yeah, you could try engineering and injecting it, but wouldn't it be easier to just stimulate our own endogenous natural production through diet? One way is through no diet at all. You may have noticed it's been dubbed the starvation hormone. That's because fasting induces FGF21, but not just a day or two. Physiologically, FGF21 expression is markedly increased in response to fasting starvation, but unlike mice, which show an increase after just six hours of fasting, humans don't get a notable surge in FGF21 until after a week. Fasting can quadruple FGF21, but it takes 10 days of fasting, which is the very poster child of an unsustainable eating pattern. So how can you get the benefits without the starvation? Might a ketogenic diet be able to mimic the fast? Nope, keto diets don't work. In fact, keep it up for a few months and you can actually get a significant decline in levels. High-fat diets may even interfere with the boost you get from exercise. What kind of diet does work, then? We'll find out next. Over a century ago, fasting was hailed not only as a means of competing 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 healthier 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. 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 things to FGF21. Even just a quite modest protein restriction regimen down to the 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, but maybe FGF21 provides an explanation. Interestingly, studies were feeding people 9% calories from protein, which is about 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, about fight cancer and as a life extension strategy, methionine is an amino acid found predominantly in the animal proteins, and so one could achieve methionine restriction by cutting down on animal foods. Well, 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. Some proteins may be more important to restrict than others. The highest methionine levels are in meat. Legumes, which are beans, split peas, chickpeas, 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 that whole food plant-based diets have been shown to have such extraordinary results. Take Dr. Asselstyn's work, for example, showing that 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 reductions. 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 market benefits reported by Asselstyn evidently reflect a variety of protective mechanisms associated with a whole food plant-based diet, and FGF21 may be one of those mechanisms. So it's not just the fat and cholesterol, but the quality and quantity of protein that 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 the 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 to 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%, just four days free of meat. 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. We would love it if you could share with us your stories about reinventing your health through evidence-based nutrition. Go to nutritionfacts.org slash testimonials. We may share it on our social media to help inspire others. To see any graphs, charts, graphics, images, or studies mentioned here, please go to the Nutrition Facts podcast landing page. There you'll find all the detailed information you need, plus links to all the sources we cite for each of these topics. 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