Chapter 189
Lower BCAA Intake
That may help explain the results of the study I described above in the section on FGF21, in which protein intake was reduced from the level of a typical American diet to the recommended amount. Compared with the control group, not only did subjects’ FGF21 double after about six weeks, but the drop in BCAA levels in their blood was also accompanied by a marked drop in blood sugar levels and pounds of fat loss, even though on average they ate hundreds more calories every day. So since metabolic health can be restored by reducing consumption of branched-chain amino acids, experts in the field suggested developing drugs to block BCAA absorption in order to “promote metabolic health and treat diabetes and obesity without reducing calorie intake.” Or we could simply try to eat fewer branched-chain amino acids.
BCAA Supplements
Dietary supplements with branched-chain amino acids are a multimillion-dollar business, promoted with the widely accepted claim that BCAAs increase muscle mass by stimulating muscle protein synthesis—a belief based on rat studies that are more than 40 years old. But the only two studies in humans showed that BCAAs actually cause a reduction in muscle protein synthesis. In see.nf/bcaas I provide an overview of the somewhat mixed research findings on BCAA supplementation in older adults, but essentially we are left with the conclusion of a recent article in a performance metabolism journal: “In conclusion, the benefit of BCAA claimed in supplement advertising is at odds with the general state of the current literature, which does not support the effectiveness of supplementation on muscle strength and hypertrophy [size].”
Lower BCAA Intake
Since BCAAs are found primarily in meat, including chicken and fish, dairy products, and eggs, that would explain why intake of animal protein increases insulin resistance and is associated with a higher diabetes risk, whereas plant foods tend to have the opposite effect. If even just 5 percent of animal protein is replaced with plant protein, diabetes risk drops by more than 20 percent. Although fasting blood levels of BCAAs in the morning do not necessarily correlate with dietary intake, meals high in animal protein can quadruple blood levels, and afterward they can remain high for seven to eight hours.
A clinical crossover study found that subjects randomized on some weekdays to replace just two servings of meat with lentils, chickpeas, split peas, or beans were able to significantly improve their fasting blood sugar and insulin levels, in addition to the predictable benefits such as lower cholesterol and triglyceride levels. According to the results of more than a dozen randomized controlled trials, simply replacing about a third of animal protein with plant protein can significantly improve blood sugar control.
As with methionine, intake of branched-chain amino acids is lower in vegetarians than in omnivores, but only vegans reach significantly lower fasting blood levels because they consume 30 percent less of them, compared with only about 15 percent less in vegetarians. When subjects are randomized to eat a purely plant-based diet for a month, they can significantly reduce their fasting blood levels of all three BCAAs, which also correlates with the anti-inflammatory effect of the switch.
BCAAs might be the reason why randomized subjects eating a plant-based diet lose significantly more internal, more dangerous fat even if they consume the same number of calories. People who eat a plant-based diet also have less fat deposited within the individual muscle fibers themselves, which would explain why vegans in particular often have the lowest risk of developing diabetes. That is by no means only because they are leaner. Even when comparing subjects of the same weight, vegans had significantly less fat in their muscle cells than omnivores, as measurements in a calf muscle showed. Therefore, it is no wonder that people eating a plant-based diet have, on average, significantly lower insulin levels and lower insulin resistance, even compared with nonvegetarians of the same weight.
Those who eat meat have up to 50 percent higher insulin levels in their blood. Compared with a control group that did not change its diet, randomized subjects who ate a plant-based diet saw significant decreases in insulin resistance, fasting blood sugar, and insulin levels. But if you add a bit of protein to the plant-based diet, that can lead to a “dramatic” increase in insulin secretion—by up to 60 percent in just four days. If you add tuna to mashed potatoes, the insulin response is about 50 percent stronger than when eating mashed potatoes alone. But if instead you add broccoli, the insulin response within the first 30 minutes after eating is about 40 percent weaker. This also does not appear to be a fiber effect, because the same amount of isolated broccoli fiber did not bring any significant benefit. The difference in the effects of plant and animal protein was attributed to their opposing amino acid profiles.
The reason branched-chain amino acids are under suspicion is that vegans can become just as insulin-resistant as omnivores by taking pure BCAA preparations, which ultimately demonstrates that BCAAs can act directly and harmfully on insulin sensitivity. Conversely, if you take a few omnivores and dare them to eat vegan for 48 hours, you achieve significant improvements in their metabolic health. After two days of healthy plant-based eating, not only did their cholesterol and triglycerides drop, but so did insulin and insulin resistance, presumably thanks to the “strongly modulating effect” on levels of circulating BCAAs. This was intended to explain some of the beneficial effects of a plant-based diet on lifespan, but because this advantage emerged so quickly, the researchers suspected that the metabolic benefit might come from “intermittent vegan eating” or even the “flexitarian approach” with alternating animal and plant protein.
You Can Take It Too Far
Note that protein restriction is the only intervention that blocks each of the eleven pathways of aging; nevertheless, the prevailing dogma in our society is to eat more protein. A survey of US adults showed that about 65 percent are also trying to do so. Although high-protein diets can help people stick with a diet while losing weight, they do not align with the recommended protein reduction for an anti-aging diet. A careful weighing of the available data supports the recommendation of gerontologists such as Valter Longo and Luigi Fontana to reduce protein intake in order to live longer: “Eating more protein than necessary … does not increase muscle mass, but accelerates the aging process and increases the risk of numerous chronic diseases.”
NAD+
We first looked at nicotinamide adenine dinucleotide (NAD+) back when it all began modestly, as a substance that a 1906 paper with the unpretentious title “The Alcoholic Fermentation of Yeast Juice” recorded as supporting the yeast fermentation process. The authors could not have known what a wave of further discoveries on NAD+ would be set in motion and would bring a total of four Nobel Prizes—so far. Today we know that NAD+ is a vital molecule for all living organisms, indispensable for the functioning of about 500 enzyme reactions, including, above all, extracting metabolic energy from food. With the realization that NAD+ is crucial for the activity of the sirtuins—those “guardians of mammalian healthspan” that I describe in detail in Part I—the 21st century has ushered in another scientific renaissance of NAD+.
NAD+ is one of the most common molecules in the human body. While it used to be considered relatively stable, today we know that it exists in a constant state of synthesis, recycling, and breakdown. Our NAD+ pool is often renewed multiple times per day. To maintain cellular vitality amid this turnover, an adequate supply of NAD+ precursor substances and sufficiently high activity of the NAD+-synthesizing enzymes are crucial. How important NAD+ is becomes apparent from the devastating consequences when one of its NAD+ precursors such as niacin (vitamin B3) is lacking. The deficiency syndrome is called pellagra, and its symptoms are dermatitis, dementia, diarrhea, and ultimately death.

