Chapter 36
What About Antioxidants from Supplements?
In seven weeks, methionine restriction in rats reduced electron leakage, the formation of free radicals, and damage to mitochondrial DNA. In line with the mitochondrial theory, this slowed aging, as could be seen in fewer age-related signs of wear and tear and an extension of life span. As shown in the chapters on other anti-aging pathways such as autophagy, dietary restriction can extend life in many ways, but methionine restriction is presumably responsible for about 50 percent of the life extension attributed to dietary restriction overall.
There are three ways to lower methionine intake. We can eat less overall, but then we remain hungry, or we can lower methionine by lowering protein intake alone. Many Americans consume more than twice as much protein as necessary, so it may simply be a matter of switching from excessive to recommended consumption. Because doing so reduces intake of branched-chain amino acids, it is a matter of weeks before the metabolic benefits show up. And while we’re on the subject of added benefits, the third way to lower our methionine intake is to eat plant protein instead of animal protein.
In the past, the comparatively low methionine content of legumes (beans, yellow peas, chickpeas, and lentils) was viewed as a nutritional disadvantage, but longevity researchers concluded that the newly discovered variety of benefits attributed to methionine restriction "ironically turns such a ‘disadvantage’ into a strong plus." This is consistent with data showing that legume consumption among older people worldwide is the most important factor predicting survival, a cornerstone of the life-extending diet in the Blue Zones. A plant-based diet as methionine restriction is "feasible as a life-extension strategy."
What About Antioxidants from Supplements?
Antioxidant supplements are a multibillion-dollar industry. They are often marketed for their purported anti-aging effect, even though hundreds of studies have been unable to find clear evidence for it. People who take antioxidant supplements do not live longer. What’s more, when tested in randomized controlled trials, beta-carotene, vitamin A, and vitamin E in supplement form appear to increase mortality. Supplement users may even be paying to live a shorter life.
In my video see.nf/antioxsupplements, I explain why that is. For example, supplements contain only a few selected antioxidants, whereas our bodies rely on hundreds of them, all working together to get rid of free radicals. High doses of a single antioxidant could disrupt this delicate balance. Rather than acting in isolation, components of antioxidants can work together synergistically. The whole is greater than the sum of its parts.
As I describe in the video, the extreme proximity to, or even physical contact between, mitochondrial DNA and the source of free radicals explains why antioxidants apparently do not slow the pace of aging, but that does not mean antioxidants cannot prevent age-related diseases, which are responsible for the oxidative damage to the 99.999995 percent of our DNA outside the mitochondria.
Free Radicals Accelerate Aging
Our non-mitochondrial DNA is compartmentalized inside the cell nucleus and is not directly in the line of fire of the mitochondria, yet it is constantly being attacked by free radicals. Every day, our genome takes an estimated 70 000 hits, largely resulting in single-strand breaks in the DNA double helix. Fortunately, there are a host of DNA repair mechanisms (the subject of the 2015 Nobel Prize) that patch the break before the cell divides and passes the DNA injury along as a mutation. Unfortunately, the capacity to repair DNA diminishes with age, which is why more DNA damage can be found in older people (though centenarians generally get by with relatively less oxidative damage). Why do we think this is not a consequence but a cause of aging? The most compelling evidence is that most rare genetically determined syndromes that cause premature aging are caused by mutations in DNA repair genes. Parallels have also been drawn to the long-term effects of cancer treatment.
Radiation and genotoxic chemotherapy intentionally create DNA damage via free radicals to destroy rapidly dividing cancer cells. But it isn’t only the cancer cells that are affected, but all cells. If DNA damage is a driving force of aging, it follows that cured cancer patients would suffer early from age-related disabilities, and that does indeed seem to be the case. Cancer survivors develop diseases like arthritis decades earlier than expected. 20 percent of those who had cancer as a child have a heart attack or stroke before they turn 50, but only 1 percent of their siblings do when they are the same age. 10 percent over 65 suffer from frailty and severe loss of endurance and strength. Among those who had cancer as children, the same percentage is already frail between 30 and 40. Whether the excessive DNA damage originates from an inherited deficiency or from genotoxic substances, the result appears to be the same: accelerated aging.
Oxidative stress is involved in hair turning gray, the development of cataracts, arthritis, frailty, and neurodegenerative, cardiovascular, kidney, and lung diseases, as well as cognitive decline, age-related macular degeneration, and muscle loss. If antioxidant defenses are lowered in mice, the results are accelerated hearing loss, the formation of cataracts, and cardiac dysfunction, whereas boosting antioxidant capacity triggers the opposite and postpones age-related diseases. On this pathway of aging, influencing life span may require suppressing the formation of free radicals, but health span might be extended by upgrading our antioxidant defenses to ward off the oxidative stress that results.
Our Original Diet
The Paleo diet view of human nutrition posits that the agricultural revolution over the last 10 000 years is, evolutionarily speaking, only the blink of an eye, and that humans are adapted to a Stone Age diet rich in lean meat. But why stop there? If you compressed our entire evolutionary history into a single year, the last 200 000 human Stone Age years would be only a few days and would account for only that last percent of the roughly 20 million years over which we have evolved since our common primate ancestor.
In our true formative years, perhaps the first 90 percent of our existence, before we learned to use tools, our dietary needs matched an ancient past in which we ate mostly leaves, flowers, and fruits, similar to the other great apes. That is why fruits and vegetables are not only good for us, but vital.
Humans are among the few mammals adapted to a plant-based diet to such an extent that, if we do not consume enough plant matter, we could die of scurvy, a disease triggered by vitamin C deficiency. Most other animals make their own vitamin C, but why should our bodies go to all that trouble when, during our evolution, we were hanging around in trees and eating fruits and vegetables all day?
It is probably no coincidence that the few other mammals that cannot synthesize their own vitamin C—for example, guinea pigs, fruit bats, and some rabbit species—are all heavy plant eaters, just like the great apes. Data from fossilized human feces from the Stone Age tell us that back then we consumed up to ten times more vitamin C and ten times more fiber than we do today. Is this incredibly high nutrient intake simply an unavoidable side effect of constantly eating plants, or do they actually serve an important function, such as antioxidant defense?