Chapter 163
Xenohormesis and microRNA Manipulation
As we saw in the chapter “Maintaining Bowel and Bladder Function,” cranberries have health benefits for the urinary tract in both men and women. Cranberries can extend the lifespan of flies and worms and slow the age-related decline in insulin production in rats, but whether they have life-extending effects in mammals has not yet been studied.
In the chapters “Maintaining the Immune System” and “Maintaining Vision,” I discussed goji berries. Also known as the Chinese wolfberry, the goji berry has long been considered a “potent anti-aging remedy” in traditional Chinese medicine and is used, for example, against premature graying of the hair. But there is little scientific evidence to confirm these effects. Goji berries do extend the lifespan of Drosophila, but the fact that fruit is good for fruit flies is not a groundbreaking insight. However, goji berries are at least four times as antioxidant as other dried fruits, such as raisins or dried cranberries, that people otherwise sprinkle over their oatmeal or mix into trail mix. Goji berries also have anti-inflammatory effects in vitro (in umbilical cord cells), as well as in randomized placebo-controlled double-blind studies in whole humans, and can even help with weight loss, as I describe in detail in the chapter “Anti-Inflammatory” in How Not to Diet.
Whatever you use raisins for, replace them with goji berries. Grapes have been cultivated for over 6000 years and are now the fruit crop with the largest yield worldwide. How do they benefit us? A meta-analysis of more than 50 randomized controlled trials with thousands of participants found that various grape products can bring about a slight reduction in LDL cholesterol levels (5 percent), but raisins apparently cannot. Presumably because most raisins are produced from “white” grapes—namely the ubiquitous light green Thompson grape. In a direct comparison between red and green grapes, consuming about three cups of red grapes per day after eight weeks led to a significant lowering of LDL cholesterol, but consuming the same amount of green grapes did not.
Accordingly, raisins also could not acutely improve arterial function, but one and a quarter cups of various fresh grapes, a mixture of red and dark blue fruits, actually prevented arterial dysfunction after a Sausage McMuffin with Egg from McDonald’s. A chronic improvement in arterial function was also demonstrated in a randomized placebo-controlled double-blind study (using powder from red grapes).
Nutritional supplements with grape seed extract
The McMuffin Mediation Study used grapes with seeds, where most of the grape’s polyphenols are found. Only one percent is in the flesh, 5 percent in the juice. The grape skin contains 30 percent of the polyphenols, the seeds the remaining 64 percent. Unfortunately, you can hardly find seeded grapes anymore today. Couldn’t you just take nutritional supplements with grape seed extract instead? At see.nf/gse I evaluate the studies available to date for you. And what’s the bottom line? Stick with seeded grapes. The best chance of finding them is in Asian markets, where you may even be lucky enough to find the Kyoho variety (Japanese Kyohō budō, “giant mountain grape”)—dark purple, round grapes with large, oval, delicious seeds.
Xenohormesis and microRNA Manipulation
Xenohormesis and microRNAs are cross-species communication pathways between plants and animals that we can use to our advantage.
Xenohormesis
The phenomenon of hormesis can be thought of as the principle “What doesn’t kill me makes me stronger.” Physical activity is a classic example: You stress muscles and the heart, and they become healthier as a result, provided they get enough time to recover. Mild stressors like exercise can trigger a protective response that, over the long term, leads to stronger defenses.
In the 16th century, the Swiss physician Paracelsus, the “father of toxicology,” coined the Latin saying dosis sola facit venenum, in English: “The dose alone makes the poison.” This aphorism is typically invoked to explain how some of the most useful or harmless substances (for example, water) can be toxic in a sufficiently large amount and how, conversely, even some of the most toxic substances (like cyanide) are harmless in a sufficiently small dose. Toxicology adopted this threshold model for the relationship between dose and effect, according to which, at a sufficiently low concentration, no effect occurs, but at higher concentrations the danger rises in proportion to the dose. Hormesis introduced a new aspect and forced toxicologists to question this assumption.
Hormesis turns the idea that “too much of a good thing can be harmful” on its head and says that sometimes a little of something harmful can be beneficial. The word hormesis comes from the Greek hormáein, “to set in motion.” Instead of a linear model in which a small dose produces a small effect and a higher dose produces the same but stronger effect, hormesis describes a biphasic effect in which a low dose has one effect and a higher dose has the opposite effect. Herbicides, for example, kill plants, but in tiny doses they can actually promote plant growth, presumably because they stress the plant, forcing it to marshal its resources to defend itself.
What began as a biological curiosity, used in a foolish 19th-century attempt to shore up homeopathy, is now attracting renewed interest. In the 1980s, one study a year on the topic of hormesis was published in the scientific literature; today it averages more than one paper per day. This is mainly due to interest in the role hormesis plays in combating aging.
Radiation bath?
More than a century ago, it was first shown that hormesis can extend life when low doses of radioactive radiation increased the lifespan of beetles, presumably by speeding up DNA repair. What didn’t kill them made them stronger. At see.nf/radiation I tell the adventurous story, which includes a study that found that survivors of an atomic bomb explosion live longer, and experiments more than a mile underground, where one is shielded from the cosmic radiation that bombards us every second. Marie Curie, who received the Nobel Prize for her pioneering work in the field of radioactivity, is said to have stated: “Nothing in life is to be feared; it is only to be understood.” However, this statement came from a woman who died because her bone marrow was so badly damaged by radioactive radiation that her body had to be buried in a lead coffin. Watch the video, but the bottom line is that we do not know enough about low-level radioactive radiation to take advantage of any hormetic effects without exposing ourselves to unacceptable risks. But there are more favorable ways to use hormesis for health and longevity.
No pain, no gain
We all know that exercise is basically good for us, but regardless of that, the body is inevitably subjected to stress in the process. Ultramarathon runners produce so many free radicals during a run that they can damage the DNA of a significant portion of their cells. Yet within a week, the DNA damage not only returns to baseline, but there is actually significantly less damage—presumably because the runners strengthened their antioxidant defenses. That means oxidative damage from exercise can ultimately be beneficial. In other words: This is classic hormesis, in which slight damage strengthens protective mechanisms so that you end up better off. If you want to know how not to undermine the benefits of recovery after exercise, see see.nf/exercisehormesis.
What doesn’t kill plants can make us stronger
Hormesis may be the reason why dietary restriction leads to a longer lifespan. The mild stress you subject the body to when you don’t eat enough can activate a variety of protective mechanisms and strengthen anti-inflammatory and antioxidant defenses. The body is preparing for a famine that it believes is ahead.