 Of more than 100 compounds measured in the bloodstream of thousands of individuals, the one most associated with the lowest rates of disease and death was ergo-thionine. Higher blood levels were associated with lower risk of heart disease, stroke, and death from all causes put together over a period of more than 20 years. Ergo-thionine is an unusual amino acid, although it was discovered more than a century ago. It was ignored until recently when researchers found that humans have a highly specific transporter protein in our body specifically designed to pull ergo-thionine out of food and into body tissue. It's even upregulated right before meal times. This suggests that ergo-thionine plays an important physiological role, but what? Our first clue was the tissue distribution. Ergo-thionine concentrates in parts of your body where there's lots of free radicals, the lens of your eye and liver, for example, as well as sensitive tissues such as bone marrow and semen. Researchers found it acts as a cytoprotectin, a cell protector. Depriving human cells of ergo-thionine leads to accelerated DNA damage and cell death. Because we can only get it in food, and there's toxicity associated with its depletion, Johns Hopkins University researchers conclude that ergo-thionine may represent a new vitamin. If it were classified as such, that would make it the first new vitamin since the last new vitamin B12 was isolated back in 1948. However, traditional vitamins are characterized by the manifestation of an overt dietary deficiency disease with a short time frame, and no specific deficiency disease has yet been identified. But perhaps deficiency diseases are staring us in the face. Low blood levels of ergo-thionine are correlated with increased risk of frailty, cardiovascular disease, cognitive impairment, dementia, and Parkinson's disease. To describe nutrients that may not necessarily be essential for life, but may be essential for long-term health, the famous biochemist Bruce Ames coined the term longevity vitamin, and identified ergo-thionine as a putative candidate. What are the best dietary sources? It's not made by plants or animals, only fungi, like mushrooms and certain soil bacteria. Plants can suck some up from the soil, and animals who eat the plants can similarly benefit, but the highest levels by far have been reported in mushrooms. Excessive tillage of the soil, which is a common practice in modern agriculture, can disrupt the mycelium network, the fungi filaments that pass ergo-thionine along to the roots of crops, leaving mushrooms and tempeh, a fungi-fermented soybean cake, as the only concentrated dietary sources. This is on a dry weight basis though, and mushrooms are like 90% water, so if you change this to prepared wet weight, tempeh does even better on more of a perserving basis. As mushrooms go, shiitake may have comparable levels to oyster mushrooms, about five times more than white button mushrooms, but may also be five times as expensive, unless you grow your own. Oyster mushrooms can be grown in less than two weeks with just-add-water kits. Here's a pick from my own personal stash. Pochinis may lead the pack though, which could explain why Italians average more than four times the average ergo-thionine intake of Americans, but even just eating a cup a day of plain white button mushrooms can double ergo-thionine concentrations in the blood. Yes, ergo-thionine is associated with reduced mortality, but it was also the blood metabolite most strongly connected to a health-conscious food pattern, so could just have been a proxy for healthier eating? And look, correlation doesn't mean causation. Instead of low ergo-thionine levels leading to disease, maybe disease somehow leads to lower ergo-thionine levels? What evidence do we have that we should go out of our way to eat mushrooms? Well, mushrooms can reduce atherosclerosis in butterfet-fed mice, and fruit flies fed a 1% oyster mushroom diet did show a slight but significant survival advantage, and we suspect it's the ergo-thionine since you can give it straight and still get a life extension effect. But what evidence do we have in people? Well, mushroom consumption is associated with a lower risk of cancer, driven mainly by lower breast cancer rates, and mushroom consumption is associated with a lower risk of dying prematurely from all causes put together. I have covered interventional trials showing, for example, that even just a few mushrooms a day can improve immune function, but ergo-thionine may be an under-recognized dietary micronutrient for healthy aging in other ways as well. Dietary ergo-thionine is known to cross the blood-brain barrier, since it can be found in human cerebrospinal fluid and post-mortem brain samples. Perhaps this is why I study in Singapore, found that those who consume more than two servings of mushrooms a week had less than half the odds of suffering from mild cognitive impairment compared to less than once a week. And I study more than 10,000 Japanese elders found that three or more times a week mushroom eaters had a significantly lower risk of developing dementia over a period of about six years. With cross-sectional studies correlating mushroom consumption with better brain function, researchers decided to put it to the test, using Lyon's main mushroom, which is especially popular in traditional Chinese medicine, randomized double-blind placebo-controlled trials on people with normal cognitive function, on people with mild cognitive impairment, and on those with early stage Alzheimer's disease did find small cognitive or functional improvements after months of a third to a full teaspoon of powdered Lyon's main mushroom a day compared to placebo. Interestingly, blood ergothionine levels appear to decline after about age 60, and this decline is tied to both cognitive decline and frailty. And this does not appear to be due to declining mushroom intake with age, so perhaps the function of the ergothionine transporter at the blood-brain barrier declines with age, potentially making mushroom intake all the more beneficial as we grow older. So if I was to create a Dr. Gregor's Baker's dozen, I would probably add mushrooms to the list.