 Let's say you're trying to find some solid information about a serious health problem that concerns you, high blood pressure, diabetes, yet everywhere you look someone's trying to sell you something like vitamins, yoga mats, blenders, drugs, well, breathe a sigh relief because all we bring you are the facts. Welcome to the Nutrition Facts Podcast, I'm your host, Dr. Michael Greger. Today we explore the power of the mighty mushroom. Did you know that it may be even more important to include mushrooms or tempeh in our diet as we age? Here's our first story. Of more than a hundred compounds measured in the bloodstream of thousands of individuals, the one most associated with the lowest rates of disease and death was ergo-fianine. 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. Ergothianine 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-fianine out of food and into body tissue. It's even up-regulated right before meal times. This suggests that ergo-fianine plays an important physiological role, but what? Our first clue was the tissue distribution. Ergo-fianine concentrates in parts of your body where there's lots of free radicals, the lens of your eye and your liver, for example, as well as sensitive tissue such as bone marrow and semen. Researchers found it acts as a cytoprotectin, a cell protector, depriving human cells of ergo-fianine 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-fianine 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. While perhaps deficiency diseases are staring us in the face, low blood levels of ergo-fianine 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-fianine as a putative candidate. One of 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 that fungi filaments that pass ergo-fianine 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 per-serving 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. Puccinis may lead the pack, though, which could explain why Italians average more than four times the average ergo-fianine intake of Americans. But even just eating a cup a day of plain white button mushrooms can double ergo-fianine concentrations in the blood. Yes, ergo-fianine 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-fianine levels leading to disease, maybe disease somehow leads to lower ergo-fianine 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-fianine 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-fianine may be an under-recognized dietary micronutrient for healthy aging in other ways as well. Dietary ergo-fianine is known to cross the blood-brain barrier, since it can be found in human cerebrospinal fluid and postmortem brain samples. Perhaps this is why a study in Singapore found that those who consumed 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 a study of 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 Lion'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 Lion's Main Mushroom a day compared to placebo. Interestingly, blood ergo-fianine levels appeared 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. Perhaps the function of the ergo-fianine 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 Bakers dozen, I would probably add mushrooms to the list. In our next story, we look at the power of medicinal mushrooms for cancer survival. Can mushrooms be medicinal? Mushroom-based products make up a sizable chunk of the $50 billion supplement market. This profitable trade provides a powerful incentive for companies to test the credulity of their customers, and sadly, unsupported assertions have come to define the medical mushroom business. For example, companies that market herbal medicines exploit references to studies on mice to promote their mushroom capsules for treating all kinds of ailments, but if you haven't noticed, we're not mice. I mean, it wouldn't be surprising if mushrooms have some potent properties. After all, fungi are where we got a bunch of drugs, not the least of which penicillin, and also a cholesterol-lowering drug lovestatin, and the powerful immunosuppressant drug cyclosporin. Still don't think a little mushroom could have pharmacological effects? Don't forget they can produce some of our most powerful poisons. Some kind of look the part like the toxic Carolina false morel, all toadstool-y and such, but others have more of an angelic look. Indeed, literally called the destroying angel, that's its name, and as little as a teaspoon can cause a painful, lingering death. So anyway, we should have respect for the pharmacological potential of mushrooms, but what can they do that's good for us? Well, consuming shiitake mushroom daily improves human immunity, giving people just one or two dried shiitake mushrooms a day, about the weight equivalent of 5 to 10 fresh ones for four weeks, resulted in an increase in proliferation of gamma-delta T lymphocytes and doubled the proliferation of natural killer cells. Gamma-delta cells act as a first line of immunological defense and even better natural killer cells kill cancer, and the shiitake did all this while lowering markers of systemic inflammation. Oyster mushroom extracts don't seem to work as well, but what we care about is if mushrooms can actually affect cancer outcomes. Shiitakes haven't been tried yet, but reishi mushrooms have after being used as a cancer treatment throughout Asia for centuries. Reishi mushroom for cancer treatment. What does the science say? A meta-analysis of five randomized controlled trials showed that patients who had been given reishi mushroom supplements, along with chemo and radiation, were more likely to respond positively compared to just chemo and radiation alone. Now although adding a reishi mushroom extract improved tumor response rates, the data failed to demonstrate a significant effect on tumor shrinkage when the mushrooms were used alone. So they aren't recommended as a single treatment, but rather an adjunct treatment for patients with advanced cancer. Now, response rate just means the tumor shrinks. What we care about is whether or not it actually improves survival or quality of life. We don't have convincing data suggesting reishi mushroom products improve survival, but those randomized to reishi were found to have relatively better quality of life, so that's a win as far as I'm concerned. What about other mushrooms? Although whole shiitake mushrooms haven't been tested yet, there's a compound that's extracted from shiitakes called lentinine, which is said to have completely inhibited the growth of a certain kind of sarcoma in mice, but in actuality it only worked in one single strain of mice and failed in nine others. So are we more like the 90% of mouse strains in which it didn't work? We need human trials, and we finally got them. There are data on nearly 10,000 cancer patients who have been treated with the shiitake mushroom extract, injected right into their veins. What did the researchers find? There is a compound called lentin extractive from shiitake mushrooms. To get about an ounce, you have to distill around 400 pounds of shiitakes. That's like 2,000 cups of mushrooms. But then you can inject the compound into cancer patients and see what happens. The pooled response from a dozen small clinical trials found that the objective response rate was significantly improved when lentinine was added to chemotherapy regimens for lung cancer. Objective response rate means like tumor shrinkage, but what we really care about is survival and quality of life. Does it actually make cancer patients live any longer or any better? Well, those in the lentinine group suffered less chemo-related toxicity to their gut and bone marrow, so that alone might be reason enough to use it. But what about improving survival? I was excited to see that lentinine evidently could significantly improve survival rates for a type of leukemia, adding lentin to increased average survival, and reduced catexia, which is like cancer-associated muscle wasting, and improved cage-side health. Wait, what? How damn it, this was improved survival for brown Norwegian rats. So that so-called clinical benefit only applies if you're a veterinarian. A compilation of 17 actual human clinical studies did find improvements in one-year survival in advanced cancer patients, but no significant difference in the likelihood of living out to two years. Even the compilations of studies that purport that lentinine offers a significant advantage in terms of survival are talking about statistical significance. Lentineine improved survival by an average of 25 days. Now, 25 days is 25 days, but we should evaluate claims made by companies about the miraculous properties of medicinal mushrooms very critically. Lentineine has to be injected intravenously. What about mushroom extract supplements you can just take yourself? Shataki mushroom extract is available through the internet for the treatment of prostate cancer for approximately $300 a month, so it's gotta be good, right? Men who regularly eat mushrooms do seem to be at lower risk for getting prostate cancer, and not apparently just because they eat less meat or more fruits and vegetables in general, so why not give a shataki mushroom extract a try? Because it doesn't work ineffective in the treatment of clinical prostate cancer. The results demonstrate that complementary and alternative medicine claims can actually be put to the test. What a concept! Maybe it should be mandatory before patients spend large sums of money on unproven treatments, or in this case, a disproven treatment. What about God's mushroom, also known as the Mushroom of Life or Rishi Mushrooms? Conclusions. No significant anti-cancer effects were found, not even a single partial response. Maybe we're overthinking it? Plain white button mushroom extracts can kill off prostate cancer cells, at least in a petri dish, but so could the fancy God's mushroom, but that didn't end up working in people. You don't know if plain white button mushrooms work or not, until you put it to the test. What I like about this study is that the researchers didn't use a proprietary extract, they just used regular whole mushrooms, dried and powdered, the equivalent of a half cup to a cup and a half of fresh white button mushrooms a day, in other words, a totally doable amount. They gave them to men with biochemically recurrent prostate cancer. What that means is the men had already gotten a prostatectomy or radiation in an attempt to cut or burn out all the cancer, but now it's back and growing, as evidenced by a rise in PSA levels and an indicator of prostate cancer progression. Of the 26 patients who got the button mushroom powder, four appeared to respond, meaning they got a drop in PSA levels by more than 50% after starting the shrooms. Now, in the majority of cases, the PSA levels continued to rise, not dipping at all. But even if there's only a 1 in 18 chance you'll be like these two with a prolonged, complete response that continues to date. We're not talking about weighing the risks of some toxic chemotherapy for the small chance of benefit, just eating some inexpensive, easy, tasty plain white mushrooms every day. 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 where we may be able to share it on social media to help inspire others. If you'd like to see any graphs, charts, graphics, images, or studies mentioned here, go to the NutritionFacts podcast landing base. There you'll find all the detailed information you need, plus links to all the sources we cite for each of these topics. My last two books were A How to Survive a Pandemic and My How Not to Diet Cookbook. Get ready this year for the launch of How Not to Age, and of course all the proceeds for the sales of all my books goes directly to charity. NutritionFacts.org is a non-profit science-based public service. We can sign up for free daily updates on the latest in nutrition research with bite-sized videos and articles uploaded nearly every day. Everything on the website is free. There are no ads, no corporate sponsorships, no kickbacks, it's strictly non-commercial, not selling anything. I just put it up as a public service as a labor of love as a tribute to my grandmother, whose own life was saved with evidence-based nutrition.