Mushroom Power

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 bloodstreams of thousands of individuals, the one most associated with the lowest rates of disease and death was ergothioneine. 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.

Ergothioneine 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 bodies specifically designed to pull ergothioneine out of food and into body tissue. It’s even upregulated right before meal times. This suggests that ergothioneine plays an important physiological role. But what? Our first clue was the tissue distribution. Ergothioneine concentrates in parts of your body where there are lots of free radicals—the lens of your eye and your liver, for example, as well as sensitive tissues such as bone marrow and semen. Researchers found it acts as a cytoprotectant—a cell protector. Depriving human cells of ergothioneine 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 concluded that ergothioneine “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 within 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 ergothioneine 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 ergothioneine 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 mycelial network, the fungi filaments that pass ergothioneine 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 percent 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. Porcinis may lead the pack, though, which could explain why Italians average more than four times the average ergothioneine intake of Americans. But even just eating a cup a day of plain white button mushrooms can double ergothioneine concentrations in the blood.

Yes, ergothioneine is associated with reduced mortality, but it was also the blood metabolite most strongly connected to a “health conscious food pattern;” so, it could just have just been a proxy for healthier eating. And look, correlation doesn’t mean causation. Instead of low ergothioneine levels leading to disease, maybe disease somehow leads to lower ergothioneine levels. What evidence do we have that we should go out of our way to eat mushrooms?

Well, mushrooms can reduce atherosclerosis in butterfat-fed mice, and fruit flies fed a one percent oyster mushroom diet did show a slight but significant survival advantage. And we suspect it’s the ergothioneine, 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 eating just a few mushrooms a day can improve immune function. But ergothioneine may be an underrecognized dietary micronutrient for healthy aging in other ways as well.

Dietary ergothioneine 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 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 mane 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 mane mushroom a day compared to placebo.

Interestingly, blood ergothioneine 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 ergothioneine 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 going to create a Dr. Greger’s Baker’s 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 had some potent properties. After all, fungi are where we got a bunch of drugs, not the least of which is penicillin, also a cholesterol-lowering drug lovastatin, and the powerful immunosuppressant drug cyclosporin. Still don’t think a little mushroom can 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 toadstooly 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 mushrooms daily improves human immunity. Giving people just one or two dried shiitake mushrooms a day (about the weight equivalent of five to ten 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 andradiation were more likely to respond positively compared to just chemo and radiation alone. 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.

“Response rate” just means the tumor shrinks. What we care about is whether or not it actually improves survival or quality of life, and we don’t have convincing data suggesting reishi mushroom products improve survival. But those randomized to reishi were found to have a 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 lentinan, 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 percent 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 lentinan, extracted 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 lentinan was added to chemo 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 lentinan 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 lentinan evidently could significantly improve survival rates for a type of leukemia. Adding lentinan increased average survival, reduced cachexia (which is like cancer-associated muscle wasting), and improved cage-side health. Wait, what? 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 lentinan offers a significant advantage in terms of survival are talking about statistical significance. It’s hard even to tell these survival curves apart. Lentinan 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.

Lentinan has to be injected intravenously. What about mushroom extract supplements you can just take yourself? Shiitake mushroom extract is available through the Internet for the treatment of prostate cancer for approximately $300 a month; so, it’s got to 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 shiitake 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 reishi mushrooms? Conclusions: No significant anticancer 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 to 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, 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 percent after starting the shrooms.

Now, in the majority of cases, the PSA levels continued to rise, not dipping at all. But even if there is only a one 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, but just eating some inexpensive, easy, tasty plain white mushrooms every day.