Newsletter #232

In his Triage Theory, Bruce Ames proposes that suboptimal nutrient intake contributes to diseases of aging due to a sort of rationing response, selected for by evolution. Here’s the basic idea: Vitamins and minerals function as co-factors required for our metabolism to function, and overt deficiency results in well-established adverse health effects. But what if you are just getting enough vitamins and minerals to keep the lights on, so to speak? In that case, vitamins and minerals preferentially go to proteins and enzymes essential for survival, while proteins and enzymes that help us maintain long-term health and fight diseases of aging are left to starve. It’s a pretty compelling idea.

Ames goes on to argue that there is a class of nutrients that are not essential for survival, but are needed for longevity, which he characterizes as “longevity vitamins.” One of these is ergothioneine, an antioxidant synthesized by fungi and soil bacteria but not by plants or animals. Ergothioneine is particularly interesting because it gets taken up by a specialized transporter, which has been shown to be essential in animal experiments (deleting the gene that codes for this transporter leads to DNA damage). That, along with its associated health benefits (see below), suggests it is pretty darn important.

There aren’t a ton of studies out there that directly examine ergothioneine levels or ergothioneine consumption. However, as you’ll see, research looking at mushroom intake can be useful for gauging the effects of ergothioneine, since they are by far the best source of ergothioneine (porcini, oyster, shiitake, and enoki mushrooms seem to be the absolute best).

Researchers at Penn State combed the literature and identified 17 observational studies, published between 1966-2020, which assessed the relationship between mushroom intake and cancer. They found that higher mushroom consumption was associated with lower risk of cancer. Dose-response meta-analysis showed that a mushroom intake of 18 grams was associated with a 45% lower risk of total cancer, compared to no mushroom consumption. The most robust association was found for breast cancer, although this may have been due to a comparatively small number of studies that looked at other cancer sites. Something else that jumps out in this meta-analysis is that studies conducted in Eastern countries found a more consistent inverse association between mushroom intake and total cancer than those in Western countries, maybe because mushroom consumption is much greater in the East (thus more participants would be getting a large enough dose to make a difference).

Prior research has shown that whole blood ergothioneine levels tend to decline significantly in elderly individuals, and people with age-related cognitive impairment have significantly lower plasma ergothioneine levels compared with age-matched healthy counterparts. To explore this association further, researchers in Singapore analyzed cross-sectional data from 663 community-living elderly participants.Nurses collected information on mushroom consumption through one-on-one interviews, and cognitive function was assessed through standardized tests. When dietary data and cognitive status were analyzed, the researchers found that older adults who consumed more than two portions of mushrooms weekly had ~57% reduced odds of a clinical diagnosis of mild cognitive impairment. This association was independent of age, gender, education, smoking, comorbidities, and other confounders. In vitro research, as well as animal models, suggest that ergothioneine may shield the brain against the ravages of beta-amyloid, the neurotoxic proteins thought to play a causative role in Alzheimer's.

Researchers affiliated with Lund University in Sweden looked at fasting plasma levels of 112 metabolites from a baseline examination of 3236 Swedish participants who did not have cardiovascular disease or type 2 diabetes at the start of the study. First, they assessed how all of these measured metabolites were associated with a specific dietary pattern that they had previously identified in this cohort which was found to be strongly associated with protection from cardiovascular disease and type 2 diabetes. Out of the 112 metabolites, they were able to pick out five that showed significant positive associations with the healthy dietary pattern. Higher ergothioneine was the metabolite most strongly associated with the health-promoting dietary pattern. Next, they analyzed how these metabolites were related to long-term outcomes over the follow-up period of 21 years. Ergothioneine shined here as well, emerging as an independent marker of lower risk of cardiovascular disease or death from any cause. Every standard deviation increment of ergothioneine was linked to a 15% lower risk of coronary disease, 19% lower risk of cardiovascular mortality, and 14% lower risk of all-cause mortality.

Thanks for reading, enjoy the weekend, and we will see y'all next week!

https://mailchi.mp/humanos.me/newsletter-232