Supplement and small molecule --insist on long term human data
TPE and aging, alz, long covid and now heart attacks?
Okay this new style of writing a weekly blog is getting too long.. but readers seem to like it so I will continue for a while; here’s today’s topics:
1. RAPA man seems wrong here too
2. Supplement and small molecule data
3. TPE and aging, alz, long covid and now heart attacks?
4. The Science—You Want to Resemble a Sirloin, Not a Rib Eye
5. A question on ergothionine from a patient with early Parkinson’s and my answer
RAPA man seems wrong here too
Let me first say that Peter Attia MD was, and probably still is, one of my heroes in Wellness but notice I said heroes in Wellness, not in Longevity; Wellness is slowing aging where longevity IMHO is reversing to a younger age. Peter, if I may use the familiar, is superb at keeping to science on most topics, and at motivating his patients and telling the world and hopefully motivating some of you as well as others to adopt healthy behaviors.
My admiration like many peoples lost some tarnish for the Epstein behaviors (really underaged kids for 10 days when your wife is delivery her and your baby?) but that is not in the field of wellness except in not exhibiting and modelling great behavior –but who among us is perfect? But in Wellness /Longevity I believe his car’s license plate read “RAPA MAN” (maybe it was his friend). That stood for his strong belief, use of, and promotion for others of low dose Rapamycin to stay healthy. But like metformin, recent data indicates it ablates some of the benefits of exercise, and doesn’t extend healthy life by slowing aging or reversing aging for anyone who can exercise.
These recent data confirm why we have the strict criteria we—the Scientific Advisory Board (SAB) -- do at the Great Age Reboot company for suggesting you talk to your doc about seeing if specific supplements are appropriate for you--- here again are our SAB’s criterial for supplements and small moleucles and the ones that pass and don’t pass muster:
2. Supplement and small molecule data
Some not to bother with—wallet biopsies as of now—either not enough data or just continually fail human tests:
Of 55, 37 –the majority fit this category—some of the major ones:
NAD: great animal data; fails all but specific mitochondrial deficit diseases human tests so far.
Resveratrol: great animal data; fails all human tests so far.
Metformin: USA data epidemiologic look great; Netherlands data look opposite—causes aging. Do not use if exercise
ACV—no benefit
Rapologues—promising but no positive human data so far
Urolitin A – promising but not enough human data so far
Melatonin Maybe for sleep and sepsis and jet lag but no long term ACM or disability studies
Ashwaghanda –good releasing agent; no long term ACM or disability studies
Some of the recent science on Rapamycin:
Here are what Dr Attia calls the Disappointing results from the first rapamycin-trial (Stanfield B, Leroux B, Kaeberlein M, Jones J, Lucas R. Exercise and weekly sirolimus (rapamycin) in older adults: RAPA-EX-01 randomised, double-blind, placebo-controlled trial. J Cachexia Sarcopenia Muscle. 2026;17(2):e70274.)
The Stanfield Rapamycin study was the first randomized, double-blind, placebo-controlled trial to pair weekly sirolimus with an exercise program in older adults Its conclusion: Rapamycin didn’t enhance functional gains from training, and appears to have modestly blunted them.
Despite the results, Dr Attia stated “the trial…represents a small addition …on one narrow dimension, namely muscle adaptation under these specific conditions, but it does not materially resolve the broader uncertainty around rapamycin’s effects on the major drivers of aging and mortality.” Wrong IMHO –if it negates the benefits of exercise on aging, and you know the benefits of exercise, then this is not at this time and until further study, a choice for anyone now to consider for its anti-aging benefits –not for wellness nor for longevity.
He went on” Secondary functional outcomes all pointed in the same direction, though none reached significance: The 6-minute walk distance difference was −4.87 meters (p=0.706), and grip strength was −1.19 kg (p=0.344), each favoring the placebo arm over rapamycin; there was even a slight trend toward inferior outcomes in the rapamycin group on the Short Form 36 (SF-36), a questionnaire that measures quality of life across eight physical and mental health domains. While each of these comparisons is individually underpowered, the consistency in direction across multiple endpoints raises the possibility that the observed effect is not purely noise.”
To make matters worse, you do careful studies to look at safety—and here again rapamycin seemed to not thrive:
· a statistically significant but very small increase in HbA1c in the rapamycin group,
· a case of pneumonia.
· The Take home of the recent science: Don’t take Metformin or Rapamycin for aging if you exercise, and do do all 4 forms of physical activity as they have much greater benefits—about 9 years for the typical 55-75 calendar year old woman and 8 + years for the typical 55-75 calendar year old man.
3. TPE and aging, alz, long covid and now heart attacks?
Myocardial infarction (MI) is the leading cause of cardiovascular-related deaths worldwide, with risk increasing sharply with age. Fibrosis and inflammation occur soon after a pathological event and reflect perturbation of tissue repair that accompanies aging in general. We previously have shown data in thnis blog that in animal models and in humans that Therapeutic Plasma Exchange (TPE) also termed neutral blood exchange (NBE) (replacing~50 to 100% of plasma with saline containing 5% albumin) decreases symptoms in randomized controlled trials (RCT’s)in long Covid and COVID vaccine injury (multiple RCT’s), sustainably improves (not just stabilizes) cognitive function in Alzheimer’s (in tow RCT’s), and in RCT’s examing aging, reproducibly improves aging biomarkers. TPE has these effects by getting rid of missignalling proteins that contribute to chronic disease and inflammation (see Lifespan-Edge.com/research). The Conboy team from Berkeley and Stanford developed a preclinical model of heart attack and found that one TPE treatment soon after a heart attack significantly and broadly improved the recovery at molecular, cellular, tissue, and functional levels in aged mice (Aging Cell, 2026; 25:e70525 https://doi.org/10.1111/acel.70525). Future studies are needed to establish the detailed processes and safety profiles of plasma dilution as a treatment of heart attacks.
· Take home as I reported in an earlier blog, I have no specific condition I was treating but had 4 TPE treatments, and feel 40 years younger than my calendar age. Still do.
4. When It Comes to Your Muscles’ Health, You Want to Resemble a Sirloin, Not a Rib Eye
Typically, 32 to 44% of a man’s body weight is muscle. For women it goes from 33% to 27%.But whatever your percentage of muscle mass, you want to make sure it doesn’t resemble a well-marbled rib eye.
Researchers at UCSF (https://pubs.rsna.org/doi/10.1148/radiol.251129) examined 615 men and women, average age of 60, who got 28% to 44% of their nutrition (or lack of it) from ultraprocessed foods. Using MRIs, they discovered that folks downing UPFs had large streaks of fat crammed in between their thigh muscles—and that over the course of 10 years, folks with the largest amount of such muscle fat infiltration were at greatest risk for knee osteoarthritis. (Chances are those kinds of unhealthy fat deposits can up the risk to other joints as well.)
Most interesting, it didn’t matter if the folks were obese or overweight or how many calories they ate, it was the amount of UPFs they consumed that upped their risk of poor muscle health and knee osteoarthritis.
The Take home: ‘Don’t eat ultraprocessed foods.” You’ve heard it a million times and yet…there are still sugary drinks, processed meats, packaged snack foods, even smoothie and other powdered suppleemnts in your fridge and pantry. Just Say No at the Store
And especially avoid fructose for your muscles-- the dangers of added fructose are even greater than we suspected. According to a study in Nature Metabolism (https://www.nature.com/articles/s42255-026-01506-y ), it ups your risk of weight gain, encourages your liver to produce excess triglycerides, ups the chance of developing metabolic syndrome, muscle fat infiltration, insulin resistance, type 2 diabetes, hypertension, heart woes, gout, and certain malignancies, --and contributes to dementia.
5. A question from a patient: Ergo for Parkinson’s
Dr. Roizen,
The email below is from my sister. Subject: Subject: Potential Protection Against Parkinson’s Disease by Ergothioneine—most abundant in mushrooms!
Interested - we take liquid drops of mushrooms daily
Summary: In a study titled “Potential Protection Against Parkinson’s Disease by Ergothioneine—Nature’s Multifactorial Neuroprotectant,” researchers from Singapore reviewed growing evidence that ergothioneine, an antioxidant found most abundantly in mushrooms, may help shield the brain from Parkinson’s and Alzheimer’s diseases. Unlike most dietary antioxidants, ergothioneine crosses the blood-brain barrier and lingers in the body for about a month. Studies in worms, flies, mice, and human neurons show it reduces toxic protein clumps, calms inflammation, and protects brain cells. Early human trials suggest it improves sleep and slows memory decline safely.
Do you have any thoughts on including mushrooms in my diet or starting a supplement—such as drops—similar to what she is doing?
Hope all is well.
Thank you, Patient X
Here’s the Ai answer:
These are results for is ergothioneine beneficial for parkinson’s disease
Search instead for is ergothianonine beneficial for parkinson’s disease
AI Overview
Current research, primarily from preclinical studies as of May 2026, suggests that ergothioneine (ET) is highly beneficial for Parkinson’s disease (PD). It acts as a potent neuroprotective agent that can cross the blood-brain barrier. t
Key Benefits Identified in Research
Extensive studies across multiple models—including fruit flies, mice, and human cell cultures—have demonstrated several protective effects:
Preservation of Dopamine Neurons: ET treatment has been shown to significantly reduce the loss of dopaminergic neurons in the midbrain, which is the primary cause of PD symptoms.
Improvement in Motor Function: In animal models, ET supplementation notably improved locomotor performance, such as climbing ability in flies and rotarod latency in mice.
Inhibition of Alpha-Synuclein Aggregation: ET has been found to inhibit the formation of alpha-synuclein plaques, a hallmark of PD pathology, and can even help disrupt existing toxic protein fibers.
Mitochondrial Protection: ET helps maintain mitochondrial integrity and ATP production, preventing the cellular “energy failure” often seen in PD.
Neurophysiological Recovery: Recent studies indicate that ET can normalize abnormal brain wave oscillations associated with motor dysfunction.
How to Get Ergothioneine
Best Sources: Mushrooms (especially oyster, king oyster, and shiitake) are the richest known dietary sources.
Bioavailability: Unlike many antioxidants, ET has an exceptionally long half-life in the human body (about one month), allowing it to accumulate in tissues where it is needed most.
Here is my answer:
Ergothionine has benefits for lung interstitial disease It is available as a supplement , which is what we prescribe for lung disease It has a pre clinical benefits for Parkinson’s but no human data on outcomes is available. It is safe to use as a supplement or in Shitake mushrooms. So no known risk to you but a benefit. Remember long term risks only show up in well designed and followed long term rigorous studies. But since safe long term in human studies for lung patients, I think long term side effects are unlikely for patients with Parkinson’s. But not enough data for everyone to use routinely for longevity.
So if you decide to use, I would not use as a mushroom extract but would either consume the real Shitake’s weekly or just as we do for lung patients, use an ergothionine supplement from a reputable source Mike R, Clinical Staff, Wellness and Executive Health
Professor CCLCM@CWRU
· The Take home of the recent RAPAMYCIN science: Don’t take Metformin or Rapamycin for aging if you exercise, and do do all 4 forms of physical activity as they have much greater benefits—about 9 years for the typical 55-75 calendar year old woman and 8 + years for the typical 55-75 calendar year old man.
· Second Take home from recent RAPAMYCIN science and on supplement and small molecule data —insist on long term human outcome studies and a discussion with your doc before you accept the risks of a supplement or a small molecule.
· Take home as I reported in an earlier blog from Therapeutic Plasma Exchange, I have no specific condition I was treating but had 4 TPE treatments, and feel 40 years younger than my calendar age. Still do.
Thanks for reading,
Mike Roizen MD,FACP