I saw Nordihydroguaiaretic acid (NDGA) on Bryan Johnson’s supplement regimen, however it doesn’t seem to be sold as a supplement from the regular outlets - such as amazon.com etc.
Does anyone know what the regulatory status of it is?
I see on the FDA site that it’s prohibited for use in human food. However, I can’t see if this extends to supplements?
I looked into this when the ITP study on it came out.
NDGA was one of the first compounds tested by the ITP, and in their initial study, NDGA was shown to significantly increase the median survival (12%) of male mice at a dosage of 2500 mg/kg diet when initiated at 9 months of age;however, this dose did not increase the life span of female mice (Strong et al., 2008).
In 2014, the ITP reevaluated the effect of NDGA on life span with a higher dose (5000 mg/kg diet). The higher dose of NDGA initiated at 6 months of age increased median life span of male mice by 9%, and again, NDGA had no effect on the life span of female mice (Harrison et al., 2014). Although the different doses of NDGA increased the median life span of male mice, it did not significantly increase the maximal life span (Strong et al., 2016). NDGA also significantly increased neuromuscular performance in 22-month-old male mice, suggesting that NDGA might improve physiological functions that decline with age (Strong et al., 2016).
Its available from some European suppliers, but it seems its a pretty toxic substance to humans, and why its no longer widely available… so I decided it wasn’t worth the risk. Perhaps it is worth the risk if you have enough testing to track and identify early any toxicities…
The creosote plant has been used in herbal medicine, but its use is controversial. It was widely used during the 1950s as a food preservative and to preserve natural fibers, but was later banned after reports of toxicity during the early 1960s. Recently, it has been used as a nutritional supplement; however, renal toxicity and hepatotoxicity are reported for chronic use of creosote bush and NDGA.
Yes, it is available:
Known as chaparral
FWIW
Three papers
https://www.nature.com/articles/s41514-019-0037-7
Nordihydroguaiaretic-acid
https://www.sciencedirect.com/topics/medicine-and-dentistry/nordihydroguaiaretic-acid
The toxicity risks make this a risky play. You may get some positive effects, or you may get negative ones. I’ll take one-sided wagers where negatives are nonexistent or minor (mouth ulcer level). No NDGA for me.
Interesting… but its pretty hard to know how much NDGA is actually in a 500mg capsule of this stuff…
I notice Bryan Johnson’s protocol is what sounds like a low dose, and pure NDGA:
I wonder what the mouse ITP studies dosing level translates to human dosing?
Some related resources:
Cases of acute toxic hepatitis in two patients – one in California and one in Texas – have been attributed to ingestion of an herbal nutritional supplement product derived from the leaves of the creosote bush known commonly as chaparral. This report summarizes the investigations of these cases.
https://www.cdc.gov/mmwr/preview/mmwrhtml/00017883.htm
heron2001.pdf (198.1 KB)
When I was looking into NDGA - I got a quote from this research chemical lab in Denmark. His price was 14,000 euros per Kilo (so about $14/gram, at kilo purchase quantity). https://www.ross.dk
The toxicity issue scared me away… but if Bryan Johnson is taking it, it suggests that Oliver Zolman and the team have identified a dosing that is probably low risk (i.e. the 50mg/day that Bryan is taking). It would be good to really do a deep dive into the research to see what the toxicity levels might be, and testing that can be done to track any possible early indicators of toxicity…
If you decide to do this research, or if we can get some feedback from Oliver @Oliver_Zolman_MD on how he/they justify the 50mg/day dosing level, perhaps people here would be interested in a group purchase?
People could buy a year’s dosing at a time, 365 X 50mg = 18,250mg, so 18 grams a year, at $14/gram = $250/year approximately. Seems like people might be interested in it if we can nail down the toxicity risk better… and perhaps get some feedback from Oliver, Bryan and the Blueprint team.
NDGA Certificate 2523-10-01-3 2018.pdf (300.1 KB)
If it only increases male lifespan, but not female, these is good chance it works on the same pathway as the much safer (and probably cheaper/easier obtainable) 17-alpha-estradiol
Perhaps… Responses to Many Anti-Aging Interventions Are Sexually Dimorphic (Different for Men / Women)
Seems like a good wormbot/million molecule type of test to start with, but then perhaps an ITP dual compound study…
Safer to take aspirin; similar results.
https://onlinelibrary.wiley.com/doi/10.1111/j.1474-9726.2008.00414.x
For NDGA, 8.6% of control mice (i.e. 30 of 350) were alive at this time point, compared to 13.1% of treated mice (22 of 168); this difference, at p = 0.12, does not meet our significance criterion. A parallel calculation for aspirin treatment found 8.9% of control males and 13.1% of aspirin-treated males alive at the 90% mortality point, again not significant at p = 0.16.Median survival for control mice was 786 days, compared to 881 days (12% increase) for NDGA and 849 days (8% increase) for aspirin.
The effect of aspirin on lifespan in mice in the present study is consistent with reports of numerous epidemiological studies showing that aspirin use reduces the risk of mortality from a variety of diseases in humans, including colon cancer, prostate cancer, and cardiovascular disease (e.g. Johnson et al., 2002; Jacobs et al., 2005; Lim et al., 2007; Chan et al., 2008). Recently, aspirin was reported to activate the NF-kappaB signaling pathway and induce apoptosis in two in vivo models of human colorectal cancer (Stark et al., 2007). Aspirin also normalized blood pressure in a rat model of hypertension (Tuttle et al., 1988). Furthermore, it reportedly improved learning of a spatial memory task in old rats (Smith et al., 2002). Interestingly aspirin use was reported to be associated with increased survival in extreme old age in humans. Aspirin use was associated with increased survival in a 5-year follow-up study of subjects in the Finnish Centenarian Study (Agüero-Torres et al., 2001). The authors concluded that the increased survival was probably not attributable simply to the anti-atherogenic effects of aspirin, because the aspirin group had significantly more cardiovascular disease than the non-aspirin users.
Seems the Ray Peat crowd are on to something.
FWIW
Am adding/starting{11/24/2023] chaparral, starting at 500mg capsules per day.