Combine them all! (Longevity Drugs and Supplements)

Hi everyone .

“The ITP started in 2002, with the DCC added in 2019. In that time, the ITP has identified nine agents that significantly increase median lifespan — acarbose (Harrison 2014, Strong 2016, Harrison 2019), aspirin (Strong 2008), canagliflozin (Miller 2020), captopril, glycine (Miller 2019), nordihydroguaiaretic acid (NDGA) (Strong 2008, Strong 2016), Protandim® (Strong 2016), rapamycin (Harrison 2009, Miller 2011, Wilkinson 2012), and 17α-estradiol (Harrison 2014, Strong 2016, Harrison 2021).”

How could they resist the temptation to not combine them all ?
Why some scientists have not do this on C.elegans, D.Melanogasters ?
That is so strange, No ?!

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Percent Lifespan increase seen in NIA ITP study results, Male and Females %

Yes - many of us are sort of trending in this direction. If you are doing this, I think the best approach is to do regular blood testing and tracking to see how things are working for you.

There are also a few issues I’ll outline here:

  1. NDGA - is toxic in humans and has been pulled from the supplement market. See: Nordihydroguaiaretic acid - Wikipedia

  2. Glycine - its fine, but you have to take a lot of it, and the effect is barely above statistical significance in terms of its longevity benefit (from the ITP studies). Listen to this segment of the interview with Richard Miller: #148 - Richard Miller, M.D., Ph.D.: The gold standard for testing longevity drugs: the ITP - YouTube
    And See: MPD: ITP survival analysis:   glycine

  3. 17-Alpha Estradiol is not FDA approved yet and is only available from Lab supply houses (and is hard to get if you are not working in a corporate or university lab or research facility).

Lastly - there is the issue of Polypharmacy. We really don’t know how these drugs and supplements interact with each other. Well-known researcher Brian Kennedy has noted that what they see is that sometimes the effect is additive, sometimes they counter each other, and sometimes the do better or worse at a multiplicative level. See this discussion here: The Challenge of Predicting Outcomes when Mixing Longevity Therapeutics - How are you thinking about this?

This issue is also covered at some level here:

This is a paper that covers the risks associated with poly pharmacy (taking numerous different drugs)… something that everyone here should be aware of. There are risks associated with increasing your “stack” of longevity drugs and supplements (note - this is focused on disease/illness oriented medications so is likely not to be as big an issue with longevity drugs for people who are not diseased/ill - but still good to be aware of, and test and validate that you are seening positive results from the longevity drugs and to catch any problems early):

An incrementally higher number of daily prescribed medications was found to be associated with increasingly higher risk for hospitalization and mortality. These associations were consistent across subgroups of age, sex, residential area, and comorbidities. Furthermore, polypharmacy was associated with greater risk of hospitalization and death: adjusted HRs (95% CIs) were 1.18 (1.18–1.19) and 1.25 (1.24–1.25) in the overall and 1.16 (1.16–1.17) and 1.25 (1.24–1.25) in the matched cohorts, respectively. Hence, polypharmacy was associated with a higher risk of hospitalization and all-cause death among elderly individuals.

Polypharmacy, hospitalization, and mortality risk: a nationwide cohort study

https://www.nature.com/articles/s41598-020-75888-8

There is a discussion about this from a group in the UK that is working (generally) on this issue:

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What’s also interesting is the many compounds not on that list that people are taking regularly.

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Yesterday Matt Kaeberlein mentioned in his presentation / webinar about how his new company is evaluating combinations of drugs and the results they are seeing so far. Below is an image from his presentation that highlights the issue.

Some drugs show synergistic effects with significant increases in lifespan (of the worms in this study) but some show no effect, and sometimes there is a toxic combination effect where the outcome is much worse than the two drugs individually (those are the green bars that extend down the furthest in this graph below).

It just reinforces that we still don’t know how all these drug / drug interactions will work out inside our bodies. I’m hoping that Matt and Ora Biomedical will share with the public all the data on combinations of drugs and supplements that show either no beneficial combination effects, or toxic effects… The toxic effect combinations below are the green bars that go downwards below the Zero effect line. It looks like about one out of every 10 or 15 combinations resulted in some toxicity and negative impact on lifespan. (the good news that in this group about one in 4 seem to have a positive boost over and above the individual compound effects).


On the last slide, Matt noted that there are in some compounds, synergistic effects both postive and negative. In this slide Metformin is the the “control” - with consistent positive results when used alone (this is in worms) of between 5% and 15%.

https://orabiomedical.com/

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Perhaps a good way to see if there are combination problems will be to check if theoretical age through biomarkers (aging.ai) decrease. A scientist do that with food on youtube : Blood Test #5 in 2022: Supplements, Diet - YouTube

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This is becoming really disconcerting. Toxidendron (nice name for the subject matter) makes an interesting suggestion. But would that be sufficient? What kind of biomarkers should we track to keep an eye on this? Perhaps we should try to make a comprehensive list.
I remember seeing a study wherein detrimental effects of combinations of supplements were mostly seen in kidney/liver function - but I doubt keeping an eye on kidney/liver function would be sufficient in this scenario wherein we combine different drugs.

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Is there a list of the combinations to avoid? The ones that were synergistic?

Not yet. I’m going to reach out to Matt and the team at Ora Biomedical and see if we might be able to get a list of the bad combinations…