What interventions or molecules act synergestically with exercise AND which get in the way of its benefits?

#1

I ask this question and try to formulate a preliminary compilation with the main goal being synergy in terms of longevity AND short-term performance. Of course the effects of interventions can be more nuanced and it could depend on what type of exercise one is doing, whether it’s during, post-workout, or pre-workout but I don’t really know if this topic has been studied with all interventions at that depth.

Off the top of my head:

Synergistic:
Sauna (some links here: FoundMyFitness Topic - Sauna)
Curcumin (?) (https://doi.org/10.1080/10408398.2020.1749025)
Creatine - https://doi.org/10.1519/jpt.0000000000000222
AAKG or CaAKG (??) – AAKG is widely used by bodybuilders
Urolithin A (??) – (see: Urolithin A - Virtual Clinical Trial by Timeline Nutrition)
Acarbose (old 2006 paper: Combined treatment with exercise training and acarbose improves metabolic control and cardiovascular risk factor profile in subjects with mild type 2 diabetes - PubMed)
Astaxanthin (?) (Astaxanthin in Exercise Metabolism, Performance and Recovery: A Review - PMC)

Anti-synergistic:
Metformin
SGLT-2 inhibitors (?) (see thread: For those who take SGLT2 inhibitors & Exercise, found this interesting)
Cold-exposure (post-workout) - Post-exercise cold water immersion attenuates acute anabolic signalling and long-term adaptations in muscle to strength training - PMC
NSAID

Double-edged:
GLP1-RA: seems to act synergestically w.r.t weight loss (139-OR: Superior Effect of 1-Year Treatment with GLP-1 Receptor Agonist and Exercise on Weight Loss Maintenance and Body Composition after a Very Low-Calorie Diet: The S-LITE Randomized Trial | Diabetes | American Diabetes Association), and glycemic control/diabetes (https://doi.org/10.1111/dom.12797)
but, apparently blunts exercise benefits on left-ventricular diastolic function and cardiovascular adaptations (Effect of exercise combined with glucagon-like peptide-1 receptor agonist treatment on cardiac function: A randomized double-blind placebo-controlled clinical trial - PubMed, https://doi.org/10.14814/phy2.13754) even though they are in general good for heart health (https://dx.doi.org/10.1155%2F2018%2F4020492).

Unknowns with strong-implications:
Rapamycin – Synergy with exercise hasn’t yet been studied even though Rapamycin and exercise are seperately known to prevent sarcopenia A New Rapamycin Human Trial for Longevity | Lifespan.io

What about polyphenols, sulforaphane, lithium, 17-alpha-estradiol?

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#2

In terms of benefit to performance there is some evidence for nitrates, beta alanine, bicarbonate, ketones, and of course caffeine.

There are also WADA banned products like EPO, HGH, cortisone, amphetamines, insulin, testosterone (and derivatives) etc though none of those have proven beneficial for longevity.

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#3

Yes, for caffeine and ketones. I think coffee and ketone supplements would also count as pro-longevity interventions.

Now all I need is a camelbak backpack for my MCT oil bulletproof coffee :sweat_smile:

I’ll need to look up the rest of compounds, thanks!

#4

Other non pharma methods of enhancing performance include altitude; BFR and heat (eg sauna immediately following HIT). Some will argue for fasted training but I am not convinced by the literature.

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#5

You could probably add Glycine, NAC and maybe Astragulus as synergistic. They will give you a hell of a lot of energy anyway.

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#6

I note PA’s newsletter this week is on nitrates. Some good info here:

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#7

Creatine use elevates DHT in the scalp, which will cause accelerated hair loss in individuals prone to it. It is something to think about for those who want to be ripped but keep the hair on their heads.