Also available as a registered drug to treat mild to moderate dementia in Alzheimer’s disease;
https://www.mayoclinic.org/drugs-supplements/galantamine-oral-route/description/drg-20067458
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This is fascinating. And I’m surprised at how many processes it seems to improve. Lysosomal function is a particularly difficult area to treat. I wonder if this will have an effects on aging beyond sarcopenia.
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I like the “lift heavy things” approach to avoiding sarcopenia but I wonder how much this drug would improve my lifts. =)
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I agree. I definitely prefer the traditional approach.
Any idea on Dosages needed to help with sarcopenia?
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Good question… I’ve done some searching and found info for the earlier mouse trial they did. Perhaps someone can find the human dosing data. In the animal study below, they use 125X more metformin than glantomine. So, if we start with a typical dosing of metformin (say the 1500mg SR metformin used in the TAME trial, that would suggest a daily dose of galantamine of 12mg/day.
Here is what I found in the article below (interestingly, they are injecting it in the mouse study):
Accordingly, the investigators examined whether RJx-01 could mitigate inflammation and denervation while preserving these two primary functions. First, sarcopenic mice were injected with RJx-01, containing 410 mg/kg metformin and 3.28 mg/kg galantamine. Then, sarcopenic mice underwent strength and conditioning testing.
Results:
The investigators found that RJx-01 significantly improved muscle strength, with treated mice exerting over 38% more muscle force than untreated controls. They also showed that treated mice ran significantly longer (3-fold increase) during the treadmill test than their untreated counterparts, suggesting that RJx-01 preserves muscle function and endurance. Moreover, untreated mice exhibited much higher inflammation and denervation than treated mice, indicating that RJx-01 improves muscle performance and fitness by suppressing inflammation and hindering denervation.
(Tezze et al., 2023 | JCI Insight) RJx-01 enhances physical performance and fitness. (Left) Mice treated with RJx-01 (purple) have fewer denervated fibers than untreated mice (black) and mice treated with metformin (blue) or galantamine (orange) alone. (Middle/Right) Treated mice run significantly longer and exert more muscular force than all other experimental groups.
Notably, the findings demonstrate that metformin and galantamine likely work in synergy, as treatment with either metformin or galantamine alone failed to promote similar protective effects in sarcopenic mice. Following testing in sarcopenic mice, Tezze and colleagues proceeded to conduct similar testing in naturally aged mice (22 months old ~ 64 human years) to further elucidate RJx-01’s synergistic effects. The results showed that RJx-01 enhanced grip strength by 32%, increased running endurance, and reduced denervation, corroborating the data seen in sarcopenic mice and confirming RJx-01’s synergistic effects.
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Still looking for information on the dosing used in the Phase 1b clinical trial RJx-01-101
No luck yet - but this pitch deck is interesting:
Rejuvenate-Biomed-Pitch-Deck-Longevity.Technology.pdf (3.0 MB)
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Searching on sarcopenia on the Clinical Trials website, but it doesn’t seem to be linked with the company in these files:
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The company presentation on this new drug combination:
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These summary graphs below seem pretty impressive (I think this is from the mouse studies).
If anyone already taking metformin decides to add galantamine to their regimen (@rberger , @DeStrider , etc ) please report back. I also wonder what the effect of this drug combo would be on regular non-sarcopenia people who are exercising.
In the animal studies they are reporting using Metformin Dose at 125X the Galantamine dose. So, if taking 1500mg SR metformin, that would be 12mg of galantamine to take a day with the metformin. Is there a slow release version of galantamine, as there is with metformin? (ah yes, there is, just found it):
Generic name: galantamine [ ga-LAN-ta-meen ]
Brand names: Reminyl, Razadyne, Razadyne ER
Dosage forms: oral capsule, extended release (16 mg; 24 mg; 8 mg), oral solution (4 mg/mL), oral tablet (12 mg; 4 mg; 8 mg)
Drug class: Cholinesterase inhibitors
Source: Galantamine Uses, Side Effects & Warnings
Do some pre-testing, and post testing over a month or two… I think I may try to get my 92 year old father to try this.
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Your father is 92 and still in good shape! What do you think his secrets are? What are his stacks?
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He’s not in great shape… and isn’t into longevity much, so other than longevity, not a model we want to follow. He tried rapamycin for a while, but didn’t continue, but I think I’ll try him again on it. And I want to try this drug combo to improve strength… he’s definitely got sarcopenia.
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I’m a ways off from sarcopenia, but my parents may be interested.
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What I can’t tell is whether or not the control group exercised. In other words, did the study compare “mice who took the drug against mice who didn’t take the drug and didn’t exercise” or “mice who took the drug against mice who didn’t take the drug but DID exercise”? If the drug doesn’t do significantly more for you than exercising, I’ll pass, although there are certainly people who can’t or won’t exercise who would benefit.
From what I can tell, in the mouse study they tracked the exercise of the control and treated mice, but did not force them to exercise (is it possible to force mice to exercise in these types of studies? I’m not sure…).
Here is what it says:
Physical performance
Opa1–/– mice.
The concentric training protocol consisted of the treadmill (Biological Instruments, LE 8710 Panlab Technology 2B) running to exhaustion, with no incline and a constant speed of 13 cm/s. Total running time was recorded for each mouse.
The in vivo muscle force is measured as previously described (41). Briefly, animals were deeply anesthetized, and the foot was mounted on a 305B muscle lever system (Aurora Scientific). The knee was blocked, and an electrical stimulation was applied to the sciatic nerve, inducing the isometric plantar flexion of the foot. The force-frequency curve was obtained by stimulating at increasing frequencies (starting with a single depolarization up to 150 Hz). Force was normalized to the weight of gastrocnemius and plantaris muscles to estimate specific force. Animals were then sacrificed by cervical dislocation according to the approved animal protocols, and muscles were dissected, weighed, and frozen. Experimental data were analyzed using a self-compiled program in LabView.
Aged mice.
At baseline and 18 weeks after treatment, mice performed concentric exercise on a treadmill (Biological Instruments, LE 8710 Panlab Technology 2B), as previously described (42). Total running time was recorded for each mouse.
Grip strength.
The grip strength was measured on forelimbs at baseline and 18 weeks after treatment using a commercially available Bioseb Grip Test device (Bioseb) as described previously (43).
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Good to know.
I guess I will rely on Indian generics for this rather than Amazon.
Though I have taken galantamine from Amazon on and off for years with no undesirable effects.
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Haven’t looked that much as this, but cost wise looks like 60 x 12 tablets are less than $60 also in the U.S.
See eg Walgreens
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Begs the question on how careful we might have to be with supplements in general.
Results
Ten brands of galantamine supplements and 11 brands of generic galantamine medications were included. Generic drugs were labeled as containing 4, 8, and 12 mg of galantamine per tablet or capsule. The actual content of galantamine in the generic drugs ranged from 97.5% to 104.2% of the labeled content (Table 1). No generic drugs were contaminated with microorganisms.
Dietary supplements were labeled as containing 4, 6, 8, and 12 mg of galantamine per serving. The actual quantity of galantamine in the dietary supplements ranged from less than 2% to 110% of the labeled quantity.
**Three supplements (30%) were contaminated with Bacillus cereus sensu stricto–encoding enterotoxin genes associated with diarrheal illness **(Table 2). The contaminated supplements contained 60%, 62%, and 75% of the labeled quantity of galantamine. All 11 generic drugs (100%) and 1 supplement (10%) contained a quantity of galantamine that was within 10% of the quantity declared on the label.
Discussion
Galantamine sold as generic drugs was accurately labeled and free of contamination, in contrast to galantamine sold as dietary supplements. The detected quantities of B cereus ss may suggest lack of appropriate quality control during manufacturing. However, adverse health effects would not be expected with these quantities of bacteria. For patients with Alzheimer disease, use of galantamine supplements instead of generic galantamine may adversely affect their care. Furthermore, the sale of inaccurately labeled galantamine supplements promoted for nonspecific memory and other cognitive problems is concerning given the lack of proven efficacy, potential drug-drug interactions, and adverse effects, including nausea, vomiting, dizziness, bradycardia, and syncope.6
The study has limitations. First, products were purchased at only 1 time point and the results may not be generalizable to galantamine supplements currently available given that manufacturers can introduce, reformulate, or withdraw supplement products without notifying the FDA. Second, whether the results are generalizable to other supplement ingredients, such as niacin, potassium, and iron, which are also available as either dietary supplements or generic drugs, is unknown.
The laws regulating dietary supplements should be reformed such that the FDA has enforcement mechanisms to ensure that dietary supplement labels accurately reflect their contents. Meanwhile, clinicians should query patients with memory concerns about the use of dietary supplements and advise patients not to use galantamine supplements.
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Exactly! @AnUser has pointed this out many times… drugs are safer than supplements simply because you know (generally) what you are getting. They have better manufacturing processes, and are regulated closely (especially if manufactured in the US).
The chance you aren’t getting at all what you expect in supplements is much higher; especially as you go away from the top brands.
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