Glucosamine instead of Metformin and Rapamycin?

I happened to read a very old blog by Vince Giuliano regarding Glucosamine

In it he gives sufficient evidence that  Glucosamine extends life in nematodes, mice, and humans, by activating AMPK, and modulating mTor.

There is one caveat: The life extension benefits are lost if antioxidants are also supplemented at the same time.

There are two questions that come to mind:

a) If this supplement is readily available, cheap, and gives the same benefits as Rapamycin and Metformin combined, without the side-effects, and since this information is available for a long time, why all the fuss about Metformin and Rapamycin? Why bother? It seems to me like a no-brainer. Am I missing something?

b) I currently supplement with antioxidants NAC and Glutathione. How can I continue to take them and still reap the benefits of Glucosamine? I would assume some intermittent schedule. But no sure about the intervas.

Any ideas will be greatly appreciated.

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  • I don’t think your #1 holds true. Efficacy of rapamycin for life extension is much higher and per dr Kaeberlein in reasonable doses rapamycin is no more dangerous than aspirin. Also per the research paper you have attached the average lifespan extension in mice is just 6%; basically, no better than Metformin or berberine. This is quite lower than rapamycin or calorie restriction in mice, which can achieve ~25% independently. Now human lifespan is much less pliable than mice, which means that 6% in mice may not extended human lifespan at all. Hence serious longevity researchers like Walter Longo don’t bother with such dubious therapies like Metformin and that’s why Glucosamine is not so exciting either. Now acarbose is much more interesting than Metformin and berberine or glucosamine as it extends an average lifespan in mice by 22%. Hence my suggestion would be to seriously consider acarbose , rapamycin and calorie restriction. These are heavy hitters and are very widely studied. Also I think your glutathione is actually a good and safe supplement although it doesn’t extend the lifespan.

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    • Joe smith 

      Thank you for info.

      In fact, I currently take Berberine, and every now and then Rapamycin. But I am trying to figure out if I should change.  I am a bit scared of Rapamycin. Dr. Alan Green has mentioned that bacterial infections can be quite dangerous while on Rapamycin. In trying to extend healthspan/lifespan using Rapamycin, we risk dying very soon from bacterial infections.

      In the link that I provided, there is a reference to an epidemiological study on about 77000 persons (age 50-76) which concludes that " the probability of death for those consuming glucosamine per unit time is 83% of that of controls". For the same group, the risk for Colorectal Cancer was reduced by 45%.  It is true that epidemiological studies do not provide "proof" of causality. They do provide a strong indication. 

      In fact, I am more concerned that the benefits of glucosamine consumption disappear when at the same time antioxidants are consumed (I.e. NAC). Since I am also taking NAC, I would probably have to take both intermittently. I also wonder whether taking NAC while also taking Rapamycin, also negates the benefits of Rapamycin.

    • Zisos Katsiapis 

      Here is a link to research that show decreased all-cause mortality among those who took Glucosamine. " A population-based prospective cohort study included 495 077 women and men (mean (SD) age, 56.6 (8.1) years) from the UK Biobank study."


      "Conclusions Regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases."


      "Regular glucosamine use is associated with a lower risk for total mortality (15%), CVD mortality (18%), cancer mortality (6%), respiratory mortality (27%) and digestive mortality (26%)."



      My first thought was that users of glucosamine usually have painful joints and that they also take NSAID - aspirin etc. And that could explain some of the disease prevention. But they say "the associations between glucosamine use and all-cause and cause-specific mortality were not significantly modified by sex, age, ethnicity, obesity, current alcohol status, physical activity, diabetes, statin and aspirin use"


      Yes Glucosamine is interesting.But does not have a long history of use in clinical settings like metformin. But according to the study I refer to it is not a shot in the dark.  


      My main question is: Am I already using substances that give me the benefits the Glucosmine will provide? In that case will there be a risk that glucosamine only will  add the possibility of negative interactions.  

  • The issue with Berberine is that it is just not as widely studied as Metformin and not fda controlled. It is probably ok and little bit beneficial for ldl-c and high blood sugar. If you take it do it just once a day 500 mg and cycle it on and off - 6 weeks on and 2 weeks off. With respect of nac and rapamycin I am not aware of any study investigating interactions between the two. That said nac being amino acid and rapamycin acting on mTOR, I suspect that they would counteract each other. I don’t see how staggering the treatments between the two be of any value. Now I think it makes for interesting lab experiment on mice but I wouldn’t try it on yourself. Idea is to minimize number of treatments and interactions as there are just too many unknowns. 

    With respect of rapamycin, I’m curious at what dosages the skin infections are observed? Can you find out from the doc who prescribed it to you?

    Anyway the idea behind combing cr and rapamycin and acarbose is that you can achieve combined effect without having to resort to extreme intervention. That is e.g. instead of doing 40% cr restriction you do 15% and instead of taking 10 mg rapamycin you take 3 mg and you still a have the same benefit without incurring a high risk like skin infections (and yes you should be concerned about it as you don’t live in sterile lab)  which comes with more extreme interventions. 

    • Joe smith 

      Thank you for info.

      I take Rapamycin and others w/o prescription. So, no doctor to ask. But Allan Green usually prescribes 5mg / week or less. So I assume that at this dosage he observed the problems with bacterial infections. This is the reason why I am a bit scared of Rapamycin, and I would much rather use something benign like Glucosamine, even if the effect is smaller than Rapamycin.

      I agree with you that it might not be wise to take many supplements. Unfortunately, I end up doing the opposite. I find information about a supplement that presumable is useful. I add it to the stack. But do not remove something. 

      You seem to know much more than me, so maybe you can answer a question for me: For antioxidants, is it better to take them all the time, or intermittently? If intermittently, what would be the most appropriate on-off interval?


      • Joe smith
      • Joe_smith
      • 6 mths ago
      • Reported - view

      Zisos Katsiapis with rapamycin you need to have comprehensive lab work done before you start and then ongoing every six months. This needs to be reviewed by doc. To me the biggest concern with rapamycin is that it suppresses mtor effectively neutralizing the benefits of strength training. You need your muscles as you get older. Hence knowing a bit more about when and how much to take are big questions here. So rapamycin today as I see it is only useful as adjunct treatment to calorie restriction.

      With respect to our question on antioxidants dosing. First of all I don’t recommend taking any antioxidant supplements (excepting some vitamins if you have low blood levels) as they shorten your lifespan perhaps excepting besides some vitamins and glutathione, which seem to be safe. The antioxidant precursors like sulforaphane make more sense to supplement and are more promising. These I would take either in low doses everyday or intermittently 6 weeks on and 2 weeks off. Now if we are talking about antioxidant vitamins then I would recommend obtaining rda doses everyday.  For example you need vitamin c, which happens to be antioxidant, before your weight training to synthesize collagen afterwards. As you know other fat solvable vitamins like vitamin d don’t have to be taken everyday. 

      • Don
      • Don
      • 5 mths ago
      • Reported - view

      Joe smith 

      I'm curious about your statement that antioxidant supplements shorten your lifespan. I hadn't heard that. Would you expand on it, with some sources?

  • I write this post because I have read that AMPK activation could possibly be detrimental in neurological some diseases. (not knowing if it is correlation or a possible causation).


     I am not bashing AMPK activation. Its has many benefits but it might be the right time for me to dig in deeper and be more specific in my AMPK activation. I consider the possibility that I AMPK can be overactivated.


    One paper stated that “results demonstrate that AMPK signaling plays a critical role in the age-related decline of hippocampal neurogenesis.”.


    “AMPK is a master energy sensor which was reported to be overactivated in the brain of patients affected by these neurodegenerative disorders. While the exact role played by AMPK in these diseases remains to be clearly established, several studies reported the implication of AMPK in various signaling pathways that are involved in these diseases’ progression.”



    “Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are neurodegenerative disorders that are characterized by a progressive degeneration of nerve cells eventually leading to dementia. While these diseases affect different neuronal populations and present distinct clinical features, they share in common several features and signaling pathways. In particular, energy metabolism defects, oxidative stress, and excitotoxicity are commonly described and might be correlated with AMP-activated protein kinase (AMPK) deregulation. AMPK is a master energy sensor which was reported to be overactivated in the brain of patients affected by these neurodegenerative disorders.”



    this leads me to the question: which are the best ways to activate AMPK in muscles, fat and liver etc without over activating it in hypothalamus. And maybe even in some situations the aim might be to inhibit hypothalamic AMPK in the brain .


    Some indications point towards Lipoic acid and quercetin as supplements that inhibit hypothalamic AMPK while activate AMPK in muscles, liver and fat cells.

    Green tea and Curcumin promote neurogenesis in hypothalamus. While activating AMPK outside the brain.


    I have not seen any research about metformin and the effect it might have on disorders in the brain. I find exercise and diet to be the safest ways to activate AMPK. But I look for the smartest combinations of drugs or supplements to activate AMPK in some cells in my body and possibly to inhibit it in the brain, or at least avoid over activating it in my brain.  I post these thoughts here and hope that some might reflect on these ideas and lead me on to a better understanding of AMPK activation.

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