Metformin + ivermectin + rapamycin (etc) << a ‘longevity’ drugs explainer

0:01Hi, I'm Sophie and this is Age Well with Dr Sophie Shotter, a space devoted to all things health, wellness and longevity. Because for me, ageing well is about looking and feeling like the best possible version of ourselves, inside as well as out. So together with my producer Fee, I'll be deep diving into the latest research, sifting fact from fiction. I'll also be talking to all kinds of trusted experts, tapping into their knowledge, along with bringing you conversations from a range of interesting women, and men finding out how they age well. So this is my show. Welcome along. And as always, thank you so much for listening.

0:46Dr Sophie Shotter:So Sophie, we have three off-licensed drugs to talk about, but should we start with metformin? Because I've been reading so much about this, particularly actually over the last two or three years when I've been going through my own health journey. So metformin, what is it? Metformin is a drug that was developed for type 2 diabetes, but it's increasingly thought to protect against cancer, heart disease, potentially even Alzheimer's and have positive effects on longevity. And the research into these anti-aging effects of metformin show positive signs that it can reduce various inflammatory skin disorders like psoriasis, acne and dermatitis.

1:26And This is because it activates an enzyme in our body called AMP activated protein kinase or AMPK for short. And this AMPK has been nicknamed the longevity enzyme. So as a little sidebar explainer, enzymes are a special kind of protein that live in our body. And they act as these tiny little helpers that speed up and actually create these chemical reactions, which are crucial to life and to a healthy functioning body. So this AMPK enzyme, for example, boosts our cells' ability to use energy. And when AMPK is activated, it also helps protect against a bodily process called telomere attrition. And again, another little explainer, regular listeners at the show might remember that telomeres are a bit like those protective plastic bits at the end of a shoelace.

2:17And these shoelace bits protect the end of our chromosomes. And chromosomes are these tiny bundles of DNA instructions inside our cells. So as we age, these telomeres get shorter and shorter. And when this happens, our cells and tissues age. This is what we mean by telomere attrition. It's this shortening of the protective caps at the ends of our chromosomes. And this shortening is a natural part of aging, but it can also lead to issues such as something called apoptosis, which is the killing off of important cells that your body needs. Although apoptosis is also a healthy process to happen, just not in excess.

2:53and when it happens in excess that's when conditions like Alzheimer's can happen or one of the reasons. But metformin blunts this process. It keeps our telomeres intact and functioning well and could potentially reduce age-related stress on our cells and I say potentially because as with many of these things the evidence is still emerging. Telomere retrition, this shortening I talked about, also plays a complex role in cancer development which perhaps we can get into. But to come full circle, metformin activates this AMPK enzyme. And when AMPK is turned on, it has a similar effect to when we have fewer calories.

3:31So it leads to lower insulin, for example. And again, do remember our very recent episode with Professor Ben Bickman on the need for lower insulin. Insulin is a hormone that regulates blood sugar in case you needed a prompt. But if AMPK is turned off, then we have higher levels of insulin. And this creates various health issues, as again Professor Ben explained. Interestingly, scientists have also shown that metformin encourages the growth of certain good gut bacteria, which leads to increased production of these short-chain fatty acids. And again, I'll name check another of my favourite episodes that we did, and that is with Dr.

4:07Will Boltsievitz, with his compelling data on the critical importance of these short-chain fatty acids. Hopefully listeners are really starting to see all these common threads by this point on the show. As a little side note, because I found this interesting, metformin is a drug with its origins in plant medicine as its active ingredients. And these are known as guanidine compounds, which were originally found in the French lilac plant. That is interesting. So what about metformin's impacts on brain health? This is a fascinating one. And there are several bits of research currently happening. To name just one study, in 2021, the Texas A &M University College of Medicine announced that metformin is showing potential in slowing down age-related cognitive impairment, so Alzheimer's and dementia.

4:52The results from their research did offer new evidence that if we take metformin from late middle age, so maybe 50-ish, it has promise for improving cognitive function in old age. But again, we do need more data.

5:06Dr Sophie Shotter:and I've heard that metformin is taken by a load of biohackers in this sort of let's call it the bro space yes but speaking with a calm head while a lot of people are getting very excited about it and yes it's had a lot of hype because of lots of famous biohackers taking it it's important to note that while we've had various very positive one-off studies a recent longitudinal study couldn't replicate these results so a lot of advocates are pushing to have funding for something called the targeting aging with metformin or TAME study so we can find out more. I also want to add that someone called Dr.

5:40Steve Austad, a prominent researcher in this space, has said most of the evidence is observational, pointing only to an association between metformin and various reduced risks. He says the evidence stops short of proving cause and effect, but to give the flip argument, that's not to say that with more research we won't have more rigorous results that prove various things. As ever, there's an issue in getting funding for these studies. And it's something that for me, I personally, at present, I'm 42. I don't take metformin. It's something I will look at at 50 because we also have to think that ultimately it is a medication and it does have potential side effects.

6:20And particularly these can be gut side effects and I'm not against having those gut side effects at a time point where I might benefit from the medication but at 42 it's unlikely I would benefit yet.

6:33Dr Sophie Shotter:Yeah see I am thinking about going on it based on the stuff that I've looked at but I can completely see why you wouldn't because you might be offsetting elsewhere and you mentioned you wouldn't mind touching on metformin and cancer which would be my area of interest. Can you just go back to that? yeah there are some people who believe that metformin essentially starves cancer because it cuts off the tumour's supply to glucose and insulin and reduces igf1 and i talked about igf1 in our weight loss jabs episode in terms of studies metformin has been found to reduce the incidence of cancer in rats and in other studies it's been found to suppress the growth of some tumours and enhance the activity of anti-cancer drugs it improves our immune systems because it lowers blood sugar and we know that various bacteria, fungi and viruses tend to feed on sugar.

7:23So by diminishing the fuel supply of bacteria, fungi and viruses, we diminish the levels of these and therefore boost our immune systems. And we of course know that a strong immune system is linked to fighting cancer. But as always, again, the data is limited and this show is purely me opening a conversation. I'm not giving medical advice or advocating anything specific here.

7:44Dr Sophie Shotter:So given that there's certainly promise in the individualized studies. I mean, I've mentioned that I would consider taking it. You've said why right now you wouldn't. Do you think it's, in terms of everyone else listening, do you think it's worth people taking it as a preventative? Yeah, I think on a case-by-case basis. So I definitely don't think someone in their 20s or 30s would see any benefit. It's a drug that works best when the body is actually aging. It can also impact certain things like your hormone levels which again isn't a great idea when you're young and some studies have again shown that metformin could inhibit muscle growth although conversely it also actually creates better quality muscle so I think more research is needed and I think fairly widely 50 is accepted as a pretty good threshold beyond which the benefits may outweigh the risks or the side effects but again it's got to be a very individual decision and given that these are prescription medications taken in conjunction with your doctor.

8:45Dr Sophie Shotter:Yeah yeah and I think for me because I went through a lot of chemo my immune system was suppressed that's why I'm looking at taking it potentially but as you say individualized. Let's say I did take it or I wanted to take it, how can I access it and who can access it? So in the UK metformin is a prescription only medication used to help reduce blood sugar levels. So if you go to your NHS GP, they won't give you a prescription for metformin to be used for any other reason. But there are several well-financed startups who are clearly jumping on the biohacking bandwagon and making it available still on prescription, but via online consultations.

9:24So as always, it's those with spare cash who are able to access it when what we really need is rigorous testing so that more, I guess, mainstream NHS doctors can prescribe it. I will also add that it's often surprisingly easy to get these prescriptions via an online pharmacy. And I say this with huge caveats because I am so concerned that many of these online pharmacies are subject to people not being genuinely honest about their health history and therefore maybe medications being made available when they shouldn't be.

9:58Dr Sophie Shotter:Very good point. I do know some people going back to your weight loss jabs episode who've been able to get weight loss jabs through basically lying on their form and it's not regulated as much it doesn't seem and is it safe to take? Yes like all prescription medications it does have its side effects which again I've mentioned some of the gut problems but people can look this up. It's been around for about 60 years though and it's generally safe for most people. When it comes to diabetes it's maybe in some cases fallen out of favour slightly with discovery of other medications. And I should add, this is specifically for type 2 diabetes.

10:36Okay. All right. Thank you for that. And should we talk about rapamycin? Let's explain rapamycin. So this was first discovered in the 1960s by scientists looking at soil samples in the South Pacific. And in one of the soil samples, the researchers found a bacterium that had these powerful antifungal properties and they named it rapamycin. Then in 2014, pharmacology researchers found it bolstered immune systems. A very small 2023 study found that nearly half of the participants said their health had improved since beginning a rapamycin regimen. And for example, around 35 % said their brain works better on the drug and 38 % said they felt younger.

11:15So again, we're talking about subjective things here, but interesting data. Dozens more reported lowered anxiety, improved arthritis pain, better quality of sleep and vision and reduced frequency of menopause related hot flashes. So it's gone on to become this wonder drug with thoughts it could potentially slow down aging and again even delay cancer development. But as we'll hopefully get into there has now been a slight backlash.

11:40Dr Sophie Shotter:Yeah and I do want to ask you about that but for now just to know more about the drug how does it work? I'll keep it brief but it's thought to block a particular protein that regulates cell growth and breakdown and from there it creates a process called autophagy, something that the fasting community will know all about. So think of autophagy as a cellular cleanup or quality control for cellular health and it's definitely still quite a buzzword out there. Okay so why the backlash? So the backlash sort of happened when the infamous biohacker Brian Johnson announced he was stopping taking it and suggested it could have made him age more.

12:16He announced this last year on Twitter or X, whatever you want to call it, and I'll quote a little bit from him directly, although I've paraphrased and shortened him slightly for brevity. But on September 28th, I decided to stop rapamycin, ending almost five years of experimentation with this molecule for its longevity potential. Despite the immense potential from preclinical trials, my team and I came to the conclusion that the benefits of lifelong dosing of rapamycin do not justify the hefty side effects, namely intermittent skin and soft tissue infections, lipid abnormalities, glucose elevations, and increased resting heart rate.

12:51Preclinical and clinical research has indicated that prolonged rapamycin use can disrupt lipid metabolism as well as induce insulin and glucose intolerance, as well as pancreatic beta cell toxicity. So despite anecdotal evidence of rapamycin slowing down tumour growth, I have concern for cancer risk in the longer run. He then went on to explain that Yale researchers found that the drug actually accelerated the biological speed in ageing across 16 different epigenetic markers instead of slowing it, which is the exact opposite of his ethos and the opposite of what all of us ultimately want. I think it's worth saying that probably the world's most famous biohacker, Andrew Huberman, has said, quote, I'm unwilling to experiment with it until human trials are done.

13:35This is absolutely not to say that we should be getting our advice from health influencers, no way, but I do think that because people like this spend inordinate amounts of time and effort in researching things, it's very interesting that one doesn't take it and the other has stopped taking it. But I'd also say that, and this is me being a bit of a scratched record, more research is needed and I certainly wouldn't dismiss the earlier positive findings out of hand. And I'll also add that it's interesting that Jeff Bezos has invested over two billion into a company called Altos Labs to try and explore more into various longevity drugs.

14:11And as always, we'll put some more links in the show notes. Very interesting.

14:15Dr Sophie Shotter:Okay, can we talk about ivermectin? Because I think this was a drug that went on people's radar after the actor Mel Gibson talked about it on Joe Rogan's infamous podcast. Yeah, and this is really controversial. The most replayed portion of this two-hour-long podcast is a segment where Mel claims that ivermectin healed stage four cancer patients. Clearly, I am not making these claims and nor would I. But let's look at the drug because it's also very controversially been touted as an anti-COVID drug. And so it'd be useful to give you all a bit of knowledge. Ivermectin is an antiparasitic drug, so something called fenbendazole.

14:52and if you search for ivermectin in cancer you'll find several hundred pre-clinical studies of ivermectin where in petri dishes it shows a potential effectiveness but these are mice studies and the issue is that the doses used in mice would likely be toxic in order to be effective in humans also just to be clear while there are personal positive stories out there there's no evidence that these drugs are effective at decreasing cancer growth certainly not in humans in fact a 2025 American Society of Clinical Oncology annual meeting looked at a study of ivermectin in combination with immunotherapy for patients with breast cancer and showed no significant benefit.

15:33It does have relatively mild side effects such as skin irritation and gastrointestinal issues which are to be fair quite common risks with many medications but again at high doses it can cause neurological and muscle problems. In severe cases it can even leave people in comas So until there's more compelling data, I would probably wait on this one.

15:53Dr Sophie Shotter:And beyond the off-license meds, there are also several supplements designed for longevity, aren't there? There's a compound called NMN, which claims to stem cells aging. And this converts into NAD and NAD Plus does all kinds of wonderful things. But as everyone who knows me knows, the real supplement to take here is Nuchido Time Plus, which is all about promoting NAD Plus levels. And it does this in many ways, not just through a precursor molecule, which is what NMN is. And if you listen to our episode with Dr. Nicola Conlon from last year, you'll know why and how this supplement works and why so many people are now on it.

16:30I think you're on it too now, Fi.

16:32Dr Sophie Shotter:Yeah, I am. Everyone, I just spread the word to everyone. My husband's on it too. Back to supplements, and there's also resveratrol. and resveratrol was previously touted again as this wondrous molecule. It's found in red wine and was previously put forward as an explanation for the French paradox. So why French people have lower rates of heart disease yet drink all that red wine. And there was a proposed mechanism where resveratrol maybe activated a gene that extends lifespan in yeast. However, any positive benefits of resveratrol has been completely debunked. so I'm not a believer in the resveratrol science.

17:14It was actually quite a big debacle on between the big biohackers on this one. One longevity supplement with better scientific evidence though is spermidine and this is one that I do take. It's a compound that we think activates autophagy in cells. This process I mentioned earlier of recycling old cells. There's certainly strong data in mice and observational studies in humans back up this finding.

17:37Dr Sophie Shotter:Okay and which spermidine brand do you take at the moment? So the one that I recommend is called Primidine. Okay, brilliant. Any final thoughts? I think with all of this, let's keep an open mind. Let's hope for more robust data, but let's not forget that if you don't have the proven pillars of health intact, there's probably not much point in taking any supplements. So focus first on what we know to be true. Good sleep, plenty of exercise, particularly strength training, and a fibre-rich diet that's rich in good bacteria these three things alone will do wonders for your health yeah great advice as ever what a useful episode Sophie thank you so much thank you so much and that ends this week's podcast if you want to find out more about me and my work or maybe book a consultation head to dr sophie shotter.com and you can find me on socials at dr sophie shotter and again thank you so much for listening Bye.