Why spermidine is the longevity supplement going mainstream in 2026 - with Primeadine’s Leslie Kenny

0:00Leslie Kenny:This show is sponsored by Primadine, a clean, natural and science-based spermidine supplement that's been a long-time staple in my own longevity stack. Because studies suggest that through autophagy, spermidine increases healthspan and upregulates a range of health markers, from memory and cognitive function to heart health, hormone balance, fertility and even hair growth. Plus, you can be assured that all ingredients undergo rigorous third-party testing. Buy Primadine now at OxfordHealthSpam.com and use the discount code DrSophie, that's D-R-Sophie for 20 % off. This show is sponsored by Microbes, an award-winning liquid probiotic that's now a staple for me, because Microbes, with a Z on the end, is different.

0:47Leslie Kenny:For one thing, they source directly from the soil on their Wiltshire farm, meaning more diversity, with at least 15 strains of good bacteria in every single shot. it's brewed so it can survive in the stomach and a remarkable 92 percent of customers say it makes a difference plus they offer micro-friendly cleaning gardening and even microbes for dogs buy now at microbes.co.uk and use the discount code sophie20 for 20 off hi 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 aging 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 new 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.

2:00Leslie Kenny:Leslie your story is as fascinating as it is inspiring in your 20s and 30s you enjoyed a highly successful career working for a Swiss bank working for the Disney brand you even launched your own venture-backed online matchmaking startup up. But then came serious burnout and at the age of 39 you had various diagnoses including lupus, rheumatoid arthritis, Hashimoto's and infertility. In fact doctors told you that you had just five years left to live. Unimaginable. Fertility treatments had failed and you were advised to go on drugs to suppress your immune system and basically accept a limited future.

2:38Leslie Kenny:Instead you completely transformed your life, reversed your autoimmune symptoms, conceived naturally at 42 and gave birth at 43. What happened? How did you get better?

2:50Dr Sophie Shotter:Yeah, that's quite a laundry list of experiences and diagnoses. Well, what happened is, as you said, 21 years ago at age 39, I was in the middle of trying to have a baby and then got these terrible diagnoses that not just changed the course of that IVF round. That was my fifth round of IVF and I was using donor eggs and that did fail. But I was told that I had in particular lupus and that there was no treatment or cure for lupus that I could expect it to get worse. That the implication was that if I, even if I was successful with the IVF round, I would be leaving a baby without a mother. And it was pretty bleak.

3:40Dr Sophie Shotter:And having been raised to see my doctors as all-knowing and all-seeing, I had always thought, well, if there's something wrong with me, I present myself to my doctor the way that I would bring my car to the garage. And the doctor is the body mechanic, just like a car mechanic. Unfortunately, it doesn't work like that. And health is not a transaction. And instead, it's more of a collaboration. And we patients have a role to play too in making ourselves as healthy as possible to make the job for the doctor as easy as possible. We also have a role to play as advocates. And having spent quite a lot of time looking at fertility bulletin boards, I had done three IUIs, and in the end, the five IVFs, all unsuccessful, including the donor egg cycle.

4:41Dr Sophie Shotter:I knew what a wonderful community there was online. So when I got my lupus and RA diagnoses, I went to those communities. And it's in these places that you will find treatments that doctors sometimes haven't yet read about. These will be studies that are smaller in size and therefore not statistically significant for doctors to pay attention to or to get press in the larger medical journals like the BMJ or JAMA, but they nevertheless might hold clues that are useful to patients. So when I went to the RA boards, I heard from other patients that their immune-suppressing drugs, these are injectable drugs, and they go under the brand names of Humira, Anbril, many others.

5:34Dr Sophie Shotter:I was given them, and other patients told me that they just would fail inexplicably after about 18 months, and then you'd start again looking for another drug that would work to keep your body from trying to attack your joints. And it would go on and on like this. It was a kind of hamster wheel of one drug to the next drug, which didn't sound very good to me. And I already had an issue with the idea of suppressing my immune system, which was a strategy with RA, because I knew that I needed my immune system to help me fight colds and flus, but also to help fight cancer. And so I didn't quite understand the theory or the strategy of bringing it down so dramatically rather than bringing it back to balance.

6:28Dr Sophie Shotter:At the same time, I went to the lupus bulletin boards, and there patients told me that four years earlier in 2000, there had been a study done in Germany with 13 lupus patients. And contrary to what my doctor was telling me, all 13 of these patients responded to the treatment, and they all improved. This was a wonderful discovery, a life-changing discovery for me. I took that evidence. I went back to my medical practitioner and said, look at this. Give this to me. And she said, not statistically significant. I can't give this to you. It's not a, I guess, an on-label treatment. So it hadn't been accepted by the U.S.

7:13Dr Sophie Shotter:Food and Drug Administration as a treatment, a legitimate treatment for lupus. So back to the patient bulletin boards where I got the name of a doctor in San Francisco who I did approach. And he was willing to prescribe me two rounds of intravenous immunoglobulin, or IVIG, as it's called. Each of them cost$12 ,000 to my insurance company. They took four hours. I didn't feel or notice really anything during the transfusions. What I knew was that these treatments, which are antibodies from anywhere from 3 ,000 to 10 ,000 patients, have an immune modulating effect. That means that they seem to reset the immune system, the dysfunctional immune system.

8:04Dr Sophie Shotter:So it's not just that they're providing antibodies to people who can't make antibodies, they have this immune modulatory effect. And I thought, gee, if I'm resetting my system like I'd reset my computer system, I'd better make sure I don't introduce anything back into my now clean environment that might trigger my immune system again. So I hunted for those triggers and I looked at everything from diet. I used Dr. Barry Sears' anti-aging zone book as a guide to avoid sugar, only stick to low glycemic index fruits, avoid lectins, nightshade plants. So these are things like potatoes. Tomatoes always cause me to flare dramatically.

8:50Dr Sophie Shotter:Avoid gluten. Gluten is the most famous lectin of them all. I tried to manage my stress. I quit my job. I optimized my sleep. I was really prioritizing movement, and I was hiking every day at that time. I lived in Boulder, Colorado then, and I was in a neighborhood that was literally just a few blocks away from the Rocky Mountains. So I would hike in nature, so getting plenty of sunlight and fresh air. And I also did trauma therapy because I had a very traumatic experience losing my father at age 39, the same age I was when I was diagnosed. So losing him to suicide. So I had not had the chance to say goodbye.

9:35I wrote letters to him to essentially say all the things I wanted to say before his death but couldn't. And when I went back to have a routine checkup with my doctor, who had then run my labs again,

9:51Dr Sophie Shotter:just to keep an eye on them, see how I was reacting to the immune-suppressing drug she put me on, she opened my file and just said, well, look at that. You don't have lupus or RA anymore. And I, what? Excuse me? She said, all your levels have returned to normal.

10:13Leslie Kenny:Thank you so much for going into what's such a fascinating story of recovery. Now, before we talk about spermidine, which is the mainstay of this conversation, and to listeners, we will explain exactly what spermidine is. Why did you go on to launch Oxford Healthspan and Primidine, this incredible spermidine supplement that I know Sophie now recommends to pretty much everyone? Like what's the story behind launching Oxford Healthspan?

10:41Dr Sophie Shotter:Well, my sort of health dramas happened quite a long time ago, 21 years ago. You have to fast forward to 12 years later. And by this time, I had adopted a little girl from China because I could not live with the indecision of IVF. And my Hashimoto's had been diagnosed. The damage from Hashimoto's to my thyroid had been diagnosed. I'd had a little girl biologically at age 43, which was great. Anybody listening who's suffering with infertility, it can definitely still happen when you're older. And I was taking my girls to school and chatting with other parents at the playground, also at school pickup.

11:23Dr Sophie Shotter:Here in Oxford, there are so many scientists. And when I would ask somebody what they did, and they told me about their research, I'd get really excited and ask where I could find the product of their research. And they'd always say, no, we just, you know, I just publish. I don't, I'm research only. I don't do anything commercial. And that led me to actively looking for companies that needed help, spin outs from the University of Oxford, but only in regenerative medicine, because I knew that there was a lot of support for pharmaceutical products that were about management of chronic disease, but there weren't so many around cure.

12:05Dr Sophie Shotter:And those were the ones I wanted to help. And I got involved with a local fund, Oxford Science Enterprises, basically fundraising for some of their spin-outs. And it was through them that I was introduced to scientists at the Kennedy Institute of Rheumatology at the University of Oxford. And they'd done experiments in elderly mice and had proven that they could rejuvenate their immune cells. And we all know that older people, if they get pneumonia or if they got COVID, we all thought, oh, that doesn't sound good. That is going to be hard to recover from because it turns out that around age 63, which is what Professor Katja Simon says, it's around age 63, but certainly by age 65, generally our immune cells begin to get a kind of amnesia.

13:02Dr Sophie Shotter:They all have recipe books for making antibodies to mount an attack against all the pathogens in the body, but they seem to forget where to find these recipes. And what Katcha's initial studies at Oxford showed were that if you gave them this awkwardly named compound called spermidine, together with a flu vaccine, they would actually have a response that outperformed the response of young mice who were also given spermidine and the flu vaccine. That is a counterintuitive result. We don't expect older mice to do better than younger mice. And the hypothesis is that these older mice have been around the block more times than the younger mice, therefore they have seen more pathogens and have more and better recipes in their antibody recipe book than the young mice.

13:58Dr Sophie Shotter:But you just have to enable them to remember to use them. And that's what spermidine seemed to do. And it was doing it through a process called autophagy. For those who don't know what this Latin word means, it just means cell renewal. And it was the subject of the 2016 Nobel Prize in Physiology or Medicine, won by a Japanese scientist. And if you think about the base material of every organ tissue component of our bodies, it's cells. And autophagy or cell renewal is amazing. If we can renew all of our cells, then that gives us the tantalizing possibility of renewing everything in the body. It's very exciting because spermidine is something that we all produce.

14:53Leslie Kenny:So what can you tell us about spermidine? Because it seems that this little molecule is one of the best kept secrets in cellular anti-aging and regenerative medicine.

15:04Dr Sophie Shotter:It is pretty phenomenal and it can activate this cell renewal process called autophagy, which is just Latin for self-eating. And it is also capable of activating a process called mitophagy or mitochondrial renewal. So those are the battery packs inside our cells. And in addition, it can inhibit nine of the 12 pathways down which scientists agree we age. Everything from inflammation, stem cell dysfunction, mitochondrial dysfunction, telomere shortening, gut dysbiosis, things like that. But spermidine is so interesting because it's found in all of us. We all make it. And when we're young, we make it in our tissues, we make it in our gut biome, and we get it in our diet in plants, primarily in mushrooms, legumes, so your lentils and beans would be good.

16:02Dr Sophie Shotter:Fermented soy is an especially rich source of it. So things like tempeh and natto in Japan. And when this internal recycling and repair system is activated, we are getting new cells. And because cells are the foundation, they're the base material for tissues, organs, skin, hair, nails, everything in the body, whether we see it on the outside or the inside, it gives us this tantalizing possibility that we can actually renew ourselves, sort of like snakes renew their skins. And we know that this works in particular with the immune system where, and this research was conducted at Oxford by Katja Simon and Dr.

16:48Dr Sophie Shotter:Gaudel-Soleil, we know that we can actually rejuvenate elderly immune cells that have already become what we call zombie cells or senescent cells. And they have been told by the body's quality control system to just sit quietly in the corner and not disturb anyone because they're not capable of replicating properly anymore. And if you give them spermidine, they will actually rejuvenate. For instance, in the heart, cardiomyocytes, which govern the rhythm of the heart, we don't have a huge number of those. We don't replace them very often. And at my age, at age 60, only half of 1 % are replaced in a year.

17:35Dr Sophie Shotter:So I really don't want them to undergo cell death. I would prefer to have them functioning properly. But spermidine also helps with reproductive health. And having just been at a conference in Geneva where we were talking about femspan or sort of reproductive lifespan, we know that when a woman is at her reproductive peak, she is at her healthiest as well. And that is just an evolutionary truth. And with spermidine, animal studies in China have shown that it increases something called oogenesis or egg production. It increases egg quality and it increases the development of the embryo. It helps also with men too, and the clue is in the name, spermidine, because it's found in sperm and semen, and you need it to make more sperm.

18:29Dr Sophie Shotter:So that's actually really important just from an evolutionary point of view. We often hear about drugs and synthetic drugs, but food-derived spermidine is something that we have all co-evolved with because it's in plants. And so again, from an evolutionary point of view, our bodies recognize these food-derived spermidine compounds. And I think that's why they are much more effective than synthetic versions. So that's a little bit of a primer on spermidine.

19:07Leslie Kenny:Can we go deeper into how it works on the immune system and internal health markers? Because that's super interesting.

19:15Dr Sophie Shotter:Well, so it doesn't just work on the immune system. It works holistically through the entire body, to my point about cells being the foundation, the foundation for everything in the body. And it inhibits nine of these 12 hallmarks of aging, the pathways down which scientists have agreed we age, including shortened telomeres, stem cell and mitochondrial dysfunction, inflammation, cell renewal, and recycling. But with immune cells specifically, we know that by rejuvenating elderly immune cells, which is kind of a holy grail, you can then allow these cells to recognize the pathogens that come their way, whether those are cold and flu viruses, whether that's a question of distinguishing between self-tissue and non-self tissue.

20:15Dr Sophie Shotter:For instance, in an autoimmune attack, it's very important that the body stops attacking its own tissue. So you want your immune system to be in peak condition so it doesn't make the wrong decision. And also, we need tip-top immune function in order to recognize cancer. So cancer surveillance goes down if we have immune cells that are old and not functioning properly. These are the senescent immune cells that I alluded to earlier that simply are not replicating properly. They're not functioning properly anymore. So the body's quality control system has parked them in the corner. Just like that drunk uncle at a wedding who's causing too many problems, you just tell him, please sit in the corner and stay quiet until the party's over.

21:10Dr Sophie Shotter:And then we'll take you home and it will be fine. Well, actually, spermidine can, it's like the best hangover cure for a senescent cell ever.

21:19Leslie Kenny:Can you also talk about how spermidine interacts with active cancer cells in the body? What's the latest research suggesting and what are your personal views?

21:30Dr Sophie Shotter:Well, this is really exciting. I'm so glad you asked this question. Last year, four papers came out, including in Cell and Science, and these are two of the top three scientific journals globally. And two of them were co-authored by Tsusuko Hanzo. He is the 2018 Nobel Prize winner in medicine for his work on cancer tumors. So here we have a cancer expert who's writing about spermidine, and his lab undertook an experiment in animals. So again, this was in mice. We are not mice, but it's still exciting nonetheless. He had elderly mice covered in cancer tumors and then gave them spermidine. And miraculously, cancer resolved in all of them.

22:22Dr Sophie Shotter:and he says the title of one of these articles is and i'm paraphrasing here spermidine improves anti-tumor immunity in mice i think we all want anti-tumor immunity and those four papers are really incredible here's another title spermidine an old molecule with a new age-defying immune function. Again, absolutely phenomenal results. And if it weren't a Nobel Prize winner co-authoring these papers, maybe I wouldn't take it so seriously. But here is one of the world's leading experts on tumors saying, this is worth me spending all this time writing papers about. So the other thing that came out was a study from China published this year, just in March of this year.

23:22And it is around breast cancer.

23:26Dr Sophie Shotter:Now, I have always been very cautious around reproductive cancers. We knew that spermidine was helpful with things like COPD and lung cancer, but we didn't know if it was how it would react with these reproductive cancers like breast cancer. This paper out of China says it's titled, Spermidine Potentiates Antitumor Immune Responses and Immunotherapy Sensitivity in Breast Cancer. It's from the Journal of Cancer. And I think that is really promising. If we can help our breast cancer patients mount a better response to the cancer and eliminate it faster, that's just an amazing win. And this is something, again, a molecule that we manufacture in the body.

24:15Dr Sophie Shotter:It's native to us. It's recognized by the body. This isn't like rapamycin, which is an obscure compound only found in very obscure bacteria. So I'm hugely excited about this. My personal views, for me, again, I'm a little bit more philosophical when it comes to these medical interventions in the same way that I never understood why my doctor wanted to suppress my immune system instead of bringing it back to homeostasis or to balance. I'm looking at spermidine and what it can do with the immune system. I'm thinking, assuming that the immune system has first call on spermidine, then it should improve cancer surveillance before cancer cells get a hold of spermidine.

25:07Dr Sophie Shotter:And I will say that there are other studies which show that in a petri dish, if you have cancer cells and you have spermidine, the cancer cells, they're very clever and they will use the spermidine to grow. But the question is, where does the spermidine go first in the body? Will it go first to the cancer cells or to the immune system? And if it goes to the immune system first, that helps the body get rid of cancer. Gosh, it sounds like we could be

25:33Leslie Kenny:talking about this as just one topic in and of itself. Really, really interesting. Thank you for that. And we'll put some studies in the show notes that people can check out the data, as Sophie said, and as you so brilliantly explained and unpacked. Should we talk more about fertility, particularly as it relates to autoimmune conditions and also thyroid issues?

25:54Dr Sophie Shotter:Well, a healthy thyroid, as I personally found out, is absolutely essential for reproductive health, for uterine and placental function. And if your thyroid is not healthy, it will be incredibly hard to conceive and incredibly hard to maintain the pregnancy. Why? Because the baby is completely reliant on you, the mother, for thyroid hormone. And we need thyroid hormone for proper brain development in the baby. And without it, the body's quality control system says this baby is not developing. Its brain is not developing the way it should. were going to very sadly abort. And I have met a number of other hypothyroid patients who have lost babies around five months.

26:46Dr Sophie Shotter:And it is an absolute tragedy because you have to have the baby go through the birth canal. Your milk comes in. You've got to cut the umbilical cord. It is absolutely a massive trauma for the mother. And in my case, thankfully, I didn't go through that, but it was very clear that I wasn't able to get pregnant because so much of my thyroid had been destroyed by my earlier autoimmune attacks. The problem was that they hadn't diagnosed the damage because I had indicated symptoms of pain and I had been sent to a rheumatologist. And rheumatologists don't swim out of their lane. So they don't look at the endocrine system because that's the work of an endocrinologist, even though lupus, rheumatoid arthritis, and Hashimoto's thyroiditis often co-occur.