In this video, the host critiques sensational media headlines claiming ketogenic diets accelerate organ aging. He examines a recent Science Advances paper that reported increased senescence-associated beta‑galactosidase in multiple mouse organs after two different ketogenic diets (one high in seed oils, one high in saturated fat). The host highlights the study’s design—use of two diet formulations to control for fatty‑acid profile—and notes the biomarker focus without health‑span or lifespan outcomes. He contrasts these findings with prior mouse work showing keto diets improve lifespan and health (e.g., Roberts et al., Cell Metabolism) and points out odd metabolic results in the new study (weight gain, higher triglycerides). Human data from the paper show a six‑month rise in pro‑inflammatory cytokines (TNF‑α, IL‑1β, IL‑6) in an overweight cohort, but the host’s own five‑year keto cytokine panel is normal, suggesting individual variability. He advises viewers to treat the new data cautiously, consider personal testing, and not be swayed by click‑bait headlines, while acknowledging the study’s merit in using dual diet formulations.
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Over the past week as I record this, there has been a flood of sensational media headlines that ketogenic diets can accelerate organ aging and damage. Here are some quotes from media outlets: "Ketogenic diets increase the buildup of zombie-like cells in the heart, kidney, lungs, and brain." And "Ketogenic diets may accelerate organ aging, raising the risk of conditions like heart disease and cancer." Or "Senescence in these organs?" can contribute to systemic inflammation and toxicity. Now, these headlines derive from a new publication in Science Advances that found two different ketogenic diets in mice increase markers of senescence, or biological aging. But the data aren't so definitive, at least not like the media headlines would have you believe, nor are they sufficiently compelling to cause me to start eating potatoes, fruit salads, and oats anytime soon. Now let me tell you why. Welcome to my channel. Stay curious. I'm going to start by reading a quote straight from the paper itself. Multiple ketogenic diet studies using murine, or mouse, models have shown anti-inflammatory effects and improvements in midlife longevity and neurological, metabolic, and obesity phenotypes. These are all good things. Conversely, there's also evidence that low carbohydrate diets can be pro-inflammatory in mice and increase the risk of cardiac fibrosis and kidney damage. There is insufficient information regarding the mechanisms responsible for these divergent outcomes, which individuals may be at risk for adverse effects, or if any interventions could mitigate these risks. It seems reasonable to suggest that specific variables of the ketogenic diet combined with those of individuals undergoing dietary intervention all contribute to determining the beneficial or detrimental effects. Basically, they're saying that there are mixed data and that individual and diet-specific factors may account for heterogeneity in the data, which I think is totally reasonable. Now, for the study, they focused on a biomarker of cellular aging called senescence-associated beta-galactosidase and compared mice on one of two different ketogenic diets with mice eating a normal, uh, standard chow mouse diet. The two ketogenic diets were one based on CRISPR, and one based on cocoa butter. Now, there's been a lot of talk about these mice being on a CRISCO diet, which is high in, quote, "seed oils," and that may be true, and that may be a concern for some people, but I do want to highlight that the authors did have another diet that was very low in omega-6 linoleic acid, only about 2-3% linoleic acid. So they were basically providing a control to say, "Look, the fatty acid profile may not be the mediating variable." here, and that even mice on a higher saturated fat, lower unsaturated fat diet can still exhibit the phenomena that they show in this paper. So I just want to highlight that because I think it was a masterful move by the researchers. I give them points for this, for using two different ketogenic diets with different fatty acid profiles. I think that was very good. Now, what did they find? They found that a biomarker of aging, senescence-associated beta-galactosidase, was increased in multiple organs in the mice on the ketogenic diets. Now, they didn't truly look at healthspan or lifespan, which will become relevant in a moment. They also reported that an intermittent ketogenic diet, i.e., carb cycling, in the mice could reverse the increase in this biomarker of aging, leading some to conclude that an intermittent ketogenic diet might be preferable or safer for cellular aging than a ketogenic diet. I will say I think these data are interesting. And not to be entirely discounted, but it's important to frame and caveat them. First, the authors note, as I read to you, that there are conflicting data. And if we're comparing apples to apples, or mice to mice as it were, then the obvious question is, well, what are the outcome data for healthspan and lifespan in mice? And the answer is typically improved healthspan and lifespan in mice on ketogenic diets, as shown for example in Roberts et al. In Cell Metabolism, which you can give a read if you like, I'll link it below. So in this paper, they showed that mice put on a ketogenic diet had improvements in lifespan, significant improvements in lifespan, and were healthier at older age, had better cognitive function and better musculature and physical function. So when you are looking particularly at the mouse data and you say there are heterogeneity in the data, and in one paper you find changes in a biomarker, and the other you find changes in outcome data, and they conflict, I'd typically go with the outcome data. That's just me. Now, I'll also note there are some what I call oddities in the data. For example, if you look at the mouse data, the mice on a ketogenic diet, especially the CRISPR diet, trended towards more weight gain, which is interesting and not typically what you see on ketogenic diets, certainly not in humans. It also had a bump in triglycerides, again opposite of what you typically see, especially in humans. So I find that odd and a bit concerning if we were to generalize these beyond this specific mouse response. That said, they do actually cite some human data from a cohort which isn't otherwise published upon. They provide the clinical, uh, trial registration, which I'll provide below, but there aren't more data published on these humans. But what they show is a change in the cytokine profile over time. So cytokines specifically TNF-alpha, interleukin-1 beta, and interleukin-6, which are kind of pro-inflammatory mediators, were elevated in these humans. From their dataset, these were humans with obesity and overweight, and/or overweight. And they showed that particularly around 6 months, there was a jump in the levels of these cytokines: TNF-alpha, interleukin-1 beta, and interleukin-6, which I find interesting. It does conflict with prior data showing that ketogenic diets in humans tend to be anti-inflammatory. Including in these cytokines, but they do provide some novel insight, as far as I'm aware, where there might be a time dependency, where the spike in the cytokines may occur only after 6 months. So I find this interesting, and I think more research is needed on this. That said, these are cytokines that can be measured in anyone, so I had the thought before I made this video to, as soon as this paper came out, I'll get these checked in myself and report back on what my levels are, because I've been on a ketogenic diet for over 5 years. So if there's supposed to be a spike in cytokines at 6 months, I should see them in myself. And here what you can see are my results. My cytokines, including the cytokines reported in this paper—TNF-alpha, interleukin-1 beta, interleukin-6—are all very normal and in the very healthy range. In fact, on two of the panels, they couldn't even measure my cytokine levels because they were below the threshold of detection. So do these data generalize to me? Are they relevant to me? Well, I would say if the mediating cytokines that they say are elevated in humans after 6 months aren't elevated in me after 5 years, then there's something different. My data are clearly divergent, to use their own word, from the data in the humans presented in this paper. Now, I won't generalize my data to you, and you can feel free to get a cytokine panel yourself, but again, it just comes back to the idea that there's something odd going on here. Relevance can actually be checked or presumed by testing something in yourself. So you're free to do that. But for me, my cytokines are not elevated, so I see no reason from these mouse data primarily, which conflict with other mouse— mice data, and the association in humans, to generalize this to me, which is why I'm not going to be adding potatoes to my diet anytime soon, or doing cyclic keto when a ketogenic diet is therapeutic for me. You can do you. So in summary, what I'd say is these are interesting data. It's an interesting study. I don't want to just discard it. I think that would be inappropriate. But it conflicts with prior data, including arguably stronger mouse data. And if you want to get a cytokine panel to see if you can replicate the results, the elevated cytokines after 6 months on a ketogenic diet in yourself, or if your personal data conflict with the human data they presented in this paper, which again is odd, I'd say, then go for it. You can kind of presume relevance in yourself that way. And I don't really think there are any reasons to freak out based on these data. The headlines are oversensationalized because they want clicks. Now, if you want to carb cycle, if that makes you feel safer, do whatever you want. I'm not opposed to it, especially if you're not using a ketogenic diet therapeutically. But those are my thoughts. I think it's an interesting paper. I wouldn't make much of it at this time.
