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The Ketogenic Diet Increases Longevity and Healthspan in Mice
Study Insight

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Quick Summary tl;dr

In normal healthy mice, a ketogenic diet increases median lifespan by 13% and also improves physical and cognitive health span.

Studies on the long-term effects of ketogenic diets on longevity and health span have not yet been conducted in humans.

Beyond being an effective way to shred body fat, reverse diabetes, and potentially treat other chronic diseases, such as dementia, the question remains: Is the ketogenic diet actually good for the average person’s long-term health?

The short answer is that we don’t really know because nobody has done a long-term controlled study in humans. However, some animal data (Roberts et al., 2017) published in one of the world’s most prestigious scientific journals, Cell Metabolism, suggests that perhaps it is!

In this study, normal healthy adult mice were split into three diet groups. One group ate a control diet containing moderate-carbohydrate mouse chow, another ate a diet that was low in carbohydrates but not quite ketogenic, and the third ate a proper ketogenic diet.

Importantly, all three diets contained equal number of calories so caloric restriction could not impact the experimental results. Fascinatingly, the ketogenic diet group not only lived the longest (their median lifespan was 13.6% longer than the control mice) but also maintained the best physical strength and cognitive ability into old age!

The ketogenic diet extends lifespan in mice by 13.6% as compared to a calorie-matched standard diet.

The scientist also did biochemical tests on the mice to try to determine some of the mechanisms underlaying these data and found some interesting changes in DNA markers (DNA acetylation) and enzyme activity levels (including mTOR) that were consistent with the longevity and healthspan results. ( Norwitz et al., 2020) (As an important aside, the low-carb group tended to perform between the control and ketogenic groups on most tests, including lifespan.)

While these data need to be replicated, and should be taken with a grain of salt because mice are not humans, they are at least consistent with the hypothesis that the ketogenic diet might be a generally positive lifestyle choice, even for healthy people.

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Comments (10)

What are some good metrics that you suggest to determine if I am aging much or not? I know skin/face is one metric but would like to know if any blood tests could help in very closely determining it.

Sorry, but not really. If you really wanted you could track the length of your telomeres every decade. That's probably the best options but even that is shotty.

Hi Nick, I know this is a bit unrelated but do you take any 'anti-aging' supplements such as ashwagandha or CoQ10?

Personally, I don't. That might be because I'm still on the younger side so those supplements that might benefit others might not be as relevant in me. For example, I know some docs who take nicotinamide riboside to boost NAD+. The data on NR/NAD+ is pretty good, as far as anti-aging data go.
Beyond that, I don't think many general supplements are worth the money and that supplementation should be tailored to biomarkers/genetics. I can't provide personal medical advice, only general thoughts, but I'm always happy to give comments on a specific product of interest or general suggestions on what could consider given an undesired biomarker/genetic finding.
In my opinion, longevity is less about extending life and more about realizing the life- and health-span potential of your genetics. I imagine that I start off life with 100 years. That's the default number and I lose years by being less than optimally metabolically healthy. That includes lifestyle and, sometimes, targeted supplementation.
Hope that helps.
Best,
Nick

Thank you so much, I didn't know about nicotinamide riboside! I like how you think about longevity. I feel that if we all were to do that we'd live a much happier and healthier life. Many people try to find the things to "fix" it when it's too late.

"I like how you think about longevity." ... I'll keep it short and sweet (well, not sweet like sugary)... I think longevity and Healthspan are the same thing. If you're unhealthy just trying to cling on, you're not living. I don't want anybody going to extreme lengths to keep me alive at the end. I want to live well and die well. Granted, that's from a 25 year-old. I don't pretend to be any sort of guru when it comes to end of life. That's just my perspective atm.

What are you thoughts on the Mediterranean diet for longevity?

The idea that a Mediterranean diet is good for longevity derives most from epidemiological data. In other words, we only have associations. Is it the diet itself that is good for longevity, or the lifestyle at a more holistic level. Maybe it's a bit of both. In my opinion, since we don't know for sure, the conservative approach would be to pick the best perceived longevity diets and combine them. That's Mediterranean-keto. From there, optimize using science. The caveat to all this, of course, is that diets should fit the individual. Some people, for example, appear to do well by eliminating plant material from their diet and focusing on health whole animal-sourced foods.
As it so happens:
ketodietapp.com/books/new-mediterranean-diet

Hello Dr. Norwitz. Thank you or the article. While I agree mouse studies don't always translate well into humans, it's certainly interesting data. My question is a little esoteric and perhaps outside the scope of the piece but I was wondering if you'd read this paper on intermittent fasting  and what your thoughts were on the potential effects of ketogenic diets are on SIRT3. https://www.nature.com/articles/s41467-019-09897-1 . It would make sense to me that IF and Keto would have convergent metabolic effects. Thank you.

Don't you love coincidences... we have a blog post specifically on SIRT3 already written. It's in the pipeline and comes with a mini lecture. Martina & Nikos have just been very busy so haven't had time to do the typesetting, but it's coming at some point. Having said that, I'll just drop an excerpt from that coming soon blog that I think answers your question:
This most recent (2020) study found that beta-hydroxybutyrate (BHB), the ketone that is produced during fasting or on a ketogenic diet, itself boosts SIRT3 levels, and that this is neuroprotective. This makes sense because BHB is a signaling molecule evolutionarily associated with metabolically stressful states. You can think of BHB as part of the pathway, upstream of SIRT3, that converts intermittent low-grade metabolic stressors (exercise and fasting) into neuroprotective adaptations.
The researchers conducting this study put two groups of young Alzheimer’s disease mice on either a ketone diet (not low-carb) or a control diet. Both diets had the same number of calories, but the ketone diet contained 22% calories from ketone ester, which is directly metabolized into BHB. The Alzheimer’s disease mice that received the BHB exhibited 50% higher SIRT3 protein levels in their brains as compared to control diet mice. Correspondingly, when the mice aged, the old mice that had received the ketone had twice as many neuroprotective GABAergic neurons, were less susceptible to seizure and excitotoxicity, and ultimately lived longer than their poor no-ketone, low-SIRT3 kin.
https://www.jneurosci.org/content/jneuro/40/3/694.full.pdf