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Prescribing a ketone-based diet to prevent or reduce the progression of age-related disease

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Brett M.
Brett M. Dec 02, 2020

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[2]https://www.un.org/en/sections/issues-depth/ageing/#:~:text=According%20to%20data%20from%20World,be%20aged%2065%20or%20over.

[3]White, M. C., Holman, D. M., Boehm, J. E., Peipins, L. A., Grossman, M., & Henley, S. J. (2014). Age and cancer risk: a potentially modifiable relationship. American journal of preventive medicine, 46(3 Suppl 1), S7–S15. https://doi.org/10.1016/j.amepre.2013.10.029

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[5]Cervenka MC, Kossoff EH. Dietary treatment of intractable epilepsy. Continuum (Minneap Minn) [Internet]. 2013;19(June): 756–66. Available from: http://www.ncbi.nlm.nih.gov/pubmed/ 23739109

[6]McDonald, T., & Cervenka, M. C. (2018). Ketogenic Diets for Adult Neurological Disorders. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 15(4), 1018–1031. https://doi.org/10.1007/s13311-018-0666-8

[7]Rieger J, Bähr O, Maurer GD, Hattingen E, Franz K, Brucker D, et al. ERGO: A pilot study of ketogenic diet in recurrent glioblastoma. Int J Oncol. 2014;45(6):1843–52.

[8]Nebeling, L.C., Miraldi, F., Shurin, S.B., Lerner, E., 1995. Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports. Journal of the American College of Nutrition 14: 202e208.

[9]Weber, D. D., Aminzadeh-Gohari, S., Tulipan, J., Catalano, L., Feichtinger, R. G., & Kofler, B. (2020). Ketogenic diet in the treatment of cancer - Where do we stand?. Molecular metabolism, 33, 102–121. https://doi.org/10.1016/j.molmet.2019.06.026

[10]Kudryavtseva, A. V., Krasnov, G. S., Dmitriev, A. A., Alekseev, B. Y., Kardymon, O. L., Sadritdinova, A. F., Fedorova, M. S., Pokrovsky, A. V., Melnikova, N. V., Kaprin, A. D., Moskalev, A. A., & Snezhkina, A. V. (2016). Mitochondrial dysfunction and oxidative stress in aging and cancer. Oncotarget, 7(29), 44879–44905. https://doi.org/10.18632/oncotarget.9821

[11]Maalouf M, Rho JM, Mattson MP. The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Res Rev [Internet]. Elsevier B.V.; 2009;59(2):293–315. https:// doi.org/10.1016/j.brainresrev.2008.09.002

[12]Taylor MK, Sullivan DK, Mahnken JD, Burns JM, Swerdlow RH. Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer’s disease. Alzheimer’s Dement Transl Res Clin Interv. Elsevier Inc.; 2018;4:28–36.

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[14]Ota M, Matsuo J, Ishida I, Hattori K, Teraishi T, Tonouchi H, et al. Effect of a ketogenic meal on cognitive function in elderly adults: potential for cognitive enhancement. Psychopharmacology (Berl)

[15]Henderson ST, Vogel JL, Barr LJ, Garvin F, Jones JJ, Costantini LC. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr Metab (Lond) [Internet]. 2009;6(1):31. Available from: http://nutritionandmetabolism. biomedcentral.com/articles/10.1186/1743-7075-6-31

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General comments

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Martina Pesce
Martina Pesce3 months ago
I really like the idea of prescribing a diet as a prevention factor, expetially for a population that is as vast as the elderly one.
It will have also a brilliant side effect which is acknowledging the importance and relevance of nutrition for the health condition.
Shubhankar Kulkarni has already presented the controversial sides of the ketogenesis diet, though.
Maybe finding a diet which is less problematic and risky could be an option.
For example, since the responsible of many benefits of the diet are the ketonic bodies, another diet which produces the same is the so called "longevity diet". It is characterized by some fasting-like periods. Their length and frequency depends on the patients health conditions, weight and other factors.

I know it is a quite radical change on your idea, but maybe it will make it less questionable, what do you think?
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Brett M.
Brett M.3 months ago
Martina Pesce interesting points. I am wondering--do you have a link to the effects of this "longevity diet"? I cannot find anything on PubMed, but I found an overview article about this diet (https://www.verywellhealth.com/the-longevity-diet-plan-overview-2223476) and it looks to be similar in approach as the plant-based diet that Shubhankar Kulkarni mentioned in his comment. This definitely sheds light on the importance of plant-based diets, especially in the later years. I'm wondering about the caloric restriction--this may have to be tailored to individual lifestyles. 800-1100 calories a day for an active 65-70-year-old may not be the best, but I'm sure as long as they stick to the ratios provided in the linked article, this form of fasting will provide benefit. Seems quite reasonable since the fasting periods are not very long either.

As I mentioned in my response to Shubhankar's comment, there is the potential of adding exogenous ketone esters and medium-chain triglycerides to a ketogenic diet to mitigate the negative side effects of low-carb and long-term increases in cholesterol and blood lipids. I think what you provide here is an interesting perspective on the idea of a nutrition-based approach to promoting longevity, which I also find is necessary for the discussion about the impact of diet on health.

I think the consensus from what I'm reading so far is that intermittent fasting on a plant-based diet seems quite feasible to promote longevity. It would be interesting to see how this diet would fare with exogenous ketone esters or MCTs since ketone bodies are more energy-efficient and may provide protection against mitochondrial-related neurological diseases (https://pubmed.ncbi.nlm.nih.gov/25101284/). Nevertheless, thanks for your comment--the longevity diet seems quite interesting. I'd like to see some more sources about the diet's efficacy in the experimental setting if you have any on hand!
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Martina Pesce
Martina Pescea month ago
Brett M.
Here you can get some papers on the research Valter Longo did behind the longevity diet:
-A Periodic Diet that Mimics Fasting Promotes MultiSystem Regeneration, Enhanced Cognitive
Performance, and Healthspan (https://www.cell.com/cell-metabolism/pdf/S1550-4131(15)00224-7.pdf)
-Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease (https://valterlongo.com/wp-content/uploads/2017/10/2017-02-Wei-Fasting-mimicking-diet-markers.pdf)

I would say these are the most relevant for longevity, but on Valter Longo's site you will find a proper list of all the papers related tot he diet (https://www.valterlongo.com/scientific-articles/)

It is actually not an exclusively plant-based diet. There is fish involved (for my joy, I would add ;) ).
The initial idea for the diet was not to have it plant-based but to observe what people who live very long eat and base it on that.

There are guidelines but ideally, the diet needs to be personalized per every single person. Age, health status, weight and lifestyle have a big impact on the diet setting. I remember checking for an average weighted person of my age (23) it was suggesting fasting of 5 days every 6 months. Very doable.

This diet, in the fasting periods, want exactly to focus on the production of ketone bodies, but in a way that avoids the negative effects of them. You can maybe call it a extremely light ketonic diet ;).
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Brett M.
Brett M.a month ago
Martina Pesce Great! Thank you for the referral links. Interesting reads...

I like the idea of a personalized diet, which is really where I think medicine is transitioning to. It's a necessity. The blanket approach for health does not work and it is clear that individuals require their own, personalized treatment. So, extending this to personalized diet plans would be a great idea as well. The following paper highlights the "person-centered" approach to measuring longevity as it relates to diet and health [1]. They also mention the measurement of biomarkers as they relate to dietary and lifestyle changes. It would be interesting to be able to take a blood sample to measure levels of biomarkers known to promote and/or impede healthy aging and prescribe a diet that specifically aims to modulate these biomarkers and thereby promote healthy aging.

As for fasting, 5 days every 6 months is definitely doable. There are other ways to fast as well, such as 12 hour fasting, which is very easy to do if you are able to get 8 hours of sleep and restrict eating between say 8PM and 8AM. Another fasting strategy that has been shown to improve overall health is the 5:2 intermittent diet [2].

The thing about ketone- based diets is that they take time to generate a state of ketosis that is generally desired to produce results -- 2-4 days for initial ketosis in some people but several weeks to adapt to the ketogenic state completely in others [3].

So, is it that the fasting periods are meant to "enhance" the production of ketones that is already occurring to optimize the ketogenic state?

References

1. Wickramasinghe K, Mathers JC, Wopereis S, Marsman DS, Griffiths JC. From lifespan to healthspan: the role of nutrition in healthy ageing. J Nutr Sci. 2020 Aug 24;9:e33. doi: 10.1017/jns.2020.26. PMID: 33101660; PMCID: PMC7550962.

2. Bjarnadottir, A. (May 31, 2018). The Beginner's Guide to the 5:2 Diet. Healthline.

3. Raman, R. (April 16, 2019). How Long Does It Take to Enter Ketosis?. Healthline.
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Shubhankar Kulkarni
Shubhankar Kulkarni3 months ago
Since the keto diet mimics starvation (caloric restriction), which is one of the strategies to promote lifespan and healthspan, it can be a lifestyle choice during old age to reduce the impact of age-related diseases.

However, the keto diet comes with its own problems. Here, I will avoid the ones associated with the keto "flu", which is only observed during the switch from the regular diet to the keto diet, in most people. I will talk about the problems associated with long-term keto diet: (https://www.health.com/weight-loss/keto-diet-side-effects)
Consuming more fat may put more pressure on the gall bladder. Several keto-dieters, therefore, experience diarrhea.
Ketoacidosis: It is not advisable to have a keto diet if the person has type and diabetes or related metabolic disorders due to the risk of ketoacidosis. Diabetics are already at risk of ketoacidosis and the keto diet increases the risk further.

Studies that do not report beficial results regarding the keto diet:
A study comprising 25,000 participants suggested that people on the lowest-carb diets had the highest risk of all-cause mortality, including that related to cancer and cardiovascular (https://academic.oup.com/eurheartj/article/40/34/2870/5475490).
Another study found that people who followed diets that were low in carbs and high in animal proteins had a higher risk of early death compared to those who consumed carbs in moderation. On the other hand, low-carb dieters who consumed plant-based proteins lived longer (https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(18)30135-X/fulltext).
Keto diet led to insulin resistance in the liver in one experiment (https://www.eurekalert.org/pub_releases/2018-08/tps-kdm080718.php).
Keto diet increases the risk of cardiovascular diseases by increasing cardiovascular risk factors like low-density lipoproteins (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452247/).

There are mixed reports regarding the effect of the keto diet on health. It might probably depend on the person's regular diet. If a person might be consuming a low-carb diet for generations, a keto-diet may not be a bad idea for them. However, for a person who has consumed mostly a plant-based diet, might present negative effects.

Since the old already suffer from one or more of these ailments, how advisable is keto diet to this population, is questionable. If there was a way to administer the diet without its downsides, that would be beneficial.