Ketones Protect Arteries

The health of arteries is vastly important for aging and prevention of chronic disease, most notably coronary artery disease, and it’s also important for the health of organs such as the kidney and the brain. Ketones, which are produced by fasting or the ketogenic diet, protect arteries.

You’re only as old as your arteries

Thomas Sydenham, a 17th-century English physician, famously said, “You’re only as old as your arteries.” (Ref.)

Coronary artery disease is a major killer in the U.S., and heart disease in general is the number one cause of death.

Aging is the most important risk factor for heart disease. See chart below.

Ketones protect arteries

Disease of the arteries is caused by inflammation in the lining, which is composed of endothelial cells.

All cells other than stem cells age, and as they age they lose function. When they’ve reached the end of the road, they become senescent.

Senescent cells are major contributors to chronic inflammation and are associated with SASP, the senescence associated secretory phenotype. Essentially, senescent cells produce inflammatory chemicals (cytokines) that cause an inflammatory response for any cells in the vicinity. (Ref.)

Chronic inflammation is associated with aging and plays a causative role in several age-related diseases such as cancer, atherosclerosis and osteoarthritis. The source of this chronic inflammation is often attributed to the progressive activation of immune cells over time. However, recent studies have shown that the process of cellular senescence, a tumor suppressive stress response that is also associated with aging, entails a striking increase in the secretion of pro-inflammatory proteins and might be an important additional contributor to chronic inflammation. 

The new science of senolytics promises the ability to rid our bodies of senescent cells, which would negate many of the effects of aging. (Ref.)

In passing, let’s note that a single bout of resistance training (lifting weights) can also eliminate senescent endothelial cells. (Ref.)

Preventing the endothelial cells that line arteries from becoming senescent means keeping them youthful and from becoming sources of inflammatory cytokines. This in turn helps maintain youthful arteries.

A recent study showed that ketones can prevent senescence of both endothelial cells and vascular smooth muscle cells. β-Hydroxybutyrate Prevents Vascular Senescence.

Beta hydroxybutyrate is one of three ketone bodies produced during ketosis.

So, how do you produce ketones?

One way is via a very low carbohydrate ketogenic diet. The absence of carbohydrates in the diet means that glucose in the body must be spared for important uses. Ketones are produced from fat to provide energy in place of glucose.

Another way to produce ketones is through intermittent fasting. Total absence of food, and especially absence of carbohydrates, induces ketone production.

Ketone supplements work too.

Calorie restriction, the most robust life-extension intervention we know of, also produces ketones.

Ketones and autophagy

Autophagy is the cellular self-cleansing process that rids cells of junk molecules, which are crucial in promoting aging.

Increased autophagy is essential for life extension. (Ref.) The decline in autophagy induction in aging allows the accumulation of junk molecules, and therefore cells don’t function as well, leading to the aging phenotype of increased susceptibility to damage, breakdown, and disease.

Ketones promote autophagy. (Ref.)

The promotion of autophagy by ketones may be another way that fasting and ketogenic diet protect arteries.

Increasing the ability to induce autophagy is one of the most promising anti-aging interventions. This can be done with calorie-restriction mimetics, such as resveratrol, rapamycin, and metformin, or of course by calorie restriction itself, as well as fasting and the ketogenic diet.

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Leave a Comment:

Mark says October 2, 2018

Mr. Mangan, since you eat a very low carb diet, how do you get your fat? I need to eat a very low carb diet for health reasons, and am eating mostly beef in various forms, but I’m interested how you get your fat. Just fatty cuts of meat? The typical beef roast doesn’t generate that much fat after cooking compared to the volume of beef meat. And since most calories will be coming from fat, not the meat per se, I’m curious how you get that fat in your diet. With 120 or so calories per tablespoon of fat, and me needing 2500 or more calories a day to maintain weight, it seems like I’d have to consume something like 15 or more tablespoons a day of fat. There just isn’t that much fat in these cuts of beef, even the fatty ones.

Fred says October 2, 2018

Does the website proprietor follow a v low carb diet? I don’t recall that, but I’ve been away from here for a few years (head in sand, I guess, as I gained 50 lbs).

    P. D. Mangan says October 2, 2018

    Hi Fred – yes, he does.

Rob says October 2, 2018

For me, intermittent fasting is a much easier and more practical approach to take, as opposed to going on a ketogenic diet, or a calorie-restriction diet. I suspect that is true for a lot of people. I don’t think it is unhealthy (for me, anyway) to consume a low-moderate amount of carbs during the day (along with plenty of veggies, protein, healthy fat), as long as I skip the evening snacks and make sure I fast for about 14 hours or so before having breakfast. When I do this, my blood test numbers are generally quite good (with regard to glucose, insulin, CRP, triglycerides, etc), so I think it is working for me. I don’t think I could last very long on a ketogenic diet, and I’m quite sure calorie restriction would never work for me.

    Steve Mitchell says October 7, 2018

    Keto diet is easy. Hard part is discipline. But that goes with most things in life. It’s the mental battle that is the hardest, not the physical.

    It took me 2-3 years to go from a “normal” diet to keto. Dropping sugar alone took a year. I’ll never go back. My immune system is so much better now. Apart from post-workout recovery I feel 15 years younger after going keto and lifting weights.

    If you want it, you’ve gotta work for it.

Mark says October 2, 2018

Point taken. So you *are* eating vegetables – I was not clear from your references to not eating/needing carbs whether you were eating nothing but protein and fat sources, or whether by “carbs” you meant mainly grains and sugar. Are you avoiding starchy vegetables like potato and sweet potato, but eating greens and other non-starchy vegetables?

In my particular situation I’d been eating poorly for a long time (lots of grains and sugar and processed crap) and have developed a case of SIBO (small intestine bacterial overgrowth) which suddenly has made any kind of starch or sugar, even the oligosaccharides in onions, cause significant problems because now they are feeding bad bacteria/yeast/fungi that have taken over down there. It has been striking how much changed in my reaction to foods in a fairly short period of time – I ate lots of resistant starches in the past with no problem, happily feeding the gut bacteria, but now I really get sick on them. The apparent change in bacterial composition has made the difference. I’ve discovered that you don’t want to be feeding the gut bacteria if the gut bacteria varieties you have are malevolent. So I’m following a strictly meat/fat diet – the only thing that seems to let me feel good – and only eating vegetables like greens that contain almost no starch or sugars.

It would be interesting if you wrote a post with more specifics about your own diet. You’ve clearly got a lot of stuff figured out in that respect that works well and I think a lot of people besides myself would be interested to hear just what it is that you eat.

Antti Heikkil says October 3, 2018

I am a Finnish doctor, but now I live in Hamburg, Germany. Thank you for your site. It´some of the best. I felt a sort of enlightenment after reading Faccin’s study on insulin resistance. If you summarize the whole current problem into one word, it is insulin resistance. Keep going man !

I am a Finnish doctor, but now I live in Hamburg, Germany. Thank you for your site. It´some of the best. I felt a sort of enlightenment after reading Faccin’s study on insulin resistance. If you summarize the whole current problem into one word, it is insulin resistance. Keep going man !


    P. D. Mangan says October 3, 2018

    Thanks, Antti!

Mattias says October 4, 2018

Regarding cell senescence. A recent paper discuss the natural polyphenol fisetin as a senolytic compound without having to be combined with artificial compounds.
It would be interesting to have your opinions. Perhaps in a future post on senolytic agents 🙂
Do you have any comment on how to guesstimate human effective dose from animal studies. I think you of someone else wrote about a division by 14 somewhere.

Fisetin is a senotherapeutic that extends health and lifespan
Author links open overlay panel. by Matthew J.Yousefzadeh et al

    P. D. Mangan says October 7, 2018

    Hi Mattias – sorry for the late reply. I’ve already started writing about that. For human equivalent of mouse doses, the equivalent for body weight is to divide by 12, to account for greater mouse metabolism. I calculated that the equivalent fisetin dose used in that study would be about 500 mg/d for a 70 kg person. There’s a clinical trial of fisetin that is going to use 1200 mg/d, but only for 2 days.

Carole says October 9, 2018

Do you use and/or recommend MCT C8: C10 supplements? And do you prefer the powder to the oil. If yes, can you suggest which brands to use? Thanks, as always, for an informative, meticulously researched and beautifully presented article.

    P. D. Mangan says October 9, 2018

    Thank you, Carole. I have used MCT oil (liquid) in the past, but haven’t in a while. They appear to raise ketones reliably, and ketone supplements can be healthful. Hard to say whether more people should use them; they do have calories so if going for max fat loss, possibly not.

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