How ketogenic diet protects against vascular aging

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It has been noticed that ketone bodies producing diets such as calorie-restricted diet and ketogenic diets exert some anti-aging effects (on test animals). This study, see the article linked below, pinpoints the mechanism of this effect to the specific ketone body molecule: β-Hydroxybutyrate.

Natural “Fasting” Molecule Exerts Anti-Aging Effects to Protect Vascular System
By NutritonReview.org - May 16, 2019


Quote:

In their study, the research team explores the link between calorie restriction (eating less or fasting) and delaying aging, which is unknown and has been poorly studied. The findings are published in the journal Molecular Cell.

The researchers identified an important, small molecule that is produced during fasting or calorie restriction conditions. The molecule, β-Hydroxybutyrate, is one type of a ketone body, or a water-soluble molecule that contains a ketone group and is produced by the liver from fatty acids during periods of low food intake, carbohydrate restrictive diets, starvation and prolonged intense exercise.

The researchers reported that β-Hydroxybutyrate delays vascular aging by providing a chemical link between calorie restriction and fasting and the anti-aging effect.

This compound can delay vascular aging of the endothelial cells, which line the interior surface of blood vessels and lymphatic vessels, preventing a type of cell aging called senescence, or cellular aging.

Senescent cells can no longer multiple and divide. The researchers found β-Hydroxybutyrate can promote cell division and prevent these cells from becoming old. Because this molecule is produced during calorie restriction or fasting, when people overeat or become obese this molecule is possibly suppressed, which would accelerate aging.

In addition, the researchers found when β-Hydroxybutyrate binds to a certain RNA-binding protein, this increases activity of a stem cell factor called Octamer-binding transcriptional factor (Oct4) in vascular smooth muscle and endothelial cells in mice.

Stem cell factor Oct4 increases a key factor against DNA damage-induced senescence, which can keep blood vessels young.

Reference:

1. "β-Hydroxybutyrate Prevents Vascular Senescence through hnRNP A1-Mediated Upregulation of Oct4",
Young-min Han et al., Molecular Cell, VOLUME 71, ISSUE 6, P1064-1078.E5, SEPTEMBER 20, 2018.

Example of a ketogenic (high fat low carb) dish.  Ketogenic diet has been described by some as BBB diet, meaning Butter, Bacon and Brie.  It is not limited to that!  

Statins review paper

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"Nuclear explosion" is probably a better term than review!

Source Wiki

"The Ugly Side of Statins. Systemic Appraisal of the Contemporary Un-Known Unknowns" by Sherif Sultan and Niamh Hynes published in Open Journal of Endocrine and Metabolic Diseases, 2013, 3, 179-185.

The whole text is well worth reading in its entirety! Some quotations:

From the Abstract:

A comprehensive review of Pubmed, EM-BASE and Cochrane review databases was undertaken for articles relating to cardiovascular primary prevention and statin side effects with the aim of harmonising their roles within contemporary clinic practice. Particular attention was paid to large-scale randomised controlled trials on contemporary cardiovascular pharmacotherapies and their specific adverse effects on metabolic pathways which feature prominently in cardiovascular primary prevention and regenerative programmes.

There is a categorical lack of clinical evidence to support the use of statin therapy in primary prevention. Not only is there a dearth of evidence for primary cardiovascular protection, there is ample evidence to show that statins actually augment cardiovascular risk in women, patients with Diabetes Mellitus and in the young. Furthermore statins are associated with triple the risk of coronary artery and aortic artery calcification.
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Utmost Medical Tragedy.

We seem to have fallen into the marketing trap and ignored the niggling side effects with regard to the HMG-CoA reductase inhibitors [1]. The only statin benefit that has actually been demonstrated is in middle aged men with coronary heart disease. However, statins were not shown to best form of primary prevention. Aspirin, as a form of primary prevention decreases the risk for total cardiovascular events and nonfatal Myocardial Infarction over any other factor [5]. In actual fact, high cholesterol levels have been found to be protective in elderly and heart failure patients and hypo-cholestereamic patients had higher incidence of intra-cerebral bleeds, depression and cancer [1].

The statin industry, with all of its spin-off, is a 20-billion-a-year industry. We are observing the revealing of the utmost medical tragedy of all times. It is unprecedented that the healthcare industry has inadvertently induced life-threatening nutrient deficiency in millions of otherwise healthy people. What is even more disparaging is that not only has there been a failure to report on these negative side-effects of statins, there has actually been active discouragement to publish any negative studies on statins.

Statins induce diabetes.

The US Veterans affair healthcare system study on 15 million veterans in 10 hospitals in Southern USA concluded that statins affect fasting and postprandial glucose level by inducing a state of hyperglycaemia in diabetic as well as non diabetic patients [12]. This relationship between statin use and rise in glucose level is independent of age and use of aspirin, beta blockers and angiotensin-converting enzyme inhibitors. Furthermore, a sub-analysis of the JUPITER study showed that statin therapy can induce full blown type 2 diabetes in women [13]. This was astonishingly shown in the sub study of PRO-VE-IT TIMI 22, in which there was a significant increased risk of developing HBA1c > 6% in both diabetics and non diabetics [14]. Moreover Huptas et al. have demonstrated that statin therapy can induce a state of insulin resistance [15].
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Statins manipulate glucose metabolism as a consequence of inhibitory effects on adipocytes. They induce insulin resistance through reduction in insulin-stimulated glucose uptake with a strong impact on glycaemic control in non obese patients.
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Preiss et al. [19] demonstrated, in a pooled analysis of data from the five major statin trials, an increased incidence of new onset diabetes with statin therapy and provided evidence of a dose dependent association.

Statins accelerate arterial calcification.

The Confirm registry had shocked the scientific world with the strongest evidence that statin use is associated with an increased prevalence and extent of coronary plaques calcification [32]. Ironically for a drug which was marketed to lower the risk of cardiovascular disease, the confirm registry identified a strong association of statin use to the progression of coronary artery plaque features. Moreover, Statin use was correlated with a greater incidence of severe coronary artery stenosis as well as increase in the numbers of coronary vessels developing obstructive coronary artery disease. Furthermore, statin use was linked to an increase in the prevalence and extent of mixed calcific plaque. Five prospective studies have borne witness to the fact that statin therapy does not induce any coronary calcium regression and evolution of coronary calcium continues regardless of statin treatment[33,34]. The Veteran Affairs Diabetes Trial [35] established that statin consumption was linked to accelerated progression of Coronary Artery Calcification (CAC) in participants with Type 2 Diabetes Mellitus without previous coronary artery disease, despite the fact that statin users had significantly lower and nearly optimal LDL-cholesterol levels.

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Updated 5-Oct-2013, press news by Irish Independent:

"HSE gags surgeon after cholesterol drug claims"

A LEADING vascular surgeon [Sherif Sultan], whose research review concluded cholesterol-lowering medicines may do more harm than good for many otherwise healthy people, has been gagged by the Health Service Executive. ...

Arterial plaque = glucose + insulin, C14 traced study

Atheroma (from wiki)

A "blast from the past": two old forgotten papers that were never followed up, as far as I was able to find.  I wonder why not?

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INSULIN STIMULATED LIPOGENESIS IN ARTERIAL TISSUE IN RELATION TO DIABETES AND ATHEROMA
R. W. Stout, Lancet p702,1968

Summary

Discussion (p1 of 2)

Discussion (p2 of 2)

INSULIN STIMULATION OF CHOLESTEROL SYNTHESIS BY ARTERIAL TISSUE

R.W. Stout, Lancet p467,1969

Summary

Discussion (p1 of 2)

Discussion (p2 of 2)

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Dav0 found a more recent paper by Stout (thanks):


Insulin and Atheroma: 20-Yr Perspective, Robert W Stout, MD, DSc, FRCP

Quote:

Five population studies have shown that insulin responses to glucose are higher in populations at greater risk of cardiovascular disease. Many of the hyperinsulinemic populations also had upper-body obesity, hypertriglyceridemia, lower highdensity lipoprotein (HDL) levels, and hypertension. These prospective studies support an independent association between hyperinsulinemia and ischemic heart disease, although their results differ in detail. Hyperinsulinemia is associated with raised triglyceride and decreased HDL cholesterol levels.

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