Diet-Heart Hypothesis

Abstract

This article examines how faith in science led physicians and patients to embrace the low-fat diet for heart disease prevention and weight loss. Scientific studies dating from the late 1940s showed a correlation between high-fat diets and high-cholesterol levels, suggesting that a low-fat diet might prevent heart disease in high-risk patients. By the 1960s, the low-fat diet began to be touted not just for high-risk heart patients, but as good for the whole nation. After 1980, the low-fat approach became an overarching ideology, promoted by physicians, the federal government, the food industry, and the popular health media. Many Americans subscribed to the ideology of low fat, even though there was no clear evidence that it prevented heart disease or promoted weight loss. Ironically, in the same decades that the low-fat approach assumed ideological status, Americans in the aggregate were getting fatter, leading to what many called an obesity epidemic. Nevertheless, the low-fat ideology had such a hold on Americans that skeptics were dismissed. Only recently has evidence of a paradigm shift begun to surface, first with the challenge of the low-carbohydrate diet and then, with a more moderate approach, reflecting recent scientific knowledge about fats.

The greatest challenge to this traditional explanation has been presented by Professor Vladimir Subbotin (9-11). The challenge hinges on two facts that are irrefutably true, and either of which by itself irretrievably undermines any proposed theory of how LDL-cholesterol from the blood crosses the lining of the arteries — i.e., the endothelium — and collects in the subendothelial space in the tunica intima, initiating the process of atherosclerosis as depicted in Figures 1 and 2.

The first point made by Subbotin as early as 2012 (9) and repeatedly since (10, 11) is that the tunica intima, including the so-called subendothelial space, is not an empty space without cells and filled only with structural proteins. This is the way it is depicted in Figures 1 and 2. Subbotin argues the only reason why the diagram is drawn that way is because Keys’ lipid hypothesis demands it to be so. Without that space, the lipid hypothesis in its original form is logically disproven.

This is the only model that would explain how LDL-cholesterol particles might be able to “slip” — Subbotin uses the word “crawl” (11) — easily through a damaged endothelial lining to enter the acellular subendothelial space, where they are engulfed by invading macrophages, thus initiating the process of progressive atherosclerosis. But if this (hypothetical) acellular subendocardial space is not acellular but instead comprises layer upon layer of mature cells, how will the LDL-particles find their way between those cells? And how, among all those layers of cells, will the macrophages be able to locate the LDL invaders?

Subbotin cites the utterly fundamental and completely ignored work of Yutaka Nakashima et al. (12-14), which reveals two essential findings that destroy Keys’ lipid hypothesis. Interestingly, Nakashima and colleagues avoid any reference to the possibility that their work disproves Keys. Only Subbotin has had the courage to advance this heretical possibility.

The first finding is that histological examination of adult coronary arteries shows the tunica intima does not comprise a single layer of endothelial cells sitting atop an acellular empty space that exists, just waiting to be filled by LDL-cholesterol and engulfing macrophages. This is shown in Figure 3.

Figure 3: The study of Nakashima et al. (12) shows the tunica intima is not an empty acellular space as depicted in Figures 1 and 2. Instead, the tunica intima comprises multiple layers of cells (panels a and b) and is in fact thicker than the tunica media. Using a special stain to identify smooth muscle cells, panel c shows the cells in the tunica intima, below the endothelial layer, are indeed smooth muscle cells. Panel d stains for the presence of macrophages, which are identified with an arrow head. This evidence shows the diagrams depicted in Figures 1 and 2 are fundamentally incorrect in depicting the tunica intima as an acellular space potentially full of macrophages. Reproduced from Figure 3 in reference 10.

In contrast, the tunica intima comprises multiple layers of smooth muscle cells — up to 50 such layers — and without any macrophages.

Free article

doi: 10.1016/j.drudis.2016.05.017. Epub 2016 Jun 2.Review. 2016 Oct;21(10):1578-1595.Drug Discov Today

Excessive intimal hyperplasia in human coronary arteries before intimal lipid depositions is the initiation of coronary atherosclerosis and constitutes a therapeutic target
Vladimir M Subbotin 1
DOI: 10.1016/j.drudis.2016.05.017

Abstract

The consensus hypothesis on coronary atherosclerosis suggests high LDL-C levels as the major cause and pursues it as the therapeutic target, explicitly assuming: (i) tunica intima of human coronaries consists of only one cell layer - endothelium, situated on a thin layer of scarcely cellular matrix; and (ii) subendothelial lipoprotein retention initiates the disease. Facts showed: (i) normal tunica intima invariably consists of multiple cellular layers; and (ii) initial lipid depositions occurred in the deepest layers of tunica intima. This review suggests that coronary atherosclerosis starts with pathological intimal expansion, resulting in intimal hypoxia and neovascularization from adventitial vasa vasorum, facilitating lipoprotein extraction by previously avascular deep intimal tissues. Until the hypothesis incorporates real knowledge, our efforts will probably be off-target

Subbotin has proposed an alternate hypothesis (10, yet to be fully tested).

He proposes the fundamental event leading to the development of atherosclerosis is a triggering of proliferation (multiplication and growth) of the smooth muscle cells in the tunica intima. These are the cells in the arterial system that are known to replicate the most. Their replication can be initiated by any of a number of stimuli, including aging, transplantation, needle puncture, irradiation, hypertension, and some pharmaceutical drugs (10).

Subbotin postulates that following the triggering of their proliferation, perhaps by initiating stimuli yet to be fully understood, the mass of these cells increases. But a point will be reached at which this enlarged mass of cells can no longer remain viable without the addition of a dedicated blood supply 

Figure 6: Subbotin has proposed that the normal coronary artery may develop diffuse (tunica) intimal hypertrophy (DIT) in response to currently unidentified stimuli. The result is that the cells in the outer layer of the tunica intima, furthest from the arterial lumen and their source of oxygen, become oxygen-deficient (hypoxic). The consequence is that new blood cells grow into the intima (left side of bottom panel) from the vasa vasorum. Blood entering the intima then deposits LDL-cholesterol, which explains how lipids enter the deep layers of the intima as depicted in Figures 4 and 5. Reproduced from Figure 7 in reference 10.

When that happens, the deepest layers of the intima recruit the development of new blood vessels (neovascularization). These blood vessels arise from the vasa vasorum, which exist in the tissue layer outside the tunica media and normally provide blood (and oxygen) to the muscle cells in the tunica media of muscular arteries.

Subbotin hypothesizes that once these new blood vessels enter the deepest layers of the tunica intima, they bring with them LDL-cholesterol, which is then deposited in that cell layer, producing the changes depicted in Figures 4 and 5.

Importantly, there is substantial evidence that the vasa vasorum are intimately involved in the development of atherosclerosis, and “present data indicate that vasa vasorum neovascularisation and atherosclerosis are seemingly inseparably linked” (15, p. 878).

Introduction The concept that diet, serum cholesterol and cardiovascular disease are causally related and  gave rise to the diet-heart hypothesis nearly 70 years ago. This hypothesis postulates that reducing dietary saturated fat reduces serum cholesterol, thereby reducing the risk of cardiovascular disease. Today, this concept has been transformed from a hypothesis into public health policy as current guidelines recommend reducing the intake of dietary saturated fat.1 Not all practitioners agree, however, and a reappraisal of the evidence may help resolve this controversy. An abbreviated history Dr  Ancel Keys first proposed the diet-heart hypothesis in the 1950s. Several years later, he published the Seven Countries Study that reported a strong correlation between dietary fat and coronary mortality in seven countries.2 His hypothesis rapidly gained support and by 1977 the US Senate Select Committee on Nutrition and Human Needs formally recommended that Americans should reduce their consumption of total and saturated fat.3 Many scientists disagreed and a vitriolic debate soon followed.4 Presently, the American Heart Association recommends ‘lowering intake of saturated fat and replacing it with unsaturated fats, especially polyunsaturated fats’ to reduce cardiovascular disease.