Atherogenesis

The putative ability of fish oils to affect cardiovascular health has focused considerable attention on lipid nutriture. Investigations of societies consuming high levels of omega-3 and -9 oils as well as both prospective and retrospective scientific studies have demonstrated the increasing importance of dietary fats.1-6 Complex mechanisms have been theorized but ultimately hinge on eicosanoid synthesis pathways. Fatty acids and other lipid substances such as cholesterol found within the circulation and as a part of the endothelial lining of blood vessels and their smooth muscle coat, and within platelets, provide an important substrate for vascular health or disease.

PLATELETS
Platelets play a pivotal role in the relationship between lipids and atherogenesis. Blood platelets are powerful biochemical packages wrapped in a phospholipid membrane. When platelets in the circulation are exposed to broken endothelial tissue lining blood vessels and underlying collagen. they become activated to stimulate the healing of the injury.

The arachidonic acid within the platelet forms two different eicosanoids, which serve two opposing functions. If the platelet is next to another platelet, thromboxane (TXA2) is formed (500 million platelets can form as much as 2 mg of thromboxane) which stimulates the aggregation and clotting of platelets and other blood components.7 For those platelets near the endothelium, prostaglandin E2 (PGE2) is formed which stimulates hyperplasia in the exposed blood vessel tissue and inhibits further clotting adjacent to the injury. Prostaglandins also stimulate bone resorption bringing calcium to the site of the injury to decrease tissue pH and further stimulate hyperplasia.

These are normal mechanisms occurring continually and are essential to life. If they did not occur, minor vascular lesions could lead to runaway hemorrhage, and healing and repair would not happen. However, when there is an excess of omega-6 fatty acids in platelets which can generate excess amounts of arachidonic acid at blood vessel injury sites, the blood clotting, vessel constricting, bone resorbing, and hyperplastic effects can exceed the countering moderating effects of prostaglandins from fatty acids such as the omega-3's.

PATHOGENESIS
High levels of dietary fat can result in high levels of low density lipoprotein (LDL). These protein-lipid complexes can contain large amounts of cholesterol, much of which can be oxidized as a result of the way modern foods are processed.8 LDL can migrate to areas of injury, be engulfed by monocytes and macrophages, and accumulate at the site of these injuries to provide more arachidonic acid and free radical generating oxidized cholesterol fuel for further endothelium damage.

This ongoing cycle, beginning with perhaps a small lesion which occurs as a matter of course in the endothelium, or induced injury as a result of high blood levels of oxidized fats, may turn out to be a self-perpetuating, out-of-control, cancerlike growth accumulating in vessels resulting in atheromas and eventual closure of coronary vessels leading to heart attacks. Additionally, hardening (sclerosis) of the arteries can result in hypertension and loss of vascular resiliency, potentially causing stroke, aneurysms, general loss of health and vigor, and predisposition to a range of other diseases.

In other words, if there is vascular injury, the normal clotting, vessel constricting, tissue regenerating mechanisms can run out of control as a result of an imbalance of moderating e1cosanoids which are ultimately derived from dietary lipids. In tissue with excess arachidonic cascade potential, vessel injury recruits excess platelets, which stimulate excess clotting, vessel constriction and vessel wall inflammation,

[ Atherosclerosis Sequence Image ]
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which in turn releases more arachidonic cascade eicosanoids, which stimulate further platelet aggregation, clotting and so on, leading to atheroma and vessel closure.

If there is no initial endothelial injury but it is being induced from high oxidized lipid blood levels, a similar cycle occurs. Oxidized LDL's are scavenged by monocytes which become macrophages, which accumulate within the vessel wall causing free radical damage, foam cell formation, calcium deposition and inflammation. This produces arachidonic cascade metabolites, which further induce inflammation leading to progressive atheroma and vessel closure. (Fig. 26, 27)

PREVENTION RATIONALE
An alteration of the diet such that oxidized fats are decreased, saturated fats are decreased, omega-6 fats are decreased (in Western societies), and omega-3 and omega-9 rich foods are increased may potentially result in a restoration of health to the vessel wall. Prostaglandins created by omega-3 and omega-9 oils create opposite effects to the vessel constricting, clot-forming effects of the omega-6 oils since they compete for the same enzyme system. (Refer to Fig. 18) Therefore, if omega-3 and -9 fatty acids are increased in the diet, they use up the enzyme systems normally used byarachidonic acid to form the atherogenic promoting eicosanoids. This is the present explanation for the epidemiological evidence showing that humans and animals consuming higher levels of the omega-3 and omega-9 classes of fatty acids develop far less of the common cardiovascular problems than exist in Western society.

There is some evidence that the incidence of cardiovascular disease is proportional to the ratios of fatty acid classes in platelets, which is in turn related to diet. Eskimos, for example, have a higher omega-3 to omega-6 ratio in their tissues reflecting their high fish diet, which is in turn related to their low risk of cardiovascular disease compared to Western nations. (Fig. 28)

[ The Formation Of Atheroma Image ]
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This is not to say omega-6 fatty acids such as linoleic are harmful per se. Balance is key. Indeed if sufficient linoleic is not present, atherosclerosis can result as evidenced in a variety of species.9,10

ASPIRIN
By shifting the balance of these same eicosanoid enzyme systems, aspirin is also believed to exert its effect as an anticlotting agent in cardiovascular disease. Aspirin is a specific inhibitor (acetylator) of cyclooxygenase which normally is used to convert arachidonic acid into TXA2 and PGE2. Aspirin's inhibition of clot forming TXA2 is several days longer than its effect on anticoagulating and vasodilating PGE2. Thus the net effect is clot inhibition. (Refer to Fig. 19)

[ Comparative Dietary Oil/Fat Composition Image ]
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However, aspirin is a bandage. It does not address the root cause, which is dietary impropriety. It is also not without its dangers since it can precipitate allergic reactions such as asthma by shunting arachidonic acid into the lipoxygenase leukotriene path and may actually increase platelet clotting if given in conjunction with fish oils.11

Excess consumption of oxidized fats and fatty acids of the omega-6 family will fuel the atherosclerotic system. Excess raw materials can exceed the ability of moderators. If the root cause is dietary, the ultimate solution must therefore also be dietary, not pharmacologic. It is ironic that the 80 million aspirin tablets taken daily by Americans may in large part be necessary to cancel the effects of 15 million pounds of omega-6-predominant processed polyunsaturated oils.

NUTRIENTS
Many nutrients found within foods have the ability to block or modulate prostaglandin synthesis. These include sulfur compounds found in garlic, onions and cruciferous vegetables, and various minerals, particularly the divalent cations zinc, copper, lithium, silver, selenium, and calcium.12 A variety of fresh whole foods, (raw if possible) grown on nutrient-rich soils (as opposed to modern agribusiness mined soils where only nitrogen, phosphorus and potassium -- NPK fertilizers -- are replaced) provides the body with raw materials which augment proper fatty acid nutrition and may lessen or obviate the need for potentially dangerous drugs.

Other nonpharmacologic factors which may help produce more "friendly" lipid profiles include decreased stress, increased exercise and the elimination of tobacco and perhaps caffeine.13 Highly refined carbohydrate and sugar diets increase cardiovascular disease risk perhaps through increased glycosylation reactions, increased lipoprotein (a) levels and decreasing HDL levels.14 Calcium at 800 mg per day can decrease cholestero1.15 Chromium deficiency can decrease glucose tolerance factor and thus affect sugar metabolism and adversely affect lipid proflies.16Legumes, soluble fiber, garlic and onions can decrease cholesterol levels.17 Vitamin C at 1000 mg per day and vitamin E at 200-400 I.U. per day are excellent antioxidants and can decrease glycosylation reactions, decrease cholesterol and increase HDL'S.18 Pantethine, a derivative of pantothenic acid at 300 mg. 3-4 times daily,19 and niacin from 1-4 grams daily can positively affect lipids. Niacin in fact is one of the few agents capable of lowering genetically controlled Lp(a) levels.20 L-carnitine, an amino acid, at 1000 mg per day can ameliorate hyperlipoproteinemia.21

These nutrients are supplied in a varied whole raw food diet. Some researchers argue, however, that therapeutic levels of some nutrients are not possible from simply consuming natural foods. An accumulated deficit from a lifetime of dietary indiscretion may indeed require a boost. Disease, an extraordinary event, may require extraordinary measures to effect a cure. But before consuming any isolated nutrient become well aware of its merits and demerits since some nutrients can present toxicities or imbalances at certain levels. Guidance by a well qualified nutritional health care professional would be advised for anyone with existing disease who desires to use isolated nutrients in therapy.

As mentioned in the previous chapter, the case for the link between diet and heart disease is not closed. Some argue that the diet-heart hypothesis began, remains, and grows because of the support of powerful institutions and personalities who subserve gigantic health-disease and food industries.22 Some have calculated that for persons aged 20-62 that a lifelong program of cholesterol reduction might increase life expectancy three days to thirty months.23 Even Sir William Osler, the most highly respected physician of his time, said in 1879 that arterial degeneration could occur even at a young age and was due to "the high pressure in which men live, and habit of working the machine to its maximum capacity," not to excesses in eating and drinking. 24

There is little doubt that singular focus on diet or exercise, for example, misses the mark. It ignores equally important factors such as self esteem, affectionate relationships and feeling in control of one's life.25 The controversy aside, living and eating in a more natural synergonic context can only help and is likely the greatest potential for life free from disease.

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