This webpage is an excerpt from my book, Cardiovascular Efficiency vs Nutritional Deficiency, available through the International Foundation for Health and Nutrition in San Diego, California (858)-488-2533. While it is rather technical, the caliber of my patients seems to demand some proof in the pudding. It is not complete by any means, but I think it will give you a broader understanding of this mis-understood topic…
Nearly every discussion of cardiovascular health includes the cholesterol status, but it is equally important to also consider triglycerides, triglyceride:HDL ratios, thyroid function, insulin, lipid peroxides, fibrinogen, lipoprotein (a) levels, uric acid levels, iron studies, plasma homocysteine, calcium:phosphorus ratios, testosterone level, etc. All of these biochemicals are related to cardiovascular disease either as markers of another underlying disturbance or along the same pathways of cholesterol metabolism.
Cholesterol is hard and waxy and either ingested or manufactured from the breakdown of sugars, fats, or proteins.
The concern about cholesterol was largely fueled by the Framingham Study and others that provided strong evidence that when large populations are observed, persons with higher than average serum total cholesterol have a higher incidence of coronary artery disease (CAD). The Framingham Study was an epidemiological study and not an investigation ofcause and effect, it merely reported the association between total serum cholesterol levels and CAD. Isadore Rosenfeld, M.D. used a great analogy with fever and pneumonia. When you have pneumonia your temperature goes up; but the fever doesn’t cause the pneumonia, and lowering it won’t cure the infection. The actual cause of CAD is thought to be initiated when there is an injury to the arterial wall, which results in calcium deposition into the arterial wall. Bacteria or other infectious agents are being looked at as part of the culprits as causative factors in initiating injury to the arterial wall. Cholesterol is then attracted to this ‘rough’ site on the blood vessel wall in an attempt to heal the wall so that blood will flow smoothly over the injured area. No research has ever shown cholesterol building up on a healthy blood vessel and slowly clogging it just as a sewage pipe might over time. Cholesterol itself is not the cause of CAD. The blood cholesterol is rather only a reflection of other metabolic imbalances in the vast majority of cases. (There are genetichyperlipoproteinemias in which excessive cholesterol is considered the primary factor). This has been the observation inSouthern Europe where elevated cholesterol levels do not correlate at all with coronary artery disease. This phenomenon can be explained in part by understanding that there are several types of cholesterol. To be precise we should use the term cholesterols when we are speaking generically about total cholesterol.
In contrast to large population studies, the majority of heart attacks do not occur in high-risk individuals based on their total serum cholesterol (D. Mark Hegsted, Ph.D. Professor of Nutrition Emeritus at Harvard). In a World Health Organization report, in the U.S., about one half of heart attacks occur in individuals with serum cholesterol below 240 mg%. Dr. William Taylor of Harvard further points out that “for many people with cholesterol levels elevated into the high risk range, cholesterol reduction by itself only adds on the average of about three weeks to total life span.” Of course, Dr. Taylor is only talking about using a medication or a dietary program designed primarily to adjust the cholesterol level, and not the underlying mechanism that raised the cholesterol in the first place.
Laboratory reports often mention two main types of cholesterol, the HDL cholesterol (often termed the “good” cholesterol) and LDL cholesterol (often mis-named the “bad” one. A more precise term would be “susceptible” cholesterol). A third cholesterol type is also mentioned, the VLDL, which we will not mention again. Let’s focus on the “bad” cholesterol, the LDL cholesterol, which is composed of two general sub-types; a large LDL and a smaller, denser LDL. Even if the total LDL is lowered, the important fraction is actually the small LDL, which is more easily oxidized into a potentially atherogenic particle than its larger, more buoyant counterpart. “Statins” were ineffective in reducing the small LDL particles according to Art Charles, M.D. at the University of California at Irvine in his work involving Insulin-dependent diabetics. Unfortunately, determining the size distribution of LDL is not readily available, and thus checking the total LDL levels is only half the story.
Most everyone agrees that a markedly elevated LDL cholesterol and total cholesterol should be lowered and a low HDL should be raised. Although the present class of medications called “statins” (Baycol ®, Lescol ®, Lipitor®, Mevacor®,Pravachol®, Zocor®, etc) does lower cholesterol and LDL, they do so by inhibiting the enzyme that participates in the synthesis of cholesterol, HMG-CoA reductase. This enzyme also participates in the production of coenzyme Q10. Coenzyme Q10 is critical in energy production. Of course, energy production is what life is all about. HMG-CoAreductase inhibitors have also been associated with carcinogenicity, liver toxicity, stomach ulcers, and breakdown of muscle. It should be noted that the active ingredient in Mevacor is also found in a commonly used red rice yeast fromChina that has been sold over-the-counter as a natural alternative for high cholesterol. For this reason, herbal remedies should be used with the same respect and caution as pharmaceutical agents.
Recently, there have been preliminary observations that one the components in Mevacor and Zocor have anti-cancer effects in certain types of tumors. The data suggests that it is a metabolite in these drugs that is the active component in this regard. Further studies are necessary to determine if these effects are clinically relevant and even related to the cholesterol-lowering activity. It is important to recall one of the major functions of LDL cholesterol, that is transport fatty acids into your cells. Anything that reduces fatty acid levels in the cell membranes has the potential to reduce cellular aerobic metabolism (see my webpage on cancer!). Could it be that if you eat healthfully with adequate amounts of essential fatty acids that the statins actually promote cancer while the individual who eats poorly by consuming trans-fatty acids (partially hydrogenated) is protected from cancer because these anaerobic-promoting fats are not delivered to the cell? Nevertheless, there a several peer-reviewed studies showing a significant increase in cancer incidence in subjects using statins. Most studies showing the increase were longer term studies as would be expected for carcinogenesis to be evident.
Another class of cholesterol-reducing agents, sometimes called the “fibrates” (Atromid-S® and Tricor® are current examples) are also used but have toxic effects on the liver. These to seem to have some proclivity to increase cancer incidence as well.
In a provocative article in Circulation (Aug 1997), rabbits were fed a diet that is known to produce atherosclerosis. In addition, the rabbits were given either extra L-arginine (an amino acid) or Mevacor (one of the statin drugs). Several of the results and conclusions were surprising. Carotid blood vessel plaquing was blocked in the group with additional L-Arginine but not by Mevacor. Aortic thickening was reduced by L-Arginine better than Mevacor. In addition,superoxide radical generation in the atherosclerotic wall was reduced with L-Arginine and increased with Mevacor. When L-arginine is infused directly into the coronary arteries, endothelium dependent vasodilation of the coronary microcirculation occurs indicating a rapid and direct effect (Circulation 1996;94(2):130-4). In other words, L-arginine seemed to be more effective than Mevacor not only in reducing the production of atherosclerosis, but also helped the smaller blood vessels.
If we assume blood lipid (fats) status are associated with some risk of cardiovascular disease. The question is which lipids are the important markers, and even more important what should we do about them. In an 18 year follow-up of 740 patients, the risk factors for having a CAD event were diabetes mellitus, triglycerides >100mg%, and HDL Cholesterol <35mg%. In fact, there was a significant reduction in survival from CAD events when the triglycerides level was>100mg%. Total cholesterol and LDL didn’t even show a statistically significant relationship (J American College Card; May 1998)! Another study published in Circulation (October 1997) compared triglycerides (TG), TG:HDL ratios, cholesterol ratios, and LDL:HDL ratios for the association with heart disease in 680 adults. By far the most important association was the TG:HDL ratio. At the XIV International Symposium on Atherosclerosis (ISA 2006), evidence was presented from clinical trials that assessing the levels of apolipoprotein (apo) B, a constituent of atherogenic lipoproteins; apo A-I, a component of antiatherogenic high-density lipoprotein (HDL) cholesterol; and the apo B/A-I ratio provides better prediction of future cardiovascular events than measuring serum low-density lipoprotein (LDL)-cholesterol levels. In 2004, the global INTERHEART study (Lancet 2004; 364:937-52) of risk factors for acute myocardial infarction (MI) in 52 countries concluded that “the apo B/A-I ratio was the most important risk factor in all geographic regions.” In addition data from the long-term follow-up of a prospective trial and analyses of major clinical trials of lipid-lowering therapy show that the predictive power of the apo B/A-I ratio is superior to, and cannot be improved by adding, any other lipid parameter or ratio. In another study published by Arteriosclerosis, Thrombosis, and Vascular Biology. 2006 (26:406-10), the apo AI /B ratio was related to the Metabolic Syndrome (discussed elsewhere), as well as to a direct measurement of insulin resistance.
Taking a closer look at triglycerides, the common reported causes of elevated triglycerides are: familial, obesity, physical inactivity, insulin excess/resistance (Diabetes mellitus; inactivity; excess fats, sugar, alcohol, and calories), drugs (ß-blockers, corticosteroids, estrogens, thiazide diuretics, etc.), liver dysfunction (alcohol, viral hepatitis, endotoxins, etc.), toxic exposures (heavy metals, chlorinated hydrocarbons), and omega-3 fatty acid deficiency. One would assume that exercise, eating less carbohydrates and avoiding excesses of any foods, and ensuring that you have an adequate amount of the proper oils should lower the triglyceride to a healthier level. The omega-3 fatty acids are usually derived from fish…
As with all things in life, there must be balance. Lowering cholesterol too aggressively (usually will ONLY occur with synthetically derived therapies, extremely imbalanced diets, or in artificial circumstances) or having too low a total cholesterol is also undesirable. In fact, as you may come to agree, elevated cholesterol is the lesser of the evils compared with a low cholesterol level. The connection of low cholesterol to cancer was first recognized in 1971 by Pearce andDayton when they observed that a diet high in poly-unsaturated fats was associated with a cholesterol lowering effect and an offsetting rise in cancer (Lancet 1971;464-7)! Ibrahim and McNamara showed that the PUFA did not lower cholesterol production or increase its secretion, but rather caused cholesterol to accumulate in the tissue and thus appear reduced in the blood (Biochem et Biophys Acta 1988;963:109-18). Using data from 6 different studies from all over the world, the total cholesterol level that correlated with an increase in cancer prevalence is below 190 mg% and an even higher risk when below 160mg%. The cancers found were lung, colon (in non-smokers), breast (beyond radiographic mammary dysplasia), prostate, and leukemia. (i.e. Nathan Pritikin). There is an increase in mental illness inversely related to cholesterol levels as well. There was a protective effect for cancer mortality with cholesterol of greater than 240mg%. The studies suggest an optimal range of cholesterol is 180-239mg%. This is a range of 60 mg/dl. One might attempt to get into the lower end of this range with heart disease patients and the higher end with cancer patients.
Levels < 180 mg/dl are associated with a
The conclusion from a study published in the American Geriatrics Society (2005; 53: 219) was that low cholesterol level is a robust predictor of mortality in the nondemented elderly and may be a surrogate of frailty or subclinical disease. After the age of 50, the lower your cholesterol level is, the lower your life expectancy. Ways to lower cholesterol are important to recognize, but more importantly, why the cholesterol is elevated and how to address the underlying cause must be considered. Here are some rather technical thoughts on how to balance cholesterol metabolism.
Rather than simply treat the lab numbers, when confronted with an elevated cholesterol or LDL cholesterol level, your investigation must begin with “why?” J. Yudkin et al (Brit Med J 1980; 281:1396) demonstrated that increased sucroseintake significantly decreases HDL cholesterol, and Reiser et al (Am J Clin Nutr 1979; 32:1659) showed an increase in dietary sucrose increases total serum cholesterol. Using fructose instead of sugar, as is the fad among food and health food marketers trying to exploit the misconception that fruit sugar is better than other forms of sugars, was shown byReiser (Science News 3/28/1988; 133: 196) to elevate LDL, cholesterol, triglycerides, and uric acid. After 5 weeks of a diet with 20% of total calories from fructose, the cholesterol increased 11% and the triglycerides jumped 56%. The national average consumption of fructose at the time of study was 10%. The percentage is probably higher now with the large push by marketers and the availability of high fructose corn syrup and white grape juice. The excess of dietary carbohydrates contributes to elevated cholesterol levels due in large part by the influence of insulin. In fact, when all the data is considered, the strongest evidence implicating dietary influences on elevated cholesterol levels involves refined carbohydrates. In your mind, refined carbohydrates should equate to any “processed or simple” carbohydrate ranging from white flour to white table sugar. The reason for this is explained by A. Guyton in his Textbook of Medical Physiology, “When the quantity of glucose entering the liver cells is more than can be stored as glycogen or can be used for local hepatocyte metabolism, insulin promotes the conversion of all this excess glucose into fatty acids. These fatty acids are subsequently packaged as triglycerides in very-low density lipoproteins and transported in that form by way of the blood to the adipose tissue and deposited as fat.”
The sugar issue is not that clear cut, however. Cardiovascular mortality rates are twice as high in patients showing reduced glucose tolerance (Lancet 1980; 1:1973-6) and 2 – 6 times higher in overt diabetics (Adv Metab Disorder 1970 [suppl]; 1:395). Sugar intake alone may not be the only culprit. The inability to manage glucose (either eaten or produced by the body) also is relevant.
Cholesterol can only be ingested from animal sources such as eggs, meat, dairy products, fish, and shellfish. Plants do not contain cholesterol. It is estimated that half of cholesterol eaten enters the body while the other half passes through. Normally, the more cholesterol we absorb, the less our bodies make (Lehninger’s Biochemistry). According to Guyton’sTextbook of Medical Physiology, “An increase in the amount of cholesterol ingested each day increases the plasma concentration of slightly. However, when cholesterol is ingested, the rising concentration of cholesterol inhibits the most essential enzyme for endogenous synthesis of cholesterol, 3-hydroxy-3-methylglutaryl CoA reductase, thus providing an intrinsic feedback control system to prevent an excessive increase in plasma cholesterol concentration. As a result, plasma cholesterol concentration usually is not changed upward or downward more than ± 15 percent by altering the amount of cholesterol in the diet, although the response of individuals differs markedly.”
To understand how to manage cholesterol better, it is important to realize cholesterol is made from small 2-carbon fragments called acetates hooked end to end. Through multiple steps the 27-carbon molecule of cholesterol is formed. How the process occurs is complex and the important question is where do the 2-carbon acetate fragments come from, and what promotes their linkage together to form cholesterol? When fatty acids are broken down for energy, they are broken down into acetate fragments. When sugars and starches are broken down for energy, they produce acetate. Proteins are generally broken down into amino acids, but with extreme protein consumption or during certain disease states, certain proteins can be broken down into acetate. Excess acetates can come from eating too many non-essential fatty acids, trans-fatty acids, and saturated fats, and refined carbohydrates (via insulin and other agents). This “pressures” the body to form cholesterol. In other words, cholesterol is formed from excess calories – most often this is from carbohydrates and fats.
Be sure not to make the common error of considering all saturated and all unsaturated fats as having equal properties. As you will see from the discussion below, the structure of unsaturated fats have a profound influence on their biological effect. With regard to the saturated fats, which are fats that do not contain any double bonds, there are three important considerations. The first is the length of their carbon backbone, the second is if they have been artificially desaturatedthrough a process called hydrogenation, and the third is what components are associated with the fat. Length: fatty acids with short chains (SCFA) have between 4 – 14 carbon atoms in length) and are the principal source of energy for the colon. They are easily absorbed into the colonic mucosa and affect nutrient absorption and digestion, which in turn impacts the cardiovascular system. One food with a high amount of SCFAs is butter. Fatty acids with a medium chain (MCT) are easily absorbed and provide an important energy source. One study shows combining coconut MCTs with omega-3 fish oils enhanced the cardioprotective effect of the omega-3 fatty acids. This study supports the observations made over and over again about the importance of the fact that saturated fat intake is essential for normal hormone production.
In a study of individuals older than 84 years, the consumption of nuts 5 times per week had a relative risk of death from cardiovascular disease of 82% compared to those that did not consume nuts (Arch Inter Med 1997;157:2249-58). In a study published in JAMA (1997;278:2145-50), there was an inverse association of strokes in men with dietary fat intake. In other words, a low fat intake was associated with a greater risk of ischemic stroke. Lowering dietary fat to 30% reduced LDL, but lowering dietary fat to <22% increased triglycerides and lowered HDL. None of the low fat diets was associated with low body weight, blood sugar, insulin, or blood pressure.
Dietary omega-3 fatty acid intake (1.5 grams/day) for two years was shown to “modestly mitigate” the course of coronary atherosclerosis in 223 patients with angiographically proven coronary heart disease (Annals of Internal Medicine 1999;130:554-62).
Peroxidation of lipids occurs when unsaturated fats are exposed to oxygen and/or light; it is responsible not only for the deterioration of fat (rancidity) but also for damaging tissue. This process may play a prominent role in promoting cancer, atherosclerosis, inflammatory diseases, autism, Parkinson’s disease, and aging. Lipid peroxidation occurs only at unsaturated double bond sites and results in a continuous supply of free radicals that can initiate further peroxidation. To control this effect, food manufacturers use antioxidants such as synthetic propyl gallate, butylated hydroxytoluene(BHT), and butylated hydroxyanisole (BHA) as food additives since they are strong antioxidants. Because quality essential fatty acids are so fragile and yet absolutely necessary, polyunsaturated oils should be purchased in small quantities, kept cool and in the dark, and used rapidly to prevent lipid peroxidation. Keeping the container in the refrigerator, tightly capped, in a light-proof container, and with added natural vitamin E helps. Many natural whole foods containing antioxidants such as red grapes are being exploited for this property. Supplementing with whole complex E (which is naturally complexed with selenium) helps combat peroxidation.
Hydrogenation, a process introduced in large scale in the 1930’s for making margarine and shortening, alters fatty acids to make them more resistant to lipid peroxidation. In this process, an oil with unsaturated fatty acids in their natural, allcis configuration, are reacted at high temperatures and under pressure with hydrogen gas in the presence of a metal catalyst (typically nickel). Hydrogenation saturates the double bonds (it puts a hydrogen atom where there was a reactive open site) so the fatty acid becomes saturated, hardens, and becomes more resistant to lipid peroxidation. Hydrogenated oil makes potato chips crisp and have a longer shelf life. Unfortunately, the consumer ends up with fats and oils that are the nutritional equivalent of other refined products — demineralized, devitaminized, fiberless, empty calories which cannot be properly digested or metabolized, and rob the body of essential nutrients in doing so.
Partial hydrogenation occurs when the above process is not brought to completion, leaving fatty acids with a few unsaturated double bonds. However, partial hydrogenation forms both trans and cis double bonds (saturated fats do not have cis and trans configurations), shifted double bonds, fragments, etc. The process is random and so no one really knows all of the resulting products. The reason processors partially hydrogenate unsaturated oils is to prolong shelf life and keep partial liquidity of the fat. Read the label on baked crackers, salad dressings, mayonnaise, hot chocolate, cereals, breakfast bars, snacks, etc. and you’ll see the extent these oils are now used.
Trans fatty acids are produced when an unsaturated fatty acid is exposed to high temperatures (which is why to preserve the natural cis configuration, cold-pressing of the vegetable oils are recommended). The slight difference in the structure between a trans and cis bond has a dramatic effect on the shape and function of the fatty acid. In nature, whether in animals or in plants, the carbons on either side of the double bond are in the cis conformation that results in a bend in the fatty acid chain. On the other hand, the trans conformation results is a straighter and more elongated fatty acid chain that can align closer together with other fatty acids, and therefore is more solid and more sticky, which encourages deposition into arteries, organs, and platelets. (Saturated fats are even stickier). For the same reasons, trans fatty acids also get in the way of cis fatty acid interactions with enzymes and with the function and permeability of cell membranes (saturated fatty acids do not). Trans fatty acids are useful only to the body as energy-creating fuel and are broken down at a slower rate than cis fatty acids. Since trans fatty acids are more stable than cis double bonds, the chance of being converted into the more desirable cis configuration is unlikely. The main dietary source of trans fatty acids is from partial hydrogenation. Read a few labels from cereals, crackers, chips, snacks, instant hot chocolate, salad dressing, etc. to see just how much partially hydrogenated oil the average American consumes without suspecting it. There are no known natural trans fatty acids. From the same study that showed nuts reduce cardiovascular deaths to 82%, the regular consumption of donuts not only increased the mortality from coronary heart disease 210% but also death from any cause 140% compared to those that did not consume donuts regularly (Arch Intern Med 1997;157:2249-58).
From JAMA (Dec 24, 1997), 832 men were followed for up to 20 years. Those with a low fat and/or a low saturated fat intake had a much higher incidence of stroke events. With higher and lower polyunsaturated fat intake the effect was not as significant. The lesson here is that low fat is detrimental which is not to say that high fat diets are necessarily beneficial.
Trans fatty acids can increase cholesterol and triglyceride levels. In a study done at Harvard on 85,000 nurses, there was a 50% greater incidence of heart disease among those women consuming the most trans fatty acids compared to those consuming the least. The researchers concluded that “consumption of partially hydrogenated vegetable oil may contribute to the occurrence of heart disease.” (Willett Lancet 1993) Recently the medical literature has been more vocal about their concern over margarines, trans-fatty acids, partial hydrogenation, etc.
Another critical component of lipid metabolism warranting discussion is that of eicosanoids popularized by Barry Sears, Ph.D. in his book, The Zone. Emmanuel Revici, M.D. provided the early conceptual model for this entire field of fat metabolism. Eicosanoids are a group of powerful chemical mediators that are derived from essential fatty acids and control virtually every aspect of metabolism and physiology. Prostaglandins, leukotrienes, and thromboxanes are among the better described eicosanoids. As in most biological systems, there is a balance among opposing eicosanoids — the series 1 pathway components (generally associated with beneficial activities) and the series 2 pathway components (generally associated with less desirable activities such as inflammation). The biochemistry of those factors that favor the series 1 eicosanoids over the series 2 eicosanoids have focused on the role of a critical enzyme that directs fats down the series 2 pathway — the delta 5 desaturase enzyme. The enzyme is activated by insulin and therefore excessive carbohydrates or carbohydrates with a high glycemic index, aging, stress, viral infection, saturated fats, alcohol, and deficiencies of vitamins and minerals. Strategies for controlling eicosanoids into a favorable balance, called “The Zone,” is the subject of Dr. Sears book and another excellent text, Protein Power, by Michael Eades, M.D.
Any discussion of fats cannot be complete without including carbohydrates, since sugars and starches can be converted into fats. Refined carbohydrates such as table sugar, fructose, syrups, puffed cereal grains, processed flours, and honey provide an excellent source of energy, but if there is no activity or exercise requiring this energy, then the body has an excess supply of glucose. The capacity to rapidly raise blood sugar is called the glycemic index. Normally, the body responds to high levels of glucose by stimulating the pancreas to secrete insulin, which stimulates the metabolism of glucose into fats for storage in fat tissue or in various organs. The fatty acids produced from glucose metabolism are saturated and therefore can only serve as fuel. In addition, high blood sugar inhibits the release of the essential fatty acid, linoleic acid, from storage fat. This could exacerbate essential fatty acid (EFA) deficiency despite having adequate stores of EFA. Complex unprocessed starches, in contrast to refined sugars, are not as rapidly absorbed and do not cause as dramatic a rise in glucose, the excess glucose. The glucose is absorbed slowly and thus provides a relatively lower, and more prolonged level of blood glucose energy; hence, a lower glycemic index. It is no surprise that a Denmark study showed that “fasting serum insulin level is a very good predictor of the development of CHD and CVD…”
According to an article in the Journal of Cardiovascular Risk, June 1995, “All dietary carbohydrates increase insulin levels. Excess carbohydrates cause elevated insulin levels…”
Angina can be induced by hypoglycemia (Am Heart J 1943;26(2):147-163)
Insulin promotes delta-5 desaturase activity lead to increased pro-inflammatory eicosanoid production. Impaired sugar metabolism stimulates adrenal exhaustion through blood sugar feedback attempts to increase blood sugar lead to excess potassium, menopause & andropause, etc.
Vegetables in general lower insulin. Mung beans and other legumes (soybeans), Bitter gourd (Momordica charantia), Ivy gourd (Coccinia indica), Brassica (cabbage, broccoli, cauliflower), green leafy vegetables, omega-3 fatty acids (fish oils), anti-oxidants (vitamin E), alpha-lipoic acid, possibly L-arginine (via NO pathway), chromium/glucose tolerance factors, vanadium, and inositols (d-chiro inositol is important in the construction of membrane proteoglycans that maintain insulin sensitivity).
Syndrome X is defined as “insulin resistance + hyperinsulinemia” usually accompanied by elevated lipids, body weight, and blood pressure. The result is reduced cellular glucose transport. Insulin affects gene expression by altering transcription factors that affect triglyceride and cholesterol synthesis and degradation, inflammatory cytokine release, shunting of estrogen to testosterone in women (PCO). Hyperinsulinism contributes to atherosclerosis, hypertension, hyperlipidemia, obesity, and diabetes.
Low blood sugar levels lead to thyroid, anterior pituitary, adrenal cortex, and sex hormones release. High blood sugar levels lead to insulin, posterior pituitary, and sex hormone release.
As a result of the Page Food Plan (dominated by protein and vegetables), which is found under my web pages for food programs, the avoidance of sugar based on the reasons above, one will quickly realize that the intake of protein necessarily goes up. This has raised concerns about over-consumption of protein and its effect on osteoporosis, etc. The British Medical Journal (October 1997) included a study of 3600 Britons over a seven-year period. The results show no correlation between meat consumption and cancer. Fresh fruits and vegetables intake as expected had a protective effect. The other concern with increased protein intake has been with promoting osteoporosis due to the systemic acidification that results from protein metabolism. The fact is that the Framingham Osteoporosis Study carried out over a four year period found that individuals with the lowest protein intake had increased rates of bone loss compared to those with higher intakes. In this study, the women who had the highest percentage protein intake had no bone loss at all during the study period. Another study in Switzerland showed the same findings – higher protein intake was associated with greater bone density. A Chinese study of elderly females found lower bone mineral densities in vegetarians than in omnivores. There was no difference between the lactovegetarians and the vegetarians with regard to bone mineral density. Concern over consistent protein intake as recommended by Page contradicts these observations.
OTHER FACTORS INVOLVED IN CHOLESTEROL AND LIPID METABOLISM
Steroid hormones play an important role in cholesterol metabolism. After all, cholesterol is a precursor to steroid hormones, including progesterone, cortisol, estrogen, and testosterone. In Denmark, testosterone has been used as a cholesterol-lowering agent for decades. They report the average reduction in serum cholesterol after testosterone initiation in males is about 25%. A 1972 World Health Organization (WHO) symposium also provided evidence that testosterone had cholesterol-lowering effects as well as increased clot dissolution, and reduced the adhesiveness of platelets (by reducing the amount of the pro-aggregation effect of ADP). Testosterone also induced suppression of lipoprotein (a) levels (Marcovina SM in Atherosclerosis 1996; 122: 89-95). These are all traditional parameters of heart disease risk. Confirming the association between testosterone and heart disease, Gerald Phillips, M.D. at ColumbiaUniversity Medical School, showed that men with the lower levels of testosterone had greater x-ray evidence of coronary artery blockage. Maurice A. Lesser, M.D. injected testosterone to 100 patients during an angina attack with “moderate to marked” improvement in 91%.
Testosterone shifts metabolism from an anaerobic state to an aerobic one by increasing the activity of enzymes in the Krebs cycle, which increases the level of ATP relative to ADP, which affords the changes mentioned above as well as a variety of other metabolic effects. Testosterone also balances glucose homeostasis by antagonizing glucocorticoids and insulin. It has also been shown “to have a direct effect on reducing blood sugar,” in addition to lowering the insulin requirements of diabetics and improving insulin resistance (J New Drugs 1965; 5: 108-224). Testosterone therapy has been useful for a variety of degenerative conditions. Clearly, the notion that testosterone is merely a sex hormone is to discount the profound effects it has on metabolism – rather it should be considered an anabolic steroid in both males and females. Testosterone also stimulates protein synthesis and decreases protein breakdown leading to improved nitrogen balance. Some common clinical findings with testosterone insufficiency are fatigue, reduced muscle energy, decreased secondary sex characteristics, reduced temperature, reduced blood pressure, cold sweaty hands, frequent/excessive urination, anemia, and compensatory prostatic hypertrophy. The blood chemistry may show low phosphorus.
Another factor involved in the balancing role of testosterone is its relationship to saturated fat intake. In a study done inFinland, a diet containing only 25% saturated fat decreased testosterone levels by 15%. The same effect occurred when the ratio of polyunsaturated fats was increased compared to saturated fats.
“Observational studies have consistently shown that estrogen replacement therapy (ERT) is associated with lower overall mortality rates. The effects on deaths due to coronary artery disease (CHD) are striking: a pooled relative risk (RR) of 63%…” (Arch Intern Med 1997;157: 2181-7). However, women who use estrogen were more likely to have healthy habits and characteristics such as not smoking, less overweight, etc. Again, the cause and effect remains uncertain. According to Joseph Collin’s 1999 book on endocrine function, estrogen has powerful anti-oxidant effects.
Estrogen has several other effects related to cardiovascular efficiency including lowering LDL levels, increasing HDL levels, decreasing Lp(a) levels, affecting endothelin-1, decreasing homocysteine levels and enhancing the effects of B-6, B-12, and folic acid supplementation, decreasing the risk of hyperinsulinemia, and possibly lowering fibrinogen levels and platelet aggregation.
Conventional care for those women with a uterus and who take estrogen in any form, progesterone are considered mandatory to offset estrogen’s uterine cancer-promoting effects. The most commonly used form of progesterone is thesynthetic derivative, methoxyprogesterone (MPA for short), Provera®. Unfortunately, a study published in March 1997 Nature Medicine showed that “moderate levels of MPA interfere with the protective effects of estradiol (E2) against coronary reactivity and vasospasm…” This is not to say that progesterone itself is detrimental. This distinction between natural progesterone and synthetic progestins like Provera can not be overemphasized.
Excess cortisol, on the other hand, not only raises blood lipids and cholesterol, but also promotes the breakdown of protein. Tissue damage, high blood sugar, sympathetic overflow, psychosocial stress leads to ACTH secretion from the anterior pituitary and subsequent cortisol release from the adrenal cortex. Testosterone counteracts this effect and normalizes carbohydrate metabolism with reported marked improvement in pathological glucose tolerance. Confirmation of this effect was recently published by IR Reid in Osteoporosis International (1996;6(suppl 1):274) in 15 asthmatic men receiving long-term oral steroid therapy. Bone density and muscle mass increased while body fat declined. Testosterone also improves circulation with many reports of healing of gangrene, etc. Since cardiac output is the ultimate determination of workload capability of the heart (i.e. the primary marker of health), it is worth understanding how the adult improves cardiac output when the demand arises. We know cardiac output = stroke volume ´ heart rate. It is a fact that, after the age of thirty, the maximal cardiac output declines. The primary way the body stimulates greater output is to increase the heart rate through an increase in the production of catecholamines. Testosterone tempers the metabolic effect of increased catecholamines as well. Goodman and Gillman’s The Pharmacologic Basis of Therapeutics (1980) reported “large or repeated doses of catecholamines given to experimental animals lead to damage to arterial wall and myocardium so severe as to cause the appearance of necrotic areas indistinguishable in the heart from myocardial infarcts.” This tells us that atherosclerosis (and cholesterol) alone must be appreciated for a rational approach to prevention and management of heart disease. A high level of stress with greater overall production of catecholamines and cortisol then must be offset by the balancing effect of other hormones, of which testosterone is included. One could put this in context of Revici’s dualism — the battle and balance between insufficient oxidation and excessive oxidation. For our patients with cortisol excess, either due to stress or medication, should we provide testosterone? Perhaps this is why tranquilizing products such as Min-Chex (Standard Process) that combine the minerals known to balance to autonomics (catecholamines) with a source for testosterone production to balance the hormones (cortisol) are so effective.
Another adrenal hormone is DHEA, which can be useful addition in select individuals. I would not recommend using it, however, without appropriate medical guidance.
At the meeting of the American College for the Advancement of Medicine in October 1997, a speaker reported that a persistently low HDL suggested pituitary hypo-function. Other lab findings include an increase in total cholesterol, low thyroid function tests, and a high fibrinogen. At the 1996 American Academy of Anti-Aging Medicine seminar in Las Vegas, Dr. Bengt-Ake reported that deficiency of growth hormone is apparently associated with an increase in atherosclerosis and cardiovascular mortality. Growth hormone has been considered an insulin antagonist. Adult growth hormone deficiency may be characterized by sagging cheeks, deep and large wrinkles, thin hair, lips, jaw bones, and skin, pseudogynecomastia, an obese floppy belly, general muscle loss, fatigue, somnolence, lack of self-assurance and esteem, anxiety, and low sociability. A mixture of arginine, lysine, ornithine, and glutamine can be used to induce growth hormone release. A variety of nutritional products have been developed claiming to stimulate the pituitary to release growth hormone. Other stimulators of growth hormone include hypoglycemia, exercise, sleep, estrogen,glucagon, and stress. Growth hormone itself, albeit in minute amounts, can be purchased over-the-counter while recombinant growth hormone is available through physicians as an injectable.
Insulin-like Growth Factor-1 (IGF-1) is a derived from metabolism of Growth Hormone in the liver. Effective Growth Hormone therapy elevates IGF-1 and IGF-1 itself has been shown to decrease insulin levels, increase stroke volume, reduce vascular resistance, and lower the filling pressures of the right and left heart.
In continuing our discussion of hormones, thyroid hormones play a major role in cholesterol metabolism and in atherosclerosis. Advocates of thyroid hormone use report over 50 percent of Americans have low thyroid function, and thyroid hormone levels within the normal range do not exclude a functional deficiency/insufficiency. Gubner and Lange showed hypothyroidism was associated with increased permeability of arteries and less strength of capillaries. A significant percentage of individuals with hypothyroidism have elevated cholesterol. In a study of 279 women, 12% with cholesterol >240mg% had an elevated TSH (Amer J Med; June 1998).
From Melvin Page, DDS and other endocrinologists, it is known that blood calcium, phosphorus, and cholesterol levels are controlled by the thyroid. With low thyroid function, a relatively high calcium, low phosphorus and high cholesterol is found. With elevated thyroid function, a relatively low calcium, high phosphorus and low cholesterol is found. Of course there are other influences on these levels beside thyroid, but with thyroid replacement, one should be able to predict the resultant changes in calcium, phosphorus, and cholesterol. The balance between calcium and phosphorus is among the most important markers of biochemical homeostasis ever identified. For further discussion, see later text.
Because there is much confusion about thyroid hormone replacement or glandular support, a brief review of thyroid metabolism is warranted. The thyroid gland secretes thyroxine (T4) and a small amount of tri-iodothyronine (T3). About 30% of T4 is de-iodinated to T3 and 40% de-iodinated to reverse-T3 (rT3) in the periphery. Both T4 and T3 are metabolized in the liver by glucuronidation and sulfation. References state that T3 is about three times* as active as T4on target tissues and is the principal regulator of thyroid action within the pituitary; rT3 has no activity. (*There are some reports that T3 has nine times the activity of T4). Dopamine and glucocorticoids reduce the pituitary’s stimulus to secrete Thyroid Stimulating Hormone (TSH). It has been reported that an excess of polyunsaturated oils, cabbage, soy foods, and improperly prepared nuts and lentils, and beta-carotene suppress thyroid function. Consider liver dysfunction or providing bioactive sulfur if thyroid support is being taken and there is no clinical response. Thyroid function can be adjusted with more than just hormones. To stimulate the thyroid, give phosphorus, polyunsaturated FA (pulls iodine out of the gland), or provide sympathetic ANS support. To depress the thyroid, give calcium, iodine (pharmacologic dose), or provide parasympathetic ANS support. It is worth noting that there is often confusion about the use of iodine with thyroid dysfunction. When there is insufficient iodine, supplemental iodine provides support for the gland. When given in excess, iodine suppresses the thyroid. One last caveat that many practitioners have observed – whenever appropriate therapy of any kind or for any reason does not provide a clinical response, consider thyroid support.
The recent popularity of soy products has raised some concerns. Not only with regard to its phytoestrogen content, but because it will be marketed in high potency and in a processed form… This is not the forum for a more thorough review but I’m going on records as having a great concern about the intake of high amount of soy. The average daily consumption of soy protein in the Orient is only a few milligrams.
Many clinical trials have shown phosphatidylcholine reduces total cholesterol and triglycerides by as much as 20-30% as well as a marked improvement in the pathological lipoprotein patterns. Overall, the profile that has been associated with the development of atherosclerosis improves including increases in HDL cholesterol. Phosphatidylcholine also increases the mobilization of cholesterol from pre-existing atheromas to the liver for metabolism and ultimate excretion as bile acids. Improvements in atherosclerotic vascular changes have been shown by several objective measures as well as in reducing symptoms of angina pectoris, cerebral circulatory disorders, and peripheral vascular disease. It is interesting to note that a study showed choline conserved carnitine (J Clin Nutr 1996;63:904-10). It is nice to get the confirmation that the balanced, comprehensive approach we’ve watched in clinical practice work more successfully than a piecemeal fractionated approach is supported in research. Lecithin is an excellent whole food complex rich in phosphatidylcholine. Symptoms suggestive of a need for lecithin include stiffness and bone spurs (phosphorus deficit), vasomotor disturbances (nerve sheath integrity), gallbladder symptoms, and an intolerance to ingested fats (complements bile in emulsification), lipomas and elevated cholesterol (lipid transporter), and forgetfulness (memory occurs in the acetylcholine-rich hippocampus).
Niacin has long been used for cardiovascular conditions, especially involving lipid metabolism. The use of niacin for managing lipid markers for cardiovascular disease is well established:
It also may help Raynaud’s Disease (excessive blood vessel constriction due to cold and symptoms of intermittentclaudication) due to insufficient blood supply to calf muscles while walking. Niacin lowers VLDL formation in the liver by activating phosphodiesterase and inhibiting adenylate cyclase which results in the reduction of cyclic AMP in fat cells which in turn reduces the release of free fatty acids from fat cells. As a result, serum VLDL, LDL, triglycerides, phospholipids, and cholesterol are decreased. Niacin also inhibits the formation of cholesterol from acetate in the liver and appears to increase its breakdown as well. There is also evidence lipoprotein A2 synthesis is reduced by niacin and that niacin converts the smaller easily oxidized LDL into larger, oxidation-resistant LDL particles.
Niacin is part of the alcohol insoluble and heat labile fraction of vitamin B (named the “G” complex that includes riboflavin, niacin, folic acid, PABA, choline, inositol, and betaine). As part of the “G” complex, it relaxes nerves and thereby acts as a vasodilator, helping selected individuals with hypertension and smooth muscle spasm without tone. According to Compiled Notes on Clinical Nutritional Products by Wally H. Schmitt Jr., D.C. (1990) and Vitamin News(1952), signs of “G” deficiency include:
According to Robert Peshek, DDS the “G” fraction of B-complex allows chloride to enter the cell, just as Valium does. Also raises cholinesterase levels. In fact checking the level of rbc-cholinesterase levels can be a guide to functional need for “G.”
Note: You may be wondering what the evidence for oral exam findings has to do with the heart. The Medical Tribune ran an article in May 1999 correlating the degree of gum disease with the degree of carotid artery plaque… I’m not making this up.
Niacin is also part of glucose tolerance factor (GTF) which is necessary for proper glucose homeostasis, in part by acting in concert with insulin to improve the body’s responsiveness to insulin. As a result, less insulin is required to accomplish blood glucose regulation. Insulin reduces DHEA and increases the production of the pro-inflammatory eicosanoids such as arachidonic acid. Interestingly, the other part of the vitamin B complex that is alcohol soluble, named the “B” fraction, is combined with even a larger amount of niacin than the commercially available “G” complex per tablet, and yet it has an opposite effect in terms of nerve transmission, heart function, blood vessel tone, and other metabolic functions. Wheat germ has been shown to bind irreversibly to the insulin receptor and mimic its function, thereby creating an artificial insulin effect. It is not known whether sprouting and/or de-fatting the wheat germ changes this effect.
Niacin is often sold as a timed-released or sustained release product to reduce the flushing that is common when using the high dosage required to effect laboratory benefit. Niacin is metabolized by two pathways. One pathway is through conjugated with Glycine resulting in Nicotinuric Acid (NUA). This results in most of the benefits of niacin mentioned above but also produces the flushing. Niacin can also be converted to niacinamide (NAM) and other metabolites which are harmless at lower levels but can be potentially hepatotoxic at doses exceeding 1.5 grams per day. The goal of a sustained-release niacin product is to release as much niacin via the first pathway (NUA) without causing flushing, while fully releasing all the niacin before the secondary pathway is able to form potentially hepatotoxic metabolites. This may be alleviated by using a wax-matrix tablet to achieve a release profile of 45% release within the first hour, 55% release by two hours, 85% in the 3.5 hour, and 90% in 7 hours (www.orthomolecularproducts.com)
Pantethine has been shown in several studies to lower cholesterol as well as inhibit the oxidation of LDL. In the cytoplasm of the cell, pantethine promotes lipid formation at the expense of cholesterol. In the mitochondria, pantethineaccelerates the beta-oxidation of fatty acids and enhances the metabolic flow into the energy-producing Krebs cycle. During conditions of inadequate blood supply, pantethine improves cellular energetics. Pantethine is a derivative ofpantothenic acid (vitamin B5).
When all is said and done, ideal cholesterol levels for adults is probably 180-200mg% with concern when it drops below 160mg% or when it is higher than 240mg%. For HDL (the “good” cholesterol), a level of >60 is worth shooting for. A LDL (the “bad” cholesterol) should be less than 140mg%. Triglycerides should be <100mg%. Apolipoprotein A1 / B ratio should be < 0.7 with an apolipoprotein B level <84.