Genetic Nutritioneering:

Dietary Recommendations to Reduce Heart Disease Risk

by Dr Jeffrey Bland

The real explanation for heart health and disease is beginning to emerge from clinics, laboratories and research institutions around the world. It is based on the principles described in this book.

Buy it Online

About the Author
     Jeffrey S Bland Ph.D is an internationally recognised researcher, educator and author in the field of nutritional biochemistry. For over 20 years, Dr Bland has been involved in clinical research and education related to nutritional medicine. As a pioneer in functional medicine, he has spoken around the world on the latest developments in this field. Dr Bland was Director of the Linus Pauling Laboratory for Nutritional Analysis and a Professor of Chemistry at the University of Puget Sound. Dr Bland has always been regarded as ‘ahead of the information curve’. For the past 16 years, he has produced a monthly 90 minute audio-cassette report reviewing the most recent health science research and journal articles and interviewing newsworthy clinicians. He is also the author of many best-selling books.
     Sara H Benum MA has worked extensively with Dr Bland and is HealthComm International’s publications manager.

     A good example of the inadequacy of the single cause/single solution medical model is the recent focus on elevated blood cholesterol as the cause of heart disease. Research, diagnosis and treatment have all been directed toward cholesterol management. Low-cholesterol/low-fat foods are marketed to promote a “healthy heart.” Cholesterol-lowering drugs are among the most prescribed medications of our time. And public health messages stress the importance of understanding the important role of elevated cholesterol in causing heart disease. Many people now mistakenly believe that, as long as they keep their cholesterol level below 200, they won’t have to worry about heart disease.
     Meanwhile, however, we keep hearing about someone whose blood cholesterol was “normal” and who seemed to be the picture of health who suddenly dropped dead of a heart attack. This couldn’t happen if cholesterol were the whole story of heart disease.
     The real explanation for heart health and disease is beginning to emerge from clinics, laboratories and research institutions around the world. It is based on the principles described in this book.

From 1979 to 1992 in Scandinavia, 15 young male athletes and one female athlete died of sudden cardiac arrest while they were competing in a sport called orienteering. Orienteering competitors run long distances through territory with no trails, using a map and compass as their only guides. This demanding sport requires agility, extraordinary fitness, strength and an uncanny sense of direction. The athletes who died had very low levels of blood cholesterol and none of the usual risk factors for heart disease. The 16 deaths of young, very fit athletes were considered to be an “epidemic” of unknown cause.
     Swedish medical researchers spent several years trying to find the cause of death of these elite athletes. Postmortem examination revealed evidence of inflammation of the heart which seemed to be caused by a chronic infection with the parasite Chlamydia pneumonia.¹
     Following up on this discovery, investigators in the cardiology division at the University of Utah School of Medicine have confirmed the strong correlation between heart disease and infection with Chlamydia.² Investigators have now also found that other organisms, such as Helicobacter pylori, the bacteria that causes stomach ulcers, are also associated with an increased risk of heart disease.³
     The organisms that cause chronic infection alter gene expression of the host individual and trigger the production of cytokines, the inflammatory markers described in the previous chapter. Laboratory analysis of individuals who have chronic infection reveal elevated levels of these markers of inflammation in their blood, including elevations of C-reactive protein and serum amyloid A protein, two well-known indicators of chronic inflammation.⁴
     This research has led to the realization that factors other than cholesterol may play a role in heart disease. The interaction between agents that lead to inflammation and genes that express inflammatory markers like C-reactive protein and serum amyloid A protein increases the risk of damage to the heart and subsequent heart disease.
     The importance of this interaction helps explain why routinely taking low-dose aspirin helps protect against heart attack. Statistically, although the reason was not previously known, taking the equivalent of a baby aspirin daily reduces the incidence of heart attack and heart disease in adults. Recently, medical investigators from the Division of Preventive Medicine and Cardiovascular Disease at Brigham and Women’s Hospital at Harvard Medical School reported that aspirin might help protect against heart disease through its ability to reduce inflammation. When the researchers measured the levels of C-reactive protein in the blood of 543 apparently healthy men participating in a physicians’ health study, they found those who had elevated levels of C-reactive protein had higher risk of heart disease. Those who took aspirin on a regular basis had a much lower risk. The investigators conclude that the reduction of heart disease risk associated with taking aspirin appears to be directly related to aspirin’s ability to lower the level of C-reactive protein.⁵
     According to renowned cardiologist Attilio Maseri, MD, the new research linking inflammation and heart disease suggests that the current approach to heart disease prevention that focuses entirely on lowering cholesterol may be ill-advised. He believes we should be trying instead to identify individuals who would benefit most from specific therapies based upon their genetic need.⁶
     Research is needed to explore the relationship between heart disease and multiple genetic susceptibilities, some of which may be related to inflammatory substances produced within the gut-associated lymphoid tissue (GALT). (See Chapter 8 for a discussion of GALT.) Many types of infection, toxic exposure or trauma could result in increased production of inflammatory alarm substances. These alarm substances, in turn, could interact with the genes in genetically susceptible individuals to produce heart inflammation and subsequent heart disease.⁷ It has been only two years since medical investigators discovered that inflammation is related to heart disease, but we now understand that these markers for inflammation may be better predictors of heart disease than elevated blood cholesterol itself.⁸

Dietary Recommendations For Reducing
Heart Disease Risk
     If cholesterol alone is not responsible for heart disease, how important is diet in preventing heart disease? Once again, we must not throw the baby out with the bathwater. Extensive research continues to indicate that elevated levels of the “bad” LDL cholesterol are associated with increased risk of heart disease. In fact, studies indicate that for every 1 percent elevation in the bad LDL cholesterol there is a 2 percent increase in risk of heart disease. This statistic clearly supports continued monitoring of diet and lifestyle aimed at reducing levels of LDL cholesterol in the blood. As William Connor, MD and Sonja Connor, RD pointed out recently, studies around the world continue to indicate that a low-fat, high-fiber diet rich in unrefined, complex carbohydrates helps lower the risk of heart disease and improve heart health.⁹
     Fat and cholesterol are not the only nutrition concerns that relate to an attempt to prevent heart disease, however. Although it is high in fat, the Mediterranean diet, in which the fats are primarily monounsaturated fats from olive oil, is associated with lower heart disease risk. Greenland Eskimos, whose diet is extraordinarily high in fat, also have a low incidence of heart disease, presumably because the fat they eat comes almost entirely from seals and coldwater fish. These fats are rich in omega-3 fatty acids, which seem to protect heart function.¹⁰ It would be misleading, therefore, to say that simply reducing all fats in the diet and eating more unrefined carbohydrates and vegetable products could prevent heart disease. We have learned that the best approach to nutrition combines a reduction in saturated animal fats and partially hydrogenated vegetable oils from processed and convenience foods with increased intake of fresh fruits and vegetables, whole grains, lean meats, fish and monounsaturated, omega-3 rich oils.
     In an article in the New England Journal of Medicine, Scott Grundy, MD, Ph.D. from the University of Texas Southwestern Medical Center, and Walter Willett, MD, DPH from the Harvard School of Public Health cautioned about the current obsession with reducing fat. They wrote,
     The intense focus on total fat intake not only is unlikely to be beneficial but also distracts people from lifestyle changes that can have real benefits. These include specific dietary reductions in saturated and trans fats (partially hydrogenated oils), increases in the consumption of fruits, vegetables and whole grains, and the prevention of excessive weight gain by greater physical activity and reductions in overall calorie intake.¹¹
     Statistically, only about 10 percent of the population is genetically predisposed to have elevated blood cholesterol as a result of elevated dietary cholesterol. Most of the cholesterol in the blood does not come directly from the diet. The intestines and liver manufacture cholesterol from other sources of fat, carbohydrate and protein. Advising people to omit cholesterol-containing foods from their diet because cholesterol produces heart disease does not balance with the facts. Some people, because they are not genetically susceptible to dietary cholesterol intake, can eat dozens of eggs a week and still maintain low blood cholesterol levels.
     Recent studies from Leiden University Medical Center in the Netherlands indicate that in people older than 85 years, high blood cholesterol levels are associated with longevity and good health, owing to a lower mortality from both cancer and infectious diseases. According to the medical report from these studies, the presumed protective effect of elevated blood cholesterol in the elderly indicates we should reevaluate the use of cholesterol- lowering therapy after a certain age. Lowering cholesterol may actually be increasing rather than decreasing the risk of disease.¹² The authors wrote, “Our study shows that a high serum blood cholesterol concentration is not a risk factor for cardiovascular disease in people aged 85 years and over – on the contrary, it is associated with longevity. On the evidence of our data, cholesterol-lowering therapy in the elderly is questionable.”

     Cholesterol has gotten a bad reputation in the past 10 years because of its presumed role in heart disease. We seem to have forgotten that cholesterol is an important substance in the body. It helps cells maintain their structure and function and it is also the substance from which the liver manufactures bile acids so we can digest and assimilate nutrients from food. It is also the material from which sex hormones are produced in the ovaries, testes and adrenal glands. In other words, cholesterol is valuable to the body. The difficulty arises when the body produces too much cholesterol or produces it in the wrong form, such as the LDL particles that increase the risk of heart disease. Medical investigators at the US Department of Agriculture Human Nutrition Research Center on Aging recently reported that cholesterol plays an important role in protecting against aging of the brain as well as the heart.¹³
     The USDA research indicates that cholesterol serves as an antioxidant in the body, retarding the effects of oxidative stress. As with many other substances in the body, proper cholesterol control can result in good health, whereas either too much or too little of it can produce increased risk of disease.
     Blood cholesterol is no different from other measurable substances in the blood. All have optimal levels that are associated with good health and healthy aging. Most medical investigators agree the optimal level of total (LDL plus HDL) blood cholesterol is between 150 and 200 mg percent. In older people, however, in whom increased oxidative stress and free radical aging present a greater concern, higher blood cholesterol levels may have a protective effect against brain and heart aging.
     For individuals whose LDL cholesterol levels exceed 130 mg percent, cholesterol-lowering therapies are still advisable, particularly if their HDL cholesterol level is lower than 35 mg percent. The objective of any prudent diet and lifestyle intervention program to reduce the risk of heart disease is to communicate with the genes in such a way that the ratio of total blood cholesterol to HDL cholesterol is five-to-one or less. This is undoubtedly one of the best markers available for determining one aspect of heart disease risk. If your total cholesterol is 200, your HDL cholesterol should be at least 40 to provide a ratio of five-to-one or less. The lower this ratio, the lower your heart disease risk related to cholesterol.¹⁴

Beyond Cholesterol
     Although medical science is very clear in acknowledging that elevated LDL cholesterol is a risk factor for heart disease, it does not completely understand why this is true. The suspicion is emerging that cholesterol may be as much the effect of other processes going on as the cause of heart disease. This means cholesterol is like the body’s smoke detector. The smoke detector does not cause the fire; it alerts us to the presence of a fire and forces us to look for its cause. Similarly, elevated blood cholesterol may not cause heart disease, but it may be very closely associated with the appearance of heart disease.
     In the late 19th century, the German physiologist Rudolph Virchow proposed that the origin of heart disease was inflammation of the heart and the arteries that bring blood to the heart. His proposition was based on his detailed autopsy studies and pathology investigations of individuals who died of heart disease. He found their arteries looked as though they had been wounded inside, which suggested they had an inflammatory condition such as what would occur with a skin abrasion that became infected.

     In the early 20th century, however, a Russian physiologist named Nikolai Anitschow proposed an entirely different mechanism as the origin of heart disease. He raised white rabbits on a high-fat, high-cholesterol diet and was able to produce serious heart and artery disease in these rabbits. He proposed that dietary fat caused fatty streaks and deposition of fat on the walls of arteries and in the heart, producing heart disease. The more investigators studied Anitschow’s hypothesis, the more they became convinced that dietary fat was the cause of heart disease and the less they reflected on the pioneering work of Virchow.
     In the 1980s, however, investigators at Harvard Medical School reevaluated the Anitschow concept.^15-16 Using the same type of white rabbits Anitschow had studied, they placed them on the same fat- and cholesterol-enriched diet and found they, too, could produce heart and artery disease in these animals. When they purified the cholesterol so it was 99.999999 percent pure before they fed it to the animals, they were unable to produce the same high level of heart disease. When they fed the rabbits a very low level of the impurity they had refined out of the normal cholesterol, suddenly the animals developed serious heart disease. The Harvard scientists concluded it was not the cholesterol itself that initiated the heart disease, but impurities in the cholesterol which were found to be cholesterol oxides.
     Cholesterol oxides are forms of cholesterol that have been damaged by oxidative stress. These forms of cholesterol cause white blood cells to infiltrate the artery walls and initiate atherosclerosis or the heart disease process. The higher the level of blood cholesterol, the more cholesterol oxides are present. And the more oxidative stress a person is under, including inflammation, the more damage there is to cholesterol, leading to the formation of cholesterol oxides. Cigarette smoking, high serum iron levels, chronic infection and dietary antioxidant deficiencies can all increase cholesterol oxide formation and may be major contributors to heart disease.

     Dr Earl Benditt, a pathologist at the University of Washington School of Medicine, found these oxidized substances may be potential mutagens that react with the genes within cells on the artery wall. They can trigger a process of atheroma formation, by which the cells grow like a benign tumor on the inside of the artery.¹⁷ Dr Benditt believes the initial stages of heart disease may be caused by exposure of the arteries to these mutagenic substances that speak to the genes in ways that alter their function. We might consider the atheroma to be like a wart on the inside of the artery, a benign tumor that becomes inflamed, irritated and later infiltrated with cholesterol and calcium to become heart and artery diseases.
     The process of atheroma formation might help explain why dietary antioxidants like vitamin E are helpful in preventing heart disease. Several studies have found that people whose diets contain more than RDA amounts of vitamin E have lower incidence of heart disease. A study of US nurses and doctors found a 30 to 40 percent reduction in the incidence of heart disease among those who had the highest level of vitamin E intake over a four- to eight-year period. The benefit seemed to be greatest in individuals taking from 100 to 250 IU of supplemental vitamin E daily, which is an intake 6 to 15 times higher than the RDA for vitamin E.¹⁸ Vitamin E is not the only important heart-protective antioxidant nutrient. Evidence suggests that vitamin C and the essential minerals magnesium, zinc, copper and selenium may also help protect against heart disease.
     In addition to inflammation, elevations in C-reactive protein and serum amyloid A protein, elevated LDL cholesterol in the blood and oxidant stress factors, scientists have identified another heart disease risk factor. Nearly 30 years ago Kilmer McCully, MD suggested that an amino acid called homocysteine, which is found in the blood of some individuals, triggers heart disease. Dr McCully recounts his discovery of the role of homocysteine and the history of its acceptance in his book, The Homocysteine Revolution.¹⁹
     Old beliefs in the medical and scientific communities about the origin of heart disease change very slowly. Evan Shute, MD, a cardiologist in London, Ontario, Canada during the 1950s and 1960s, can certainly attest to this fact.²⁰ Dr Shute was the first cardiologist to talk about the benefit of vitamin E in the protection and even treatment of heart disease. He did fastidious clinical work and documented his observations of the benefits of vitamin E in heart disease, burn recovery and wound healing in thousands of patients. His medical colleagues not only would not accept his observations, they branded him a “kook.” Nearly 50 years later, Dr Shute’s observations of the benefits of vitamin E are now being validated by the scientific community. Unfortunately, he and his brother, who was also actively involved in this research, did not live long enough to see the vindication of their efforts.
     At age 63, on the other hand, Dr McCully is still an active investigator at the Veterans Administration Hospital in New England. He is witnessing the acceptance of his idea that one of the major, unrecognized causes of heart disease is the elevation of the toxic amino acid homocysteine in the blood.²¹
     This is not just an academic discussion. An article in a recent issue of Time magazine²² told of the deaths of 64 men and women in Norway between 1992 and 1996. No one questioned the deaths. After all, all of the deceased had had heart disease, and many had undergone coronary bypass surgery. “Deaths like these are not the stuff of headlines.” Retrospective analysis, however, revealed that the premature deaths of these Norwegians, like countless thousands of others around the world, resulted from the elevated levels of the amino acid homocysteine.²³
     Extensive medical research now indicates that at least 10 percent of the population (and perhaps even more) carries the genetic risk for production of elevated levels of homocysteine. Therefore, they are at increased risk of heart disease. Elevated levels of homocysteine in the blood are now universally accepted as a strong predictor of death from heart disease. Standard medical exams physicians have been doing for decades provide no information about homocysteine levels. In a sense, homocysteine has been a “silent killer” for years. Fortunately, however, many medical laboratories now offer cardiovascular screening tests that assess homocysteine level and provide information to the doctor and patient about genetic risk for this disorder.
     Dr McCully discovered the relationship between homocysteine and heart disease when he investigated the cause of death of an 8-year-old boy who died of a stroke in 1969. It is rare for a child of this age to have a stroke, and as a pathologist, Dr McCully had his interest piqued by this case. It was not until years later, however, when the boy’s sister developed what appeared to be heart disease in her 30s, that McCully began to put the pieces together. He believed homocysteine elevation, which was common to both cases, might be the cause of the stroke in the boy and heart disease in his sister. Although the link between homocysteine and heart disease had been known for some time, it was believed to be very uncommon and limited to a few unique genotypes. What Dr McCully discovered was that there is a range of severity within this genotype. A number of genes interact to give rise to homocysteine elevation. Mild, moderate and severe forms of homocysteine elevation, therefore, resulted in varying risks of heart disease. An even more remarkable outcome of his investigations was the discovery that these characteristics of genetic risk to homocysteine could be modified through application of the principles of genetic nutritioneering.
     Dr McCully found that elevated homocysteine levels could be reduced by increasing the intake of specific nutrients that communicated with the genes and with the products of the genes in such a way as to reduce homocysteine levels to zero. These nutrients are folic acid, vitamin B12, vitamin B6 and the B-complex substance betaine.
     A recent collaborative investigation by European medical scientists resulted in a “consensus opinion,” which they published in the Journal of the American Medical Association regarding the importance of elevated blood homocysteine levels. “An increased plasma total homocysteine level confers an independent risk of vascular disease similar to that of smoking or hyperlipidemia. It powerfully increases the risk associated with smoking and hypertension. It is time to undertake randomized controlled trials of the effect of vitamins that reduce plasma homocysteine levels on vascular disease risk.”²⁴ By the same token, there is increasing evidence that the risk of dementia in the elderly increases in individuals with elevated homocysteine in their blood.²⁵
     The homocysteine/methionine association also has important implications related to the risk from the toxic effects of homocysteine associated with a diet that is high in animal protein. Animal proteins, particularly egg protein, are very high in sulfur amino acids like methionine. Individuals who carry the mild form of defect in the metabolism of homocysteine, therefore, might have more risk of heart disease and dementia if they regularly consume a high-protein diet that is inadequate in vitamin B6, folate and vitamin B12.
     The level of vitamins necessary to promote proper metabolism of homocysteine in individuals who carry these genetic uniquenesses is higher than the Recommended Dietary Allowances. Depending on the severity of the genetic uniqueness, a person might have to consume from 5 times to as much as 100 times the RDA levels of folate, vitamin B12 or vitamin B6 to lower his or her homocysteine levels.
     It is worth noting that even Victor Herbert, MD, JD, an outspoken critic of vitamin supplementation, recently urged his medical and scientific colleagues to petition the Food and Drug Administration to supplement US flour with higher-than-RDA levels of vitamin B12 and folate to protect against homocysteine- induced disease. He suggests the minimum safe daily oral dose of vitamin B12 should be 25 mcg per 100 grams of flour, which is four times the RDA for vitamin B12, along with 400 mcg of folate. He justifies this sug-gested supplementation of grains with high levels of folate and vitamin B12 by stating,
     The combined supplement will also prevent millions of Americans from getting vasculotoxic hyperhomocystemia, with its enormous cost in heart attack, stroke and other vasculotoxic morbidity and mortality, and billions more health-care dollars. We estimate that approximately 20 percent of all heart attacks, 40 percent of all thrombotic strokes, and 60 percent of all peripheral venous thromboses will be prevented by FDA implementation of our petition.²⁶
     This advocacy for nutrient supplementation of the food supply seems to be a remarkable change in position for Dr Herbert, who for years has been a vociferous opponent of the nutritional supplementation or fortification of foods with micronutrients. Since Dr Herbert is a recognized expert in vitamin B12 physiology and metabolism, his recent position indicates he now recognizes the benefits of nutritional supplementation for individuals at specific genetic risk.
     Another important B-complex vitamin should be added to vitamin B12, folate and B6 in the Genetic Nutritioneering Program for individuals who want to reduce the risk of the toxic effects of homocysteine. This is the B-complex nutrient betaine. David Wilcken, MD and Bridget Wilcken, MBChB reported that some individuals with elevated homocysteine do not respond to administration of vitamin B12, folic acid and vitamin B6 alone. These individuals frequently respond to the addition of higher levels of betaine, however.²⁷
     The Wilckens found these individuals have a unique genetic need for supplemental betaine that is independent of vitamin B12, folate and vitamin B6. In their paper they reported that administering high doses of betaine to individuals whose elevated homocysteine condition was unresponsive to the traditional vitamin supplementation resulted not only in a reduction of homocysteine but also in a number of other positive influences on their health.
     We are once again reminded that our bodies work not as a collection of individual organs in isolation but as a collection of organ systems operating synergistically in a web-like manner. The role of homocysteine in the heart and brain illustrates the interconnectedness among organ systems. It points up the mistake we have traditionally made in medicine in isolating one system without examining its effect on others. Medical specialization has taught us more and more about the function of specific organs. Unfortunately, however, we have often failed to understand the interaction and synergy of the whole. The concept of genetic nutritioneering requires that we think in web-like patterns, in which interacting organ systems give rise to the function of the individual.

References
1.    Wesslen L, Pahlson C, Lindquist O et al. An Increase in Sudden Unexpected Cardiac Deaths among Young Swedish Orienteers During 1979-1992. European Heart Journal. 17: 902-10. 1996.
2.    Muhlestein JB, Hammond EH, Cariquist JF et al. Increased Incidence of Chlamydia Species within the Coronary Arteries of Patients with Symptomatic Atherosclerotic Versus Other Forms of Cardiovascular Disease. Journal of the American College of Cardiology. 27: 1555-61. 1996.
3.    Patel P, Mendall MA, Carrington D et al. Association of Helicobacter pylori and Chlamydia pneumoniae Infections with Coronary Heart Disease and Cardiovascular Risk Factors. British Medical Journal. 311: 11-14. 1995.
4.    Mendall MA, Patel P, Ballam L, Strachan D and Northfield TC. C-Reactive Protein and Its Relation to Cardiovascular Risk Factors: A Population Based Cross Sectional Study. British Medical Journal. 312: 1061-65. 1996.
5.    Ridker PM, Cushman M, Stampfer MJ, Tracy RP and Hennekens CH. Inflammation, Aspirin, and the Risk of Cardiovascular Disease in Apparently Healthy Men. New England Journal of Medicine. 336: 973-79. 1997.
6.    Maseri A. Inflammation, Atherosclerosis and Ischemic Events – Exploring the Hidden Side of the Moon. New England Journal of Medicine. 336: 1014-15. 1997.
7.    Murray WM. Inflammation, Aspirin, and the Risk of Cardiovascular Disease. New England Journal of Medicine. 337: 422-24. 1997.
8.    Haverkate F, Thompson SG, Pyke SD, Gallimore JR and Pepys MB. Production of C-Reactive Protein and Risk of Coronary Events in Stable and Unstable Angina. Lancet. 349: 462-66. 1997.
9.    Connor WE and Connor SL. Should a Low-Fat, High-Carbohydrate Diet Be Recommended for Everyone? New England Journal of Medicine. 337: 562-67. 1997.
10.    Harris WS, Connor WE and McMurry MP. The Comparative Reductions of the Plasma Lipids and Lipoproteins by Dietary Polyunsaturated Fats: Salmon Oil Versus Vegetable Oils. Metabolism. 32: 179-84. 1983.
11.    Katan MB, Grundy SM and Willett WC. Beyond Low-Fat Diets. New England Journal of Medicine. 337: 563-66. 1997.
12.    Weverling-Rijnsburger AW, Blauw GJ, Lagaay AM, Knook DL, Meinders AE and Westendorp RG. Total Cholesterol and Risk of Mortality in the Oldest Old. Lancet. 350: 1119-23. 1997.
13.    Joseph JA, Villalobos-Molinas R, Denisova NA, Erat S and Strain J. Cholesterol: A Two-Edged Sword in Brain Aging. Free Radical Biology & Medicine. 22: 455-62. 1997.
14.    Superko HR. The Atherogenic Lipoprotein Profile. Science & Medicine. 4(5): 36-45. 1997.
15.    Taylor CB, Peng SK and Lee KT. Spontaneously Occurring Angiotoxic Derivatives of Cholesterol. American Journal of Clinical Nutrition. 32: 40-57. 1979.
16.    Peng S and Taylor CB. Cytotoxicity of Oxidation Derivatives of Cholesterol on Cultured Aortic Smooth Muscle Cells and Their Effects on Cholesterol Biosynthesis. American Journal of Clinical Nutrition. 32: 1033-42. 1979.
17.    Benditt E. The Origin of Atherosclerosis. Scientific American. 236: 74-85. 1977.
18.    Diaz MN, Frei B, Vita JA and Keanet JE. Antioxidants and Atherosclerotic Heart Disease. New England Journal of Medicine. 337: 408-09. 1997.
19.    McCully K. The Homocysteine Revolution: Medicine for the New Millennium. Keats Publishing, Inc. New Canaan, Conn. 1997.
20.     Shute E. The Vitamin E Story: The Medical Memoirs of Evan Shute. Welch Publishing Company. Burlington, Ontario, Canada. 1985.
21.    Stacey M. The Fall and Rise of Kilmer McCully. New York Times Magazine. 25-29. August 10, 1997.
22.    Kluger J. Beyond Cholesterol. Time. P48. August 4, 1997.
23.    Nygard O, Nordrehaug JE, Refsum H et al. Plasma Homocysteine Levels and Mortality in Patients with Coronary Artery Disease. New England Journal of Medicine. 337: 230-36. 1997.
24.    Graham IM, Daly LE, Refsum HM et al. Plasma Homocysteine as a Risk Factor for Vascular Disease. Journal of the American Medical Association. 277: 1775-81. 1997.
25.    Fredman P, Wallin A, Blennow K et al. Sulfatide as a Biochemical Marker in Cerebrospinal Fluid of Patients with Vascular Dementia. Acta Neurologica Scandinavica. 85: 103-06. 1992.
26.    Herbert V and Bigaouette J. Call for Endorsement of a Petition to the Food and Drug Administration to Always Add Vitamin B-12 to Any Folate Fortification or Supplement. American Journal of Clinical Nutrition. 65: 572-73. 1997.
27.    Wilcken DE, Wilcken B, Dudman NP and Tyrrell PA. Homocystinuria –The Effects of Betaine in the Treatment of Patients Not Responsive to Pyridoxine. New England Journal of Medicine. 309: 448-53. 1983.

•    Extracted with permission from Genetic Nutritioneering by Jeffrey S Bland, Ph.D with Sara H Benum MA. Keats Publishing Inc. New Canaan, Connecticut. 1999. ISBN 0-87983-921-X £13.99 Distributed in the UK by Airlift Book Company, Tel: 020-8804 0400.