Vitamin C appears to lessen the negative effects of many other risk factors, including stress, diseased gums, unhealthy diet, and smoking. Smoking severely depletes the body of vitamin C; vitamin C, on the other hand, destroys free radicals produced in smoke and protects against endothelial dysfunction. Even secondhand smoke breaks down blood antioxidant defenses and accelerates lipid peroxidation, which leads to an accumulation of LDL cholesterol (Tribble et al. 1993). Vitamin C should be a part of an individual's nutritional fortress against the ravages of both firsthand and passive smoke.

A dosage suggestion is 6 grams daily in divided dosages. (A loose stool may result from higher doses of vitamin C. Should this occur simply reduce the dose to a level that is not problematic to the bowel.) Under periods of stress, a great deal more vitamin C can be taken without bowel derangement.

Reader's guide to vitamin C food sources, enhancers, and antagonists.
Vegetables and fresh, uncooked fruits (especially citrus) are vitamin C-rich sources. Raw foods represent excellent choices, having escaped the rigors of processing and preparation.

All vitamins and minerals work synergistically to enhance vitamin C absorption, particularly the bioflavonoids. Alcohol, coffee, sulfa drugs, antibiotics, analgesics, antidepressants, anticoagulants, oral contraceptives, and steroids can drain vitamin C from the body. Smoking seriously depletes vitamin C levels.

Vitamin D--reduces heart disease risk in women
It was reported at the 42nd annual conference on Cardiovascular Disease and Epidemiology Prevention (in Honolulu, HI, on April 23, 2002) that women who take vitamin D supplements lowered their risk of death from heart disease by one-third. The finding was an unexpected dividend extracted from an osteoporosis trial to determine the incidence of bone fracture in nearly 10,000 older women. From the trial participants, 4200 women reported taking vitamin D supplements at the onset of the study; another 733 reported a prior history of supplementation. After tracking the women for an average of nearly 11 years, researchers found that the risk of heart disease death was 31% lower in those taking vitamin D at the time of the study (Mercola 2002b).

Recent studies indicate that moderate or severe hypovitaminosis D was present in 66% of patients taking daily vitamin D in amounts less than the recommended dosage for their age; 37% of the patients taking daily vitamin D in excess of the recommended amount for their age were nonetheless still deficient. Thus, experts recommend at least 400 IU of vitamin D a day; if the individual is elderly and not participating in outdoor activities (and sunlight exposure), 800 IU a day is recommended (Thomas et al. 2000).

Vitamin E--prevents plaque formation, protects LDL from oxidation, strengthens blood vessels, reduces blood viscosity and platelet aggregation, is helpful in atrial and ventricular fibrillation, is an antioxidant and antidiabetic nutrient, improves insulin sensitivity, is protective to smokers, reduces C-reactive protein, has diuretic activity, and is beneficial to those with hemochromatosis
Dr. Richard Passwater commented in June 2001 that good research is timeless. The following is an example of an excellent study that should not be lost in the archives. In 1974, Dr. Passwater enrolled 17,894 persons (ages 50-98) in a study to determine the effects of long-term vitamin E supplementation. He found the length of time the individual used vitamin E was more important than the amount of the nutrient used. The trend was especially apparent beyond 9 years of usage. Taking 400 IU of vitamin E daily for 10 years or more strikingly reduced the occurrence of heart disease prior to 80 years of age (Passwater 1977).

An ongoing study involving 87,245 nurses (ages 34-59) and 39,910 male health professionals (ages 40-75) showed a significant relationship between the use of vitamin E supplements and a reduced risk of heart disease (Rimm et al.1993; Stampfer et al. 1993). A study reported in The Lancet may have eclipsed all others, showing that 2002 individuals with documented heart disease (supplemented with 400-800 IU of vitamin E daily) reduced their risk of nonfatal heart attacks 77% (Stephens 1996; Challem 2001).

These dramatic results occur in part because vitamin E prevents white blood cells from adhering to arterial walls. Researchers from the University of Texas Southwestern Medical Center explain that when monocytes are suppressed from bonding to the artery, a primary step in arterial closure has been averted (Devaraj et al. 2000a).

According to researchers at Georgetown University Medical School, vitamin E also renders the blood less sticky and platelets less prone to clump. In animal models of endothelial dysfunction, vitamin E improved the activity of endothelium-derived nitric oxide; this effect was not dependent upon the antioxidant protection of LDL cholesterol. Instead, it appears vitamin E inhibits platelet aggregation through a mechanism that involves protein kinase C inhibition, not its antioxidant activity as previously suspected (Freedman et al. 2001).

French scientists found that alpha-tocopherol supplementation prevented lethal ventricular arrhythmias associated with ischemia and reperfusion. In addition, animals with coronary arteries occluded for experimentation experienced a significant decrease in the ventricular fibrillation threshold; animals similarly occluded, but vitamin E supplemented, realized no decrease in the threshold (Dzhaparidze et al. 1986; Fuenmayor et al. 1989; Sebbag et al. 1994). Comment: Ventricular tachycardia represents at least three consecutive ventricular complexes with a heart rate of more than 100 beats a minute. Ventricular fibrillation is a cardiac arrhythmia marked by rapid, disorganized depolarizations of the ventricular myocardium. Blood pressure falls to zero, resulting in unconsciousness; without defibrillation and resuscitation, death can promptly ensue.

According to Ron Kennedy, M.D., atrial fibrillation is a condition in which the regular pumping function of the atria is replaced by a disorganized, ineffective quivering caused by the chaotic conduction of electrical signals through the upper chambers of the heart. The patient has various corrective options, including antiarrhythmic drugs, anticoagulants, radio-frequency ablation, a pacemaker, and, according to Dr. Kennedy, high-dose (2000 IU a day) vitamin E. Recall that vitamin E reduces blood viscosity and platelet aggregation. If the patient is receiving anticoagulant therapy and wishes to add vitamin E, close monitoring by a physician is essential to avoid compromising the clotting mechanism (Kennedy 1999).

Researchers from the University of Naples reported encouraging data regarding pharmacological doses (about 900 mg a day) of vitamin E administered to elderly patients with coronary heart disease and insulin resistance. Lower fasting and 2-hour blood glucose levels, reduced plasma insulin and triglyceride concentrations, and an improved HDL-LDL ratio indicate vitamin E is useful in stabilizing insulin-resistant patients with coronary heart disease (Paolisso et al. 1995).

According to Dr. Ishwarlal Jialal and Dr. Sridevi Deveraj (University of Texas Southwestern Medical Center at Dallas), diabetics have increased inflammation and are more prone to cardiovascular disease (Deveraj et al. 2000). It appears that vitamin E, by decreasing inflammation, may contribute to a reduction in cardiovascular disease in both diabetic and nondiabetic subjects. Vitamin E lowered levels of IL-6 50%; 1200 IU of vitamin E reduced C-reactive protein (CRP) 30% (Devaraj et al. 2000b; O'Brien 2001). CRP levels remained constant 2 months postsupplementation. For an in-depth review of CRP, consult the CRP subsection under the sections Newer Risk Factors and The Link Between Infections and Inflammation in Heart Disease, in this protocol.

Vitamin E appears to be decreased in patients with hereditary hemochromatosis or iron overload. Iron loading, in experimental studies, significantly decreases hepatic and plasma vitamin E, a shortage amenable with supplementation. Free-radical index markers increase three- to fivefold in an iron-loaded liver, but supplementation with vitamin E has been shown to reduce levels by about 50% (Brown et al. 1996).

Free radicals activate a gene that encourages overgrowth of smooth muscles in the blood vessel walls, a process that can contribute to closure (Gonzalez-Flecha 2002). Vitamin E, a reliable antioxidant, has the opposite effect, that is, it turns off the gene responsible for smooth muscle proliferation. Vitamin E's antioxidant powers extend to protect the cells and organs (particularly the lungs) from damage caused by smoking.

Vitamin E has (for decades) been credited with diuretic activity, stimulating urine excretion (Davis 1965). This action is of a significant advantage to patients with edematous tissues and elevated blood pressure.

The type and blend of vitamin E used affects the end results. Studies have shown that alpha-tocopherol may not protect as aggressively against coronary heart disease unless it is combined with the gamma-tocopherol form. Both alpha-tocopherol and gamma-tocopherol can decrease platelet aggregation, inhibit blood clot formation, protect LDL cholesterol against oxidation, and increase endogenous SOD production (an enzyme with antioxidant activity); gamma-tocopherol, however, shows greater activity on each function.

Unfortunately, gamma-tocopherol has a couple of factors working against its utilization. For example, gamma-tocopherol can be obtained from foodstuffs, but it is poorly retained, and much of it is excreted in urine after being metabolized by the liver. Furthermore, a protein, referred to as alpha-tocopherol transfer protein, identifies and selectively chooses alpha-tocopherol over other forms of vitamin E. As a result, alpha-tocopherol is found more abundantly in lipids, blood, and body tissues. This scenario does not allow for maximum protection against free-radical attack.

It is strongly recommended that individuals relying upon the cardioprotective effects of vitamin E include (as part of their intake) the gamma-tocopherol form, but the complexing process determines the benefit. A union of alpha-tocopherol (80%) with gamma-tocopherol (20%) appears ideal; too much alpha-tocopherol may oppose the antioxidant qualities of gamma-tocopherol.

In addition, the hypolipidemic value of toco-trienols, the lesser known half of vitamin E, should not be overlooked. The most dramatic cholesterol reduction is seen when tocotrienol supplements are combined with dietary changes (a high-fiber, low-fat diet). In a 12-week, double-blind trial, those who responded to tocotrienol therapy saw a reduction of approximately 23% in total cholesterol and 32% in LDL cholesterol using dietary modification plus toco-trienol supplements. Tocotrienols alone yielded a 16% decrease in total cholesterol and a 21% decrease in LDL cholesterol (Quereshi et al. 1993; ACCM 1998). apo-B, a protein component found in LDL, VLDL, and IDL cholesterol also appears to be tocotrienol responsive (Qureshi et al. 1997).

Tocotrienols degrade the enzyme 3-hydroxy-3-methylgulutaryl coenzyme A reductase, a rate-limiting enzyme that participates in cholesterol synthesis. Researchers credited this function as being the mechanism delivering tocotrienol's hypolipidemic edge (Qureshi et al. 2001). A team of researchers from Switzerland reported greater hypolipidemic value when using gamma-tocotrienol rather than a mixture of tocotrienols (Raederstorff et al. 2002). To read more about tocotrienols and dosing recommendations, please consult the Tocotrienols subsection appearing earlier in this section.

A suggested dosage of vitamin E is 400-1200 IU a day. Comment: Initially, blood pressure rose in approximately one-third of hypertensive individuals treated with vitamin E (Shute 1976). Therefore, individuals who are hypertensive should use 100 IU a day for 1 month and add 100 IU each month until 400 IU a day is reached (Balch et al. 1997). Because of the reductions in blood glucose levels, diabetic individuals wishing to use vitamin E should begin with low dosages. Gradually increase the dosage, allowing for appropriate insulin or drug adjustments. Lastly, Pracon, Inc., a hospital outcomes analysis firm in Reston, VA, estimated that healthcare expenses could be reduced $7.7 billion annually if the public regularly took vitamin E supplements.

Reader's guide to vitamin E food sources, enhancers, and antagonists.
Vitamin E is found in wheat germ, whole grains (brown rice, cornmeal, oatmeal, and wheat), vegetable oils (soybean, corn, and cottonseed), egg yolk, butter, milk fat, meat (especially liver), dark green leafy vegetables, legumes, nuts, and seeds.

Vitamin E enhancers are vitamin A, B complex vitamins, vitamin C, magnesium, manganese, selenium, inositol, and essential fatty acids. For optimal vitamin E absorption, excessive fat intake should be avoided, as well as birth control pills and the chronic use of mineral oil.

Vitamin K--modulates calcium levels; reduces inflammation, C-reactive protein (CRP), IL-6, the risk of thrombosis, and the progression to valvular stenosis; and has a role in glucose management
As important as calcium is as a hypotensive and antiarrhythmic mineral, it has a detrimental side if it seeps into arteries. Arterial calcification, common to the aging process, is a risk factor leading to the development of heart disease, atherosclerosis, and mitral and aortic valve stenosis. Researchers recently reported the results of a comprehensive study evaluating 2213 individuals over a 10.4-year period in regard to coronary calcium levels. Those with a calcium score in the fourth quartile were 3.7 times more likely to die over the 10 years than were individuals in the first quartile (Buenano et al. 2000).

Harvard Medical School announced that about 25% of adults over 65 years of age have arterial calcification, increasing their risk of severe heart disease 50% (Harvard Heart Letter 1999). However, the Framingham Heart Study determined that the risks imposed by thoracic aortic calcification are not restricted to senior subjects; 35-year-old men with aortic calcification had 7 times the risk of dying of a sudden heart attack (Witteman et al. 1990).

The cumulative results of 8 years of research determined that women with severe kyphosis (increased convexity in the curvature of the thoracic spine) increased their risk of pulmonary death (likely a blood clot) by 2.6 times. Compared with women who were fracture-free, those with one or more vertebral fractures had a 1.23 times greater mortality rate. Mortality increased as the number of fractures increased (Kado et al. 1999).

It was also noted that women with atherosclerotic calcification had 7% less bone mass. Dutch researchers connected the dots and determined that postmenopausal women with calcification in bone tissue and atherosclerotic vessels had diminished vitamin K levels. It was concluded that vitamin K status affects the mineralization process in both bone and atherosclerotic plaque (Jie et al. 1996).

Vitamin K, an underutilized fat-soluble vitamin, overcomes the pathological effects of a calcium imbalance by promoting the deposition of calcium in its primary site (bone) and out of arterial walls.

Note: Because of the number of individuals using anticoagulants, it is important to note that warfarin (Coumadin) caused extensive arterial calcification in laboratory animals (Howe et al. 2000). Humans on long-term warfarin therapy may be at an increased risk for developing arterial calcification due to a drug-induced vitamin K deficiency.

So interrelated is bone loss to cardiovascular disease that measuring bone density has become a predictive factor for cardiovascular health. If bone density deviates one standard from the norm, the risk of stroke increases 3 times (Mitchell 2000). Vitamin K thus emerges as a star player in cardiovascular health, keeping calcium in bones and out of arteries and valves. Note: Be aware that the risks imposed by low bone density have no gender preference. Low bone density is a strong and independent predictor of all-cause and cardiovascular mortality in both men and women (Trivedi et al. 2001).

A group of animals with induced atherosclerosis were given vitamin K (100 mg/kg of body weight), vitamin E (40mg/kg), or a placebo to assess reversal of the atherosclerotic process. At the conclusion of the study, the control group showed aortic calcium of 17.5 microns/mg; those receiving vitamin K had approximately 1 micron/mg of calcium, and vitamin E reduced it even further (Seyama et al. 1999) (for more information relating to valvular calcification, consult the section devoted to Valvular Disease in this protocol).

With age, the levels of IL-6 increase. This creates an imbalance between anti-inflammatory and pro-inflammatory cytokines (Ferrucci et al. 1999). Disproportionate numbers of good and bad cytokines increase inflammation, as well as bone degradation.

IL-6 is germane to this untoward sequence, promoting not only the inflammatory process, but also bone resorption, that is, the loss of substance from the skeletal system (Paule 2001). Vitamin K reduces the levels of IL-6; subsequently, the assault targeted at bone, as well as inflammation (a risk factor for both cardiovascular disease and cancer) is reduced (Reddi et al. 1995). Since C-reactive protein (CRP) is synthesized in response to IL-6, it appears vitamin K may be valuable in reducing elevations in CRP, as well.

Japanese researchers also found that a vitamin K deficiency can mimic the symptoms of diabetes. (The pancreas, which produces insulin, has the second highest levels of vitamin K in the body.) Low levels of vitamin K appear to induce a tendency toward a poor early insulin response and late hyperinsulinemia, following a glucose load in laboratory animals (Sakamoto et al. 1999). Lastly, vitamin K's antioxidant powers are rated (by some) as superior to either vitamin E or coenzyme Q10, other highly respected free-radical fighters (Mukai et al. 1993).

Typically, vitamin K would not be indicated if a patient is on anticoagulant therapy. However, The Lancet reported that asymptomatic patients on warfarin should consider low-dose vitamin K if blood-clotting time, as measured by the international normalized ratio (INR), is 4.5-10.0 (Crowther et al. 2000). Follow-up studies to determine the success of vitamin K therapy (1 mg a day) showed that 4% of the patients who received vitamin K therapy had bleeding episodes, compared with 17% of those in the placebo group. The conclusion of the study was that low-dose vitamin K, an inexpensive intervention without known toxicity, might prevent a hemorrhage in patients on warfarin therapy.

A suggested vitamin K dosage for patients not on anticoagulant therapy is 10 mg a day.

Reader's guide to vitamin K food sources and antagonists
Friendly bacteria in the intestines synthesize the majority of vitamin K. However, persistent low-grade levels of intestinal bacteria in the small intestine could hamper vitamin K synthesis. Acidophilus cultures in the form of yogurt or kefir serve not only as a good food source, but also ensure that sufficient friendly intestinal flora are present for vitamin K production.

Green leafy vegetables are vitamin K-rich; other sources include alfalfa, egg yolks, blackstrap molasses, asparagus, Brussels sprouts, cauliflower, oatmeal, and rye. Antibiotics increase the need for vitamin K, and vitamin E (doses greater than 600 IU) antagonizes vitamin K activity.

The calcium paradox
It is important to look at the ways calcium can become an atheromatous material. Most body stores of calcium are found in the bones and teeth, and 1% is found in the bloodstream. This 1% performs so many vital functions, including cardiac health, that the body vigorously defends this minute percentage. If inadequate calcium is available, vitamin D is mobilized in the kidney and rushes to the intestinal wall to pull more calcium into the bloodstream. If inadequate amounts of vitamin D are available, the parathyroid gland delivers a message to bones to release calcium. Because the calcium mass in the bone is so great, it is easy for too much of the mineral to be extracted, overwhelming the amount needed in the blood. After compensating for deficiencies, the excess calcium ties up in soft tissues, the lining of arteries, and brain tissue.

Poor calcium regulation also affects arterial plaque, causing it to become harder but more brittle (Harvard Heart Letter 1999). This occurs as calcium deposits in the blood attach to cholesterol deposits on the walls of arteries, making an almost impenetrable union (Shappell 2000). This process further narrows the artery, causing symptoms ranging from fainting spells to sudden death due to abrupt changes in blood pressure (Doss 2001).

It is important to grasp that excesses of calcium (potentiating arterial disease) come essentially from the bone. Furthermore, the results of a test indicating adequate blood calcium levels can be totally misleading, for the supply may have been extracted from the skeletal system. Because secondary pathways, important in maintaining homeostasis, are not well regulated, it is imperative to maintain adequate calcium levels without summoning the parathyroid gland into service.

Z

Zinc--is important in weight and blood pressure management, regulates glucose and insulin levels, and increases testosterone
Zinc, the second most abundant trace mineral in the body, is important in glucose and insulin management, as well as weight control. Individuals with the lowest dietary intake of zinc showed the greatest prevalence of coronary artery disease, diabetes, and obesity; conversely, as patients made corrections to include more zinc in their dietary program, blood pressure, blood glucose, triglycerides, and central abdominal obesity decreased (Challem et al. 2000).

Zinc is a vital component of insulin, but its worth extends to the cellular receptors, where zinc increases insulin sensitivity. When zinc levels are too low, the pancreas cannot supply enough insulin to control blood glucose levels, and the amount that is produced is less functional (Challem 2000).

However, the emphasis is upon correcting a zinc deficiency, not dosing at will. The journal Diabetes reported that administering large doses of zinc sulfate (220 mg 3 times a day, 90 mg of actual zinc) increased fasting blood glucose levels in Type II diabetic patients from an average of 177 mg/dL-207 mg/dL (Raz et al. 1989). Glycosylated hemoglobin levels also increased among a group of Type I diabetics receiving 50 mg of zinc a day (Cunningham et al. 1994). Considering these poor statistics, if prediabetic or diabetic, use no more than 35 mg of zinc a day without close blood glucose monitoring.

Zinc assists in controlling weight through various mechanisms. According to Jack Challem (the nutrition reporter), zinc is a copper antagonist (meaning it competes with copper for intestinal absorption). Challem states that this is significant because in test tube and animal experiments, excess copper increases fat (or triglyceride) synthesis from sugar. Zinc supplementation lowers copper levels, so it may decrease the synthesis of triglycerides, which show up as either triglycerides in the bloodstream or fat on the body (Challem 2000).

Lower androgen levels have an adverse effect on lipid metabolism, coagulative function, and insulin sensitivity. For the cardiovascular patient with low testosterone levels, a healthier heart profile may emerge with either testosterone therapy or supplementation to increase androgen levels (Xu et al. 2001). The benefits of zinc as an androgen potentiator were exemplified when 22 men with chronically low testosterone levels were given 50 mg of zinc sulfate daily for 45-50 days to promote fertility. (The 22 had experienced infertility longer than 5 years.) All 22 experienced a significant increase in testosterone levels during zinc therapy. In fact, nine of the 22 wives became pregnant during the study (Netter et al. 1981).

It appears that zinc therapy, although beneficial to most, is not risk-free. Occasionally, emphasizing zinc without copper can lead to copper-deficiency anemia, lower levels of HDL, and higher levels of LDL cholesterol; for some, the lack of balance between the two trace minerals can result in an irregular heartbeat (Klevay 1975). Copper is not risk-free either: it can potentiate free-radical activity.

Epidemiologic and metabolic data are convincing concerning the theory that a zinc-copper imbalance is a major factor in the etiology of coronary heart disease. For this reason, if consuming over 50 mg of zinc daily, 2 mg of copper is recommended several times a week. Since copper is widely distributed in selected foods, such as poultry, organ meats, shellfish, oysters, chocolate, nuts, dried legumes, and cereals, 2 mg a day can usually be obtained by favoring dietary selections from this list.

Reader's guide to zinc food sources, enhancers, and antagonists.
Zinc content is highest in flesh foods, such as meats, poultry, liver, and oysters. Legumes and whole grain products are also sources of zinc, but larger quantities must be consumed to deliver significant amounts. Other good sources of zinc per kilocalorie (according to Whitney et al. 1998) are spinach, broccoli, green peas, green beans, tomato juice, plain yogurt, Swiss cheese, tofu, shrimp, and crab.

Vitamins A, B3, B6, and C, as well as calcium, copper, magnesium, essential fatty acids, and essential amino acids enhance zinc absorption. Alcohol, oral contraceptives, excesses of copper and calcium, saturated and trans fats, steroids, obesity, and smoking interfere with zinc utilization. Diarrhea, kidney disease, cirrhosis of the liver, and diabetes can also contribute to a zinc deficiency.

Cardiovascular Disease Protocol Pg (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14)

These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease