Nutraceutical Approaches to Coronary Artery Disease
Mitchell J. Ghen, D.O., Ph.D.

Anticoagulants
    One of the primary treatments applied for patients with coronary artery disease are anticoagulants. The aging process lends itself to increased coagulability. The obvious consequence of hypercoagulability is clot formation and subsequent artery occlusion. Increase in blood viscosity can create a hemodymamic state of ischemia, with its own set of circumstances. Ischemia is defined as low blood flow, which may or may not have total obstruction associated with it. Ischemia can lead to apoptosis and inflammation. Evaluation of ischemic potential can be approached with a functional coagulation panel. This composite of tests includes the typical PT, PTT tests and also the more comprehensive combination of fibrinogen, prothrombin fragments one and two, thrombin-anti-thrombin complexes, soluble fibrin monomers and platelet CD62P (Selectin) receptors. A valuable test for evaluation of clotting is platelet aggregation testing. Platelet aggregation occurs with the presence of adenosine, epinephrine, collagen and thrombin. Most anti-platelet aggregation medications work only in the presence of adenosine (aspirin for example). This may explain why type A personalities using aspirin still have clot formation. In contrast EDTA (ethylene diaminetetracetic acid), inhibits aggregation to all of the substances above with the exception of collagen. Acute phase reaction, particularly a high c-reactive protein, is related to vascular inflammation and or infection. Substances, such as coumadin affect prothrombin/thrombin activation. Natural products like vitamin E and magnesium have similar properties. Platelet hyperactivity is minimized by aspirin and similarly by other natural products like ginkgo and ginger. Fibrinogen/fibrin monomers can be addressed with enzymatic therapy like bromelain and pancreatin. Natural substances, that have similar reaction to heparin, are arginine, niacin, bromelain and papain. I have found clinically that increased fibrinogen levels of greater than 400 mg respond quickly and effectively to Curcuma longa.

Vasodilation
    An important component to coronary artery disease treatment is vasodilation. The consequence of vasodilation is improved blood flow and subsequent increase in tissue oxygenation. The object of nitrates or nitrate therapy, a mainstay of both acute and chronic coronary arterial disease care is to increase blood flow to constricted blood vessels, whether this stricture is created by plaque or by vasospasm. The natural substance, arginine, for example, is said to increase nitric oxide, a free radical (part of a group of compounds known as endothelial releasing factor, EDRF) that functions as a vasodilator. Nitric oxide has a secondary effect to potentially reduce the damage created by homocysteine. It has been hypothesized that EDTA’s benefit can, to a large degree, be attributed to its release of nitric oxide. Of course, EDTA is an excellent anti-coagulant.

    Also worthy of note, cayenne pepper has excellent effects on blood lipids, platelet activity, and vasodilatory action. As a wonderful first aid remedy, one teaspoon of cayenne in a glass of water can quickly relieve the discomfort of acute chest pain caused by angina.

Lipid Modulation
    There are many products that effectively control dyslipidemia without the side effects often associated with conventional medical drugs. For elevated cholesterol, a combination of pantethine and inositol hexacotinate can demonstrate profound improvements in one month. For those patients with elevated triglyceride levels, L-Carnitine, as well as EFAs, can often solve the problem. I prefer the inositol hexanicotinate form of niacin due to its absence of the troublesome side effects of flush and liver irritation. Its mechanism of action is similar to all niacin compounds to reduce plasma triglycerides, VLDL, LDL synthesis and total cholesterol. Pantethine is the active hormone of pantethenic acid. It is considered to be one of the most important parts of coenzyme A (CoA) that transports fats to and from the cells. It has a potent effect on cholesterol as well as triglycerides. L-Carnitine is synthesized from lysine with the help of methionine. It improves triglyceride levels, total cholesterol and increases HDL. The n-3-polyunsaturated acids in large enough doses have been shown to be helpful in many studies. The DART study and most recently the GISSI study (published in The Lancet) are good examples. The role of omega-3 fatty acids are several, but recent studies report that their most profound effects may be on arrhythmogenesis as well as inflammation. The GISSI study reported a substantial decrease in cardiovascular events as a result of fish oil supplementation. I believe the study results, although impressive, would have been even more dramatic had the investigation used omega-6 fatty acids as well. In refractory cases of elevated lipids, which have failed to respond to the above regimen, consider the combination of methionine, inositol and choline in doses of 200-400 mg of each taken 3 times daily. Lipoprotein a (Lpa) is an apolipoprotein, i.e. an LDL particle, to which an additional protein is attached. Because of Lpa’s similarity with plasminogen, it interferes with fibrinolysis, and of course ultimately speeds up clot formation. Several substances as shown Table 3 can be helpful. Coenzyme Q10 for example, can inhibit the Lpa receptor expression.

Homocysteine Reduction
    There are many published studies supporting homocysteine as a risk factor for vascular disease. Homocysteine has also been considered a good marker for B6, B12 and folic acid deficiency. Even Raloxefen’s benefit as seen in the Ruth Study “Raloxefen use for heart study” suggested this drug’s action on coronary artery disease, may in part be due to its homocysteine-lowering qualities. Regular supplementation with the three B vitamins (B6, B12 and folate) will control a great majority of elevated homocysteine levels. A simple blood test confirming the patient’s level of homocysteine should be performed with their annual routine exam. Although laboratories suggest that a level below 15 is normal, a level of less than 10 is ideal and less than 7 is considered optimal.

Insulin Resistance Reduction
    Receptor sensitivity for insulin decreases and the body compensates by secreting increased amounts of insulin. This is known as ‘insulin resistance’. Increased insulin levels promote lipogenesis, increased thrombosis from increase in plaminogen activator/inhibitor, and decreases through a hepatic mechanism, which will decrease HDL while increasing triglyceride production. One of the most devastating effects is the glycosylation process, whereby circulating glucose attaches to proteins. Eventually this leads to advanced glycosylation end products (AGE), which can be a precursor to microvascular disease. The abnormal glucose/insulin metabolism augments formation of free radicals. Of course, oxidative stress is often responsible for many of the factors contributing to coronary artery disease. Other than the substances noted in Table 5, caloric restriction is an excellent way to decrease free radical formation and improve insulin sensitivity. Equally as important is a regular exercise program given that insulin receptors are located within muscle tissue. In addition, repletion with antioxidants is also imperative (see Table 6).

Antioxidants and Biological Enzymes
    There are many studies that support the importance of adequate antioxidant levels and the occurrence of coronary artery disease. In several instances, it has been postulated that antioxidant use is more important than the control of lipid levels. It is well known that cholesterol in itself is not problematic, but the exposure of cholesterol to the oxidation process certainly can generate plaque. Grapeseed extract, vitamin E and vitamin C are important components of antioxidant therapy. Grapeseed extract alone has been shown to reduce plaque size. Since most diets have poor consumption of antioxidants and flavanoids, supplementation with larger doses than usual for coronary artery disease (C.A.D.) patients may be helpful.

    Bromelain has been shown to have numerous therapeutic benefits, including effects on cytokines such as TNF-alpha, IL-1beta, IL-6 and IL-8. Studies also give evidence that bromelain may inhibit platelet aggregation, an important cardioprotective property. Some have claimed that bromelain can not be effective orally, but this has since been refuted.

    Researchers report that soluble fibers have a positive effect on hypertension as well as serum-fasting insulin. Patients should be regularly tested for glycosylated hemoglobin, fasting blood sugar and fasting insulin levels.

Inflammation and Infection
    Presently, most recognize that there are several infectious agents that are associated with coronary vascular disease. Human herpes virus 6, nanobacteria, chlamydia and cytomegalo virus all have been implicated as part of the epigenesis of heart disease. Studies have even shown 89% of patients have chlamydia in their hearts at the time of bypass surgery. Most investigators agree that, although these infectious organisms may not be the primary cause of heart disease, they significantly contribute to a hypercoagulable state. The use of lowdose broad-spectrum antibiotics such as tetracycline has been suggested along with aggressive enzyme usage. It seems that this combination affords the best result of reducing infection and inflammation. Several studies have shown the overall effectiveness of enzyme use is greater than the non-steroidal anti-inflammatories.

Sympathetic Tone
    The sympathetic nervous system (flight or fight) plays an important role in C.A.D. Greater than usual sympathetic tone will increase heart rate and elevate blood pressure. Increased sympathetic activity has often been demonstrated in patients with C.A.D. Increased levels of adrenal medulla hormones, i.e., norepinephrine and epinephrine damage the arterial lining, increase platelet aggregation and increase oxidized cholesterol, all which lead to a faster generation of arthrogenesis. Remember, calcium stimulates sympathetic discharge, whereas, magnesium has antagonistic properties. Therefore, appropriate levels of magnesium and melatonin help to control an imbalanced sympathetic nervous system.

    Researchers have demonstrated that patients with C.A.D. have nighttime melatonin levels that are 1/5 lower than healthy controls. Explanatory physiology is likely to be related to increased nighttime sympathetic discharge and the subsequent increase in epinephrine/norepinephrine. Also, melatonin levels could possibly explain why the majority of heart attacks occur in the early morning hours. Melatonin has also been found to inhibit platelet aggregation. Saliva melatonin sampling can be obtained from several laboratories throughout the country.

    Table 9 depicts several substances with either ionotropic (increase heart contractibility) or chronotropic (rhythm heart stabilizing) effects on the heart. Regular use of these substances can often augment typical conventional medications of similar nature, i.e., digitalis and antiarrythmics. Several studies have shown magnesium to be an excellent preventative of dysrythmias and can be especially useful in intravenous doses of 2-3 gm in the early stages of heart attack and for several days thereafter. Its use can prevent the serious rhythm disturbances that often accompany myocardial infarction. Long-term use is also suggested since most patients are magnesium deficient. Other studies have determined that the use of coenzyme Q10 in dosages of 300 mg/day one week prior to cardiac surgery improves three-fold the serum levels and tissue levels in the heart of this nutraceutical. This improvement seems to reduce the heart failure associated with low coenzyme Q10. Another study on the usefulness on coenzyme Q10 in clinical cardiology demonstrated large doses over time will reduce overall cardiac medication requirements significantly. (See insert on this page “Coenzyme Q10) Taurine, an amino acid has likewise been shown to have positive cardiac effects and diuretic properties. Hawthorne berry has been used for years by western herbologists as a good ionotropic natural agent.

Summary
    A multiangle assertive approach seems to be appropriate when treating the coronary artery disease patient. Hormonal issues should also be examined and a saliva profile may prove efficacious in determining DHEA, estrogen, progesterone, and testosterone levels. Recently, much has been written about hormones and their inverse relationship with coronary artery disease. By routinely screening with these saliva and blood tests, you will be able to note lipid levels, coagulability, glucose/insulin levels, melatonin level, hormone levels, inflammatory status, and homocysteine levels. A practitioner could then choose, from the tables provided, those nutritional supplements that would address areas of concern revealed by the test results. Abnormal tests would be noted and repeated after an appropriate length of treatment and adjustment of the treatment plan, by either increasing doses of already-prescribed nutraceuticals, with or without the addition of new agents. Further adjustment in the program would be necessary when the patient is taking concurrent medicine(s). Drugs that have similar properties to those nutraceuticals, that your patient is already taking, would require appropriate adjustment. For example, patients taking anti-coagulants would require lower doses of those supplements mentioned in Table 1. However, other patients, taking lipid-lowering drugs, may require increased doses of CoQ10. Remember, many coronaryrelated medications cause other nutritional deficiencies and I suggest that you refer to a text describing drug-herbal and drug-nutrient interactions.

Final thoughts:
    The use of EDTA, although it is considered by the conventional medical community as controversial, has revealed in many studies to have a significant place in the treatment of coronary artery disease along side the nutraceuticals presented in this paper. Heavy metals do play a role in artherogenesis and should be studied further. Don’t forget, in the midst of this complex array of nutraceuticals, water itself may improve the outcomes of coronary events. Simply drinking 4 or more glasses of pure water each day, can decrease myocardial infarction by more than 50%.

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