Supplemental Omega-6 and Omega-3 Fatty Acids: What to Buy
To introduce the reader to various omega-6 and omega-3 fatty acids, the following examples are given:

Perilla oil, 1000-mg per capsule, provides 550-620 mg of alpha-linolenic acid, a precursor to EPA and DHA. Use 6 softgels daily.
Flaxseed oil (1000-mg softgels) provides 520-570 mg per capsule of gamma-linolenic acid. Use 6 softgels a day.
Super GLA/DHA provides 920 mg of GLA, 1000 mg of DHA, and 400 mg of EPA. Use 6 capsules daily.
Evening primrose oil is a source of GLA. Use one to two 1300-mg softgels daily.
Borage oil also supplies GLA. A 1300-mg softgel supplies 300 mg of GLA. As a preventive, use 1-2 softgels a day and up to 5 a day as a therapeutic.
Note: Prothrombin time usually remains within a normal range when using omega-3. As the number of platelets decreases, platelet size typically increases; therefore, there is no overall decrease in platelet mass. The New England Journal of Medicine reported that the blood-thinning functions of fish oil are small compared to aspirin, but other researchers caution that bleeding time could increase to inappropriate levels if baseline platelet activity is impaired or fibrinogen concentrations are low (Katan 1995).

F

Fiber--is a hypolipidemic and antidiabetic agent, aids in weight loss, and blocks iron absorption
The intake of dietary fiber among people living in Western countries is low (about 17 grams a day in the United States), according to the Third National Health and Nutrition Examination Survey (NHANES). This is unfortunate, for soluble fiber offers significant protection against a number of risk factors associated with cardiovascular disease. For example, mucilages, guar gum, psyllium powder, oat bran, and pectin reduce cholesterol levels. Guar gum (5 grams with meals), psyllium powder (5 grams before meals), or pectin (10 grams with meals) reduce fasting and postprandial blood glucose, as well as insulin levels, in both healthy and diabetic subjects. If taken with meals, soluble fibers (6-10 grams a day) reduce iron absorption from foods, important to those with hemochromatosis or iron overload (Monnier et al. 1980) (to read about hemochromatosis as a contributor to cardiovascular disease, turn to Iron Overload in the section devoted to Traditional Risk Factors).

Illustrative of the value of fiber, researchers from the Veterans Affairs Medical Center, the University of Kentucky (Lexington), and the Procter & Gamble Company (Cincinnati, OH) evaluated the effectiveness of psyllium as a hypocholesterolemic and blood glucose modulator. Thirty-four men with Type II diabetes and mild-to-moderate hypercholesterolemia were randomly assigned to receive 5.1 grams of psyllium or a cellulose placebo twice daily for 8 weeks. The psyllium group showed significant improvements in glucose and lipid values compared with the placebo group. Serum total and LDL-cholesterol concentrations were 8.9% and 13.0% lower, respectively, in the psyllium group compared to the placebo group. All-day and postlunch postprandial glucose concentrations were 11.0% and 19.2% lower in the psyllium group (Anderson et al. 1999). These impressive results occur as fiber binds bile acids, cholesterol, and fats, preventing their absorption. Short-chain fatty acids, products of fiber fermentation in the colon, further inhibit cholesterol synthesis by the liver.

Studies in the New England Journal of Medicine confirmed the value of a high fiber diet in improving glycemic control and reducing hyperinsulinemia and plasma lipid levels in patients with Type II diabetes (Chandalia et al. 2000). In a randomized, 6-week crossover study, 13 patients with Type II diabetes were given diets containing either moderate or high amounts of fiber. The moderate fiber allowance was 24 grams (8 grams of soluble and 16 grams of insoluble), an amount compliant with guidelines established by the ADA. The high-fiber diet consisted of 50 grams of fiber (25 grams soluble and 25 grams insoluble).

During the sixth week of the high-fiber diet (as compared with the sixth week of the ADA diet) the diet supplying 50 grams a day of fiber lowered plasma glucose 10%, insulin concentrations 12%, total cholesterol 6.7%, triglyceride levels 10.2%, VLDL 12.5%, and LDL cholesterol 6.3%. It is speculated that the decrease in triglycerides and VLDL may be due more to improved glycemic control than to a direct relationship with the fiber. There was no significant difference between the two diets in terms of HDL cholesterol levels. Note: The fiber-rich foods included in the study were cantaloupe, grapefruit, raisins, oranges, papayas, lima beans, okra, sweet potatoes, winter squash, zucchini, oat bran, and oatmeal.

Fiber is also of advantage to individuals who wish to lose weight. Bulk tends to render a feeling of fullness, negating the desire to overeat. An overweight individual should consider using bulk fibers stirred into an 8-oz glass of water; drink the mixture about 20 minutes before meals.

Diabetics and those not accustomed to higher levels of fiber should initially use the material cautiously. Fiber can significantly alter insulin or sulfonylurea requirements and some individuals experience gastrointestinal distress until the GI tract becomes better acquainted with the new material. A suggested initial dosage is 1 tsp daily; gradually increase to 1 tsp 3 times daily.

Reader's guide to foods high in fiber
Grains are excellent sources of fiber, but many individuals find the addition of cereal grains problematic due to food sensitivities. Vegetables and fruits (raw and with peel intact) are pleasant fibrous additions to the diet.

G

Garlic--acts as a hypotensive, decreases fibrinogen, inhibits platelet aggregation, thins the blood, protects against LDL oxidation and arterial wall damage, reduces the incidence of arrhythmias, modestly reduces blood glucose levels, protects against iron overload, and is vasodilating
The consensus surrounding the benefits of garlic as a hypolipidemic is not unified. The Archives of Internal Medicine found garlic powder (900 mg a day for 12 weeks) to be ineffective in lowering blood lipids (Isaacsohn et al. 1998). Researchers concede that variations in preparations could be distorting results as well as gender. For example, women showed favorable effects in terms of coronary heart disease risk factors (i.e., increases in HDL-C and reductions in total cholesterol) using garlic oil, whereas men had small adverse effects. There was a significant difference in the garlic oil effect for glucose, with a reduction seen for men and an increase for women (Zhang et al. 2001).

Interestingly, the American Journal of Natural Medicine reported that 4000 mg of fresh garlic (guaranteeing an allicin content of at least 10,000 mcg or a total allicin yield of 4000 mcg) typically lowers total cholesterol levels 10-12%, triglycerides by about 15%, and LDL 15%, while increasing HDL cholesterol levels 10% (Murray 1995a). Healthy human volunteers given 600 mg a day of a garlic preparation (providing 7.8 mg of allicin for 2 weeks) reduced lipoprotein oxidation 34% compared to controls. It should be noted that garlic could cause a transient elevation in blood lipids, as garlic unseats fats deposited in tissues. With continued garlic supplementation, lipid stores complete the breakdown process and blood cholesterol levels modulate.

While much of the research has focused on improving lipid levels, researchers have isolated hypotensive factors in garlic as well. An analysis of published and unpublished randomized, controlled trials (415 patients) showed that 600-900 mg a day of dried garlic powder may be of clinical value in subjects with mild hypertension (Silagy et al. 1994). Other researchers have noted a 5.5% decrease in systolic blood pressure and a modest reduction in diastolic blood pressure in response to aged garlic extract (Steiner 1996).

Garlic, a sulfur-rich plant from the lily family, exerts its hypotensive nature through the following pathways:

Supplementation with aged garlic significantly reduced epinephrine, a vasoconstricting hormone released from the adrenal medulla (Steiner et al. 1998).
Garlic moderately inhibited (both in vivo and in vitro) the activity of ACE, an enzyme that increases blood pressure by catalyzing the conversion of angiotensin I to angiotensin II. This sequence constricts blood vessels, conserves water and sodium ions, and, unless interrupted, results in an increase in blood pressure (Rietz et al. 1993).
Garlic increases the activity of nitric oxide synthase, an enzyme essential for nitric oxide synthesis (Morihara et al. 2002). Nitric oxide, a relaxing factor, not only reduces blood pressure by acting as a vasodilator, but also lessens platelet aggregation, suppresses smooth muscle proliferation, reduces leukocyte adherence to vessel walls, and has antianginal and antispasmodic activity.
Garlic contains chemicals that act as calcium antagonists, reducing blood pressure and lessening the incidence of arrhythmias (Duke Database 1992).
Garlic exhibits additional cardiovascular protection by thinning the blood and acting as a fibrinolytic. German researchers reported successes in treating ventricular tachycardia and fibrillation with garlic, as well as the duration of arrhythmias (Isensee et al. 1993). Garlic also modestly reduces blood glucose levels, while EDTA-garlic combinations appear to decrease iron stores. Dosage suggestions are 1-2 Kyolic caplets (1000 mg) twice daily with meals or 2-8 capsules of Pure-Gar Caps (900 mg) daily with food. (One Pure-Gar Cap contains 900 mg of garlic bulb powder extract standardized to supply 9 mg of allicin, the highest potency available.)

Ginger--reduces cholesterol, prevents blood clots, is an anti-inflammatory, and has chemical components that are calcium antagonists, vasodilators, and ACE inhibitors
Ginger (Zingiber officinale) is reliable in treating a wide variety of cardiovascular complaints. Among ginger's protective properties is its ability to reduce cholesterol by promoting cholesterol excretion, impairing cholesterol absorption, and encouraging bile secretion and bile acid production. (Bile acid is a steroid acid of bile, produced during the metabolism of cholesterol.) Ginger exerts some of its hypolipidemic effects by stimulating cholesterol-7-alpha-hydroxylase, a rate-limiting enzyme of bile acid synthesis (Srinivasan et al. 1991).

Researchers reported the effects of administering ginger (200 mg/kg orally) to 61 cholesterol-fed rabbits (Bhandari et al. 1998). The marked rise in cholesterol, triglycerides, lipoproteins, and phospholipids (which normally follows 10 weeks of cholesterol feeding) was significantly reduced by ginger. The favorable results obtained from ginger were comparable to the hypolipidemic effects of the drug Lopid, known generically as gemfibrozil.

Various chemicals contained in ginger are calcium antagonists, vasodilators, ACE inhibitors, and diuretics, suggesting additional value in reducing blood pressure and the incidence of arrhythmias (Duke Database 1992).

Ginger reduces the likelihood of a blood clot through the following mechanisms:

Ginger, ginkgo, olive leaf, and garlic each contain chemicals that inhibit platelet-activating factor, PAF (Duke Database 1992). Adequate amounts of PAF are essential to coagulation and inflammatory processes; excesses are associated with blood clot formation, stroke, and heart disease.
Thromboxane A-2, a platelet-aggregating factor, is inhibited more by ginger than by either garlic or onions (Srivastava 1984).
Prostacylin, an inhibitor of platelet aggregation, is pressed into service by ginger, a process that further reduces the likelihood of blood clot formation (Backon 1986).
Although all of these effects are similar (blood clot reduction), a study involving healthy volunteers showed no irregularities in blood coagulation among participants receiving 2 grams of ginger a day (McCaleb et al. 2000). Nonetheless, caution is indicated for those individuals with baseline disturbances in platelet numbers or prothrombin time. Furthermore, the activity of prescribed blood thinners may be heightened if used in concert with ginger.

Ginger also appears to protect the heart during periods of inflammation. (Recall that inflammation is considered a trigger in heart disease.) Ginger's anti-inflammatory properties are due to interruption of the prostaglandin-leukotriene cascade, blocking damaging prostaglandins but leaving beneficial prostaglandins unaffected. Ginger root (gingerols) has been shown to inhibit cyclooxygenase pathways, sharing anti-inflammatory traits with other popular COX-2 inhibitors (Newmark et al. 2000; Faloon 2001).

A preventive dose of ginger is one to two 300-mg capsules 1-3 times a day. Interestingly, a researcher recently recommended 10 grams (approximately 1 tsp a day) to reduce platelet aggregation (Bordia et al. 1997). A qualified healthcare practitioner must monitor this dosage. JAMA published an article raising a cautionary flag concerning the risk of cardiovascular events among users of COX-2 inhibitors (such as Celebrex and Vioxx) (Mukherjee et al. 2001). The FDA has also objected to claims and promotional activities by Pharmacia Corporation minimizing the potentially serious risk of bleeding associated with Celebrex (Fort 2001). It is hoped further prospective evaluations will characterize and determine the magnitude of the risks. In the interim, natural COX-2 inhibitors (including ginger) loom as welcome alternatives.

Ginkgo Biloba--improves circulation and memory; reduces platelet aggregation and excesses of fibrinogen; has antioxidant and anti-inflammatory activity; prevents capillary fragility; lessens angina attacks, dyspnea, and intermittent claudication; limits brain damage following stroke; increases insulin secretion; and is a vasodilator
Ginkgo biloba is one of the oldest surviving species on earth. But this ancient herb, renowned for its ability to retard aging, has survived the test of time and is yielding remarkable benefits for millions of Americans and Europeans. Heart, circulatory, and cognitive disorders are the principal reasons individuals rely upon ginkgo. More than 300 clinical and experimental studies have supported the worth of Ginkgo biloba.

Ginkgo has won favor among the Chinese as a heart tonic by lessening coronary demands for oxygen, thus reducing shortness of breath and chest pain (Duke 1997).
Ginkgo's antioxidant properties, particularly the flavones, assist in strengthening blood vessel walls and improving tone and elasticity (Joyeuz et al. 1995).
Ginkgo is a vasodilator, making it useful in lowering blood pressure and treating many forms of heart disease (120 mg a day at bedtime for 3 months reduced systolic blood pressure from 125 mmHg to 118 mmHg and diastolic from 86 mmHg to 68 mmHg) (Kudolo 2000). Some of the chemicals contained in ginkgo are ACE inhibitors, further explaining its hypotensive nature (Duke Database 1992).
Ginkgo is also an anti-inflammatory, adding additional merit to its cardiac profile (Hopes 2000). Consult the section entitled Link Between Infections and Inflammation in Heart Disease (in this protocol) to understand the value of anti-inflammatories in a comprehensive cardiovascular program.
Ginkgolide B infusions are comparable to standard antiarrhythmic drugs in controlling irregular heartbeats (Koltai et al. 1989).
Patients with chronic cerebral vascular insufficiency typically respond well to ginkgo biloba extract (GBE), reporting improvement in vertigo, headache, ringing in the ears, and memory (Murray 1995c).
GBE also significantly improves the supply of blood to the limbs. As resting blood flow and peripheral circulation improve, intermittent claudication, a cramp-like pain in the calves, diminishes. In fact, 40 mg of GBE twice a day is from 10-45% more effective at controlling intermittent claudication than pentoxifylline (Trental) (Duke 1997).
Varro Tyler, Ph.D. (dean and professor emeritus at Purdue University), profiles ginkgo in his book Herbs of Choice as a treatment for peripheral vascular disease and cerebral circulatory disturbances (Robbers 2000). Ginkgo can, in fact, act as a prophylaxis against strokes by reducing fragility of capillaries and counteracting erythrocyte and platelet hyperaggregability. The nature of platelets is strongly influenced by platelet-activating factor (PAF), which ginkgo inhibits.

The American Academy of Neurology reported that ginkgo reduced the extent of brain damage caused by artificially induced strokes in mice (June-July 2000 edition). Mice receiving low-dose GBE 1 week prior to stroke reduced the area in the brain that was affected by 30%. The journal Stroke concurred that GBE reduced stroke infarct volume but noted the beneficial effect appears to be dose related. In fact, researchers found that higher doses had the potential for increasing the risk of intracerebral hemorrhage. The combined clinical use of GBE with antiplatelet, anticoagulant, and thrombolytic agents could potentially further increase the risk (Clark et al. 2001).

Researchers recently reported a function of ginkgo biloba not frequently credited to the herb, that is, an ability to increase insulin secretion. A study was undertaken to determine the effect of GBE on glucose-stimulated pancreatic beta-cell function in normal glucose-tolerant individuals: 20 participants (14 females and six males, ages 21-57) underwent a 2-hour, 75-gram oral glucose tolerance test before and after ingestion of GBE (120 mg a day at bedtime). During the 3-month evaluation, both fasting plasma insulin and C peptide (a biologically inactive residue of insulin formation) increased. Dr. G.B. Kudolo (principal researcher) believes the changes in the insulin-C peptide response curves are due to increased production and secretion of insulin (Kudolo 2000).

Note: Herbals that influence glycemic control by increasing insulin secretion would be contraindicated in cases of existing hyperinsulinemia. If insulin production declines to the point that hypoinsulinemia exists, herbs that encourage insulin release would then be appropriate.

High quality GBE is typically standardized to contain a minimum of 24% ginkgo flavone glycosides and 6% terpene lactones. Side effects are rare when using the standardized extract; however, concomitant use with an anticoagulant medication or administering GBE to individuals with prolonged prothrombin time may make ginkgo inappropriate. (Ginkgo is not recommended for pregnant or lactating women.) A dosing suggestion is 120-240 mg a day. (A dose of 120 mg a day assists in reducing excessive fibrinogen levels, i.e., levels greater than 300 mg/dL).

Grapefruit Pectin--is hypocholesterolemic
Grapefruit pectin and other food sources rich in soluble fibers are useful adjuvants in the treatment of hypercholesterolemia. In fact, grapefruit pectin, a stringy white fiber, appears equal to or more effective than most popularly prescribed drugs for lowering cholesterol. Since grapefruit pectin is highly soluble, the pectin is broken down in the small intestine so that 100% of the fiber is utilized.

Illustrative of its potential, guinea pigs administered grapefruit pectin reduced their cholesterol by greater than 40% over a 6-week period (Cerda 1994b). No side effects were noted, a vast departure from the potential risks associated with many prescription drugs.

In addition, researchers found citrus pectin effective in reducing atheromatous plaque. Substantiating its worth, an atherogenic diet was fed to a group of microswine to induce hypercholesterolemia. Plasma cholesterol levels rose rapidly and for 360 days were sustained at levels 6-12 times the norm. Half of the microswine were then fed a diet containing 3% grapefruit pectin; the remaining animals received the original diet. Animals were slaughtered 270 days later, and the extent of atherosclerosis determined. The mean surface area covered by plaque in the aorta was 13.6% in the group not receiving pectin compared to 5.3% in the group receiving pectin. Mean coronary artery narrowing was 45% without pectin and 24% with pectin (Cerda et al. 1994a).

Human trials have also been gratifying. Hypercholesterolemic subjects using no other cholesterol lowering agents and without lifestyle modification significantly lowered total cholesterol and LDL while increasing HDL levels (Cerda et al. 1988). Begin with less than 1 scoop of grapefruit pectin (with meals) and gradually increase until 2-3 scoops are used daily. If using grapefruit pectin tablets, use 1000 mg with meals.

Gugulipid--lowers total cholesterol, LDL, and triglycerides; increases HDL cholesterol; regresses plaque formation; opposes platelet aggregation; and has fibrinolytic activity
Numerous studies have demonstrated that gugulipid is beneficial to about 70% of individuals with disorganized lipid profiles, that is, elevations in LDL and total cholesterol or triglycerides. Human clinical trials showed gugulipid dropped total cholesterol levels by 14-27% in a 4- to 12-week period and reduced triglycerides 22-30%. HDL cholesterol increased in 60% of cases considered gugulipid-responsive. In addition, gugulipid regressed plaque formation, opposed platelet aggregation, and encouraged fibrinolysis. Gugulipid is regarded as nontoxic, with liver and kidney function, blood sugar control, and hematological parameters unaffected during clinical trials (Agarwal et al. 1986; Nityanand et al. 1989; Murray 1995c).

Comparing gugulipid to clofibrate, hypercholesterolemic patients appeared more responsive to gugulipid therapy, while patients with hypertriglyceridemia responded better to clofibrate (Nityanand et al. 1989). A suggested dosage is 500 mg (5% guggulsterone content) 3 times a day.

H

Hawthorn Berry (Crataegus oxyacantha)--normalizes blood pressure; is beneficial to dieters and those with congestive heart failure; prevents premature ventricular contractions and hypoxia; has diuretic and antioxidant potential; lowers cholesterol; acts as a vasodilator; is an ACE inhibitor, beta-blocker, and anti-inflammatory; increases exercise tolerance; and reduces the incidence of tachycardia and palpitations
Dr. James Duke, botanist, says that when hawthorn is evaluated chemically, it appears that the herb covers most of the cardiovascular bases. For example, it contains a calcium-antagonist (magnesium), ACE inhibitors (procyanidins), and beta-blockers (catechin, epicatechin, and procyanidins), plus numerous diuretics, cholesterol-lowering compounds, anti-inflammatories, and antioxidants (Duke 2000b).

The hawthorn berry is considered a smart herb with adaptogenic qualities in regard to normalizing blood pressure. Hawthorn gains much of its hypotensive and weight management properties through its diuretic action. Also, its ACE inhibiting factors interrupt the renin-angiotensin sequence, resulting in lower blood pressure and improved cardiac output (Duke 2000b). Clinicians compare the effectiveness of hawthorn to Captopril, a drug prescribed for congestive heart failure (CHF) and hypertension that also works by inhibiting ACE. (Hawthorn, although helpful in blood pressure management, should not be regarded as the sole therapeutic for hypertension.)

The bioflavonoid content of hawthorn appears to be responsible for much of the herb's cardiac potential, that is, dilating blood vessels, enhancing vitamin C absorption, and protecting against vascular breaks or leaks. Bioflavonoids are powerful antioxidants that not only protect against free-radical damage, but also increase oxygen delivery and blood flow to the heart. This reduces the effort and stress imposed upon the heart to circulate blood, and as an additional bonus, a reduction in blood pressure usually occurs. The risk of stroke was, in fact, 73% lower among individuals who consumed greater amounts of flavonoid-rich foods compared to individuals who consumed less (Keli et al. 1996; Roanoke Times 1996).

During the Middle Ages, hawthorn was used to treat dropsy, a condition now recognized as CHF. Today, European physicians still use hawthorn to treat early signs of CHF, relying upon the herb to strengthen the heart and the power of cardiac contractions. Drugs that have the ability to power up the heart can cause cardiac irregularities; conversely, it appears hawthorn can energize the heart without prompting arrhythmias. Hawthorn, in fact, has a normalizing effect upon the heartbeat, lessening the incidence of tachycardia (a heart rate greater than 100 beats per minute) and palpitations (Santillo 1990).

Studies confirm the multiplicity of hawthorn's actions:

Various clinicians report an excellent patient response, treating valvular insufficiency, heart fibrillations, and hypoxia with hawthorn (Santillo 1990; Ritchason 1995; Duke 1997).
Hawthorn appears to stabilize heart rhythm and increase exercise tolerance (Duke 1997). Problem-free exercise occurs as the heart becomes stronger and less taxed by exertion.
Hawthorn reduces cholesterol levels and the size of existing atherosclerotic plaque (Wegrowski 1984).
Hawthorn is best used long-term because the active constituents do not produce rapid results. It may take 4-8 weeks for improvement in subjective complaints and increased exercise tolerance. Although it is regarded as gentle and safe for chronic usage, a physician should evaluate the patient's drug list before adding hawthorn to the total package. A dosage suggestion is 250-900 mg daily.

Homocysteine-Lowering Nutrients and Elimination Pathways

Homocysteine, a naturally occurring amino acid, is derived from methionine and produced in small amounts by the body. When homocysteine is not detoxified or reduced through metabolic processes (i.e., remethylation or transsulfuration) and begins to accumulate, various biological failures occur. According to some experts, homocysteine is now recognized as the single greatest biochemical risk factor for heart disease (McCully 1996) (for an introduction to homocysteine, consult Newer Risk Factors appearing earlier in this protocol).

The published literature emphasizes that folic acid, vitamin B12, and zinc (nutrient cofactors) and trimethylglycine (a methyl donor) are critical to the remethylation of homocysteine, the most common detoxification pathway. Remethylation occurs as methyl groups are donated to homocysteine to transform it to methionine and S-adenosylmethionine (SAMe) (Porter et al. 1993; Undas et al. 1993; Malinow et al. 1998; Baker-Racine 2002).

SAMe, the chief methyl donor, is crucial to the methylation process. Initially, methionine reacts with ATP to produce SAMe. SAMe is then used for methylation and a byproduct of this reaction, homocysteine, is recycled back to methionine. This cyclic dance continues faultlessly, unless something throws it out of sync.

Too much methionine will disrupt the delicate balance. Flesh foods and dairy products are rich in methionine and require greater amounts of nutrient cofactors to preserve the methylation process. Chronic inflammation, high intensity exercise, and age can also put the brakes on methylation. When this occurs, the cycle is broken, and homocysteine detoxification stagnates. The problem comes full circle, as excessive amounts of homocysteine interfere with the methylation process.

Trimethylglycine (TMG), also called betaine, emerges as one of the most important nutrients to prevent and reverse existing heart disease, in part by supporting remethylation (Baker-Racine 2002). TMG usually causes a substantial lowering of homocysteine, but regular dosing must continue to sustain the improvement. The dosage varies from one to eight 500-mg tablets a day, depending upon the amount needed to maintain healthy levels (below 7 micromol/L of blood).

Choline, another methyl donor, can act independently (not requiring cofactors) to lower homocysteine levels, but it only influences remethylation in the liver and kidneys, leaving the heart and brain less protected. Methylating factors, as vitamin B12 and folic acid, add additional protection.

The second means of homocysteine disposal is via the transsulfuration pathway, a sequence dependent upon vitamin B6. This pathway converts homocysteine to the powerful antioxidants cysteine and glutathione, but a deficiency of the B6-dependent enzyme, cystathione-B-synthase, can hamper this process. An alternative is to take larger doses of vitamin B6, but this course is not without risk. Chronic megadose vitamin B6 supplementation (300-500 mg daily) can result in neurological symptoms that typically fade when the dosage is reduced or discontinued. Careful monitoring to determine the lowest vitamin B6 dose capable of controlling homocysteine levels is essential.

Some individuals lack the enzyme necessary to convert vitamin B6 to its active form (Robinson et al. 1995). In this case, use the biologically active pyridoxal-5-phosphate to control elevations in homocysteine. Note: Vitamin B6 is also a reliable diuretic, making it of particular advantage to patients with high blood pressure and congestive heart failure.

For most individuals, hyperhomocysteinemia is a modifiable cardiovascular risk factor. In fact, about one-half of individuals with hyperhomocysteinemia respond favorably to vitamin B6 supplementation. Researchers selected 421 patients, mildly hyperhomo-cysteinemic, to determine their response to vitamin B6 (250 mg daily). After 6 weeks of vitamin B6 supplementation, 56% of the patients had normal homocysteine levels. Non-normalized homocysteine concentrations were treated with a combination of supplements, vitamin B6 (250 mg daily) and/or folic acid (5 mg daily) and/or TMG (6 grams daily). The more aggressive treatment normalized homocysteine levels in 95% of the remaining cases (Franken et al. 1994).

Another 20% of hyperhomocysteinemic patients have a mutation in the gene, methylenetetrahydrofolate reductase, disrupting the conversion of folic acid to 5-methyltetrahydrofolate, an active contributor in the methyl donation pathway of folate. In this incidence, it is necessary to use 5-methyltetrahydrofolate supplementation to bypass the metabolic block (James et al. 1999; Bland 2000a) (additional information regarding methylenetetrahydrofolate reductase appears in the section devoted to Heredity, one of the traditional risk factors, in this protocol).

A Polish study showed that administering folic acid (5 mg a day), vitamin B6 (300 mg a day), and B12 (1000 microgram a day) over an 8-week period reduced benchmark homocysteine levels by one-half (from 20 micromol/L to 10 micromol/L) and also reduced thrombin, an intermediate in the production of fibrinogen (Undas et al. 1999). Individuals with low folate status, regardless of age or sex, have a 69% greater risk of fatal heart disease compared to individuals with higher levels (greater than 13.6 nanomol/L) (Morrison 1996; Pirisi 2001; Tice et al. 2001). It is theorized that properly administered folate might prevent as many as 13,500-50,000 premature deaths annually (Boushey et al. 1995).

The New England Journal of Medicine reported that a combination of folic acid, vitamin B12, and pyridoxine reduced homocysteine levels and also the necessity for revascularization procedures. (Revascularization refers to restoring adequate blood supply by means of a coronary bypass or angioplasty.) Researchers concluded that this inexpensive nutritional therapy, with minimal side effects, should be considered as adjunctive therapy for all patients undergoing coronary angioplasty (Schnyder et al. 2001).

The American Journal of Clinical Nutrition reported that a chemical component of coffee and black tea (chlorogenic acid) could raise plasma homocysteine levels (Olthof et al. 2001). Another team of researchers targeted unfiltered coffee as being most contributory to hyperhomocysteinemia (Grubben et al. 2000). On the other hand, a diet rich in fruits and vegetables may decrease the risk of heart disease (7-9%) by reducing blood levels of homocysteine. Fresh and unaltered foods have a more reliable nutrient bank and are capable of delivering more homocysteine-lowering vitamins and minerals.

It should be noted that niacin may increase plasma homocysteine levels (from 1-4 micromol/L) in some people (Desouza et al. 2002; Berkeley Heart Lab). Researchers at Pantox Laboratories (California) explain that niacin appears to interfere with homocysteine clearance by depleting SAM-e. Concurrent TMG supplementation may represent a cost-effective way to prevent niacin-mediated depletion of SAMe and thus avoid hepatotoxicity and possibly other adverse niacin side effects (McCarty 2000).

Administering homocysteine-lowering nutrients is so individualized that testing is essential to determine adequate dosages. To assume that homocysteine is not a threat (because you have the B vitamins in your supplemental protocol) is not a guarantee that the dosage is appropriate to render protection. The following daily supplements (used alone or in combination) have demonstrated homocysteine-lowering effectiveness: 500-9000 mg of TMG, 800-5000 mcg of folic acid, 1000-3000 mcg of vitamin B12, 250-3000 mg of choline, 250-1000 mg of inositol, 30-90 mg of zinc, 100-500 mg of vitamin B6, and 200-800 mg of SAM-e. SAM-e is of value in lowering homocysteine levels only if folic acid and vitamins B6 and B12 are also present; without nutrient cofactors, SAM-e will eventually break down into homocysteine.

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