When CRP levels are factored in as a cardiovascular risk, along with hypertension, diabetes, elevated cholesterol, family history, and BMI, there is significant improvement in predicting cardiac health compared with models that exclude CRP testing. Ten prospective studies (six in the United States and four in Europe) have consistently shown that hs-CRP is a powerful predictor of a future first coronary event in apparently healthy men and women. ("hs" refers to high sensitivity testing, the only method able to discriminate the subtle differences in CRP in a range that accurately predicts coronary risk.)

As new as CRP is to many as a risk factor in coronary artery disease, Rudolf Virchow, a German pathologist (1821-1902), hypothesized that inflammation was the causative factor in the atherogenic process. Decades later, scientists confirmed that increased monocytes (white blood cells critical in early plaque development) and macrophages (mononuclear phagocytic cells capable of scavenging and ingesting dead tissue and degenerated cells) are present, particularly at points of plaque rupture. It appears that CRP and several other inflammatory markers may be elevated many years prior to a coronary event.

However, data from the University of Texas Health Sciences Center indicate that CRP is more than a measurable antecedent preceding a cardiac problem. CRP, along with the cooperative efforts of an unidentified serum factor, acts directly upon the blood vessels to activate adhesion molecules in endothelial cells: the intercellular adhesion molecule (ICAM-1) and the vascular cell adhesion molecule (VCAM-1). VCAM-1 appears to be an early molecular marker of lesion-prone areas as a response to experimental hypercholesterolemia. In humans, ICAM-1 and VCAM-I expression is increased in the endothelium of atherosclerotic plaque. Researchers concluded that CRP appears intricately involved in the inflammatory process, thus proving to be a potential target for the treatment of atherosclerosis (Pasceri et al. 2000; Biomedical Science 2001; Alvaro et al. 2002).

The journal Circulation reports that CRP appears able to affect the activity of LDL cholesterol (increasing atherogenesis). The cycle begins as stranded LDL is taken up by macrophages; macrophages, gorged with fats contained in blood, become bloated and develop into foam cells. When foam cells have reached their maximum load, they explode, discharging their fatty contents into the blood vessel wall at the site of injury. The presence of added fat signals the need for more macrophages to clean up the mess. They stuff themselves, explode, and the cycle starts anew. Since native LDL does not induce foam cell formation, CRP appears to ready LDL for uptake by the macrophages, initiating the sequence (Braley 1985; Zwaka et al. 2001).

In the Physicians' Health Study, middle-aged men deemed healthy at baseline were evaluated over an 8-year period in regard to CRP levels and a cardiovascular event. This study showed that those in the highest quartile of hs-CRP had a twofold higher risk of (future) stroke, a threefold higher risk of (future) heart attack, and a fourfold higher risk of (future) peripheral vascular disease (Rifai et al. 2001a, 2001b). Stroke patients with the highest CRP levels were nearly 2.4 times more likely to die within the next year compared to patients with the lowest levels (DiNapoli et al. 2001). Another of hs-CRP's strengths is its ability to detect at-risk patients with normal cholesterol levels.

The risk of stroke, according to data reported in the New England Journal of Medicine, decreased among those using statin drugs (White et al. 2000). The Cholesterol and Recurrent Events Trial concluded that pravastatin (administered long term) appears to be doing more than reducing cholesterol, perhaps acting as an anti-inflammatory. Another study (also published in the New England Journal of Medicine) reported that pravastatin reduced CRP levels after both 12- and 24-weeks' administration, independent of LDL cholesterol levels. It appears statin therapy may prevent coronary events among individuals with relatively low lipid levels but with elevated levels of CRP (Ridker et al. 2001). Conversely, some drugs, including hormone replacement therapy, actually increase CRP levels and the inflammatory response.

Researchers hypothesized in the Journal of the American College of Cardiology that the cytomegalovirus (CMV) (herpes-type viruses) may stimulate an inflammatory response, reflected by elevated CRP levels. The journal Circulation reported that older people who have IgG antibodies to the herpes simplex-I virus experienced a twofold increase in the risk of a myocardial infarction or coronary heart disease death. Since the relationship between CMV and coronary heart disease is not observed in all people, researchers consider the ability of individuals to control CMV inflammatory activities, the variable in the progression to a myocardial infarction (Zhu et al. 1999; Siscovick et al. 2000).

The infectious process in heart disease is chronicled in numerous studies, but the microorganisms involved remain of interest. Subsequently, a group of researchers from Johannes Gutenberg University (in Mainz, Germany) evaluated 572 heart patients. They tested for antibodies in the bloodstream that would show that the immune system had at some stage been exposed to a variety of different viruses and bacteria. These included herpes simplex-1 and -2, which cause cold sores and genital herpes; Epstein-Barr virus, which causes mononucleosis, chlamydia, and flu virus; and Helicobacteria pylori, which causes stomach ulcers. Then they looked at the patients again 3 years later to see how many had survived. The death rate was 3.1% in patients who tested positive for only a few of the viruses or bacteria, 9.8% for those with four or five, and 15% in those positive for six to eight. Among those who had the most advanced artery hardening, 20% of those exposed to between six and eight infections had died, compared to 7% of those with three or fewer (BBC 2002b).

Japanese researchers concentrated upon finding a method to distinguish between bacterial and viral infection by measuring inflammatory markers, among them C-reactive protein (CRP). They found that during the acute stage of bacterial infections, CRP levels were moderately or highly increased, whereas in viral infections, CRP levels were normal or slightly increased. The researchers propose that the measurement of CRP (among various inflammatory markers) during the acute phase of illness, that is, within 5 days of onset, is of value to determine whether the infection is caused by a bacteria or virus (Sasaki et al. 2002). For an opposing view regarding the association between viruses and CRP levels, please consult the section entitled Link Between Infections and Inflammation in Heart Disease in this protocol.

Figure 4 shows the risk factors associated with CRP (data extracted from publications authored by Dr. Paul Ridker). It is important to note that risk factors vary according to individual publications and may change with future publications.

Risk Factors Associated with CRP

Current research indicates that persistent CRP elevation, lasting longer than 96 hours following a successful coronary stent implantation, is predictive of prolonged inflammation leading to re-stenosis (Gottsauner-Wolf et al. 2000). Patients who developed restenosis within the first 6 months had increases in CRP levels for up to 96 hours following the procedure, although their baseline CRP had been normal. Patients without restenosis displayed an increased CRP level that was sustained for no longer than 48 hours and subsequently decreased. Higher CRP levels appear predictive of less satisfactory end results, following angioplasty and stent procedures.

Although many of the newer risk factors are not yet standardized, some laboratories are using a CRP reference range of 0.24-1.69 mg/L. Recent medical events resulting in tissue injury, infections, or inflammation may increase CRP levels and, if not factored into clinical interpretations, can distort results.

To read more about factors affecting CRP levels, consult the sections referring to Smoking, Obesity, Sedentary Lifestyle, Gender, Gum Disease, and The Link Between Infections and Inflammation in Heart Disease. Improved glycemic control and normalizing blood pressure may also assist in reducing inflammation and (subsequently) CRP levels.

CRP appears responsive to aspirin, DHEA, fish oil, pravastatin, vitamin C, vitamin E, and vitamin K supplementation (consult the Therapeutic Section to learn more about natural products). As research continues, it may be found that many other nutrients and herbs known for their anti-inflammatory properties are equally valuable in maintaining healthy CRP levels. Note: CRP appears to reduce levels of vitamins A, C, and E, as well as carotenoids, zinc, and selenium. Individuals with elevations in CRP may wish to emphasize these nutrients for their contribution to cardiac health.

THE LINK BETWEEN INFECTIONS AND INFLAMMATION IN HEART DISEASE

Infections are of particular interest because of the increasing attention paid to the role of inflammation in heart disease, according to David S. Siscovick, M.D., professor of medicine and epidemiology at the University of Washington. The data incriminate the infectious process in various phases known to contribute to heart disease. For example, current research suggests that infection may be an important determinant of fibrinogen levels, offering one possible explanation for the association between chronic or acute infection and vascular events (Woodhouse et al. 1997). Many researchers class inflammation as worse than cholesterol at triggering heart attacks. Note: Men with hypercholesterolemia and inflammation have a significantly higher risk of cardiovascular death (2.4) compared to those with only high cholesterol levels (1.4) (Engstrom et al. 2002).

Dr. Paul Ridker (Boston's Brigham and Women's Hospital) recently explained that everyone reaching middle age has some degree of fat buildup, that is, plaque in the vasculature. New evidence suggests the plaque becomes threatening if weakened by inflammation, which makes the buildup squishy and fragile. Even a small lump can burst, promoting the formation of a clot that in turn chokes off blood flow and causes a heart attack. Thus, reducing the inflammatory process is of equal importance to lipid monitoring in controlling the dangers of plaque (Associated Press 2002).

Researchers observed that mortality from ischemic heart disease markedly increases during the flu season, particularly among the elderly. One reason for this appears to be that patients with influenza A, a flu virus, tend to have much higher levels of CRP. Researchers at Rochester General Hospital and Rochester School of Medicine and Dentistry showed that CRP increased 370% during infection and that old age magnified the increase (Falsey et al. 2001; Horan et al. 2001).

A higher white blood cell count, common when the body is fighting off infection, is associated with an increased coronary risk by diminishing blood flow to the heart muscle and encouraging blood clot formation. The higher the white blood cell count, the greater the patient's risk of death from a heart attack or of developing congestive heart failure (Barron et al. 2000).

In fact, angina pectoris appears less a prognosticator of a forthcoming heart attack than a febrile (flu-like, feverish) infection prior to the attack. Peter Ammann, M.D. (Switzerland), stated that he has observed significantly higher numbers of myocardial infarctions among patients with febrile conditions, mainly of the upper airways, within 2 weeks prior to infarction (Ammann et al. 2000; Healthlink 2000).

Bacteria appear to gain entry into the heart via immune cells, most likely activated in the process of clearing infections from the respiratory passages. The bacteria most suspected of initiating coronary problems are Chlamydia pneumoniae, Pasteurella aerogenes, Enterococcus endocarditis, Staphylococcus aureus, Enterococcus faecalis, Candida albicans, and Viridan streptococcus. (Some researchers add H. pylori, a bacteria associated with duodenal ulcers, peptic ulcers, and chronic gastritis, to the list.)

Tissue specimens from patients who had undergone a carotid endarterectomy showed high levels of C. pneumoniae in 11 of 17 cases (64%). The American Heart Association also reported that C. pneumoniae was found in the infected arteries of autopsied cardiac patients. Dr. Tatu Juvonen (Oulu University Hospital in Finland) explains that C. pneumoniae is a specific microbial antigen that causes inflammation and atherosclerotic cells to proliferate (Juvonen 2000; Mosorin et al. 2000; Vink et al. 2001).

An alternative to this dismal situation may be antibiotic therapy, controlling the inflammatory process attacking the vessel wall. An American study of more than 16,000 British patients showed that people treated with two types of antibiotics had a significantly reduced risk of heart attack. Those treated with tetracyclines were at 30% less risk than patients not given antibiotics, while those who took quinolones (antimicrobials) had a 55% reduced risk. It appears antibiotics may act in the same fashion as anti-inflammatory drugs, reducing inflammation in the arteries (BBC News 1999, 2002a).

Inflammation appears to be an independent risk factor that may explain cardiovascular disease in the presence of normal cholesterol, blood pressure, and coronary arteries. MINC patients, individuals experiencing a myocardial infarction with normal coronary arteries, should be at lower risk for a cardiac event because they most often have normal electrocardiograms, higher HDL levels, and no significant impairment in LDL cholesterol. Dr. Ammann believes the trigger may be systemic inflammation or specific infective agents, advancing a benign complaint to a life-threatening condition. Interestingly, migraine headaches have also been observed as forerunners to a heart attack in otherwise healthy individuals (Ammann et al. 2000; HealthLink 2000).

IS ATRIAL FIBRILLATION PREDICTIVE OF CARDIAC MORTALITY?

Atrial fibrillation, a condition shared by over 2 million Americans, occurs when the atria, the upper chambers of the heart, beat faster than the lower two chambers, the ventricles. Many problems can cause atrial fibrillation, including a leaky heart valve, hypertension, obesity, stimulants (including caffeine and alcohol), medications (such as sumatriptan, a headache drug), and thyroid disorders. Dr. Robert Atkins, M.D., adds that patients should be evaluated for heavy metal intoxication and mycoplasmal infections, factors also capable of provoking atrial fibrillation.

Although not immediately life-threatening, atrial fibrillation may cause up to a 30% reduction in cardiac output, resulting in shortness of breath, fatigue, and reduced exercise capacity. In fact, the American Heart Association no longer regards atrial fibrillation as a benign disorder. About 75,000 strokes related to atrial fibrillation occur each year in the United States. Up to 23% of such patients die, and 44% experience significant neurologic deficits. (The mortality rate from other causes of stroke is about 8%.) Nonetheless, Dr. H.J. Crijns (University Hospital Gröningen, the Netherlands), declares that even patients with heart failure should not be in greater danger because of atrial fibrillation if the condition is well managed (Kennedy 1999; Alpert 2000; Crijns et al. 2000).

Blood thinners are often prescribed for atrial fibrillation, but a program based in natural medicine is also helpful. While full correction of the chaotic rhythm associated with atrial fibrillation is often difficult to achieve, nutritional supplements can lessen the risk of a blood clot. Dr. William Campbell Douglass, M.D., states that vitamin E (800 IU daily), cod liver oil capsules (4 daily), olive oil (1 tbsp daily), and bromelain (about 750 mg 3 times a day on an empty stomach) have similar action to Coumadin and aspirin, thinning the blood and reducing the risk of a thrombotic event (Douglass 1996). Other heart nutrients such as CoQ10, hawthorn, carnitine, taurine, magnesium, and ginkgo biloba are also important. To read more about the supplements recommended for atrial fibrillation, please consult the Therapeutic section of this protocol. Also refer to the Thrombosis Prevention protocol in this book.

Conversely, in chronic aortic regurgitation, a number of compensatory adjustments occur, rendering aortic regurgitation less dangerous. In fact, the majority of patients remain asymptomatic through this compensated phase, which may last for decades. With time, the left ventricle progressively enlarges and depressed myocardial contractility increases. This can progress to the extent that the full benefits of surgical correction, that is, recovery of left ventricular function and improved survival, are no longer possible.

The results of several studies, involving 490 asymptomatic patients with chronic aortic regurgitation who were followed for an average of 6.4 years, give a brief history regarding the developmental patterns of the condition.

The rate of progression to symptoms and/or left ventricle dysfunction averaged 4.3% a year. (As the left ventricle goes, so goes the heart.)
Sudden death occurred in six of the 490 patients (an average mortality rate of < 0.2% a year).

Are Artificial Valves as Good as Natural Valves?
The replacement of diseased natural heart valves with artificial valve can be life-saving, but the replacement valves are never considered as good as healthy natural ones. There are two general types of valves: mechanical and bioprosthetic (usually taken from pigs). The mechanical valves last longer but require the patient to take anticoagulants. The bioprosthetic valves do not require long-term anticoagulation therapy, but they frequently must be replaced after about 10 years in adults. Their replacement comes quicker in children and persons on kidney dialysis. The major risk of prosthetic heart valves is stroke. Those taking anti-coagulants reduce the incidence of stroke, but the risk is not totally eliminated.

The following natural products may be of value to patients with valvular disease. The herbs profiled have one or more chemicals that convey the biological property delineated and are subsequently not equal in therapeutic strengths (Duke Database). Researchers state that carnitine may provide independent benefit in ischemia when used as monotherapy, or additional benefit when used in combination with conventional beta-blockers or calcium antagonists (Jackson 2001). To learn more about the following supplements, please consult the Therapeutic section.

Vasodilators. Angelica, garlic, ginger, ginkgo biloba, hawthorn, magnesium, niacin, and olive leaf
ACE inhibitors. Angelica, garlic, ginger, ginkgo biloba, grape seed, green tea, hawthorn, olive leaf, procyanidins, and taurine
Calcium blocking properties. Angelica, garlic, ginger, ginkgo biloba, grape seed, green tea, hawthorne, magnesium, and olive leaf
Digitalis-like activity. Bugleweed and taurine
Diuretic activity. Angelica, bugleweed, curcumin, garlic, ginger, grape seed, green tea, hawthorn, olive leaf, taurine, vitamin B6, vitamin C, and vitamin E
Anti-inflammatories. Angelica, bromelain, bugleweed, chondroitin, curcumin, DHEA, EFAs, garlic, ginger, ginkgo biloba, grape seed, green tea, hawthorn, olive leaf, and vitamin C
Beta-blocking activity. Grape seed, green tea, hawthorn, magnesium, and taurine

Therapeutic Section

Alpha-Lipoic Acid (a.k.a. Thiotic Acid)--beneficial in preventing and treating Syndrome X, has antioxidant and antidiabetic activity, protects LDL cholesterol against oxidation, lowers total cholesterol, is beneficial in congestive heart failure and strokes, inhibits protein glycation, and stabilizes arrhythmias
Some researchers credit alpha-lipoic acid with being the principal supplement for preventing and reversing Syndrome X. Lipoic acid earned this reputation by increasing the burning of glucose. The mitochondria (the powerhouse of the cell) are one of the benefactors of enhanced glucose utilization, via the Krebs's cycle, a process that utilizes glucose, amino acids, and fatty acids to yield high energy. Many of the B vitamins assist in maximizing production from the Krebs's cycle, but perhaps none is as efficient as lipoic acid (Challem et al. 2000).

Note: Free radicals are produced as a byproduct of the energy generated during the Krebs's cycle. Alpha-lipoic acid appears to quench free radicals that are not contained during the reactions.

As glucose is provided to fuel the Krebs's cycle, blood glucose and insulin levels decrease and simultaneously another perk occurs: insulin sensitivity increases. Lipoic acid resulted in a 50% increase in insulin-stimulated glucose disposal and a significant improvement in insulin sensitivity compared to a nonsupplemented placebo group. Blood glucose levels often drop 23-45% in lipoic acid-treated diabetic animals. The journal Hypertension also reported alpha-lipoic acid, a thiol compound known to increase tissue cysteine and glutathione levels, reduced systolic blood pressure in spontaneously hypertensive rats (Jacob 1995, 1996, 1997; Vasdev et al. 2000).

Lipoic acid is of value in treating diabetic and nondiabetic subjects with congestive heart failure. Researchers from Beijing University added that lipoic acid, because of its free-radical scavenging effects, is able to protect the myocardium from free-radical damage and subsequently decrease the incidence of malignant arrhythmias (Gao et al. 1991). Antioxidants are extremely important in cardiac health, for the heart is one of the most susceptible of all organs to free-radical damage. (There are three times more free radicals produced in aging hearts compared to young hearts.)

Alpha-lipoic acid is, in fact, regarded as the universal antioxidant because it enhances the activity of other antioxidants. It acts like a big brother in regard to vitamin E, coenzyme Q10, and vitamin C, assisting in recycling these important antioxidants for continued service. Lipoic acid's antioxidant qualities appear greater than vitamin E's because vitamin E works only in the fatty parts of cells, whereas lipoic acid works in both watery and fatty portions (Challem et al. 2000).

Stroke deaths dropped from 78% to 26% in lipoic acid animal studies conducted by Lester Packer. The journal Stroke confirmed that alpha-lipoic acid reduced stroke infarct volume and free-radical activity, inhibited platelet-leukocyte activation and adhesion, and increased cerebral blood flow (Clark et al. 2001).

Lipoic acid reduced the formation of glycosylated end products (AGEs) (Jain et al. 1998). Glycation occurs when proteins react with sugar to form AGEs. This process increases the risk of cardiovascular disease by oxidizing LDL cholesterol and rendering blood vessels tough and inflexible. This gradually affects the left ventricle, reducing its ability to pump oxygen-rich blood into the circulation. Stiffness occurring in the myocardium increases diastolic pressure, and arterial rigidity increases systolic pressure. Also, glycosylated cholesterol-carrying proteins are no longer capable of binding to receptors on liver cells to signal the cessation of cholesterol manufacturing. A healthy cholesterol-carrying protein halts the copious supply of cholesterol. Without this binding process, cholesterol continues to be pumped out. Lipoic acid interrupts all of these processes at the starting point, by inhibiting glycation.

Note: Although a normal byproduct of oxidative metabolism, free radicals in excess are considered germane to the onset of vascular disease. When out of control, these highly unstable electrons can cause extensive damage to lipid membranes, organelles, and DNA itself. But most all of nature is two-pronged, having a good side as well as a bad. For example, free radicals participate in many positive reactions, including mitochondrial respiration, prostaglandin synthesis, platelet activation, and leukocyte-phagocytosis, (the engulfing and destruction of microorganisms and cellular debris). It is thus extremely important to supply sufficient nutrient cofactors to support endogenous antioxidant enzyme systems (such as superoxide dismutase, catalase, and glutathione peroxidase) but to retain enough free-radical oxidative activity to carry on essential life processes (Sinatra 2001).

Some researchers believe 50-250 mg a day (in concert with other antioxidants) may be sufficient to protect against Syndrome X. Most Life Extension members have been taking between 250-500 mg a day of alpha-lipoic acid. If the patient has unstable blood glucose levels, higher doses of lipoic acid will be required. German practitioners frequently use 600 mg daily as adjunctive therapy in coronary artery disease and 600-1800 mg of alpha-lipoic acid to improve insulin sensitivity and diabetic conditions. Higher doses should be administered with the help of a qualified physician who can adjust insulin requirements as indicated. Note: Dr. Lester Packer, in The Antioxidant Miracle, recommends taking biotin supplements with alpha-lipoic acid when the daily intake exceeds 100 mg. Alpha-lipoic acid may compete with biotin and interfere with biotin's activities in the body.

Reader's guide to lipoic acid food sources
Liver, yeast, spinach, broccoli, potatoes, and red meat.

Angelica (Angelica archangelica)--an antianginal, anti-inflammatory calcium antagonist, ACE inhibitor, and diuretic
Angelica, a member of the carrot family, contains 15 compounds considered to be calcium channel blockers. One of the calcium antagonists in angelica is, in fact, more potent than verapamil (Calan, Isoptin), a popular calcium channel blocker prescribed for angina, atrial fibrillation, and spasms occurring in the blood vessels (Duke 1997).

James Duke, Ph.D. (botanist), comments that it is well known that vegetarians have a low incidence of heart disease. Usually their low-fat diet gets the credit, but Dr. Duke speculates that it may be because they eat lots of plants from the carrot family, such as carrots, celery, fennel, parsley, and parsnips, which (like angelica) contain compounds with calcium channel blocking activity. Calcium channel blockers (whether natural or pharmaceutical) are powerful anti-anginals.

Angelica bestows its cardiac advantage through various pathways. For example, angelica not only reduces the incidence of angina attacks, but also regulates an erratic heartbeat. It has diuretic properties, making it of value in the treatment of congestive heart failure and hypertension. Chemicals contained in angelica exhibit another mechanism to reduce blood pressure, that is, the inhibition of ACE, the angiotensin-converting enzyme (Duke Database 1992).

Inflammation, one of the newer risk factors for heart disease, is also reduced by angelica (read about the inflammation-heart disease connection in the sections dedicated to Newer Risk Factors). A suggested angelica dosage is 15-30 drops 1-3 times a day.

Comments: How many milligrams (mg) of herb are in a drop of extract? According to Herb Pharm, a respected name in the herbal industry, the milligrams represented by 1 milliliter of extract (about 30-40 drops) from a dried herb are given by the herb-to-menstruum ratio (menstruum is a solvent--a liquid that dissolves a solid). This number varies for extracts made from fresh herbs due to the increased yield of these extracts. Liquid extracts are more assimilable than powdered herbs so the weights are not comparable. If trying to follow a recommendation, the form of the recommendation (powdered herb, liquid extract, etc.) needs to be considered. Quality and quantity are separate issues and even liquid extracts cannot be accurately compared on a mg-to-mg basis. Many factors determine the quality of an herbal extract, including the makeup of the menstruum, extraction technique, and raw herb quality. The following is only an approximate calculation, but it may be helpful:

1 mL is equal to about 33 drops of many extracts
1 mL of a 1:4 ratio contains extractives from gram of herb (0.25 gram = 250 mg)
The strength ratio does not directly address quality. Quality is dependent on other factors such as the quality of the herb, the plant part used, special handling, the extraction process and technique, as well as storage. Always follow dosage instructions (and caveats) appearing on the label.

L-Arginine--dilates blood vessels, reduces blood pressure, replicates the activity of nitroglycerine, and is needed to produce nitric oxide
L-arginine, along with a properly planned exercise program, assists in amending abnormalities occurring in blood vessels. Individuals with congestive heart failure often have blood vessels that fail to dilate in response to certain drugs, a sign that the inner blood vessel wall, or endothelium, is compromised.

A study reported in the American College of Cardiology concluded that treatment with L-arginine produced a fourfold increase in blood vessel dilation from 2.2-8.8% (Hambrecht et al. 2000). Regular forearm exercises increased the dilation response by the same amount, but the combination of L-arginine and exercise training resulted in an improvement from 2.9-12%. Doses of 5.6-12.6 grams of arginine increased blood flow to the extremities 29%; the distance walked on a treadmill in 6 minutes increased 8% (Rector et al. 1996).

Much of L-arginine's effectiveness comes by way of increasing nitric oxide, a blood vessel dilator and clot buster produced in endothelial cells by the enzyme nitric oxide synthase (Brunini et al. 2002). Nitric oxide counteracts the vasoconstriction and platelet-aggregating effects of the stress hormone adrenaline (epinephrine) and assists in maintaining vascular elasticity. Nitric oxide (the endothelial relaxing factor) is needed for expansion and contraction of the arterial system (Rohdewald 1999). L-arginine increases nitric oxide, but hypertension, hyperhomocysteinemia, diabetes, and smoking decrease it.

Because of arginine's vasodilating properties, it is frequently used as a treatment for angina pain and hypertension. Researchers at the University of Southern California (Los Angeles) speculate that a defect in nitric oxide production may be a possible mechanism of hypertensive disease (Campese et al. 1997). Some cardiologists, in fact, recommend L-arginine over nitroglycerine, since the two substances appear to replicate a similar vascular function: the ability to relax smooth muscles and dilate blood vessels.

In their current book, The Arginine Solution, Drs. Robert Fried and Woodson C. Merrell note that as people age and develop disorders such as hypertension, hypercholesterolemia, and atherosclerosis, their ability to make sufficient amounts of nitric oxide from arginine is impaired, contributing to a decline in their cardiovascular health. Drs. Fried and Merrell contend that increasing arginine intake addresses various cardiovascular risks associated with decreased nitric oxide synthesis, often improving symptomatic and clinical evaluations (Fried et al. 1999). A suggested dosage is 2 grams before bedtime. Arginine caveat: Individuals who have frequent herpes outbreaks may find arginine-rich foodstuffs or supplementation contraindicated.

Reader's guide to arginine food sources
Most protein foods and carob, chocolate, nuts, seeds, beans, oats, peanuts, and wheat and wheat germ.

Artichoke Extract--reduces cholesterol and triglycerides
Artichoke (Cynara scolymus), a delicious table vegetable, has a reputation that extends beyond culinary enhancement. It has long been used to improve digestive and liver complaints, but more recently artichoke has become popular as a hypolipidemic. Studies have shown that the more lipid correction needed, the greater artichoke's cholesterol-lowering effects. Caffeoylquinic acids and flavonoids, constituents of artichoke, appear to deliver much of the plant's positive effects.

In a multicenter, placebo-controlled, randomized trial, 143 patients with initial cholesterol levels greater than 280 mg/dL took either a placebo or 450 mg of artichoke dry extract 4 times a day. After 6 weeks, those taking the artichoke extract showed an 18.5% reduction in cholesterol compared to a 5.6% reduction in the placebo group. LDL-cholesterol decreased 22.9% among those taking the artichoke extract and 6.3% in the placebo group. The LDL/HDL ratio showed a decrease of 20.2% among the artichoke users (Englisch et al. 2000). Another short-term study (6 weeks) showed that artichoke reduced triglycerides from 214.97 mg/dL to 188.07 mg/dL (Fintelmann 1996a, 1996b). There were no drug related adverse events during the course of these studies, indicating an excellent tolerability.

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