~Cardiovascular Disease Comprehensive 7 - Therapeutic A-B

THERAPEUTIC SECTION

The following therapeutics are arranged alphabetically and not by order of importance, providing greater accessibility to readers.

Alpha-Lipoic Acid (a.k.a. Thioctic 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.

Artichoke reduces cholesterol by decreasing the synthesis of cholesterol in the liver and increasing the conversion of cholesterol to bile acids. (Cholesterol is a building block for bile acids.) According to Michael Murray, N.D., cholesterol levels are sometimes high because of the impaired conversion of cholesterol to bile acids. Thus, low bile acid levels send a powerful signal to the liver to provide more cholesterol. Artichoke extract intercepts this signal, and the liver complies with less cholesterol production (Murray 1998b).

The flavonoid luteolin appears to be pivotal in the hypocholesterolemic effects of artichoke. Statin drugs reduce cholesterol by competitively inhibiting the binding of HMG-CoA reductase. Tocotrienols also degrade this enzyme. Artichoke research has found no direct inhibition of HMG-CoA reductase. Other enzymatic steps occurring later in the biosynthesis of cholesterol appear unaffected. It seems luteolin inhibits cholesterol below the level of HMG-CoA reductase and therefore spares coenzyme Q10 synthesis. Recall that the cholesterol cascade begins with acetyl-CoA being converted to HMG-CoA. HMG-CoA reductase reduces HMG-CoA to mevalonic acid. Mevalonic acid participates in several steps that reduce it to squalene. Squalene is then converted to cholesterol (Murray 1998b; Sardesai 1998).

A suggested dosage is 1 capsule 3 times a day, containing 300 mg of artichoke standardized to contain 13-18% caffeoylquinic acid. Note: The American Journal of Clinical Nutrition recently reported that chlorogenic acid, a component of black tea and coffee, could increase homocysteine levels (Olthof et al. 2001). Chlorogenic acid also appears in artichoke and would therefore be contraindicated in refractory hyperhomocysteinemia. Lastly, individuals with gallstones or biliary tract obstruction should not use artichoke.

Aspirin-- reduces C-reactive protein (CRP), platelet aggregation, and cardiac inflammation

Aspirin has been used for over a century to relieve pain; research suggests that it may play an equally important role in heart health. A study involving 51,085 participants showed a total of 2284 cardiovascular endpoints occurring during an aspirin trial. The risk of a first nonfatal heart attack was reduced 32% among aspirin users compared to nonusers. The researchers concluded that aspirin therapy could prevent a third of myocardial infarctions occurring in apparently healthy individuals (Hebert et al. 2000). JAMA also reported that aspirin usage was associated with reduced all-cause mortality, particularly among older subjects with known coronary artery disease and impaired exercise capacity (Gum et al. 2001).

Three studies looked at the incidence of stroke subtypes among aspirin users. A 1.69-fold increase in the risk of hemorrhagic stroke occurred among aspirin users, but no increase in ischemic strokes was noted. Secondary prevention trials, evaluated by Drs. Patricia R. Hebert (Yale University) and Charles Hennekens (University of Miami) indicated that aspirin therapy administered to 10,000 persons would prevent about 67 myocardial infarctions and cause approximately 11 hemorrhagic strokes. In November 2001, the New England Journal of Medicine published that over a 2-year period, no difference was found between aspirin and warfarin in the prevention of recurrent ischemic stroke or death or in the rate of major hemorrhage (Hebert et al. 2000; Mohr et al. 2001).

The drug disposition of aspirin is persuasive when applied to a cardiovascular model. For example, low-dose aspirin (81 mg) appears to provide partial protection against abnormal blood clot formation, having a 2-day lasting effect on blood platelets. Platelets become less sticky and the risk of a heart attack and transient ischemic attacks (TIAs) is subsequently reduced.

Aspirin exerts some of its cardioprotection by inhibiting the enzyme cyclooxygenase, a trigger in the inflammatory process (Newmark et al. 2000). One molecule of aspirin will destroy the cyclooxygenase enzyme for 4-6 hours (read the sections devoted to C-Reactive Protein and The Link Between Infections and Inflammation in Heart Disease to learn how the inflammatory process advances cardiac disease).

Aspirin appears to lower C-reactive protein (CRP). In the Physician's Health Study, participants were randomly assigned at baseline to receive 323 mg of aspirin on alternate days and were then followed through first myocardial infarction. The study showed that low dose aspirin reduced heart attack risk by about 44% compared to the control group; the risk was 55% lower than that of placebo-treated men with high CRP levels. The results of this study suggest that in addition to aspirin's antagonism toward platelet clumping, it may also attenuate thrombosis through anti-inflammatory mechanisms (Physicians Weekly 1998a).

Aspirin significantly cut the death rate from cardiac disease among 2368 noninsulin-dependent diabetic patients with coronary artery disease. (The aspirin benefit was greater among diabetic patients than nondiabetics.) Diabetic patients using aspirin had a 10.9% mortality risk from cardiac diseases, while diabetics not using aspirin had a 15.9% risk (Harpaz et al. 1998).

The aspirin advantage extended to include carotid endarterectomy patients. Individuals using low-dose aspirin (81-325 mg a day) reduced the risk of myocardial infarction, stroke, and death for a 30-day to 3-month interval following surgery. Individuals taking 650-1300 mg were not similarly protected, illustrating that the dose can alter the end response (Taylor et al. 1999).

Current information indicates that aspirin can also reduce the level of heart damage during a heart attack. When taking aspirin because one believes they are experiencing an acute heart attack, the aspirin should be chewed rather than swallowed and is best taken within 30 minutes of the onset of symptoms.

In conclusion, the Antithrombotic Trialists' Collaboration (representing a review of 287 studies involving 135,000 patients) announced that over 40,000 lives are lost worldwide every year because aspirin is underused. According to the report, aspirin (or other antiplatelet drugs) is protective in most patients at increased risk of occlusive vascular events, including those with acute myocardial infarction or ischemic stroke, unstable or stable angina, previous myocardial infarction, cerebral ischemia, peripheral arterial disease, or atrial fibrillation (Antithrombotic Trialists' Collaboration 2002).

Aspirin (75-150 mg a day) appears to be an effective antiplatelet regimen for long-term usage, but in acute settings, an initial loading dose of at least 150 mg may be required. Adding a second antiplatelet drug to aspirin may produce additional benefits in some clinical circumstances (Antithrombotic Trialists' Collaboration 2002). Note: The New England Journal of Medicine recently published that warfarin, in combination with aspirin or given alone, was superior to aspirin alone in reducing the incidence of composite events following an acute myocardial infarction. Warfarin was, however, associated with a higher risk of bleeding (Hurlen et al. 2002).

The American College of Chest Physicians suggests that all people over 50 years of age, with one cardiac risk factor and no condition that would negate treatment, consider aspirin therapy. The cautionary includes those individuals who have increased prothrombin time, disturbed gastric mucosa, or hypertension. As acclaimed as low-dose aspirin is, studies have shown that aspirin does not appear comprehensive enough to prevent a heart attack if fibrinogen levels are excessively high. It should also be noted that a concomitant administration of ibuprofen (but not rofecoxib, acetaminophen, or diclofenac) antagonizes the platelet inhibition activity induced by aspirin. Thus, treatment with ibuprofen in patients with increased cardiovascular risk may limit the cardioprotective effects of aspirin (Catella-Lawson et al. 2001).

Bromelain-- is an anti-inflammatory, reduces fibrinogen, lessens risk of blood clots, is beneficial in atrial fibrillation, is hypotensive, relieves angina, and is basic to smokers

Bromelain, derived from pineapple (Ananas comusus), is regarded as a natural anti-inflammatory, acting as a protein-digesting enzyme. Since the revelation that inflammation may be causal to cardiovascular disease, bromelain has attained new stature. Proteolytic enzymes work directly on the inflammation, neutralizing and removing damaged cell tissue. The digesting nature of bromelain suggests that it can also reduce atherosclerotic plaque accumulating in arteries.

Bromelain lowers blood pressure, breaks down fibrinogen, and relieves angina. It opposes platelet aggregation and is helpful in thrombophlebitis. Many of bromelain's qualities make it particularly valuable to smokers and patients with atrial fibrillation (Murray 1995c; Duke 1997).

A suggested bromelain dosage is 1/8-1/4 teaspoon taken between meals to relieve inflammation. The strength of enzymes is often expressed as milk-clotting units (MCU) and gelatin-digestive units (GDU) per gram. One level teaspoon of Life Extension Bromelain Powder (2.9 grams) has enzymatic strength of 3500 MCU or 2000 GDU. Bromelain tablets (500 mg) are also available. Typically, bromelain is used 3 times a day.

Bugleweed (Lycopus virginicus)-- is a diuretic and has a digitalis mentality

Bugleweed has a reputation that dates to folk medicine. Historically, herbalists used bugleweed to regulate the heart and improve circulation. Bugleweed's repute is enduring, for practitioners still use the herb to stabilize a rapid or irregular heart rhythm, whether the problem is functional or organic.

Bugleweed is beneficial in the treatment of hypertension and congestive heart failure, ridding water from edematous tissues and organs. It has been called a natural digitalis, milder but with some of the same characteristics as the drug. Bugleweed does not accumulate and is therefore considered nontoxic (Santillo 1990; Ritchason 1995). A suggested dosage is 30-40 drops in a little water 2-4 times a day. (For an explanation regarding milligrams per drop, turn to Angelica, appearing alphabetically in this section.)

Continued . . .


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