A Study Of Nutraceutical Drinks For Cholesterol (Evaluating Effectiveness and Tolerability)

Cholesterol is the principle component of cardiovascular disease. It deposits in the walls of blood vessels and contributes to both chronic vascular insufficiency manifested as claudication, ischemic ulceration, or angina, and acute vascular insufficiency presenting as heart attack, stroke or sudden death.

Coronary heart disease is the number one killer worldwide. Approximately 50% of males and one-third of females will develop a coronary heart disease related acute event in their lifetime. The cost of coronary heart disease is staggering. In the United States alone, over $120 billion is spent annually in direct and indirect costs attributed to this killer (10).

The Framingham Heart Study has shown that coronary heart disease incidence rises proportionately to serum cholesterol (1). More importantly, numerous studies demonstrate a reduction in coronary heart disease related events with falling cholesterol levels on treatment (18).

There are four classes of commonly used cholesterol lowering drugs:

1. statins
2. fibric acid derivates
3. niacin
4. bile acid sequestrants.

Of these, the most widely used are the statins. Statins produce potent LDL lowering, reduce cardiovascular events, and are relatively safe. However, despite their proven effectiveness and relative safety, even statins have their limitations. First, as many as 30% of people who take statins develop myalgias. Second, many drug interactions exist. Third, most of the LDL lowering is seen with the lowest dose, making up-titration of limited value (3) (20). With fibrates, niacin, and bile acid sequestrants, tolerability is even more problematic with titration, and end point data somewhat weaker than with statins, especially for monotherapy (4)(7)(14)(17).

Beyond the efficacy and safety limitations of the selected drug, there are socioeconomic barriers to effective cholesterol lowering. Although people are cognizant of the importance of cholesterol reduction, many evade the doctor/patient relationship at all cost. Others do not like, forget to take, or have difficulty swallowing pills. Some do not have access to health care, drug plans, or lack the financial means to afford pharmaceuticals. Furthermore, high cholesterol represents a label that might adversely affect one's ability to procure inexpensive life and health insurance. Therefore, there is a need for alternative cholesterol lowering approaches that circumvent these limitations.

In devising these approaches, it is crucial to incorporate a relatively new concept in cholesterol lowering and/or maintenance. Recently, it has become apparent that targeting a single mechanism, either of absorption or endogenous production of cholesterol, may augment the other potentially compensatory mechanism, thus decreasing the effectiveness of any type of monotherapy. Hence, raising the dose of any one medication may enhance toxicity out of proportion to any gain in efficacy. To be effective without substantial toxicity, several medications or active ingredients that lower cholesterol via different mechanisms should be employed simultaneously. The rationale for this application has been tested and proven for combination statin/niacin therapy (12) (15) (22) and also combination statin/phytosterol therapy (16). In each case, the reduction from combination therapy is greater than that expected from the sum reductions of the constituents, thereby, allowing for lower doses of drugs and lower toxicity compared to single drug therapy (21).

There are several non-pharmaceutical products available to the public that have cholesterol lowering properties; L-carnitine and vitamin C are two such examples, and these substances are thought completely safe at the low dose ranges shown effective for cholesterol lowering. L-carnitine facilitates fatty acid transfer and intracellular mitochondrial metabolism, removing cholesterol from the blood and thereby reducing serum cholesterol. Though side effects are very rare and dose related, lowering of seizure threshold in patients with a history of seizures has been reported (5) (8). Vitamin C has statin-like HMG-coA reductase inhibitory activity, but unlike statins, lowers cholesterol without raising LPa or depleting Co-enzyme Q-10 (two counterproductive effects of statins). Vitamin C has been shown completely safe to a dosage of 3 grams per day (9).

Co-Q-10 has been demonstrated to mitigate the side effects of statins (myalgias) and its depletion may reduce cardiac muscle function. Side effects of Co-Q-10 are rare and usually involve skin irritation so minor GI side effects (19).

Red Yeast Rice is a Chinese dietary supplement available as a flavoring and coloring agent for centuries. It is known to contain at least nine different statins as well as phytosterols. Thus, it decreases both the body's synthesis of cholesterol and its absorption. Though the form augmented for Lovastatin content is illegal in the United States, the naturally fermented product is available legally at health food stores to promote favorable cholesterol levels. The red coloration may also stimulate appetite and hence compliance with food or dietary supplements that contain it. Though Red Yeast Rice is, in general, well-tolerated, headache, GI side effects, muscle pain or weakness, liver abnormalities and dizziness have rarely been reported. The psychological benefit of enhanced compliance through the red coloration of Red Yeast Rice may be further augmented by L-carnitine, which has been shown to stimulate a mild sense of euphoria (2) (11).

Niacin is a B vitamin that lowers LDL and triglycerides and raises HDL, in part, by decreasing the hepatic release of lipoproteins that bind cholesterol. Though comparatively high doses of niacin are often needed to lower LDL, the beneficial effects on HDL have been realized on very low doses. Though greater than 2 grams, predominantly of the long-acting niacin formulation, have been associated with side effects including flushing, GI side effects, hyperglycemia, gout, abnormal liver function and myopathy. Very low doses of niacin are very well-tolerated (22).

Phytosterols are natural plant products that lower cholesterol by competing with cholesterol for absorption in the intestine (13). The data in support for cholesterol reduction and cardiovascular health improvement is so strong that the FDA allows products that contain sufficient quantities of phytosterols to make special claims concerning cardiovascular benefits (6). Very well-tolerated, up to 3 grams per day, is thought to be essentially devoid of side effects (13).

An ideal cholesterol lowering product would be proven effective, and with minimal side effects. It would not require one to take pills, and would preferably be in liquid form as a suspension or soluble drink. It would contain multiple active ingredients that would work by different mechanisms at different sites to allow a lower side effect profile with synergistic efficacy.