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.