A Study Of Nutraceutical Drinks For Cholesterol (Evaluating Effectiveness and Tolerability)
Condition: Hyperlipidemia
MeSH terms: Hyperlipidemias; Hyperlipoproteinemias
Study type: Interventional

Summary: 
      Great controversy exists about the feasibility and safety of a product that can be employed
      for self-directed cholesterol reduction. The position that self-directed cholesterol lowering
      could lead those that do not need lower cholesterol to take the product is likely unfounded.
      This is because there is no convincing evidence to suggest that there are cholesterol levels
      so low that a lower one would not be beneficial or conversely be dangerous. Ample evidence
      exists that cholesterol causes cardiovascular disease and that lower cholesterol places
      individuals and populations at lower risk. Because of the high cost, insurance concerns and
      suboptimal access to physician care, a self-directed, effective and safe approach to
      cholesterol maintenance or reduction would be very desirable. Drug therapy also has been
      associated with suboptimal results. Though a new concept that addresses cholesterol by
      several mechanisms simultaneously has been shown to be more consistently effective and with
      better tolerability, there is still a need for a self-directed cholesterol optimizing
      alternative. It is, therefore, our intent in this study to evaluate certain foods,
      specifically nutraceutical containing fruit flavored drinks in the hopes that they can be
      proven a safe and effective alternative approach for cholesterol management.
    

Detailed description: 
      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.
    

Intervention name(s): Placebo; Second Formulation; Third Formulation
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): Each subject will be expected to consume a twice daily drink of approximately 4 ounces per serving taken with the morning and evening meals for a total of 8 weeks. Each bottle will contain two servings.; Each subject will be expected to consume a twice daily drink of approximately 4 ounces per serving taken with the morning and evening meals for a total of 8 weeks. Each bottle will contain two servings.; Each subject will be expected to consume a twice daily drink of approximately 4 ounces per serving taken with the morning and evening meals for a total of 8 weeks. Each bottle will contain two servings.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Keywords: Cholesterol; Statin; Nutraceuticals; Niacin; Hyperlipidemia; Liquid