OTC Supplements for the Management of High Cholesterol

US Pharm. 2017;42(2):8-11.

Cardiovascular disease remains the leading cause of mortality and morbidity in the United States, with coronary artery disease (CAD) being the number-one cause of death.¹ Dyslipidemia is a major contributor to the development of CAD and other forms of atherosclerosis; individuals with high total cholesterol levels (≥240 mg/dL) have about twice the risk for heart disease. Approximately 100 million adults in the U.S. have total cholesterol levels >200 mg/dL (borderline high), and almost 74 million have high levels of low-density lipoprotein cholesterol (LDL-C).^2,3 Adults aged >20 years should have their cholesterol measured at least once every 5 years.²

Treatment Guidelines

There are many pharmacologic therapies to treat dyslipidemia, including HMG-CoA reductase inhibitors or statins, cholesterol absorption inhibitors, niacin, bile acid sequestrants, fibrates, and omega-3 fatty acids; however, statins are the mainstay of treatment. In 2013, the American College of Cardiology (ACC) and the American Heart Association (AHA) released guidelines for the treatment of blood cholesterol.⁴ Rather than providing specific cholesterol targets, the current guidelines focus on intensity of statin treatment in four different groups (TABLE 1). This shift in treatment can potentially increase the number of adults who are eligible to take statins by 12.8 million.⁵ The National Lipid Association’s recommendations released in 2014 provide non–high-density lipoprotein cholesterol (non–HDL-C) goals, but like the ACC/AHA guidelines, treatment focuses on statins as the primary agent of choice.⁶

Despite this, nearly half of treatment-eligible adults are not taking cholesterol-lowering drugs.⁷ This can be attributed to many reasons, including cost, perceived susceptibility to cardiovascular risks, and, most commonly, fear and concerns regarding safety and adverse effects.^8,9

OTC Supplements

Some of these patients may be looking for alternative ways to lower their cholesterol and reduce their risk for cardiovascular disease. About 34% of adults in the U.S. are using some form of complementary and alternative medicine (CAM).¹⁰ Cholesterol is included as one of the top 10 conditions for which adults are using CAM.¹¹ Fish oil and garlic, two supplements commonly used for the reduction of high cholesterol, were among the top 10 most frequently used natural products.¹⁰ Pharmacists are in an ideal position to educate patients about the use of OTC products for the management of high cholesterol. They can help patients make informed decisions based on the available data. The following is a discussion of the more popular OTC agents utilized in the management of dyslipidemia.

Garlic: Garlic has been used as a medicinal agent for thousands of years. Today, many people use garlic for its purported cardiovascular benefits, such as lowering blood pressure and cholesterol. Garlic contains the amino acid alliin. When crushed, alliin is converted to allicin, a substance that inhibits cholesterol synthesis; however, clinical studies have demonstrated inconsistent results.^12-15 In pooled analyses of studies, garlic was shown to improve triglyceride and total cholesterol levels, but it had no effect on LDL-C or HDL-C.^13,15 However, a recent meta-analysis found garlic to have beneficial effects on total serum cholesterol and LDL-C, lowering each by 17 ± 6 mg/dL and 9 ± 6 mg/dL, respectively.¹² This effect was seen if garlic was taken for at least 2 months. Data suggest that the benefits of garlic on cholesterol may be short-term, showing no significant benefit after 6 months.^16,17

Garlic is associated with several adverse effects and drug interactions. The most common adverse effects include bad breath and body odor, upset stomach, and heartburn. Garlic has antiplatelet effects and can increase a patient’s risk for bleeding. Patients who are on anticoagulants and antiplatelet agents should be warned about this potential risk.^12-17

Niacin (Vitamin B₃ ): Niacin is one of the most effective agents to raise HDL-C levels; it can raise HDL-C by almost 35%.¹⁸ Niacin also reduces LDL-C levels by up to 25% and triglycerides by 20% to 50%.^18,19 This effect is dose-related, requiring 1 to 4 g per day. There are a variety of niacin products available: immediate-release, long-acting (sustained-, controlled-, or timed-release), and extended-release. The first two products are available OTC, while the extended-release products require a prescription. There is also a no-flush formulation available OTC; however, the active ingredient is not niacin but inositol hexaniacinate, which has been shown to be ineffective as a lipid-lowering agent.²⁰ Nicotinamide (niacinamide) should not be used in place of niacin because it does not effectively lower cholesterol or triglyceride levels.

Niacin is associated with several side effects. It can cause hyperglycemia and worsen A1C control, but these increases are often clinically insignificant or readily treatable.²⁰ Doses up to 2,000 mg/day have been well tolerated in diabetic patients with little increase in fasting plasma glucose.^18,21 Other reported adverse effects include hyperuricemia, nausea, vomiting, diarrhea, and hypotension. Hepatotoxicity and flushing are also associated with its use, but these effects are dependent on the formulation. OTC long-acting formulations should never be recommended because they are associated with hepatotoxicity, evident by abnormal hepatic enzymes and, in severe cases, jaundice.¹⁸

Niacin-induced flushing is a major barrier to its use; this effect limits niacin’s utilization and achievement of therapeutic dosing. Most patients will experience flushing, which is often more intense with the start of therapy, but usually subsides with continued use. Patients taking immediate-release niacin should be told to gradually increase the dose, take it with meals, and pretreat with aspirin to help minimize the occurrence of flushing.²¹

Omega-3 Fatty Acids/Fish Oils: Omega-3 fatty acids are the most frequently used natural product among adults, with consumption increasing almost 10-fold this past decade.^10,22 Omega-3 fatty acids include alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). The most studied forms of omega-3 fatty acids are EPA and DHA. They have shown to be effective in lowering serum triglycerides up to 50%; however, DHA can raise LDL-C and HDL-C.²³

There are over 400 OTC products currently marketed as omega-3 fish oil dietary supplements.²⁴ These products not only contain EPA and DHA, but may also include saturated fats, fat-soluble vitamins, and cholesterol.²⁵ Fish oil supplements vary in their EPA and DHA concentrations, ranging anywhere from 20% to >80%. The AHA recommends 2 to 4 g per day of EPA plus DHA to lower triglycerides; if patients require more than 3 g they should be under a physician’s supervision.²⁶ On average, patients would need to take 11.2 servings per day (1 to 3 capsules per serving) to achieve this higher recommended dose.²³ Many patients will have difficulty with this high pill burden; they should speak with their healthcare providers about a prescription omega-3 product.

Overall, these products are generally well tolerated. The most common adverse effects include stomach upset, diarrhea, and reflux. Many patients will complain about a “fishy” taste, especially if they are taking higher doses. Advising them to take enteric-coated formulations or freezing the capsules may help reduce this. Another effect associated with omega-3 supplement use is excessive bleeding. Patients on anticoagulants or antiplatelet agents should use omega-3 fatty acids cautiously.^21-25

Red Yeast Rice (RYR): RYR is produced by culturing a yeast, Monascus purpureus, on white rice. Chinese culture has used this agent as a food preservative and food colorant, and to make rice wine.²⁷ This fermented product contains a group of compounds called monacolins, substances that inhibit cholesterol synthesis via HMG-CoA reductase. One of the produced monacolins, monacolin K, is an analogue of the FDA-approved medication lovastatin. Clinical trials have demonstrated significant reductions in total cholesterol, LDL-C, and triglycerides and increases in HDL-C.^19,20,27,28 However, the FDA has determined that any product that contains more than a trace amount of monacolin K cannot be sold legally as a dietary supplement.²⁹

There are many OTC preparations containing RYR; it is unknown whether these agents have any cholesterol-lowering effects. To avoid being considered a drug, manufacturers do not disclose the amount of monacolin in their products, if any. Another concern is that there is no standardization across manufacturers. If the product is fermented incorrectly, citrinin is produced, a toxic byproduct known to be nephrotoxic. Studies have analyzed various RYR products and have demonstrated great variability in monacolin and citrinin contents.^27,28,30 Some products, if ingested accordingly with the daily recommended dose, would provide the equivalent of lovastatin 20.5 mg daily.²⁷ This can be a concern, especially if patients are already on a statin or on medications that may potentially increase the risk of muscle-related side effects. These products should not be recommended until improved oversight by the FDA and standardization of products have been implemented to ensure equivalence of active ingredient contents and limitation of harmful byproducts.

Soluble Fiber: The use of soluble fibers, such as oats, psyllium, pectin, and guar gum, have been associated with lowering total cholesterol and LDL-C. Psyllium husk fiber appears to be one of the most effective soluble fibers with the least adverse effects.³¹ Consuming 7 to 10 g of psyllium per day demonstrated a reduction in total cholesterol levels by 4% to 15% and LDL-C levels by 6% to 18%.^31,32 Although most individuals will require a larger reduction than what fiber monotherapy can provide, it is probably best when used in combination with other therapies.

The recommended amount of daily dietary fiber intake is 25 to 38 g per day; most people are only consuming about half that amount.^33,34 Examples of high-fiber foods include whole grains, oats, fruits, and vegetables. Fiber supplements may be helpful to those patients who are having difficulties in achieving this daily goal. Pharmacists need to ensure that they are recommending fiber supplements containing a soluble viscous, gel-forming fiber (psyllium), although there are some data to indicate that inulin may be beneficial in reducing cholesterol levels.^35,36

Adverse effects associated with fiber supplements include gastrointestinal upset, bloating, diarrhea, constipation, and flatulence. Fiber should be increased gradually and taken with plenty of water. Patients should also be told to separate fiber supplements from other medications by at least 2 hours to avoid potential drug interactions.³⁶

Conclusion

Dyslipidemia is a prevalent condition affecting over 100 million patients that can more than double a person’s risk for the development of cardiovascular disease.^1,2 Because of this, many individuals are seeking alternative ways to lower their cholesterol. Pharmacists can play a vital role in this process by educating patients and helping them make informed decisions regarding the use of the various available supplements.

Supplements that are supported by clinical evidence and guidelines include immediate-release niacin, omega-3 fatty acids, and soluble fiber. Pharmacists should keep in mind, however, that these products are not regulated by the FDA and there may be inconsistencies between different manufacturers and batches. Pharmacists should also avoid recommending garlic, RYR, sustained-release niacin, no-flush niacin, and niacinamide due to lack of efficacy or documented adverse effects. A strong emphasis should be placed on the benefits associated with therapeutic lifestyle changes, such as maintaining a healthy weight, eating a low-fat, low-cholesterol, high-fiber diet, and exercising regularly. Patients should also be reminded to inform their healthcare providers of any supplements they may be taking.

PATIENT INFORMATION

What Is Cholesterol?

Cholesterol is a substance that your body needs to remain healthy. It comes from two sources: our bodies themselves and the food we eat, such as meat, poultry, and dairy products. Too much cholesterol can increase your risk for heart disease.

What Is the Difference Between “Good” and “Bad” Cholesterol?

“Bad” cholesterol, also known as low-density lipoprotein (LDL), will build up in the inner walls of your arteries, making them narrow. This slows down blood flow. If this buildup of plaque breaks off, a clot forms that can completely block the flow of blood, causing a heart attack.

“Good” cholesterol, also known as high-density lipoprotein (HDL), helps protect us from heart attacks and strokes. This type carries the bad cholesterol away from the arteries.

What Are “Normal” Cholesterol Numbers?

Everyone aged 20 years and older should have his or her cholesterol levels checked at least once every 5 years. The blood test should be taken after fasting for 9 to 12 hours.

You should aim for a total cholesterol level of <200 mg/dL. Levels of 240 mg/dL or above are considered high. For LDL, lower levels are better, and the goal should be below 130 mg/dL, with <100 mg/dL being optimal. For HDL, higher numbers are better. An HDL level <40 mg/dL is a major risk factor for developing heart disease. You want to aim for levels of 60 mg/dL or better to help lower this risk.

How Can I Improve my Cholesterol?

Eating healthy foods, maintaining a healthy weight, and staying physically active are all ways to help improve your cholesterol.

What Foods Should I Eat? What Foods Should I Avoid?

Maintaining a healthy diet can help lower your cholesterol. Recommended foods include fruits and vegetables; whole grain foods; fat-free, 1%, or low-fat milk products; poultry without skin and lean meats; fatty fish such as salmon, trout, albacore tuna, and sardines; and unsalted nuts, seeds, and legumes.

A diet high in cholesterol, saturated fats, and trans fats should be avoided. This includes high-sodium foods; sweetened or sugary beverages; red, fatty, or processed meats; full-fat dairy products; baked goods with saturated and trans fats (e.g., cakes, cookies); solid fats or fried foods; and hydrogenated and saturated oils.

Can Supplements Help?

There are a few things you can take to help you lower your cholesterol, but you should speak with a healthcare provider before starting. Supplements that may have some benefit include immediate-release niacin, omega-3 fatty acids/fish oil, and soluble fibers (psyllium). Supplements that should be avoided include red yeast rice, garlic, sustained-release niacin, no flush niacin, and niacinamide. These supplements have no data to support their use in lowering cholesterol levels or have been associated with liver damage.

Remember, if you have Questions, Consult Your Pharmacist.

REFERENCES

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