HeartSure Red Yeast Rice 600 mg [Discontinued] by Nature's Way

LIKELY EFFECTIVE

• Hyperlipidemia. Most research shows that red yeast rice supplements lower lipid levels in patients with high cholesterol. This effect is likely due to the monacolin K (lovastatin) content of red yeast rice products. Details: Clinical research shows that taking certain red yeast rice products 1-5 grams daily for up to 24 weeks can lower total cholesterol by up to 23% and low-density lipoprotein (LDL) cholesterol by up to 34% when compared with placebo or control. Some of these products include Cholestin (Pharmanex), Xuezhikang (WBL Peking University Biotech Co, Ltd.) , Red Yeast Rice (Sylvan Bioproducts), and HypoCol (AsiaPharm Biotech) (2624,6988,16836,17089,70491,70509,95666,107951). Meta-analyses of clinical studies, which include some of these studies, show that taking red yeast rice 100-4800 mg daily for up to 4.5 years reduces LDL cholesterol by about 21-29 mg/dL and triglycerides by 20-27 mg/dL, and increases high-density lipoprotein (HDL) cholesterol by about 3 mg/dL, when compared with placebo. These meta-analyses included various patient populations, including those with hyperlipidemia, cardiovascular disease, or hypertension (103310,110583,110584). These and other red yeast rice products provide up to 10-20 mg daily of monacolin K, which is identical to the drug lovastatin (95666). The United States Food and Drug Administration (FDA) considers red yeast rice products that contain statins to be illegal, unapproved drugs (6610). In Germany, red yeast rice products with a daily monacolin K (lovastatin) dose greater than 5 mg are classified as drugs (98822). Health Canada allows red yeast rice products containing only trace amounts of lovastatin (i.e. 1 mg or less daily) to be marked as natural health products (110586). The European Union limits the amount of monacolin K (lovastatin) content to less than 3 mg daily in red yeast rice products (110587). However, the amount of monacolin K in products is not always clearly stated on the label. While some red yeast rice products available in the US contain little or no statin constituents, many still contain significant concentrations of statins. One analysis shows that that some of these products can contain up to 5 mg of statins per tablet (95903). It is not known whether red yeast rice products that contain a lower concentration of statins can significantly reduce cholesterol levels in patients with hyperlipidemia. Accordingly, the recommendations from various clinical societies differ regarding red yeast rice. While the American College of Cardiology/American Heart Association guidelines do not mention red yeast rice, the European Society of Cardiology recommends against its use (110588,110589). The International Lipid Expert Panel suggests consideration of red yeast rice for certain patients for primary cardiovascular prevention, including those who are statin-intolerant or unwilling to take a statin, but recommends against use of red yeast rice for secondary cardiovascular prevention (110585). Some studies have also evaluated combination products containing red yeast rice, such as Limicol (Laboratoire Lescuyer), Armolipid Plus (Rottapharm S.p.A.), and Prelipid Prevention Meds, Inc. Taking these products for 4-24 weeks seems to modestly reduce total and LDL cholesterol levels in patients with dyslipidemia (18110,34262,89451,89452,89454,92142,95663). One of these products (Armolipid Plus, Rottapharm S.p.A.), containing red yeast rice, berberine, policosanol, and other ingredients, which has been studied in over 12 clinical trials in patients with hypercholesterolemia, modestly reduces total and LDL cholesterol and triglyceride levels, and improves HDL cholesterol, when compared with baseline or placebo (34283,89438,92142,107952). This product has also been shown to further lower lipid levels when added to low-dose statin or ezetimibe therapy in patients with coronary heart disease and a history of percutaneous intervention (97232,97233). Another combination product (DIF1STAT) containing monacolin K 2.5-2.9 mg, niacin 27 mg, and unknown doses of olive oil extract, green tea extract, and various B vitamins decreases total and LDL cholesterol when compared with placebo (107953).

POSSIBLY EFFECTIVE

• HIV/AIDS-related dyslipidemia. Oral red yeast rice seems to reduce lipid levels in patients with dyslipidemia due to HIV. Details: A very small clinical study in adults with dyslipidemia due to HIV shows that taking red yeast rice (Cholestin) 1.2 grams twice daily for 8 weeks seems to reduce total and low-density lipoprotein cholesterol when compared with placebo (9475).
• Myocardial infarction (MI). Oral red yeast rice seems to reduce recurrence of non-fatal MI in some patients. Details: A meta-analysis of 4 clinical trials in over 10,000 individuals with a previous MI shows that taking red yeast rice 1.2 grams in two divided doses daily for 4 or 4.5 years reduces the incidence of nonfatal MI by 58%, revascularization by 42%, and sudden death by 29% when compared with placebo; however, there was no effect on the incidence of fatal MI (103310). All clinical trials used a specific red yeast rice extract (Xuezhikang, WBL Peking University Biotech Co, Ltd.) (70508,70513,70520,103310). Furthermore, all of the available research has been conducted in China; it is unclear if these benefits can be extrapolated to other geographic locations.

POSSIBLY INEFFECTIVE

• Hypertension. Adding oral red yeast rice to antihypertensive medications does not seem to further lower blood pressure. Details: Small clinical studies in patients with hypertension with or without a history of myocardial infarction shows that taking a specific red yeast rice extract (Xuezhikang, WBL Peking University Biotech Co, Ltd.) 1200 mg daily for up to 2 years, along with antihypertensive drugs such as nifedipine and valsartan, does not further reduce blood pressure when compared with using antihypertensive drugs alone (70519,70521,70526,70530).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atherosclerosis. It is unclear if oral red yeast rice is beneficial for reducing atherosclerotic plaque. Details: A meta-analysis of 20 mostly low-to-moderate quality clinical studies that included 2217 patients with atherosclerosis shows that taking red yeast rice alone or with other statins improves markers of carotid atherosclerosis and modestly reduces blood lipid levels when compared with placebo, usual care, or statins. Studies were with specific red yeast rice products Xuezhikang (WBL Peking University Biotech Co, Ltd) or Zhibitai at daily doses up to 1800 mg or 960 mg, respectively, for 3-12 months (110582). The validity of the findings from this meta-analysis is limited by the heterogeneity of the included studies. Furthermore, all of these studies were conducted in China; it is unclear if these benefits can be extrapolated to other geographic locations.
• Cancer. It is unclear if oral red yeast rice is beneficial for reducing cancer mortality. Details: Clinical research in Chinese adults with a history of heart attack shows that taking red yeast rice extract (Xuezhikang, WBL Peking University Biotech Co, Ltd.) 1.2 grams daily for an average of 4.5 years decreases the risk of cancer mortality by 22% to 56% when compared with placebo (70513,70520). However, it is not clear if red yeast rice reduces the risk of cancer development or recurrence.
• Coronary heart disease (CHD). Although there is interest in using oral red yeast rice for CHD, there is insufficient reliable information about the clinical effects of red yeast rice for this condition.
• Diabetes. Although there is interest in using oral red yeast rice for diabetes, there is insufficient reliable information about the clinical effects of red yeast rice for this condition.
• Liver cancer. It is unclear if red yeast rice lowers the risk of developing liver cancer. Details: In a large population study conducted in Taiwan, people who consumed a specific red yeast rice product (LipoCol Forte) 600 mg (equivalent to about 6 mg of lovastatin) twice daily for at least one year had a 9% lower risk of developing liver cancer than people who had not taken red yeast rice. The risk of developing liver cancer continued to decrease with ongoing use of the supplement, with the lowest rate seen after 6 years of follow-up (112090).
• Metabolic syndrome. It is unclear if oral red yeast rice is beneficial in patients with metabolic syndrome. Details: A meta-analysis of mostly small, low-to-moderate quality studies in adults with metabolic syndrome suggests that taking red yeast rice modestly reduces glycated hemoglobin (HbA1c), fasting glucose, and lipid levels, and improves markers of insulin resistance, when compared with placebo, usual care, or other lipid-lowering treatments. Most studies were short-term and used a specific red yeast rice product (Xuezhikang, WBL Peking University Biotech Co, Ltd.) at an unknown dose (110580¬). The validity of the findings from this meta-analysis is limited by the heterogeneity of the included studies. Furthermore, the included studies were conducted in China; it is unclear if these benefits can be extrapolated to other geographic locations. Red rice yeast has also been evaluated in combination with other ingredients. A small clinical study in adults with metabolic syndrome shows that taking a specific combination product (Liposcudil Plus, Piam Farmaceutici SPA) containing monacolin K 10 mg and coenzyme Q10 30 mg once daily for 2 months, in conjunction with a Mediterranean diet, seems to modestly decrease blood pressure and lipid levels when compared with following the diet alone (98821). Clinical research in patients with metabolic syndrome and left ventricular hypertrophy shows that taking a specific product (Armolipid Plus, Rottapharm Madaus Spa) containing red yeast rice extract 200 mg, berberine 500 mg, and policosanol 10 mg daily for 6 months improves lipid profile and reduces left ventricular mass (LVM) when compared with placebo. LVM reduction occurred in 57% of patients taking the product, compared with 28% of those taking placebo (103311). It is unclear if any of these benefits are due to red yeast rice, other ingredients, or the combinations.
• Nonalcoholic fatty liver disease (NAFLD). Although there is interest in using oral red yeast rice for NAFLD, there is insufficient reliable information about the clinical effects of red yeast rice for this condition.
• Overall mortality. It is unclear if oral red yeast rice reduces mortality. Details: A meta-analysis of 2 moderate quality studies that included 3295 adults suggests that taking a specific red yeast rice product (Xuezhikang, WBL Peking University Biotech Co, Ltd.) at an unknown dose for up to 4-4.5 years reduces mortality by 38% when compared with placebo. This analysis also suggests red yeast rice reduces the incidence of major adverse cardiovascular events (MACE) by 46% when compared with placebo or routine care (110580). The validity of the findings from this meta-analysis is limited by the heterogeneity of the included patients. Furthermore, the included studies were conducted in China; it is unclear if these benefits can be extrapolated to other geographic locations.
• Postoperative recovery. It is unclear if oral red yeast rice is beneficial for recovery after surgery. Details: Observational research in Taiwanese patients has found that taking red yeast rice prior to major inpatient surgery is associated with lower odds of postoperative bleeding, pneumonia, stroke, and mortality, as well as a shorter hospital stay, when compared with a control group (100246).
• Stroke. It is unclear if oral red yeast rice reduces the risk of stroke. Details: Observational research in Taiwanese adults without a prior stroke suggests that taking a specific red yeast rice product (LipoCol Forte) is associated with a 35% reduction in the risk of stroke when compared with patients who did not take red yeast rice (110581). However, it is unclear if these results are due to red yeast rice or other factors, since patients who took red yeast rice were less likely to have comorbidities such as hypertension, diabetes, or ischemic heart disease. More evidence is needed to rate red yeast for these uses.

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POSSIBLY SAFE ...when used orally and appropriately. Red yeast rice 1.2 grams daily has been used with apparent safety in clinical studies for up to 4.5 years (512,2624,6988,6995,6996,17089,18110,70508,70513) (70520,70525,70530,95664,95666). However, red yeast rice products can contain an HMG-CoA reductase inhibitor identical to lovastatin, and can cause the same side effects as this drug. It is recommended that people taking red yeast rice products be monitored for the same hepatic and muscle-related adverse effects that are seen with lovastatin (98822).

PREGNANCY: LIKELY UNSAFE
when used orally. The red yeast rice constituent, lovastatin, has induced fetal skeletal malformations in animals (2619). The US Food and Drug Administration (FDA) recommends that most patients discontinue statin therapy during pregnancy due to the risks to the fetus; however, in certain high-risk patients, a prescription statin may be continued during pregnancy (107954).

LACTATION:
Insufficient reliable information available; avoid using. The US FDA recommends against breastfeeding while taking statins (107954).

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CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking red yeast rice in combination with cyclosporine might increase the risk of myopathy.  Details Red yeast rice contains varying levels of the statin drug lovastatin (9587,15017). Cyclosporine has been reported to increase plasma levels of lovastatin by 5- to 20-fold, resulting in reports of myopathy and rhabdomyolysis (104951).

CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, drugs that inhibit the CYP3A4 enzymes might increase levels of lovastatin from red yeast rice.  Details Red yeast rice contains varying levels of the statin drug lovastatin, which is metabolized by CYP3A4 (104951). Combining red yeast rice with CYP3A4 inhibitors might increase serum levels of lovastatin from red yeast rice.

GEMFIBROZIL (Lopid) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking red yeast rice in combination with gemfibrozil might increase the risk of rhabdomyolysis.  Details Red yeast rice contains varying levels of the statin drug lovastatin (9587,15017). Gemfibrozil has been reported to increase the risk of rhabdomyolysis when used in combination with lovastatin (104951).

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the risk of liver damage.  Details Red yeast rice contains varying levels of the drug lovastatin. Lovastatin can cause liver damage in some people (104951). Some clinical research suggests that supplements containing red yeast rice might increase liver enzyme levels in some, but not all, participants (42692,70491). Cases of acute hepatitis have been associated with red yeast rice (16654,54477). Combining it with hepatotoxic drugs might further increase this risk.

HMG-CoA REDUCTASE INHIBITORS ("Statins") Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking red yeast rice with other statins might increase the risk of potential adverse effects.  Details Red yeast rice contains varying levels of the statin drug lovastatin and might result in supratherapeutic levels when used with other statins. Based on evaluation of data from the US Food and Drug Administration's adverse event reporting system (FAERS), it is recommended that red yeast rice products be avoided in people taking prescription statins (98822).

NIACIN Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking red yeast rice in combination with high-dose niacin might increase the risk of rhabdomyolysis.  Details Red yeast rice contains varying levels of the statin drug lovastatin and has been linked to reports of myopathy (9587,15017). Niacin has been reported to increase the risk of rhabdomyolysis when used in combination with lovastatin (104951).

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General ...Orally, red yeast rice seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal discomfort, diarrhea, dizziness, flatulence, headache, heartburn, myopathy, and nausea.
Serious Adverse Effects (Rare):
Orally: There have been reports of hepatotoxicity and rhabdomyolysis, likely related to the lovastatin content of red yeast rice. Contaminated red yeast rice might cause renal toxicity.

Cardiovascular ...Orally, red yeast rice used in combination with other natural ingredients, such as green tea extract and policosanol, has been associated with a case of chest pain and a case of tachycardia requiring hospitalization, in post marketing surveillance (94001).

Dermatologic ...Orally, red yeast rice has been rarely associated with mild cases of pruritus and rash in clinical trials and post marketing surveillance (70531,94001,95664). Two cases of alopecia were reported in patients taking red yeast rice in clinical research (17089).

Gastrointestinal ...Orally, red yeast rice has been associated with mild adverse effects including abdominal discomfort, bloating, heartburn, flatulence, diarrhea or loose stools, nausea, vomiting, abdominal distention or pain, and reduced appetite, in clinical trials and post marketing surveillance (2624,6988,16836,70556,94001,95664). Taking red yeast rice with food may reduce the risk of heartburn, gas, and abdominal discomfort.

Genitourinary ...Orally, red yeast rice has been associated with rare reports of erectile dysfunction (70520). In one case report, a 39-year-old male developed erectile dysfunction after taking red yeast rice for one week. The dysfunction resolved after discontinuation of red yeast rice (98822).
A case of cystitis has been reported in a patient taking a specific combination product (Limicol, Laboratoire Lescuyer) containing red yeast rice extract, sugar cane extract, dry artichoke leaf extract, dry garlic extract, pine bark extract, vitamin E, riboflavin, and inositol hexanicotinate (89451). However, it is unclear if this event was associated with red yeast rice or other ingredients in the supplement.

Hepatic ...Orally, red yeast rice preparations have been linked to case reports of hepatotoxicity, including increased liver enzymes and acute hepatitis (16654,54477,94001,95664,98822,112644). Since red yeast rice often contains significant concentrations of the statin-like monacolin constituents, including lovastatin, it has the potential to cause similar side effects, including elevated liver enzymes. Clinical trials have shown that red yeast rice intake is associated with mild increases in levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which suggests possible liver damage (42692,70491,70513,70531,70547,107952). A case report describes a 62-year-old female who developed mixed hepatocellular and cholestatic hepatitis while taking red yeast rice. Signs and symptoms included fever, dark colored urine, weight loss, hyperbilirubinemia, and elevated ALT levels, all of which resolved after stopping red yeast rice (112089). A small study in various patient populations shows that taking a specific combination product (Armolipid Plus, Rottapharm S.p.A.) containing red yeast rice, berberine, policosanol, and other ingredients modestly increases levels of ALT, but not AST (107953). Clinical reviews of red yeast rice products show the risk of liver injury is comparable to the placebo or active control group, including pravastatin or lovastatin, when taken for up to 24 weeks (95664,95666).

Immunologic ...In one case report, a 58-year-old male presented with complaints of chronic dysphagia from eosinophilic esophagitis 12 months after starting an oral red yeast rice supplement (Artechol) containing monacolin K. Eosinophilic esophagitis resolved after cessation of red yeast rice (104465).
Inhalation of red yeast rice powder has resulted in one case of anaphylaxis (6997).

Musculoskeletal ...Orally, red yeast rice preparations have been linked to cases of myalgia, muscle spasm, rhabdomyolysis, and myopathy (9587,15017,16654,16834,16836,17089,70475,94001,95664,98822)(103311,112644,112645). Also, elevated creatine kinase levels up to 10 times normal, suggesting muscle injury and inflammation, have been reported in clinical and post-marketing research reports (6988,9587,15017,42692,70530,70567,94001,95664). The risk of muscle injury with red yeast rice seems to be similar to that with statins. In a small 3-month clinical trial in patients with previous statin intolerance, the rate of therapy discontinuation due to myalgia was similar between patients taking a specific red yeast rice product (Red Yeast Rice, Sylvan Bioproducts) 2400 mg twice daily (containing a daily dose of about 10 mg lovastatin) and patients taking pravastatin 20 mg twice daily (17089). However, in one case report, a 53-year-old patient experienced myalgia after 4 months of taking a red yeast rice product containing 4-8 mg lovastatin. Another case report describes a 50-year-old female who developed generalized myalgias and rhabdomyolysis, with elevated creatine phosphokinase, lactate dehydrogenase, and myoglobin levels, while taking red yeast rice (112306). The risk of myopathy seems to depend on the specific red yeast rice formulation and dose used (95903).

Neurologic/CNS ...Orally, red yeast rice has been associated with dizziness, headache, fatigue, and tingling in the extremities (6988,16836,17089,18110,94001). A case of peripheral neuropathy occurred in a 60-year-old male with a gastrointestinal tumor who was taking imatinib 400 mg daily along with red yeast rice for 3 years (89453). Three months after cessation of red yeast rice, symptoms resolved.

Ocular/Otic ...Orally, red yeast rice in combination with policosanol has been associated with one post-marketing report of hazy vision (94001).

Renal ...Orally, red yeast rice contaminated with citrinin may cause renal toxicity. Analyses of red yeast rice products have found that about one-third to two-thirds of these products contain citrinin (9588,17501,95666). Citrinin is a nephrotoxin that results from incorrect rice fermentation processes (9588,17501,70543). In vitro and in animal research, citrinin has been reported to cause kidney damage (70482,70542,70540).

Other ...Orally, red yeast rice has been associated with rare cases of edema (70508,70520,70525).

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