Dr. Ron’s Research Review – February 26, 2020

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This week’s research review focuses on Red Yeast Rice

Monacolin K

Monacolin K is an active compound naturally present in red yeast rice, which is chemically identical to cholesterol statin drugs like lovastatin.
A study found great variability in the strength of red yeast rice supplements purchased from mainstream retailers.  Monacolin K was not detected in two brands. In the 26 brands that contained monacolin K, the quantity ranged more than 60-fold from 0.09 to 5.48 mg per 1200 mg of red yeast rice. Unfortunately the brand names are not mentioned in the article. (Cohen et al., 2017)
An older article does mention the product names and manufacturers. Cholestene by HPF contains 2.87 mg per capsule. Cholester-Reg by Nature’s Sunshine contains 3.37 mg per capsule, which has been reformulated to Cholester-Reg II. The testing was done at the UCLA Center for Human Nutrition, UCLA School of Medicine, Los Angeles, California. (Klimek et al., 2009) (Heber et al., 2001)

Safety of Red Yeast Rice

A meta-analysis examined the safety data of red yeast rice derived from the available randomized controlled clinical trials (RCTs). (Fogacci et al., 2019)
Primary outcomes were musculoskeletal disorders (MuD). Secondary outcomes were non-musculoskeletal adverse events (Non-MuD) and serious adverse events (SAE). Subgroups analyses were carried out considering the intervention (RYR alone or in association with other nutraceutical compounds), monacolin K administered daily dose (≤3, 3.1-5 or >5 mg/day), follow-up (>12 or ≤12 weeks), with statin therapy or statin-intolerance and type of control treatment (placebo or statin treatment). Data were pooled from 53 RCTs comprising 112 treatment arms, which included 8535 subjects, with 4437 in the RYR arm and 4303 in the control one.
Monacolin K administration was not associated with increased risk of musculoskeletal disorders (odds ratio (OR) = 0.94, 95% confidence interval (CI) 0.53,1.65).
Moreover, the data showed reduced risk of non-musculoskeletal adverse events (OR = 0.59, 95%CI 0.50, 0.69) and serious adverse events (OR = 0.54, 95%CI 0.46, 0.64) vs. control.
Subgroups analyses confirmed the high tolerability profile of red yeast rice. Furthermore, increasing daily doses of monacolin K were negatively associated with increasing risk of Non- musculoskeletal disorders (slope: -0.10; 95%CI: -0.17, -0.03; two-tailed p < 0.01).
Based on our data, red yeast rice use as lipid-lowering dietary supplement seems to be overall tolerable and safe in a large kind of moderately hypercolesterolaemic subjects. (Fogacci et al., 2019)

Red Yeast Rice Supplements Reviewed by ConsumerLab
https://www.youtube.com/watch?v=p8brUpqMPqI

Cholestene has 6.44 mg as of 2018 according to Consumerlab.com. Lovastatin content is down almost 50% from where it was four years ago!

 

Cholestene by HPF, 1200 mg, 120 caps $14
http://www.hpfonline.com/

Red Yeast Rice Extract by Arazo Nutrition, 1200 mg , 120 caps $18
Standardized to 0.2% Monacolin K (2.4 mg) Optimum Dose
https://arazonutrition.com/products/red-yeast-rice
https://www.amazon.com/gp/product/B01MEGYQ6X/

Dr. Ron

 


Articles

 

Variability in strength of red yeast rice supplements purchased from mainstream retailers.
            (Cohen et al., 2017) Download
The United States Food and Drug Administration (FDA) has introduced manufacturing standards for dietary supplements, including red yeast rice, to assure their identity, purity, strength, and composition. One supplement commonly used to self-treat high cholesterol, red yeast rice, may contain monacolin K, an ingredient identical to prescription lovastatin. We examined whether FDA's manufacturing standards led to standard concentrations of the statin monacolin K in red yeast rice supplements. We analyzed 28 brands of red yeast rice supplements by ultra-high performance liquid chromatography-diode array detector-quadrupole time-of-flight mass spectrometry for monacolin K content. Monacolin K was not detected in two brands. In the 26 brands that contained monacolin K, the quantity ranged more than 60-fold from 0.09 to 5.48 mg per 1200 mg of red yeast rice. Following the manufacturers' recommendations for daily servings, the quantity of monacolin K consumed per day would range more than 120-fold from 0.09 to 10.94 mg. Despite FDA manufacturing standards, strength and composition of red yeast rice supplements sold at mainstream retail stores in the United States remains unpredictable.

Safety of red yeast rice supplementation: A systematic review and meta-analysis of randomized controlled trials.
            (Fogacci et al., 2019) Download
Recently, concerns regarding the safety of red yeast rice (RYR) have been raised after the publication of some case reports claiming toxicity. Since the previous meta-analyses on the effects of RYR were mainly focused on its efficacy to improve lipid profile and other cardiovascular parameters, we carried out a meta-analysis on safety data derived from the available randomized controlled clinical trials (RCTs). Primary outcomes were musculoskeletal disorders (MuD). Secondary outcomes were non-musculoskeletal adverse events (Non-MuD) and serious adverse events (SAE). Subgroups analyses were carried out considering the intervention (RYR alone or in association with other nutraceutical compounds), monacolin K administered daily dose (≤3, 3.1-5 or >5 mg/day), follow-up (>12 or ≤12 weeks), with statin therapy or statin-intolerance and type of control treatment (placebo or statin treatment). Data were pooled from 53 RCTs comprising 112 treatment arms, which included 8535 subjects, with 4437 in the RYR arm and 4303 in the control one. Monacolin K administration was not associated with increased risk of MuD (odds ratio (OR) = 0.94, 95% confidence interval (CI) 0.53,1.65). Moreover, we showed reduced risk of Non-MuD (OR = 0.59, 95%CI 0.50, 0.69) and SAE (OR = 0.54, 95%CI 0.46, 0.64) vs. control. Subgroups analyses confirmed the high tolerability profile of RYR. Furthermore, increasing daily doses of monacolin K were negatively associated with increasing risk of Non-MuD (slope: -0.10; 95%CI: -0.17, -0.03; two-tailed p < 0.01). Based on our data, RYR use as lipid-lowering dietary supplement seems to be overall tolerable and safe in a large kind of moderately hypercolesterolaemic subjects.

An analysis of nine proprietary Chinese red yeast rice dietary supplements: implications of variability in chemical profile and contents.
            (Heber et al., 2001) Download
OBJECTIVES:  Some strains of Chinese red yeast rice, when prepared by solid fermentation, produce compounds called monacolins that inhibit cholesterol production. When used as a dietary supplement to achieve and maintain healthy cholesterol levels, Chinese red yeast rice has significant potential to reduce health care costs and contribute to public health by reducing heart disease risk in individuals with moderate elevations of circulating cholesterol levels. Whereas one proprietary strain of Chinese red yeast rice has been demonstrated to lower cholesterol levels significantly in clinical trials, other strains being sold as Chinese red yeast rice dietary supplements have not undergone similar evaluation. In order to determine whether the results of a clinical trial conducted with one strain of Chinese red yeast rice could be generalized to other preparations of Chinese red yeast rice, nine different commercially available dietary supplements were purchased tested for chemical constituents. DESIGN:  Monacolins were measured by high performance liquid chromatography (HPLC) that separates the various monacolins in Chinese red yeast rice. Citrinin concentration, a toxic fermentation byproduct, was measured by radioimmunoassay. RESULTS:  Total monacolin content varied from 0% to 0.58% w/w and only 1 of 9 preparations had the full complement of 10 monacolin compounds. Citrinin was found at measurable concentrations in 7 of the 9 preparations. CONCLUSIONS:  The findings from clinical trials demonstrating significant and clinically relevant cholesterol reduction using a defined Chinese red yeast rice preparation containing 10 different monacolins cannot be generalized to preparations that do not contain the same levels and profile of monacolins. Standardized manufacturing practices should be established for Chinese red yeast rice sold as a dietary supplement in order ensure equivalence of content of active ingredients in preparations being sold to the public and to limit the production of unwanted byproducts of fermentation such as citrinin. In common with other botanical dietary supplements, the full potential of this product will not be realized until standards for production and labeling of Chinese red yeast rice are further developed.


 

Safety and efficacy of red yeast rice (Monascus purpureus) as an alternative therapy for hyperlipidemia.
            (Klimek et al., 2009) Download
Red yeast rice is a Chinese fermented rice product (Monascus purpureus) that some have claimed improves blood circulation by decreasing cholesterol and triglyceride levels in humans. The supplement contains naturally occurring monacolin K, the active ingredient found in Merck's prescription agent lovastatin (Mevacor). Lovastatin is associated with various adverse effects such as myopathy and abnormal liver function test results, which can lead to serious problems if patients are not monitored and treated. The inclusion of lovastatin in red yeast rice and the lack of dietary supplement regulation by the FDA raise safety concerns for health care professionals as well as for patients. Studies have shown that red yeast rice products can be beneficial in lowering serum cholesterol levels, but they are not without risk. Furthermore, product uniformity, purity, labeling, and safety cannot be guaranteed.

 

References

Cohen, PA, B Avula, and IA Khan (2017), ‘Variability in strength of red yeast rice supplements purchased from mainstream retailers.’, Eur J Prev Cardiol, 24 (13), 1431-34. PubMed: 28641460
Fogacci, F, et al. (2019), ‘Safety of red yeast rice supplementation: A systematic review and meta-analysis of randomized controlled trials.’, Pharmacol Res, 143 1-16. PubMed: 30844537
Heber, D, et al. (2001), ‘An analysis of nine proprietary Chinese red yeast rice dietary supplements: implications of variability in chemical profile and contents.’, J Altern Complement Med, 7 (2), 133-39. PubMed: 11327519
Klimek, M, S Wang, and A Ogunkanmi (2009), ‘Safety and efficacy of red yeast rice (Monascus purpureus) as an alternative therapy for hyperlipidemia.’, P T, 34 (6), 313-27. PubMed: 19572049