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Scientific Opinion on the substantiation of health claims related to monacolin K from red yeast rice and maintenance of normal blood LDL-cholesterol concentrations (ID 1648, 1700) pursuant to Article 13(1) of Regulation (EC) No 1924/2006[sup]1[/sup] EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA)2, 3 European Food Safety Authority (EFSA), Parma, Italy
Słowa kluczowe: LDL-cholesterol   Monacolin K   Monascus purpureus   health claims   red yeast rice  
ID:    1700      1648  
Produkty: Monakolina K  

1. Charakterystyka żywności / składnika

The food that is the subject of the health claim is red yeast rice (i.e. rice fermented with the red yeast Monascus purpureus).
Red yeast rice is a traditional Chinese food product which is still a dietary staple in many Asian countries (Heber et al., 1999). Various red yeast rice preparations are available as food supplements. The preparations from red yeast rice typically contain starch, protein, fat (including monounsaturated fatty acids, plant sterols), isoflavones, and other compounds. Depending on the Monascus strains used and the fermentation conditions, the products may contain polyketides called monacolins, which are secondary metabolites produced during fermentation (Liu et al., 2006).
Monacolin K, in lactone (also known as lovastatin or mevinolin) and hydroxy acid forms, is the main monacolin in Monascus purpureus-fermented rice (75-90 % of total monacolin content) (Heber et al., 1999; Li et al., 2004). Commercial red yeast rice products have variable contents of monacolin K and total monacolins (Gordon et al., 2010; Li et al., 2004).
From the conditions of use provided, the Panel notes that monacolin K from Monascus purpureus-fermented rice has been specified as the food constituent which may be responsible for the claimed effect considered in this opinion. Monacolin K from Monascus purpureus-fermented rice is a well defined compound, which can be measured in foods by established methods.
The Panel considers that, whereas red yeast rice is not sufficiently characterised in relation to the claimed effect, the food constituent, monacolin K from red yeast rice, is sufficiently characterised.

2. Znaczenie oświadczenia dla zdrowia człowieka

The claimed effects are “cholesterol” and “cholesterol management/heart health”. The Panel assumes that the target population is adults in the general population.
In the context of the proposed wordings, the Panel assumes that the claimed effects refer to maintenance of normal blood LDL-cholesterol concentrations.
Low-density lipoproteins (LDL) carry cholesterol from the liver to peripheral tissues, including the arteries. Elevated LDL-cholesterol, by convention >160 mg/dL (>4.14 mmol/L), may compromise the normal structure and function of the arteries.
The Panel considers that maintenance of normal blood LDL-cholesterol concentrations is a beneficial physiological effect.

3. Naukowe uzasadnienia wpływu na zdrowie człowieka - Utrzymanie prawidłowego stężenia cholesterolu LDL we krwi

Among the references provided were an editorial of a scientific journal, letters-to-the-editor, monographs, and narrative reviews on Monascus purpureus, red yeast rice supplements or 3-hydroxy- 3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, which did not contain original data that could be used for the scientific substantiation of the claim. Some studies did not address the food which is the subject of the claim but rather other foods (e.g. arginine) or did not address blood lipids as an outcome but rather other outcomes (e.g. bioavailability of monacolin K from fermented red yeast rice). One pilot study compared the effect of a combination of Monascus purpureus extract, octacosanols and niacin with pravastatin on blood cholesterol concentrations. The Panel considers that no conclusions can be drawn from a study using a combination of food constituents for the substantiation of a health claim on monacolin K from red yeast rice alone. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claim.
One systematic review and some human intervention studies investigated the effect of red yeast rice preparations on blood cholesterol concentrations but did not report the monacolin K content of the preparations used. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claim.
A meta-analysis of randomised clinical trials which investigated the effect of fermented red yeast rice preparations on blood lipid concentrations in subjects with primary hyperlipidaemia was provided (Liu et al., 2006). The Panel notes that the meta-analysis reported to include studies of poor methodological quality (lack of information on randomisation, blinding, drop-outs) and considers that no conclusions can be drawn from this meta-analysis for the scientific substantiation of the claim.
Eight of the studies identified in the meta-analysis evaluated the effect of fermented red yeast rice preparations against placebo on blood LDL-cholesterol concentrations. Seven studies were published in Chinese and no translation in an EU language was available to the Panel. The remaining study is described below (Heber et al., 1999).
Two human intervention studies (Heber et al., 1999; Lin et al., 2005) investigated the effect of red yeast rice preparations with known monacolin K content on total and LDL-cholesterol concentrations.
In a double-blind, randomised, placebo-controlled trial (RCT) (Heber et al., 1999), 88 subjects with hypercholesterolaemia, who were not taking lipid-lowering medications, received either fermented red yeast rice (Cholestin, 2.4 g/day) or a placebo (rice powder) in capsules daily for 12 weeks. The fermented red yeast rice preparation contained 0.3 % monacolin K (0.2 % in lactone form, 0.1 % in hydroxy acid form) by weight, corresponding to a daily dose of around 7.5 mg. The content of other monacolins was 0.1 %, i.e. 2.5 mg/day. A total of 83 subjects completed the study (n=42 in the treatment group vs. n=41 in the placebo group; 46 men and 37 women, 34-78 years). Significant differences between groups were observed at weeks 8 and 12 for LDL-cholesterol concentrations (p<0.001 at both time points, per protocol (PP) analysis) and total cholesterol concentrations (p<0.05 at both time points, PP analysis). ANCOVA showed main effects of baseline LDL-cholesterol/total cholesterol concentrations and treatment group on LDL-cholesterol/total cholesterol concentrations respectively at 12 week (p<0.001 for all). At week 12, the mean LDL-cholesterol concentrations in the treatment group was reduced by 22 % from baseline, compared with a 3 % reduction in the
placebo group. The mean total cholesterol concentration was reduced by 16 % in the treatment group compared to 2 % in the placebo group.
In a double-blind RCT (Lin et al., 2005), 79 subjects with hypercholesterolaemia who were not taking lipid-lowering medications during the trial, received either fermented red yeast rice (Monascus purpureus Went rice, 1.2 g/day) or a placebo (grounded rice) daily for eight weeks. Patients taking lipid-lowering medications were considered after a four-week wash-out period, with the exception of probucol, which had to be discontinued for at least six months. The fermented red yeast rice preparation contained 0.95 % lovastatin by weight corresponding to a daily dose of around 11.4 mg. The Panel assumes that this dose corresponds to monacolin K in the lactone form only. The amount of monacolin K in its hydroxy acid form was not provided. The preparation also contained 0.21 % other monacolins by weight, i.e. 2.5 mg/day. A total of 75 subjects completed the study (n=38 in treatment group, 59 % men, vs. n=37 in placebo group, 55 % men; 23-65 years). At week eight, a significantly greater reduction in LDL-cholesterol concentrations was observed in the treatment group compared to the placebo group (-26.3 % vs. -1.4 %, p<0.001, intention-to-treat (ITT) analysis). The reduction in total cholesterol concentrations was also significantly higher in the treatment group than in the placebo group (-20.4 % vs. -0.4 % p<0.001, ITT analysis).
Pure monacolin K (lovastatin) has been shown to be effective in reducing total cholesterol and LDL-cholesterol concentrations in individuals with hypercholesterolaemia and is a well-known inhibitor of HMG-CoA reductase. A significant inhibitory effect of a fermented red yeast rice preparation (Cholestin) on HMG-CoA reductase activity and cholesterol concentrations was observed in vitro in human hepatic cells (HepG2) (Man et al., 2002).
In weighing the evidence, the Panel took into account that two RCTs provided from which conclusions could be drawn for the scientific substantiation of the claim showed an effect of red yeast rice preparations providing a daily dose of about 10 mg monacolin K on LDL-cholesterol concentrations in individuals with hypercholesterolaemia, that the effect of pure monacolin K on LDL-cholesterol concentrations is well established and that the mechanism by which monacolin K can contribute to the claimed effect is well known.
The Panel concludes that a cause and effect relationship has been established between the consumption of monacolin K from red yeast rice and maintenance of normal blood LDL-cholesterol concentrations.

4. Uwagi do zaproponowanego brzmienia oświadczenia

The Panel considers that the following wording reflects the scientific evidence: “Monacolin K from red yeast rice contributes to the maintenance of normal blood cholesterol concentrations”.

5. Warunki i możliwe ograniczenia stosowania oświadczenia

The Panel considers that in order to obtain the claimed effect, 10 mg of monacolin K from fermented red yeast rice preparations should be consumed daily. The target population is adults in the general population.
In relation to restrictions of use, the Panel refers to the Summary of Product Characteristics of lovastatin-containing medicinal products available on the EU market.

Wnioski

On the basis of the data presented, the Panel concludes that:
The food, red yeast rice, which is the subject of the health claim is not sufficiently characterised in relation to the claimed effect, whereas the food constituent monacolin K from red yeast rice is sufficiently characterised.
The claimed effects are “cholesterol” and “cholesterol management/heart health”. The target population is assumed to be adults in the general population. Maintenance of normal blood LDL-cholesterol concentrations is a beneficial physiological effect.
A cause and effect relationship has been established between the consumption of monacolin K from red yeast rice and maintenance of normal blood LDL-cholesterol concentrations.
The following wording reflects the scientific evidence: “Monacolin K from red yeast rice contributes to the maintenance of normal blood cholesterol concentrations”.
In order to obtain the claimed effect, 10 mg of monacolin K from fermented red yeast rice preparations should be consumed daily. The target population is adults in the general population.
In relation to restrictions of use, reference is made to the Summary of Product Characteristics of lovastatin-containing medicinal products available on the EU market.