El éxito empírico de los modelos nucleares

As cardiovascular diseases are among the leading causes of death in the developed world, prevention receives a great deal of attention. Lowering cholesterol levels is one of the most important means of achieving this end. Many modern drugs are available, but patients prefer supplementing (sometimes even replacing) medical treatment with natural cures. One of the latest wonder foods is red yeast rice, which is considered very effective and safe.

High cholesterol levels increase the long-term risk of the thickening and harden- ing of arteries, which is often caused by the deposition of the oxidized and insoluble form of this cholesterol on the walls of blood vessels. This deposition decreases the diameter of arteries and veins. As a consequence, the flow of blood to body parts deteriorates, and this may cause damage over time. If the deposition is formed in the heart, this organ is unable to function properly.

Cholesterol lowering medicines usually work by inhibiting the uptake of this compound or slowing down its synthesis in the liver. Herbs used for this purpose exert their effects in the same way. A decrease of 20–50 % in cholesterol levels is the usual result of medical treatments, but this can be improved by a low-cholesterol diet and the use of some herbs and vegetables (artichoke or garlic). Red yeast rice is quite heavily advertised as a very effective and natural substance, and millions of people purchase these products. Red yeast rice is sold in dietary supplements and is not a listed medicine, which—most ironically—just adds to its popularity (Fig. 3.26).

Red yeast rice has been known for a long time. Its first application was described in China during the Tang dynasty in the eighth century, but, needless to say, not as a cholesterol drug. Red rice was used as a dye, spice and preservative in food, and during the production of rice wine to speed up fermentation. In Southeast Asia, red yeast rice is still a common food. Records of some medical applications were found from the Ming dynasty (fourteenth to seventeenth century) from a medicine book that recommended it to help blood circulation and digestion.

Red yeast rice is prepared by fermentation of rice with fungi. The red color of the marketed product is caused by pigments produced by microscopic fungi. The most common Chinese names are Ang Khak and Hong Qu, whereas in Japan it is known as Beni-Koji. Chemical testing of red rice began in 1979, when Akira Endo reported the isolation of a compound named monacolin K from Thai red yeast rice. This substance was proven to have strong cholesterol lowering potential in animal tests. The discovery was by no means an accident: it was part of a systematic search. Eight thousand samples were tested, and the microbe producing the compound, Monascus ruber, was identified. The project also found eight additional compounds similar to monacolin K. Fermented rice contains about 0.4 % monacolin derivatives,

177 3.18 Red Rice Remedy: Cholesterol Relief?

about half of which is monacolin K. Sterols and unsaturated fatty acid also present in the product may contribute to the physiological effects somewhat. The pigments of the fungi include yellow, orange and red dyes. The fermentation of rice wine is aided by the enzyme amylase present in red rice, which breaks down starch in rice to glucose, which in turn ferments into alcohol.

Prior to the discovery of monacolin K, Endo isolated a compound called mevas- tatin from grain ferment. This is the “parent compound” of most modern cholesterol drugs. Some of its derivatives can be used more favorably, but mevastatin is still a useful medicine. In 1980 Lovastatin (or mevinolin), a mevastatin-related compound isolated form of the fungus Aspergillus terreus (Fig. 3.27), had been shown to be identical to monacolin K. This discovery was not particularly useful for some time.

Lovastatin proved to be an effective and very popular drug, but red yeast rice was not used for medical purposes for a long time. It was only “discovered” in the 1990s, at the dawn of the age of dietary supplements. Red yeast rice is relatively inexpensive. Marketing it as a dietary supplement rather than a medicine makes the approval process simpler and faster, and distribution is also more convenient than for drugs which are only available in pharmacies by prescription.

However, lovastatin and its derivatives may cause adverse effects. The most common side effect is muscle pain, and in the most severe cases, muscle damage may also develop. The monacolin K content of freely available red yeast rice prod- ucts may lead to abuse (overdosage) resulting in health damage. This was the reason why all food supplements containing red yeast rice were removed from the USA market by the Food and Drug Administration in 2001.

Nevertheless, the business has never been better. These natural products can be sold without significant restrictions in many parts of the world (for example in the European Union), despite their confirmed content of active substances that also have serious side effects. A daily dose of a typical product is 1.2–2.4 g, which may contain 5–10 mg of monacolin K. This amount was proven to lower cholesterol levels in clinical tests. The cost of the treatment can vary greatly for both prescrip- tion drugs and dietary supplements, but average costs per day are similar. From a strictly scientific point of view, red rice products do not have advantages over medicines, but they may be more attractive to patients, especially those who are prejudiced against medicines. However, the amount of active substances in dietary

Fig. 3.26  Chicken, spinach,

red rice—a healthy meal? (Copyright-free Wikipedia picture)

178 3 Medicines

supplements is generally unreliable. In a study of red rice products, the dose of mo- nacolin K in a single capsule was shown to vary between 0.1 and 10 mg. In addition, some of the ingredients may not be favorable to human health, occasionally even outright harmful. One of these ingredients is a fungal toxin called citrinin, which was proven to cause kidney damage in animal tests. Human data are not available, but the fact that more than 1 µg was detectable in 70 % of the products in one study, may warrant some caution.

Tests showed that although side effects of red rice products are not more com- mon or more severe than those of competitor medications, safety issues must be considered very carefully. Red rice has been tested under controlled conditions on fewer people that the pure active substances in medicines. Another cause for caution is that the known side effects of drugs have to be registered by authorities, whereas no similar obligation exists for dietary supplements. Side effects may very easily remain hidden or totally unrecognized, especially if they only develop in the long term, which makes establishing causality difficult.