Hypercholesterolaemia

Because of their high fibre content, sterol content and low calorific value, mushrooms are an ideal food for diets designed to prevent cardiovascular disease and have been extensively investigated for their potential therapeutic application in this regard. In animal models a range of mushrooms, including Agaricus bisporus (common button mushroom), Grifola frondosa, Lentinula edodes, Ganoderma lucidum and Flammulina velutipes, all show increased excretion of cholesterol, decreases in LDL and triglycerides and increase in HDL when included in the diet at 5% of feed1-6. Similar effects are seen from dietary inclusion of other beta-glucan sources such as oats and barley and it is considered that the action of beta-glucans on cholesterol levels is mediated by their binding affinity for bile acids, leading to activation of cholesterol 7α-hydroxylase and upregulation of low-density lipoprotein receptor and thus increased transportation of LDL into hepatocytes and conversion of cholesterol into bile acids7.

In addition, several medicinal mushrooms are natural sources of lovastatin (also called monakolin K or mevinolin) with high levels in a number of Pleurotus species as well as Ganoderma lucidum and higher levels in the myceliumthan the fruiting bodies8-10. Levels of lovastatin show significant variation from one strain to another however, making standardised protocols difficult, and better results are achieved clinically with another lovastatin-producing fungus, Monascus purpureus (Hong Qu Mi – Red Yeast Rice), for which standardised strains are available and for which a much greater impact on cholesterol levels has been demonstrated than achieved by the equivalent dosage of pure lovastatin, implying synergistic action between it and other compounds found in M. purpureus.

Eritadenine, a compound isolated from L. edodes has demonstrated strong cholesterol lowering properties and it has been suggested that it acts through alteration of hepatic phospholipid metabolism by inhibition of S-adenosylhomocysteine hydrolase, increased excretion and decomposition of ingested cholesterol, and reduced secretion of VLDL by the liver10. L. edodes fed at 10-50g/kg of diet led to significant decreases in both plasma cholesterol concentration and PC:PE ratio of liver microsomes in rats and eritadenine included at 50mg/kg diet had a similar effect11. In clinical trials dried L. edodes (9g/day) decreased serum cholesterol 7-10% in patients suffering from hypercholesterolemia and 90g/day fresh L. edodes (equivalent to 9g/day dried mushroom) led to a decrease in total cholesterol of 9-12%and triglycerides of 6-7%12.

Saito et al reported levels of eritadenine of 400-700mg/kg, although Enman et al suggest that the true level may be 10 times greater13,14. However, without standardised strains, levels of eritadenine in L. edodes are hard to quantify. It has also been shown that stirring rather than shaking during mycelial fermentation can produce a five-fold increase in production of eritadenine, implying significant potential variability in response to cultivation parameters15.

CLINICAL NOTE
Two strains of M. purpureus are commercially available, one containing 0.4% lovastatin and the other 0.8%, with clinical trials showing 1200mg/day of the the 0.4% strain to be effective at lowering cholesterol in patients not on prescription statins and 1200mg/day of the 0.8% strain (or 2400mg/day of the 0.4% strain) to be an effective substitute for lovastatin at 10mg/day.
Because the eritadenine present in L. edodes works via a different enzymatic pathway from prescription statins or statin-containing fungi, it can usefully be combined with them to enhance their impact on cholesterol control.

REFERENCES
1.White button mushroom (Agaricus bisporus) lowers blood glucose and cholesterol levels in diabetic and hypercholesterolemic rats. Jeong SC, Jeong YT, Yang BK, Islam R, Koyyalamudi SR, Pang G, Cho KY, Song CH. Nutr Res. 2010;30(1):49-56.
2. Cholesterol-lowering effects of maitake (Grifola frondosa) fiber, shiitake (Lentinus edodes) fiber, and enokitake (Flammulina velutipes) fiber in rats. Fukushima M, Ohashi T, Fujiwara Y, Sonoyama K, Nakano M. Exp Biol Med (Maywood). 2001;226(8):758-65.
3. Maitake extracts and their therapeutic potential – A Review. Mayell M. Alt Med Rev, 2001;6:1.
4. Cholesterol-lowering properties of Ganoderma lucidum in vitro, ex-vivo, and in hamsters and minipigs. Berger A, Rein D, Kratky E, Monnard I, Piguet-Welsch C, Hauser J, Mace K, Niederberger P. Lipids in Health and Disease 2004;3:2.
5. Dose and time dependent hypercholesterolemic effect of oyster mushroom (Pleurotus ostreatus) in rats. Nutrition. 1998;14:282-286.
6. Effect of high beta-glucan barley on serum cholesterol concentrations and visceral fat area in Japanese men – A randomised, double-blinded, placebo controlled trial. Shimizu C, Kihara M, Aoe S et al. Plant Foods Hum Nutr. 2008;63:21-5.
7. Pleurotus fruiting bodies contain the inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase – lovastatin. Gunde-Cimerman N, Cimerman A. Exp Mycol. 1995;19(1):1-6.
8. Comparative study of contents of several bioactive components in fruiting bodies and mycelia of culinary-medicinal mushrooms. Lo YC, Lin SY, Ulziijargal E, Chen SY, Chien RC, Tzou YJ, Mau JL. Int J Med Mushrooms. 2012;14(4):357-63.
9. Comparative study of contents of several bioactive components in fruiting bodies and mycelia of culinary-medicinal mushrooms. Lin SY, Chen YK, Yu HT, Barseghyan GS, Asatiani MD, Wasser SP, Mau JL. Int J Med Mushrooms. 2013;15(3):315-23.
10. Hypocholesterolemic action of eritadenine is mediated by a modification of hepatic phospholipid metabolism in rats. Sugiyama K, Akachi T, Yamakawa A. J Nutr. 1995;125(8):2134-44.
11. Eritadenine-induced alterations of plasma lipoprotein lipid concentrations and phosphatidylcholine molecular species profile in rats fed cholesterol-free and cholesterol-enriched diets. Shimada Y, Morita T, Sugiyama K. Biosci Biotechnol Biochem. 2003 May;67(5):996-1006.
12. Shiitake (Lentinus edodes) Wasser SP. Encyclopedia of Dietary Supplements. 2005.
13. Quantitative analysis of eritadenine in ‘Shii-take’ mushroom and other edible fungi. Saito M, Yamashita T, Kaneda T. Eiyo to Shokuryo. Pub Informa Healthcare. 1975;28:503-505.
14. Quantification of the bioactive compound eritadenine in selected strains of shiitake mushroom (Lentinus edodes). Enman J, Rova U, Berglund KA. J Agric Food Chem. 2007;55(4):1177-80.
15. Production of the bioactive compound eritadenine by submerged cultivation of shiitake (Lentinus edodes) mycelia. Enman J, Hodge D, Berglund K.A, Rova U.J. Agric Food Chem. 2008;56(8):2609-12.