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Journal of Food Protection, Vol. 53, No. 10, Pages 883-894 (October 1990) Copyright© International Association of Milk, Food and Environmental Sanitarians

Nutritional and Medicinal Value of Specialty Mushrooms

WILLIAM M. BREENE

Department of Food Science and Nutrition, University of Minnesota, 1334 Eckles Avenue, St. Paul, MN 55108

(Received for publication October 12, 1989) Downloaded from http://meridian.allenpress.com/jfp/article-pdf/53/10/883/1657928/0362-028x-53_10_883.pdf by guest on 02 October 2021

ABSTRACT Thailand, and Belgium. In 1986, China was the major producer of straw mushrooms, Pleurotus spp. and Auricularia Although the button mushroom (Agaricus bisporus) accounts spp. with 56.3%, 59.0%, and 67.2%, respectively, of total for slightly over half of total world mushroom production, specialty world production (4). In 1974, Japan and Taiwan pro­ mushrooms, e.g., shiitake (Lentinula edodes), straw (Volvariella duced 90% and 10%, respectively, of the world crop of volvacea), oyster (Pleurotus spp.), and enokitake (Flammulina enokitake (13). It should be noted that much of the success velutipes), are increasing in popularity. These species contain by the Japanese in the expansion of specialty mushroom moderate quantities of good quality protein and are good sources cultivation can be traced to the efforts of the late Dr. of dietary fiber, vitamin C, B vitamins, and minerals. Lipid Kisaku Mori who established the Mushroom Research levels are low, but unsaturated to saturated fatty acid ratios are high (about 2.0 - 4.5:1). Some species (e.g., shiitake) accumu­ Institute of Japan (39,46). late cadmium and selenium and other heavy metals, and some Agaricus bisporus is the predominant mushroom grown may contain toxic substances such as the heat labile cardiotoxic and consumed in the United States. Although most of these proteins volvatoxin in the straw mushroom and flammutoxin in specialty mushrooms are grown and consumed primarily enokitake. Extensive clinical studies, primarily in Japan, have in the Far East, there is a definite potential for their expanded clearly demonstrated that a number of species have medicinal production in the West (5,14). and therapeutic value, by injection or oral administration, in the This paper will address the nutritional value and prevention/treatment of cancer, viral diseases (influenza, polio), medicinal properties of the second most popular mush­ hypercholesterolemia, blood platelet aggregation, and hyperten­ room in the world, shiitake, as well as those of V. volva­ sion. Most of the studies have focused on shiitake, enokitake, cea, Pleurotus spp., F. velutipes, and other species includ­ Pleurotus spp., and on the generally nonculinary Ganoderma ing wild types, where appropriate. spp. Many of the active substances which include polysaccha­ rides (e.g., G-glucans), nucleic acid derivatives (the hypocholesterol- emic eritadenine), lipids, peptides, proteins, and glycoproteins, Part I. Nutritional Value have been isolated and identified. Some of the mechanisms of A comprehensive review of the nutritional value of activity have been elucidated, e.g., antiviral activity via stimu­ lation of interferon production in the host. Additional medical mushrooms was presented by Crisan and Sands (12). They claims less well documented may nonetheless have some valid­ noted the problem of evaluating data published by differ­ ity and merit further study. ent investigators working with even the same species of mushrooms, since the composition of a given species is The total annual world production of cultivated affected by many variables. Composition, per se, cannot mushrooms is estimated at well over 1.2 million metric be translated directly into nutritional value because of such tons (6,92). The 1986 world production of cultivated things as differences in digestibility of components, rela­ mushrooms was about 2.2 million metric tons (fresh tive availability of nutrients, and inherent inaccuracies of equivalent weight), with the common button mushroom analytical procedures. (Agaricus bisporus) accounting for 56% of total produc­ Moisture. Fresh mushrooms generally contain 85-95% tion Other important species include shiitake (Lentinula moisture, whereas commercially available, air-dried speci­ edodes), 14%; straw mushroom (Volvariella volvacea), 8%; mens contain 5-20% moisture, depending on duration and oyster mushroom (Pleurotus spp.), 8%; wood ear mush­ conditions of storage prior to analysis. On average, how­ room (Auricularia spp.), 6%; enokitake (Flammulina ve­ ever, fresh and air-dried mushrooms contain about 90% lutipes), 5%, and all other species, 3% (4). and 10-12% moisture, respectively (12). Published data on An estimated 314,000 metric tons of shiitake were composition of mushrooms are often expressed on a dry produced in 1986; major producing countries were Japan weight basis. As a rule of thumb, assuming 10% dry matter (51%), China (38.3%), Taiwan (10.2%), Korea (0.3%), content in fresh mushrooms, data can be converted from and United States (0.1%) with the remaining 0.1% spread fresh weight to dry weight basis and vice versa by multi­ among Canada, Singapore, Holland, Philippines, Finland, plying or dividing by 10, respectively.

JOURNAL OF FOOD PROTECTION, VOL. 53, OCTOBER 1990 884 WILLIAM M. BREENE

Protein. Mushrooms are considered to be good sources total protein amino acids in shiitake mushrooms; essential of protein. Crisan and Sands (12) have pointed out some amino acids constituted about 32% of the total. Essential special considerations relating to the protein content of amino acids accounted for about 40% of the total in P. mushrooms. The crude protein content of most foods is ostreatus (31). calculated from nitrogen content (N X 6.25), assuming that Approximately 25-35% of the total amino acids occur the protein contains 16% nitrogen, that it is digestible, and in the free state (12). The limiting amino acids reported in that it contains negligible amounts of nonprotein nitrogen. mushrooms across 14 different literature reports were, in However, mushrooms contain significant amounts of order of decreasing frequency, methionine, cystine, leuc­ nonprotein nitrogen in the form of chitin in their cell walls. ine, isoleucine, valine, lysine, phenylalanine, tyrosine, Therefore, mushroom protein as N X 6.25 has been re­ threonine, and tryptophan (12). Lentinula edodes was limiting ported to be only 34-89% digestible, with a number of in methionine, cystine, valine, and isoleucine; P. ostreatus studies indicating 60-70% digestibility. The conversion factor was limiting in methionine, cystine, tryptophan, lysine, N X 4.38 has been adopted for mushrooms in several food leucine, phenylalanine, and tyrosine. Calculated protein composition tables based on 70% protein digestibility (0.7 nutritional scores based on amino acid profiles showed a Downloaded from http://meridian.allenpress.com/jfp/article-pdf/53/10/883/1657928/0362-028x-53_10_883.pdf by guest on 02 October 2021 X 6.25 = 4.38). Recent studies (54,66) have supported the high degree of variability within as well as among species, adoption of N x 4.38. USDA Handbook No. 8-11 (19) thus pointing out the impossibility of making general used the factor N X 6.25 but reported that the amino acid statements extolling mushrooms as a source of dietary protein. profile for shiitake was based on 59% of total nitrogen as Ogawa et al. (54) determined the amino acid profiles protein nitrogen. On the other hand, at least one study has of the protein and nonprotein nitrogen (NPN) fractions of indicated that a purified mushroom protein isolate con­ four different cultivated mushrooms, including F. veluti­ tained only 11.79% nitrogen which would call for a pes; they concluded that mushroom proteins are relatively conversion factor of 8.48, if one considers only "true" abundant in essential amino acids except for methionine protein (12). and cystine. The predominant "protein amino acids" (i.e., In data compiled by Crisan and Sands (12), protein amino acids normally occurring in protein) in the NPN content as percentage of dry weight varied from 4-9% for fraction were alanine, glutamic acid, and glutamine. About Auricularia spp. to as high as 44% for Agarkus spp. Protein 38% of the nitrogen in F. velutipes existed as NPN. Other content was 24 to 44% in A. bisporus, 10-17% inL. edodes, workers have published amino acid profiles for P. ostrea­ 21-30% in V. voh 'cicea, 10-30% in Pleuwtus spp., and 18- tus (16,31,92). A so-called naturally isolated P. ostreatus 22% in F. velutipes. Handbook 8-11 (19) reported 10.6% strain had a total amino acid content 2-3 times higher than protein, dry basis, in shiitake mushrooms calculated as N the other four strains tested, i.e., 27 versus 8-14 g/100 g X 6.25. dry matter (76). Wahid et al. (92) found 19% protein, diy weight basis, Yamashita et al. (95) determined the free amino acid in Pleuwtus ostreatus; they did not specify a nitrogen profile of shiitake mushrooms before and after storage in conversion factor. Rai et al. (66) analyzed seven different air or in modified atmosphere (MA) packaging. The pre­ Pleurotus spp. grown under identical conditions. They dominant protein amino acids were glutamine, glutamic determined protein content by micro-Kjeldahl using both acid, aspartic acid, alanine, and arginine. They noted N X 6.25 and N X 4.38, by Lowry's method and by a dye increases in most amino acids as duration of storage binding method. They found excellent agreement between increased. A 185% increase was noted in the total quantity Lowry's method and Kjeldahl N X 4.38; values by dye of free amino acids after 7 d storage in air at 10°C but only binding were lower and those by Kjeldahl N X 6.25 were a 3% increase after 21 d storage under MA conditions at higher. Actual protein contents (Lowry's) were 1.6-2.5%, 1°C. wet weight basis, and 20-32%, dry weight basis, across the Sato et al. (68) reported total free amino acid contents seven species. Soluble protein accounted for 26-35% of ranging from 0.06 to 730 ^mol/g dry matter in 113 differ­ total protein. Li and Chang (41) reported 46 and 59% ent kinds of mushrooms; L. edodes, P. ostreatus and F. protein in two strains of L. edodes; 26 and 28% protein, velutipes contained 128, 289, and 532 ^mol/g, respectively. respectively, in less mature and more mature Pleurotus Alanine, glutamic acid, and glutamine predominated. No ostreatus; 40 and 25% protein, respectively, in less mature obvious correlation could be found between the free amino and more mature Pleurotus sajor-caju; and 46 and 32% acid pool and taxonomic groups of mushrooms. Oka et al. protein, respectively, in "button" and "elongated" V. volva- (60) found that alanine, glutamic acid, proline, and argin­ cea. All values were on dry weight basis with analysis by ine were the predominant free protein amino acids in A. the Lowry method. bisporus. Rai et al. (66) reported free amino acid contents Crisan and Sands (12) presented amino acid profiles of 237-502 mg/100 g (fresh weight basis) in seven species of more than 20 different cultivated and wild mushrooms, of Pleurotus. including L. edodes and Pleurotus species, from 14 differ­ The bottom line on the nutritional value of mush­ ent literature sources. They concluded that mushrooms rooms, from a protein standpoint, is that 1) protein content contain all of the essential amino acids which comprise varies considerably among and within species; 2) mush­ 25-40% of the total amino acid content. Handbook 8-11 rooms are generally limiting in the sulfur-containing amino (19) listed glutamic acid as constituting over 25% of the acids (methionine and cystine) and in several other essen-

JOURNAL OF FOOD PROTECTION, VOL. 53, OCTOBER 1990 NUTRITIONAL AND MEDICINAL VALUE OF MUSHROOMS 885 tial amino acids; and 3) mushrooms contain a substantial acids) in the mycelia (20). According to Handbook 8-11 proportion of protein amino acids in the free form. Crisan (19), shiitake mushrooms contained 18:1, 18:2, 16:0, 18:0, and Sands (12) concluded their review with the comment and 18:3 fatty acids in quantities of 19, 18, 16, 7, and 2%, that edible mushrooms are usually considered for their respectively, of the total fatty acids. flavor and condiment value, but that it may become in­ The sterol compositions of 10 different mushroom creasingly important in the future to consider their nutri­ species were determined (96). Ergosterol, the most impor­ tional value. tant of the pro-vitamins D, occurred in all 10 species and Fat. Crude fat in mushrooms contains all classes of comprised more than 70% of total sterols in all but two. lipid compounds including free fatty acids, mono-, di-, Ergosterol represented 84 and 45%, respectively, of the and triglycerides, sterols, sterol esters, and phospholipids. total sterols in L. edodes and F. velutipes. The latter contained It can comprise from less than 1% to as high as 15-20% substantia] proportions (10-30% of total sterols) of three of the dry weight with 2-8% as an average range (12). other sterols. Ergosterol levels among 44 different mush­ Values were reported of 1.2-8.0% in L. edodes, 5.7-10.1% room species ranged from 19 mg/100 g mushroom dry in V. volvacea, 1.0-7.2% in Pleurotus spp., 2.1-8.3% in matter in Auricularia auricula to 780 mg/100 g in Grifola Downloaded from http://meridian.allenpress.com/jfp/article-pdf/53/10/883/1657928/0362-028x-53_10_883.pdf by guest on 02 October 2021 Auricularia spp., and 1.9-5.8% in F. velutipes, all on a dry frondosa. Shiitake and enokitake contained 325 and 272 weight basis (12). Fat contents of 2.5-15.6% were reported mg/100 g, respectively (37). Dry basis ergosterol contents in the dry matter of 10 different mushrooms species; L. of 350, 420, and 570 mg/100 g, respectively, were found edodes and F. velutipes contained 5.3 and 5.0%, respec­ in pileus, stipe, and gill portions of shiitake mushrooms tively (96). The dry matter of seven Pleurotus species (62). About 55-65% of it occurred in the free form with contained 1.4-1.9% fat (66). The cap (pileus) and stalk the remainder in the ester form. (stipe) portions of shiitake mushrooms contained 0.50% The lipid fraction is a minor quantitative fraction in (4.58%, dry basis) and 0.45% (2.65%, dry basis) total lipid, mushrooms and, therefore, it is of relatively minor impor­ respectively (18). Within the lipid fraction, neutral lipids tance nutritionally except, perhaps, for the ergosterol (pro­ (about 48%) and phospholipids (about 43%) were high vitamin D) component. The good news is that on a quali­ and glycolipids (about 9%) were low. Among neutral lipids, tative basis, the fatty acids are predominantly unsaturated the distribution was: triglycerides, 58%; sterol esters, 17%; in nature. sterols, 16%; diglycerides, 6%; and monoglycerides, 1%; Carbohydrate and fiber. Fresh mushrooms contain 3- and among phospholipids; phosphatidyl ethanolamine, 60%; 28% carbohydrate and 3-32% fiber on a dry weight basis phosphatidyl choline (lecithin), 18%; cardiolipin, 13%; and (12). A. bisporus, which has been studied extensively, lyso-phosphatidyl choline, 6%. The main fatty acid was C contains pentoses (xylose, ribose), hexoses (glucose, ga­ 18:2 (linoleic) followed by C 16:0 (palmitic) and C 18:1 lactose, mannose), sucrose, sugar alcohols (mannitol, (oleic). The ratios of unsaturated to saturated fatty acids in inositol), sugar acids (galacturonic, glucuronic), methyl the cap and stalk were 3.4:1 and 4.5:1, respectively, in pentoses (rhamnose, fucose), and amino sugars (glucosam­ agreement with values published by others (5,12). Hand­ ine, N-acetylglucosamine). As mentioned above, chitin, a book 8-11 (19) reported 1.1% total lipid, dry weight basis, polymer of N-acetylglucosamine, is a structural compo­ in shiitake mushrooms, but a somewhat lower ratio of nent of cell walls. Since most studies of different mush­ unsaturated to saturated fatty acids of 1.8:1. room species have indicated a remarkable similarity in Hiroi (21) studied wild and cultivated strains of P. overall composition, nearly all of these substances are ostreatus and found little difference in their total lipid probably common to most species. Handbook 8-11 data content; both contained 3-5% total lipid, dry basis. However, (19) apparently included fiber in the carbohydrate compo­ the total lipid content was generally higher in the cap than nent, reporting 83% total carbohydrate and 13% fiber, dry in the stalk. In general, neutral lipid, glycolipid, and basis, in shiitake mushrooms. phospholipid contents constituted 20-30%, about 10% and Wahid et al. (92) reported 57% and 14% carbohydrate 60-70%, respectively, of total lipids, and linoleic acid and crude fiber contents, respectively, in the dry matter of constituted 70-80% of total fatty acids. Phosphatidyl choline P. ostreatus. Rai et al. (66) found 20-32% carbohydrate and phosphatidyl ethanolamine were the principal phosphol­ and 10-13% crude fiber, dry basis, in seven different ipids. Pleurotus species. Because of the recent surge of interest Koyama et al. (37) analyzed 44 different mushroom in dietary fiber, Kurasawa et al. (38) analyzed 26 species species and found 3.38 and 6.91% total lipid in the dry of mushrooms for crude fiber (CF), lignin, and pectin as matter of shiitake and enokitake, respectively. Fatty acids well as neutral detergent fiber (NDF) and acid detergent common to all species included the 18:2, 18:1, 18:0, and fiber (ADF). This also enabled them to estimate cellulose 16:0 acids. In shiitake, C 18:2 and C 16:0 comprised 73% and hemicellulose contents and to calculate the ratios of and 15%, respectively, of the total fatty acids. Enokitake total dietary fiber (TDF) to total crude fiber. All of their was the only species to contain an appreciable quantity of values were reported on the dry basis. Ranges in values linolenic acid (18:3); the 18:2, 18:3, and 16:0 fatty acids were: crude fiber, 1.1-16.4%; lignin, 0.6-6.1%; pectin, 1.0- made up 46, 30, and 12%, respectively, of the total fatty 9.1%; NDF, 16.4-50.5%; ADF, 2.0-24.7%; TDF, 18.4-55.5%, acids. Similar values were reported for enokitake fruit bodies, cellulose, 0-21.0%; hemicellulose, 7.7-38.4%; and ratio, but linolenic acid was much lower (2-8% of total fatty TDF:CF, 1.7-44.3. Among mushrooms of primary interest

JOURNAL OF FOOD PROTECTION, VOL. 53, OCTOBER 1990 886 WILLIAM M. BREENE in this review, total crude fiber ranged from 7.4% (shiitake) compare reasonably well with those of Kikuchi et al. (36) to 12.2% (enokitake); total dietary fiber contents were 37.5, for shiitake. 38.5, 46.1, and 47.5% in shiitake (Donko), enokitake, shiitake Bisaria et al. (3) studied the influence of 13 different (Koshin), and P. ostreatus, respectively. The mean ratio of lignocellulosic agro-residues (e.g., straw, leaves) on the TDF:CF was 5.7 compared to a range of 1.5-2.6 for other mineral composition (P, K, Na, Mg, Fe, Mn, Zn, Cu, Ca) vegetables and a mean ratio of 2.8 for 35 kinds of edible of Pleurotus sajor-caju mushrooms. In general, substrates wild plants studied. Thus, a large proportion of the carbo­ higher in a particular mineral produced mushrooms rela­ hydrate of mushrooms consists of dietary fiber. tively high in their content of that mineral. Values agreed Ash and minerals. Mushrooms probably contain every well with those of other workers (35,36) except that sodium mineral present in their growth substrate including sub­ contents were much higher and zinc and copper contents stantial quantities of phosphorous, potassium, a lesser amount were lower. of calcium, and a very low amount of iron (12). Total ash The above results agree quite well with values com­ content was 7.6 to 10.4% in seven different Pleurotus piled from eight literature sources for mineral content of species (66) and 8% in P. ostreatus, dry weight basis (93). A. bisporus and about 20 other wild and cultivated spe­ Downloaded from http://meridian.allenpress.com/jfp/article-pdf/53/10/883/1657928/0362-028x-53_10_883.pdf by guest on 02 October 2021 These are somewhat higher than the 5% total ash (dry cies, including L. edodes, P. ostreatus, and F. velutipes basis) given in Handbook 8-11 (19) for shiitake mush­ (12). In addition to the elements already discussed, that rooms. compilation included the contents (mg/100 g, dry basis) in Kikuchi et al. (36) examined 21 different species of L. edodes of silicon (262), sulfur (237), and chlorine (73). edible mushrooms for their contents, on wet basis, of 18 Several mineral elements have received special atten­ different mineral elements. Three metals, vanadium, tin, tion. Crisan and Sands (12) noted that mushrooms have and antimony, were not detected in any of the samples at been analyzed for their content of undesirable minerals the respective detection limits of 2, 2, and 0.8 fig/g of such as lead, cadmium, and selenium. However, Finnish fresh mushrooms. Cobalt was detected in Ramaria botrytis workers (64) analyzed 38 different mushroom species for (0.19 (ig/g), selenium in Sarcodon aspratus (6-10 fig/g), selenium content in the hope that they might help to al­ nickel in Naematoloma sublateritium and R. botrytis (0.2- leviate a deficiency of selenium in the Finnish diet. Sele­ 1.3 (ig/g), chromium in S. aspratus, a Tricholoma sp. and nium content, on a fresh weight basis, ranged from 0.2 |ig/ R. botrytis (0.16-0.22 fig/g), and lead in Lepista nuda, 100 g in Hydnum repandum to 190 |ig/100 in Boletus Hygrophorus poetarum, N. sublateritium, and R. botrytis edulis; A. bisporus and L. edodes, respectively, contained (0.4-2.0 fig/g). Cadmium was detected in all but one species 7 and 0.5 |ig/100 g. (Suilus bovinus) at 0.04 to 1.02 (ig/g of mushrooms. Nine Ohe et al. (55) reported that the mean level of cad­ other metals, in decreasing order of concentration (fig/g), mium in shiitake mushrooms, at 0.17 (ig/g of fresh prod­ were detected in all species: potassium (946-3500), mag­ uct, was about six times that found in 37 different species nesium (59-274), sodium (8-396), calcium (5-78), alumi­ of vegetables. Of six different metals (Cd, Zn, Cu, Fe, Mn, num (1.2-98), iron (3.5-27), zinc (3.3-19.5), copper (0.4- Ni) in the growth media (wood), Cd and Zn were concen­ 26.6), and manganese (0.8-7.4). Only these nine plus trated about six and three times (ppm metal in mushrooms/ cadmium were detected in P. ostreatus, L. edodes, and F. ppm metal in wood), respectively. Concentration factors velutipes from 4, 3, and 2 sampling areas, respectively. ranged from 0.01 (Ni) to 0.70 (Cu) for the other four Lentinula edodes was generally low in sodium and iron, metals. They isolated two cadmium binding components high in calcium and aluminum, and average in cadmium, from shiitake; one had a molecular weight of about 3,500 zinc and manganese. Flammulina velutipes was generally daltons and other had a molecular weight of about 40,000 low in cadmium, zinc, copper, iron, manganese, calcium, daltons. The chemical form of the former could not be aluminum and sodium, average in potassium, and high in determined; the latter was a glycoprotein high in acidic magnesium. Pleurotus ostreatus was generally low in amino acid content (56). calcium, aluminum and sodium, average in iron, manga­ Zurera-Cosano et al. (100) examined eight species of nese and potassium, and high in zinc, copper and magne­ edible mushrooms, including P. ostreatus, for lead and sium. cadmium contents; ranges in caps were 0.12 to 0.77 fig/ Kawai et al. (35) analyzed 24 species of wild edible g lead and 0.04 to 3.48 |ig/g cadmium on a fresh weight mushrooms and 5 species of cultivated mushrooms, including basis. Cultivated P. ostreatus contained 0.29 fig/g lead and P. ostreatus. Their values for P. ostreatus contents of K, 0.07 (ig/g cadmium. Psalliota campestris contained the Na, Ca, Mg, Fe, Cu, Zn, Mn, Cd, and Pb agreed closely highest levels of both metals. On average, caps contained with those of Kikuchi et al. (36). In addition, they assayed 1.43 times as much lead as stems; the ratio was 1.57 for for phosphorus, arsenic, and mercury which were detected cadmium. These authors concluded that levels of Cd and in P. ostreatus (86.6% moisture) at levels of 1406 mg/100 Pb in mushrooms are species-factor dependent but could g and 2.7 and 0.1 (ig/g, respectively, dry weight basis. not identify a responsible factor or mechanism. Handbook 8-11 (19) presented contents of six miner­ As sources of mineral nutrition, mushrooms in general als in dried shiitake mushrooms (9.5% moisture) in mg/ and shiitake in particular bring both good and bad news, 100 g: calcium, 11; iron, 1.72; magnesium, 132; phospho­ the bad news being the accumulation of cadmium and rus, 294; potassium, 1534; and sodium, 13. These values perhaps other heavy metals.

JOURNAL OF FOOD PROTECTION, VOL. 53, OCTOBER 1990 NUTRITIONAL AND MEDICINAL VALUE OF MUSHROOMS 887

Vitamins. Mushrooms appear to be good sources of mushroom, but their nutritional significance is unknown. thiamin (Bj) riboflavin (B2), niacin, biotin, and ascorbic Lin et al. (42,43) isolated cardiotoxic proteins from V. acid (vitamin C), but a great deal of species specificity volvacea (volvatoxin A) and F. velutipes (flammutoxin); exists. Vitamins A and D are relatively uncommon al­ the former consisted of two fractions with molecular weights though several species contain detectable amounts of B- of 50,000 and 24,000 daltons (9). Flammutoxin (M.W. carotene and many contain ergosterol, which converts to 22,000) was similar in amino acid composition and func­ active vitamin D when subjected to ultraviolet irradiation tion to the lower molecular weight protein of volvatoxin. (12). Each lowered blood pressure and lysed human group 0 Crisan and Sands (12) listed thiamin, riboflavin, nia­ erythrocytes. They caused similar electrocardiographic cin, and ascorbic acid values in mg/100 g, dry basis, from changes, depressing the ST segment and inverting the T eight literature sources for about 20 different mushrooms wave. They also had antitumor activity against Ehrlich species. Among species of interest in this present review, ascites tumor cells. Toxicity and biological activities were values were given for L. edodes, P. ostreatus, and F. eliminated by heating at 100°C for 20 min. Cochran (9) velutipes. In fresh, raw samples of these three species, cautioned those responsible for breeding stocks to be on Downloaded from http://meridian.allenpress.com/jfp/article-pdf/53/10/883/1657928/0362-028x-53_10_883.pdf by guest on 02 October 2021 thiamin content ranged from 4.8 to 7.8 mg/100 g, ribofla­ the alert for mutants producing high concentrations of such vin from 4.7 to 4.9 mg/100 g, and niacin from 55 to 109 cardiotoxins. mg/100 g, all on dry basis. Only F. velutipes contained In summary, edible mushrooms, while certainly add­ ascorbic acid, at 46 mg/100 g dry matter. Handbook 8-11 ing variety, flavor and eye-appeal to our foods, are also (19) gave values (mg/100 g) for these vitamins, on as is nutritious, containing moderate quantities of good quality basis, for cooked shiitake (83% moisture): thiamin, 0.04; protein and a generally high content of dietary fiber along riboflavin, 0.17; niacin, 1.5: ascorbic acid, 0.3 and for with vitamin C, B vitamins, and minerals. dried shiitake (9.5% moisture, as is basis) vitamin contents (mg/100 g) were thiamin, 0.3; riboflavin, 1.3; niacin, 14, Part II. Medicinal Value and ascorbic acid, 3.5. In approximately ten-fold greater It is interesting to note that the popular cultivated concentrations in the dried product are partially a reflec­ mushroom species have been shown to contain substances tion of its higher solids content. that prevent or alleviate cancer, heart disease, and diseases Differential pulse polarography was used to determine caused by viral infections, certainly three of the greatest the ascorbic acid contents of fresh samples of two differ­ scourges of mankind. Much of the credit for initiating ent strains of shiitake and one each of P. ostreatus, P. research into the medicinal value of mushrooms, as well sajor-caju, and V. volvacea of two different maturities as for providing the impetus for the development of the (41). Ascorbic acid content (mg/100 g, dry basis) was highest specialty mushroom industry to its present state, must go in shiitake (40-60), only slightly lower in the Pleurotus to the late Dr. Kisaku Mori. Dr. Mori, in his book "Mush­ species (36-58), and much lower in V. volvacea (8-10). rooms as Health Foods" (45), recalled that he was inspired These results were contrary to earlier reports (12,45) that to improve cultivation methods when he came upon a shiitake mushrooms did not contain vitamin C. Buddhist priest and some shiitake growers who were Irradiation of shiitake mushrooms containing about entreating: "Grow, please, shiitake mushrooms, or we shall 0.5% ergosterol, dry basis, with a fluorescent sunlamp have to leave the village." In 1936, Dr. Mori founded what sufficient to produce 400 IU of vitamin D per g dry weight is now The Mushroom Research Institute of Japan. His did not reduce thiamin, riboflavin, or niacin contents (62). nephew, Dr. Kanichi Mori, is its present Director of Other constituents. A. bisporus has been shown to Laboratory. contain a phenylhydrazine glutamic acid derivative called While there is an element of folklore and traditional agaritine, which although not a proven carcinogen, be­ medicine associated with the medicinal properties of longs to a class of compounds containing known carcino­ mushrooms, a vast body of information exists in the sci­ gens (71,72). However, 43 other species, including L. edodes, entific literature, going back to the 1940s and 1950s. Dr. P. ostreatus, F. velutipes, and V. volvacea, were found to Cochran (University of Michigan), one of the premier U.S. be free of agaritine (72). researchers in this area, who has collaborated with Japa­ Because the Protein Advisory Group of the United nese scientists, including Dr. Mori, reviewed the medical Nations has suggested a daily maximum dietary intake of effects of mushrooms up until 1978. Dr. Mori (45) related 4 g of nucleic acids, Li and Chang (40) analyzed A. bisporus, that he was contacted by Dr. Cochran in 1963 which marks two Pleurotus species, and V. volvacea for their nucleic the beginning of the modern-day research on the effects of acid contents (dry weight basis); DNA ranged from 0.17% mushrooms on cancerous tumors, suppression of viral (A. bisporus) to 0.37% (P. cystidiosus) and RNA ranged diseases, and lowering of blood serum cholesterol levels, from 2.49% (A. bisporus) to 3.85% (P. sajor-caju). They among others. Vo (91) prepared a concise but comprehen­ concluded that nucleic acid contents do not limit the use sive review (unpublished) of research on the medicinal of mushrooms as a daily vegetable. effects of exotic mushrooms. Eighteen different volatile sulfur-containing compounds Anticancer!antitumor effects. Cochran (9) traced the have been identified in fresh shiitake mushrooms (7). These history of research on antitumor effects of mushrooms compounds contribute to the distinctive flavor of the beginning with the some work in the late 1950s showing

JOURNAL OF FOOD PROTECTION, VOL. 53, OCTOBER 1990 888 WILLIAM M. BREENE that a substance called calvacin in Calvatia gigantea, the ceutical Development at Kirin Brewery Co. described an giant puffball, was a possible antitumor agent. antitumor polysaccharide extracted from L. edodes myce- Most of the research on antitumor effects of mush­ lia (not fruit bodies) grown on stillage from whiskey rooms or mushroom extracts has been conducted in Japan, manufacture (75). The substance, called KS-2, consisted much of it at the National Cancer Center Research Insti­ mainly of a-linked mannose and a small amount of pep­ tute in Tokyo. The Mushroom Research Institute has also tide composed mainly of serine, threonine and alanine. been active in such research. Ikekawa et al. (28), at the The molecular weight of KS-2 was estimated at 60,000- National Cancer Center, demonstrated that intraperitoneal 95,000 daltons. Oral as well as i.p. administration of KS- (i.p.) injection of aqueous extracts of six of seven edible 2 suppressed the growth of Ehrlich ascitic and Sarcoma mushroom species tested highly inhibited growth of tu­ 180 tumors in mice with concomitant induction of inter­ mors (by 72-92%, versus controls) arising from Sarcoma feron in the sera. This is interesting because lentinan was 180 ascites cells implanted in Swiss albino mice. These not effective when administered orally (17,25). species were L. edodes (81%), F. velutipes (81%), P. Work was also done with extracts of shiitake mycelia, ostreatus (75%), P. spodoleucus (72%), Pholiota nameko using a mixture (5:1, m/m) of bagasse and defatted rice Downloaded from http://meridian.allenpress.com/jfp/article-pdf/53/10/883/1657928/0362-028x-53_10_883.pdf by guest on 02 October 2021 (86%), and Tricholoma matsutake (92%). A. auricula- bran as a growth medium. A water-soluble fraction called judae showed only 43% inhibition. Tricholoma matsutake LEM and two alcohol-insoluble fractions called LAP and is considered to be the most prized edible mushroom in LAP1 (73) were obtained. All three fractions exhibited Japan (34) but has not yet been successfully cultivated. A anticarcinogenic activity in rats. LAP and LAP1 contained, white powder showing 97% inhibition of Sarcoma 180 respectively, 58 and 65% sugar and 25 and 34% protein. tumor growth was isolated from L. edodes: it appeared to The major sugar was xylose (>30%) with appreciable be a polysaccharide. amounts of glucose, galactose and arabinose (13-20%), In further studies at the National Cancer Center (8), about 9% mannose, and 1-2% each of fructose and rham- the antitumor material in shiitake was separated into six nose. fractions which were purified and tested for antitumor Ikekawa et al. (24,27) further purified and fraction­ activity. One fraction, called lentinan, markedly inhibited ated the EA3 and EA,. fractions extracted from F. velutipes. the growth of Sarcoma 180 implanted in mice, inducing They confirmed the structure of EA3 as a B-(l—>3)-glucan 13 almost complete regression of tumors when given (i.p.) in by applying C nuclear magnetic resonance analysis. EA5 10 doses of 1 mg/kg body weight, with no sign of toxicity. was fractionated into three subcomponents on a Sephadex Lentinan was shown to be a B-(l —> 3)-glucan (17). Evi­ G-200 column; the antitumor activity (i.p. administration) dence suggested that lentinan acted via immunological against Sarcoma 180 tumors in mice increased with in­ response of the host animal, perhaps by interferon induc­ creasing molecular weight. The fraction with the highest tion. activity contained 42.3% D-glucose, 17.3% D-galactose, As work continued at the National Cancer Center, 14.7% L-arabinose, 12.2% D-mannose, and 6.7% D-xy- antitumor polysaccharides were extracted from F. velutipes lose. Fraction EA6 of F. velutipes extract, which exhibited and P. ostreatus and shown to be capable of in vitro only weak antitumor activity, markedly augmented the anti­ inactivation of the hemolytic activity of the C3 component tumor effects of cryosurgery when administered i.p. to of complement in guinea pig serum (67). The active Sarcoma 180 bearing mice (58). Similar results were reported antitumor component of a water-soluble extract of P. when rabbits with Vx2 carcinoma tumors were treated with ostreatus was characterized as consisting of a (1 —>3)-B- cryosurgery and orally administered EA6 (57). Orally glucan skeleton, probably having branches of galactose administered EA combined with cryosurgery augmented and mannose residues and also containing acidic sugars the immune response of Sarcoma 180 bearing mice (59). (97,98). One antitumor component of the aqueous extract EA was described as a protein-bound polysaccharide of F. velutipes (enokitake), called EA was shown to be containing 3.82% nitrogen as peptides (29,99). EA6 also a B-(l —>3) glucan (24) and other (EA5) was a polymer augmented the antitumor activity of a murine leukemia of glucose (45%), galactose (32%), mannose (13%), arabi- (L1210) vaccine when given i.p. at 40 mg/kg after injec­ nose (7%), and xylose (2%) (29,99). EA. stimulated his­ tion of the vaccine into mice implanted with the leukemia tamine production in tumor tissue but had no effect on cells (63). serotonin levels (26). Lentinan exhibits its host-mediated Virus-like particles were observed to occur in normal antitumor activity by restoring the immune response of mycelia and fruit bodies of L. edodes (47) in three basic thymus, or T-cells, after it has been lowered by the cancer shapes: spherical (S), filamentous (F), and rod-shaped (R). (17). Purified S and F particles and the double-stranded RNA Subsequent research at the National Cancer Center, extracted from S particles had antitumor activity against Tohoku University, Kumamoto University, Hokushin General Ehrlich ascites carcinoma in mice when administered i.p. Hospital, Toyama Medical and Pharmaceutical University, (79). All three induced interferon production in mouse Kobe University, Kobe Women's College of Pharmacy, sera; S-derived RNA was most active and F particles were The Mushroom Research Institute, and several industrial least active. laboratories have focused primarily on shiitake and enokitake. Most of the research on antitumor effects of mush­ Researchers in the Department of Medical and Pharma­ rooms until the 1980s involved adminstration to test ani-

JOURNAL OF FOOD PROTECTION, VOL. 53, OCTOBER 1990 NUTRITIONAL AND MEDICINAL VALUE OF MUSHROOMS 889

mals by intraperitoneal injections, although some intrave­ production of superoxide in one strain of mice (C3H) but nous (i.v.) and subcutaneous (s.c.) injections were also only weak antitumor effect and no change in phagocytic made. Indeed, lentinan and various polysaccharides were activity or superoxide production in another strain (CDF1) ineffective when administered orally. In September 1982, (50). Research at Kobe Women's College of Pharmacy Dr. Ikekawa of the National Cancer Center presented a also demonstrated antitumor effects of fruit bodies of L. paper (27) at the 13th International Cancer Congress in edodes (51,53), G. frondosa (22), and A. bisporus (52) Seattle in which he described a new oral antitumor agent given orally to tumor bearing mice. Mechanisms appeared (proflamin, or PRF) extracted from the mycelia of F. ve- to involve activation of various effector cells to attack the lutipes. cancer cells and prevention of the decreased immune function The preparation, physicochemical properties, and which accompanies tumor growth. antitumor activity of proflamin have been described (25). It is interesting that the antitumor components of Proflamin is a weakly acidic glycoprotein containing more mushrooms vary in their chemical nature, including poly­ than 90% protein and less than 10% carbohydrate and saccharides, proteins, glycoproteins, nucleic acids and lipids.

having a molecular weight of 13,000 + 4,000 daltons. Major It is yet unknown whether specialty mushrooms will some­ Downloaded from http://meridian.allenpress.com/jfp/article-pdf/53/10/883/1657928/0362-028x-53_10_883.pdf by guest on 02 October 2021 amino acid components were glutamic and aspartic acids, day provide therapeutic control over the most dreaded of alanine, leucine and glycine, and major sugars were glu­ human diseases, cancer, but the studies to date do show cose, galactose and mannose. At an oral dosage in mice of some potential. It does appear that the inclusion of culti­ 10 mg/kg body weight over 10 d, proflamin suppressed the vated mushrooms, particularly shiitake and enokitake, in growth of the syngeneic tumors, B-16 melanoma and the diet is likely to provide some protection against some adenocarcinoma 755 and also Lewis lung carcinoma tumors manifestations of the disease. (25,27). Proflamin had no demonstrable in vitro or in vivo Antiviral effects. Cochran (9) summarized work on toxicity; its oral LD50 was greater than 20 g/kg for mice the antiviral effects of mushrooms, including L. edodes' (27). activity against influenza virus. Cochran and Lucas (10) Some of the most recent studies on anticarcinogen- evaluated several mushroom extracts for antiviral activity icity have involved oral administration of powdered, dried expressed as survival index. This index consisted of the mushroom fruit bodies, and powders from which the ratio of the harmonic mean survival time of the treated carbohydrate fraction (B-glucan) and/or lipid fraction was groups of test animals to that of control groups. Indices removed (48,49,50). The mushroom powders were added greater than 1.0 indicated antiviral activity. Agaricus to commercial laboratory mouse food at 10-30%. Initial campestris had a survival index of 1.6 against polio virus. results indicated suppression of Sarcoma 180 tumors in These authors pointed out that some overlapping is appar­ mice fed rations containing L. edodes or Grifola frondosa. ent of the two areas of antiviral and antitumor activity. Results of the tests with extracted powders at 20% of the Cochran et al. (77) examined extracts of different parts ration indicated that, for L. edodes, growth of the tumors of many different plants and fungi for activity against was inhibited 67% by the whole powder, 57% by defatted influenza virus in vitro and in mice. About 70 species powder, 39% by powder free of polysaccharides, and 0% including apples, beans and spinach had no antiviral activ­ by powder free of both lipid and carbohydrate. Addition ity. Of the basidiomycetes (mushrooms) tested, shiitake of extracted lipid increased tumor growth inhibition by had a level of activity (expressed as percent decrease in 25%. lung lesion score compared to control) of 46%. For Further study (49,50) showed suppression of Sarcoma comparison purposes, amantadine hydrochloride, a drug 180 tumor growth in mice by feeding L. edodes as well as commonly prescribed for influenza, had a score of 40%. eight other species (20% of ration): L. edodes (78%), G. A white powder isolated from a water extract of dried frondosa (86%), A. bisporus (71%), P. ostreatus (63%), F. shiitake by acetone precipitation, called Ac2P (94), was velutipes (62%), Pholiota glutinosa (63%), Tremella found by in vitro and in vivo (i.p. injection in mice) tests fuciformis (81%), Auricularia minor (68%), and V. volvacea to be a selective inhibitor of orthomyxoviruses (e.g., influ­ (68%). The fact that the inhibition rate (%) was greater enza viruses). It was active only when present in virus- when mushrooms were fed over a longer period of time infected cultures and had no effect when treatment was suggested that ingredients present may activate the cellu­ limited to periods before infection. Ac2P did not produce lar immune system. detectable interferon activity in vitro or in vivo. Ac2P was Mori et al. (49,50) also tested six mushroom species a high molecular weight polysaccharide composed mainly against MM-46, IMC-carcinoma, and Lewis lung carci­ of pentose sugars; it was distinctly different from lentinan. noma in mice at 20% of ration. All suppressed growth of The LD50 values in mice were over 1,000 mg, 1,500 mg, MM-46 tumors; P. glutinosa (99%), A. bisporus (98%), P. and 150 mg per g body weight by intravenous, intraperi­ ostreatus (90%), and T. fuciformis (79%) were most effec­ toneal or subcutaneous, and intracerebral single-dose in­ tive and A. minor and V. volvacea were least effective. jections, respectively. Pleurotus ostreatus was most effective against IMC-carci­ The S and F virus-like particles described by Mori noma (66%) and none suppressed Lewis lung carcinoma. and Mori (47) were found by them to induce interferon Oral feeding of L. edodes fruit bodies increased antitumor production in sera of rabbits after intravenous injection. effect and phagocytic activity of macrophages as well as Suzuki et al. (76) extracted double-stranded RNA from

JOURNAL OF FOOD PROTECTION, VOL. 53, OCTOBER 1990 890 WILLIAM M. BREENE spores of L. edodes. Eleven mice received a single i.p. Their progress was reported in a series of papers published injection of 8 mg/kg of the RNA 1 h before being infected over a period of almost a decade (32,69,70,81,83,84,86, intranasally with A/Swine/Iowa/15/30 (Hsw/NI) strain of 87,88). This work was summarized in English (33,74,82). influenza virus. As a negative control, 22 mice received Kaneda's group fed rats for 10 weeks on a control an equal volume of saline and as a positive control, 11 diet, diets containing 1% added cholesterol alone or to­ mice received i.p. 8 mg/kg of amantadine hydrochloride 3 gether with either 5% ground dried shiitake mushroom or 1/2 h before and 1 and 3 h after virus infection and once 0.5% ergosterol, and a diet containing no added choles­ daily for 4 consecutive days. All control mice died within terol but 5% ground dried shiitake. The ergosterol was 10 d, whereas the single dose of mushroom RNA pro­ included because shiitake contains about 0.3% ergosterol duced a survival rate of 60% compared to 18% for aman­ (dry basis) and because phytosterols have been known to tadine treatment. Tests with rabbits demonstrated that the reduce cholesterol levels in rats. Mean serum cholesterol RNA induced interferon production. levels (8 rats/group) were 119 mg/100 ml in the control, F and S virus-like particles were purified and double- 185 mg/100 ml for the 1% cholesterol diet, and only 100 stranded RNA was extracted from the S particles; F and mg/100 ml for the cholesterol plus shiitake caps (Donko Downloaded from http://meridian.allenpress.com/jfp/article-pdf/53/10/883/1657928/0362-028x-53_10_883.pdf by guest on 02 October 2021 S particles and RNA were evaluated for antiviral activity type) diet. Koshin caps were less effective (121 mg/100 (78,90). In vitro tests with rabbit kidney (RK-13) cells ml) as were Donko stems (131 mg/100 ml). Interestingly, showed that all three entities induced interferon produc­ Agaricus bisporus (117 mg/100 ml cholersterol) was about tion with S particles being more effective than F particles as effective in a 1% cholesterol diet as shiitake. Auricu- and the extracted RNA being much more effective than laria polytricha (149 mg/100 ml) and F. velutipes (159 either. In vivo studies showed that a single i.p. administra­ mg/100 ml) showed some activity. Ergosterol had no effect. tion of S particles prior to virus challenge significantly Cholesterol content and total lipid of the livers of mush­ reduced the mortality of mice infected with western equine room-fed animals were higher than those of the controls. encephalitis virus. Again, F particles had some antiviral The active hypocholesterolemic substance was even­ effect but were considerably less effective than S particles. tually isolated and identified (81,82) as eritadenine. Other In subsequent work (80), RNA having the same molecular Japanese workers had also isolated this compound from weight as that extracted from the S particles of L. edodes shiitake. In 1969, Kamiya and co-workers gave it the name spores was derived from L. edodes fruit bodies. The fruit "lentysine" and Chibata and co-workers called it "lenti- body RNA (Fr-RNA) inhibited viral growth in vitro as did nacin"; eritadenine is the name in current use (74). The the S-RNA but less effectively; the same was true for in structure of eritadenine is given in Fig. 1. Two other vitro induction of interferon. compounds related to eritadenine were isolated from shiitake; The so-called peptidomannan, KS-2, extracted from deoxyeritadenine and 9-(3-carboxypropyl)-adenine had no mycelia of L. edodes (15) also was shown to have antiviral hypocholesterolemic activity. activity (77). KS-2, when administered orally or i.p. to It is now known why A. bisporus was almost as effec­ mice infected intranasally with influenza virus, afforded tive as L. edodes. Subsequent work has been concentrated significant protection by therapeutic as well as prophylac­ almost entirely on shiitake, although a very low concen­ tic treatment. The mechanism of its effect was via its tration (dry basis) of eritadenine (0.7 mg/100 g) was reported interferon inducing activity. However, a diet containing in A. bisporus compared to 60-70 mg/100 g in shiitake 5% dried shiitake was ineffective in protecting mice against stem (67); F. velutipes and A. auricula-judae were devoid the viral disease scrapie (93). of eritadenine. Recently, it was reported that a "sugar protein" The chemical nature of eritadenine has been described (glycoprotein) extract of shiitake mycelia was found by by Tokita et al. (82) and a detailed review of the com­ researchers at Yamaguchi University to be more effective pound, the history of its discovery, and its chemistry has than azidothymidine (AZT) in the treatment of AIDS (2). been presented by Suhadolnik (74). The latter is particu­ This substance was said to be free of side effects and larly useful because it integrates a great deal of informa­ might replace AZT in treatment of AIDS. The National tion, much of which was originally published in Japanese. Institutes of Health (NIH) has issued a permit for clinical Kaneda's group at Tohoku University studied the testing of shiitake extracts. According to Toby Farris of mechanism of eritadenine in reducing cholesterol levels Carolina Agro-Tech Corp. (Personal Communication), (74,85,89). Eritadenine was shown to lower all lipid hospitals in New York and California, in collaboration components of serum lipoproteins (i.e., chylomicron, VLDL, with a Japanese pharmaceutical company, will be testing HDL) in animals and man. Eritadenine had very low toxicity sulfated 8-glucans from shiitake for their effectiveness against in rats. It had no hypocholesterolemic activity in rabbits. the AIDS virus. Eritadenine exerts its activity in rats without causing fatty Hypolidemic activity. Cochran (9) noted that the ability livers. It is effective when administered orally to rats although of various edible fungi to lower blood serum cholesterol, only 10% of it is absorbed from the intestinal tract. The like antitumor activity, was uncovered through verifica­ effect continues when it is removed from the diet. Japa­ tion of folklore. Initial work on the cholesterol lowering nese researchers showed that eritadenine treatment remained effects of mushrooms was done at Tohoku University in effective in maintaining lowered cholesterol levels for up Sendai, Japan, by Dr. Takashi Kaneda and his coworkers. to one year; in other words, metabolism in test animals did

JOURNAL OF FOOD PROTECTION, VOL. 53, OCTOBER 1990 NUTRITIONAL AND MEDICINAL VALUE OF MUSHROOMS 891

diets all decreased serum cholesterol levels by 9% in 7 d. However, rather than declining steadily over time as with young women, levels dropped sharply between 5 and 7 d. It was speculated that this may have been due to slower response in older people. In another experiment, butter (60 g/d) in the diet increased the mean serum cholesterol level by 14% in one week, but a diet of 60 g butter plus 90 g shiitake/day decreased the mean cholesterol level by 4%. Because shiitake mushrooms are a rich source of dietary fiber, Kurasawa et al. (38) fed rats for (presumably) 10 d on a standard control diet and one containing 1% choles­ terol along with 10% whole shiitake (presumably dried) or 2.5,5.0,7.5, or 10.0% neutral detergent fiber (NDF) extracted

from shiitake and measured cholesterol contents of serum Downloaded from http://meridian.allenpress.com/jfp/article-pdf/53/10/883/1657928/0362-028x-53_10_883.pdf by guest on 02 October 2021 and livers. The NDF was free of eritadenine. They were able to demonstrate that the shiitake NDF had a choles­ H-C-H terol lowering effect distinct from that of eritadenine. The minimum effective dosage was 5% of the diet. Hy­ pocholesterolemic activity was attributed to the binding of cholic acid salts to NDF. HO-C-H Antithrombotic effects. Workers at the Cancer Center of Hawaii (23) discovered that low molecular weight compounds extracted from L. edodes, Auricularia species, I and A. bisporus were capable of inhibiting aggregation of blood platelets. The highest yield of the inhibitors was HO-C-H obtained from shiitake. Inhibition was measured as 50% inhibition concentration (IC 50). The IC 50 was lowest I (highest inhibition effect) for Auricularia polytricha (10 |i.g/ml), followed by L. edodes (80 |i.g/ml). Agaricus bisporus COOH had an IC 50 of 3300 (ig/ml. The active compounds were Figure 1. Eritadenine. believed to be nucleosides and/or other nucleic acid de­ rivatives. Other medicinal effects. In addition to the antitumor, not adapt to minimize the hypocholesterolemic effective­ antiviral, anticholesterol, and antithrombotic effects of ness over time. This was confirmed by feeding mice for mushrooms and of shiitake in particular, which are docu­ 14 months on a diet containing 5% dried shiitake (93). mented by sound scientific data, many health and medici­ Intravenously administered eritadenine is ineffective; it is nal claims are made which are not so strongly supported. rapidly cleared from circulation and excreted through the Some of these are more in the realm of folklore but may kidneys. Of 124 derivatives or eritadenine synthesized and very well have some validity. Supporting evidence is usually tested, the most active were the carboxylic acid esters with anecdotal. Dr. Mori (45) hyped shiitake in his book, often short-chain monohydroxy alcohols. They were up to 50 with little or no supporting evidence. He stated, for ex­ times more active in lowering serum cholesterol in rats at ample, that shiitake can help prevent high blood pressure, a dose of 0.0001% in the diet when compared to eritad­ atherosclerosis (which it might do by lowering cholesterol enine. It appears that a carboxyl group and one hydroxyl levels), softening of the brain, kidney ailments, diabetes, group along with the intact adenine ring are necessary for cataracts, neuralgia, gallstones, numbness of the hands and biological activity. Eritadenine has no effect on the en­ feet, and hemorrhoids. Shiitake imparts long life and vigor. dogenous synthesis of cholesterol from [1-14C] acetate; its Shiitake consumption assists people in recovering from hypocholesterolemic activity is due to increased excretion fatigue. An intoxicated person who has eaten shiitake remains of cholesterol into feces. in good spirits and never becomes obnoxious. Shiitake Suzuki and Ohshima (75) of the National Institute of consumption prevents hangovers and relieves allergies and Nutrition in Tokyo stated that tests were made repeatedly constipation, probably due to its high content of fiber. on the effectiveness of shiitake mushrooms on blood serum And, of course, no worthwhile medicinal food would be cholesterol in human subjects since 1967. They found that really worthwhile if it did not improve sexual powers. 90 g/day of fresh shiitake, 9 g/day of dried shiitake, and Shiitake does. Dr. Mori supported some of these claims by 9 g/day of ultraviolet-irradiated dried shiitake for 7 d lowered anecdotal evidence, some by referring to experiments that mean blood serum cholesterol levels in young women (10/ were perhaps not published or were perhaps published in group) by 12, 7, and 6%, respectively. Similar tests were Japanese in journals not readily available in the United run with 30 people, 60 years or more of age; the three States. However, the basis for many of these claims is the

JOURNAL OF FOOD PROTECTION, VOL. 53, OCTOBER 1990 892 WILLIAM M. BREENE

cholesterol lowering effect of shiitake, which will prevent glycoside, saponin, coumarin, phenolic compounds, fat, atherosclerosis which will prevent high blood pressure and and various microelements. Added to the previous list of improve circulation which will prevent diabetes, etc., which ailments that it relieves are angina pectoris, arthritis, cerebral may very likely be true, but for which little clinical supporting embolism, apoplexy, lumbago, hemorrhoids, constipation, data exist. Recent research has shown clinical evidence of headache, shoulder pain, cough and phlegm, and depres­ an agent in the ether-soluble fraction of Grifola frondosa sion of gonadotropic function. fruit bodies that lowered blood pressure in spontaneously Because much of the clinical research on Ganoderma hypertensive rats (7). has been published in Chinese, it is difficult to determine Medicinal aspects of Ganoderma species. This paper the extent of it. Ito et al. (30) found that four different would not be complete without some discussion of the polysaccharides (containing small amounts of protein) medicinal value of Ganoderma spp. Ganoderma spp. are extracted from G. lucidum were highly effective against not normally eaten as a food item but have a long history Sarcoma 180 tumors in mice when administered i.p. These of use as traditional medicine in China and Japan (30,44,65). substances were not toxic. Liu et al. (44) reported that

These mushrooms belong to the order Aphyllophorales and many authors have demonstrated the effectiveness of Downloaded from http://meridian.allenpress.com/jfp/article-pdf/53/10/883/1657928/0362-028x-53_10_883.pdf by guest on 02 October 2021 are generally called polypores. They differ from ordinary Ganoderma against chronic bronchitis and viral hepatitis, mushrooms belonging to the order Agaricales in that they coronary heart disease, granulocytopenia, chronic Keshan have pores rather than gills on the under surfaces of the disease, and neurasthenia. Liu's group at the Chinese fruit bodies. The fruit bodies are usually tough and leath­ Academy of Medical Sciences, Beijing, have made in­ ery, reddish in color and grow as shelf-like forms on tree jectable solutions from Ganoderma for trial on human trunks, logs and stumps. Common species are G. lucidum, patients with progressive muscular dystrophy, atrophic G. applanatum, and G. japonicum. They are called Ling- myotonia, and certain neurological diseases with some good Zhi in China and mannentake in Japan. Other names include results. The studies reported in detail by this group (44) Reishi, Rokukakushi, and Fushisou (30,65). A common or showed that water soluble preparations of the spores of G. usual name for Ganoderma is "monkey's seat" or "mon­ lucidum and of the mycelium of G. capense, when admini­ key's chair", and indeed, they may actually serve that stered to mice, decreased spontaneous motor activity, purpose. The term "elixir of life" is often used in connec­ prolonged barbiturate sleeping time, prevented nicotine tion with Ganoderma, as is also true for shiitake. The fruit convulsions, and inhibited pilocarpine-induced salivary bodies have traditionally been used for medicinal purposes. secretion. Powdered, dried fruit bodies may be taken in hot water or The ether-soluble mycelial extract had no such ac­ whiskey or they may be boiled in water to produce a "tea" tions but did lower elevated SGPT levels induced by carbon (65). tetrachloride, promoted regeneration of the liver in par­ Quimio (65) has pointed out that both the mycelia and tially hepatectomized mice, and reduced the mortality rate fruit bodies can be used for medicine and has briefly of mice intoxicated by large doses of indomethacin. The described how they are cultivated in Japan and China. water-soluble preparation lacked these functions. It ap­ Ganoderma medicines have been offered for sale in the peared that the water-soluble substances acted mainly on United States. According to a "press release" dated March the central nervous system and the ether-soluble substances 15, 1982, the Kinoko Company of San Francisco, Dr. Henry on the liver. Mee, President, offered LING-ZHI Herbal Tea under the A Japanese Company, Reishisogokenkyujyo Ltd., in trade marked name Kinoko's Happy Herb. It was described Tokyo, produced a Ling-Zhi product in the form of a tablet as a powder consisting of 40% red Ling-Zhi (G. lucidum), during the early 1980s and attempted to find U.S. markets 40% white Ling-Zhi (Coriolus versicolor), and 20% L. for it through one of the large Japanese trading companies. edodes. The press release noted that white Ling-Zhi con­ In this connection some English language reports exist but tains CRESTIN, also called PS-K, which is a polysaccha­ are apparently "unpublished" in the academic sense and ride. CRESTIN was described as a product of Kureha thus cannot be properly referenced. This work is credited Chemical Co. of Japan, marketed by Sankyo Industry as to S. Arichi and co-workers and M. Kubo and co-workers an anticancer drug. It reportedly has been licensed to nine at Kinki University and N. Kirigaya of Morinaga & Co., major Japanese pharmaceutical firms and during 1980 Ltd. They conducted studies which indicated that G. lucidum reached sales of over $100 million (U.S.) in Japan. Red relieved or corrected both hypertension and hypotension Ling-Zhi, according to the press release, is used in China and were effective in treating almost all of the ailments to treat neurasthenia, insomnia, coronary heart disease, listed in the Kinoko press release mentioned above. The hypercholesterolemia, chronic hepatitis, bronchial asthma, effective ingredient was identified as a 8-(l —>3)-D-glucan stomach ulcers and indigestion, chronic inflammation of having a molecular weight of 300,000-400,000 daltons and the liver, kidney and bone joints (sic), and high blood containing 45-50% sugars as well as amino acids. pressure. In summary, it is quite obvious that mushrooms contain An article obtained from Dr. T. H. Quimio (not dated) some unique and interesting chemical compounds that have entitled "Efficacious Ganoderma lucidum" and apparently been shown in carefully controlled clinical studies at issued by Korea Industrial Technology Corp., Pyongyang, prestigious research institutions to be effective in treating stated that the mushroom contains much steroid, flavonoid, the diseases responsible for the majority of suffering and

JOURNAL OF FOOD PROTECTION, VOL. 53, OCTOBER 1990 NUTRITIONAL AND MEDICINAL VALUE OF MUSHROOMS 893

death in the developed countries of the world. It is hoped 16. Ginterova, A., and A. Lazarova. 1987. Amino acid composition of that this line of research will continue and that inclusion wood-rotting fungi (Pleurotus) and total amino acid balance of the cultivating system. Food Chem. 23:35-41. of more shiitake and other specialty mushrooms in peoples' 17. Hamuro, J., Y. Maeda, F. Fukuoka, and G. Chihara. 1974. Antitumor diets as well as the development of life-extending and life- polysaccharides, lentinan and pachymaran as immunopotentiators. saving medications based on the research will eventually Mushroom Sci. 9(l):477-487. occur. 18. Hashiguchi, M., S. Itoh, and H. Tsuyuki. 1984. Lipids in cap and stalk of shiitake mushroom. Studies on the lipids of shiitake. Part I. J. Jap. Soc. Food Sci. Technol. 31:436-442. (Japanese). ACKNOWLEDGMENTS 19. Haytowitz, D. B., and R. H. Matthews. 1984. Composition of foods: The author thanks the following individuals who kindly sent refer­ Vegetables and vegetable products. Raw, processed, prepared. ence lists, reprints of their published papers, and otherwise furnished USDA Agric. Handbook No. 8-11. Washington, DC. information without which the preparation of this paper would not have 20. Hiroi, M. 1982a. Fatty acid composition of fruit body and mycelium been possible: Dr. Yusuke Asano, Kanro Co.; Dr. S. T. Chang, Dept. of of Flammulina velutipes. Trans. Mycol. Soc. Japan. 23:85-89. (Japa­ Biology, The Chinese University of Hong Kong; Dr. Kenneth W. Co­ nese). chran, University of Michigan; Mr. Toby Farris, Carolina Agro-Tech 21. Hiroi, M. 1982b. Fatty acid composition of mushroom lipids. Part 5. Comparison of lipid components of wild and cultivated mushroom

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