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1 maart 2018: zie ook dit artikel:
Op de studie gedaan met een mix van paddenstoelen is wel een commentaar geleverd. Niet voor leken denk ik maar artsen en wetenschappers kunnen hier wel wat mee denk ik. Zie ook gerelateerde artikelen voor meer informatie over AHCC, maar zie ook bij PSK en andere extracten van medicinale paddenstoelen informatie
It could have been something they ate - functional food and the treatment of liver cancer
Nathan M. Bass *
Division of Gastroenterology, University of California, 513 Parnassus Avenue, PO Box 0538, S-357, San Francisco, CA 94143, USA See Article, pages 78-86 Journal of Hepatology 37 (2002) 147-150 www.elsevier.com/locate/jhep
The title of the paper by Matsui and colleagues  that appears in the pages of this issue of the Journal raises two questions at first glance. Firstly, what are functional foods and secondly, did this unusual fare make a difference to outcomes in the authors’ patients operated on for hepatocellular carcinoma?
Consider first the term ‘functional food’. It is not one with which many readers will be immediately familiar, although the related and ultimately intertwined field of ingestible microbial probiotics, their indigestible oligosaccaharide substrates (prebiotics) and the combination of the two (synbiotics) has captured the attention of physicians treating a variety of digestive and other diseases over the past 5 years [2-8]. The term functional food is better known to the community of nutrition scientists and probably also to the lay person with a strong interest in
alternative nutritional therapies. The origin of this term is attributed to a phrase initiated in Japan in the late 1980s used to describe foods fortified with ingredients capable of producing health benefits [9,10]. From a scientific perspective, the current definition of functional food is elusive, and definitions vary according to different sources . After all, given that we need to eat to live, is not all food functional
in the strictest sense? There is clearly, however, a desire implicit in this terminology to define a quality that goes beyond the already complex, life-sustaining nutritional
property of food, which has been expressed in related popular terms such as ‘neutaceuticals’, ‘immunoceuticals’, ‘dietary supplements’ and ‘designer foods’ [12,13]. Simply put, a functional food, it would seem, is one that occupies a position somewhere between a simple or conventional nutri-ent and a medicine. The definition proposed by the International Food Information Council is that functional foods are ‘foods that provide health benefits beyond basic nutrition’
. The Institute of Medicine of the National Academy of Sciences on the other hand proposed a more complex definition, limiting the term to ‘any modified food or food ingredient that may provide a health benefit beyond the traditional nutrients it contains’ . The American Dietetic Association sees the spectrum of functional foods as including
‘whole foods, and fortified, enriched, or enhanced foods, which have a potentially beneficial effect on health when consumed as part of a varied diet on a regular basis, at
effective levels’ . The sheer breadth of view existing around the concept and definition of functional foods would seem in the rigorous scientific mind to invite the opening of a Pandora’s Box of opportunism in alternative nutritional therapeutics. Indeed, a driving force in the concept of foods as medicine is the growing interest in alternative, herbal and nutritional therapies, often by an aging population interested in preventative self-care as an alternative to expensive conventional medical therapies
But there is also a bedrock of solid evidence for the quantitative and qualitative impact of nutrition on public health and a progressive accumulation of data concerning the intrinsic benefits of certain types of natural foods on cancer risk, cardiovascular disease and gastrointestinal health [11,14]. In the latter category, the concept of probiotics
has received wide acceptance as a promising therapeutic approach to the management of inflammatory bowel disease, peptic ulcer disease and infectious diarrheal diseases [2,4]. Phytoestrogens present in soy-based foods are accepted for their ability to reduce menopausal symptoms and possibly some cancers . Indeed, the list of the specific health benefits from specific foods appears to be growing rapidly along with a better understanding of the active principles involved in these benefits, be they specific minerals, complex antioxidants, phytosterols, lipids or oligosaccaharide components of the foods in question
. Of course, once an active principle in food is chemically well-defined along with its physiological action and potential or established therapeutic activity, it would seem
pointless to separate it conceptually from the mainstream of medicinal therapeutics. At that point, the concept of a functional food must give way to the more clearly etched terminology of biological and pharmaceutical chemistry.
The last decade of the 20th century saw considerable interest and involvement of regulatory and government agencies in the field of nutritional therapies and supplements.
In the United States, The Office of Dietary Supplements was authorized as part of the Dietary Supplement Health and Education Act of 1994 to promote the scientific study of dietary supplements in ‘maintaining health and preventing chronic disease and other health-related conditions’
. In Japan, the government took a proactive stance with respect to the systematic investigation of food functions, funding a large number of research programs toward
this end in the early 1980s . Since 1993, The Japanese Ministry of Health and Welfare has officially approved several items as ‘Foods for Specified Health Uses’, i.e.
foods that are used to improve people’s health and for which claims for specific health effects are allowed [9,15].
Interest in functional foods has extended, particularly in Asia, to polysaccharide peptides found in many species of mushroom which have been studied experimentally as immunomodulators for the treatment of infections and the suppression of tumorigenesis [13,16]. Over 30 mushroom species have been studied with respect to these properties, for the most part in experimental animals, and the effects attributed to b-d-glucans (linear polymers of d-glucose with other monosaccharides) or b-d-glucans linked to proteins (proteoglycans) . Few human studies are available to date to support the proposed anticancer properties of mushroom- derived chemicals, but early promise has been noted for derivatives polysaccharide-K and polysaccharide-peptide from controlled trials .
Active hexose correlated compound (AHCC) is a proprietary extract first prepared in 1989 from co-cultured mycelia of several species of Basidiomycete mushrooms, including
shiitake (Lentinus edodes). Details of the mushroom sources and methods of preparation are not available, but the extract contains polysaccharides, amino acids, and minerals .
The anticancer properties of shiitake mushroom extracts have been the subject of research since the 1960s and one particular compound, lentinan, has been reported to show favorable results in a randomized clinical trial in advanced and recurrent stomach and colorectal cancer . The glucans in AHCC have low molecular weight (around 5000 Da) and are of the alpha-1,3 type. Both the low molecular weight and alpha-glucan properties are unusual for the class of mushroom glucans with reported immunomodulatory properties . Animal research and preliminary human studies indicate AHCC has anticancer efficacy [13,19]. Preliminary, uncontrolled studies with this extract in 300 patients with various cancers has been reported . Of these, 58 showed a response, with 46 showing complete or partial regression and 12 showing no change in tumor size. Responses were observed with cancers of the lung, breast, stomach, esophagus, colon, liver, and other sites. In 1992, Kamiyama commenced a trial in Japan to evaluate the preventive effect of AHCC against recurrence of hepatocellular carcinoma following surgical resection. Favorable preliminary results were reported . The paper published by Matsui et al.  in this issue of the Journal represents the final, detailed publication of this study.
The authors report that 222 patients with hepatocellular carcinoma and relatively well-compensated cirrhosis, mostly from viral hepatitis, were prospectively assigned to
treatment with AHCC (113 patients) or no treatment (109 patients) after undergoing planned curative resection of hepatocellular carcinoma. Patients were not randomized to
the treatment and no treatment arms of the study, but rather were allowed to choose their preference for either taking or not taking AHCC. The outcomes reported show a statistically
significant improvement in survival, and period of freedom from disease recurrence for the AHCC-treated cohort. The authors also include data showing an improvement in three laboratory variables (aspartate aminotransfer-ase, g-glutamyl transpeptidase and cholinesterase), and report that these variables improved in AHCC ingesting patients even after removal from the analysis of the patients in whom recurrence of cancer occurred. The implication is that AHCC bestowed a beneficial effect on liver function with the speculation that this is a primary effect of the agent which in turn explains its anticancer effect or which is responsible for improved survival independent of its anti-cancer effect. The latter seems unlikely though, as more than 90% of deaths in both cohorts were cancer-related.
Hepatocellular carcinoma is a devastating and increasingly common disease , and progress in the management of this cancer has been slow. A high rate of recurrence has been a limiting factor in the success of surgical resection . New therapies to prevent post-surgical recurrence are eagerly sought, and studies of measures including adoptive immunotherapy , interferon and polyprenoic acid in preventing recurrence after resection have reported favorable outcomes. AHCC has been available for a relatively short time, as have several other anticancer glucans. The lack of regulation in the preparation and sale of these substances has accelerated their use in treatment studies and by the population at large in a manner that differs radically from conventional drug development and regulation. That is all the more reason for them to be held to the same if not more rigorous standards of scientific proof of efficacy, but this is more easily preached than accomplished. Matsui et al.  are well aware of the shortcomings of their lengthy, detailed and carefully reported study. The lack of randomization, with allocation of patients to treatment according to their personal choice, introduces the probability of extraordinary self-selection bias that seriously weakens the study. Also, a greater proportion of patients chose treatment over no treatment in the later part of the study than in the earlier part.
This almost predictable late ‘rush to catch the wave’ resulted in a shorter median follow-up for the AHCC-treated patients than the untreated patients, introducing yet a further
source of bias. The authors point out that randomization may not have worked, given that AHCC was already sold on the open market without prescription, and patients could
easily have obtained this outside of the trial. Of course, in the design employed, the self-selected, no-treatment cohort of patients may have changed their minds along the way as well. At least four patients who were known to have done so were dropped from the analysis. But how many more might have surreptitiously taken the AHCC after they had chosen to be in the non-treatment arm? The authors document no method or procedure for testing patients for compliance or contamination with AHCC. Patients in both arms must at some point have become aware through advertising and word of mouth that AHCC was available, possibly effective, and not unsafe or that unpleasant to take. What would stop them? Perhaps Japanese patients are on average more reliable as participants in trials, but in my city, the control group might well have ended up buying and taking double the dose of AHCC consumed by the open treatment arm. For argument’s sake, if this behavior had occurred in the current trial, evidence for a possible beneficial effect of AHCC would effortlessly convert to evidence for an adverse effect.
This, of course, is the key problem with respect to supporting any claim regarding the efficacy of AHCC on the basis of available data. But, as the authors note, 'it is difficult to complete a randomized trial in regard to ' functional foods. In truth, under current conditions, it may be close to impossible.
AHCC is marketed worldwide. In the United States, it is sold on the internet under a number of proprietary names, but is usually also identified as AHCC, at $70-$100 per bottle of sixty 500 mg capsules. The range of cost of 5 years of treatment at the 3 g per day dosage used by the authors would therefore be about $13 000-$18 000. (Noot redactie: PSK, een voedingssupplement met een een soortgelijke samenstelling als AHCC, is ook in Nederland beschikbaar en wordt vaak voorgeschreven door orthomoleculaire artsen. Zie pagina nuttige adressen voor adressen van deze artsen. Apotheek Mierlo Hout, adres op zelfde pagina levert deze PSK/PSP. Zie ook pagina andere alternatieven wat PSK/PSP precies is.) Not much compared with some of the therapies we use to treat cancer today, but a sizeable piece of out-of-pocket change if it is no better than a sugar pill. Currently, marketing of AHCC in the United States over the internet makes no claims regarding any antineoplastic property (although there is no lack of data accessible through a simple search addressing this potential property), remaining on the relatively safe and vague ground of promoting its claimed immunostimulant properties. The publication of Matsui and colleagues’ study might encourage some relaxation in this cautious restraint - but this would be most premature.
Nutritional therapy encompasses a fascinating field of possibilities emerging from traditional medical practices that are just beginning to establish a dialogue with Western
medical ethos . The potential now for poorly substan-tiated claims to swamp out science is considerable, given the unregulated and unrestricted availability of many of the
principles involved. The great tragedy would be to miss the opportunity to prove a real therapeutic effect because of this problematic situation. The identification of a true therapeutic effect of unregulated, and often poorly characterized functional foods and so-called dietary supplements thus poses a considerable challenge for physicians that will not be easily solved. Despite this, the standard of proof to which functional foods, by this or any other name, particularly in the treatment of serious and life-threatening diseases, should be held in establishing a true medicinal effect, should be no less than that applied to a new pharmaceutical agent. The study published herein by Matsui et al.  alerts us to important new possibilities. But, as succinctly put by Kassirer and Angell : 'There is only medicine that has been adequately tested and medicine that has not, medicine that works and medicine that may or may not work '. 'Alternative treatments should be subjected to scientific testing no less rigorous than that required for conventional treatments'.
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* Tel.: 1 1-415-476-0719; fax: 1 1-415-476-0659.
E-mail address: email@example.com (N.M. Bass).
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- Paddenstoelenextract - AHCC geneest bij 60 procent (versus 10 procent bij placebo) binnen 6 maanden HPV positieve patienten
- Wetenschappelijk commentaar op studie AHCC bij leverkanker.
- Het effect van functionele voeding AHCC - mix van medicinale paddestoelen - bij levertumoren positief en significant bewijst negenjarige studie.
- AHCC, een mix van paddestoelen zorgt voor groot therapeutisch effect bij levertumoren blijkt uit fase III studie