Draft Monographs of Glucosamine, Melatonin, Saw Palmetto Online 36130

Draft Monographs of Glucosamine, Melatonin, Saw Palmetto Online

WASHINGTON--The National Academy of Sciences'(NAS) Committee on the Framework for Evaluating the Safety of DietarySupplements released three of the final four draft prototype monographs Jan. 15.A joint project of the Food and Nutrition Board (FNB) of the Institute ofMedicine (IOM) and the Board on Life Sciences of the National Research Council(NRC), the monographs cover glucosamine, melatonin and saw palmetto. These arethree in a series of six monographs the committee was developing to test theprinciples behind the Proposed Framework for Evaluating the Safety of DietarySupplements Report, released July 24, 2002. Late last year, two other monographswere released; one on chaparral and another on shark cartilage. At press time,only chromium picolinate had yet to receive a monograph.

As with all of the prototype monographs, these three drafts areintended to be a concise rather than a comprehensive literature review thatfocus specifically on possible safety issues behind each ingredient rather thanits potential role in health.

Within the glucosamine monograph, the alternative forms (D-Glucosaminehydrochloride, D-Glucosamine sulfate, N-Acetyl-glucosamine and glucosaminehydroiodide), preparations (tablets, capsules, caplets, powders and liquids) anddosages (500 mg/d to 2,000 mg/d) were some of the information discussed.

In the area of safety data, the incidence of adverse events forglucosamine ranged from none to 94 percent, with the number of adverse eventsalmost identical to those taking placebo. In trials comparing the aminomonosaccharide compound to NSAIDs, event rates were consistently higher amongthose taking NSAIDs.

Other adverse events included those noted in a case seriesconsisting of 10 out of more than 200 patients that were followed while takingglucosamine and/or chondroitin supplements. Clinical syndromes includedphotosensitization, hypertension and proteinuria (excess excretion of protein inthe urine). There was also one case study in which a patient developed renaldysfunction, possibly due to glucosamine interacting with the person'smedication (cyclosporine).

In terms of processing issues, the draft monograph's authorsreported that the quality of glucosamine may not be consistent from batch tobatch, as experienced by investigators at the National Institutes of Healthsourcing the supplement for a clinical trial; in the end, they had tomanufacture these products themselves.

More on this monograph can be found at www.iom.edu/iom/iomhome.nsf/WFiles/Glucosamine/$file/Glucosamine.Draft.monograph.pdf.

Another monograph covered the hormone melatonin, available in avariety of forms, including immediate-release, sustained-release, sublingual andliquid preparations. From an overview of products on the market today, melatoninmost often comes in the form of a single-ingredient dietary supplement or incombination with other dietary supplement ingredients (i.e., vitamin B6, zincpicolinate). The typical amount suggested for melatonin intake on manufacturers'labels is between 0.5 g/d to 10 g/d. However, the monograph authors noted,"Since endogenous melatonin is considered a hormone, a 20-fold range forthe amount to be ingested is unusual. Typically, a consumer seeking assistancein falling asleep more quickly might ingest 1 mg of melatonin on a daily basis,being careful to ingest the supplement at the appropriate time of day, usuallyin the evening (30 minutes to 1 hour before bedtime)."

The primary adverse events associated with melatonin intakeincluded headache, confusion/agitation, depression and alterations in the levelsof other hormones. However, these effects were most evident with large doses ofmelatonin (i.e., 5 mg/d to 1 g/d). Less toxicity was noted at lower intakelevels (0.5 mg/d to 1 mg/d).

The hormone seems to have drug interactions, including thosewith the anti-depressant fluvoxamine, and with sedating and antipsychotic drugssuch as haloperidol, phenothiazines and benzodiazepines. Melatonin is also anantagonist of calcium channel blockers (used for heart health).

There was evidence that melatonin doses of 10 mg/d or less maycause adverse events of the cardiovascular (i.e., hypertension),gastrointestinal (i.e., autoimmune hepatitis, constipation) and central nervous(i.e., seizures, nightmares) systems. Melatonin supplementation may also makesymptoms of depressive disorders worse. In animal studies, the hormone has beenfound to also affect testicular health.

Currently, melatonin in single-ingredient products is marketedfor jet lag, depression, seasonal affective disorder, cardiovascular disease,hypertension and, occasionally, for migraine and episodic cluster headaches.

More on this monograph can be found at www.iom.edu/iom/iomhome.nsf/WFiles/Melatonin/$file/Melatonin.Draft.monograph.pdf.

The monograph on saw palmetto reported the extracts of thisfruit are commonly categorized as hexane-extractable (i.e., phytosterols,phenolic components), ethanol-extractable (i.e., flavonoid components, phenolicglycosides) or water-soluble (i.e., polysaccharides). The monograph's authorsnoted the hexane extract of saw palmetto fruit is the preparation that has beenused most commonly in clinical trials. In data gathered from numerous clinicaltrials, the monograph indicated a typical dose of saw palmetto for treatingbenign prostatic hyperplasia (BPH)--one of the more popular health conditionslinked with this botanical--is 320 mg/d.

Adverse events associated with the herb are mild and occur at arate similar to placebo. There was one case report of a serious adverse eventthat may have been associated with saw palmetto; during brain surgery, a patientexperienced excess bleeding. However, this appeared to be atypical. Also, nosignificant drug interactions have been reported for use of saw palmetto.

In vitro studies on saw palmetto indicate the herb inhibitsmuscle contraction, androgen-dependent proliferation and cellular stimulation,and induces apoptosis--which are factors in prostate health and even prostatecancer.

Currently, preparations of saw palmetto fruit are marketed toconsumers for prostate and urinary health in men and for urinary function inmature men. Occasionally, saw palmetto is marketed to women (for urinaryfunction, milk production during lactation or, rarely, breast enlargement).

More on this monograph can be found at www.iom.edu/iom/iomhome.nsf/WFiles/SawPalmetto/$file/SawPalmetto.Draft.monograph.pdf.

"At this point, no safety conclusions have been drawn, butthese drafts weren't meant to have had any," said Phil Harvey, Ph.D.,director of science and quality assurance at the National Nutritional FoodsAssociation (NNFA). "My take on these monographs is that they arepreliminary and extensive literature reviews, and quite neutral in balance whenpooling all of the information together." He added, "These monographshave information that will benefit suppliers and those in the scientificcommunity."

The draft prototype monograph for chromium picolinate had beenpushed back to Jan. 22. At press time, it had still not been posted. When itdoes, it will be available at www.iom.edu/iom/iomhome.nsf/pages/FNB+Dietary+Supplements.