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Discussione: Glucosammina [Eng]

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    Post Glucosammina [Eng]


    Citazione Originariamente Scritto da Drugo84
    è un pò che nn posto due righe qua, mi scuso ma anceh se la cosa mi fa piacere nn ho al momento tutto il tempo e la libertà memomnica x farlo ho paura che sarà così x ancora un mesetto o due, ma per farmi eprdonare posto uno studio interessante che dimostra la parità d'effetto tra la glucosamina e i rispettivi farmaci ma con minoranza di sides, scusate se nn è in Ita, se qualcuno vuole tradurre mi faccia sapere

    Glucosamine Effects in Humans: A Review of Effects on Glucose Metabolism, Side Effects,
    Safety Considerations, and Efficacy
    James W. Anderson, MD
    University of Kentcuky
    Lexington, KY
    Glucosamine, 2-amino-2-deoxy-D-glucose, is an amino monosaccharide that is an
    essential component of mucopolysaccharides and chitin. Glycosaminoglycans, or
    mucopolysaccharides, are large complexes of negatively-charged carbohydrate chains that are
    incorporated into mucous secretions, connective tissue, skin, tendons, ligaments and cartilage.
    Glucosamine and its acetylated derivative, N-acetylglucosamine, are readily synthesized in the
    body from glucose. Because of its high concentration in joint tissues, the hypothesis that
    glucosamine supplements would provide symptomatic relief for osteoarthritis was developed
    more than 30 years ago.(1) Many clinical trials have tested this hypothesis(2) and glucosamine
    supplements are widely used to relieve arthritic complaints.(3)
    To meet the demand for glucosamine nutritional supplements, three forms of
    glucosamine are commonly available: glucosamine hydrochloride, glucosamine sulfate, and N-acetyl-
    glucosamine. These glucosamine compounds are generally derived from chitin, a
    biopolymer present in the exoskeleton of marine invertebrate animals. The glucosamine derived
    from chitin in the cell walls of many fungi appears to be chemically identical to that found in
    marine invertebrates.(2)
    Glucosamine directly enters into the hexosamine biosynthetic pathway. There is
    disagreement as to the presence of any undesired side effects of this exogenous glucosamine in
    animal systems.(site references if you believe necessary) Some, but not all, studies in animals
    suggest that glucosamine administration may produce insulin resistance and hyperglycemia by
    affecting insulin secretion and action.(2;4) However, most in vitro and animal studies have
    achieved blood and tissue levels 250 to 2500 times higher than would be expected with
    glucosamine doses used in humans.(4-7) Thus, it is important to rigorously review available data
    in humans to assess the effects of glucosamine intake on glucose homeostasis. Glucosamine is
    usually taken orally, as opposed to intra-arterially or intramuscularly, and 90% is absorbed.(8)
    Orally administered glucosamine has only 26% the bioavailability of intravenously administered
    glucosamine.(9) A significant fraction of orally administered glucosamine undergoes first-pass
    metabolism in the liver.(9) Blood levels achieved after oral glucosamine are only 20% those
    achieved with intravenous glucosamine.(2;8)
    This review will examine the available data from humans to assess the effects of
    glucosamine on glucose metabolism. The effects of chronic glucosamine intake on blood
    chemistries, hematologic parameters, urinanalysis, occult blood in the feces, blood pressure and
    pulse rate will be tabulated. Side effects reported with glucosamine compared to placebo from
    placebo-controlled trials will be compared. Finally, an overview of the efficacy of glucosamine
    for arthritic complaints will be provided.
    Materials and Methods
    This review focuses on clinical studies performed with human subjects. The relevant
    articles were identified by Medline search and by review of articles referenced in primary reports
    and review articles. A previous review(2) and two meta-analyses(10;11) have performed detailed

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    literature searches. For this current review we reviewed the articles from these three previous
    reports and performed a Medline search for the years 2000-2003 using these key words:
    glucosamine and humans. We reviewed the references of all relevant articles for additional
    references. Articles included in this review relate to glucosamine administration to humans for
    investigational or therapeutic purposes. Appropriate articles were tabulated and the relevant data
    was extracted and tabulated. Semiquantitative and statistical analyses of data were performed.
    The total number of patients represents the sum of all patients studied or the sum of all
    patients who had the specific measure described. Patient-years were calculated as follows:
    Number of patients multiplied by number of study days divided by 365.
    The ratio of side effects from glucosamine or placebo was calculated as follows:
    Number of patients treated with glucosamine with side effects divided by number
    of patients treated with placebo with side effects.
    The average ratio of side effects in each study for glucosamine and placebo was
    averaged, the standard error of these values calculated, and the 95% upper and lower confidence
    interval were calculated.
    Significant differences were reported for 22 studies from patients with osteoarthritis.
    Since two meta-analyses(10;11) have carefully evaluated efficacy we tabulated reported
    outcomes and used simple arithmetic means and median values to characterize these reports. The
    P value reported represents the median of P values reported for each individual study since many
    studies had multiple P values reported. When significance difference was reported but the P
    value was not provided, a value of 0.05 was assigned. When values were not clinically
    significant, a value of 0.1 was assigned; this is justified because these studies reported favorable
    trends in efficacy or significant values for some outcome measures. The average P value is
    simply the average of reported P values. Five studies included comparisons of glucosamine to
    ibuprofen. These values are reported as percentages of patients who developed side effects in
    these two groups.
    Results
    Studies suitable for analysis
    Thirty-five studies, including 32 studies of chronic glucosamine administration, were
    included in this analysis (Table 1). This includes data on 3073 patients treated with glucosamine
    for a total of 979 patient-years. Twenty-six chronic studies use a randomized, controlled trial
    (RCT) design, two were controlled studies and five studies were observational. Of the chronic
    studies, 29 used glucosamine alone, five included chondroitin sulfate and one included other
    supplements in the test preparation. Seven studies were comparator trials in which glucosamine
    was compared to other agents (ibuprofen in five studies, phenylbutazone in one study and
    piroxicam in one study). Of the 32 chronic studies, 28 used oral therapy exclusively, one used
    intramuscular administration alone, and three used oral administration in conjunction with
    intravenous, intramuscular, or intra-articular administration. The short-term studies were
    included to assess glucose metabolism. Four studies, one on skin wrinkles(12) and three on
    temporomandibular joint complaints(13-15) were included to make the safety assessment as
    comprehensive as possible.
    Effects of glucosamine on glucose metabolism in humans
    The reviewed studies are listed in Table 2. Four clinical trials reported fasting blood
    glucose values and mean values decreased nonsignificantly from 95.6 to 92.6 mg/dl. The

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    Reginster study enrolled 108 subjects and followed them for 3 years; they reported that blood
    glucose values were slightly lower.(16) Four other clinical trials indicated that there were no
    significant changes in clinical chemistry values implying no change in blood glucose values. One
    study(17) measured glycosylated hemoglobin (HbA1c) in 22 diabetic and 12 control subjects
    over 90 days. There were no significant changes in these values for diabetic or control subjects.
    In total, 9 studies assessed fasting glucose values and none reported deterioration of the blood
    glucose values. These 9 studies included 336 subjects treated for a total of 567 patient-years. For
    the entire group of 32 chronic studies of older subjects, three developed diabetes with placebo
    treatment and two developed diabetes with glucosamine treatment.
    In two other studies (7;18) performed on metabolic research wards, large amounts of
    glucosamine-- ~7.2 grams or 9.7 grams of the glucosamine free base—were infused over 5 hours
    with no change in blood glucose values. These studies indicate that intake of glucosamine at
    recommended doses of 1500 mg or greater daily has essentially no effect on fasting blood
    glucose values in humans. These observations were reinforced by the recent report of Yu et al.
    (19) indicating that administration of 1500 mg glucosamine for 28 days had no effect on glucose
    tolerance or insulin sensitivity of 10 non-diabetic subjects.
    Exposure to glucosamine in humans
    Research volunteers or patients with arthritic complaints or skin conditions have received
    glucosamine for periods of 21-1095 days. The most common dose was 500 mg three times daily
    or 1500 mg/day. One group of 50 subjects received glucosamine hydrochloride at a dose of 3200
    mg/day for 35 days. In terms of patient years (number of patients multiplied by duration of
    treatment), 3073 human volunteers or patients have received glucosamine for 979 patient-years.
    There have no serious or life-threatening effects reported.
    In two metabolic ward studies, volunteers have received large doses of glucosamine
    intravenously over 300 minutes. Pouwels and colleagues(18) intravenously infused ~7.2 grams
    of glucosamine as the sulfate salt over a 300 minute period into 10 healthy volunteers. This was
    well tolerated and not associated with reported side effects. Monauni and colleagues(7)
    intravenously infused 9.7 grams of glucosamine over a 300 minute period into 10 healthy
    volunteers. Again this was well tolerated with no reported side effects. When they subsequently
    intravenously infused 30.5 grams of glucosamine (more than 20 times the usual daily dose) into
    5 healthy volunteers, this dose was well tolerated by 4 subjects and only one had symptoms—he
    developed a headache. These amounts (7.2 grams, 9.7 grams, and 30.5 grams) were of the free-base
    glucosamine.
    These studies indicate that glucosamine is well tolerated by healthy volunteer subjects at
    very high doses. Individuals with degenerative joint disease also tolerate 1500-3200 mg/day for
    periods of 3 years. Thus, 3200 mg/day or 49 mg/kg/day has been tolerated by older subjects for
    periods of 35 days. Because the blood level achieved with intravenous glucosamine is
    approximately five-fold higher than with oral administration,(8) it appears that humans can
    easily tolerate more than 9.7 grams/day. In calculating the acceptable daily intake (ADI) of
    glucosamine, these calculations were used. Humans tolerate more than 9.7 grams of free-base
    glucosamine. These young men have average weights of ~ 70 kg. The calculation of mg/kg is as
    follows: 9700 mg divided by 70 kg equals more than 138 mg/kg/day of the free base
    glucosamine. Because glucosamine hydrochloride provides 83% free base, humans tolerate more
    than 166 mg/kg/day (138 divided by 0.83) of glucosamine hydrochloride. Furthermore, since
    only 90% of glucosamine is absorbed,(20) humans tolerate more than 184 mg/kg/day (166

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    divided by 0.9) of the glucosamine hydrochloride. Thus, 184 mg/kg/day is a conservative
    recommendation for an acceptable daily intake (ADI) of glucosamine hydrochloride.
    Objective measures of safety
    Thirteen studies reported specific safety measures including some of these assessments:
    chemistry panel including liver and kidney safety assessments, hematologic parameters (white
    blood count, red blood count, hemoglobin, and platelet count), urinalyses, occult blood
    measurements of stool, and cardiovascular parameters including blood pressure and pulse rate
    (Table 2). None of the studies reported adverse effects on these measurements from glucosamine
    administration. In general these safety reports included about 700 subjects representing
    approximately 600 patient-years. Specifically the number of studies assessing various parameters
    were as follows: chemistry panel, 11; hematologic parameters, 13; urinalyses, 10; occult blood,
    3; and cardiovascular parameters, 6. Blood pressure and pulse rate were monitored continuously
    for the 21 subjects who had large amounts of glucosamine infused intravenously with no
    reported adverse effects.(7;18) None of the studies reported significant changes in these
    parameters.
    Common symptoms with placebo or glucosamine
    Nonspecific symptoms are commonly reported in clinical trials. In a 3-year study, 93% of
    subjects receiving placebo reported symptoms.(16) The most common symptoms reported with
    placebo or glucosamine were these: mild gastrointestinal symptoms including constipation,
    diarrhea, nausea, dyspepsia, excessive gas, abdominal distension, and abdominal cramps;
    headache; and skin rash or pruritis. Eighteen chronic studies that provided side effect data
    comparing glucosamine to placebo were analyzed. These studies, as summarized in Table 2,
    included 988 subjects and 706 patient-years of observation. In 13 of the 18 studies, symptoms
    were reported less commonly in glucosamine-treated subjects than in placebo-treated subjects.
    The ratio of symptoms for glucosamine compared to those for placebo is presented for each
    study. The placebo has a score of 1.0 and the frequency of symptoms with glucosamine is a
    fraction of this. When the frequency of symptoms is the same the ratio for glucosamine is 1.0.
    When less symptoms are reported for glucosamine that placebo, the ratio is less than 1.0. Only
    two studies reported that symptoms were more common with glucosamine than placebo. The
    frequency of symptoms with glucosamine ranged from none (0.0) to 143% (1.43) of those
    reported for placebo. The average for the ratio of symptoms for glucosamine compared to
    placebo was 0.76 (95% confidence interval, 0.61 to 0.92). This suggests that symptoms were
    24% less common with glucosamine than placebo and that this was statistically significant.
    Richy and colleagues,(11) in their meta-analysis, indicated that the adverse effect rate with
    glucosamine was 80% of that for placebo.
    The Institute of Medicine report(2) summarizes case reports and other adverse events
    occurring with glucosamine use. This report concludes that: “Human studies show an equal
    incidence of mild, transient adverse effects in placebo control groups and glucosamine
    groups.”(2)
    Five studies compared side effects of glucosamine with ibuprofen, the most commonly
    used non-steroidal anti-inflammatory agent for arthritis. The prevalence of side effects in patients
    using glucosamine was 10.0% compared to 32.5% for patients using ibuprofen. The Institute of
    Medicine report also concluded that side effects were less common with glucosamine than with
    ibuprofen.(2)

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    Efficacy assessment
    The efficacy of glucosamine for arthritic complaints has been extensively studied and two
    recent meta-analyses(10;11) are available. McAlindon and colleagues(10) conclude that
    glucosamine was moderately efficacious for relief of arthritic complaints. Richy and
    colleagues(11) conclude that glucosamine had highly significant efficacy on all aspects of knee
    osteoarthritis including joint space narrowing, pain, and mobility scores. Twenty-two clinical
    studies of patients with osteoporosis were reviewed (Table 3); this does not include the three
    studies of TMJ symptoms. Twelve studies reported significant differences and included P values
    (from 0.05 to 0.001). Seven indicated that significant improvement was seen but did not provide
    P values; a P value of 0.05 was assigned to these studies. Only three studies indicated that no
    significant difference was seen and two noted a slight improvement with glucosamine
    administration; a P value of 0.1 was assigned to these studies since they reported favorable but
    not quite statistically significant results. The average of all reported and imputed P values for the
    22 studies was 0.040 and the median P value was 0.05. While a detailed analysis of efficacy was
    not undertaken, this survey indicates that glucosamine administration, at a dose of 1500 mg/day,
    is moderately effective in decreasing arthritic complaints.
    Discussion
    Glucosamine has been extensively studied in animals and humans. We reviewed data
    from 32 clinical trials including 3073 individuals treated with glucosamine for periods of 21-
    1095 days (979 patient-years). Like the Institute of Medicine review,(2) we conclude that mild,
    transient side effects are seen in placebo and glucosamine treated individuals. Our analysis of
    side effects suggests that side effects are about 24% less frequent in glucosamine-treated
    individuals than in placebo-treated individuals; Richy et al.(11) calculated that side effects are
    20% less common in glucosamine-treated subjects than in the placebo groups. Our analysis and
    that of the Institute of Medicine(2) indicate that side effects from glucosamine are substantially
    lower than from ibuprofen, a widely uses non-steroidal anti-inflammatory drug.
    The effects of glucosamine on glucose metabolism have interested laboratory
    investigators for many years because pharmacologic concentrations of glucosamine affect insulin
    action and secretion. Glucosamine is a common metabolic product in most tissues of the body
    and is incorporated into glycosaminoglycans.(8) Setnikar and Rovati(8) have reviewed the
    metabolism of glucosamine in humans and these data can be summarized. Glucosamine sulfate
    or hydrochloride salts are dissociated in the stomach and free glucosamine enters the small
    intestine where 90% is absorbed. Much of the glucosamine is metabolized in the first pass
    through the liver. The blood level of glucosamine after oral administration approximates 20% of
    that observed with intravenous administration. Glucosamine is taken up by cells by glucose
    transporter proteins but the affinity of glucosamine for these transporters is substantially lower
    than that of glucose.(5) Thus, it seems likely that the concentration of glucosamine in most cells
    would be substantially lower than that in plasma. With intravenous administration of 9.7 grams
    over 5 hours, serum glucosamine concentrations of 0.7 mmol/l were achieved.(7) With
    administration of 500 mg in three divided doses it seems unlikely that serum concentrations
    above 0.01 mmol/l would be achieved. In vitro studies that show effects of glucosamine on
    glucose metabolism have used concentrations of 2.5 to 50 mmol/l.(5;6;21) The effective dose for
    a 50% change (ED50) in insulin-stimulated glucose uptake in isolated fat cells is 25-30 mmol/l(6)
    or ~2500 times the tissue level likely to be achieved with oral administration of glucosamine in

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    humans. Thus, it seems very unlikely that oral administration of 1500 mg/d (the commonly used
    amount) to 3200 mg/d (an amount used in one chronic study) of glucosamine would have a
    discernable effect on metabolic pathways involved in glucose metabolism in humans.
    Because of the effects of large concentrations of glucosamine on glucose metabolism in
    animal and in vitro models we rigorously examined the available data related to this question in
    humans. In clinical trials there is no evidence that glucosamine in usual doses affects fasting
    plasma glucose concentrations. In one clinical trial(19) glucosamine administration had no effect
    on estimates of insulin sensitivity. Finally, when large amounts of glucosamine (7.2 or 9.7
    grams) was infused into healthy volunteers, no adverse effects on blood glucose concentrations
    were observed over the 5-hour period of study.(7;18) These observations indicate that 9.7 grams
    of glucosamine, as free base, or 138.6 mg/kg are well tolerated. Since glucosamine
    hydrochloride provides 83% free base, the tolerated dose would be 167.0 mg/kg. Since only 90%
    of glucosamine is absorbed(8), the tolerated dose would increase to 186 mg/kg. This a
    conservative estimate of the acceptable daily intake (ADI). If one uses the blood level after oral
    administration to be 20% of that after intravenous administration,(2;8) one could calculate that
    the tolerable dose of free base glucosamine would be 693 mg/kg (i.e., 138.6 divided by 0.2).
    Thus, we conclude that 186 mg/kg is a conservative estimate of the ADI for glucosamine
    hydrochloride.
    In reviewing these clinical trials we tabulated data on efficacy of glucosamine
    administration on symptoms of osteoarthritis. Our observations are consistent with the rigorous
    meta-analyses of McAlindon et al.(7) and Richy et al.(10;11) Individuals with osteoarthritis of
    the knee or spine have significantly less symptoms while taking glucosamine that those taking
    placebo. McAlindon et al.(10) conclude that glucosamine is moderately efficacious for relief of
    symptoms of osteoarthritis. Richy et al.(11) conclude that glucosamine has highly significant
    effects on all aspects of knee osteoarthritis. The effects of glucosamine sulfate compared to
    glucosamine hydrochloride have not been examined in a comparator trial. Because of the
    disassociation of the salt in the stomach, it seems unlikely that the two preparations would have
    differing effects. Comparing side effects and reports of efficacy across trials suggests that the
    two glucosamine salts have similar effects.

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    Conclusions
    Results from 32 clinical trials with glucosamine were reviewed. These trials included
    3073 subjects studied for 979 patient-years. While there have been concerns originating from
    some animal studies that glucosamine might adversely affect glucose metabolism, careful studies
    in humans show not adverse effects on glucose homeostasis. Overall, 9 studies including 336
    subjects for 567 patient-years reported no adverse effects on glucose metabolism. Glucosamine
    is well tolerated by humans for periods of up to three years. While the usual dose is 1500 mg/day
    in three doses, doses of up to 3200 mg/day were well tolerated. Healthy young subjects had no
    adverse effects from infusion of 9.7 grams and only one of five developed a headache when 30.5
    grams was infused. This suggests that an acceptable daily intake for glucosamine hydrochloride
    (ADI) is higher than 186 mg/kg/day. In 13 clinical trials reporting safety information there were
    no adverse effects of glucosamine on blood chemistries, hematologic parameters, urinalysis,
    occult blood in feces, or cardiovascular parameters. Symptoms or side effects were reported
    significantly less frequently with glucosamine than with placebo. Reported side effects were
    24% less common in subjects treated with glucosamine than with placebo. Finally, glucosamine
    appears to be moderately to highly effective in decreasing symptoms resulting from
    osteoarthritis.

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    Table 1. Studies evaluated.
    Study Type Glucosamine Other Route* Dose No.of Duration Patient-Study
    form Treatment mg/d subjects days Years
    Almada (22) RCT SO4 None Oral 1500 6 84 1.4
    Braham (23) RCT HCl None Oral 2000 25 84 5.8
    D'Ambrosio (1) RCT SO4 None oral/iv/im 1500 15 21 0.9
    Das (24) RCT HCl CHS Oral 2000 46 192 24.2
    Drovanti (25) RCT SO4 None Oral 1500 40 30 3.3
    Forster (26) RCT SO4 None Oral 1500 78 90 19.2
    Giordano (27) Observational SO4 None Oral 1500 20 365 20.0
    Houpt (3) RCT HCl None Oral 1500 45 147 18.1
    Hughes (28) RCT SO4 None Oral 1500 39 168 18.0
    Leffler (29) RCT HCl CHS, Mn Oral 1500 31 112 9.5
    Monauni: First(7) Controlled uncertain None Iv 9.7g 10 300" 0.0
    Second study (7) Controlled uncertain None Iv 30.5 g 5 300" 0.0
    Muller-FaBbender
    (30) RCT-C SO4 Vs. ibuprofen Oral 1500 100 28 7.7
    Mund-Hoym (31) Controlled SO4
    vs
    phenylbutazone oral/im 1000 40 32 3.5
    Murad(12) Controlled SO4 Supplement Oral uncert 57 35 5.5
    Nguyen (13) RCT HCl CHS Oral 1500 19 84 4.4
    Noack (32) RCT SO4 None Oral 1500 120 28 9.2
    Pavelka (33) RCT SO4 None Oral 1500 84 1095 252.0
    Pouwels (18) Controlled SO4 None Iv ~7.2g 6 300" 0.0
    Pujalte (34) RCT SO4 None Oral 1500 11 49 1.5
    Qiu (35) RCT-C SO4 vs ibuprofen Oral 1500 88 28 6.8
    Reicheit (36) RCT SO4 None IM 114 73 42 8.4
    Reginster (16) RCT SO4 None Oral 1500 87 1095 261.0
    Rindone (37) RCT SO4 None Oral 1500 49 60 8.1
    Rovati (38) RCT-P-C SO4 vs piroxicam Oral 1500 80 150 32.9
    Rovati 1 (39) RCT SO4 None Oral 1500 123 28 9.4
    Second study
    (39) RCT SO4 None Oral 1500 76 42 8.7
    Third study (39) RCT-C SO4 vs ibuprofen Oral 1500 100 28 7.7
    Scroggie (17) RCT HCl CHS Oral 1500 22 90 5.4
    Shankland (14) Observational HCl CHS Oral 3200 50 35 4.8
    Tapadinhas (40) Observational SO4 None oral 1500 1367 50 187.3
    Thie (15) RCT-C SO4 vs ibuprofen oral 1500 22 90 5.4
    Yu (19) Observational SO4 None oral 1500 12 28 0.9
    Vajranetra (41) Observational SO4 None oral/ia 1500 108 84 24.9
    Vas (42) RCT-C SO4 vs ibuprofen oral 1500 19 56 2.9
    Sum 3073 979
    * Abbreviations: RCT- randomized controlled trial; C, comparator; P, placebo; CHS, chondrotin sulfate; iv, intravenous; im,
    intramuscular; ia, intraarticular.

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    Table 2. Evaluation of fasting plasma glucose and safety parameters.
    Study Glucose mg/dl Sum- Blood CBC UA Occult BP Side
    before after mary chem blood P Effects
    GluN/P
    Almada (22) 94 94 NA NA NA NA NA NA
    Braham (23) NA NA NA NA NA NA 1.10
    D'Ambrosio (1) 109 97 NSC NSC NSC NA NSC 1.00
    Das (24) NA NA NA NA NA NA 0.89
    Drovanti (25) 82 82 NSC NSC NA NSC NA 0.83
    Forster (26) NA NA NA NA NA NA 0.20
    Giordano (27) NSC NSC NSC NSC NA NA 1.00
    Houpt (3) NA NA NA NA NA NA 1.00
    Hughes (28) NSC NSC NSC NSC NA NA 0.90
    Leffler (29) NA NA NSC NA NSC NSC 0.97
    Monauni 1 (7) NSC NA NA NA NA NSC** NA
    Second study (7) minimal
    effect
    NA NA NA NA NSC** NA
    Muller-FaBbender
    (30)
    NA NA NA NA NA NSC NA
    Mund-Hoym (31) NA NA NA NA NA NA NA
    Murad (12) NA NA NA NA NA NA NA
    Nguyen (13) NA NA NA NA NA NA 1.43
    Noack (32) NSC NSC NSC NSC NA NSC 0.62
    Pavelka (33) NSC NSC NSC NSC NA NA 0.56
    Pouwels (18) NSC NA NA NA NA NSC** NA
    Pujalte (34) NA NSC NSC NSC NA NA 0.00
    Qiu (35) NA NSC NSC NSC NA NA NA
    Reicheit (36) NA NA NA NA NA NA NA
    Reginster (16) slightly
    lower
    NSC NSC NSC NA NSC 0.82
    Rindone (37) NA NA NA NA NA NA 0.50
    Rovati (38) NA NA NA NA NA NA 0.62
    Rovati 1 (39) NA NSC NSC NSC NA NA 0.62
    Second study (39) NA NSC NSC NSC NA NA 0.71
    Third study (39) NA NSC NSC NSC NA NA NA
    Scroggie (17) HbA1c NSC NA NA NA NA NA NA
    Shankland (14) NA NA NA NA NA NA NA
    Tapadinhas (40) NA NA NA NA NA NA NA
    Thie (15) NA NA NA NA NA NA NA
    Yu (19) 97.2 97.2 NA NA NA NA NA NA
    Vajranetra (41) NA NA NA NA NA NA NA
    Vas (42) NA NA NSC NA NSC NSC NA
    Average 95.6 92.6
    No. with reports 4 4 9 11 13 10 3 6 18
    Total patients 336 703 753 663 90 372 988
    Total patient years 567 591 603 587 16 290 706
    Abbreviations: NA, not available; NSC, not clinically significant; HbA1c, glycosylated hemoglobin; chem., chemistry; UA,
    urinalysis; occult blood, stool measurement; BP, blood pressure; P, pulse; GlucN/P, ratio of side effects from
    glucosamine divided by those from placebo.

  11. #10
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    Table 3. Overview of efficacy of glucosamine for arthritic complaints.
    Study Joints Arthritis Symptoms
    Evaluated Significant difference
    Braham(23) knees 0.038
    D'Ambrosio(1) generalized OA 0.01
    Das(24) knees 0.04
    Drovant(25) generalized OA 0.005
    Forster(26) knees sign diff (0.05)
    Giordano(27) generalized OA 0.001
    Houpt(3) Knees NCS (0.1)
    Hughes(28) knees NCS (0.1)
    Leffler(29) knees or back 0.02
    Muller-FaBbender(30) knees sign diff (0.05)
    Mund-Hoym(31) back sign diff (0.05)
    Noack.(32) knees 0.05
    Pavelka(33) knees 0.01
    Pujalte(34) generalized OA 0.01
    Qiu(35) knees sign diff (0.05)
    Reicheit(36) Knees Sign diff (0.05)
    Reginster(16) Knees sign diff (0.05)
    Rindone(37) knees NCS (0.1)
    Rovati (38) knees sign diff (0.05)
    Rovati: First study(39) knees 0.014
    Second study(39) knees 0.012
    Tapadinhas(40) generalized OA 0.001
    Vajranetra(41) knees sign diff (0.05)
    Average 0.040
    Median 0.050
    No. with reports 23
    Total patients 2645
    Total patient years 933
    Abbreviations: NA= not applicable; OA, osteoarthritis; NA, not available; NCS, not clinically signficant

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