Glucosamine, chondroitin

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Hot flash frequency was not reduced in meta-analyses of red clover isoflavone extracts, and results were mixed for soy isoflavone abstracts. Evidence efficacy of ...

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Is subclinical thyroid dysfunction in the elderly associated with depression or cognitive dysfunction?

Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis

Roberts LM, Pattison H, Roalfe A, Franklyn J, Wilson S, Hobbs FD, Parle JV.

Clegg DO, Reda DJ, Harris CL, Klein MA, O’Dell JR, Hooper MM, Bradley JD, Bingham 3rd CO, Weisman MH, Jackson CG, Lane NE, Cush JJ, Moreland LW, Schumacher Jr HR, Oddis CV, Wolfe F, Molitor JA, Yocum DE, Schnitzer TJ, Furst DE, Sawitzke AD, Shi H, Brandt KD, Moskowitz RW, Williams HJ.

Ann Intern Med. 2006;145(4):573-81.

BACKGROUND: Thyroid dysfunction is common in older persons, and some organizations have recommended screening to detect this problem, especially in older women. As a result, subclinical thyroid dysfunction (both hypothyroidism and hyperthyroidism) have been increasing recognized. Frequently, this dysfunction is treated, although it is uncertain whether these disorders are symptomatic or respond of treatment. AIM: To determine the associations between subclinical hypothyroidism and hyperthyroidism and depressive and cognitive dysfunction. METHODS: A cross-sectional study was done of 5685 patients ≥ 65 years of age who were not receiving treatment for a thyroid disorder in 20 primary care practices in central England. Blood specimens were obtained for serum thyroid-stimulating hormone (TSH) and free thyroxine and free triiodothyronine, if the TSH level was low. Cognition was assessed by using the Mini-Mental State Examination (MMSE) and the Middlesex Elderly Assessment of Mental State (MEAMS). Depression and anxiety were assessed by using the Hospital Anxiety and Depression Scale (HADS). RESULTS: In multiply adjusted (for age, sex, physician practice, comorbid conditions, socioeconomic status, and selected medications) models, patients with subclinical hyperthyroid or subclinical hyperthyroidism patients did not differ from euthyroid patients on anxiety, depression, or MMSE or MEAMS scores. In adjusted models. TSH level was associated with anxiety such that a 50-mlU/L increase in TSH level is associated with a 1-point reduction in HADS anxiety score, which not clinical meaningful. TSH level was significantly positively associated with MMSE score (higher levels and higher scores), but this finding was not confirmed by the MEAMS. CONCLUSION: Subclinical hyperthyroidism or hypothyroidism is not associated with mood or cognitive disorders. IMPACT ON INTERNAL MEDICINE: Although subclinical thyroid dysfunction is easy to treat, the case for doing so is weakened considerably by this study. Moreover, data from the Leiden 85-Plus study suggest that among persons 85-89 years of age, those with higher TSH levels and lower free thyroxine levels actually have a survival benefit. For many patients with subclinical thyroid dysfunction, observation may be the best strategy.

REFERENCES Gussekloo J, van Exel E, de Craen AJ, et al. Thyroid status, disability and cognitive function, and survival in old age. JAMA. 2004;292:2591-9.

In this 3.7 years longitudinal study of 599 persons who were 85 and 87 years of age, plasma levels of TSH and free thyroxine were not associated with disability in daily life, depressive symptoms, and cognitive impairment at baseline or during follow-up. Increasing levels of TSH were associated with a lower mortality rate that remained after adjustments were made for baseline disability and health status.



Increasing TSH levels were associated with a lower mortality rate that remained after adjustments were made for baseline disability and health status.

Presented at IM 2007 by David B. Reuben, MD, FACP. Reprinted with permission.  Copyright 2007 The American College of Physicians.

einstein: Educ Contin Saúde. 2007, 5(3 Pt 2): 72-78

N Engl J Med. 2006;354:795-808.

BACKGROUND: Osteoarthritis (OA) of the knee is a common disorder of older persons. The mainstays of managing OA are physical activity; assistive devices, including orthotics; analgesics, especially nonsteroidal anti-inflammatory agents; and surgery. Recently, the dietary supplements glucosamine and chondroitin have been increasingly used, but with only moderate supporting evidence. AIM: To compare the effectiveness of glucosamine hydrochloride, sodium chondroitin sulfate, and the combination of both agents on pain due to knee OA. METHODS: A 24-week, 5-armed randomized clinical trial (glucosamine hydrochloride, 500 mg 3 times daily; sodium chondroitin sulfate, 400 mg 3 times daily; both supplements in combination; celecoxib, 200 mg/d; or placebo) was done in 1583 person with clinical (knee pain) and radiographic evidence of OA. The primary outcome was a 20% decrease in summed Western Ontario and McMaster Universities Osteroarthritis Index (WOMAC) pain subscale from baseline to week 24. Secondary outcome measures included other WOMAC subscales, patient and investigator global assessments of disease status, knee physical examination findings, the MOS??? Short Form-36 health-related quality-of-life instrument, the Health Assessment Questionnaire, and acetaminophen use. RESULTS: Overall the response to glucosamine or chondroitin sulfate, alone or in combination, and to celecoxib was no better than response to placebo\. Aside from joint swelling and effusions, which were less in those taking chondroitin or celecoxib, none of the secondary outcomes differed across treatment arms. Among study patients with moderate-to-severe pain at baseline, the combine treatment was significantly more effective than placebo on the primary outcome on several other WOMAC subscales, and by the patients global assessment of response to therapy. None of the other treatment arms were beneficial in patients who had moderate-to-severe pain at baseline. CONCLUSIONS: Glucosamine, chondroitin sulfate, the combination of both supplements, and celecoxib did not reduce pain in patients with knee pain from OA. A subset of patients with moderate-to-severe pain may benefit from the combination.   IMPACT ON INTERNAL MEDICINE: Despite this mostly negative trial, the jury is still out on glucosamine and chondroitin sulfate. The accompanying editorial notes some of the limitations of the study (e.g., high attrition rate in the placebo group, high response to the placebo, lack of response to celecoxib in the group with severe pain, use of glucosamine hydrochloride rather than glucosamine sulfate). Moreover, people with severe pain may benefit from the combination of supplements.

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REFERENCES Hochberg MC. Nutritional supplements for knee osteoarthritis-still no resolution. N Engl J Med. 2006;354(8):858-60.

This accompanying editorial provides insight into the limitations of the study and gives some practical advice.

Presented at IM 2007 by David B. Reuben, MD, FACP. Reprinted with permission.  Copyright 2007 The American College of Physicians.

Saw palmetto for benign prostatic hyperplasia Bent S, Kane C, Shinohara K, Neuhaus J, Hudes ES, Goldberg H, Avins AL. N Engl J Med. 2006;354(6):557-66

BACKGROUND: Saw palmetto is commonly used to treat benign prostatic hyperplasia (BPH), although its mechanism of action and effectiveness are unknown. AIM: To assess the effectiveness of saw palmetto extract on symptoms or objective measures of BPH. METHODS: A 1-year randomized clinical trial was done of saw palmetto (160 mg twice daily) versus placebo in 225 men with moderate to severe symptoms of BPH. Primary outcomes were the American Urologic Association Symptom Index (AUASI) and maximal urinary flow rate; secondary outcomes were prostate size, postvoid residual volume, and quality of life. RESULTS: Although both groups had a small but significant improvement in the AUASI during the runin period and during the 1-year study, the groups did not differ significantly in mean change in AUASI scores, peak urinary flow rate, or any secondary outcome measures. In preplanned subgroup analysis (stratified according to AUASI score, prostate size, or prostate-specific level), there were no differences between treatment groups. CONCLUSIONS: Saw palmetto did not improve clinical or objective measures of BPH. IMPACT ON INTERNAL MEDICINE: Although it is possible that different preparations of saw palmetto might ave yielded different results, the composition of the preparation used in the study was similar to other products on the market. Currently, there are several effective treatments for BPH, including alpha-blockers and 5 alpha-reductase inhibitors. Physicians and patients should rely on these agents for BPH that requires treatment. Presented at IM 2007 by David B. Reuben, MD, FACP. Reprinted with permission. Copyright 2007 The American College of Physicians.

Nonhormonal therapies for menopausal hot flashes: systemic review and meta-analysis

fro treatment of hot flashes. AIM: To assess the efficacy and adverse effects of nonhormonal treatments for hot flashes by reviewing published randomized, controlled trials. METHODS: Published English-language, double-blind, placebo-controlled trials providing data on treatment for hot flashes using one or more nonhormonal therapies were identified by database searches supplemented by manual searches of systematic reviews and consultation with experts. RESULTS: The number of daily hot flashes decreased with active therapy compared with placebo in meta-analyses of seven comparisons of selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) (mean difference -1.13; 95% CI: -1.70 to -0.57), four trials of clonidine (mean difference -0.95: 95% CI: -1.44 to -0.47) and two trials of gabapentin (-2.05; 95% CI: -2.80 to -1.30). Hot flash frequency was not reduced in meta-analyses of red clover isoflavone extracts, and results were mixed for soy isoflavone abstracts. Evidence efficacy of other therapies was limited by small numbers and poor quality of trials. Because trials do not compare different therapies head to head, relative efficacy cannot be determined. CONCLUSIONS: SSRIs, clonidine, and gabapentin are superior to placebo in reducing hot flashes. Although comparative trials are lacking, they are probably less effective than estrogen. IMPACT ON INTERNAL MEDICINE: Many women with hot flashes cannot or do not want to take estrogen. Paroxetine, paroxetine CR, venlafaxine, fluoxetine, citalopram, clonidine, and gabapentin have each been shown to be more effective than placebo in reducing hot flashes. SSRIs and SNRIs are generally effective at low doses (similar to starting doses used to treat depression). Three hundred milligrams of gabapentin three times daily is effective; however, 100 miligramas of gabapentin three times daily was not effective in one study. Clonidine 0.1 mg orally or transdermally has also been shown to be effective.

Complementary treatments for hot flashes are popular. However, no complementary therapy has been consistently shown to be better than placebo for hot flashes in well-conducted randomized, controlled trials. A well-conducted study of black cohosh published after this meta-analysis showed it to be no better than placebo in treating hot flashes.



It is important to recognize that the placebo effect in all published studies has been large. Hot flash reductions of 25-50% are generally demonstrated in the placebo arm. This probably accounts for clinical improvements noted by many women when using such treatments as red clover, soy, and black cohosh, which are no better than placebo in reducing hot flashes in well-conducted, randomized, controlled trials.

SUGGESTED READING Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial. Ann Intern Med. 2006;145(12):869-79. Presented at IM 2007 by Carolyn Crandall, MD, MS, FACP and Janet P. Pregler, MD, FACP. Reprinted with permission.  Copyright 2007 The American College of Physicians.

Nelson HD, Vesco KK, Haney E, Fu R, Nedrow A, Miller J, Nicolaidis C, Walker M, Humphrey L. JAMA.2006;295(17):2057-2071.

BACKGROUND: There is strong interest in nonhormonal alternatives einstein: Educ Contin Saúde. 2007, 5(3 Pt 2): 72-78

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