User login
Does breastfeeding protect against viral GI infections in children
While breastfeeding protects against all-cause diarrhea in infants1- 5 (strength of recommendation [SOR]: B, based on cohort studies and 1 randomized controlled trial), no evidence shows that breastfeeding confers specific protection against viral gastrointestinal infections. Several studies demonstrate that breastfeeding does not prevent acquisition of rotavirus but does decrease the severity of its course (SOR: B, based on cohort, case-control studies, and a systematic review lacking homogeneity).6-10
Evidence summary
Breastfeeding has been associated with decreased overall rates of diarrhea in infants in developed2-4 and developing1,5 countries. Many cases of gastroenteritis without a confirmed enteropathogen have viral causes. Rotavirus is a common viral pathogen in children aged <2 years, and much of the evidence about breastfeeding and viral gastroenteritis comes from studies about rotavirus infections.
Prospective cohort studies conducted in Canada6 and the United States7 showed no difference in the incidence of rotavirus gastroenteritis between infants up to 2 years of age who were breastfed and those who were not. Although differences were not found between either the incidence or the duration of rotavirus infections, these studies showed a significant decrease in the frequency of vomiting among breastfed infants.
A case-control study in Bangladesh suggests that breastfed infants have a higher incidence of rotavirus diarrhea, but selection of diarrhea patients as controls may have underestimated the protective effect.8 Although breastfeeding was not found to provide overall protection from developing rotavirus gastroenteritis, exclusive breastfeeding appeared to protect against severe rotavirus diarrhea for infants aged <2 years.
Another US study showed that risk for rotavirus infection did not differ for infants who were exclusively breastfed, partially breastfed, or exclusively formula-fed.10 However, the breastfed infants were more likely to have milder symptoms.
RECOMMENDATIONS FROM OTHERS
The American Academy of Family Physicians11 and the American Academy of Pediatrics12 recommend exclusive breastfeeding for a minimum of the first 6 months of life, and continuation of breastfeeding to supplement age-appropriate foods through the next 6 months. The World Health Organization13 recommends exclusive breastfeeding for the first 4 to 6 months of life, and continuation of breastfeeding for 2 years of age or beyond.
Another reason to encourage mothers to breastfeed
Mark Ellis, MD, MSPH
Cox Health Systems Family Practice Residency, Springfield, Mo
This review affirms that breast milk protects against diarrheal illness while questioning a specific effect in preventing rotavirus infections. Evidence that breast milk reduces severity of the world’s major cause of diarrheaassociated death, however, is sufficient basis to support breastfeeding.
I educate expectant mothers about breast milk’s disease-mitigating qualities and compliment breastfeeding mothers on giving this gift to their children. I discuss the impact of breastfeeding on incidence of otitis media, asthma, obesity, and all-cause diarrhea. I also counsel that breast milk may decrease severity of diarrhea because it is “easier on the digestive system” (lower osmolality) than formula.
1. Hogan R, Martinez J. Breastfeeding as an intervention within diarrheal diseases control programs: WHO/CDC activities. Int J Gynaecol Obstet 1990;31(Suppl 1):115-119.
2. Dewey KG, Heinig MJ, Nommsen-Rivers LA. Differences in morbidity between breast-fed and formula-fed infants. J Pediatr 1995;126:696-702.
3. Scariati PD, Grummer-Strawn LM, Fein SB. A longitudinal analysis of infant morbidity and the extent of breastfeeding in the United States. Pediatrics 1997;99:E5.-
4. Wright AL, Bauer M, Naylor A, Sutcliffe E, Clark L. Increasing breastfeeding rates to reduce infant illness at the community level. Pediatrics 1998;101:837-844.
5. Kramer MS, Chalmers B, Hodnett ED, et al. Promotion of Breastfeeding Intervention Trial (PROBIT): a randomized trial in the Republic of Belarus. JAMA. 2001;285:413-420.
6. Gurwith M, Wenman W, Hinde D, Feltham S, Greenberg H. A prospective study of rotavirus infection in infants and young children. J Infect Dis 1981;144:218-224.
7. Weinberg RJ, Tipton G, Klish WJ, Brown MR. Effect of breast-feeding on morbidity in rotavirus gastroenteritis. Pediatrics 1984;74:250-253.
8. Clemens J, Rao M, Ahmed F, et al. Breast-feeding and the risk of life-threatening rotavirus diarrhea: prevention or postponement?. Pediatrics 1993;92:680-685.
9. Golding J, Emmett PM, Rogers IS. Gastroenteritis, diarrhoea and breast feeding. Early Hum Dev 1997;49(suppl):S83-S103.
10. Heinig MJ. Host defense benefits of breastfeeding for the infant. Effect of breastfeeding duration and exclusivity. Pediatr Clin North Am 2001;48:105-123.
11. AAFP Policy Statement on Breastfeeding Leawood, Kansas: American Academy of Family Physicians, 2001. Available at: http://www.aafp.org/x6633.xml. Accessed on September 10, 2003.
12. Breastfeeding and the use of human milk. American Academy of Pediatrics Work Group on Breastfeeding. Pediatrics 1997;100:1035-1039.
13. Nutrition: Infant and Young Child Geneva: World Health Organization, 2002. Available at: www.who.int/child-adolescent-health/NUTRITION/infant_exclusive.htm. Accessed on September 10, 2003.
While breastfeeding protects against all-cause diarrhea in infants1- 5 (strength of recommendation [SOR]: B, based on cohort studies and 1 randomized controlled trial), no evidence shows that breastfeeding confers specific protection against viral gastrointestinal infections. Several studies demonstrate that breastfeeding does not prevent acquisition of rotavirus but does decrease the severity of its course (SOR: B, based on cohort, case-control studies, and a systematic review lacking homogeneity).6-10
Evidence summary
Breastfeeding has been associated with decreased overall rates of diarrhea in infants in developed2-4 and developing1,5 countries. Many cases of gastroenteritis without a confirmed enteropathogen have viral causes. Rotavirus is a common viral pathogen in children aged <2 years, and much of the evidence about breastfeeding and viral gastroenteritis comes from studies about rotavirus infections.
Prospective cohort studies conducted in Canada6 and the United States7 showed no difference in the incidence of rotavirus gastroenteritis between infants up to 2 years of age who were breastfed and those who were not. Although differences were not found between either the incidence or the duration of rotavirus infections, these studies showed a significant decrease in the frequency of vomiting among breastfed infants.
A case-control study in Bangladesh suggests that breastfed infants have a higher incidence of rotavirus diarrhea, but selection of diarrhea patients as controls may have underestimated the protective effect.8 Although breastfeeding was not found to provide overall protection from developing rotavirus gastroenteritis, exclusive breastfeeding appeared to protect against severe rotavirus diarrhea for infants aged <2 years.
Another US study showed that risk for rotavirus infection did not differ for infants who were exclusively breastfed, partially breastfed, or exclusively formula-fed.10 However, the breastfed infants were more likely to have milder symptoms.
RECOMMENDATIONS FROM OTHERS
The American Academy of Family Physicians11 and the American Academy of Pediatrics12 recommend exclusive breastfeeding for a minimum of the first 6 months of life, and continuation of breastfeeding to supplement age-appropriate foods through the next 6 months. The World Health Organization13 recommends exclusive breastfeeding for the first 4 to 6 months of life, and continuation of breastfeeding for 2 years of age or beyond.
Another reason to encourage mothers to breastfeed
Mark Ellis, MD, MSPH
Cox Health Systems Family Practice Residency, Springfield, Mo
This review affirms that breast milk protects against diarrheal illness while questioning a specific effect in preventing rotavirus infections. Evidence that breast milk reduces severity of the world’s major cause of diarrheaassociated death, however, is sufficient basis to support breastfeeding.
I educate expectant mothers about breast milk’s disease-mitigating qualities and compliment breastfeeding mothers on giving this gift to their children. I discuss the impact of breastfeeding on incidence of otitis media, asthma, obesity, and all-cause diarrhea. I also counsel that breast milk may decrease severity of diarrhea because it is “easier on the digestive system” (lower osmolality) than formula.
While breastfeeding protects against all-cause diarrhea in infants1- 5 (strength of recommendation [SOR]: B, based on cohort studies and 1 randomized controlled trial), no evidence shows that breastfeeding confers specific protection against viral gastrointestinal infections. Several studies demonstrate that breastfeeding does not prevent acquisition of rotavirus but does decrease the severity of its course (SOR: B, based on cohort, case-control studies, and a systematic review lacking homogeneity).6-10
Evidence summary
Breastfeeding has been associated with decreased overall rates of diarrhea in infants in developed2-4 and developing1,5 countries. Many cases of gastroenteritis without a confirmed enteropathogen have viral causes. Rotavirus is a common viral pathogen in children aged <2 years, and much of the evidence about breastfeeding and viral gastroenteritis comes from studies about rotavirus infections.
Prospective cohort studies conducted in Canada6 and the United States7 showed no difference in the incidence of rotavirus gastroenteritis between infants up to 2 years of age who were breastfed and those who were not. Although differences were not found between either the incidence or the duration of rotavirus infections, these studies showed a significant decrease in the frequency of vomiting among breastfed infants.
A case-control study in Bangladesh suggests that breastfed infants have a higher incidence of rotavirus diarrhea, but selection of diarrhea patients as controls may have underestimated the protective effect.8 Although breastfeeding was not found to provide overall protection from developing rotavirus gastroenteritis, exclusive breastfeeding appeared to protect against severe rotavirus diarrhea for infants aged <2 years.
Another US study showed that risk for rotavirus infection did not differ for infants who were exclusively breastfed, partially breastfed, or exclusively formula-fed.10 However, the breastfed infants were more likely to have milder symptoms.
RECOMMENDATIONS FROM OTHERS
The American Academy of Family Physicians11 and the American Academy of Pediatrics12 recommend exclusive breastfeeding for a minimum of the first 6 months of life, and continuation of breastfeeding to supplement age-appropriate foods through the next 6 months. The World Health Organization13 recommends exclusive breastfeeding for the first 4 to 6 months of life, and continuation of breastfeeding for 2 years of age or beyond.
Another reason to encourage mothers to breastfeed
Mark Ellis, MD, MSPH
Cox Health Systems Family Practice Residency, Springfield, Mo
This review affirms that breast milk protects against diarrheal illness while questioning a specific effect in preventing rotavirus infections. Evidence that breast milk reduces severity of the world’s major cause of diarrheaassociated death, however, is sufficient basis to support breastfeeding.
I educate expectant mothers about breast milk’s disease-mitigating qualities and compliment breastfeeding mothers on giving this gift to their children. I discuss the impact of breastfeeding on incidence of otitis media, asthma, obesity, and all-cause diarrhea. I also counsel that breast milk may decrease severity of diarrhea because it is “easier on the digestive system” (lower osmolality) than formula.
1. Hogan R, Martinez J. Breastfeeding as an intervention within diarrheal diseases control programs: WHO/CDC activities. Int J Gynaecol Obstet 1990;31(Suppl 1):115-119.
2. Dewey KG, Heinig MJ, Nommsen-Rivers LA. Differences in morbidity between breast-fed and formula-fed infants. J Pediatr 1995;126:696-702.
3. Scariati PD, Grummer-Strawn LM, Fein SB. A longitudinal analysis of infant morbidity and the extent of breastfeeding in the United States. Pediatrics 1997;99:E5.-
4. Wright AL, Bauer M, Naylor A, Sutcliffe E, Clark L. Increasing breastfeeding rates to reduce infant illness at the community level. Pediatrics 1998;101:837-844.
5. Kramer MS, Chalmers B, Hodnett ED, et al. Promotion of Breastfeeding Intervention Trial (PROBIT): a randomized trial in the Republic of Belarus. JAMA. 2001;285:413-420.
6. Gurwith M, Wenman W, Hinde D, Feltham S, Greenberg H. A prospective study of rotavirus infection in infants and young children. J Infect Dis 1981;144:218-224.
7. Weinberg RJ, Tipton G, Klish WJ, Brown MR. Effect of breast-feeding on morbidity in rotavirus gastroenteritis. Pediatrics 1984;74:250-253.
8. Clemens J, Rao M, Ahmed F, et al. Breast-feeding and the risk of life-threatening rotavirus diarrhea: prevention or postponement?. Pediatrics 1993;92:680-685.
9. Golding J, Emmett PM, Rogers IS. Gastroenteritis, diarrhoea and breast feeding. Early Hum Dev 1997;49(suppl):S83-S103.
10. Heinig MJ. Host defense benefits of breastfeeding for the infant. Effect of breastfeeding duration and exclusivity. Pediatr Clin North Am 2001;48:105-123.
11. AAFP Policy Statement on Breastfeeding Leawood, Kansas: American Academy of Family Physicians, 2001. Available at: http://www.aafp.org/x6633.xml. Accessed on September 10, 2003.
12. Breastfeeding and the use of human milk. American Academy of Pediatrics Work Group on Breastfeeding. Pediatrics 1997;100:1035-1039.
13. Nutrition: Infant and Young Child Geneva: World Health Organization, 2002. Available at: www.who.int/child-adolescent-health/NUTRITION/infant_exclusive.htm. Accessed on September 10, 2003.
1. Hogan R, Martinez J. Breastfeeding as an intervention within diarrheal diseases control programs: WHO/CDC activities. Int J Gynaecol Obstet 1990;31(Suppl 1):115-119.
2. Dewey KG, Heinig MJ, Nommsen-Rivers LA. Differences in morbidity between breast-fed and formula-fed infants. J Pediatr 1995;126:696-702.
3. Scariati PD, Grummer-Strawn LM, Fein SB. A longitudinal analysis of infant morbidity and the extent of breastfeeding in the United States. Pediatrics 1997;99:E5.-
4. Wright AL, Bauer M, Naylor A, Sutcliffe E, Clark L. Increasing breastfeeding rates to reduce infant illness at the community level. Pediatrics 1998;101:837-844.
5. Kramer MS, Chalmers B, Hodnett ED, et al. Promotion of Breastfeeding Intervention Trial (PROBIT): a randomized trial in the Republic of Belarus. JAMA. 2001;285:413-420.
6. Gurwith M, Wenman W, Hinde D, Feltham S, Greenberg H. A prospective study of rotavirus infection in infants and young children. J Infect Dis 1981;144:218-224.
7. Weinberg RJ, Tipton G, Klish WJ, Brown MR. Effect of breast-feeding on morbidity in rotavirus gastroenteritis. Pediatrics 1984;74:250-253.
8. Clemens J, Rao M, Ahmed F, et al. Breast-feeding and the risk of life-threatening rotavirus diarrhea: prevention or postponement?. Pediatrics 1993;92:680-685.
9. Golding J, Emmett PM, Rogers IS. Gastroenteritis, diarrhoea and breast feeding. Early Hum Dev 1997;49(suppl):S83-S103.
10. Heinig MJ. Host defense benefits of breastfeeding for the infant. Effect of breastfeeding duration and exclusivity. Pediatr Clin North Am 2001;48:105-123.
11. AAFP Policy Statement on Breastfeeding Leawood, Kansas: American Academy of Family Physicians, 2001. Available at: http://www.aafp.org/x6633.xml. Accessed on September 10, 2003.
12. Breastfeeding and the use of human milk. American Academy of Pediatrics Work Group on Breastfeeding. Pediatrics 1997;100:1035-1039.
13. Nutrition: Infant and Young Child Geneva: World Health Organization, 2002. Available at: www.who.int/child-adolescent-health/NUTRITION/infant_exclusive.htm. Accessed on September 10, 2003.
Evidence-based answers from the Family Physicians Inquiries Network
Does glucosamine relieve arthritis joint pain?
Glucosamine may provide some pain relief. Studies have shown varied results, ranging from glucosamine being superior or equivalent to other agents, to no difference between glucosamine and placebo. However, most of these studies have small sample sizes, short duration, and often other significant flaws. Meta-analyses of available studies suggest a trend toward benefit from glucosamine (strength of recommendation: B).
Glucosamine may help osteoarthritis pain, but it is premature to recommend it universally until better studies are done. Even if glucosamine is effective, this sector of the market is currently unregulated, and products may not contain the amount or kind of glucosamine material advertised on their labels.
Evidence summary
Multiple methodological flaws have characterized studies trying to answer this question over the past 30 to 35 years. The companies manufacturing glucosamine have funded most studies. The overwhelming proportion of positive but marginal results raises the possibility of a publication bias (the tendency to publish only positive or supportive results), and the funding sources for the positive studies make that bias plausible.
Identified flaws in the studies include small sample size, inconsistent diagnostic criteria, variable disease sites, differing routes of administration, inconsistent doses, compositions and forms of glucosamine, the brief durations of studies, and poorly defined endpoints.1 Those problems account for the relatively low quality scores of the studies used in meta-analyses, particularly in earlier ones. Quality scores range from 12% to 52% of optimal and make any definitive conclusions suspect.2
The magnitude of the treatment effect is variable. Meta-analyses demonstrate aggregate treatment effects ranging from 0.36 to 1.02— where a small effect is 0.2, a moderate effect is 0.5, and a large effect is 0.8.2
When more recent, higher-quality studies are analyzed, trends toward benefit and the effect sizes for glucosamine diminish but remain at aggregate values ranging from 0.26 to 0.44.2-4 Statistically significant differences exist in some subgroup analyses and secondary endpoints.5 Typical trends suggest that glucosamine is superior to placebo for pain relief, and less effective but safer than nonsteroidal anti-inflammatory agents.6
Statements about safety are speculative given the brief duration of available trials, most of which lasted <10 weeks.6 Reported adverse effects are few. Mild gastrointestinal, skin, and constitutional symptoms predominate, but seldom at rates much higher than placebo.3-4 Pain relief may require as much as 4 to 6 weeks of therapy, and short studies may not demonstrate these benefits. The possibility of site-specific benefits or a difference in effect from a different dose or form is impossible to determine based on the current literature.
Recommendations from others
The American College of Rheumatology Subcommittee on Osteoarthritis believes that it is too early to issue recommendations for use of glucosamine sulfate or chondroitin sulfate for treatment of osteoarthritis.7
The National Institutes of Health Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) began recruiting in May 2002. The design of this study is specifically directed at addressing the flaws of previous studies. This study will enroll 1588 patients at 13 study sites, and will use standardized products and doses with a single route of administration in a double-blinded, placebo-controlled fashion.
The GAIT study will measure change in joint space width (baseline to 2 years) and consists of 4 arms: glucosamine vs placebo, chondroitin vs placebo, glucosamine and chondroitin vs placebo, and celecoxib vs placebo. It is likely that the National Institute of Arthritis, Musculoskeletal and Skin Diseases, in collaboration with the National Center for Complementary and Alternative Medicine, will issue recommendations regarding the efficacy of glucosamine when the study is complete in 2005 or 2006. Updates are available at http://nccam.nih.gov/clinicaltrials/ glucosamine.htm.
Russell W. Roberts, MD
Louisiana State University Health Sciences Center, Shreveport, La
Patients frequently ask me if glucosamine, in combination with chondroitin or methylsulfonylmethane (MSM), reduces or prevents arthritis pain. It appears that glucosamine is safe and offers some promise.
I think a 6-week trial in patients with osteoarthritis is reasonable, preferably using glucosamine—a type that complies with the United States Pharmacopia/National Formulary standards—500 mg orally 3 times daily, once it becomes widely available. In my experience, very few patients who give glucosamine an enthusiastic and adequate trial of therapy continue the course for more than a few months. Those who use it longer often acknowledge only modest relief but continue with the hope of preventing further joint degeneration and increased pain, another currently unsubstantiated expectation.
1. Deal CL, Moskowitz RW. Nutraceuticals as therapeutic agents in osteoarthritis. The role of glucosamine, chondroitin sulfate and collagen hydrolysate. Rheum Dis Clin North Am 1999;25:379-395.
2. McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA 2000;283:1469-1475.
3. Barclay TS, Tsourounis C, McCart GM. Glucosamine. Ann Pharmacother 1998;32:574-579.
4. Heyneman CA, Rhodes RS. Glucosamine for osteoarthritis: cure or conundrum? Ann Pharmacother 1998;32:602-603.
5. Houpt JB, McMillan R, Wein C, Paget-Dellio SD. Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee. J Rheumatol 1999;26:2423-2430.
6. Towheed TE, Anastassiades TP, Shea B, Houpt J, Welch V, Hochberg MC. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev 2001;(1):CD002946.-
7. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum 2000;43:1905-1915.
Glucosamine may provide some pain relief. Studies have shown varied results, ranging from glucosamine being superior or equivalent to other agents, to no difference between glucosamine and placebo. However, most of these studies have small sample sizes, short duration, and often other significant flaws. Meta-analyses of available studies suggest a trend toward benefit from glucosamine (strength of recommendation: B).
Glucosamine may help osteoarthritis pain, but it is premature to recommend it universally until better studies are done. Even if glucosamine is effective, this sector of the market is currently unregulated, and products may not contain the amount or kind of glucosamine material advertised on their labels.
Evidence summary
Multiple methodological flaws have characterized studies trying to answer this question over the past 30 to 35 years. The companies manufacturing glucosamine have funded most studies. The overwhelming proportion of positive but marginal results raises the possibility of a publication bias (the tendency to publish only positive or supportive results), and the funding sources for the positive studies make that bias plausible.
Identified flaws in the studies include small sample size, inconsistent diagnostic criteria, variable disease sites, differing routes of administration, inconsistent doses, compositions and forms of glucosamine, the brief durations of studies, and poorly defined endpoints.1 Those problems account for the relatively low quality scores of the studies used in meta-analyses, particularly in earlier ones. Quality scores range from 12% to 52% of optimal and make any definitive conclusions suspect.2
The magnitude of the treatment effect is variable. Meta-analyses demonstrate aggregate treatment effects ranging from 0.36 to 1.02— where a small effect is 0.2, a moderate effect is 0.5, and a large effect is 0.8.2
When more recent, higher-quality studies are analyzed, trends toward benefit and the effect sizes for glucosamine diminish but remain at aggregate values ranging from 0.26 to 0.44.2-4 Statistically significant differences exist in some subgroup analyses and secondary endpoints.5 Typical trends suggest that glucosamine is superior to placebo for pain relief, and less effective but safer than nonsteroidal anti-inflammatory agents.6
Statements about safety are speculative given the brief duration of available trials, most of which lasted <10 weeks.6 Reported adverse effects are few. Mild gastrointestinal, skin, and constitutional symptoms predominate, but seldom at rates much higher than placebo.3-4 Pain relief may require as much as 4 to 6 weeks of therapy, and short studies may not demonstrate these benefits. The possibility of site-specific benefits or a difference in effect from a different dose or form is impossible to determine based on the current literature.
Recommendations from others
The American College of Rheumatology Subcommittee on Osteoarthritis believes that it is too early to issue recommendations for use of glucosamine sulfate or chondroitin sulfate for treatment of osteoarthritis.7
The National Institutes of Health Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) began recruiting in May 2002. The design of this study is specifically directed at addressing the flaws of previous studies. This study will enroll 1588 patients at 13 study sites, and will use standardized products and doses with a single route of administration in a double-blinded, placebo-controlled fashion.
The GAIT study will measure change in joint space width (baseline to 2 years) and consists of 4 arms: glucosamine vs placebo, chondroitin vs placebo, glucosamine and chondroitin vs placebo, and celecoxib vs placebo. It is likely that the National Institute of Arthritis, Musculoskeletal and Skin Diseases, in collaboration with the National Center for Complementary and Alternative Medicine, will issue recommendations regarding the efficacy of glucosamine when the study is complete in 2005 or 2006. Updates are available at http://nccam.nih.gov/clinicaltrials/ glucosamine.htm.
Russell W. Roberts, MD
Louisiana State University Health Sciences Center, Shreveport, La
Patients frequently ask me if glucosamine, in combination with chondroitin or methylsulfonylmethane (MSM), reduces or prevents arthritis pain. It appears that glucosamine is safe and offers some promise.
I think a 6-week trial in patients with osteoarthritis is reasonable, preferably using glucosamine—a type that complies with the United States Pharmacopia/National Formulary standards—500 mg orally 3 times daily, once it becomes widely available. In my experience, very few patients who give glucosamine an enthusiastic and adequate trial of therapy continue the course for more than a few months. Those who use it longer often acknowledge only modest relief but continue with the hope of preventing further joint degeneration and increased pain, another currently unsubstantiated expectation.
Glucosamine may provide some pain relief. Studies have shown varied results, ranging from glucosamine being superior or equivalent to other agents, to no difference between glucosamine and placebo. However, most of these studies have small sample sizes, short duration, and often other significant flaws. Meta-analyses of available studies suggest a trend toward benefit from glucosamine (strength of recommendation: B).
Glucosamine may help osteoarthritis pain, but it is premature to recommend it universally until better studies are done. Even if glucosamine is effective, this sector of the market is currently unregulated, and products may not contain the amount or kind of glucosamine material advertised on their labels.
Evidence summary
Multiple methodological flaws have characterized studies trying to answer this question over the past 30 to 35 years. The companies manufacturing glucosamine have funded most studies. The overwhelming proportion of positive but marginal results raises the possibility of a publication bias (the tendency to publish only positive or supportive results), and the funding sources for the positive studies make that bias plausible.
Identified flaws in the studies include small sample size, inconsistent diagnostic criteria, variable disease sites, differing routes of administration, inconsistent doses, compositions and forms of glucosamine, the brief durations of studies, and poorly defined endpoints.1 Those problems account for the relatively low quality scores of the studies used in meta-analyses, particularly in earlier ones. Quality scores range from 12% to 52% of optimal and make any definitive conclusions suspect.2
The magnitude of the treatment effect is variable. Meta-analyses demonstrate aggregate treatment effects ranging from 0.36 to 1.02— where a small effect is 0.2, a moderate effect is 0.5, and a large effect is 0.8.2
When more recent, higher-quality studies are analyzed, trends toward benefit and the effect sizes for glucosamine diminish but remain at aggregate values ranging from 0.26 to 0.44.2-4 Statistically significant differences exist in some subgroup analyses and secondary endpoints.5 Typical trends suggest that glucosamine is superior to placebo for pain relief, and less effective but safer than nonsteroidal anti-inflammatory agents.6
Statements about safety are speculative given the brief duration of available trials, most of which lasted <10 weeks.6 Reported adverse effects are few. Mild gastrointestinal, skin, and constitutional symptoms predominate, but seldom at rates much higher than placebo.3-4 Pain relief may require as much as 4 to 6 weeks of therapy, and short studies may not demonstrate these benefits. The possibility of site-specific benefits or a difference in effect from a different dose or form is impossible to determine based on the current literature.
Recommendations from others
The American College of Rheumatology Subcommittee on Osteoarthritis believes that it is too early to issue recommendations for use of glucosamine sulfate or chondroitin sulfate for treatment of osteoarthritis.7
The National Institutes of Health Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) began recruiting in May 2002. The design of this study is specifically directed at addressing the flaws of previous studies. This study will enroll 1588 patients at 13 study sites, and will use standardized products and doses with a single route of administration in a double-blinded, placebo-controlled fashion.
The GAIT study will measure change in joint space width (baseline to 2 years) and consists of 4 arms: glucosamine vs placebo, chondroitin vs placebo, glucosamine and chondroitin vs placebo, and celecoxib vs placebo. It is likely that the National Institute of Arthritis, Musculoskeletal and Skin Diseases, in collaboration with the National Center for Complementary and Alternative Medicine, will issue recommendations regarding the efficacy of glucosamine when the study is complete in 2005 or 2006. Updates are available at http://nccam.nih.gov/clinicaltrials/ glucosamine.htm.
Russell W. Roberts, MD
Louisiana State University Health Sciences Center, Shreveport, La
Patients frequently ask me if glucosamine, in combination with chondroitin or methylsulfonylmethane (MSM), reduces or prevents arthritis pain. It appears that glucosamine is safe and offers some promise.
I think a 6-week trial in patients with osteoarthritis is reasonable, preferably using glucosamine—a type that complies with the United States Pharmacopia/National Formulary standards—500 mg orally 3 times daily, once it becomes widely available. In my experience, very few patients who give glucosamine an enthusiastic and adequate trial of therapy continue the course for more than a few months. Those who use it longer often acknowledge only modest relief but continue with the hope of preventing further joint degeneration and increased pain, another currently unsubstantiated expectation.
1. Deal CL, Moskowitz RW. Nutraceuticals as therapeutic agents in osteoarthritis. The role of glucosamine, chondroitin sulfate and collagen hydrolysate. Rheum Dis Clin North Am 1999;25:379-395.
2. McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA 2000;283:1469-1475.
3. Barclay TS, Tsourounis C, McCart GM. Glucosamine. Ann Pharmacother 1998;32:574-579.
4. Heyneman CA, Rhodes RS. Glucosamine for osteoarthritis: cure or conundrum? Ann Pharmacother 1998;32:602-603.
5. Houpt JB, McMillan R, Wein C, Paget-Dellio SD. Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee. J Rheumatol 1999;26:2423-2430.
6. Towheed TE, Anastassiades TP, Shea B, Houpt J, Welch V, Hochberg MC. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev 2001;(1):CD002946.-
7. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum 2000;43:1905-1915.
1. Deal CL, Moskowitz RW. Nutraceuticals as therapeutic agents in osteoarthritis. The role of glucosamine, chondroitin sulfate and collagen hydrolysate. Rheum Dis Clin North Am 1999;25:379-395.
2. McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA 2000;283:1469-1475.
3. Barclay TS, Tsourounis C, McCart GM. Glucosamine. Ann Pharmacother 1998;32:574-579.
4. Heyneman CA, Rhodes RS. Glucosamine for osteoarthritis: cure or conundrum? Ann Pharmacother 1998;32:602-603.
5. Houpt JB, McMillan R, Wein C, Paget-Dellio SD. Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee. J Rheumatol 1999;26:2423-2430.
6. Towheed TE, Anastassiades TP, Shea B, Houpt J, Welch V, Hochberg MC. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev 2001;(1):CD002946.-
7. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum 2000;43:1905-1915.
Evidence-based answers from the Family Physicians Inquiries Network