Lectin Shield by Gundry MD

There is insufficient reliable information available about the effectiveness of algin.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Abdominal pain. Although there has been interest in using oral ambrette for abdominal pain, there is insufficient reliable information about the clinical effects of ambrette for this purpose.
• Anorexia nervosa. Although there has been interest in using oral ambrette for anorexia nervosa, there is insufficient reliable information about the clinical effects of ambrette for this purpose.
• Anxiety. Although there has been interest in using oral ambrette for anxiety, there is insufficient reliable information about the clinical effects of ambrette for this purpose.
• Cancer. Although there has been interest in using oral ambrette for cancer, there is insufficient reliable information about the clinical effects of ambrette for this purpose.
• Congestive heart failure (CHF). Although there has been interest in using oral ambrette for CHF, there is insufficient reliable information about the clinical effects of ambrette for this purpose.
• Constipation. Although there has been interest in using oral ambrette for constipation, there is insufficient reliable information about the clinical effects of ambrette for this purpose.
• Depression. Although there has been interest in using oral ambrette for depression, there is insufficient reliable information about the clinical effects of ambrette for this purpose.
• Diabetic nephropathy. Oral ambrette has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of randomized trials that included patients with diabetic nephropathy shows that taking ambrette 7.5 grams orally and tripterygium glycosides 30-60 mg orally daily for 8-12 weeks moderately improves urinary protein, serum creatinine, and blood urea nitrogen levels when compared with control. It is unclear if this effect is due to ambrette, tripterygium glycosides, or the combination. The validity of this study is limited by high heterogeneity (111435).
• Dyspepsia. Although there has been interest in using oral ambrette for dyspepsia, there is insufficient reliable information about the clinical effects of ambrette for this purpose.
• Gonorrhea. Although there has been interest in using oral ambrette for gonorrhea, there is insufficient reliable information about the clinical effects of ambrette for this purpose.
• Headache. Although there has been interest in using oral ambrette for headache, there is insufficient reliable information about the clinical effects of ambrette for this purpose.
• Hypertension. Although there has been interest in using oral ambrette for hypertension, there is insufficient reliable information about the clinical effects of ambrette for this purpose.
• Nausea and vomiting. Although there has been interest in using oral ambrette for nausea and vomiting, there is insufficient reliable information about the clinical effects of ambrette for this purpose.
• Osteoarthritis. Although there has been interest in using oral ambrette for osteoarthritis, there is insufficient reliable information about the clinical effects of ambrette for this purpose.
• Sexual dysfunction. Although there has been interest in using oral ambrette for sexual dysfunction, there is insufficient reliable information about the clinical effects of ambrette for this purpose.
• Urinary incontinence. Although there has been interest in using oral ambrette for urinary incontinence, there is insufficient reliable information about the clinical effects of ambrette for this purpose. More evidence is needed to rate ambrette for these uses.

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LIKELY EFFECTIVE

• Carbohydrate-deficient glycoprotein syndrome type 1b. Oral D-mannose prevents certain hematologic and gastrointestinal complications in patients with this condition. However, it's unclear if it helps to prevent liver complications. Details: Carbohydrate-deficient glycoprotein syndrome type 1b is a rare and often lethal congenital disorder of glycosylation (CDG). It is characterized by protein loss in the digestive tract, gastrointestinal symptoms, hypoglycemia, liver disease, and failure to thrive. The disorder is also called phosphomannose isomerase (PMI) deficiency or mannose-phosphate-isomerase CDG (MPI-CDG). Taking D-mannose 300-1020 mg/kg daily in 3-6 divided doses long-term can reduce protein loss, hypoglycemia, coagulation disorders, and gastrointestinal symptoms in patients, usually infants and children, with this disorder (13344,13345,13346,13348,100978,100979,100980,100981). While D-mannose seems to be effective for stabilizing the signs and symptoms of this condition, it is not clear whether it can prevent liver complications. In two cases, D-mannose reduced hepatomegaly after 6 months or 2 years of therapy (13348,100980). In other cases, however, hepatic fibrosis developed despite D-mannose treatment for up to 6 years (13345,100978). These discrepant finding are thought to be due to the variable levels of liver disease severity at the time of D-mannose treatment initiation (100977).

POSSIBLY INEFFECTIVE

• Urinary tract infections (UTIs). Clinical studies suggest that oral D-mannose does not reduce the rate of UTI recurrence in community dwelling pre- and postmenopausal adults. It is unclear if oral D-mannose is beneficial for the treatment of UTIs when used alone or in combination with other ingredients. Details: A large clinical trial of about 600 community dwelling pre- and postmenopausal females with a recent history of recurring UTI (defined as 3 UTIs in the past year or 2 UTIs in the past 6 months) shows that taking D-mannose powder 2 grams daily for 6 months does not reduce the rate of UTI recurrence when compared with placebo (113576). Additionally, a small clinical study of postmenopausal females with a history of recurrent UTI which compared D-mannose powder 2 grams daily with standard of care was halted early due to likely futility (111756). Prior to the publication of these two studies, a systematic review of the available research concluded that there was no strong evidence for or against the use of D-mannose for UTI prevention or treatment (110013). One relatively large clinical trial included in this body of evidence shows that D-mannose reduces UTI recurrence when compared with no prophylaxis, with rates of 32% and 61%, respectively, but is less effective than nitrofurantoin 50 mg daily (20%) (91141). D-mannose has also been evaluated for UTI prevention in combination with other ingredients. A small clinical study in older adults undergoing cystoscopy shows that taking D-mannose 500 mg plus Saccharomyces boulardii 3 billion CFU twice daily for 6 days after the procedure reduces the incidence of positive urine cultures (0% vs. 19%) when compared with no treatment (112363). However, this study did not report on the rate of symptomatic UTIs. Additionally, it is unclear if these effects are due to D-mannose, Saccharomyces boulardii, or the combination. Low-quality research suggests that taking specific combination products containing D-mannose may be beneficial for UTI prevention. These products have combined D-mannose 250 mg with cranberry extract, tara gum, and probiotic bacteria (1-2.5 billion live cells of L. plantarum LP01, L. paracasei LPC09, and Streptococcus thermophilus ST10) (93884); D-mannose (dose unspecified) with cranberry, and L. paracasei (Lactoflorene Cist, Montefarmaco) (104210); and D-mannose 500 mg with noni fruit extract 200 mg and N-acetylcysteine 100 mg (97360). D-mannose has also been evaluated in small, low-quality studies as a treatment for existing UTI, alone or in combination with other ingredients. A small clinical study in females with an acute UTI shows that taking a specific D-mannose product (Mannocist, Laboratori Farmaceutici Krymi) 1.5 grams twice daily for 3 days, and then once daily for 10 days, improves some symptoms of UTI when compared to baseline (93883). The validity of this finding is limited by the lack of a comparator group. A clinical study in females aged 18-45 with uncomplicated UTIs shows that taking a supplement containing D-mannose 2 grams, astragalus, citric acid, dandelion, and prebiotics dissolved in water twice daily for 5 days improves complete resolution of UTI symptoms and clearance of bacteriuria at days 6 and 35 when compared with placebo (111757). However, it is unclear if these effects are due to D-mannose, other ingredients, or the combination. There is insufficient reliable information available about the effectiveness of D-mannose for its other uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. Although there has been interest in using topical Fucus vesiculosus for aging skin, there is insufficient reliable information about the clinical effects of Fucus vesiculosus for this purpose.
• Cardiovascular disease (CVD). Although there has been interest in using oral Fucus vesiculosus for CVD, including atherosclerosis and hypertension, there is insufficient reliable information about the clinical effects of Fucus vesiculosus for this purpose.
• Constipation. Although there has been interest in using oral Fucus vesiculosus for constipation, there is insufficient reliable information about the clinical effects of Fucus vesiculosus for this purpose.
• Diarrhea. Although there has been interest in using oral Fucus vesiculosus for diarrhea, there is insufficient reliable information about the clinical effects of Fucus vesiculosus for this purpose.
• Dyspepsia. Although there has been interest in using oral Fucus vesiculosus for dyspepsia, there is insufficient reliable information about the clinical effects of Fucus vesiculosus for this purpose.
• Hypercholesterolemia. It is unclear if oral Fucus vesiculosus is beneficial in hypercholesterolemia. Details: A small clinical study in patients with obesity or overweight and low-density lipoprotein (LDL) cholesterol levels exceeding 77 mg/dL shows that taking a polyphenol-rich extract of Fucus vesiculosus (Maritech Synergy, Marinova) 2000 mg, providing 560 mg of polyphenols, daily for 12 weeks increases levels of high-density lipoprotein (HDL) cholesterol by 10%, compared with 2% in those receiving placebo. No differences were observed for total cholesterol, LDL cholesterol, or triglycerides (106723).
• Hypothyroidism. Although there has been interest in using oral Fucus vesiculosus for hypothyroidism, there is insufficient reliable information about the clinical effects of Fucus vesiculosus for this purpose.
• Impaired glucose tolerance (prediabetes). Oral Fucus vesiculosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with prediabetes and dysglycemia shows that taking a specific product (Gdue, Aesculapius), containing extracts of Fucus vesiculosus and Ascophyllum nodosum in a 5:95 ratio along with chromium picolinate three times daily for 6 months reduces fasting and postprandial blood glucose, glycated hemoglobin (HbA1c), insulin, and insulin resistance when compared with placebo (100847). It is unclear if these effects are due to Fucus vesiculosus, other ingredients, or the combination. Another small clinical study in adults with prediabetes and also overweight or obese shows that taking a specific product (InSea2, InnoVactiv Inc.) containing 500 mg of Fucus vesiculosus and Ascophyllum nodosum extracts daily for 12 weeks reduces postprandial blood glucose but does not improve fasting blood glucose, HbA1c, body weight, lipids, or blood pressure when compared with placebo (110560).
• Iodine deficiency. Although there has been interest in using oral Fucus vesiculosus for iodine deficiency and goiter, there is insufficient reliable information about the clinical effects of Fucus vesiculosus for this purpose.
• Metabolic syndrome. Oral Fucus vesiculosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Observational research in adults with one or more components of metabolic syndrome has found that taking a specific combination product (Gdue, Aesculapius) containing extracts of Fucus vesiculosus and Ascophyllum nodosum in a 5:95 ratio along with chromium picolinate two to three times daily with meals for around 6 months is associated with reductions in body weight by 7.3 kg, waist circumference by 7.5 cm, fasting blood glucose by 16 mg/dL, glycated hemoglobin (HbA1c) by 0.55%, systolic blood pressure by 7 mmHg, diastolic blood pressure by 4 mmHg, low-density lipoprotein (LDL) cholesterol by 18 mg/dL, and 10-year cardiovascular risk scores by 1.8% when compared to baseline (110559). It is unclear if these effects are due to Fucus vesiculosus, other ingredients, or the combination. Further, the validity of these findings is limited by a lack of control group.
• Obesity. Oral Fucus vesiculosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in moderately overweight females shows that seaweeds such as Fucus vesiculosus, taken in combination with lecithin and vitamins for up to 2 years, do not result in sustained weight loss when compared to baseline (13663). Another small clinical study in adults with prediabetes and also overweight or obese shows that taking a specific product (InSea2, InnoVactiv Inc.) containing 500 mg of Fucus vesiculosus and Ascophyllum nodosum extracts daily for 12 weeks does not reduce body weight, body mass index (BMI), body fat, lipids, blood pressure, or measures of glycemic control when compared with placebo (110560).
• Wound healing. Although there has been interest in using topical Fucus vesiculosus for wound healing, there is insufficient reliable information about the clinical effects of Fucus vesiculosus for this purpose. More evidence is needed to rate Fucus vesiculosus for these uses.

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LIKELY EFFECTIVE

• Osteoarthritis. Oral glucosamine sulfate taken for at least 4 weeks is modestly beneficial for improving pain and function in knee osteoarthritis. However, oral glucosamine hydrochloride seems to only be beneficial when used in combination with chondroitin and other ingredients. It is unclear if glucosamine can slow disease progression or improve symptoms in other forms of osteoarthritis. Details: Meta-analyses of the available research in adults with KNEE osteoarthritis show that taking glucosamine SULFATE 1500 mg daily for up to 3 years modestly improves pain, function, and joint space narrowing when compared with placebo (14305,89521,94382,95785,99684,113636). Individual studies show 28% to 41% pain reduction and 21% to 46% improvement in function when compared with placebo (7026,8942,12461,20084,94382). Some research suggests that glucosamine sulfate reduces pain similarly to various non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen 400 mg three times daily and piroxicam 20 mg daily. However, NSAIDs appear to relieve symptoms within 2 weeks, while glucosamine sulfate takes 4-8 weeks. Notably, glucosamine sulfate appears to sustain benefit for longer after treatment withdrawal when compared with piroxicam (2604,20094,20096). Other clinical research shows that glucosamine sulfate 1500 mg once daily for 6 months might be more effective for reducing symptoms than acetaminophen 1 gram three times daily or 650 mg once daily in patients with moderate knee osteoarthritis (13578,20098). However, not all research shows benefit. One meta-analysis of clinical studies in adults with knee osteoarthritis shows that taking glucosamine sulfate 1500 mg daily for 4 weeks to 3 years reduces some, but not all, measures of pain intensity and does not reduce pain when moving or improve function when compared with placebo (113636). Furthermore, small clinical studies suggest that glucosamine sulfate 1500 mg daily for 2-6 months may NOT work for severe, long-standing osteoarthritis (1330,11459). It is unclear if glucosamine sulfate can slow disease progression. A specific crystalline glucosamine sulfate product (Dona, Rotta Pharmaceuticals) taken as 1500 mg daily for up to 3 years seems to prevent joint space narrowing of greater than 0.5 mm by up to 54% when compared with placebo (7026,8942,13719,42420). In contrast, other glucosamine sulfate formulations have not consistently been shown to improve symptoms or prevent joint space narrowing when compared with placebo (14305,89558,94382,95788). It is unclear if the benefit seen with this specific product (Dona) is due to bias introduced by industry funding or due to a higher quality product (42492). Glucosamine products associated with quality concerns have demonstrated inconsistent benefits in research (8128,102116). Limited research on the use of a different salt, glucosamine HYDROCHLORIDE, has found no benefit for knee osteoarthritis. A meta-analysis of clinical research and two other clinical trials show that taking glucosamine hydrochloride 1500 mg daily for up to 18 months does not seem to reduce pain when compared with placebo (18344,89519,89521). However, one small, unblinded clinical study in patients with mild to moderate osteoarthritis shows that taking a combination of glucosamine hydrochloride 480 mg every 12 hours and celecoxib 200 mg daily reduces pain scores, osteoarthritis severity, and inflammatory markers to a greater extent than celecoxib alone (106883). There is mixed evidence of benefit when glucosamine hydrochloride is used with chondroitin. Clinical research in patients over 40 years of age shows that taking a noncommercial preparation of glucosamine hydrochloride 1500 mg daily in combination with chondroitin sulfate 1200 mg daily for 6-24 months does not reduce pain when compared with placebo. The placebo response in these studies was sometimes as high as 60% (13579,14809,42477). However, a large, prospective observational study in adults with knee or hip osteoarthritis suggests that taking glucosamine hydrochloride 500 mg and chondroitin sulfate 400 mg (Theraflex, Bayer) three times daily for the first 3 weeks then twice daily thereafter for up to 64 weeks is associated with reductions in pain, stiffness, and the need for concomitant analgesic therapy and improvements in daily function and knee- or hip-related quality of life when compared to baseline. The most pronounced improvements were from 16-24 weeks (111647). The validity of these effects is limited by subjective outcomes, a lack of control group, and the observational design of the study. Furthermore, another clinical trial shows that taking a prescription product available in Spain (Droglican, Bioibérica S.A.), providing a similar daily dose of glucosamine hydrochloride with chondroitin sulfate for 6 months is non-inferior to celecoxib 200 mg daily for relieving pain, but not stiffness or function (89516). Small clinical studies show that taking a specific combination product (Cosamin or Cosamin DS, Nutramax Laboratories) containing glucosamine hydrochloride 1500-2000 mg, low molecular weight chondroitin sulfate 1200-1600 mg, and manganese ascorbate 228-304 mg, in 2-3 divided doses daily for 2-6 months improves pain in patients with mild or moderate, but not severe, osteoarthritis when compared with placebo (4237,7169). A different combination product (Gurukosamin & Kondoroichin, Suntory Wellness Ltd.) containing glucosamine hydrochloride 1200 mg, chondroitin sulfate 60 mg, and quercetin glycosides 45 mg, taken daily for 16 weeks, also seems to improve symptoms of knee osteoarthritis when compared with placebo (42514). It is unclear if the findings of any of these studies are due to glucosamine, chondroitin, other ingredients, or the combination. Despite evidence suggesting differing benefit (89521,94382), head-to-head comparisons of glucosamine sulfate and glucosamine hydrochloride are limited, and it is not universally acknowledged that these salts have different effectiveness profiles. One large clinical study in patients with knee osteoarthritis shows that taking a specific product (Artrolive, Aché Laboratórios Farmacêuticos S.A.) containing glucosamine sulfate 500 mg and chondroitin sulfate 400 mg three times daily for 4 months seems to be no different for reducing pain when compared with taking glucosamine hydrochloride 500 mg and chondroitin sulfate 400 mg (Cosamin DS, Nutramax Laboratories, Inc.) three times daily (89520). This study was funded by the supplement manufacturer. Many meta-analyses have pooled studies of both glucosamine salts together, producing largely inconsistent results (94381,99683,99685,112444). Experts have conflicting stances on the use of glucosamine. The American College of Rheumatology (ACR) strongly recommends against the use of any glucosamine products for any form of osteoarthritis (102114). Conversely, the European Society of Clinical and Economic Aspects of Osteoarthritis (ESCEO) strongly recommends the use of pharmaceutical-grade glucosamine sulfate products, such as Dona (Rotta Pharmaceuticals), in patients with osteoarthritis. Additionally, the ESCEO provides a weak recommendation against the use of glucosamine in combination with chondroitin (102141). These differing recommendations seem to be related to interpretation of the evidence for pharmaceutical-grade products. The ACR has determined that the inconsistent evidence may indicate the presence of industry bias; the ESCEO has determined that the inconsistent evidence is due to inconsistent product quality. Limited research has found mixed benefit of using glucosamine on osteoarthritis of the SPINE, HIP, or HAND. In one study of patients with osteoarthritis of the lumbar spine, taking glucosamine sulfate (Dona, Rotta Pharmaceuticals) 1500 mg daily for 6 weeks reduced pain in more patients when compared with placebo (1316). However, in another study, using a different glucosamine sulfate product (Glucosamine Sulfate, PharmaNord) 1500 mg daily for 6 months did not reduce pain when compared with placebo (89562). In patients with hip osteoarthritis, taking glucosamine sulfate 1500 mg once daily for 2 years did not reduce symptoms or slow disease progression when compared with placebo (16717,20100); however, there was a high rate of hip replacement, which may have confounded results (16717,16718). In patients with erosive osteoarthritis of the hand, observational research has found that taking glucosamine sulfate (Dona, Rotta Pharmaceuticals) 1500 mg daily along with conventional therapy for 6 months is associated with reduced hand pain, a shorter duration of morning stiffness, and improved hand function when compared with conventional therapy alone (108897). Limited research has also evaluated INTRAMUSCULAR and TOPICAL glucosamine sulfate. A clinical study in patients with mild to moderate knee osteoarthritis (radiological stage I-III) shows that giving intramuscular glucosamine sulfate 400 mg twice per week for 6 weeks reduces the severity of symptoms when compared with placebo (2605). There is also a small study showing that a topical preparation of glucosamine sulfate in combination with chondroitin sulfate, shark cartilage, and camphor reduces osteoarthritis symptoms when compared with placebo. However, any symptom relief is most likely due to the counterirritant effect of camphor and not the other ingredients (10327,12467). There is no evidence that glucosamine is absorbed topically. Glucosamine sulfate does not seem to PREVENT osteoarthritis. Clinical studies in overweight healthy females aged 50-60 years shows that taking crystalline glucosamine sulfate 1500 mg orally daily for 2.5 years does not reduce the incidence of osteoarthritis after a 6-7 year follow-up; however, it may reduce the percentage of patients who experience knee joint space narrowing (95789,97053).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. Topical N-acetyl glucosamine has only been evaluated in combination with niacinamide for reducing hyperpigmentation and liver skin spots on aging skin; its effect when used alone is unclear. Details: A clinical study in females ages 40-60 years with skin hyperpigmentation and solar lentigines (liver spots) primarily due to aging and sun exposure shows that applying a cream containing 2% N-acetyl glucosamine and 4% niacinamide to the face twice daily with sunscreen for 10 weeks decreases facial hyperpigmentation when compared with sunscreen alone (92721). The effect of N-acetyl glucosamine alone is unclear.
• Aromatase inhibitor-induced arthralgia. Oral glucosamine sulfate has only been evaluated in combination with chondroitin; its effect when used alone is unclear. Details: A small open-label clinical study in patients with aromatase inhibitor-induced arthralgia shows that taking a combination of glucosamine sulfate 1500 mg and chondroitin sulfate 1200 mg in 2-3 divided doses daily for 24 weeks improves pain when compared to baseline in postmenopausal adults with early stage breast cancer (89561). The validity of this finding is limited by a lack of control group.
• Back pain. Although there is interest in using oral glucosamine for back pain, there is insufficient reliable information about the clinical effects of glucosamine for this condition.
• Cancer. Some low-quality observational studies have inconsistently found that glucosamine may be associated with a lower risk of different cancers; however, better quality evidence is needed. Details: A meta-analysis of observational research has found that use of glucosamine with or without chondroitin is associated with a 7% to 12% lower risk of cancer when compared with no use of glucosamine. A subgroup analysis showed a reduction in the risk of colorectal cancer, but not other types of cancer (110625). Observational research report conflicting relationships between glucosamine and cancer. Some observational research in adults in the United Kingdom has found that taking glucosamine is associated with 4% higher risk of cancer over a median follow up for 13 years. However, a subgroup analysis showed a reduction in the risk of lung cancer (110627). Other observational research in adults in the United Kingdom has found that taking glucosamine is associated with a 5% reduced risk of cancer mortality over a median follow-up of around 12 years, with reductions specifically occurring in those with kidney, lung, and rectal cancers. However, glucosamine use was not linked to a reduced risk of mortality due to bladder, brain, breast, colon, ovarian, prostate, skin, stomach, thyroid, or uterine cancer (109645). Other large, propensity-score-adjusted, observational research in adults with osteoarthritis in the United Kingdom suggests that treatment with glucosamine, with an average of 8 years of follow-up, is not associated with a reduction in cancer, including lung, colorectal, breast, or prostate cancer, when compared with patients not prescribed glucosamine (114571). These studies are limited by observational designs, which also did not clarify the form of glucosamine used, or the dose, frequency, or duration of use. Furthermore, the adults that reported glucosamine use also reported overall healthier lifestyle habits than those that were not taking glucosamine. Although some studies attempted to control for these differences, higher quality, prospective research is needed to clarify the relationship, if any, between glucosamine and the risk for cancer and/or cancer-related mortality. Of note, some researchers have called into question the results from observational research linking glucosamine use to a lower rate of cancer, claiming that these studies suffer from a high risk of selection bias (109646).
• Cardiovascular disease (CVD). It is unclear if oral glucosamine prevents fatal or non-fatal CVD events. Details: Some observational research of adults in the United Kingdom has found that taking glucosamine is associated with an overall 15% reduced risk for fatal and non-fatal CVD events, including coronary heart disease (CHD) and stroke (99682). However, this study did not clarify the form of glucosamine used, or the dose, frequency, or duration of use. Furthermore, the adults that reported glucosamine use also reported overall healthier lifestyle habits than those that were not taking glucosamine. Conversely, an observational study in Chinese patients with osteoarthritis has found that glucosamine use is associated with a 10% increase in the risk of CVD events and a 12% increase in the risk of CHD, with no increase in the risk of stroke. The risk for these outcomes was greatest in patients with higher adherence to glucosamine and in those taking larger doses (109642). However, this study also did not clarify the form of glucosamine used or provide specifics related to the frequency or duration of use. Furthermore, glucosamine users were generally older, more likely to be on antihyperlipidemic or antiplatelet therapy, and more likely to have multiple comorbidities compared with non-users. Both studies attempted to control for the differences in characteristics between glucosamine users and non-users; despite this, higher quality, prospective research is needed to clarify the relationship, if any, between glucosamine and CVD risk.
• Colorectal adenoma. Oral glucosamine has only been evaluated in combination with chondroitin; its effect when used alone is unclear. Details: An observational study in older adults has found that taking glucosamine and chondroitin is associated with a 26% reduced risk of high-risk adenoma and 10% reduced risk of conventional adenoma when compared with not using these supplements. This benefit was not seen in a subgroup of younger females (104444). This study did not clarify the form of glucosamine used, or the dose, frequency, or duration of use.
• Colorectal cancer. It is unclear if oral glucosamine reduces the risk of colorectal cancer. Details: A meta-analysis of observational research has found that use of glucosamine with or without chondroitin is associated with a 7% to 12% lower risk of cancer when compared with no use of glucosamine. A subgroup analysis showed a reduction in the risk of colorectal cancer, but not other types of cancer (110625). However, not all research agrees. A large, observational study in adults has found that regular use of oral glucosamine is not associated with a reduced risk of colorectal cancer over a median of 7 years of follow-up, regardless of sex, age, body mass index, smoking status, or non-steroidal anti-inflammatory drug use (108018). Other large, propensity-score-adjusted, observational research in adults with osteoarthritis in the United Kingdom suggests that treatment with glucosamine, with an average of 8 years of follow-up, is not associated with a reduction in cancer, including colorectal cancer, when compared with patients not prescribed glucosamine (114571).These studies did not clarify the form or dose of glucosamine used or the frequency or duration of use.
• Coronavirus disease 2019 (COVID-19). It is unclear if oral glucosamine is beneficial for COVID-19. Details: A large observational study in adults suggests that regular glucosamine use over a median of 1.7 years is not linked to a lower odds of COVID-19 infection but is associated with a 20% lower risk of hospital admission and a 19% lower risk of mortality due to COVID-19 when compared with adults not using glucosamine (111649). This study did not clarify the form or dose of glucosamine used or the frequency or duration of use.
• Dementia. Observational studies suggest that long-term, regular glucosamine intake might reduce the risk of developing certain types of dementia. Details: An observational study has found that regularly taking glucosamine for an average of 8.9 years is associated with a 19% lower risk of developing dementia, including Alzheimer disease and vascular dementia (110630). Another large observational study in older adults without dementia suggests that regularly taking glucosamine for a median of 12 years is associated with an 18% lower risk of vascular dementia. However, habitual glucosamine consumption is not associated with a reduced risk of Alzheimer disease or frontotemporal dementia (112461).
• Depression. It is unclear if oral glucosamine hydrochloride reduces depression symptoms. Details: A small, open-label clinical trial in patients with unipolar depression shows that taking glucosamine hydrochloride 1 gram daily for 1 week, followed by 2 grams daily for 3 weeks, reduces scores on the Hamilton Rating Scale for Depression (HAM-D) and Montgomery-Asberg Depression Rating Scale (MADRS) by 31% or 33% when compared to baseline. However, only 20% of patients experienced a 50% or greater reduction in HAM-D scores, and there were no improvements in Clinical Global Impression scores (103281). The lack of a control group limits the validity of these findings.
• Diabetes. It is unclear if oral glucosamine reduces the risk of developing type 2 diabetes in adults. Details: Observational research in adults in the United Kingdom has found that glucosamine use is associated with a 17% lower risk of type 2 diabetes. The relationship between glucosamine use and diabetes appears to be even more pronounced in patients with high baseline levels of C-reactive protein, a marker of inflammation (103234). However, this study did not clarify the form of glucosamine used, or the dose, frequency, or duration of use. Furthermore, the adults that reported glucosamine use also reported overall healthier lifestyle habits than those that were not taking glucosamine. Although this study attempted to control for these differences, higher quality, prospective research is needed to clarify the relationship, if any, between glucosamine and the risk for diabetes.
• Gout. It is unclear if oral glucosamine reduces the risk of developing gout. Details: Observational research in adults in the United Kingdom has found that glucosamine use is associated with a 19% lower risk of gout in females, but not males (109644). However, this study did not clarify the form of glucosamine used, or the dose, frequency, or duration of use. Furthermore, the adults that reported glucosamine use also reported overall healthier lifestyle habits than those that were not taking glucosamine. Although this study attempted to control for these differences, higher quality, prospective research is needed to clarify the relationship, if any, between glucosamine and the risk for gout.
• Heart failure. It is unclear if oral glucosamine prevents heart failure. Details: A large, prospective observational study in adults without heart failure suggests that taking glucosamine regularly over a median of 9 years is associated with a 13% lower risk of developing heart failure when compared with adults not taking glucosamine (111646). This study did not clarify the form or dose of glucosamine used or the frequency or duration of use.
• Hyperlipidemia. It is unclear if oral glucosamine hydrochloride improves hyperlipidemia when used with conventional medicine. Details: Preliminary clinical research shows that glucosamine hydrochloride does not reduce cholesterol or triglyceride levels in patients with hyperlipidemia. A small crossover study in older adults taking simvastatin or atorvastatin shows that adding a specific glucosamine hydrochloride product (Artrox, Pfizer) 750 mg twice daily for 4 weeks does not seem to affect lipid levels when compared with placebo (18341).
• Inflammatory bowel disease (IBD). It is unclear if oral or rectal N-acetyl glucosamine improves symptoms of IBD in children. Details: A very small clinical study in children ages 8-17 years with Crohn disease or ulcerative colitis that were unresponsive to conventional treatment suggests that oral or rectal N-acetyl glucosamine 1.5-2 grams in 10 mL water twice daily for 6 weeks might decrease symptoms of IBD when compared with baseline (10234). The validity of this finding is limited by a lack of control group.
• Interstitial cystitis. Oral glucosamine sulfate has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: An open-label clinical study in patients with interstitial cystitis shows that taking a specific product (CystoProtek, Tischon Corporation) containing glucosamine sulfate 120 mg, sodium hyaluronate 10 mg, chondroitin sulfate 150 mg, quercetin 150 mg, and rutin 20 mg per capsule, as two capsules twice daily for 12 months, reduces symptom severity by up to 52% when compared with baseline (42391). The validity of this finding is limited by a lack of control group.
• Joint pain. Oral glucosamine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with joint pain shows that taking capsules of a specific combination product (Instaflex Joint Support, Direct Digital) containing glucosamine sulfate 1500 mg, methylsulfonylmethane 500 mg, white willow bark extract 250 mg, ginger root concentrate 50 mg, Boswellia serrata extract 125 mg, turmeric root extract 50 mg, cayenne 40 m H.U. 50 mg, and hyaluronic acid 4 mg, daily in three divided doses for 8 weeks, reduces joint pain severity by 37% compared to only 16% with placebo. However, the specific combination product does not appear to improve joint stiffness or function compared with placebo (89560).
• Kashin-Beck Disease. It is unclear if oral glucosamine hydrochloride improves Kashin-Beck Disease symptoms such as pain. Details: A small clinical study in Chinese adults with Kashin-Beck Disease shows that taking glucosamine hydrochloride 480 mg three times daily along with chondroitin sulfate 600 mg twice daily for 6 months decreases pain scores by at least 20% to 50% in more patients when compared with placebo. Taking glucosamine alone had a non-significant trend toward pain reduction in these patients (42516). An open-label study in Chinese adults with Kashin-Beck Disease shows that taking glucosamine hydrochloride 750 mg twice daily for 6 weeks seems to be no different for improving pain and physical function when compared with taking to diclofenac 50 mg twice daily or naproxen 300 mg twice daily (18339). The validity of this finding is limited by a lack of blinding.
• Kidney stones (nephrolithiasis). Oral glucosamine might reduce the risk of developing kidney stones. Details: A large observational study in adults without kidney stones suggests that regularly taking glucosamine is associated with a 28% lower risk of new-onset kidney stones in people with a total sedentary time under 3.5 hours daily. This association follows a dose-dependent relationship. However, regular glucosamine use does not seem to reduce the risk of new-onset kidney stones in people with total sedentary time exceeding 3.5 hours daily (112451).
• Knee pain. Small clinical studies suggest that oral glucosamine hydrochloride might improve exercise-induced knee pain and chronic knee pain. However, it is unclear if glucosamine sulfate, N-acetyl glucosamine, or lower doses of glucosamine hydrochloride are beneficial in these patients. Details: A small clinical study in athletes following an acute knee injury shows that taking glucosamine sulfate 500 mg three times daily for 28 days does not improve pain but might modestly improve mobility when compared with placebo (20103). Glucosamine has also been evaluated for chronic knee pain. A small clinical study in patients with chronic knee pain of unclear origin shows that taking glucosamine hydrochloride 2000 mg daily for 12 weeks might modestly improve pain when compared with placebo (10312). However, lower doses of glucosamine hydrochloride and N-acetyl glucosamine used in combination with other ingredients have not demonstrated benefit for chronic knee pain. A small clinical trial in Japanese adults over 40 with knee pain shows that taking a combination supplement with glucosamine hydrochloride and other ingredients for 16 weeks does not improve pain, function, or walking speed when compared with placebo. The combination supplement provided glucosamine hydrochloride 1200 mg, chondroitin sulfate 60 mg, type II collagen peptides 45 mg, quercetin glycosides 90 mg, imidazole peptides 10 mg, and vitamin D 200 IU daily (95784). Another small clinical study in Japanese patients over 50 years of age with chronic knee pain shows that taking a specific supplement (Walker's Glucosamine, Kyowa) containing N-acetyl glucosamine 100 mg and chondroitin sulfate 180 mg daily for 24 weeks does not reduce pain or improve knee function when compared with placebo (95795).
• Metabolic dysfunction-associated steatotic liver disease (MASLD). It is unclear if oral glucosamine is beneficial in patients with MASLD. Details: Observational research in adults with MASLD and type 2 diabetes suggests that regular use of glucosamine orally for an average follow up of 11 years is associated with a lower risk of adverse liver outcomes when compared with those not regularly using glucosamine. Non-users of glucosamine had 35% to 44% higher risk of cirrhosis, encephalopathy, and esophageal varices. This study did not report the glucosamine dose or frequency (114573).
• Multiple sclerosis (MS). It is unclear if oral glucosamine sulfate is beneficial in patients with MS. Details: A small clinical study in patients with MS shows that taking glucosamine sulfate 1000 mg once daily for 6 months modestly reduces relapse when compared to baseline, but not when compared with placebo (20104).
• Overall mortality. It is unclear if oral glucosamine reduces overall mortality. Details: An observational study in the United States has found that regular use of oral glucosamine, with or without chondroitin, for an average of 8 years is associated with a 30% lower risk of mortality when compared with no glucosamine use. However, when adjusted for covariates such as age, body-mass index, and comorbidities, there was no difference in overall mortality (110626). In contrast, a cross-sectional observational study has found that using oral glucosamine and chondroitin for at least one year is associated with 27% reduced incidence of overall mortality and 58% reduced incidence of cardiovascular mortality when compared with not using these supplements (104445). This study did not clarify the form of glucosamine used, or the dose, frequency, or duration of use. Furthermore, the adults that reported glucosamine and chondroitin use also reported overall healthier lifestyle habits than those that were not taking glucosamine and chondroitin. Although this study attempted to control for these differences, higher quality, prospective research is needed to clarify the relationship, if any, with overall mortality. Of note, some researchers have called into question the results from observational research linking glucosamine use to a lower rate of overall mortality, claiming that these studies suffer from a high risk of selection bias (109646).
• Postoperative recovery. It is unclear if oral glucosamine sulfate improves recovery after surgery. Details: A small clinical study in male athletes who have undergone anterior cruciate ligament (ACL) reconstruction shows that taking glucosamine sulfate (Solgar Inc.) 1000 mg daily for 8 weeks does not improve rehabilitation outcomes such as functional ability, pain, and muscular performance when compared with placebo (95584).
• Rheumatoid arthritis (RA). It is unclear if oral glucosamine hydrochloride is beneficial in patients with RA. Details: A small clinical study in patients with RA shows that taking glucosamine hydrochloride tablets (Rohto Pharmaceutical Co.) 500 mg three times daily by mouth for 12 weeks reduces pain, but not the number of painful or swollen joints, when compared with placebo (17407).
• Stroke. It is unclear if oral glucosamine is beneficial for reducing stroke risk. Details: An observational cohort study of adults in the United Kingdom found that taking glucosamine is associated with a modest 9% reduced risk for overall stroke; however, sub-analyses show that glucosamine use is not associated with a reduced risk for fatal or non-fatal stroke, hemorrhagic stroke, or ischemic stroke (99682). This study did not clarify the form of glucosamine used, or the dose, frequency, or duration of use. Furthermore, the adults that reported glucosamine use also reported overall healthier lifestyle habits than those that were not taking glucosamine. A case-control study in Spanish patients found that glucosamine use is associated with 45% lower odds of ischemic stroke when compared with non-use; however, the benefit was only observed in patients taking glucosamine for 1 year or less (109643). This study did not clarify the form of glucosamine used or the dose or frequency of use. Furthermore, patients in the control group were generally healthier and less likely to have a history of cardiovascular disease, diabetes, or hyperlipidemia. Although both studies attempted to control for differences between patient populations, higher quality, prospective research is needed to clarify the relationship, if any, between glucosamine and stroke risk.
• Temporomandibular disorders (TMD). It is unclear if oral glucosamine sulfate is beneficial in patients with temporomandibular joint osteoarthritis. Details: A small and low-quality clinical study in patients with temporomandibular joint osteoarthritis shows that taking glucosamine sulfate 500 mg three times daily for 90 days seems to be no different than taking ibuprofen 400 mg three times daily for relieving pain and improving functional abilities such as chewing, yawning, talking, and laughing (3714). However, another small clinical study in patients with the same condition shows that taking glucosamine sulfate 1200 mg daily for 6 weeks does not improve pain or jaw opening capacity when compared with placebo (20105). Glucosamine sulfate has also been evaluated in combination with chondroitin for this condition. A meta-analysis of two small clinical studies in patients with TMD shows that taking glucosamine sulfate 1500 mg and chondroitin sulfate 1200 mg daily for 2 months does not reduce pain or increase maximum mouth opening when compared with tramadol 50-100 mg daily (109647). Other meta-analyses have reported similar results, however, these analyses may have been inadequately powered to detect a difference between groups (114572). Another small clinical trial in children aged 10-13 years with class II malocclusion shows that application of a specific combination gel product containing glucosamine, chondroitin, and essential oils (Jointace Gel, Vitabiotics) with an expander device, twice daily for 3 months does not improve temporomandibular space measures or pain or tension scores, when compared with placebo (110629).
• Wound healing. Although there is interest in using topical glucosamine for wound healing, there is insufficient reliable information about the clinical effects of glucosamine for this condition. More evidence is needed to rate glucosamine for these uses.

(Read more about GLUCOSAMINE)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Common cold. Preliminary clinical research shows that taking a specific larch arabinogalactan extract (ResistAid, Lonza Ltd.) 4.5 grams daily for 12 weeks does not significantly decrease the number, intensity, or symptoms of common colds when compared with placebo in patients who frequently suffer from colds. However, larch arabinogalactan appears to increase the percentage of patients who experience no cold episodes. About 42% of patients receiving larch arabinogalactan extract had no cold episodes, compared to only 28% of patients receiving placebo (93104).
• Hyperlipidemia. Preliminary clinical research shows that taking larch arabinogalactan 8.4 grams daily for 6 months, or 15-30 grams daily for 6 weeks, does not significantly lower total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein B (apo B), apolipoprotein A-1, body weight, blood pressure, or glucose levels in healthy people (15617,15620). It is not known if larch arabinogalactan lowers lipid levels in patients with hyperlipidemia. More evidence is needed to rate larch arabinogalactan for these uses.

(Read more about LARCH ARABINOGALACTAN)

POSSIBLY EFFECTIVE

• Osteoarthritis. Most clinical research shows that MSM is modestly beneficial when used alone or in combination with other ingredients. Details: Clinical research shows that taking MSM 1.5-6 grams orally in two to three divided doses daily, either alone or in combination with glucosamine, can modestly improve joint function and some symptoms of osteoarthritis such as pain and swelling (12469,14335,17127,19312). However, MSM does not seem to reduce stiffness or total symptom score (14335). Also, some patients may not consider the modest benefit to be clinically significant (17127). Some clinical research has evaluated MSM in combination with other ingredients. One clinical study in adults with knee osteoarthritis shows that taking MSM 500 mg, glucosamine sulfate 1500 mg, and chondroitin sulfate 1200 mg daily for 12 weeks is associated with greater reductions in pain and osteoarthritis scores when compared with glucosamine sulfate and chondroitin sulfate alone (96447). Clinical studies using combination products containing MSM 5 grams daily and boswellic acid 7.2 mg daily with or without vitamin C (Lignisul, Triterpenol; Artosulfur C, Laborest Italia S.p.A), orally for 60 days show reductions in anti-inflammatory drug use, but conflicting results for pain reduction (19313,96446). Also, one small study suggests that taking a combination of MSM with collagen type II, cetyl myristoleate, lipase, vitamin C, turmeric, and bromelain (AR7 Joint Complex, Robinson Pharma) orally for 12 weeks improves scores for joint pain and tenderness, but does not improve X-rays of affected joints (19314).

POSSIBLY INEFFECTIVE

• Chronic venous insufficiency (CVI). Clinical research suggests that topical MSM is not beneficial in CVI. Details: Clinical research shows that topical application of MSM plus EDTA can reduce the circumference of the calf, ankle, and foot in patients with CVI. However, application of MSM alone appears to increase swelling in these patients (19315).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. It is unclear if oral MSM improves the appearance of aging skin to a clinically meaningful extent. Details: Preliminary clinical research shows that taking MSM (OptiMSM, Bergstrom Nutrition) 3 grams daily for 16 weeks improves facial wrinkles associated with aging by a moderate amount when compared with placebo. When compared with baseline, taking MSM 1 gram daily for 16 weeks is as effective as taking 3 grams for reducing fine lines and wrinkles and improving smoothness, radiance, firmness, and elasticity (102000).
• Allergic rhinitis (hay fever). It is unclear if oral MSM is beneficial in patients with allergic rhinitis. Details: Preliminary clinical research shows that taking MSM (OptiMSM 650 mg) 2600 mg orally for 30 days might relieve some symptoms of seasonal allergic rhinitis when compared with baseline (8574). However, this study lacked blinding and a control group, and also did not provide information on severity of symptoms (12000).
• Alzheimer disease. Although there is interest in using oral MSM for Alzheimer disease, there is insufficient reliable information about the clinical effects of MSM for this condition.
• Androgenic alopecia. Although there is interest in using oral and topical MSM for androgenic alopecia, there is insufficient reliable information about the clinical effects of MSM for this condition.
• Aromatase inhibitor-induced arthralgia. Oral MSM has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with estrogen receptor positive (ER+) breast cancer and aromatase inhibitor-induced arthralgia shows that taking a specific combination product (Opera, GAMFARMA s.r.l) containing MSM 200 mg, boswellia 40 mg, alpha-lipoic acid 240 mg, and bromelain 20 mg once daily for 6 months reduces arthralgia intensity when compared to baseline, with around 22% of patients having complete symptom resolution at the end of the study (109570). The validity of these findings is limited by a lack of control group.
• Asthma. Although there is interest in using oral MSM for asthma, there is insufficient reliable information about the clinical effects of MSM for this condition.
• Athletic performance. It is unclear if topical MSM is beneficial for improving athletic performance. Details: A small clinical study in healthy, physically active adults shows that applying a specific cream containing magnesium and MSM (MagPro, Custom Prescription Shoppe) prior to stretching and pedaling on a stationary bicycle does not appear to improve flexibility or endurance when compared with a placebo cream (19317).
• Chemotherapy-induced peripheral neuropathy. Oral MSM has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with chemotherapy-induced peripheral neuropathy shows that taking a specific product (OPERA, GAMFARMA s.r.l.) containing MSM 200 mg, alpha-lipoic acid 240 mg, boswellia 40 mg, and bromelain 20 mg daily for 12 weeks reduces overall pain when compared with baseline (96449). The validity of these findings is limited by the lack of a placebo group. Additionally, it is not clear if benefit is associated with MSM, other ingredients, or the combination.
• Chronic fatigue syndrome (CFS). Although there is interest in using oral MSM for CFS, there is insufficient reliable information about the clinical effects of MSM for this condition.
• Chronic obstructive pulmonary disease (COPD). Although there is interest in using oral MSM for COPD, there is insufficient reliable information about the clinical effects of MSM for this condition.
• Constipation. Although there is interest in using oral MSM for constipation, there is insufficient reliable information about the clinical effects of MSM for this condition.
• Diabetes. Although there is interest in using oral MSM for diabetes, there is insufficient reliable information about the clinical effects of MSM for this condition.
• Dyslipidemia. It is unclear if oral MSM is beneficial for dyslipidemia. Details: A very small clinical study in adults with overweight or obesity shows that taking a specific MSM product (OptiMSM, Bergstrom Nutrition) 3 grams daily for 16 weeks modestly increases high-density lipoprotein (HDL) cholesterol when compared with baseline, but not when compared with placebo. Taking MSM also did not improve total cholesterol, low-density lipoprotein (LDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol, or triglycerides (110572). However, this study may have been underpowered to detect differences between groups.
• Dyspepsia. Although there is interest in using oral MSM for dyspepsia, there is insufficient reliable information about the clinical effects of MSM for this condition.
• Exercise-induced muscle damage. It is unclear if oral MSM is beneficial for preventing exercise-induced muscle damage. Details: Clinical research shows that taking MSM 50 mg/kg in 200 mL water orally daily beginning 10 days prior to a 14-km run can attenuate the increase in creatine kinase (CK) and bilirubin levels caused by exercise-induced muscle damage (19320). However, other clinical research shows that taking MSM (OptiMSM, Bergstrom Nutrition) 3 grams daily beginning 3 weeks prior to a 13.1-mile run and continuing for 2 days after does not reduce muscle or joint pain or alter serum markers of oxidative stress or muscle damage when compared with placebo (96448).
• Hangover. Although there is interest in using oral MSM for hangover, there is insufficient reliable information about the clinical effects of MSM for this condition.
• Hemorrhoids. Topical MSM has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study shows that applying a specific gel containing MSM in combination with hyaluronic acid and tea tree oil (Proctoial, BSD Pharma) for 14 days improves symptoms of hemorrhoids, including pain during defecation, visible bleeding, and inflammation/irritation, when compared with placebo (19318). It is not clear if these effects are due to MSM, the other ingredients, or the combination.
• Insect bite. Although there is interest in using oral MSM for preventing insect bites, there is insufficient reliable information about the clinical effects of MSM for this condition.
• Interstitial cystitis. Although there is interest in using oral MSM for interstitial cystitis, there is insufficient reliable information about the clinical effects of MSM for this condition.
• Knee pain. It is unclear if oral MSM is beneficial for knee pain. Details: A moderate-sized clinical study in healthy adults with mild knee pain shows that taking MSM (OptiMSM, Bergstrom Nutrition) 1000 mg twice daily for 12 weeks modestly improves morning pain and pain while standing but does not benefit nocturnal or movement-associated pain, stiffness, or activities of daily living when compared with placebo (114751).
• Muscle cramps. Although there is interest in using oral MSM for muscle cramps, there is insufficient reliable information about the clinical effects of MSM for this condition.
• Obesity. It is unclear if oral MSM is beneficial for obesity. Details: A very small clinical study in adults with overweight or obesity shows that taking a specific MSM product (OptiMSM, Bergstrom Nutrition) 3 grams daily for 16 weeks does not improve body weight, body mass index, waist circumference, or body composition when compared with placebo. (110572). However, this study may have been underpowered to detect differences between groups.
• Osteoporosis. Although there is interest in using oral MSM for osteoporosis, there is insufficient reliable information about the clinical effects of MSM for this condition.
• Periodontitis. Although there is interest in using topical MSM for periodontitis, there is insufficient reliable information about the clinical effects of MSM for this condition.
• Pneumonia. Although there is interest in using oral MSM for pneumonia, there is insufficient reliable information about the clinical effects of MSM for this condition.
• Postoperative pain. Oral MSM has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients who have undergone arthroscopic rotator cuff repair shows that taking a specific combination product (Tenosan, Agave s.r.l.) containing MSM 550 mg, arginine alpha-ketoglutarate 500 mg, collagen peptides 300 mg, apple and grape polyphenols 125 mg, bromelain 40 mg, and vitamin C 60 mg for 3 months can reduce postoperative pain and slightly improve repair integrity (19322). However, improvement in overall functional outcomes was not observed.
• Rheumatoid arthritis (RA). Although there is interest in using oral and topical MSM for RA, there is insufficient reliable information about the clinical effects of MSM for this condition.
• Rosacea. Oral MSM has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with rosacea shows that topical application of a cream containing silymarin and MSM twice daily for one month improves skin redness, papules, itching, hydration, and skin color when compared to baseline (19319). The validity of these findings is limited by the lack of a comparator group.
• Scleroderma. Although there is interest in using oral and topical MSM for scleroderma, there is insufficient reliable information about the clinical effects of MSM for this condition.
• Stretch marks (striae distensae). Although there is interest in using topical MSM for stretch marks, there is insufficient reliable information about the clinical effects of MSM for this condition.
• Systemic lupus erythematosus (SLE). Although there is interest in using oral MSM for SLE, there is insufficient reliable information about the clinical effects of MSM for this condition.
• Temporomandibular disorders (TMD). Although there is interest in using oral MSM for TMD, there is insufficient reliable information about the clinical effects of MSM for this condition.
• Tendinopathy. Oral MSM has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with Achilles tendinopathy shows that taking two sachets orally daily of a specific combination product (Tenosan, Agave s.r.l.) each containing MSM 550 mg, arginine alpha-ketoglutarate 500 mg, collagen peptides 300 mg, apple and grape polyphenols (Vinitrox) 125 mg, bromelain 50 mg, and vitamin C 60 mg for 60 days might improve the outcomes of extracorporeal shock wave therapy (ESWT) (19321). However, it is unclear if any benefit is due to MSM, other ingredients, or the combination.
• Wound healing. Although there is interest in using topical MSM for wound healing, there is insufficient reliable information about the clinical effects of MSM for this condition. More evidence is needed to rate MSM for these uses.

(Read more about METHYLSULFONYLMETHANE (MSM))

LIKELY SAFE ...when used orally in amounts typically found in foods (11). There is insufficient reliable information available about the safety of algin when used orally in medicinal amounts.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about ALGIN)

LIKELY SAFE ...when the seed is used orally in the amounts commonly found in food (11). Ambrette has Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of ambrette when used orally or topically in medicinal amounts.

PREGNANCY:
Insufficient reliable information available; avoid using.

LACTATION: POSSIBLY UNSAFE
when used orally or topically. Ambrette passes into mother's milk (6), but the effect is unknown.

(Read more about AMBRETTE)

POSSIBLY SAFE ...when used orally and appropriately, short-term. D-mannose 3 grams daily for up to 2 weeks or 2 grams daily for up to 6 months has been used with apparent safety in clinical research (91141,93883,99656). There is insufficient reliable information available about the safety of taking D-mannose long-term.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately in children with carbohydrate-deficient glycoprotein syndrome type 1b. D-mannose 300-1020 mg/kg daily, taken in 3-6 divided doses, has been used with apparent safety, long-term (13345,13346,13348,100978,100979,100980,100981). While total daily doses up to 1020 mg/kg have been used safely when taken in divided doses, single doses greater than 200 mg/kg are more likely to cause osmotic diarrhea (100977). There is insufficient reliable information available about the safety of using D-mannose in children with other conditions.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about D-MANNOSE)

POSSIBLY SAFE ...when applied topically to the skin. A gel containing 1% Fucus vesiculosus extract, applied to the skin twice daily, has been used in clinical research with apparent safety for up to 5 weeks (12799).

POSSIBLY UNSAFE ...when used orally due to its iodine content and possible heavy metal content. Fucus vesiculosus contains up to 0.05% iodine or 226 mcg/gram dry weight (12789,74217). Ingesting more than 150 mcg of iodine daily can cause hyperthyroidism or exacerbate existing hyperthyroidism (12788). Fucus vesiculosus can also contain heavy metals, including cadmium, arsenic, and lead, and can cause heavy metal nephropathy (12789,12800,74213).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally because it may contain iodine and heavy metals (12789,74213,74217); avoid using.

(Read more about FUCUS VESICULOSUS)

LIKELY SAFE ...when glucosamine sulfate is used orally and appropriately. Glucosamine sulfate has been used safely in multiple clinical trials at a dose of 1000-1500 mg daily for 4 weeks to 3 years (2604,7026,8942,11340,12461)(14305,16717,89558,89567,94380,94382,95785).

POSSIBLY SAFE ...when glucosamine hydrochloride is used orally and appropriately. Glucosamine hydrochloride has been used with apparent safety at a dose of 1400-1600 mg daily for up to 2 years (4237,13579,14809,18344,42477,89516,89519,95784). Glucosamine hydrochloride 2 grams daily has also been used with apparent safety for up to 3 weeks (103281). ...when N-acetyl glucosamine is used orally and appropriately. N-acetyl glucosamine 100 mg daily has been used with apparent safety for up to 24 weeks (95795). ...when N-acetyl glucosamine is applied topically and appropriately. A 2% N-acetyl glucosamine cream has been safely used for up to 10 weeks (92721). ...when N-acetyl glucosamine is used rectally and appropriately. N-acetyl glucosamine 3-4 grams daily in 2 divided doses has been safely used (10234). ...when glucosamine sulfate is used intramuscularly and appropriately, short-term. Intramuscular glucosamine sulfate seems to be well tolerated when given twice weekly for up to 6 weeks (2605).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about GLUCOSAMINE)

LIKELY SAFE ...when used orally in amounts found in foods. Larch arabinogalactan has Generally Recognized As Safe (GRAS) status in the US (3529).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Larch arabinogalactan has been safely used at doses of 1.5-8.4 grams daily for up to 6 months (15617,15618,17370,93102,93104,104281). Higher doses of 15-30 grams daily have been used with apparent safety for up to 6 weeks (15620). There is insufficient reliable information available about the safety of larch arabinogalactan when used long-term.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about LARCH ARABINOGALACTAN)

POSSIBLY SAFE ...when used orally and appropriately, short term. MSM in doses of 1.5-6 grams daily or 50 mg/kg daily has been used safely in studies lasting up to 6 months (8574,12469,14335,17127,19312,96446,96448,102555). One specific product (OptiMSM, Bergstrom Nutrition) is Generally Recognized As Safe (GRAS) by the United States Food and Drug Administration (FDA) (102555). ...when used topically. Topical cream containing MSM and silymarin, as well as topical gel containing MSM, hyaluronic acid, and tea tree oil, have been used with apparent safety for up to 20 days (19318,19319).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about METHYLSULFONYLMETHANE (MSM))

(Read more about ALGIN)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of ambrette with antidiabetes drugs might increase the risk of hypoglycemia.  Details Animal research shows that myricetin, a constituent of ambrette, can lower blood glucose levels (31096,31097,31098,93700).

(Read more about AMBRETTE)

(Read more about D-MANNOSE)

AMIODARONE (Cordarone) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, combining Fucus vesiculosus with amiodarone might cause excessively high iodine levels.  Details Fucus vesiculosus contains high concentrations of iodine (7135). Amiodarone contains 37.3% iodine and can increase iodine levels. Concomitant use might increase the risk of having excessive iodine levels and adversely affecting thyroid function (7135,17574). Monitor thyroid function.

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, taking Fucus vesiculosus with antiplatelet or anticoagulant drugs might increase the risk of bruising and bleeding.  Details In vitro evidence suggests that a constituent of Fucus vesiculosus, known as fucoidan, has anticoagulant effects (12797,74149,74183,74240). However, in clinical research, fucoidan does not seem to have significant anticoagulant activity when taken orally, possibly due to poor absorption (74183).

ANTITHYROID DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Due to its iodine content, Fucus vesiculosus might alter the effects of antithyroid drugs.  Details Fucus vesiculosus contains high concentrations of iodine (7135). Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Taking Fucus vesiculosus while using antithyroid drugs could alter the effects of the antithyroid drugs (2138,17574).

CYTOCHROME P450 2C8 (CYP2C8) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of Fucus vesiculosus with CYP2C8 substrates might increase the risk for adverse effects.  Details In vitro research shows that fucoidan, a constituent of Fucus vesiculosus, inhibits CYP2C8 (97791). This interaction has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of Fucus vesiculosus with CYP2C9 substrates might increase the risk for adverse effects.  Details In vitro research shows that fucoidan, a constituent of Fucus vesiculosus, inhibits CYP2C9 (97791). This interaction has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of Fucus vesiculosus with CYP2D6 substrates might alter the effects of these substrates.  Details In vitro research shows that fucoidan, a constituent of Fucus vesiculosus, both inhibits and induces CYP2D6 (97791). This interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of Fucus vesiculosus with CYP3A4 substrates might increase the risk for adverse effects.  Details In vitro research shows that fucoidan, a constituent of Fucus vesiculosus, inhibits CYP3A4 (97791). This interaction has not been reported in humans.

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Concomitant use of Fucus vesiculosus and lithium has resulted in hyperthyroidism.  Details There is a case of hyperthyroidism occurring in a patient taking Fucus vesiculosus and lithium (74217). Monitor thyroid hormones closely in patients taking lithium and Fucus vesiculosus concomitantly.

THYROID HORMONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Due to its iodine content, Fucus vesiculosus might alter the effects of thyroid hormone.  Details Fucus vesiculosus contains high concentrations of iodine (7135). Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Taking Fucus vesiculosus while using thyroid hormone could alter the effects of thyroid hormone.

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ACETAMINOPHEN (Tylenol, others) Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = B Acetaminophen might interfere with the activity of glucosamine sulfate by interacting with the sulfate portion.  Details Anecdotal reports suggest that adding glucosamine to an acetaminophen regimen might decrease pain control in patients with osteoarthritis (14806). Some research suggests that the sulfate portion of glucosamine sulfate might contribute to its effect in osteoarthritis. Since acetaminophen metabolism requires sulfur and reduces serum sulfate concentrations, acetaminophen could theoretically interfere with the action of glucosamine sulfate. Conversely, the administration of sulfate could theoretically decrease the effectiveness of acetaminophen in sulfate-deficient people by increasing its clearance (10313).

ANTIDIABETES DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Despite initial concerns, it is unlikely that glucosamine will interfere with the effects of antidiabetes drugs.  Details In vitro and animal research has suggested that glucosamine might increase insulin resistance or decrease insulin production (371,372,3406,18342,18343). This has raised concerns that taking glucosamine might worsen diabetes and decrease the effectiveness of diabetes drugs. However, clinical research suggests that glucosamine does not have adverse effects on blood glucose or glycated hemoglobin (HbA1C) in healthy, obese, or type 2 diabetes patients (7026,7075,8942,10311,10317,15111).

TOPOISOMERASE II INHIBITORS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically glucosamine may induce resistance to topoisomerase II inhibitors.  Details In vitro research suggests that glucosamine might induce resistance to etoposide (VP16, VePesid) and doxorubicin (Adriamycin) by reducing inhibition of topoisomerase II, an enzyme required for DNA replication in tumor cells (7639). This effect has not been reported in humans.

WARFARIN (Coumadin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Glucosamine might increase the anticoagulant effects of warfarin and increase the risk of bruising and bleeding.  Details In two individual case reports, glucosamine/chondroitin combinations were associated with a significant increase in international normalized ratio (INR) in patients previously stabilized on warfarin (11389,16130). In one case, the increase in INR occurred only after tripling the dose of a glucosamine/chondroitin supplement from 500 mg/400 mg daily to 1500/1200 mg daily (16130). Additionally, 20 voluntary case reports to the U.S. Food & Drug Administration (FDA) have linked glucosamine plus chondroitin with increased INR, bruising, and bleeding in patients who were also taking warfarin (16130). There have also been 20 additional case reports to the World Health Organization (WHO) that link glucosamine alone to increased INR in patients taking warfarin (16131). The mechanism of this interaction is unclear. Glucosamine is a small component of heparin, but is not thought to have anticoagulant activity; however, animal research suggests that it might have antiplatelet activity (16131).

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General ...Orally, algin is well tolerated in amounts typically found in foods (11). No adverse effects related to medicinal amounts of algin have been reported. However, a thorough evaluation of safety outcomes has not been conducted.

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General ...There is currently a limited amount of information on the adverse effects of ambrette. A thorough evaluation of safety outcomes has not been conducted.

Dermatologic ...Topically, ambrette has been reported to cause contact dermatitis and photosensitivity (6,31100).

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General ...Orally, D-mannose seems to be well tolerated.
Most Common Adverse Effects:
Orally: Bloating, diarrhea, and nausea.

Gastrointestinal ...Orally, D-mannose can cause loose stools, diarrhea, abdominal bloating, and nausea (13344,91141,100979,100981,104209). In children, loose stools and abdominal bloating have been reported at D-mannose doses ranging from 100 mg/kg three times daily to 150 mg/kg five times daily (13344,100979). Diarrhea has been reported in adults taking D-mannose 2 grams daily for 6 months (91141). While diarrhea and loose stools have been reported at lower doses, taking a single D-mannose dose greater than 200 mg/kg is more likely to cause osmotic diarrhea (100977).

Renal ...Orally, there is concern that excessive doses (toxic amounts unspecified) of D-mannose might be toxic to the kidneys (13348).

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General ...When used orally, Fucus vesiculosus may be unsafe due to its iodine content. Topically, Fucus vesiculosus appears to be well tolerated.
Most Common Adverse Effects:
Orally: Goiter, hyperthyroidism, hypothyroidism.
Serious Adverse Effects (Rare):
Orally: Thyroid cancer.

Cardiovascular ...In one report, a young adult with obesity developed palpitations and syncope after taking an oral weight loss supplement containing a combination of Fucus vesiculosus, dandelion, and boldo for 3 weeks. The patient was found to have a prolonged QT interval on ECG and frequent episodes of sustained polymorphic ventricular tachycardia (14321). It is not clear whether Fucus vesiculosus, another ingredient, or the combination of ingredients is responsible for this adverse effect. The product was not analyzed to determine the presence of any potential toxic contaminants.

Endocrine ...Orally, Fucus vesiculosus can cause or exacerbate hyperthyroidism due to its high iodine content (12789,13061,74217). One case of hyperthyroidism has been reported for a 60-year-old patient taking lithium for bipolar disorder and a combination product containing Fucus vesiculosus 0.125 grams, cascara 0.170 grams, and Frangula 0.222 grams per tablet for laxative purposes. The patient had been taking one tablet of the combination laxative product daily for several years. Following discontinuation of the supplement, thyroid levels normalized (74217). Similar cases of hyperthyroidism have been reported for patients taking other seaweed-containing herbal supplements (Dream Shape; Ever Youth). Analyses of these supplements shows that these products contain triiodothyronine 1 mcg and thyroxine 3-4 mcg. In addition to seaweed, Dream Shape also contains hydrangea vine, maltose, chrysanthemum, Chinese matrimony vine, and sucrose, while Ever Youth contains radish, lotus leaf, chrysanthemum, hawthorn, senna tea, and Chinese matrimony vine (13061).
Orally, prolonged use of Fucus vesiculosus has been associated with hypothyroidism (13664). The iodine in Fucus vesiculosus can cause idiosyncratic reactions.
According to the Institute of Medicine Food and Nutrition Board, prolonged, high dietary intake of iodine is associated with goiter and an increased risk of thyroid cancer (7135).

Genitourinary ...A case of hemorrhagic cystitis characterized by dysuria and polyuria has been reported in a young adult who took a specific product (Slim-Kombu, Balestra and Mech) containing Fucus vesiculosus and 19 other herbal extracts orally for weight loss. Upon discontinuation, symptoms improved (46959). It is unclear if this effect was due to Fucus vesiculosus or other ingredients in the supplement.

Renal ...A case of hemorrhagic cystitis characterized by dysuria and polyuria has been reported in a young adult who took a specific product (Slim-Kombu, Balestra and Mech) containing Fucus vesiculosus and 19 other herbal extracts orally for weight loss. Upon discontinuation, symptoms improved (46959). It is unclear if this effect was due to Fucus vesiculosus or other ingredients in the supplement. Nephrotoxicity has been associated with oral intake of Fucus vesiculosus that was contaminated with arsenic (12800).

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General ...Orally, all forms of glucosamine seem to be well tolerated. Topically and rectally, N-acetyl glucosamine also seems to be well tolerated. Intramuscularly, glucosamine sulfate seems to be well tolerated. However, a thorough evaluation of safety outcomes has not been conducted for non-oral routes of administration.
Most Common Adverse Effects:
Orally: Bloating, constipation, cramps, diarrhea, heartburn, nausea.
Serious Adverse Effects (Rare):
Orally: There have been rare reports of severe allergic reactions and hepatotoxicity.

Cardiovascular ...One case of mesenteric occlusion in a clinical trial was considered possibly related to use of oral glucosamine hydrochloride and chondroitin sulfate (89520).
Some observational research has found that glucosamine use in patients with osteoarthritis is associated with a higher risk of cardiovascular disease (CVD) events when compared with non-use (109642). However, glucosamine users tended to be older, have multiple comorbidities, and be on antihyperlipidemic or antiplatelet therapy. Furthermore, other observational research in healthy adults has found that glucosamine use is associated with a reduced risk of fatal and non-fatal CVD events (99682). Higher quality, prospective research is needed to clarify the relationship, if any, between glucosamine and CVD risk.

Dermatologic ...Orally, glucosamine might cause skin reactions, including itching, rash, and erythema (2608,20084,89567,110628,113636). Also, fingernail and toenail toughening, with an increased rate of growth, has been reported (89572). Topically, N-acetyl glucosamine 2% with niacinamide 4% cream might cause rare skin reactions (92721). Photosensitization that was reproducible with re-challenge was reported in a case report of an individual using glucosamine (form unknown) and chondroitin (10408).

Endocrine ...Orally, glucosamine does not seem to impact blood glucose. Preliminary research and anecdotal reports have found that various forms of glucosamine might increase insulin resistance or decrease insulin production, increasing fasting plasma glucose levels (22,371,372,1203,3406,5059,7637,14810). This has raised concerns that taking glucosamine sulfate might worsen diabetes and decrease the effectiveness of diabetes drugs. However, clinical research suggests that various forms of glucosamine do not have adverse effects on blood glucose or glycated hemoglobin (HbA1C) in healthy, obese, patients with type 2 diabetes or impaired glucose tolerance (7026,7075,7638,8942,10311,10317,12107,14808,15111,89563).

Gastrointestinal ...Orally, glucosamine has been associated with gastrointestinal problems, including epigastric and abdominal pain, cramps, heartburn, diarrhea, nausea, dyspepsia, vomiting, constipation, and flatulence (1520,2608,16717,20084,20104,20105,89561,89562,89567,89568)(108897,110628,111647,113636). In older persons, use of glucosamine sulfate is associated with oral dryness (89564). In a clinical trial, a case of Helicobacter pylori gastritis was considered probably related to the use of glucosamine hydrochloride (89516).

Hepatic ...Although relatively uncommon, combinations of glucosamine and chondroitin sulfate have been associated with acute liver injury that mimics autoimmune hepatitis. Of 151 patients at an outpatient clinic for liver diseases, 23 acknowledged use of products containing glucosamine (form unspecified) and/or chondroitin. However, only 2 cases had an apparent relationship between transaminase elevation and the use of recommended doses of glucosamine and chondroitin sulfate. Aminotransferase levels, which were increased by four- to seven-fold, returned to normal following discontinuation of treatment (89515). In another case, a 65-year-old male presented to the hospital with signs and symptoms of drug-induced autoimmune hepatitis. The patient had used Condrosulf, containing chondroitin sulfate, for two years, followed by Vita Mobility Complex, containing chondroitin sulfate and glucosamine sulfate, for 8 weeks. The patient required maintenance treatment with azathioprine to remain in remission (89518). A case of acute cholestatic hepatitis due to Glucosamine Forte, which contains glucosamine hydrochloride, chondroitin sulfate, Devil's claw, and shark cartilage, has been reported (89522). It is unclear whether these adverse events were related to glucosamine, other ingredients, or the combination.

Immunologic ...There is some concern that glucosamine products might cause allergic reactions in sensitive individuals. One review of glucosamine-related adverse events in Australia found that 72% of all reports involved hypersensitivity reactions. Of these reactions, 35% were mild, including pruritis, urticaria, and lip edema, 49% were moderate, including dyspnea, and 16% were severe, including gait disturbance, somnolence, and hypotension. Anaphylaxis was reported in 1.5% of cases (102115). Also, in one clinical trial, a single patient developed allergic dermatitis considered to be likely due to glucosamine hydrochloride (89516). Glucosamine is derived from the exoskeletons of shrimp, lobster, and crabs. However, it is unclear if these adverse reactions were due to a shellfish sensitivity or general atopy. Additionally, shellfish allergies are caused by IgE antibodies to antigens in the meat of shellfish, not to antigens in the exoskeleton. Regardless, it is possible that some glucosamine products might be contaminated by this allergen during production (102115).

Neurologic/CNS ...Orally, glucosamine has been reported to cause drowsiness and headache (2608,89561,113636). Glucosamine plus chondroitin combination products that also contain manganese (e.g., CosaminDS) should always be taken according to product directions. When taken at doses slightly higher than the recommended dose, these products can sometimes supply greater than the tolerable upper limit (UL) for manganese which is 11 mg/day. Ingestion of more than 11 mg/day of manganese might cause significant central nervous system toxicity (7135).

Ocular/Otic ...In older persons, use of glucosamine sulfate has been associated with ocular dryness (89564). Increased intraocular pressure has occurred with glucosamine sulfate supplementation (89573,112460). Data from the FDA MedWatch adverse event reporting system shows that 0.21% of subjects taking glucosamine reported glaucoma, which is significantly greater than the 0.08% of subjects who reported glaucoma while using any other drug (112460).

Pulmonary/Respiratory ...Cases of asthma exacerbations associated with the use of glucosamine (form unknown)-chondroitin products have been reported (10002).

Renal ...Anecdotal reports have associated glucosamine with nephrotoxicity signals such as modestly elevated creatine phosphokinase and 1+ to 2+ proteinuria, but changes in kidney function have not been reported in long-term studies (7026,8942,10408,10409). It was also noted that effects may have been due to other concurrent medications or impurities in glucosamine-chondroitin products. Cases of acute interstitial nephritis induced by glucosamine (form unknown) have also been reported (89523).

Other ...There has been concern that glucosamine might increase the risk of metabolic disturbances resulting in increased cholesterol levels and blood pressure. However, glucosamine does not appear to increase the risk of these adverse effects. Taking glucosamine sulfate for up to 3 years does not significantly increase blood glucose or lipid levels, or cause any other disturbances in metabolism (7026,7075,8942,10311,10317).

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General ...Orally, larch arabinogalactan is generally well tolerated (3530,17370,93102). Some people can experience bloating and flatulence (3530).

Gastrointestinal ...Orally, larch arabinogalactan can cause bloating and flatulence (3530).

(Read more about LARCH ARABINOGALACTAN)

General ...Orally, MSM is generally well tolerated.
Most Common Adverse Effects:
Orally: Bloating, diarrhea, gastrointestinal discomfort, nausea.

Dermatologic ...In rare cases, MSM has caused pruritus when taken orally (8574).

Gastrointestinal ...Orally, MSM may cause mild gastrointestinal discomfort, nausea, bloating, and diarrhea (8574,12469).

Immunologic ...Orally, MSM may increase allergy symptoms (8574).

Neurologic/CNS ...Orally, MSM may cause headache, fatigue, insomnia, and difficulty concentrating (8574,14335).

Ocular/Otic ...In a case report, a 35-year-old female presented with bilateral acute angle closure glaucoma, which resolved 4 days after discontinuing a multi-ingredient product. Although the product contained over 35 vitamins, minerals, and other ingredients, only MSM contained sulfur, which the authors suggest acted like a sulfa-drug to cause acute angle closure glaucoma (90613).

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