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Osteoarthritis. Oral Boswellia serrata extracts, taken alone or in combination with other ingredients, appear to reduce pain and stiffness and improve function in knee osteoarthritis. However, most clinical studies have been small and of relatively short duration. Details: A meta-analysis of 11 moderate- to lower-quality clinical studies in adults with knee osteoarthritis shows that taking an herbal formulation containing Boswellia (15-600 mg daily) or a Boswellia extract exclusively (100-1000 mg daily) for 1 to 8 months does not improve subjective scores evaluating pain, stiffness, and physical function when compared with a control such as glucosamine sulfate or valdecoxib. However, sub-group analyses show improvement in pain, stiffness, and functionality with an herbal formulation containing Boswellia compared with placebo, although the clinical significance is unclear (115731). The validity of these results are limited due to the lack of data on the herbal formulations. A similar meta-analysis including 7 of the same clinical studies plus 2 other, higher quality clinical studies shows that taking Boswellia serrata extract reduces pain and stiffness and improves function when compared with placebo (114684). Furthermore, individual trials, some included in the meta-analyses above, have shown similar results with specific Boswellia serrata supplements or extracts including 5-Loxin, Aflapin, Boswellin, Wokvel, and Boswellin Super (109564,100699,12432,103784,115735). Several studies also show that taking specific combination products containing Boswellia serrata and other ingredients can improve pain and functionality in patients with osteoarthritis. These products have combined Boswellia serrata 100 mg with ashwagandha 450 mg, turmeric 50 mg, and zinc complex 50 mg (Articulin-F) three times daily for 3 months (19276); Boswellia serrata 100 mg with ginger 33.33 mg, Tinospora cordifolia 73.33 mg, and Indian gooseberry 166.66 mg three times daily for 6 months (89557); a specific Boswellia serrata extract (BosPure, Arjuna Natural Extracts Ltd) 300 mg with turmeric extract (BCM 95, Arjuna Natural Extracts Ltd) 700 mg daily for 12 weeks (89719); boswellic acid 7.2 mg (from Boswellia serrata) with methylsulfonylmethane 5 grams and vitamin C daily for 2 months (96446); and a specific combination product (Tregocel, Max Biocare) providing Boswellia serrata extract 1 gram, curcumin 100 mg, devil's claw tuber 1 gram, celery seed 1 gram, and ginger rhizome 330 mg daily for 36 weeks (106078). However, research in patients with osteoarthritis of the hand suggests that taking a combination of Boswellia serrata extract 250 mg, pine bark extract 100 mg, methylsulfonylmethane 1500 mg, and curcumin 168 mg daily for 12 weeks does not improve pain or functionality (109563).

Allergic rhinitis (hay fever). Although there is interest in using oral Boswellia serrata for hay fever, there is insufficient reliable information about the clinical effects of Boswellia serrata for this condition.
Alzheimer disease. It is unclear if oral Boswellia serrata improves cognitive function in patients with Alzheimer disease. Details: A small clinical study in adults with mild to moderate Alzheimer disease shows that taking a specific Boswellia serrata extract (K-Vie, Kondor Pharma) 1200 mg daily for 6 months improves neuropsychiatric symptoms, dementia severity, and some but not all measures of cognitive function when compared with placebo (112807).
Aromatase inhibitor-induced arthralgia. Oral Boswellia serrata 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 Srl) containing Boswellia serrata 40 mg, alpha-lipoic acid 240 mg, methylsulfonylmethane 200 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. It is unclear if oral Boswellia serrata can improve symptoms of asthma. Details: One small preliminary clinical study in patients with asthma suggests that taking a specific Boswellia serrata gum resin (S-compound, Rahul Pharma) 300 mg three times daily for 6 weeks may improve symptoms of asthma, such as forced expiratory volume (FEV), the number of asthma attacks, and dyspnea and rhonchi, in 70% of patients, compared to only 27% of patients in a control group (1708).
Brain tumor. It is unclear if oral Boswellia serrata improves outcomes in patients with brain tumors. Details: One small clinical study in adults with brain tumors undergoing radiation therapy shows that taking an H15 Boswellia serrata extract 4200 mg in three divided doses daily throughout radiotherapy reduces cerebral edema and tumor volume, but not dexamethasone dosage, when compared with placebo (21149).
Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS). Rectal Boswellia serrata has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Two small, open-label clinical studies in males with prostatitis-like symptoms or CP/CPPS types IIIa or IIIb shows that rectal administration of a specific suppository containing Boswellia serrata resin extract and propolis polyphenols (MICTALASE) once daily for 20 days or once daily for 15 days per month for 3 months improves pain, urinary symptoms, quality of life, and total symptom scores, as measured by the Chronic Prostatitis Symptom Index (CPSI), when compared to baseline. However, there were no improvements in scores on the International Index of Erectile Dysfunction (IIED), and studies showed mixed findings regarding improvements on the International Prostate Symptoms Score (IPSS) (102091,109566). The validity of these results is limited by the lack of a comparator group.
Cluster headache. Although there is interest in using oral Boswellia serrata for cluster headache, there is insufficient reliable information about the clinical effects of Boswellia serrata for this condition.
Coronavirus disease 2019 (COVID-19). Oral Boswellia serrata has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults hospitalized with moderate COVID-19 infection in Egypt shows that taking Boswellia serrata extract 300 mg and licorice extract 300 mg twice daily for 14 days, along with conventional therapy, reduces the risk of death, shortens the time to hospital discharge by around 5.5 days, and reduces the rate of mechanical ventilation when compared with placebo. For every five patients treated with this combination product, one additional patient survived. The standard treatments administered in this study included azithromycin, vitamin C, and zinc (108579). Another large clinical study in adults hospitalized with moderate COVID-19 infection in India shows that taking a specific product containing Boswellia serrata, ashwagandha, ginger, and turmeric (Artovid-20, Bioved Pharmaceuticals, Inc) 1,776 mg twice daily after meals for 14 days, starting within 48-96 hours of symptom onset along with conventional therapy, decreases the duration of illness by about 1 day and reduces patient-assessed severity scores of various symptoms (e.g. nasal congestion, sore throat, cough, taste and smell disorders) when compared with placebo. Almost all patients in this study also received steroids, and over 50% received remdesivir. Study results were similar in the subgroup of patients who received remdesivir (109899). However, the validity of this study is limited by use of data only from patients who fully adhered to the study protocol per protocol analysis and exclusion of patients with risks for progression to severe COVID-19, including uncontrolled hypertension, asthma, chronic obstructive pulmonary disease, diabetes, obesity, or immunocompromise.
Crohn disease. It is unclear if oral Boswellia serrata reduces relapse rates in patients with Crohn disease. Details: One small clinical study in patients with Crohn disease who are in remission shows that taking Boswellia serrata (Boswelan, Pharmasan) 800 mg orally three times daily for one year does not decrease relapse rates or improve quality of life when compared with placebo (17241).
Diabetes. It is unclear if oral Boswellia serrata improves glycemic control in patients with diabetes. Details: A meta-analysis of five moderate- to low-quality studies in adults with type 2 diabetes shows that taking Boswellia gum resin 500 -900 mg daily or Boswellia powder 1200 mg daily for 6-12 weeks reduces glycated hemoglobin (HbA1C) but not fasting blood glucose when compared with placebo or no treatment. Additionally, triglycerides were reduced, but other lipid parameters were not improved (115732). A smaller meta-analysis pooling the results of two trials included in the previously described meta-analysis shows that Boswellia serrata reduces HbA1c by about 0.5% and fasting blood glucose by about 24 mg/dL, with no improvement in lipid levels, when compared with placebo (111503). Overall, the validity of these findings is limited by heterogeneous methods between clinical trials, such as treatment dose and duration, and the lack of data regarding other medications used for diabetes.
Diarrhea. It is unclear if oral Boswellia serrata is beneficial in patients with acute diarrhea. Details: A small clinical study in adults with acute diarrhea shows that taking a specific lecithin-based delivery form of Boswellia serrata extract (Casperome, Indena S.p.A.) 250 mg twice daily for 5 days decreases the time to diarrhea resolution by nearly 1.4 days, reduces stool frequency, and improves symptoms of abdominal pain and nausea when compared with placebo (109568).
Dysmenorrhea. Oral Boswellia serrata has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with moderately painful dysmenorrhea shows that taking a single dose of a combination product containing Boswellia serrata, turmeric, and sesame (Rhuleave-K, Arjuna Natural Private Ltd.) 1000 mg at the start of menstruation relieves menstrual cramp pain and reduces pain intensity for up to 6 hours when compared with placebo (112806). It is unclear if these effects are due to Boswellia serrata, other ingredients, or the combination.
Exercise-induced muscle soreness. Oral Boswellia serrata has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in healthy active adults with moderate to severe exercise-induced muscle pain shows that taking a single, 1000-mg dose of Boswellia serrata and turmeric extracts in black sesame oil (Rhuleave-K; Arjuna Natural Private Ltd.) improves pain relief when compared with placebo, with maximal benefits within about 3 hours. The number of people needed to treat to obtain pain relief of at least 50% over a 6-hour period was 1.1 (109277).
Irritable bowel syndrome (IBS). Small clinical studies suggest that an oral Boswellia serrata extract may improve symptoms of IBS. Details: A small clinical study in patients with mild IBS shows that taking a specific lecithin-based delivery form of Boswellia serrata extract (Casperome, Indena S.p.A.) 250 mg daily for 6 months reduces abdominal pain, cramps, and gas when compared with standard management with hyoscine butylbromide or papaverine hydrochloride plus belladonna extract 10 mg. Patients receiving Casperome required fewer rescue medications and had a 46% lower risk of needing additional medical care, including hospitalization (100713). In a short-term clinical trial of the same Boswellia serrata extract 250 mg daily for 4 weeks, the risk for requiring additional medical care was reduced by 67% when compared with the same standard treatment options above. While IBS symptoms improved over baseline, significant differences between Casperome and standard treatment options were lacking (102089). These studies were funded by the supplement manufacturer, which may limit the reliability of these findings.
Knee pain. It is unclear if oral Boswellia serrata is beneficial for knee pain. Details: A small clinical study in otherwise healthy adults with knee pain shows that taking Boswellia serrata extract 12.5% tablets twice daily for 8 weeks improves physical function and pain but not stiffness, functional mobility, muscle function, or level of physical activity when compared to baseline (112808).
Menorrhagia. It is unclear if oral Boswellia serrata is beneficial for menorrhagia. Details: A small clinical study in otherwise healthy adults with menorrhagia shows that taking Boswellia serrata oleoresin powder 300 mg three times daily for 7 days, repeated over 2 menstrual cycles, improves quality of life and modestly reduces the average duration of menstrual bleeding after the second cycle when compared with placebo. All patients were permitted to use ibuprofen 200 mg as needed (105401).
Microscopic colitis. There is limited evidence on the oral use of Boswellia serrata in patients with collagenous colitis. Details: One small clinical trial shows that taking Boswellia serrata extract 400 mg three times daily for 6 weeks increases the clinical remission rate by 64% when compared with placebo in patients diagnosed with a type of microscopic colitis called collagenous colitis. Clinical remission was defined as having an average of three or fewer soft or solid stools daily during the last week of the study (21152).
Pain (acute). Oral Boswellia serrata has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with acute musculoskeletal pain shows that taking a specific combination product containing Boswellia serrata and turmeric extracts in black sesame oil (Rhuleave-K; Arjuna Natural Private Ltd.) 1000 mg daily for 7 days is as effective as acetaminophen 1000 mg daily for pain relief, onset of pain relief, and onset of maximal pain relief (109287). This study is limited by its lack of blinding and placebo control. Additionally, the dose of acetaminophen used in this study is below the standard recommended daily dose.
Pharyngitis. Although there is interest in using oral Boswellia serrata for pharyngitis, there is insufficient reliable information about the clinical effects of Boswellia serrata for this condition.
Postoperative pain. Oral Boswellia serrata has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical study in adults undergoing hernioplasty shows that taking a specific combination product (Siben®, Agaton Srl) containing 200 mg each of Boswellia serrata and bromelain twice daily for 11 days after surgery reduces pain on postoperative days 7 and 21, but not day 1, when compared with placebo. While the difference in pain scores on day 21 was statistically significant, pain was rated as mild in both groups; any difference may not be considered clinically significant (114687).
Rheumatoid arthritis (RA). Oral Boswellia serrata has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical trial in patients with RA shows that taking two capsules of a specific product containing Boswellia serrata 100 mg, ashwagandha 450 mg, turmeric 50 mg, and zinc complex 50 mg (Articulin-F) three times daily for 3 months improves pain, morning stiffness, grip strength, and disability scores when compared with placebo (21154). However, another clinical trial in patients with RA shows that taking two tablets of a standardized extract formulation (RA-1) containing Boswellia serrata, ashwagandha, ginger, and turmeric three times daily for 16 weeks does not improve most symptoms when compared with placebo (21155).It is unclear if these findings are due to Boswellia serrata, other ingredients, or the combination.
Rhinosinusitis. Oral Boswellia serrata has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients over 12 years of age with chronic sinusitis shows that taking a combination product containing Boswellia serrata, black currant, bromelain, and vitamin D (Flogostop Forte, Humana Italia) with inhaled corticosteroids daily for 30 days reduces rhinorrhea, hyperemia of mucosa, and local inflammation when compared with inhaled corticosteroids alone (111501). It is unclear if these findings are due to Boswellia serrata, other ingredients, or the combination.
Stroke. It is unclear if oral boswellic acids improve neurological function after stroke. Details: One small clinical study in adults with recent ischemic stroke who are taking aspirin and clopidogrel shows that taking boswellic acids 800 mg three times daily for 30 days improves neurological function, as measured using the National Institutes of Health Stroke Scale, when compared with placebo (102092).
Traumatic brain injury (TBI). It is unclear if oral Boswellia serrata is effective for reducing disability, or improving cognitive function or memory in adults recovering from TBIs. Details: A small clinical crossover study in adults admitted to the hospital for diffuse axonal injury shows that taking powdered Boswellia serrata oleogum resin 360 mg three times daily for 6 weeks does not improve disability when compared with placebo (91379). However, another small clinical study in patients suffering from a TBI 3 months to 3 years earlier shows that taking a specific Boswellia serrata extract (K-Vie, Kondor Pharma) 400 mg three times daily for 3 months improves performance on cognitive function tests, including those assessing processing speed, memory, and overall cognitive function, when compared with placebo (109567). A moderate-size clinical study in adults with memory dysfunction due to a recent mild traumatic brain injury in Iran shows that taking a specific product containing Boswellia serrata 360 mg and ginger 36 mg (Memoral, Goldarou) three times daily for 1 month modestly improves practitioner-assessed memory function scores when compared with placebo (110132). However, it is unclear if this effect is due to Boswellia serrata, ginger, or the combination.
Ulcerative colitis. Small clinical studies suggest that oral Boswellia serrata extracts may improve symptoms of ulcerative colitis. Details: Two very small clinical trials in patients with active ulcerative colitis suggest that taking Boswellia serrata gum resin 300-350 mg three times daily for 6 weeks improves symptoms and disease markers comparably to taking sulfasalazine 1 gram three times daily (1709,12438). These findings are limited because the sample size may have been inadequate to assess differences between groups. In patients with ulcerative colitis in remission, one observational study has found that taking a specific lecithin-based delivery form of Boswellia serrata extract (Casperome, Indena S.p.A.) 250 mg daily for 4 weeks is associated with a reduction in abdominal pain, cramps, and malaise, a decrease in the need for additional medications, and a 58% lower risk for requiring additional medical care when compared with no treatment. Additionally, weekly episodes of bloody diarrhea, bowel movements, and watery stools were reduced when compared with baseline (102090).
Urinary incontinence. Oral Boswellia serrata has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in postmenopausal adults with urinary incontinence shows that taking a 3 tablets of a multi-ingredient herbal product containing Boswellia serrata 100 mg and five other herbs twice daily for 4 weeks reduces urinary incontinence frequency and leakage amount when compared with placebo, with improvements similar to those reported with solifenacin as standard therapy (111502). It is unclear if these effects are due to Boswellia serrata, other ingredients, or the combination.
Urinary tract infections (UTIs). Oral Boswellia serrata has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small observational study in patients with an uncomplicated UTI has found that taking two tablets of a specific combination product (Acidif plus) containing Boswellia serrata gummy dry extract 100 mg, L-methionine 400 mg, and hibiscus 100 mg daily for 7 days is associated with reduced UTI symptoms and reduced bacteriuria when compared with taking an unreported dose of fosfomycin for 2 days (103783). The validity of this study is limited by its observational nature and a lack of information on the severity of UTI at baseline. Also, it is unclear if these effects are due to Boswellia serrata, other ingredients, or the combination. More evidence is needed to rate Boswellia serrata for these uses.

CHONDROITIN SULFATE (Chondroitin Sulfate, Sodium)

Cataracts. Chondroitin sulfate in combination with sodium hyaluronate is approved as a medical device to be ophthalmically injected during cataract surgery. It is unknown if other routes of administration are beneficial. Details: Injecting ophthalmic viscosurgical devices (OVDs) containing a combination of chondroitin sulfate and sodium hyaluronate into the eye protects the corneal endothelium during small-incision cataract surgery. Various medical devices containing chondroitin sulfate and sodium hyaluronate (Viscoat, Alcon Laboratories) have been granted approval by US Food and Drug Administration (FDA) for use as an adjunct to cataract surgery (89436,89437). However, OVDs that cannot be easily removed after surgery can cause intraocular pressure (IOP) spikes and reduced visual acuity. A meta-analysis of small clinical studies shows that using a specific chondroitin sulfate 4% and sodium hyaluronate 3% solution (Viscoat, Alcon Laboratories) after small-incision cataract surgery increases IOP at postoperative days 1 and 2, but not at any later postoperative days for up to 1 month (104452).
Osteoarthritis. Chondroitin sulfate seems to modestly reduce osteoarthritis pain and improve function. Pharmaceutical-grade chondroitin sulfate products have shown the most benefit. Details: Meta-analyses of randomized controlled trials in patients with mostly knee osteoarthritis show that taking chondroitin sulfate 800-2000 mg in single or divided doses daily for at least 3 months modestly reduces pain and disability when compared with placebo. However, included studies were heterogeneous and most had high attrition bias. A sub-group analysis of high-quality studies shows that 16 patients need to take chondroitin sulfate for 6 months for one patient to experience at least a 20% reduction in pain (94381,95792,99685,104446). When compared with conventional treatments like diclofenac 50 mg three times daily, chondroitin sulfate improves symptoms more slowly; however, the improvement seems to persist for up to 3 months after treatment cessation (322). Chondroitin also seems to have disease-modifying benefits. Clinical research in patients with osteoarthritis of the knee or hip shows that taking chondroitin sulfate 800 mg daily or more for 2 years might modestly reduce joint degeneration and narrowing when compared with placebo or celecoxib (42348,42398,94381,95516). Overall, most of the positive research involved pharmaceutical-grade chondroitin sulfate products, which are available as prescription products in some countries, such as Chondrosulf (IBSA Institut Biochimique SA) (17732,42348,42398,42536,89596,94360,104446), Chondrosan (Bioibérica, S.A.) (42463,42513), and Structum (Laboratoires Pierre Fabre) (22212,42520,89593). One clinical study shows that taking a pharmaceutical-grade chondroitin product (Chondrosulf) 800 mg daily seems to be comparable to taking celecoxib 200 mg daily for reducing pain and improving knee function (94360). Pharmaceutical-grade chondroitin products might demonstrate greater benefit due to higher quality (94360,102116). It is also important to note that most clinical studies using pharmaceutical-grade products are manufacturer-funded (94381). Furthermore, they may not be readily available for purchase in the US. Experts have conflicting stances on the use of chondroitin for osteoarthritis. The American College of Rheumatology (ACR) strongly recommends against the use of chondroitin for any form of osteoarthritis (102114). Conversely, the European Society of Clinical and Economic Aspects of Osteoarthritis (ESCEO) strongly recommends for the use of pharmaceutical-grade chondroitin products. Additionally, the ESCEO provides a weak recommendation against the use of chondroitin in combination with glucosamine (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. Chondroitin is often used in combination with glucosamine and/or other products. Long-term studies in patients with osteoarthritis show that taking non-branded chondroitin sulfate with glucosamine sulfate modestly reduces joint-space narrowing when compared with control (89558,94380,95792). However, meta-analyses and individual clinical studies assessing non-branded preparations of chondroitin sulfate with glucosamine hydrochloride or glucosamine sulfate do not show reduced pain in patients with knee osteoarthritis when compared with control (13579,89558,95788,99683,99685). In contrast, pain reduction was reported for branded formulations such as chondroitin sulfate with glucosamine hydrochloride and manganese ascorbate (Cosamin DS, Nutramax Laboratories) (4237,7169); chondroitin sulfate with glucosamine hydrochloride (Droglican, Bioiberica, S.A.) (89516); or chondroitin sulfate with collagen peptides and hyaluronic acid (BioCell Collagen, BioCell Technology, LLC) (28678,28680). 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 are from 16-24 weeks (111647). It is unclear if the benefit seen with these specific products is due to bias introduced by industry funding or due to higher quality. Limited research has also evaluated INTRAMUSCULAR and TOPICAL chondroitin. Some clinical research shows that receiving daily intramuscular injections of chondroitin sulfate for 6 months improves pain and function in patients with osteoarthritis (42396,42397). A topical preparation of chondroitin sulfate in combination with glucosamine sulfate, shark cartilage, and camphor also seems to reduce arthritis symptoms. However, any symptom relief is most likely due to the counterirritant effect of camphor and not the other ingredients (10327). There is no research showing that chondroitin is absorbed topically.

Aging skin. Oral chondroitin sulfate has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in females with aging skin shows that taking a specific combination product (BioCell Collagen, BioCell Technology, LLC) containing chondroitin sulfate 200 mg, collagen peptides 600 mg, and hyaluronic acid 100 mg daily for 12 weeks reduces lines and wrinkles by about 13% when compared with baseline (28681). The validity of these findings is limited by the lack of a comparator group. It is also unclear if these improvements are due to chondroitin sulfate, other ingredients, or the combination. Furthermore, it should be noted that this study was funded by the product manufacturer.
Aromatase inhibitor-induced arthralgia. Oral chondroitin sulfate has only been evaluated in combination with glucosamine sulfate; its effect when used alone is unclear. Details: A small open-label clinical study in postmenopausal females with early stage breast cancer 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 and symptoms associated with aromatase inhibitor-induced arthralgias when compared to baseline (89561). The validity of this finding is limited by the lack of a control group.
Cancer. Some low-quality observational studies suggest that oral chondroitin use is not associated with a lower risk of cancer. Details: A meta-analysis of observational research has found that use of chondroitin with or without glucosamine is not associated with a lower risk of cancer when compared with no use (110625).
Colorectal adenoma. Oral chondroitin has only been evaluated in combination with glucosamine; its effect when used alone is unclear. Details: An observational study in older adults has found that taking oral chondroitin and glucosamine is associated with a 26% reduced chance of high-risk adenoma and 10% reduced chance of conventional adenoma when compared with not using these supplements. This benefit was not seen in a subgroup of younger females (104444).
Dry eye. It is unclear if ophthalmic chondroitin sulfate improves dry eye symptoms. Details: A small clinical study in patients with dry eye suggests that administering an ophthalmic preparation of chondroitin sulfate every two hours while awake for 2 weeks seems to improve symptoms when compared to baseline (1974). Chondroitin has also been used in combination with other ingredients. A large clinical trial in patients with mild to moderate dry eye disease shows that applying preservative-free eye drops containing chondroitin sulfate with sodium hyaluronate (Humylub Ofteno PF, Laboratorios Sophia), one drop into each eye four times daily for 90 days, seems to be no different for improving dry eye severity when compared with using polyethylene/propylene glycol eye drops (Systane Ultra, Alcon Laboratories) (104443). Another small clinical trial in patients with mild to moderate dry eye shows that using specific eye drops containing chondroitin sulfate and xanthan gum (PRO-148, Laboratorios Sophia) four times daily for 60 days does not improve tear stability, but might improve dry eye severity, when compared with using polyethylene/propylene glycol eye drops (Systane, Alcon Laboratories) (89591).
Exercise-induced muscle soreness. It is unclear if oral chondroitin sulfate improves muscle soreness from exercise. Details: Preliminary clinical research in untrained males shows that taking chondroitin sulfate 1800 mg twice daily for 14 days before exercise does not reduce post-exercise muscle soreness when compared with placebo (42352). However, another small clinical study in healthy, recreationally active adults shows that a specific combination product (BioCell Collagen, BioCell Technology, LLC) containing chondroitin sulfate 300 mg, collagen peptides 900 mg, and hyaluronic acid 150 mg, taken twice daily for 6 weeks prior to two bouts of resistance exercise, attenuates muscle damage and decreases delayed-onset muscle soreness when compared with placebo (96301). It is unclear if these effects are due to chondroitin sulfate, the other ingredients, or the combination.
Gastroesophageal reflux disease (GERD). Oral chondroitin sulfate has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Patients with non-erosive GERD are thought to be less responsive to conventional acid suppression with proton pump inhibiters (PPIs) and H-2 blockers. A small preliminary clinical study shows that taking a syrup containing hyaluronic acid and chondroitin sulfate along with PPIs, H2-receptor antagonists, and/or antacids, reduces the intensity of symptoms associated with non-erosive GERD by about 3.5-fold when compared with placebo (89592). A larger clinical study in patients with non-erosive GERD shows that taking the same combination agent (Esoxx by Alfa Wassermann) in addition to acid suppression with PPIs improves GERD symptom severity by 21%, heartburn by 15%, and regurgitation by 10% when compared with PPIs with a placebo (101271). This product is available in Canada as EsopH (Exzell Pharma). It is unclear if the benefit of this combination product is due to chondroitin sulfate, hyaluronic acid, or the combination. Chondroitin sulfate has also been evaluated in patients with GERD who experience extraesophageal symptoms. A small clinical study in patients reporting symptoms of cough, hoarseness, postnasal drip, sore throat, and/or throat clearing shows that taking a specific combination product (Gerdoff, SOFAR S.p.A.) containing chondroitin sulfate, hyaluronic acid, and aluminum hydroxide three times daily with omeprazole 40 mg once daily for 6 weeks does not reduce overall symptom scores, based on the Reflux Symptoms Index (RSI) score, when compared with omeprazole alone. However, it does increase the probability of treatment response, defined as a 50% or greater improvement in RSI score, by nearly 40% (109648). This product is available in Italy. It is unclear if these findings are due to chondroitin sulfate, other ingredients, or the combination.
Gastritis. Oral chondroitin sulfate has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with gastritis shows that taking a specific liquid product (Esoxx, Alfa Wasserman Spa) containing chondroitin sulfate and hyaluronic acid four times daily for 4 weeks modestly reduces upper abdominal pain when compared with placebo (99687). It is not clear if this effect is due to chondroitin sulfate, hyaluronic acid, or the combination.
Hyperlipidemia. Although there is interest in using oral chondroitin for hyperlipidemia, there is insufficient reliable information about the clinical effects of chondroitin for this condition.
Interstitial cystitis. Small clinical studies suggest that intravesical chondroitin sulfate may not improve interstitial cystitis symptoms. Oral chondroitin sulfate has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Several uncontrolled, open-label studies suggest that intravesical chondroitin sulfate, with or without hyaluronic acid, improves clinical symptoms of interstitial cystitis and reduces the problems caused by symptoms in these patients (42338,42371,42373,42385,42387). However, in controlled clinical trials, intravesical chondroitin sulfate 2%, instilled weekly for 6-7 weeks, does not significantly improve symptoms when compared with a placebo solution (42473,42517). Furthermore, a meta-analysis of clinical research shows that intravesical chondroitin sulfate with hyaluronic acid does not improve pain due to interstitial cystitis better than using hyaluronic acid solution alone (97054). Oral chondroitin has been evaluated in combination with other ingredients. Preliminary clinical research 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, as two capsules twice daily for 12 months, reduces symptoms of interstitial cystitis by 44% to 52% (42391). It is not clear if this effect is due to chondroitin, other ingredients, or the combination.
Kashin-Beck disease. It is unclear if oral chondroitin sulfate improves Kashin-Beck disease symptoms such as pain. Details: A small clinical study in Chinese adults with Kashin-Beck disease shows that taking chondroitin sulfate 600 mg twice daily with or without glucosamine hydrochloride 480 mg three times daily for 6 months decreases pain and stiffness when compared with placebo (42516).
Osteoporosis. Although there is interest in using oral chondroitin for osteoporosis, there is insufficient reliable information about the clinical effects of chondroitin for this condition.
Overall mortality. Oral chondroitin has only been evaluated in combination with glucosamine; its effect when used alone is unclear. Details: A cross-sectional observational study suggests that using oral chondroitin and glucosamine for at least one year is associated with a 27% lower incidence of overall mortality and 58% lower incidence of cardiovascular mortality when compared with not using these supplements (104445). However, this study did not clarify the forms of chondroitin and glucosamine used, or the doses, frequencies, or durations 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. Another observational study suggests that regular use of chondroitin with glucosamine for an average of 8 years is associated with a 30% lower risk of mortality when compared with no use. However, when these findings are adjusted for differences in age, body mass index, and comorbidities, overall mortality risk does not seem to be reduced with chondroitin and glucosamine supplementation (110626). Higher quality, prospective research is needed to clarify the relationship, if any, with overall mortality. Additionally, it is unclear if the effects on mortality are due to chondroitin, glucosamine, or the combination.
Psoriasis. It is unclear if oral chondroitin sulfate is beneficial for reducing psoriasis disease severity. Details: A clinical study in patients with plaque psoriasis and knee osteoarthritis shows that taking chondroitin sulfate (Condrosan, CS Bio-Active, Bioibérica S.A.) 800 mg daily for 3 months does not appear to reduce the extent or severity of plaque psoriasis when compared with placebo (42463).
Stroke. It is unclear if oral chondroitin sulfate is beneficial for reducing stroke risk. Details: An observational study in Spanish patients found that chondroitin sulfate use is associated with 23% lower odds of ischemic stroke when compared with non-use; however, the benefit was only observed in patients taking at least 800 mg for no more than one year (109643).
Temporomandibular disorders (TMD). Oral and topical chondroitin sulfate has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of two small clinical studies in patients with TMD shows that taking chondroitin sulfate 1200 mg and glucosamine sulfate 1500 mg daily for 2 months does not reduce pain or increase maximum mouth opening when compared with tramadol 50-100 mg daily (109647). 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 pain, tension, or temporomandibular space measures when compared with placebo (110629).
Urinary incontinence. Although there is interest in using intravesical chondroitin for urinary incontinence, there is insufficient reliable information about the clinical effects of chondroitin for this condition.
Urinary tract infections (UTIs). It is unclear if intravesical administration of chondroitin sulfate alone is beneficial in patients with recurrent UTIs. Most research has evaluated the effects of chondroitin sulfate in combination with hyaluronic acid, with promising results. Details: One small observational study in patients with recurrent UTIs has found that intravesical administration of 40 mL of chondroitin sulfate 0.2% weekly for 6 weeks, then every 2 weeks for 2 months, then every 3 weeks for 2 months, and finally every 6 weeks for a total treatment duration of 1 year is associated with a lower number of UTIs and urologist visits when compared with low-dose long-term antibiotic therapy (109649). Most research on the use of chondroitin sulfate for UTIs has evaluated its effects when used in combination with hyaluronic acid. Several small clinical studies and a pooled analysis of the available clinical research show that intravesical administration of 50 mL of specific solutions containing chondroitin sulfate 2% and hyaluronic acid 1.6% (iAluRil, IBSA Farmaceutici; Cystistat, Bioniche) for up to 6 months reduces the rate of UTI recurrence by about 2-3 incidents per year and delays the time to the first UTI recurrence when compared with placebo or prophylaxis with sulfamethoxazole-trimethoprim (42511,42519,89590,89594,99688). However, the validity of these findings is limited by the low quality and high heterogeneity of the included studies, as well as concerns for publication bias (99688). More evidence is needed to rate chondroitin sulfate for these uses.

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).

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.

SODIUM

LIKELY EFFECTIVE

Cystic fibrosis. Long-term nebulized hypertonic sodium chloride improves lung function and reduces pulmonary exacerbations in patients with cystic fibrosis. Details: Meta-analyses of clinical research in adults with cystic fibrosis show that, when taken along with a bronchodilator and other standard therapies, nebulized hypertonic sodium chloride in concentrations of 3% to 7%, up to 10 mL twice daily for 4 weeks, increases forced expiratory volume at one second (FEV1) when compared with isotonic saline (sodium chloride 0.9%) (26230,26230). This benefit was not seen at 48 weeks. Other clinical research in adults with cystic fibrosis shows that inhaling sodium chloride 7%, 4 mL twice daily for 48 weeks, does not improve FEV1 when compared with isotonic saline. However, chronic treatment with hypertonic saline does reduce the number of pulmonary exacerbations and increase the number of patients without pulmonary exacerbations when compared with isotonic saline (29402). It is not clear if this benefit occurs in children with cystic fibrosis. The Pulmonary Clinical Practice Guidelines Committee of the Cystic Fibrosis Foundation recommends that individuals with cystic fibrosis aged 6 years or older use nebulized hypertonic saline long-term to improve lung function, reduce the number of exacerbations, and improve quality of life (29403).

Amphotericin B nephrotoxicity. Oral sodium chloride seems to prevent nephrotoxicity associated with use of amphotericin B. Details: Clinical research shows that administering oral or intravenous sodium chloride 150 mEq daily during treatment with amphotericin B can attenuate the rise in serum creatinine levels and preserve renal function when compared to treatment with amphotericin B alone (26226).

Bipolar disorder. It is unclear if oral sodium is beneficial in preventing lithium level fluctuations in patients with bipolar disorder. Details: A moderate-sized open-label clinical study in adults with type I bipolar disorder receiving lithium carbonate shows that taking sodium chloride 1 gram daily for 12 weeks along with dietary salt restriction of 1 gram daily reduces the percentage of patients with lithium level fluctuations above 0.8 mEq/L, but does not significantly affect serum sodium, potassium, aldosterone, or creatinine levels when compared with controls who were not salt restricted, but were advised not to consume additional salt at the table (112909). However, the interpretation of these findings is limited by missing data in both groups.
Canker sores. Although there is interest in using topical sodium chloride for canker sores, there is insufficient reliable information about the clinical effects of sodium chloride for this condition.
Congestive heart failure. It is unclear if oral sodium is beneficial in patients with acute decompensated heart failure requiring decongestive therapy with diuretics. Details: A moderate-sized clinical study in adults hospitalized with acute decompensated heart failure requiring high-dose intravenous furosemide shows that taking sodium chloride 2 grams three times daily for up to 96 hours does not affect patient weight or serum creatinine levels when compared with placebo (112911). However, the clinical relevance of this study is unclear and it may have been inadequately powered to detect a difference between groups.
Conjunctivitis. Although there is interest in using ophthalmic sodium chloride for conjunctivitis, there is insufficient reliable information about the clinical effects of sodium chloride for this condition.
Hyponatremia. Although there is interest in using oral sodium chloride for hyponatremia, there is insufficient reliable information about the clinical effects of oral sodium chloride for this condition.
Pharyngitis. Although there is interest in using topical sodium chloride for pharyngitis, there is insufficient reliable information about the clinical effects of sodium chloride for this condition.
Prematurity. It is unclear if oral sodium is beneficial for premature infants. Details: Preliminary clinical research in infants born at less than 32 weeks' gestation shows that adding sodium 4 mEq/kg daily to enteral feedings, starting from the 7th day after birth and continuing through the 35th day, reduces the risk of developing hyponatremia and improves weight gain when compared with adding water (98180). A small, open-label clinical study in newborns less than 35 weeks gestation shows that high sodium intake, defined as an average of 0.25% sodium in maintenance fluids, for 48 hours on day 2 and 3 after birth results in less weight loss within the first 72 hours of life when compared with control, but does not improve mortality, length of hospital stay, or complications from prematurity (112908). However, interpretation of these findings is limited by varied concentrations of sodium as an intervention. More evidence is needed to rate sodium for these uses.

TURMERIC (Turmeric (Curcuma longa) rhizome extract)

Allergic rhinitis (hay fever). Oral turmeric seems to improve symptoms in people with allergic rhinitis. Details: A large clinical study in people with allergic rhinitis shows that taking a specific curcumin product (Organika Health Products) 500 mg daily for 2 months reduces nasal symptoms, including sneezing, itching, runny nose, and congestion, when compared with placebo (96138).
Depression. Most research shows that oral curcumin, a constituent of turmeric, when used at doses of at least 1 gram daily for at least 6 weeks improves symptoms of depression when taken alone or in combination with antidepressant medications. Details: Curcumin appears to be most beneficial for depression in middle aged patients compared to older patients, when taken for at least 6 weeks, and when used at a dose of at least 1 gram daily. In adults with major depressive disorder, a meta-analysis of data from 6 clinical studies, as well as individual studies not included in this analysis, show that taking curcumin 1 gram daily along with an antidepressant moderately improves depression symptoms when compared with placebo (96131,96139). Another meta-analysis of 10 studies shows symptom reductions in patients with major depression when combined with conventional antidepressants, but not when used alone in patients with milder depressive symptoms. However, the quality of the evidence is low (104971). Additionally, a large clinical study in adults with mild-moderate symptoms of depression shows that taking curcumin 750 mg twice daily for 12 months modestly reduces depression symptoms when compared with placebo (114898). When used alone, one clinical study shows that curcumin 1 gram daily for 6 weeks may be similarly effective to fluoxetine 20 mg daily. Taking both products together seems to be more effective than either product alone, increasing the response rate from 65% to 78% (89728). Guidelines from The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce state that curcumin extract at doses of 500-1000 mg daily is provisionally recommended for monotherapy or adjunctive use in mild to moderate depression (110318).
Dyspepsia. Oral turmeric may be modestly beneficial for some patients with dyspepsia. In patients with functional dyspepsia, small clinical studies show that oral curcumin, a constituent of turmeric, is similarly effective when compared with the proton-pump inhibitor omeprazole. Details: Clinical research shows that taking turmeric 500 mg four times daily for 7 days can relieve overall symptoms of dyspepsia in 64% more patients than taking placebo (11144). A small, unblinded clinical study in patients with a type of dyspepsia called postprandial distress syndrome shows that taking turmeric 250 mg or 500 mg orally three times daily after meals for 4 weeks is associated with reductions in symptom scores which are similar to those seen with simethicone 60 mg three times daily for 4 weeks. However, the recurrence rate upon stopping therapy was about 14% with simethicone, compared with 43% to 46% with turmeric (104963). In patients with functional dyspepsia, taking the constituent curcumin appears similarly effective when compared with omeprazole, but might not provide further symptom reduction in those also taking famotidine or omeprazole (106063,106801,111599). One small clinical study in Iran shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg daily in addition to famotidine 40 mg daily for 30 days is no more effective for reducing overall symptoms of dyspepsia, such as abdominal pain, heartburn, bloating, and nausea, when compared with famotidine alone (106063). Another small clinical study in Thailand shows that taking curcumin 500 mg four times daily for 4 weeks is similarly effective for reducing dyspepsia severity and improving satisfaction when compared with an unspecified dose of omeprazole and more effective when compared with placebo (106801). Similarly, a moderate-size clinical study in Thailand shows that taking curcumin 500 mg four times daily for 4 weeks is similarly effective for reducing dyspepsia severity when compared with omeprazole 20 mg daily. However, taking curcumin and omeprazole in combination did not provide further symptom reduction (111599). The validity of these results is limited by the high rate of study dropouts.
Hyperlipidemia. Research is conflicting on whether oral turmeric, curcumin, or curcuminoids can reduce serum lipids. Any improvement in lipids is likely to be small. Reasons for the conflicting findings may relate to turmeric formulation, duration of treatment, and/or the baseline cholesterol status of the included patients. Details: Results from meta-analyses of clinical research show inconsistent and conflicting results. One large meta-analysis of over 50 clinical studies in healthy adults and those with a variety of conditions shows that supplementation with turmeric or curcumin 80-4000 mg daily for 4-24 weeks reduces total cholesterol by 4 mg/dL, low-density lipoprotein (LDL) cholesterol by 5 mg/dL, and triglycerides by 7 mg/dL and increases high-density lipoprotein (HDL) cholesterol by 2 mg/dL when compared with placebo (112119). Two other meta-analyses of 27 clinical studies agree that taking turmeric, curcumin, or curcuminoids moderately reduce triglyceride levels but suggest that turmeric does not improve total cholesterol when compared with placebo. However, the meta-analyses contradict one another on whether turmeric and its constituents reduce LDL cholesterol or increase HDL cholesterol. (96128,96135). Additionally, a third meta-analysis of 10 clinical trials shows that taking up to 2400 mg daily of curcumin or curcuminoids, from turmeric or isolated sources, for up to 12 weeks, does not significantly improve triglycerides, LDL cholesterol, HDL cholesterol, or total cholesterol (110220).
Nonalcoholic fatty liver disease (NAFLD). Oral curcumin, a constituent of turmeric, seems to attenuate fat deposition and improve some metabolic parameters in adults with NAFLD. Details: Clinical research shows that taking curcumin daily reduces NAFLD severity in 30% to 79% of patients, compared to 5% to 27.5% of patients receiving placebo. Curcumin also reduces the quantity of additional fat deposition in the liver to 0% to 4.5%, compared to 17.5% to 26% in those taking placebo. Most research shows that taking curcumin also reduces liver enzyme levels, body mass index (BMI), blood glucose levels, glycated hemoglobin (HbA1c), and total cholesterol when compared with placebo. Although some clinical research shows that taking curcumin improves levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides, a meta-analysis of clinical research shows that these lipid levels are not improved in patients with NAFLD, specifically (97430,97431,100258,102350,106062,107120,109279,111349,114901). However, another meta-analysis of 14 small, heterogeneous clinical studies in adults with NAFLD, that included some of these studies, shows that taking various doses and forms of turmeric or curcumin modestly reduces liver enzyme levels, improves measures of insulin resistance, reduces waist circumference, and improves LDL, HDL, and triglyceride levels when compared with placebo (111348). A small clinical trial in patients with NAFLD given specific lifestyle recommendations shows that taking curcumin modestly reduces the frequency of metabolic syndrome and fatty liver but does not have beneficial effects on fatty liver-associated indices, adiposity, or the atherogenic index, when compared with placebo (109285). Findings for specific endpoints are mixed between individual studies and may depend on the dose and formulation of curcumin used or the duration of treatment. These studies have used various doses and formulations. In one study, 500 mg of a dispersion formulation equivalent to 70 mg of curcumin daily for 8 weeks was used (97430). Also, 250 mg once daily or 500 mg twice daily of a specific phytosomal formulation (Meriva, Indena) containing curcumin and soy phosphatidylcholine in a 1:2 ratio and standardized to an overall curcuminoid content of 20% was taken for 8 weeks (97431,106062). Another study used 1 gram of powdered turmeric rhizome taken three times daily with meals for 12 weeks (102350). One study used a curcumin-piperine complex (Curcumin C3 complex 500 mg plus Bioperine 5 mg) daily for 8 weeks (107120). One study used curcumin (Arjuna Natural Extract) 500 mg three times daily for 12 weeks (109285). Despite positive results with curcumin in several small clinical studies of patients with NAFLD, there is some concern that curcumin might cause hepatotoxicity in rare cases, especially when highly bioavailable formulations are used in high doses (103633). There is also evidence that the risk for hepatotoxicity with curcumin may be increased in individuals with the HLAB*35:01 allele (109288). Curcumin-induced hepatotoxicity has not been reported in clinical trials of patients with NAFLD, and its potential mechanism is unclear. However, patients seeking to take curcumin for NAFLD should be advised to monitor for symptoms of hepatotoxicity, including abdominal pain, dark urine, fatigue, jaundice, nausea, and pruritus.
Oral mucositis. Oral curcumin or curcumin-containing mouthwash seem to reduce the development of severe oral mucositis, as well as reduce the severity and pain of oral mucositis, associated with cancer treatment. Details: Clinical research in patients receiving radiotherapy following recent radical surgery for oral cancer shows that taking turmeric (BCM-95, Arjuna Natural Pvt. Ltd., India) during radiotherapy reduces the incidence of severe oral mucositis to 25% or 20% in those taking turmeric 500 mg two or three times daily, respectively, compared with 65% in those taking placebo. The incidences of severe oral pain, dysphagia, and dermatitis were also reduced by at least 50% (105398). A small clinical study in patients receiving chemotherapy with or without head and neck radiotherapy shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg twice daily for 7 weeks improves severity of oral mucositis at weeks 1, 4, and 7 and reduces pain at week 7 when compared with placebo. Effects were more pronounced in those with chemotherapy-induced oral mucositis than radiotherapy-induced oral mucositis (106800). In patients with head and neck cancer receiving radiotherapy, preliminary clinical research shows that swishing with 10 mL of turmeric solution (prepared by dissolving turmeric 400 mg in 80 mL of water) six times daily for 6 weeks delays mucositis and reduces the number of cases of intolerable mucositis by 49% when compared to swishing with 10 mL of povidone-iodine solution twice daily for 6 weeks (89726). Another small clinical study shows that swishing with 10 mL of nanoparticulate curcumin 0.1% mouthwash three times daily for 6 weeks is associated with a 50% lower risk of developing oral mucositis, and a delay of 2 weeks in the onset of mucositis, when compared with benzydamine 0.15% mouthwash (104969). A small clinical study in patients with mucositis due to head and neck radiotherapy shows that taking curcumin nanoparticles (SinaCurcumin, ExirNanoSina) 40 mg daily or using 10 mL of a curcumin 0.1% mouthwash three times daily for up to 21 days improves scores related to pain, burning, ulceration, and erythema when compared with placebo. Results with either oral or topical curcumin were similar (111350).
Osteoarthritis. Some oral turmeric extracts and combination products containing turmeric seem to improve certain symptoms of knee osteoarthritis. However, it is unclear how turmeric compares to the use of non-steroidal anti-inflammatory drugs (NSAIDs). Details: Several meta-analyses of clinical studies show that turmeric extracts and/or curcuminoid products reduce knee pain and stiffness, improve physical function, and reduce the need for rescue medication when compared with placebo (104970,106792,109280,110222). However, a reduced effect was noted in patients with increasing age or body mass index (104790). The studies evaluated in these meta-analyses are heterogeneous, of low- to moderate-quality, and utilized a variety of products and/or dosing strategies (104970,106792,109280,110222). Small to moderate-sized clinical studies show that specific products (Meriva, Indena; Theracurmin, Theravalues Corp) containing curcumin 90-100 mg twice daily for up to 6 months, or specific turmeric extracts (Turmacin, Natural Remedies Pvt. Ltd.; Curcugen, DolCas Biotech, LLC) 500 mg twice daily for 6-12 weeks, reduce pain and analgesic use and improve functionality when compared with placebo (17953,80988,89721,97424,104148,107118). A specific turmeric extract (CuraMed, EuroPharma USA) 1500 mg daily for 12 weeks improves functionality, but not pain, when compared with placebo (96127). Also, a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina), 40 mg twice daily for 6 weeks, improves pain, stiffness, and physical activity scores and reduces intake of rescue acetaminophen by about 60% when compared with placebo (102349). However, not all turmeric products seem to be effective for improving symptoms of osteoarthritis. One small clinical study shows that taking a specific turmeric extract (B-Turmactive, PLAMECA S.A.) 500 mg daily for one week does not reduce knee pain when compared with placebo (104147). Also, a meta-analysis of clinical research shows that benefits are limited to bio-optimized forms of curcuminoids, and benefits related to pure extracts are lacking (110222). Turmeric has also been compared with conventional treatments for knee osteoarthritis in small meta-analyses, a network meta-analysis, and individual clinical studies. However, the evidence is mixed as to whether turmeric is as effective or more effective than NSAIDs, such as ibuprofen 400 mg taken 2-3 times daily, diclofenac 25-100 mg daily, or chondroprotective drugs (17952,89720,89722,106792,109280,110222,113607). A network meta-analysis comparing 6 interventions in adults with knee osteoarthritis suggests that curcumin monotherapy, curcumin with chondroprotective agents, or curcumin with NSAIDs improves scores related to pain, function, and stiffness while reducing the need for rescue medication and the incidence of adverse events (113607). Individual studies are heterogenous with respect to comparator medication and dosing schedule. Doses included a non-commercial turmeric extract 500 mg 3-4 times daily for 4-6 weeks (17952,89720) or turmeric extract 500 mg twice daily for 3 months (89722). Topical turmeric has also been evaluated. One clinical study shows that applying curcumin topically as a 5% ointment in Vaseline twice daily for 6 weeks reduces pain associated with knee osteoarthritis by a mean of about 11 on a 100-point visual analog scale when compared with placebo (104964). Another clinical study in patients with knee osteoarthritis shows that applying curcumin in a self-nano-emulsifying polyethylene glycol organogel 1.5 grams to the knee twice daily for 8 weeks reduces pain, stiffness, and difficulty with physical function scores by 72%, 62%, and 46%, respectively, when compared to baseline, with improvements superior to placebo for all outcomes (113357). Research also shows that taking specific combination products containing turmeric and other ingredients can improve pain and functionality in patients with osteoarthritis. These combination products have combined turmeric with chondroitin sulfate and glucosamine hydrochloride (CartiJoint Forte, Fidia Farmaceutici SpA); boswellic acid (Curamin, EuroPharma USA; Rhulief); Boswellia serrata (Rhulief); ashwagandha, Boswellia serrata, and zinc (Articulin-F, Eisen Pharmaceutical Co. Pvt. Ltd.); devil's claw and bromelain (AINAT, Laboratoire de Rhumatologie Appliquée); Boswellia serrata, guggul, and valerian (Phytoproflex, OPTM Healthcare); Boswellia serrata and terminalia (LI73014F2, Laila Nutraceuticals); ashwagandha, Boswellia serrata, and ginger (Artrex, Mendar); or extracts of ginger rhizome, devil's claw tuber, Boswellia serrata resin, and celery seed (Tregocel, Max Biocare) (19276,51950,81466,89717,89719,96127,97419,97421,97428,106078)(109280).
Pruritus. Oral turmeric has been evaluated for the management of pruritus of various etiologies, with promising results. Details: Clinical research in patients with kidney failure shows that taking turmeric 500 mg orally three times daily for 8 weeks decreases symptoms of uremic pruritus by 1.9-fold when compared with placebo (89724). Also, a small clinical study in patients with sulfur mustard-induced chronic pruritus shows that taking a specific combination product (C3 Complex, Sami Labs LTD) containing curcumin 1 gram plus extract from black pepper or long pepper (Bioperine) daily for 4 weeks reduces pruritus severity and improves quality of life when compared with placebo (81120,81176).

POSSIBLY INEFFECTIVE

Alzheimer disease. Neither oral turmeric nor its constituent curcumin appears to improve cognitive function or attenuate cognitive decline in adults with this condition. Details: A small clinical trial shows that taking the turmeric constituent, curcumin, 1-4 grams daily for 6 months does not improve mental state examination scores when compared with placebo (17096). Furthermore, a meta-analysis of this study and another small clinical study in patients with Alzheimer disease shows that the turmeric group experienced greater cognitive decline when compared with placebo (100261). While this research is limited by small study sizes and heterogeneous patient populations, the current evidence does not support the use of turmeric in patients with this condition.
Peptic ulcers. Oral turmeric does not seem to improve the healing of peptic or gastric ulcers when compared with placebo or liquid antacids. Details: Some clinical research shows that taking turmeric 2 grams three times daily for 8 weeks does not improve the healing of peptic ulcers when compared with placebo in Vietnamese patients (81444). Also, taking powdered turmeric rhizome 250 mg four times daily for 6 weeks seems to be less effective than a liquid aluminum-magnesium-hydroxide antacid for promoting gastric ulcer healing (81284).

Acne. Although there has been interest in using topical turmeric for acne, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
Age-related cognitive decline. Some small clinical studies suggest that oral curcumin, a constituent of turmeric, may modestly improve cognition in elderly patients experiencing cognitive decline. Details: A meta-analysis of three small clinical trials shows that curcumin modestly improves cognition in the elderly (100261). One of these clinical trials shows that taking a specific brand of curcumin (Theracurmin, Theravalues Corp.) 90 mg twice daily for 18 months improves long-term memory and attention when compared with placebo in middle-aged and older adults with or without mild cognitive impairment (96161).
Amenorrhea. Although there has been interest in using oral turmeric for amenorrhea, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
Ankylosing spondylitis. Although there has been interest in using oral turmeric for ankylosing spondylitis, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
Anxiety. Some clinical research show that oral curcumin reduces symptoms of anxiety. Details: A meta-analysis of 8 mostly low-quality clinical studies in adults with anxiety symptoms or an anxiety disorder diagnosis shows that taking curcumin 500-1000 mg daily for up to 12 weeks modestly reduces symptoms of anxiety when compared with placebo (114902). The validity of the meta-analysis is limited by the heterogeneity of the included studies, including differences in the patient populations, form and doses curcumin, treatment durations, and types of anxiety scales used. Additionally, all studies were conducted in either Iran or Australia which may limit generalizability of results to other populations.
Aromatase inhibitor-induced arthralgia. It is unclear if oral curcumin, a constituent of turmeric, is beneficial for aromatase inhibitor-induced arthralgia. Details: A small clinical trial in patients experiencing aromatase inhibitor-induced arthralgia shows that taking curcuminoids as a nanoemulsion (Curcumin C3 Complex, Sabinsa Corporation) 200 mg daily for 3 months does not improve grip strength or joint symptoms when compared with placebo (113345). However, this study may have been underpowered to detect a difference between groups.
Asthma. Some small clinical studies suggest that oral turmeric, as an adjunct to conventional asthma treatment, does not improve lung function or symptoms in adults and children with asthma. Details: One small clinical study in adults with mild to moderate asthma shows that adjuvant therapy with turmeric as curcumin 500 mg twice daily for 30 days does not improve lung function based on FEV1, or improve symptoms such as dyspnea, wheezing, cough, or tightness, when compared to standard treatment alone (99349). A small clinical trial in children 7-18 years of age with moderate to severe asthma shows that adding turmeric 500-1000 mg (containing 20-40 mg curcuminoids) daily for 6 months to standard therapy does not improve overall asthma symptoms when compared with placebo and standard therapy, although it may decrease the frequency of nighttime awakenings and the use of rescue inhalers (99348). Due to their small sizes and high drop-out rates, these studies may have been underpowered to detect a difference between groups.
Athletic performance. It is unclear if oral curcumin, a constituent of turmeric, is beneficial for athletic performance. Details: Preliminary clinical research in middle-aged male long-distance runners shows that taking a turmeric extract providing 2 grams of curcumin 95% and piperine 5% daily for 6 weeks does not improve aerobic capacity when compared with placebo (109286).
Benign prostatic hyperplasia (BPH). It is unclear if oral curcumin, a constituent of turmeric, is beneficial in BPH. Details: A clinical study in patients with BPH shows that taking curcumin 2250 mg once daily along with tamsulosin and finasteride for 6 months improves lower urinary tract symptoms related to storage, but not overall symptoms or symptoms related to voiding, by about 35%, compared with 25% in those receiving tamsulosin and finasteride alone. Periprostatic fat thickness, quality of life, and erectile function also were improved (106799).
Beta-thalassemia. It is unclear if oral turmeric is beneficial for iron overload in patients with beta-thalassemia. Details: A small clinical study in patients with beta-thalassemia major and iron overload shows that taking turmeric extract containing curcumin 500 mg twice daily for 12 weeks modestly reduces non-transferrin bound iron (NTBI) by 0.6 micromol/L, but not hemoglobin, transferrin saturation, total iron binding capacity, ferritin, or hepcidin, when compared with placebo (99306). Another small clinical study in adult males with beta-thalassemia intermedia and iron overload shows that taking a higher dose of curcumin 500 mg three times daily for 12 weeks modestly reduces serum iron and ferritin turmeric levels and transferrin saturation when compared with placebo (108871).
Bruises. Although there has been interest in using topical turmeric to alleviate bruising, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
Cachexia. It is unclear if oral curcumin, a constituent of turmeric, is beneficial for cancer cachexia. Details: A small clinical trial in patients with cancer anorexia-cachexia syndrome shows that taking curcumin 800 mg twice daily for 8 weeks does not reduce weight loss or improve body composition or handgrip strength when compared with placebo (109283).
Canker sores. Some preliminary research suggests that topical curcumin, a constituent of turmeric, is beneficial for minor canker sores. Details: Preliminary clinical research in young adults with minor canker sores shows that applying a 2% curcumin oral gel for 6 months reduces ulcer size, pain, and recurrence rate and increases healing rate similarly to 0.1% triamcinolone oral paste (104962). The validity of the study is limited by a lack of investigator blinding and the lack of an intention to treat analysis. Another small clinical study shows that applying a 1% curcumin nanomicelle gel (SinaCurcumin Pharmaceuticals) on lesions three times daily for one week is modestly more effective than applying a 2% curcumin gel for reducing pain and ulcer size (109282). The validity of this finding is limited by the lack of a non-curcumin comparator group.
Carpal tunnel syndrome. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. It is unclear if topical curcumin, a constituent of turmeric, is beneficial for carpal tunnel syndrome. Details: A moderate-sized clinical study in adults with mild to moderate carpal tunnel syndrome shows that taking a combination product containing turmeric, alpha-lipoic acid, acetyl-L-carnitine, phosphatidylserine, and vitamins C, E, B1, B2, B6, and B12 twice daily for 60 days reduces symptom severity and pain but does not improve measures of hand and wrist function when compared with control (111702). The validity of these effects is limited by a lack of blinding. The study may also be inadequately powered to detect a difference between groups. Additionally, it is unclear if the effects are due to turmeric, other ingredients, or the combination. Topical turmeric has also been investigated. A small clinical study in patients with mild to moderate carpal tunnel syndrome shows that applying a 1% curcuminoid gel (Sinanomin) to the wrists twice daily for 8 weeks modestly decreases symptom severity and improves function when compared with a placebo gel. However, there was no change in electrodiagnostic testing of the injury. All patients also used a night splint (113356).
Chemotherapy-induced acral erythema. It is unclear if oral or topical turmeric reduces the risk for acral erythema from capecitabine. Details: A small clinical trial in adults with cancer shows that taking turmeric 4 grams daily for 6 weeks starting at the beginning of treatment with capecitabine does not reduce the incidence of acral erythema overall; however, it does seem to reduce acral erythema grade 2 or higher when compared with expected incidence rates (99309). Topical turmeric has also been evaluated. A clinical study in patients with colorectal, gastric, pancreatic, or breast cancer receiving capecitabine shows that applying a specific ointment (Alpha) standardized to contain curcumin extract 0.5% and henna extract 10% to the soles and palms twice daily, beginning on day 1 of chemotherapy and continued for 4 cycles, does not prevent acral erythema or improve World Health Organization severity scores when compared with placebo. A post-hoc analysis suggests that there may have been a trend toward delayed onset and progression; however, this study was not structured to assess these outcomes (108874).
Chemotherapy-induced constipation. It is unclear if oral curcumin reduces symptoms of chemotherapy-induced constipation. Details: A small clinical study in patients with various forms of cancer receiving standard chemotherapy for that cancer type shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg twice daily for 9 weeks does not reduce symptoms of constipation when compared with placebo (107111).
Chemotherapy-induced diarrhea. It is unclear if oral curcumin reduces symptoms of chemotherapy-induced diarrhea. Details: A small clinical study in patients with various forms of cancer receiving standard chemotherapy for that cancer type shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg twice daily for 9 weeks does not reduce symptoms of diarrhea when compared with placebo (107111).
Chemotherapy-induced nausea and vomiting (CINV). It is unclear if oral curcumin reduces CINV. Details: A small clinical study in patients with various forms of cancer receiving standard chemotherapy for that cancer type shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg twice daily for 9 weeks modestly reduces symptoms of nausea, but not vomiting, in the second and third months after the start of treatment when compared with placebo (107111).
Chemotherapy-induced peripheral neuropathy. It is unclear if oral curcumin reduces symptoms of chemotherapy-induced peripheral neuropathy. Details: A small clinical study in patients with various forms of cancer receiving standard chemotherapy for that cancer type shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg twice daily for 9 weeks modestly reduces symptoms of chemotherapy-induced peripheral neuropathy over a three-month period when compared with placebo (107111).
Chronic kidney disease (CKD). It is unclear if oral turmeric is beneficial for CKD. Details: A meta-analysis of four small clinical trials in patients with CKD related to diabetic nephropathy or lupus nephritis shows that taking curcumin or turmeric for 0.5-4 months moderately reduces proteinuria when compared with placebo (109276). Also, a small clinical trial in children and young adults ages 6-25 years with vascular dysfunction related to autosomal dominant polycystic disease (PKD) shows that curcumin powder 25 mg/kg daily for 12 months does not improve vascular function or kidney function when compared with placebo (107117).
Colorectal adenoma. It is unclear if oral turmeric is beneficial for managing colorectal adenoma. Details: Preliminary clinical research in adults with familial adenomatous polyposis shows that taking curcumin 1500 mg twice daily for 12 months does not reduce the quantity or size of lower intestinal adenomatous polyps when compared with placebo (97427). A very small clinical trial in patients with familial adenomatous polyposis shows that taking 8 capsules daily of a turmeric extract, in a formulation also containing pepper fruit, spirulina, seaweed, and ginger root, for 6 months does not affect total polyp number or burden when compared with placebo. However, both number and burden were modestly reduced in the left colon. Each capsule provided curcuminoids 123.65 mg and turmerones 26.79 mg (110223).
Colorectal cancer. It is unclear if oral turmeric is beneficial for the prevention or treatment of colorectal cancer. Details: A small clinical trial in patients undergoing chemotherapy following colorectal cancer surgery shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg daily for 8 weeks modestly improves some measures of quality of life when compared with placebo (107109). In addition, a small clinical study in people at high risk for colorectal cancer, such as those who smoke, shows that taking the turmeric constituent, curcumin, 4 grams daily for 30 days can reduce the number of precancerous rectal aberrant crypt foci (18204). It is not clear if this results in a reduced risk for colorectal cancer.
Coronary artery bypass graft (CABG) surgery. One small study suggests that oral turmeric may reduce the risk for myocardial infarction after CABG surgery. Details: Preliminary clinical research shows that taking the turmeric constituent, curcuminoids, 4 grams daily in four divided doses, beginning 3 days prior to surgery and continuing for 5 days post-surgery, decreases the relative risk of myocardial infarction following CABG by approximately 56% when compared with placebo (81143).
Coronavirus disease 2019 (COVID-19). It is unclear if oral turmeric or its constituent, curcumin, is beneficial for reducing symptoms of COVID-19. Details: Small studies have evaluated curcumin as an adjunctive therapy in adults hospitalized with confirmed COVID-19. Patients in these studies also received treatments such as antimicrobials, anti-inflammatory medications, anticoagulants, antiretrovirals, and immunosuppressants (104966,105393,107119). One study shows that adding curcumin reduces the duration of shortness of breath by 6-9 days when compared with patients who received other treatments in combination with probiotics. However, there were no differences in the duration of other symptoms, including fever, cough, or sore throat. Subgroup analyses suggest that taking curcumin may improve oxygenation and reduce the need for supplemental oxygen or ventilation (105393). Another study shows that adding curcumin modestly reduces the time to resolution of COVID-19 symptoms, the length of supplemental oxygen use, and the likelihood for deterioration in the patients' condition when compared with patients who received other treatments alone (104966). A third study shows some benefit of curcumin on fever and cough when compared with baseline; however, it is unclear if any changes were significant when compared with placebo (107119). Doses of curcumin used in these studies include curcumin 525 mg with piperine 2.5 mg (C3 Complex, SamiDirect) twice daily, starting at admission and continuing for 14 days (105393), or a specific nanocurcumin product (SinaCurcumin, ExirNanoSina) 80 mg twice daily for 2 weeks or 240 mg daily in divided doses for 7 days (104966,107119). Limitations of these studies include the small number of patients with severe symptoms, the large number of outcomes evaluated, the inconsistencies in other treatments used, the lack of clarity related to presentation of some results, and, in most cases, a lack of blinding. Turmeric has also been evaluated in adults in the outpatient setting with suspected or confirmed mild to moderate COVID-19. One small clinical study shows that taking curcumin (SinaCurcumin, ExirNanoSina) 80 mg twice daily for 14 days in addition to other COVID-19 treatments (mainly hydroxychloroquine and azithromycin) reduces the duration of cough, chills, myalgia, and smell and taste disturbance, but not dyspnea, fever, sore throat, or others, by 1-2 days when compared with placebo with other treatments (106802). The validity of this study is limited by the lack of confirmatory diagnosis at baseline and lack of consistency with other treatments, as well as the unclear reporting of symptom duration in relation to the initiation of treatment. Another small clinical study in outpatients confirmed to have COVID-19 shows that taking curcumin 1000 mg plus piperine 10 mg (Sami Labs Limited) daily for 14 days modestly improves weakness, but not cough, pain, headache, difficulty breathing, or biochemical indices, when compared with placebo (109278). However, a clinical study in adults with confirmed asymptomatic or mild COVID-19 shows that taking curcumin (curcuRouge®, TheraBioPharma) 360 mg twice daily for 7 days within 5 days of COVID-19 diagnosis does not reduce the risk of fever or oxygen saturation below 96% when compared with placebo (114905). Some research has also examined the effect of turmeric as part of a polyherbal combination. Clinical research in patients hospitalized for moderate COVID-19 symptoms shows that using an Ayurvedic formulation 1776 mg twice daily containing turmeric, ashwagandha, ginger, and Boswellia serrata (BV-4051) for 14 days modestly reduces the duration of illness and reduces the severity of fever, cough, and smell and taste dysfunction when compared to placebo. There was no beneficial effect on other symptoms, including nasal congestion, breathing difficulty, headache, and gastrointestinal symptoms. More than half of the patients were also treated with remdesivir which did not impact the majority of these findings (109899).
Crohn disease. It is unclear if oral turmeric is beneficial for improving symptoms of active Crohn disease. Details: Some clinical research shows that taking the turmeric constituent, curcumin, 1.08 grams daily for one month, then 1.44 grams daily for one month, can reduce bowel movements, diarrhea, and abdominal pain when compared to baseline in patients with Crohn disease (79730). The validity of these findings is limited by the lack of a comparator group.
Denture stomatitis. Topical turmeric may be beneficial for treating denture stomatitis. Details: A small clinical study in patients with denture stomatitis shows that applying topical curcumin gel (Curenext, Abbott Laboratories) three times daily for 2 weeks resolves denture stomatitis lesions similarly to clotrimazole ointment (106797).
Diabetes. Lower quality clinical studies suggest that oral curcumin, a constituent of turmeric, may modestly improve glycemic control in patients with diabetes. Details: A meta-analysis of small clinical trials in patients with diabetic kidney disease shows that curcumin reduces levels of fasting glucose by approximately 8.3 mg/dL when compared with placebo. Curcumin was used in doses of 66.3-1670 mg daily for 2-6 months (107114). Preliminary clinical research included in the analysis shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily for 12 weeks reduces fasting blood glucose by about 20 mg/dL (104149). Other meta-analyses of low- to moderate-quality clinical studies in patients with a variety of conditions including type 2 diabetes show that taking turmeric extract, curcumin, or curcuminoids for 4-36 weeks improves glycated hemoglobin (HbA1c) by 0.4-0.7% and reduces fasting glucose by approximately 13 mg/dL when compared with placebo or conventional treatment (106806,108877,113604). The validity of these findings is limited by the heterogeneity of the included studies and broad curcuminoid doses ranging from 46-1500 mg daily. Conversely, other meta-analyses in patients with type 2 diabetes show that curcumin does not reduce HbA1c or insulin levels when compared with placebo (104965,108877,113604).
Diabetic foot ulcers. It is unclear if oral curcumin is beneficial in patients with diabetic foot ulcers. Details: Preliminary clinical research in patients with grade 3 diabetic foot ulcers shows that taking nanocurcumin 80 mg orally daily for 12 weeks does not improve glycated hemoglobin (HbA1c) or change the rate of ulcer healing when compared with placebo. Taking turmeric did result in modest decreases in fasting blood glucose, insulin levels, and insulin resistance (104972).
Diabetic nephropathy. It is unclear if oral curcumin is beneficial in patients with diabetic nephropathy. Details: Meta-analyses of two to four small clinical trials in patients with diabetic kidney disease show that curcumin modestly improves serum levels of creatinine, total cholesterol, and fasting glucose, and reduces systolic blood pressure by 4 mmHg, when compared with placebo. However, there was no effect on diastolic blood pressure, proteinuria, or serum levels of other plasma lipids or blood urea nitrogen. Curcumin was used in doses of 66.3-1670 mg daily for 2-6 months (107114). One small study included in this analysis, which evaluated patients receiving hemodialysis, shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily for 12 weeks reduces fasting blood glucose by about 20 mg/dL when compared with placebo (104149).
Dysmenorrhea. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in university students aged 18 to 24 in Iran with mild to severe primary dysmenorrhea and premenstrual syndrome (PMS) shows that taking a specific combination product containing curcumin 500 mg plus extract from black pepper 5 mg (C3 Complex, Sami Labs) daily, starting 7 days prior to menstruation and continuing for 3 days after menstruation for 3 consecutive menstrual cycles, does not improve the severity of symptoms when compared with placebo (106805). Conversely, a small clinical study in adults with moderately painful dysmenorrhea shows that taking a single dose of a combination product containing turmeric, Boswellia serrata, and sesame (Rhuleave-K, Arjuna Natural Private Ltd.) 1000 mg at the start of menstruation relieves menstrual cramp pain and reduces pain intensity for up to 6 hours when compared with placebo (112806). However, it is unclear if these effects are due to turmeric, other ingredients, or the combinations.
Endometriosis. It is unclear if oral turmeric is beneficial for reducing pain due to endometriosis. Details: A small clinical study in adults with endometriosis shows that taking the turmeric constituent, curcumin, 500 mg twice daily for 8 weeks does not affect pain associated with endometriosis or quality of life when compared with placebo (113603).
Erythema. Although there has been interest in using topical turmeric for reducing erythema, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
Exercise-induced muscle damage. It is unclear if oral curcumin, a constituent of turmeric, is beneficial for reducing muscle damage from exercise. Details: A meta-analysis of 12 small, lower-quality clinical studies in adults shows that taking curcumin 150-500 mg as a single dose before or after exercise or 180-5000 mg daily for up to 56 days reduces markers of muscle damage (i.e. serum creatine kinase levels) when compared with placebo. Curcumin seems most beneficial for this effect in untrained adults and when administered as a single dose. Additionally, a meta-analysis of 3 of these clinical studies shows that curcumin improves range of motion (114897). The interpretation of these findings is limited by significant heterogeneity.
Exercise-induced muscle soreness. It is unclear if oral turmeric or its constituent, curcumin, is beneficial for reducing muscle soreness from exercise. Details: A meta-analysis of 12 small, lower-quality clinical studies in trained and untrained adults shows that taking curcumin 150-500 mg as a single dose before or after exercise or 180-5000 mg daily for up to 56 days time reduces muscle soreness when compared with placebo. Subgroup analysis indicated that the largest effect size is observed at 96 hours post-exercise with progressively smaller effect sizes at earlier time points (114897). The interpretation of these findings is limited by significant heterogeneity. Turmeric has also been examined in combination with other ingredients. Clinical research in healthy active adults with moderate to severe exercise-induced muscle pain shows that taking a single, 1000-mg dose of turmeric and Boswellia serrata extracts in black sesame oil (Rhuleave-K; Arjuna Natural Private Ltd.) improves pain relief when compared with placebo, with maximal benefits within about 3 hours. The number of people needed to treat to obtain pain relief of at least 50% over a 6-hour period was 1.1 (109277).
Gingivitis. Small clinical studies suggest that oral turmeric and turmeric mouthwash may reduce the severity of gingivitis. Turmeric mouthwash appears to be similarly effective to chlorhexidine mouthwash. Details: A meta-analysis of generally preliminary clinical research shows that rinsing with a mouthwash containing curcumin for 3-4 weeks is as effective as rinsing with chlorhexidine for reducing the severity of gingivitis or plaque (106059). Mouthwashes in these studies contained 0.05% to 20% curcumin and were usually used twice daily for 3-4 weeks (81127,89723,106059). One mouthwash contained 0.05% turmeric extract and 0.005% eugenol (89723). Another small clinical trial shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily by mouth after breakfast for 4 weeks reduces the severity of gingivitis and gingival bleeding, but not plaque, when compared with placebo in patients with gingivitis and mild periodontitis (104146).
Gout. Although there is interest in using oral turmeric for gout, there is insufficient reliable information about the clinical effects of turmeric for this condition.
Gulf war syndrome. It is unclear if oral curcumin is beneficial in patients with Gulf war syndrome. Details: A small preliminary clinical trial in patients with Gulf war syndrome shows that taking curcumin (Meriva, Indena, S.p.A.) 500 mg twice daily for 30 days reduces overall symptoms, including pain, fatigue, gastrointestinal distress, and others, by 19% when compared with baseline. Taking a higher dose of 2000 mg twice daily for an additional 30 days appears to be no more effective than the lower dose (105395).
Hearing loss. It is unclear if oral turmeric is beneficial for treating hearing loss. Details: A small clinical study in adults with mild to moderate hearing impairment shows that taking curcumin 500 mg daily for 12 weeks improves some measures of auditory function, such as auditory brain stem response threshold, when compared with placebo (114906).
Helicobacter pylori. Small clinical studies suggest that oral turmeric is not beneficial for eradicating H. pylori when used alone or in combination with standard triple therapy or famotidine. Details: One small clinical study in patients with H. pylori gastritis shows that taking turmeric 2.1 grams daily for 4 weeks is less effective for eradicating H. pylori than taking an omeprazole-based triple regimen for one week (80957). Another small study in adults with peptic ulcers shows that taking a specific curcumin product (C3 Complex, Sami Labs LTD) 500 mg daily for 7 days, in conjunction with standard triple therapy, does not improve H. pylori eradication rates when compared with standard triple therapy alone. The addition of curcumin increased the resolution of dyspepsia symptoms by an additional 21%, but the clinical significance of this outcome is unclear (97420). In patients with dyspepsia, most of whom tested positive for fecal H. pylori antigen, clinical research shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg daily in addition to famotidine 40 mg daily for 30 days is no more effective for reducing fecal H. pylori antigen levels than taking famotidine alone (106063).
Hypertension. It is unclear if oral curcumin is beneficial in patients with hypertension. Details: A meta-analysis of approximately 30 clinical studies in healthy adults or patients with a variety of conditions shows that taking turmeric, curcumin, curcuminoids, or nano-curcumin for 4 to 24 weeks reduces systolic blood pressure by about 2 mmHg and diastolic blood pressure by about 0.8 mmHg when compared with placebo (113602). However, these blood pressure reductions may not be clinically meaningful. In addition, most of the included studies were small and utilized heterogeneous dosing regimens.
Impaired glucose tolerance (prediabetes). Oral turmeric may modestly improve glucose control in some patients with prediabetes. Details: In overweight or obese individuals with prediabetes, clinical research shows that taking a turmeric extract (BCM95 or Cucugreen; M/s Arjuna Natural Pvt Ltd.) 500 mg daily, providing 95% curcuminoids and at least 65% curcumin, for 90 days, either alone or in combination with zinc 30 mg as zinc gluconate, results in a small reduction in fasting glucose and glycated hemoglobin (HbA1c) when compared with placebo. There was also a small benefit in insulin sensitivity (105391). Other preliminary clinical research in adults with prediabetes shows that taking 500 mg of a combination of turmeric extract and Indian gooseberry extract in a 1:2 ratio along with phosphatidylcholine (EmbliQur) twice daily for 6 months modestly reduces fasting glucose and improves insulin resistance, when compared with placebo. However, changes in most other endpoints were not significantly different from placebo. Each 500 mg capsule contained turmeric extracts 29.86% and turmeric oil 1.27% (113355). The effect of turmeric on progression to type 2 diabetes in patients with prediabetes has also been investigated. Preliminary clinical research shows that taking a turmeric extract containing curcumin 750 mg twice daily for 9 months reduces the percentage of patients with prediabetes who develop type 2 diabetes when compared with placebo (81163).
Irritable bowel syndrome (IBS). It is unclear if oral turmeric is beneficial for improving symptoms of IBS. Details: Preliminary clinical research in otherwise healthy adults with IBS shows that taking a turmeric extract (Cynara Turmeric, Lichtwer Pharma) 72-144 mg daily for 8 weeks reduces IBS symptoms by about 40% to 60% when compared to baseline (79565). The validity of this finding is limited by the lack of a comparator group. Taking a combination product (CU-FEO, Alfa Wasserman S.p.A.) containing curcumin 42 mg and fennel essential oil 25 mg per capsule twice daily for 60 days improves overall ratings of abdominal pain, abdominal distention, and quality of life by 24% when compared with placebo (97422). It is unclear if these effects are due to turmeric, fennel, or the combination. Observational research suggests that adding a supplement (Enterofytol PLUS) providing curcumin 42 mg and berberine 200 mg twice daily for 2 months to conventional IBS treatment is associated with improvements in symptoms, such as abdominal discomfort, distension, and stool status, by up to 48% when compared with conventional treatment alone. Use of the supplement was also associated with a 64% reduced need for conventional treatments (113354).
Joint pain. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research 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 extract 125 mg, turmeric root extract 50 mg, cayenne 40 m H.U. 50 mg, and hyaluronic acid 4 mg in three divided doses daily for 8 weeks reduces joint pain severity by 37% compared to only 16% with placebo. However, it does not improve joint stiffness or function when compared with placebo (89560). It is unclear if these effects are due to turmeric, other ingredients, or the combination.
Juvenile idiopathic arthritis (JIA). Although there is interest in using oral turmeric for JIA, there is insufficient reliable information about the clinical effects of turmeric for this condition.
Knee pain. It is unclear if oral turmeric is beneficial for knee pain. Details: Clinical research in individuals with knee pain not related to existing arthritis shows that taking turmeric extract (TurmXTRA 60N; Inventia Healthcare Ltd. and Laila Nutraceuticals) 250 mg, providing 60% curcuminoids, once daily for 90 days modestly reduces pain associated with walking 80 meters when compared with placebo. The time taken to walk 80 meters and to climb nine steps was reduced by 4-5 seconds (105396).
Lichen planus. Evidence is conflicting on whether turmeric is beneficial for lichen planus. Details: A meta-analysis of several small, heterogeneous, mostly low-quality clinical and observational studies in adults with oral lichen planus shows that oral or topical curcumin with or without corticosteroids for 2-12 weeks does not improve erythema, lesion size, or pain when compared with control (113605). Similarly, a network meta-analysis of small clinical trials in patients with oral lichen planus shows that applying topical turmeric gel does not improve symptoms, clinical resolution, clinical scores, or reduce pain when compared with other available interventions (111640). However, small individual clinical studies have shown some benefit in using turmeric for lichen planus. A small clinical study shows that taking a specific turmeric extract (Curcumin C3 Complex, Sabinsa Corporation) containing curcuminoids 6000 mg daily in three divided doses for 12 days can reduce erythema and ulceration associated with lichen planus when compared with placebo (81109). Another small clinical study shows that taking a nanocurcumin product (SinaCurcumin, ExirNanoSina) 80 mg orally once daily for 1 month reduces oral lichen planus lesion size, pain, and burning similarly to prednisolone 10 mg taken orally once daily for 1 month (104961).
Metabolic syndrome. It is unclear if oral turmeric is beneficial for metabolic syndrome. Details: Research is conflicting on how turmeric, curcumin, and other formulations affect various measures of metabolic syndrome. Some clinical research and a meta-analysis of 13 clinical studies in patients with metabolic syndrome show that taking turmeric or curcumin decreases low-density lipoprotein (LDL) cholesterol, waist circumference by 2 cm, fasting blood glucose by 9 mg/dL, and diastolic blood pressure by 3 mmHg and increases high-density lipoprotein (HDL) cholesterol by 5 mg/dL when compared with placebo. However, other research shows that turmeric or curcumin have no effect on body weight, lipids, blood pressure, or blood glucose when compared with placebo (98999,99311,105400,109284,111347,112118). The validity of these effects is limited by high heterogeneity within the included studies and incomplete information about randomization and blinding. Studies have used turmeric, curcumin, and curcumin extract 80-2400 mg, in divided doses, daily for 4-12 weeks, nano-curcumin 80 mg daily for 12 weeks, or calebin A (CurCousin, Sabinsa), which is a constituent of turmeric, 25 mg twice daily for 3 months (98999,99311,105400,109284,111347,112118). Also, taking crude or phosphorylated curcuminoids 1 gram daily for 6 weeks does not improve sleep or reduce weight in these patients (105397).
Migraine headache. It is unclear if oral curcumin is beneficial for migraine headache. Details: A small clinical trial in females with regular migraines shows that taking curcumin 500 mg twice daily for 8 weeks reduces the severity and duration, but not the frequency, of migraine headaches when compared with placebo. In individuals taking curcumin, the duration of headache per month was reduced by approximately 10.3 hours from baseline (107116).
Myocardial infarction (MI). It is unclear if oral curcumin is beneficial for reducing myocardial injury following a MI. Details: Clinical research in patients with an acute MI shows that taking curcuminoids 500 mg plus piperine (Bioperine) 5 mg daily (Sami Labs) for 8 weeks does not improve ejection fraction, serum levels of cardiac troponin 1, blood pressure, levels of fasting blood glucose, or kidney function parameters when compared to placebo. However, there were some modest benefits on levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, glycated hemoglobin, and certain liver enzymes such as aspartate aminotransferase (AST) and alkaline phosphatase (ALP) (107115). The validity of this study is limited by its short duration and relatively small sample size.
Obesity. Oral turmeric might modestly improve weight loss, although any effect is unlikely to be clinically significant. Details: Multiple meta-analyses of small, mostly low-quality clinical studies in adults with a variety of comorbid conditions show that taking various forms and doses of turmeric or curcumin results in an average weight loss of about 0.6-1 kg, a decrease in body mass index (BMI) of about 0.2-0.5 kg/m2, and a decrease in waist circumference of about 1.3 cm when compared with control (102345,111351,111352). A sub-analysis of dose and duration shows that a reduction in waist circumference only occurs with curcumin daily doses above 1000 mg, and duration of treatment longer than 8 weeks (102345).
Oral submucous fibrosis. Small studies suggest that topical or oral curcumin might be beneficial for oral submucous fibrosis. However, the research is heterogenous with respect to outcomes, comparators, and the turmeric preparations, doses, and routes of administration utilized. Details: A meta-analysis of 3 small clinical trials shows that turmeric modestly improves mouth opening when compared with control. In addition, a systematic review of 11 studies shows that turmeric improves overall symptoms, including mouth opening, tongue protrusion, burning sensation, and cheek flexibility. However, studies were small with short duration and used variable dosing strategies. Most trials have studied oral turmeric 300-400 mg, either alone or with black pepper 100 mg or piperine 5 mg, for 3-6 months. Less commonly, turmeric was provided in lozenge form (105399). Also, a network meta-analysis suggests that the turmeric constituent curcumin with or without piperine is most the effective for reducing tongue protrusion when compared indirectly with various medical and antioxidant therapies; however, this analysis suggests that curcumin does not rank among the most effective interventions for improving mouth opening, burning sensation, or cheek flexibility (113514). Other preliminary clinical research shows that taking a specific oral product containing curcumin 300 mg and piperine 5 mg (Turmix tablets, Sanat Products), three times daily for 12 weeks, improves mouth opening, burning sensation, and tongue protrusion when compared with baseline, but not when compared with an antioxidant product containing alpha-lipoic acid, beta-carotene, copper, lycopene, selenium, and zinc. Mouth opening is further improved by concurrent use of a mouthwash (Turmix mouthwash, Sanat Products), containing 0.1% w/v turmeric extract (standardized to 95% curcumin), with thymol, eucalyptol, clove oil, mentha oil, and tea tree oil, twice daily for 12 weeks (102347). A small clinical study shows that applying topical curcumin gel (Curenext, Abbott Laboratories) 5 mg daily in 3-4 divided doses for 6 weeks, in combination with oral physical therapy, improves mouth opening similarly to using an aloe vera gel in combination with oral physical therapy. However, decreases in burning sensation are greater with aloe gel than curcumin gel (104967). It is not clear whether the gels, oral physical therapy, or the combination of both is responsible for the outcome. Finally, clinical research shows that applying a paste providing turmeric and holy basil 10 grams each, mixed in 10 mL of honey, to the oral mucosa 4 times daily for 3 months modestly improves mouth opening, tongue protrusion, and burning sensation and reduces the presence of fibrous bands when compared with taking a vitamin B supplement. There was no effect on the shape of the uvula (113325).
Pain (acute). Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with acute musculoskeletal pain shows that taking a specific combination product containing turmeric and Boswellia serrata extracts in black sesame oil (Rhuleave-K; Arjuna Natural Private Ltd.) 1000 mg daily for 7 days is as effective as acetaminophen 1000 mg daily for pain relief, onset of pain relief, and onset of maximal pain relief (109287). This study is limited by its lack of blinding and placebo control. Additionally, the dose of acetaminophen used in this study is below the standard recommended daily dose.
Periodontitis. There is limited evidence on the oral or topical use of turmeric or its constituent curcumin in patients with periodontitis. Details: A meta-analysis of heterogenous clinical studies in patients with chronic periodontitis suggests that use of local delivery gel products, usually turmeric 2% or a specific product containing curcumin (Curenext), modestly reduces pocket depth when compared with routine products, such as chlorhexidine. However, limited research suggests that curcumin products do not affect plaque or gingivitis measures, and curcumin irrigation does not affect pocket depth based on limited research (107108). A small preliminary clinical study in patients with severe chronic periodontitis shows that placing curcumin gel 2 mg on one side of the mouth along with scaling and root planing (SRP) reduces plaque and probing pocket depth, but not gingival index, when compared with SRP alone (101339). The use of oral curcumin has also been investigated. A small clinical trial in patients with gingivitis and mild periodontitis shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily after breakfast for 4 weeks reduces the severity of gingivitis and gingival bleeding, but not plaque, when compared with placebo (104146).
Physical performance. It is unclear if oral turmeric may be beneficial for improving physical performance in older adults. Details: A very small clinical study in moderately functioning, sedentary adults over age 65 with low-grade chronic inflammation shows that that taking a specific turmeric extract (Curcumin C3 Complex, Sabinsa Corporation) 500 mg twice daily for 12 weeks does not improve measures of physical function, walking speed, or muscle strength when compared with placebo (111357). However, this study may have been inadequately powered to detect any possible differences between groups.
Polycystic ovary syndrome (PCOS). Small clinical studies suggest that oral curcumin may improve some metabolic parameters in patients with PCOS, but these improvements may not be considered clinically significant. Details: Clinical research in patients with PCOS shows that taking curcumin 500 mg one to three times daily for 6-12 weeks improves some metabolic parameters (104968,105394,106795). Conversely, a small clinical study in patients aged 18 to 45 with PCOS in Iran shows that taking curcumin 1000 mg daily for 12 weeks modestly reduces fasting glucose but does not improve other metabolic parameters when compared with placebo. Taking curcumin also did not improve testosterone levels or hirsutism scores (111355). Meta-analyses show that taking curcumin modestly decreases body mass index (BMI) and improves measures of glycemic control, including fasting glucose and insulin resistance, and levels of total cholesterol when compared with placebo or metformin alone. However, effects on high-density lipoprotein (HDL) cholesterol levels were mixed and there was no effect on low-density lipoprotein (LDL) cholesterol or triglyceride levels (105394,106795,110219). Other preliminary clinical research shows that taking curcumin decreases plasma dehydroepiandrosterone and fasting plasma glucose levels when compared with placebo (104968). Some clinical research also shows that taking nano-curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily for 3 months is beneficial in patients already taking metformin 1500 mg daily. Taking curcumin had modest beneficial effects on fasting insulin and insulin resistance, as well as levels of testosterone, LDL cholesterol, HDL cholesterol, and triglycerides, when compared with metformin alone. There was no effect of curcumin on body weight, fasting blood glucose, or other hormones (106060).
Postoperative pain. Small clinical studies suggest that oral curcumin, a constituent of turmeric, may modestly reduce pain in various postoperative recovery settings. Details: One small clinical study in patients undergoing laparoscopic cholecystectomy shows that taking curcumin 2 grams daily reduces postoperative pain, fatigue, and the need for analgesics by the second postoperative week when compared with placebo (81099). In patients undergoing surgery for inguinal hernia and/or hydrocele, taking curcumin 1.2 grams daily for 5 days reduces inflammation and tenderness by the sixth postoperative day when compared with placebo (81206). Curcumin was taken in 3-4 divided doses daily in these studies. Finally, taking a single dose of curcumin 200 mg after surgical removal of impacted third molars modestly reduces acute postoperative pain when compared with taking mefenamic acid 500 mg (99305).
Premenstrual syndrome (PMS). It is unclear if oral turmeric may be beneficial for improving symptoms of PMS. Details: Some preliminary clinical research in patients with PMS shows that taking curcumin 100 mg twice daily, starting 7 days prior to menstruation and continuing for 3 days after menstruation, improves physical, behavioral, and mood symptoms, as well as overall severity of symptoms, when compared with placebo (97433). Conversely, in university students aged 18 to 24 in Iran with mild to severe PMS and primary dysmenorrhea, a clinical study shows that taking a specific combination product containing curcumin 500 mg plus extract from black pepper 5 mg (C3 Complex, Sami Labs) daily, starting 7 days prior to menstruation and continuing for 3 days after menstruation for 3 consecutive menstrual cycles, does not improve the severity of symptoms when compared with placebo (106805).
Prostate cancer. It is unclear if oral turmeric is beneficial for the prevention or treatment of prostate cancer. Details: One small clinical study shows that taking curcumin 1.8 grams orally three times daily for 7 days, starting 4 days prior to docetaxel and prednisone treatment and continuing for up to 6 cycles, reduces PSA levels by at least half in 59% of patients when compared to baseline. Also, all patients with measurable lesions showed at least stable disease after treatment, and 40% of patients showed partial response when compared with baseline (96132). It is unclear if the addition of turmeric is beneficial when compared with docetaxel and prednisone alone. In contrast, an additional small clinical trial shows that taking curcumin 6 grams daily for 7 days every 3 weeks, starting four days before docetaxel, does not improve PSA levels or progression-free or overall survival when compared with docetaxel alone (105392).
Psoriasis. Evidence is limited to one small study of topical use in patients with scalp psoriasis. Details: Preliminary clinical research in adults with scalp psoriasis shows that applying a tonic of turmeric to the scalp twice daily for 9 weeks modestly improves overall symptoms and quality of life when compared with a placebo tonic (97429).
Quality of life. Some preliminary clinical research suggests that oral curcumin might improve quality of life in patients with various chronic conditions. Details: Small or low-quality clinical trials in various patient populations show that taking curcumin improves at least some measures of quality of life when compared with placebo. Research has been conducted in patients with cancer, sulfur mustard-induced chronic pruritus, benign prostatic hyperplasia (BPH), or irritable bowel syndrome (IBS). Studies have evaluated curcumin 2250 mg once daily for 6 months, a specific combination product (C3 Complex, Sami Labs LTD) containing curcumin 500-1000 mg plus piperine (Bioperine) daily for 4-9 weeks, or a combination product (CU-FEO, Alfa Wasserman S.p.A.) containing curcumin 42 mg and fennel essential oil 25 mg per capsule twice daily for 60 days (81120,81176,97422,106799,107109,107111). Also, in patients with scalp psoriasis, applying a tonic of turmeric to the scalp twice daily for 9 weeks modestly improves quality of life when compared with a placebo tonic (97429).
Radiation dermatitis. It is unclear if oral or topical turmeric is beneficial for reducing the severity of radiation dermatitis. Details: A meta-analysis of 4 clinical studies in patients with breast cancer shows that taking curcumin 500-2000 mg three times daily for 3-7 weeks or applying curcumin gel 500 mg three times daily for 7 weeks reduces the radiation dermatitis severity score by about 0.5 points (on a 4-point scale) when compared with placebo or other control (111354). The validity of this analysis is limited by the heterogeneity of the included studies. However, a small clinical study in patients with breast cancer shows that taking nanocurcumin 80 mg twice daily during and for up to 2 weeks after treatment does not reduce skin reaction severity overall, but does modestly reduce pain, when compared with taking placebo. Also, there was a small reduction in skin reaction severity near the end of the study. All patients also used aloe vera leaf as part of the hospital protocol (109281). Another small preliminary clinical study in head and neck cancer patients shows that a specific cream (Vicco turmeric cream, Vicco Laboratories) containing turmeric and sandalwood oil, applied 5 times daily during radiation therapy, seems to reduce frequency and severity of radiation dermatitis when compared with baby oil (99307).
Radiation proctopathy. It is unclear if oral turmeric is beneficial for preventing proctitis or cystitis in patients receiving radiotherapy for prostate cancer. Details: A small clinical study in patients with prostate cancer shows that taking a specific nanocurcumin product (SinaCurcumin, ExirNanoSina) 120 mg daily, for 3 days before and also during a course of radiotherapy, does not reduce the occurrence of proctitis or cystitis when compared with placebo (100259). This study may have been underpowered to detect small treatment effects.
Respiratory tract infections. Although there is interest in using oral turmeric for various respiratory tract infections, including bronchitis and the common cold, it has not been clinically evaluated.
Rheumatoid arthritis (RA). Small clinical studies suggest that oral curcumin, a constituent of turmeric, may modestly improve some symptoms of RA. Details: Meta-analyses of small clinical trials in patients with RA show that taking curcumin alone or with other treatments modestly reduces overall RA symptoms, pain, and markers of inflammation when compared with control groups, including placebo or other treatments. However, some research shows that there is no beneficial effect on tender or swollen joint count from the limited available clinical research (109280,111358), while other research shows that there is a benefit (112117). Clinical studies have evaluated curcumin 120-1200 mg daily for 2 weeks to 3 months (11149,18205,96129). The validity of these findings is limited by the small size of the studies, and in some cases, the lack of a comparator group.
Sarcopenia. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in elderly patients with sarcopenia shows that taking a specific slow-release product containing turmeric, protein, carbohydrate, and fiber (Cureit, Aurea Biolabs), 500 mg orally daily for 3 months, increases handgrip strength by about 1% and distance walked before feeling tired by about 6% when compared with placebo. It also increases weightlifting capacity by about 6% from baseline, compared with a 5% decrease from baseline in those taking placebo (104973). It is unclear whether these small changes are clinically meaningful.
Schizophrenia. Although there is interest in using oral turmeric for improving cognitive function in patients with schizophrenia, there is insufficient reliable information about the clinical effects of turmeric for this use.
Sepsis. It is unclear if oral curcumin, a constituent of turmeric, is beneficial in patients with sepsis. Details: A small clinical trial in patients admitted to the intensive care unit (ICU) with sepsis shows that a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina), 80 mg dissolved in water and administered via gastric tube following lavage twice daily for 10 days does not affect length of ICU stay, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, blood pressure, or heart rate when compared with placebo (108873).
Smoking cessation. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in adults with a history of smoking 5 or more cigarettes daily for at least 3 years shows that taking a specific combination product containing turmeric 50 mg, ashwagandha, Indian gooseberry, tribulus, bacopa, Albizia lebbeck, licorice, clove, ginger, cowhage, and holy basil (Smotect, Smotect India) daily for 3 months reduces the number of cigarettes smoked by approximately 3 per day when compared with placebo. This product also reduces levels of alveolar carbon monoxide and carboxyhemoglobin but does not improve lung capacity (112115). However, only data from patients who completed treatment were analyzed, which limits the validity of this study. It is unclear if these effects are due to turmeric, other ingredients, or the combination. A moderate-sized clinical study in adults with a history of smoking 5 or more cigarettes daily for at least 3 years shows that taking a specific combination product containing turmeric 100 mg, ashwagandha, Indian gooseberry, tribulus, bacopa, Albizia lebbeck, licorice, clove, ginger, cowhage, and holy basil (Smotect, Smotect India) twice daily for 3 months reduces the number of cigarettes smoked by approximately 3 per day when compared with placebo. This product also reduces levels of alveolar carbon monoxide and carboxyhemoglobin but does not improve lung capacity (112115). However, only data from patients who completed treatment were analyzed, which limits the validity of this study. It is unclear if these effects are due to turmeric, other ingredients, or the combination.
Stress. It is unclear if oral turmeric is beneficial for reducing occupational stress in healthy adults. Details: A small clinical trial in healthy adults with occupational stress-related anxiety and fatigue shows that taking a specific type of turmeric (CurQfen, Akay Flavours and Aromatics Pvt Ltd.) that contains fenugreek dietary fiber for improved bioavailability at a dose of 500 mg twice daily for 30 days reduces stress and fatigue and improves quality of life when compared with placebo, and also when compared with a standard curcumin supplement with lower bioavailability (99308).
Stroke. It is unclear if oral turmeric is beneficial for stroke. Details: A small clinical study conducted in Iran in adults with a recent ischemic stroke shows that taking curcumin 500 mg and piperine, a pepper constituent, 5 mg (Sami Lans, India) daily for 12 weeks reduces carotid intima-media thickness, triglycerides, total cholesterol, and systolic and diastolic blood pressure, but does not improve low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or quality-of-life indicators when compared with placebo (113601). The validity of this study is limited by the lack of statistical adjustment for multiple comparisons which can lead studies to erroneously show differences between treatment groups.
Systemic lupus erythematosus (SLE). There is limited evidence on the oral use of turmeric in adults with lupus nephritis. Details: Preliminary clinical research in adults with lupus nephritis shows that taking turmeric 1.5 grams daily in three divided doses for 3 months reduces systolic blood pressure and improves kidney function when compared to baseline (81104). The validity of this finding is limited by the lack of a comparator group.
Tuberculosis. It is unclear if oral turmeric is beneficial in patients receiving treatment for tuberculosis. Details: A small clinical study in adults receiving antituberculosis treatment shows that taking a formulation containing turmeric 0.5 grams and Tinospora cordifolia 0.5 grams twice daily for 4 months can reduce levels of Mycobacterium tuberculosis in the sputum and improve lesion healing when compared with antituberculosis treatment alone. Also, liver toxicity associated with the antituberculosis treatment seems to be reduced when administered with this formulation (80424). It is unclear if these effects are due to turmeric, Tinospora cordifolia, or the combination.
Ulcerative colitis. It is unclear if oral or rectal turmeric, or its constituent, curcumin, is beneficial in adults with ulcerative colitis. Details: Although two small clinical studies in adults with ulcerative colitis show that taking oral turmeric extract 2-3 grams daily for 1-6 months improves the rate of remission and reduces relapse rate (79966,97423), a meta-analysis of these studies and one additional clinical study shows that turmeric does not improve remission rates when compared with placebo (99000). A specific product (Cur-Cure, Bara Herbs Inc) was used in some of these studies. Reasons for the conflicting findings are unclear, but may be due to small patient populations, concerns about blinding, and the inclusion of patients who were also taking immunomodulating drugs. It may also be due to differences in how a study measures remission. A meta-analysis of small clinical studies in patients with mild to moderate ulcerative colitis shows that adding oral curcumin 0.5-3 grams daily to standard treatment for 1-6 months may improve clinical remission rates, but not endoscopic remission rates, when compared with placebo (108872). However, the validity of this finding is limited by the small number of studies that evaluated endoscopic remission. A small clinical study shows that administering an enema form of turmeric extract (NCB-02, Himalaya Drug Company) as 20 mL, containing turmeric extract 140 mg, daily for 8 weeks increases response rate from 50% to about 93% and increases remission rate from about 31% to 71% when compared with placebo in patients with active ulcerative colitis. However, patients using the turmeric extract enema for shorter durations did not improve when compared with placebo (89729). Turmeric has also been investigated in combination with the Mediterranean diet. A small clinical trial shows that taking curcumin (VeNatura Curcumin Supplement) 800 mg twice daily while following the Mediterranean diet for 8 weeks is no more effective for improving ulcerative colitis symptom severity than following the Mediterranean diet without supplemental curcumin (113339).
Uveitis. It is unclear if oral curcumin is beneficial for uveitis. Details: Observational research in patients with acute non-infectious uveitic macular edema shows that taking a specific hydrophilic curcumin product (Cucrcuwin, Diabec, Alfa Intes) 60 mg twice daily for 6 months, in conjunction with standard corticosteroid treatment, and then alone for an additional 6 months, modestly improves best corrected visual acuity, but not macular thickness or intraocular pressure, when compared with standard treatment alone for 6 months (107110).
Wound healing. Although there is interest in using topical turmeric for wound healing, there is insufficient reliable information about the clinical effects of turmeric for this condition. More evidence is needed to rate turmeric for these uses.

Safety view details

Below is general information about the safety of the known ingredients contained in the product Fast-Acting. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

BOSWELLIA SERRATA (ApresFlex Boswellia serrata gum extract)

LIKELY SAFE ...when used orally and appropriately. Boswellia serrata extract in doses up to 1000 mg daily has been safely used in several clinical trials lasting up to 6 months (1708,1709,12432,12434,12438,17948,17949,17950,91379)(100699,100713,102089,109568,115735). Boswellia serrata extract has been used with apparent safety at a dose of 2400 mg for up to 1 month (102092).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (4912). There is insufficient reliable information available about the safety of using Boswellia serrata in medicinal amounts; avoid using.

CHONDROITIN SULFATE (Chondroitin Sulfate, Sodium)

LIKELY SAFE ...when used orally and appropriately. Chondroitin sulfate has been used safely in doses of up to 2000 mg daily for up to 6 years (1955,2533,13579,17732,22212,42339,42343,42348,42389,42396)(42398,42463,42477,42513,42520,42536,42541,89516,89558,89592)(89596,94360,94381,95788,95792). However, since chondroitin is often derived from bovine cartilage, historically, there was concern about contamination with diseased animal parts (1825). So far, there are no reports of disease transmission to humans due to use of contaminated chondroitin preparations. ...when used topically and appropriately as an ophthalmic viscosurgical device (OVD). Various products containing chondroitin sulfate and sodium hyaluronate have been granted approval by the US Food and Drug Administration (FDA) for use as an adjunct to cataract surgery (89436,89437).

POSSIBLY SAFE ...when used intramuscularly (10149,42397). ...when used topically as eye drops, short-term. Eye drops containing chondroitin sulfate with xanthan gum or glucosamine have been used with apparent safety four times daily for up to 3 months (89591,104443). ...when administered intravesically under the supervision of a physician (42338,42371,42373,42385,42387,42473,42511,42517,42519,109649).

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

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.

SODIUM

LIKELY SAFE ...when used orally and appropriately. Sodium is safe in amounts that do not exceed the Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams daily (100310). Higher doses can be safely used therapeutically with appropriate medical monitoring (26226,26227).

POSSIBLY UNSAFE ...when used orally in high doses. Tell patients to avoid exceeding the CDRR intake level of 2.3 grams daily (100310). Higher intake can cause hypertension and increase the risk of cardiovascular disease (26229,98176,98177,98178,98181,98183,98184,100310,109395,109396,109398,109399). There is insufficient reliable information available about the safety of sodium when used topically.

CHILDREN: LIKELY SAFE
when used orally and appropriately (26229,100310). Sodium is safe in amounts that do not exceed the CDRR intake level of 1.2 grams daily for children 1 to 3 years, 1.5 grams daily for children 4 to 8 years, 1.8 grams daily for children 9 to 13 years, and 2.3 grams daily for adolescents (100310).

CHILDREN: POSSIBLY UNSAFE
when used orally in high doses. Tell patients to avoid prolonged use of doses exceeding the CDRR intake level of 1.2 grams daily for children 1 to 3 years, 1.5 grams daily for children 4 to 8 years, 1.8 grams daily for children 9 to 13 years, and 2.3 grams daily for adolescents (100310). Higher intake can cause hypertension (26229).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately. Sodium is safe in amounts that do not exceed the CDRR intake level of 2.3 grams daily (100310).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in higher doses. Higher intake can cause hypertension (100310). Also, both the highest and the lowest pre-pregnancy sodium quintile intakes are associated with an increased risk of hypertensive disorders of pregnancy, including gestational hypertension and pre-eclampsia, and the delivery of small for gestational age (SGA) infants when compared to the middle intake quintile (106264).

TURMERIC (Turmeric (Curcuma longa) rhizome extract)

LIKELY SAFE ...when used orally and appropriately, short-term. Turmeric products providing up to 8 grams of curcumin have been safely used for up to 2 months (10453,11144,11150,17953,79085,89720,89721,89724,89728,101347)(81036,101349,107110,107116,107117,107118,107121,109278,109283,114899) and products providing up to 1500 mg of curcumin daily have been safely used for up to 12 months (114898) . Additionally, turmeric in doses up to 3 grams daily has been used with apparent safety for up to 3 months (102350,104146,104148,113357,114906). ...when used topically and appropriately (11148).

POSSIBLY SAFE ...when used as an enema, short-term. Turmeric extract in water has been used as a daily enema for up to 8 weeks (89729). ...when used topically as a mouthwash, short-term. A mouthwash containing 0.05% turmeric extract and 0.05% eugenol has been used safely twice daily for up to 21 days (89723).

PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in food.

PREGNANCY: LIKELY UNSAFE
when used orally in medicinal amounts; turmeric might stimulate the uterus and increase menstrual flow (12).

LACTATION: LIKELY SAFE
when used orally in amounts commonly found in food. There is insufficient reliable information available about the safety of using turmeric in medicinal amounts during lactation.

BOSWELLIA SERRATA (ApresFlex Boswellia serrata gum extract)

Interactions with Drugs view details

Below is general information about the interactions of the known ingredients contained in the product Fast-Acting. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, Boswellia serrata might increase the levels of CYP1A2 substrates.

Details

In vitro research shows that Boswellia serrata gum resin inhibits CYP1A2 enzymes (21178).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, Boswellia serrata might increase the levels of CYP2C19 substrates.

Details

In vitro research shows that Boswellia serrata gum resin inhibits CYP2C19 enzymes (21178).

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, Boswellia serrata might increase the levels of CYP2C9 substrates.

Details

In vitro research shows that Boswellia serrata gum resin inhibits CYP2C9 enzymes (21178).

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, Boswellia serrata might increase the levels of CYP2D6 substrates.

Details

In vitro research shows that Boswellia serrata gum resin inhibits CYP2D6 enzymes (21178).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, Boswellia serrata might increase or decrease the levels and clinical effects of CYP3A4 substrates.

Details

In vitro research shows that Boswellia serrata gum resin inhibits CYP3A4 enzymes (21178). Other in vitro research shows that Boswellia serrata extract inhibits CYP3A4 enzymes at most concentrations, although it may modestly induce enzyme activity at low concentrations (111404).

IMMUNOSUPPRESSANTS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, Boswellia serrata might alter the effects of immunosuppressive drugs.

Details

Some in vitro research suggests that Boswellia serrata extracts might inhibit mediators of autoimmune disorders such as leukotrienes and reduce production of antibodies and cell-mediated immunity (12432,12435,12437,12438). However, other in vitro research suggests that, when coupled with calcium ions, boswellic acids containing the keto group have immunostimulant properties within specific cell signaling pathways (21180).

CHONDROITIN SULFATE (Chondroitin Sulfate, Sodium)

WARFARIN (Coumadin)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Unlikely • Level of Evidence = D

Taking chondroitin in combination with glucosamine might increase the anticoagulant effects of warfarin. However, the effect of chondroitin alone is unclear.

Details

There have been multiple reports of increased international normalized ratio (INR) in patients taking warfarin with glucosamine, with or without chondroitin. The lack of reports with chondroitin alone seem to suggest that the interactions occurring in these reports may have been due to glucosamine. In two individual case reports, glucosamine/chondroitin combinations were associated with a significant increase in INR in patients previously stabilized on warfarin (11389,16130). Additionally, 20 voluntary case reports to the US 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, without chondroitin, to increased INR in patients taking warfarin (16131).

None known.

SODIUM

ANTIHYPERTENSIVE DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = A

Theoretically, a high intake of dietary sodium might reduce the effectiveness of antihypertensive drugs.

Details

High intake of dietary sodium can increase systolic and diastolic blood pressure (26222). Also, high intake of sodium may necessitate increased use of antihypertensive medications to achieve blood pressure control in some patients, such as those with chronic kidney disease (26223).

CORTICOSTEROIDS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Concomitant use of mineralocorticoids and some glucocorticoids with sodium supplements might increase the risk of hypernatremia.

Details

Mineralocorticoids and some glucocorticoids (corticosteroids) cause sodium retention. This effect is dose-related and depends on mineralocorticoid potency. It is most common with hydrocortisone, cortisone, and fludrocortisone, followed by prednisone and prednisolone (4425).

LITHIUM

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = B

Altering dietary intake of sodium might alter the levels and clinical effects of lithium.

Details

High sodium intake can reduce plasma concentrations of lithium by increasing lithium excretion (26225). Reducing sodium intake can significantly increase plasma concentrations of lithium and cause lithium toxicity in patients being treated with lithium carbonate (26224,26225). Stabilizing sodium intake is shown to reduce the percentage of patients with lithium level fluctuations above 0.8 mEq/L (112909). Patients taking lithium should avoid significant alterations in their dietary intake of sodium.

SODIUM-CONTAINING DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Concomitant use of sodium-containing drugs with additional sodium from dietary or supplemental sources may increase the risk of hypernatremia and long-term sodium-related complications.

Details

The Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams of sodium daily indicates the intake at which it is believed that chronic disease risk increases for the apparently healthy population (100310). Some medications contain high quantities of sodium. When used in conjunction with sodium supplements or high-sodium diets, the CDRR may be exceeded. Additionally, concomitant use may increase the risk for hypernatremia; this risk is highest in the elderly and people with other risk factors for electrolyte disturbances.

TOLVAPTAN (Samsca)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = C

Theoretically, concomitant use of tolvaptan with sodium might increase the risk of hypernatremia.

Details

Tolvaptan is a vasopressin receptor 2 antagonist that is used to increase sodium levels in patients with hyponatremia (29406). Patients taking tolvaptan should use caution with the use of sodium salts such as sodium chloride.

TURMERIC (Turmeric (Curcuma longa) rhizome extract)

ALKYLATING AGENTS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.

Details

In vitro research suggests that curcumin, a constituent of turmeric, inhibits mechlorethamine-induced apoptosis of breast cancer cells by up to 70%. Also, animal research shows that curcumin inhibits cyclophosphamide-induced tumor regression (96126). However, some in vitro research shows that curcumin does not affect the apoptosis capacity of etoposide. Also, other laboratory research suggests that curcumin might augment the cytotoxic effects of alkylating agents. Reasons for the discrepancies may relate to the dose of curcumin and the specific chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effect, if any, turmeric might have on alkylating agents.

AMLODIPINE (Norvasc)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Taking turmeric with amlodipine may increase levels of amlodipine.

Details

Animal research shows that giving amlodipine 1 mg/kg as a single dose following the use of turmeric extract 200 mg/kg daily for 2 weeks increases the maximum concentration and area under the curve by 53% and 56%, respectively, when compared with amlodipine alone (107113). Additional animal research shows that taking amlodipine 1 mg/kg with a curcumin 2 mg/kg pretreatment for 10 days increases the maximum concentration and area under the curve by about 2-fold when compared with amlodipine alone (103099).

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = B

Turmeric may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.

Details

Curcumin, a constituent of turmeric, has demonstrated antiplatelet effects in vitro (11143,81204,81271). Furthermore, two case reports have found that taking turmeric along with warfarin or fluindione was associated with an increased international normalized ratio (INR) (89718,100906). However, one clinical study in healthy volunteers shows that taking curcumin 500 mg daily for 3 weeks, alone or with aspirin 100 mg, does not increase antiplatelet effects or bleeding risk (96137). It is possible that the dose of turmeric used in this study was too low to produce a notable effect.

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, taking turmeric with antidiabetes drugs might increase the risk of hypoglycemia.

Details

Animal research and case reports suggest that curcumin, a turmeric constituent, can reduce blood glucose levels in patients with diabetes (79692,79984,80155,80313,80315,80476,80553,81048,81219). Furthermore, clinical research in adults with type 2 diabetes shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg decreased postprandial glucose levels for up to 24 hours when compared with glyburide alone, despite the lack of a significant pharmacokinetic interaction (96133). Other clinical studies in patients with diabetes show that taking curcumin daily can reduce blood glucose levels when compared with placebo (104149,114898,114900).

ANTITUMOR ANTIBIOTICS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.

Details

In vitro and animal research shows that curcumin, a constituent of turmeric, inhibits doxorubicin-induced apoptosis of breast cancer cells by up to 65% (96126). However, curcumin does not seem to affect the apoptosis capacity of daunorubicin. In fact, some research shows that curcumin might augment the cytotoxic effects of antitumor antibiotics, increasing their effectiveness. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effects, if any, antioxidants such as turmeric have on antitumor antibiotics.

CYTOCHROME P450 1A1 (CYP1A1) SUBSTRATES

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, turmeric might increase or decrease levels of drugs metabolized by CYP1A1. However, research is conflicting.

Details

Most in vitro and animal research suggests that the turmeric constituent, curcumin, INHIBITS CYP1A1, primarily in the liver (15823,21495,80876,81411). However, some evidence from in vitro research suggests that curcumin may INDUCE CYP1A1 in the intestines (21500).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, turmeric might increase levels of drugs metabolized by CYP1A2. However, research is conflicting.

Details

In vitro and animal research show that the turmeric constituent, curcumin, inhibits CYP1A2 (15823,21497,81304). However, other in vitro research suggests that curcumin does not significantly affect CYP1A2 (22000).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Turmeric might increase levels of drugs metabolized by CYP3A4.

Details

In vitro and animal research show that turmeric and its constituents curcumin and curcuminoids inhibit CYP3A4 (21497,21498,21499). Also, 8 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking turmeric and cancer medications that are CYP3A4 substrates, including everolimus, ruxolitinib, ibrutinib, and palbociclib, and bortezomib (111644). In another case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels after consuming turmeric powder at a dose of 15 or more spoonfuls daily for ten days prior. It was thought that turmeric increased levels of tacrolimus due to CYP3A4 inhibition (93544).
Conversely, other in vitro research suggests that turmeric induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates (111404). However, this interaction has not been reported in humans.

DOCETAXEL (Taxotere)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, turmeric might increase blood levels of oral docetaxel.

Details

Animal research suggests that the turmeric constituent, curcumin, enhances the oral bioavailability of docetaxel (80999). However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.

ESTROGENS

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, large amounts of turmeric might interfere with hormone replacement therapy through competition for estrogen receptors.

Details

In vitro research shows that curcumin, a constituent of turmeric, displaces the binding of estrogen to its receptors (21486).

GLYBURIDE (Diabeta, others)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = B

Theoretically, taking turmeric and glyburide in combination might increase the risk of hypoglycemia.

Details

Clinical research shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg increases blood levels of glyburide by 12% at 2 hours after the dose in patients with type 2 diabetes. While maximal blood concentrations of glyburide were not affected, turmeric modestly decreased postprandial glucose levels for up to 24 hours when compared to glyburide alone, possibly due to the hypoglycemic effect of turmeric demonstrated in animal research (96133).

HEPATOTOXIC DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, turmeric might increase the risk of liver damage when taken with hepatotoxic drugs.

Details

There is concern that turmeric might cause hepatotoxicity, especially when highly bioavailable formulations are used in high doses (103633,107122,109288,110221).

LOSARTAN (Cozaar)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, turmeric might increase the effects of losartan.

Details

Research in hypertensive rats shows that taking turmeric can increase the hypotensive effects of losartan (110897).

METHOTREXATE (Trexall, others)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, turmeric might have additive effects when used with hepatotoxic drugs such as methotrexate.

Details

In one case report, a 39-year-old female taking methotrexate, turmeric, and linseed oil developed hepatotoxicity (111644).

NORFLOXACIN (Noroxin)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, turmeric might increase the effects and adverse effects of norfloxacin.

Details

Animal research shows that taking curcumin, a turmeric constituent, can increase blood levels of orally administered norfloxacin (80863).

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, turmeric might increase blood levels of OATP4C1 substrates.

Details

In vitro research shows that the turmeric constituent curcumin competitively inhibits OATP4C1 transport. This transporter is expressed in the kidney and facilitates the renal excretion of certain drugs (113337). Theoretically, taking turmeric might decrease renal excretion of OATP substrates.

P-GLYCOPROTEIN SUBSTRATES

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, turmeric might increase the absorption of P-glycoprotein substrates.

Details

In vitro and animal research shows that curcuminoids and other constituents found in turmeric can inhibit P-glycoprotein expression and activity (21472,21473,21474,21475,21476,21477,21478,21479,21480)(21482,21484,111644).

PACLITAXEL (Abraxane, Onxol)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, turmeric might alter blood levels of paclitaxel, although any effect may not be clinically relevant.

Details

Clinical research in adults with breast cancer receiving intravenous paclitaxel suggests that taking turmeric may modestly alter paclitaxel pharmacokinetics. Patients received paclitaxel on day 1, followed by either no treatment or turmeric 2 grams daily from days 2-22. Pharmacokinetic modeling suggests that turmeric reduces the maximum concentration and area under the curve of paclitaxel by 12.1% and 7.7%, respectively. However, these changes are not likely to be considered clinically relevant (108876). Conversely, animal research suggests that curcumin, a constituent of turmeric, enhances the oral bioavailability of paclitaxel (22005). However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.

SULFASALAZINE (Azulfidine)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = B

Turmeric might increase the effects and adverse effects of sulfasalazine.

Details

Clinical research shows that taking the turmeric constituent, curcumin, can increase blood levels of sulfasalazine by 3.2-fold (81131).

TACROLIMUS (Prograf)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Turmeric might increase the effects and adverse effects of tacrolimus.

Details

In one case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels of 29 ng/mL. The patient previously had tacrolimus levels within the therapeutic range at 9.7 ng/mL. Ten days prior to presenting at the emergency room the patient started consumption of turmeric powder at a dose of 15 or more spoonfuls daily. It was thought that turmeric increased levels of tacrolimus due to cytochrome P450 3A4 (CYP3A4) inhibition (93544). In vitro and animal research show that turmeric and its constituent curcumin inhibit CYP3A4 (21497,21498,21499).

TALINOLOL

Interaction Rating = Moderate Be cautious with this combination.

Severity = Mild • Occurrence = Probable • Level of Evidence = B

Turmeric may reduce the absorption of talinolol in some situations.

Details

Clinical research shows that taking curcumin for 6 days decreases the bioavailability of talinolol when taken together on the seventh day (80079). The clinical significance of this effect is unclear.

TAMOXIFEN (Nolvadex)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = B

Theoretically, turmeric might reduce the levels and clinical effects of tamoxifen.

Details

In a small clinical trial in patients with breast cancer taking tamoxifen 20-30 mg daily, adding curcumin 1200 mg plus piperine 10 mg three times daily reduces the 24-hour area under the curve of tamoxifen and the active metabolite endoxifen by 12.8% and 12.4%, respectively, as well as the maximum concentrations of tamoxifen, when compared with tamoxifen alone. However, in the absence of piperine, the area under the curve for endoxifen and the maximum concentration of tamoxifen were not significantly reduced. Effects were most pronounced in patients who were extensive cytochrome P450 (CYP) 2D6 metabolizers (107123).

TOPOISOMERASE I INHIBITORS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Turmeric has antioxidant effects. There is some concern that this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.

Details

In vitro research shows that curcumin, a constituent of turmeric, inhibits camptothecin-induced apoptosis of breast cancer cells by up to 71% (96126). However, other in vitro research shows that curcumin augments the cytotoxic effects of camptothecin. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agents. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effect, if any, turmeric might have.

WARFARIN (Coumadin)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Turmeric might increase the risk of bleeding with warfarin.

Details

One case of increased international normalized ratio (INR) has been reported for a patient taking warfarin who began taking turmeric. Prior to taking turmeric, the patient had stable INR measurements. Within a few weeks of starting turmeric supplementation, the patient's INR increased to 10 (100906). Additionally, curcumin, the active constituent in turmeric, has demonstrated antiplatelet effects in vitro (11143,81204,81271), which may produce additive effects when taken with warfarin.

Report an Adverse Reaction to Fast-Acting

Adverse Effects view details

Below is general information about the adverse effects of the known ingredients contained in the product Fast-Acting. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

BOSWELLIA SERRATA (ApresFlex Boswellia serrata gum extract)

General ...Orally, Boswellia serrata extract is generally well-tolerated. For information on the safety of Boswellia serrata when applied topically or used as aromatherapy, see the Frankincense monograph.
Most Common Adverse Effects:
Orally: Abdominal pain, diarrhea, headache, heartburn, itching, nausea.
Serious Adverse Effects (Rare):
Orally: Large amounts of Boswellia serrata gum resin can cause bezoar formation.

Dermatologic ...Orally, Boswellia serrata extract (5-Loxin) has been associated with itching at doses of 100-250 mg daily (17948).

Gastrointestinal ...Orally, Boswellia serrata extract may cause diarrhea, nausea, abdominal pain, and heartburn (1708,12432,12438,17948,17949,17950,21149,109567,114685). A case of a large gastrointestinal bezoar has been reported in a 17-year-old female who chewed and swallowed large quantities of boswellia gum resin (Boswellia species not specified) for celiac disease (36914).

Musculoskeletal ...Orally, Boswellia serrata extract (5-Loxin) has been associated with one case of foot edema and four cases of generalized weakness in one clinical study (17948).

Neurologic/CNS ...Orally, Boswellia serrata extract may cause dizziness, headache, and vertigo. In one clinical study, nearly 11% of patients taking a specific Boswellia serrata extract (K-Vie) reported headache. Dizziness and vertigo were also reported, but at lower rates (109567). In another study, headache was reported in one patient taking a specific Boswellia serrata extract (5-Loxin) (17948).

Psychiatric ...Orally, one case of mania is reported in a 73-year-old male who took Boswellia powder mixed with honey for 3 days. The patient recovered after hospitalization and treatment with olanzapine (110526).

CHONDROITIN SULFATE (Chondroitin Sulfate, Sodium)

General ...Orally and topically, chondroitin sulfate is generally well tolerated. Intramuscular and ophthalmic use also seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, bloating, constipation, diarrhea, heartburn, nausea.
Serious Adverse Effects (Rare):
Orally: There have been rare reports of hepatotoxicity.

Cardiovascular ...One case of congestive heart failure and another case of myocardial infarction has been possibly attributed to use of glucosamine hydrochloride and chondroitin sulfate (13579,42477). Also, a case of mesenteric occlusion in one patient was considered possibly related to treatment with chondroitin sulfate and glucosamine (89520).

Dermatologic ...Orally, chondroitin sulfate has been associated with skin symptoms, such as eyelid edema, lower limb edema, alopecia, and skin rash (42513). Combinations of chondroitin sulfate along with glucosamine hydrochloride may also be associated with rash, water retention around eyes and scars, and hives on face, chest, torso, and legs when taken orally (42436,110628). A case of photosensitization that was reproducible with rechallenge has been reported following treatment with oral glucosamine-chondroitin products. However, it is not clear if this effect was due to glucosamine, chondroitin sulfate, or contaminants in the product (10408). A case of rash following treatment with intravesical chondroitin sulfate has been reported to be possibly related to the product (42385).

Gastrointestinal ...Orally, chondroitin might cause nausea, bloating, abdominal pain, diarrhea, constipation, vomiting, dyspepsia, and epigastric burning (42396,42436,42541,89561,110628,111647).

Genitourinary ...Intravesical chondroitin sulfate has been associated with cases of vulvar burning, vaginitis, urinary tract infection (UTI), dysuria, pelvic pain, and other bladder symptoms, such as increased frequency, urgency, or incontinence. However, these effects might be due to catheterization rather than chondroitin sulfate (42385,42387,42473).

Hematologic ...Concern has been expressed about possible anticoagulant activity of oral chondroitin sulfate. However, hematological changes have not occurred in patients taking chondroitin sulfate in clinical trials (760).

Hepatic ...Although relatively uncommon, combinations of glucosamine and chondroitin sulfate have been associated with acute liver injury that mimics autoimmune hepatitis. Two cases of elevated aminotransferase levels have been reported for patients taking glucosamine (form unspecified) and chondroitin sulfate at recommended doses. Aminotransferase levels, which were increased by four- to seven-fold, returned to normal following discontinuation of treatment (89515). Another case of abdominal pain, jaundice, fatigue, and elevated liver enzymes has been reported for a patient who used chondroitin sulfate (Condrosulf) for 2 years followed by a combination of glucosamine sulfate and chondroitin sulfate (Vita Mobility Complex) 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 chondroitin sulfate, other ingredients, or the combination.

Musculoskeletal ...Orally, chondroitin has been associated with musculoskeletal and connective-tissue events and disorders (13579,42520,95516).

Neurologic/CNS ...Rare cases of headache have been reported following treatment with products containing a combination of oral chondroitin sulfate and glucosamine hydrochloride or glucosamine sulfate (42436,89561). It is unclear if this effect was due to chondroitin, glucosamine, or the combination.
Patients should adhere to product directions when using chondroitin sulfate products that contain manganese. When taken at doses slightly higher than the recommended dose, these products can sometimes supply greater than the tolerable upper limit (UL) for manganese of 11 mg per day. Ingestion of more than 11 mg per day of manganese might cause significant central nervous system toxicity (7135).

Ocular/Otic ...A case of bilateral pinna chondritis (inflammation of the cartilage of the external ear) has been reported for a patient who received supplements containing glucosamine and chondroitin sulfate (42503).

Pulmonary/Respiratory ...A case of asthma exacerbation has been reported occurred following use of an oral glucosamine and chondroitin sulfate combination product (10002).

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).

SODIUM

General ...Orally, sodium is well tolerated when used in moderation at intakes up to the Chronic Disease Risk Reduction (CDRR) intake level. Topically, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: Worsened cardiovascular disease, hypertension, kidney disease.

Cardiovascular ...Orally, intake of sodium above the CDRR intake level can exacerbate hypertension and hypertension-related cardiovascular disease (CVD) (26229,98176,100310,106263). A meta-analysis of observational research has found a linear association between increased sodium intake and increased hypertension risk (109398). Observational research has also found an association between increased sodium salt intake and increased risk of CVD, mortality, and cardiovascular mortality (98177,98178,98181,98183,98184,109395,109396,109399). However, the existing research is unable to confirm a causal relationship between sodium intake and increased cardiovascular morbidity and mortality; high-quality, prospective research is needed to clarify this relationship (100312). As there is no known benefit with increased salt intake that would outweigh the potential increased risk of CVD, advise patients to limit salt intake to no more than the CDRR intake level (100310).
A reduction in sodium intake can lower systolic blood pressure by a small amount in most individuals, and diastolic blood pressure in patients with hypertension (100310,100311,106261). However, post hoc analysis of a small crossover clinical study in White patients suggests that 24-hour blood pressure variability is not affected by high-salt intake compared with low-salt intake (112910). Additionally, the available research is insufficient to confirm that a further reduction in sodium intake below the CDRR intake level will lower the risk for chronic disease (100310,100311). A meta-analysis of clinical research shows that reducing sodium intake increases levels of total cholesterol and triglycerides, but not low-density lipoprotein (LDL) cholesterol, by a small amount (106261).
It is unclear whether there are safety concerns when sodium is consumed in amounts lower than the adequate intake (AI) levels. Some observational research has found that the lowest levels of sodium intake might be associated with increased risk of death and cardiovascular events (98181,98183). However, this finding has been criticized because some of the studies used inaccurate measures of sodium intake, such as the Kawasaki formula (98177,98178,101259). Some observational research has found that sodium intake based on a single 24-hour urinary measurement is inversely correlated with all-cause mortality (106260). The National Academies Consensus Study Report states that there is insufficient evidence from observational studies to conclude that there are harmful effects from low sodium intake (100310).

Endocrine ...Orally, a meta-analysis of observational research has found that higher sodium intake is associated with an average increase in body mass index (BMI) of 1. 24 kg/m2 and an approximate 5 cm increase in waist circumference (98182). It has been hypothesized that the increase in BMI is related to an increased thirst, resulting in an increased intake of sugary beverages and/or consumption of foods that are high in salt and also high in fat and energy (98182). One large observational study has found that the highest sodium intake is not associated with overweight or obesity when compared to the lowest intake in adolescents aged 12-19 years when intake of energy and sugar-sweetened beverages are considered (106265). However, in children aged 6-11 years, usual sodium intake is positively associated with increased weight and central obesity independently of the intake of energy and/or sugar-sweetened beverages (106265).

Gastrointestinal ...In one case report, severe gastritis and a deep antral ulcer occurred in a patient who consumed 16 grams of sodium chloride in one sitting (25759). Chronic use of high to moderately high amounts of sodium chloride has been associated with an increased risk of gastric cancer (29405).

Musculoskeletal ...Observational research has found that low sodium levels can increase the risk for osteoporosis. One study has found that low plasma sodium levels are associated with an increased risk for osteoporosis. Low levels, which are typically caused by certain disease states or chronic medications, are associated with a more than 2-fold increased odds for osteoporosis and bone fractures (101260).
Conversely, in healthy males on forced bed rest, a high intake of sodium chloride (7.7 mEq/kg daily) seems to exacerbate disuse-induced bone and muscle loss (25760,25761).

Oncologic ...Population research has found that high or moderately high intake of sodium chloride is associated with an increased risk of gastric cancer when compared with low sodium chloride intake (29405). Other population research in patients with gastric cancer has found that a high intake of sodium is associated with an approximate 65% increased risk of gastric cancer mortality when compared with a low intake. When zinc intake is taken into consideration, the increased risk of mortality only occurred in those with low zinc intake, but the risk was increased to approximately 2-fold in this sub-population (109400).

Pulmonary/Respiratory ...In patients with hypertension, population research has found that sodium excretion is modestly and positively associated with having moderate or severe obstructive sleep apnea. This association was not found in normotensive patients (106262).

Renal ...Increased sodium intake has been associated with impaired kidney function in healthy adults. This effect seems to be independent of blood pressure. Observational research has found that a high salt intake over approximately 5 years is associated with a 29% increased risk of developing impaired kidney function when compared with a lower salt intake. In this study, high salt intake was about 2-fold higher than low salt intake (101261).

TURMERIC (Turmeric (Curcuma longa) rhizome extract)

General ...Orally and topically, turmeric is generally well tolerated.
Most Common Adverse Effects:
Orally: Constipation, dyspepsia, diarrhea, distension, gastroesophageal reflux, nausea, and vomiting.
Topically: Curcumin, a constituent of turmeric, can cause contact urticaria and pruritus.

Cardiovascular ...Orally, a higher dose of turmeric in combination with other ingredients has been linked to atrioventricular heart block in one case report. It is unclear if turmeric caused this adverse event or if other ingredients or a contaminant were the cause. The patient had taken a combination supplement containing turmeric 1500-2250 mg, black soybean 600-900 mg, mulberry leaves, garlic, and arrowroot each about 300-450 mg, twice daily for one month before experiencing atrioventricular heart block. Heart rhythm normalized three days after discontinuation of the product. Re-administration of the product resulted in the same adverse effect (17720).

Dermatologic ...Following occupational and/or topical exposure, turmeric or its constituents curcumin, tetrahydrocurcumin, or turmeric oil, can cause allergic contact dermatitis (11146,79270,79470,79934,81410,81195). Topically, curcumin can also cause rash or contact urticaria (79985,97432,112117). In one case, a 60-year-old female, with no prior reactivity to regular oral consumption of turmeric products, developed urticaria after topical application of turmeric massage oil (97432). A case of pruritus has been reported following topical application of curcumin ointment to the scalp for the treatment of melanoma (11148). Yellow discoloration of the skin has been reported rarely in clinical research (113356). Orally, curcumin may cause pruritus, but this appears to be relatively uncommon (81163,97427,104148,114899). Pitting edema may also occur following oral intake of turmeric extract, but the frequency of this adverse event is less common with turmeric than with ibuprofen (89720). A combination of curcumin plus fluoxetine may cause photosensitivity (89728).

Gastrointestinal ...Orally, turmeric can cause gastrointestinal adverse effects (107110,107112,112118), including constipation (81149,81163,96135,113355), flatulence and yellow, hard stools (81106,96135), nausea and vomiting (10453,17952,89720,89728,96127,96131,96135,97430,112117,112118), diarrhea or loose stool (10453,17952,18204,89720,96135,110223,112117,112118,114898,114899), dyspepsia (17952,89720,89721,96161,112118), gastritis (89728), distension and gastroesophageal reflux disease (18204,89720), abdominal fullness and pain (81036,89720,96161,97430,114898,114899), epigastric burning (81444), and tongue staining (89723).

Hepatic ...Orally, turmeric has been associated with liver damage, including non-infectious hepatitis, cholestasis, and hepatocellular liver injury. There have been at least 70 reports of liver damage associated with taking turmeric supplements for at least 2 weeks and for up to 14 months. Most cases of liver damage resolved upon discontinuation of the turmeric supplement. Sometimes, turmeric was used concomitantly with other supplements and medications (99304,102346,103094,103631,103633,103634,107122,109288,110221). The Drug-Induced Liver Injury Network (DILIN) has identified 10 cases of liver injury which were considered to be either definitely, highly likely, or probably associated with turmeric; none of these cases were associated with the use of turmeric in combination with other potentially hepatotoxic supplements. Most patients (90%) presented with hepatocellular pattern of liver injury. The median age of these case reports was 56 years and 90% identified as White. In these case reports, the carrier frequency on HLAB*35:01 was 70%, which is higher than the carrier frequency found in the general population. Of the ten patients, 5 were hospitalized and 1 died from liver injury (109288).
It is not clear if concomitant use with other supplements or medications contributes to the risk for liver damage. Many case reports did not report turmeric formulation, dosing, or duration of use (99304,103094,103631,103634,109288). However, at least 10 cases involved high doses of curcumin (250-1812.5 mg daily) and the use of highly bioavailable formulations such as phytosomal curcumin and formulations containing piperine (102346,103633,107122,109288,110221).

Neurologic/CNS ...Orally, turmeric has been associated with headache and vertigo (81163,114898).

Psychiatric ...Orally, the turmeric constituent curcumin or a combination of curcumin and fluoxetine can cause giddiness, although this event seems to be uncommon (81206,89728).

Renal ...Orally, turmeric has been linked to one report of kidney failure, although the role of turmeric in this case is unclear. A 69-year-old male developed kidney failure related to calcium oxalate deposits in the renal tubules following supplementation with turmeric 2 grams daily for 2 years as an anti-inflammatory for pelvic pain. While turmeric is a source of dietary oxalates, pre-existing health conditions and/or chronic use of antibiotics may have contributed to the course of disease (113343).

Other ...There is a single case report of death associated with intravenous use of turmeric. However, analysis of the treatment vial suggests that the vial contained only 0.023% of the amount of curcumin listed on the label. Also, the vial had been diluted in a solution of ungraded polyethylene glycol (PEG) 40 castor oil that was contaminated with 1.25% diethylene glycol. Therefore the cause of death is unknown but is unlikely to be related to the turmeric (96136).

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