dietary supplements

Importance Restless legs syndrome (RLS) is a sleep-related movement disorder that affects approximately 3% of US adults to a clinically significant extent and can cause substantial sleep disturbance.

Observations Restless legs syndrome is characterized by an overwhelming urge to move the limbs, typically the legs, often accompanied by unpleasant limb sensations (eg, achiness, tingling). Symptoms, provoked by immobility, are relieved while moving and are typically present or most severe in the evening or at night. Restless legs syndrome symptoms may lead to difficulty falling asleep, staying asleep, or returning to sleep. According to population-based studies, approximately 8% of US adults experience RLS symptoms of any frequency annually and 3% experience moderately or severely distressing symptoms at least twice weekly. Patients with RLS have impaired quality of life and elevated rates of cardiovascular disease (29.6% with coronary artery disease, stroke, or heart failure), depression (30.4%), and suicidal ideation or self-harm (0.35 cases/1000 person-years). Restless legs syndrome is common among patients with multiple sclerosis (27.5%), end-stage kidney disease (24%), and iron deficiency anemia (23.9%); during pregnancy and especially in the third trimester (22%); with peripheral neuropathy (eg, diabetic, idiopathic; 21.5%); and with Parkinson disease (20%). Other risk factors include family history of RLS, northern European descent, female sex (2:1 vs male sex), and older age (RLS prevalence of 10% in adults ≥65 years). Restless legs syndrome is diagnosed based on clinical history; polysomnography is not recommended for diagnosis. Iron supplementation with ferrous sulfate (325-650 mg daily or every other day) or intravenous iron (1000 mg) should be initiated for serum ferritin level less than or equal to 100 ng/mL or transferrin saturation less than 20%. If possible, medications associated with RLS, including serotonergic antidepressants, dopamine antagonists, and centrally acting H1 antihistamines (eg, diphenhydramine), should be discontinued. Gabapentinoids (eg, gabapentin, gabapentin enacarbil, pregabalin) are first-line pharmacologic therapy. In randomized clinical trials, approximately 70% of patients treated with gabapentinoids had much or very much improved RLS symptoms vs approximately 40% with placebo (P < .001). Dopamine agonists (eg, ropinirole, pramipexole, rotigotine) are no longer recommended as first-line medications due to the risk of augmentation, an iatrogenic worsening of RLS symptoms, which has an annual incidence of 7% to 10% with these medications. Patients who do not improve with first-line treatment or have augmented RLS often benefit from low-dose opioids (eg, methadone 5-10 mg daily).

Conclusions and Relevance Restless legs syndrome affects approximately 3% of adults and can have negative effects on sleep and quality of life. Initial management includes cessation of exacerbating medications, as well as iron supplementation for patients with low-normal iron indices. If medication therapy is indicated, gabapentinoids are first-line treatment.

Author/s:

John W. Winkelman, Benjamin Wipper

The association between medication use and vitamin B12 deficiency in the elderly population: a cross- sectional study

Megan George — Mon, 09 Feb 2026 16:51:18 +0000

Date Added:

February 9, 2026

Journal/Publication:

BMC Geriatrics

Publication Date:

February 3, 2026

URL:

The association between medication use and vitamin B12 deficiency in the elderly population: a cross- sectional study

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1186/s12877-026-07040-6

Keywords

Vitamin B 12 Deficiency

PMID (1):

41634610

MeSH

Vitamin B 12 Deficiency

Perhaps patients who are taking metformin should be routinely put on oral B12 and then monitored, James W. Mold, MD, MPH

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Background
Vitamin B12 deficiency is common in the elderly population and can cause severe complications. The use of certain medication has in previous studies been associated with vitamin B12 deficiency in the general population. To identify elderly patients at risk for vitamin B12 deficiency due to medication use, we evaluated the association between medication use and vitamin B12 deficiency in the elderly population.

Methods
Hospitalized geriatric patients 65 years of age or over with a serum vitamin B12 measurement within one week of the admittance date were included. Patients were classified as either B12 normal (258–635 pmol/L) or B12 deficient (< 148 pmol/L). Upon hospital admission patients’ medication use was verified. The association between vitamin B12 deficiency and the use of antacid, antiepileptic, antidiabetic, lipid lowering and other medication was evaluated by univariate and multivariate analyses.

Results
Of the 7132 patients included in the study, 532 (7.5%) had vitamin B12 deficiency and 3433 (48.1%) patients had normal vitamin B12 concentrations. Metformin use was significantly and independently (adjusted OR 2.5; 95% CI 1.7–3.6) associated with a dose-dependent higher risk of vitamin B12 deficiency. The use of other medication evaluated in this study was not associated with vitamin B12 deficiency.

Conclusions
Metformin use is significantly associated with vitamin B12 deficiency in the elderly, and this risk rises with higher metformin doses. Monitoring and timely start of vitamin B12 supplementation along with the lowest possible metformin dose are essential to prevent complications.

Author/s:

Monique P H Tillemans, Thijs J Giezen, Toine C G Egberts, Kees J Kalisvaart

Vitamin D for Prevention of Disease

Erin Blanchette — Mon, 28 Apr 2025 16:44:37 +0000

Date Added:

April 28, 2025

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

April 23, 2025

URL:

Vitamin D for Prevention of Disease

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2025.2278

Keywords

PMID (1):

40266611

MeSH

A guideline from the Endocrine Society regarding Vitamin D supplementation in healthy children and adults. James W. Mold, MD, MPH

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Vitamin D regulates bone homeostasis,1 and epidemiologic studies suggest that lower vitamin D levels may be associated with increased risk of RTIs, cardiovascular disease, malignancy, and metabolic disorders.2,3 Increased awareness of possible health benefits associated with higher 25(OH)D levels has resulted in widespread vitamin D testing and supplementation in the general US population. Nonetheless, there is no consensus on a threshold value below which people should be offered vitamin D supplementation.3,4 In 2021, the US Preventive Services Task Force reported that there was insufficient evidence to recommend routine screening of asymptomatic adults for vitamin D deficiency.4 Rates of marked vitamin D deficiency (25[OH]D ≤12 ng/mL) vary by race and ethnicity, with higher rates in non-Hispanic Asian (8%), non-Hispanic Black (18%), and Hispanic (6%) people compared with non-Hispanic White people (2%).3

Author/s:

Eva S Liu, Andrew M Davis, Sherri-Ann M Burnett-Bowie

Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial

Erin Blanchette — Mon, 17 Mar 2025 15:16:55 +0000

Date Added:

March 17, 2025

Journal/Publication:

Nature Communications

Publisher:

Nature Portfolio

Publication Date:

February 29, 2024

Issue:

Volume:

Pages:

1859

URL:

Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1038/s41467-024-46116-y

Keywords

aging

cognition

dietary supplements

Gastrointestinal Microbiome

gut microbiome

gut health

PMID (1):

38424099

MeSH

Gastrointestinal Microbiome* / physiology

gastrointestinal microbiome

Muscular Diseases

Specific prebiotic supplements appear to improve cognition in older adults. James W. Mold, MD, MPH

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Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (β = 0.579; 95% CI -1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (β = -0.482; 95% CI,-0.813, -0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. ClinicalTrials.gov registration: NCT04309292.

Author/s:

Mary Ni Lochlainn, Ruth C E Bowyer, Janne Marie Moll, María Paz García, Samuel Wadge, Andrei-Florin Baleanu, Ayrun Nessa, Alyce Sheedy, Gulsah Akdag, Deborah Hart, Giulia Raffaele, Paul T Seed, Caroline Murphy, Stephen D R Harridge, Ailsa A Welch, Carolyn Greig, Kevin Whelan, Claire J Steves

The Women’s Health Initiative Randomized Trials and Clinical Practice

Alex Haga — Mon, 13 May 2024 21:25:57 +0000

Date Added:

May 13, 2024

Journal/Publication:

JAMA

Publisher:

JAMA

Publication Date:

May 1, 2024

URL:

The Women’s Health Initiative Randomized Trials and Clinical Practice

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jama.2024.6542

Keywords

PMID (1):

38691368

A summary review of the results of the Womens Health Initiative Study pertaining to HRT, Vit D/calcium supplementation, and low-fat diet in menopausal women. James W. Mold, MD, MPH

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Importance: Approximately 55 million people in the US and approximately 1.1 billion people worldwide are postmenopausal women. To inform clinical practice about the health effects of menopausal hormone therapy, calcium plus vitamin D supplementation, and a low-fat dietary pattern, the Women's Health Initiative (WHI) enrolled 161 808 postmenopausal US women (N = 68 132 in the clinical trials) aged 50 to 79 years at baseline from 1993 to 1998, and followed them up for up to 20 years.

Observations: The WHI clinical trial results do not support hormone therapy with oral conjugated equine estrogens plus medroxyprogesterone acetate for postmenopausal women or conjugated equine estrogens alone for those with prior hysterectomy to prevent cardiovascular disease, dementia, or other chronic diseases. However, hormone therapy is effective for treating moderate to severe vasomotor and other menopausal symptoms. These benefits of hormone therapy in early menopause, combined with lower rates of adverse effects of hormone therapy in early compared with later menopause, support initiation of hormone therapy before age 60 years for women without contraindications to hormone therapy who have bothersome menopausal symptoms. The WHI results do not support routinely recommending calcium plus vitamin D supplementation for fracture prevention in all postmenopausal women. However, calcium and vitamin D are appropriate for women who do not meet national guidelines for recommended intakes of these nutrients through diet. A low-fat dietary pattern with increased fruit, vegetable, and grain consumption did not prevent the primary outcomes of breast or colorectal cancer but was associated with lower rates of the secondary outcome of breast cancer mortality during long-term follow-up.

Conclusions and relevance: For postmenopausal women, the WHI randomized clinical trials do not support menopausal hormone therapy to prevent cardiovascular disease or other chronic diseases. Menopausal hormone therapy is appropriate to treat bothersome vasomotor symptoms among women in early menopause, without contraindications, who are interested in taking hormone therapy. The WHI evidence does not support routine supplementation with calcium plus vitamin D for menopausal women to prevent fractures or a low-fat diet with increased fruits, vegetables, and grains to prevent breast or colorectal cancer. A potential role of a low-fat dietary pattern in reducing breast cancer mortality, a secondary outcome, warrants further study.

Author/s:

Manson, J.E., Crandall, C.J., Rossouw, J.E.

Geographic Tongue

Bethie Seay — Mon, 13 Sep 2021 05:00:00 +0000

Date Added:

September 13, 2021

Type:

Meta-analyses, Reviews, and Guidelines

DOI (1):

10.1503/cmaj.202855

MeSH

Glossitis, Benign Migratory

A good picture and quick summary about geographic tongue.

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A 37-year-old woman presented to the outpatient ear, nose and throat department with a 1-year history of intermittent burning and changes in appearance of her tongue. The patient had no history of bleeding, pain or concurrent skin or genital lesions, and she had no dermatologic history. A course of clotrimazole and vitamin B supplementation had been ineffective. On examination, she had well-defined annular lesions with central erythema and a raised white serpentine border involving the dorsal anterior two-thirds of her tongue (Figure 1). There was no fissuring. Based on her history, the appearance of her tongue and an otherwise normal physical examination, we diagnosed geographic tongue. We prescribed topical benzydamine, as required, for symptomatic relief of burning. At 6-month follow-up, she was free of symptoms, with patchy tongue changes.

Author/s:

Prasanth, V. J., Singh, A.

The effect of high-dose vitamin D supplementation on serum vitamin D levels and milk calcium concentration in lactating women and their infants

Bethie Seay — Fri, 03 Sep 2021 05:00:00 +0000

Date Added:

September 3, 2021

Type:

Clinical Research Results

DOI (1):

10.1089/bfm.2006.1.27

PMID (1):

17661558

MeSH

Adult

Bone Density Conservation Agents

calcium

dietary supplements

Dose-Response Relationship

Infant Nutritional Physiological Phenomena

infant, newborn

Lactation

Maternal Nutritional Physiological Phenomena

Milk, Human

Nutritional Requirements

Nutritional Status

prospective studies

vitamin D

This study provides guidance on Vitamin D supplementation in lactating women and their babies.

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Objective: Improve vitamin D status in lactating women and their recipient infants, and measure breast milk calcium concentration [Ca] as a function of vitamin D regimen.

Design/methods: Fully breastfeeding mothers were randomized at 1 month postpartum to 2000 (n = 12) or 4000 (n = 13) IU/day vitamin D for 3 months to achieve optimal vitamin D status [serum 25(OH)D > or =32 ng/mL (80 nmol/L)]. Breast milk [Ca], maternal and infant serum 25(OH)D and serum Ca, and maternal urinary Ca/Cr ratio were measured monthly.

Results: Mothers were similar between groups for age, race, gestation, and birth weight. 25(OH)D increased from 1 to 4 months in both groups (mean +/- SD): +11.5 +/- 2.3 ng/mL for group 2000 (p = 0.002) and +14.4 +/- 3.0 ng/mL for group 4000 (p = 0.0008). The 4000 IU/day regimen was more effective in raising both maternal and infant serum levels and breast milk antirachitic activity than the 2000 IU/day regimen. Breast milk [Ca] fell with continued lactation through 4 months in the 2000 and 4000 IU groups. Decline in breast milk [Ca] was not associated with vitamin D dose (p = 0.73) or maternal 25(OH)D (p = 0.94). No mother or infant experienced vitamin D-related adverse events, and all laboratory parameters remained in the normal range.

Conclusion: High-dose vitamin D was effective in increasing 25(OH)D levels in fully breastfeeding mothers to optimal levels without evidence of toxicity. Breast milk [Ca] and its decline in both groups during 1 to 4 months were independent of maternal vitamin D status and regimen. Both the mother and her infant attained improved vitamin D status and maintained normal [Ca].

Author/s:

Basile, L. A., Taylor, S. N., Wagner, C. L., Horst, R. L., Hollis, B. W.

Effect of Vitamin D3 Supplements on Development of Advanced Cancer: A Secondary Analysis of the VITAL Randomized Clinical Trial

Brian Desmarais — Thu, 19 Nov 2020 18:03:28 +0000

Date Added:

November 19, 2020

Journal/Publication:

JAMA Network Open

Publication Date:

November 8, 2020

Issue:

Volume:

URL:

Effect of Vitamin D3 Supplements on Development of Advanced Cancer: A Secondary Analysis of the VITAL Randomized Clinical Trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jamanetworkopen.2020.25850

MeSH

cardiovascular diseases

This large RCT suggests that supplementation with Vit D3 2000 IU daily may reduce the risk of metastatic cancer. James W. Mold, MD, MPH

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Importance Epidemiologic and trial data suggest that vitamin D supplementation may reduce metastatic cancer and cancer mortality, reflecting shared biological pathways.

Objective To follow up on the possible reduction in cancer death in the Vitamin D and Omega-3 Trial (VITAL) with an evaluation of whether vitamin D reduces the incidence of advanced (metastatic or fatal) cancer and an examination possible effect modification by body mass index.

Design, Setting, and Participants VITAL is a randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial of vitamin D3 (cholecalciferol, 2000 IU/d) and marine omega-3 fatty acids (1 g/d). This multicenter clinical trial was conducted in the United States; participants included men aged 50 years or older and women aged 55 years or older who were free of cancer and cardiovascular disease at baseline. Randomization took place from November 2011 through March 2014, and study medication ended on December 31, 2017. Data for this secondary analysis were analyzed from November 1, 2011, to December 31, 2017.

Interventions Vitamin D3 (cholecalciferol, 2000 IU/d) and marine omega-3 fatty acids (1 g/d) supplements.

Main Outcomes and Measures For the present analysis, the primary outcome was a composite incidence of metastatic and fatal invasive total cancer, because the main VITAL study showed a possible reduction in fatal cancer with vitamin D supplementation and effect modification by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) for total cancer incidence reduction for individuals with normal BMI, but not for individuals with overweight or obesity. Secondary analyses included examination of BMI (<25, 25 to < 30, and ≥30) as effect modifiers of the observed associations.

Results Among 25 871 randomized VITAL participants (51% female; mean [SD] age, 67.1 [7.1] years), 1617 were diagnosed with invasive cancer over a median intervention period of 5.3 years (range, 3.8-6.1 years). As previously reported, no significant differences for cancer incidence by treatment arm were observed. However, a significant reduction in advanced cancers (metastatic or fatal) was found for those randomized to vitamin D compared with placebo (226 of 12 927 assigned to vitamin D [1.7%] and 274 of 12 944 assigned to placebo [2.1%]; HR, 0.83 [95% CI, 0.69-0.99]; P = .04). When stratified by BMI, there was a significant reduction for the vitamin D arm in incident metastatic or fatal cancer among those with normal BMI (BMI<25: HR, 0.62 [95% CI, 0.45-0.86]) but not among those with overweight or obesity (BMI 25-<30: HR, 0.89 [95% CI, 0.68-1.17]; BMI≥30: HR, 1.05 [95% CI, 0.74-1.49]) (P = .03 for interaction by BMI).

Conclusions and Relevance In this randomized clinical trial, supplementation with vitamin D reduced the incidence of advanced (metastatic or fatal) cancer in the overall cohort, with the strongest risk reduction seen in individuals with normal weight.

Trial Registration ClinicalTrials.gov Identifier: NCT01169259

Author/s:

Chandler, P.D., Chen, W.Y., Ojala, O.N.

Association between vitamin D supplementation and mortality: systematic review and meta-analysis

Brian Desmarais — Mon, 30 Sep 2019 13:33:28 +0000

Date Added:

September 30, 2019

Journal/Publication:

BMJ

Publication Date:

August 12, 2019

URL:

Association between vitamin D supplementation and mortality: systematic review and meta-analysis

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1136/bmj.l4673

Keywords

cancer

cancer mortality

vitamin D

Vitamin D3 supplimentation

MeSH

cardiovascular diseases

Outcome Assessment (Health Care)

Vitamin D3 supplementation appears to reduce cancer-related mortality. It is a little hard to tell whether it works regardless of initial 25OH VitD levels as this analysis suggests. James W. Mold, MD, MPH

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Abstract

OBJECTIVE:

To investigate whether vitamin D supplementation is associated with lower mortality in adults.

DESIGN:

Systematic review and meta-analysis of randomised controlled trials.

DATA SOURCES:

Medline, Embase, and the Cochrane Central Register from their inception to 26 December 2018.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES:

Randomised controlled trials comparing vitamin D supplementation with a placebo or no treatment for mortality were included. Independent data extraction was conducted and study quality assessed. A meta-analysis was carried out by using fixed effects and random effects models to calculate risk ratio of death in the group receiving vitamin D supplementation and the control group.

MAIN OUTCOME MEASURES:

All cause mortality.

RESULTS:

52 trials with a total of 75 454 participants were identified. Vitamin D supplementation was not associated with all cause mortality (risk ratio 0.98, 95% confidence interval 0.95 to 1.02, I2=0%), cardiovascular mortality (0.98, 0.88 to 1.08, 0%), or non-cancer, non-cardiovascular mortality (1.05, 0.93 to 1.18, 0%). Vitamin D supplementation statistically significantly reduced the risk of cancer death (0.84, 0.74 to 0.95, 0%). In subgroup analyses, all cause mortality was significantly lower in trials with vitamin D3 supplementation than in trials with vitamin D2 supplementation (P for interaction=0.04); neither vitamin D3 nor vitamin D2 was associated with a statistically significant reduction in all cause mortality.

CONCLUSIONS:

Vitamin D supplementation alone was not associated with all cause mortality in adults compared with placebo or no treatment. Vitamin D supplementation reduced the risk of cancer death by 16%. Additional large clinical studies are needed to determine whether vitamin D3 supplementation is associated with lower all cause mortality.

STUDY REGISTRATION:

PROSPERO registration number CRD42018117823.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Author/s:

Zhang, Y., Fang, F., Tang, J., Jia, L., Feng, Y., Xu, P., Faramand, A.

Dietary Supplement Ingredient Advisory List

Brian Desmarais — Sun, 19 May 2019 01:19:00 +0000

Date Added:

May 18, 2019

Publisher:

Food and Drug Administration

Publication Date:

May 8, 2019

URL:

Dietary Supplement Ingredient Advisory List

Type:

Public Health Announcements

Format:

Web Page

Keywords

MeSH

Tetrahydroisoquinolines

The FDA is warning consumers not to purchase dietary supplements containing four specific substances considered hazardous to health, andarine, higenamine, hordenine, and 1,4-DMAA, all of which have a variety of other names listed in the article.

James W. Mold, MD, MPH

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The FDA Dietary Supplement Ingredient Advisory List is intended to quickly alert the public when the FDA identifies ingredients that do not appear to be lawfully included in products marketed as dietary supplements.

Antioxidants: In Depth

Jeffrey Wilson — Sun, 24 Feb 2019 20:01:46 +0000

Date Added:

February 24, 2019

Publication Date:

May 4, 2016

URL:

Antioxidants: In Depth

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Web Page

Keywords

MeSH

A review of the evidence related to the use of anti-oxidant supplements from the NIH.

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Antioxidants are man-made or natural substances that may prevent or delay some types of cell damage. Diets high in vegetables and fruits, which are good sources of antioxidants, have been found to be healthy; however, research has not shown antioxidant supplements to be beneficial in preventing diseases. Examples of antioxidants include vitamins C and E, selenium, and carotenoids, such as beta-carotene, lycopene, lutein, and zeaxanthin. This fact sheet provides basic information about antioxidants, summarizes what the science says about antioxidants and health, and suggests sources for additional information.

Author/s:

National Institutes of Health, Chun, Ock, Frei, Balz, Gardner, Christopher, Alekel, D. Lee, Killen, John Jr.

Turmeric Dosage: How Much Should You Take Per Day?

Tracy Ashby — Fri, 22 Feb 2019 06:00:00 +0000

Date Added:

February 22, 2019

Journal/Publication:

Healthline

Publisher:

Healthline Media

Publication Date:

June 11, 2018

URL:

Turmeric Dosage: How Much Should You Take Per Day?

Type:

Patient Education Materials

Format:

Article

Keywords

MeSH

A patient-friendly, evidence-based, referenced summary of the possible benefits and hazards of supplemental curcumin.

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You may know turmeric primarily as a spice, but it’s also used in Ayurvedic medicine, a holistic approach to health that originated in India over 3,000 years ago.

Turmeric supplements are now widely available for medicinal use, but knowing how much to take can be confusing.

Here’s a look at the uses and benefits of turmeric, effective doses and safety concerns.

Author/s:

Meixner, Makayla