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Vitamin D for Prevention of Disease

Author/s: 
Eva S Liu, Andrew M Davis, Sherri-Ann M Burnett-Bowie

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

Keywords 
guideline nutrition vitamin D Disease Prevention

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

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

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.

Keywords 
aging cognition dietary supplements Gastrointestinal Microbiome gut microbiome gut health

The Women’s Health Initiative Randomized Trials and Clinical Practice

Author/s: 
Manson, J.E., Crandall, C.J., Rossouw, J.E.

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.

Keywords 
vitamin D calcium menopause Menopausal women Women's Health

Geographic Tongue

Author/s: 
Prasanth, V. J., Singh, A.

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.

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

Author/s: 
Basile, L. A., Taylor, S. N., Wagner, C. L., Horst, R. L., Hollis, B. W.

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].

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

Author/s: 
Chandler, P.D., Chen, W.Y., Ojala, O.N.

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

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

Author/s: 
Zhang, Y., Fang, F., Tang, J., Jia, L., Feng, Y., Xu, P., Faramand, A.

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.

Keywords 
cancer cancer mortality vitamin D Vitamin D3 supplimentation

Antioxidants: In Depth

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

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.

Keywords 
antioxidants diet dietary supplements

Turmeric Dosage: How Much Should You Take Per Day?

Author/s: 
Meixner, Makayla

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.

Keywords 
turmeric holistic approach dietary supplements
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