Vitamin D

Vitamin D contributes to the maintenance of normal bones, teeth and normal immune system function. A 2016 UK government commissioned report said that everyone over the age of one should have a daily intake of 10ug of Vitamin D per day to protect bone and muscle health. This can mean supplementing, particularly during autumn and winter. Along with the well-known musculoskeletal effects, vitamin D and its hormonal action also plays a role in other parts of the body.

Gastrointestinal

Increasingly vitamin D has evidence for benefit in such inflammatory gut disorders. In a recent study sixty patients with IBS and 100 healthy individuals had their vitamin D blood level assessed. There was a statistically significant difference in the mean vitamin D level between healthy and IBS patients, with vitamin D deficiency detected in 49 patients (82%) in the IBS group and 31 patients (31%) in the control group.[1] A subsequent study found that there was a significant association between circulating vitamin D level and quality of life (“How much has IBS affected your life?”) when people were enrolled onto the study. Supplementation of vitamin D3 had a beneficial effect.[2]

Another recent study of 90 IBS patients participated in a double-blind, randomised, placebo-controlled study where participants were randomised to receive either 50,000 IU vitamin D3 or a placebo fortnightly for a period of 6 months. Over the 6-month intervention period, a significantly greater improvement in IBS symptoms such as abdominal pain and distention, flatulence, rumbling, and overall gastrointestinal (GI) symptoms (except dissatisfaction with bowel habits) was observed in the patients receiving vitamin D as compared to the placebo group. The IBS-QoL scores in the vitamin D group significantly improved compared to the placebo group afterwards, and average IBS-QoL score change was significantly improved.[3]

There is much evidence to show that patients with inflammatory bowel disease (IBD) benefit from vitamin D3 supplements. Up to 72% of Crohn’s Disease (CD) sufferers worldwide have been found to have insufficient vitamin D, and up to 64% of people with ulcerative colitis (UC).[4] Vitamin D levels change according to the seasons[5-9] and clinical deficiency was seen in up to 76% of patients in winter and up to 19% in the summer months. Vitamin insufficiency, where reported, was up to 100% in winter and 59% in the summer.[8,9] In a recent study, researchers found a link between vitamin D deficiency/insufficiency and disease activity in IBD patients.[10]

A number of studies have therefore aimed to improve vitamin D levels as a means of IBD therapy. One group of researchers found disease activity decreased in 78% of patients on a 24-week vitamin D3 supplementation programme. Sixty-seven per cent of patients were in remission and their quality of life had significantly improved.[11]

Another study compared the effects of vitamin D3 supplementation vs vitamin D2 in CD patients. After six weeks the D3 group was experiencing more positive effects, but by week 52 there was no difference between the groups.[12]

Elsewhere, ninety-four CD patients in remission received either vitamin D3 with 1200 mg of calcium or 1200 mg of calcium alone. During a one-year follow-up, serum 25(OH)D3 levels increased significantly in vitamin D-supplemented patients, but free serum calcium did not change. The relapse rate was not significantly lowered.[13]

In an uncontrolled clinical trial, 18 active CD patients were treated with vitamin D3 daily over two weeks, after which the dose was steadily increased until a serum concentration of 40 ng/mL of 25(OH)D3 was reached. After 24 weeks, a significant reduction of the CDAI and an improvement of the IBDQ score were observed.[14]

A recent clinical trial involved 141 CD patients and 79 UC patients. Twenty six of these took vitamin D3 supplements for over three months. In all patients, health-related quality of life was measured along with serum vitamin D levels at the outset and approximately six months later. Results showed that a higher concentration of vitamin D in the blood related to a higher health-related quality of life, but was reliant on the season and amount of sun exposure. 800IU of vitamin D3 per day for up to six months was not enough to raise serum levels and it did not affect quality of life.[15] Higher doses were therefore required.

Clinical Depression

Recently, vitamin D has been studied for the amelioration of depressive symptoms and as an adjunctive therapy for depression. Vitamin D receptors exist in the brain and play an important role in neuroendocrine functioning.[16,17] Research indicates that lower levels of vitamin D can negatively affect growth, cellular signalling, and neural activity in the brain.[16,18] Since vitamin D has also been linked with the production of serotonin and low levels of serotonin are present in depression, it may benefit persons who are depressed.[19]

Regarding depression, a summary of early studies suggested that effective detection and treatment of low vitamin D in persons with depression might be a therapy that could improve their health outcomes and quality of life.[20] Several systematic reviews and meta-analyses have examined the relationship of vitamin D and depression. Ju et al.[21] conducted a meta-analysis of cross-sectional and cohort studies examining serum 25-hydroxyvitamin D [25 (OH) D] levels and the risk of depression. Both the cross-sectional and the cohort studies demonstrated a significantly reduced risk for depression with a 10 ng/ml increase in 25 (OH) D levels (OR: 0.96, 95% CI 0.94 to 0.99 and OR: 0.92, 95% CI 0.87 to 0.98, resp.). Another meta-analysis reported similar findings. Anglin et al.[22] reported that for the cross-sectional studies, there was an increased risk for depression for the lowest as compared to the highest vitamin D categories; however, it was not significant (OR = 1.31, 95% CI 1.0 to 1.71, p = 0.05).

There is no evidence to suggest that people without depression can improve their mental wellbeing, by taking vitamin D, even if they have a deficiency.

Falls and fractures

Vitamin D supplementation may reduce the number of falls among the elderly. There is also likely an overall reduction in the number of “fallers” (a less biased outcome), although these results are less consistent.[23-30]

The best available evidence shows an apparent reduction in fractures associated with vitamin D when given at moderate doses (≥800 IU/day) together with calcium at low to moderate doses (perhaps 500 mg/day). The RR reductions are approximately 10–15 % for non-vertebral/total or hip fractures. At a 15 % baseline risk of any fracture, approximately 45–67 individuals would have to take vitamin D and calcium every day for 10 years to prevent one fracture.[31-35]

Safety

Vitamin D supplementation in the general adult population is safe, and supplementation without testing is reasonable. Once yearly mega-doses eg 300,000 IU or more, are not recommended but there is little risk to adults in taking common elevated doses of 1000-5000 IU per day. Testing may be appropriate when clinically indicated (e.g., parathyroid disease). When testing is performed, ≥50 nmol/L indicates vitamin D sufficiency.

References

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2. Tazzyman S, Richards N, Trueman AR et al. Vitamin D associates with improved quality of life in participants with irritable bowel syndrome: outcomes from a pilot trial. BMJ Open Gastroenterol. 2015 Dec 21;2(1):e000052.
3. Abbasnezhad A, Amani R, Hajiani E et al. Effect of vitamin D on gastrointestinal symptoms and health-related quality of life in irritable bowel syndrome patients: a randomized double-blind clinical trial. Neurogastroenterol Motil. 2016 May 7.
4. Ardesia M, Ferlazzo G, Fries W. Vitamin D and Inflammatory Bowel Disease. BioMed Research International. 2015;2015:470805.
5. McCarthy D, Duggan P, O’Brien M, et al. Seasonality of vitamin D status and bone turnover in patients with Crohn’s disease. Alimentary Pharmacology & Therapeutics. 2005;21(9):1073–1083.
6. Alkhouri R H, Hashmi H, Baker RD et al. Vitamin and mineral status in patients with inflammatory bowel disease. Journal of Pediatric Gastroenterology and Nutrition. 2013;56(1):89–92.
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10. Torki M, Gholamrezaei A, Mirbagher L et al. Vitamin D Deficiency Associated with Disease Activity in Patients with Inflammatory Bowel Diseases. Dig Dis Sci. 2015 Jun 2. [Epub ahead of print].
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14. Yang L, Weaver V, Smith J. P et al. Therapeutic effect of vitamin D supplementation in a pilot study of Crohn’s patients. Clinical and Translational Gastroenterology. 2013;4, article e33.
15. Hlavaty T, Krajcovicova A, Koller T et al. Higher vitamin D serum concentration increases health related quality of life in patients with inflammatory bowel diseases. World J Gastroenterol. 2014;20(42):15787-96.
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26. Michael YL, Whitlock EP, Lin JS, et al. Primary care-relevant interventions to prevent falling in older adults: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2010;153(12):815–825. doi: 10.7326/0003-4819-153-12-201012210-00008.
27. Kalyani RR, Stein B, Valiyil R, Manno R, Maynard JW, Crews DC. Vitamin D treatment for the prevention of falls in older adults: systematic review and meta-analysis. J Am Geriatr Soc. 2010;58(7):1299–1310. doi: 10.1111/j.1532-5415.2010.02949.x.
28. Murad MH, Elamin KB, Abu Elnour NO, et al. Clinical review: The effect of vitamin D on falls: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2011;96(10):2997–3006. doi: 10.1210/jc.2011-1193.
29. Cranney A, Horsley T, O’Donnell S, et al. Effectiveness and safety of vitamin D in relation to bone health. Evid Rep Technol Assess (Full Rep) 2007;158:1–235.
30. Bolland MJ, Grey A, Gamble GD, Reid IR. Vitamin D supplementation and falls: a trial sequential meta-analysis. Lancet Diabetes Endocrinol. 2014;2(7):573–580. doi: 10.1016/S2213-8587(14)70068-3.
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32. Bischoff-Ferrari HA, Willett WC, Orav EJ, et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012;367(1):40–49. doi: 10.1056/NEJMoa1109617.
33. Chung M, Lee J, Terasawa T, Lau J, Trikalinos TA. Vitamin D with or without calcium supplementation for prevention of cancer and fractures: an updated meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med. 2011;155(12):827–838. doi: 10.7326/0003-4819-155-12-201112200-00005.
34. Avenell A, Mak JCS, O’Connell D. Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men. Cochrane Database Syst Rev. 2014;4
35. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med. 2009;169(6):551–561. doi: 10.1001/archinternmed.2008.600.