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LETTERS TO THE EDITOR
Year : 2019  |  Volume : 23  |  Issue : 6  |  Page : 650-652

Vitamin D supplementation, insulin resistance, and cardiovascular risk factors: Who are likely to benefit the most?


1 Department of Rheumatology, Center for Endocrinology Diabetes Arthritis and Rheumatism (CEDAR) Superspeciality Clinics, Dwarka, New Delhi, India
2 Department of Endocrinology, CEDAR Superspeciality Clinics, Zirakpur, Punjab, India
3 Department of Endocrinology, CEDAR Superspeciality Clinics, Dwarka, New Delhi, India

Date of Web Publication20-Jan-2020

Correspondence Address:
Deep Dutta
Department of Endocrinology, CEDAR Superspeciality Clinics, 33 DDA MIG, Pocket-1, Sector 13, Dwarka, New Delhi - 110 078
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijem.IJEM_594_19

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How to cite this article:
Sharma M, Kumar M, Dutta D. Vitamin D supplementation, insulin resistance, and cardiovascular risk factors: Who are likely to benefit the most?. Indian J Endocr Metab 2019;23:650-2

How to cite this URL:
Sharma M, Kumar M, Dutta D. Vitamin D supplementation, insulin resistance, and cardiovascular risk factors: Who are likely to benefit the most?. Indian J Endocr Metab [serial online] 2019 [cited 2020 Feb 17];23:650-2. Available from: http://www.ijem.in/text.asp?2019/23/6/650/276223



Varshney et al. in their double-blinded randomized controlled trial (RCT) suggested that “high-dose vitamin D supplementation” in vitamin D deficient obese children and adolescents and young adults over 12 months was not associated with meaningful changes in insulin resistance, inflammatory cytokines, and other surrogate measures of cardiovascular risk.[1] However, the treatment protocol used for correcting vitamin D deficiency in that study is not commonly used in clinical practice (as per recommendations by different international guidelines like that from the Indian Academy of Pediatrics), and is definitely not “high-dose”.[2] This is because the authors have used cholecalciferol at dose of 60,000 IU fortnightly (120,000 IU/month) for treating severe vitamin D deficiency (8.36 ± 5.45 ng/mL) which is lower than the standard recommendations of 60,000 IU cholecalciferol weekly for at least 6 weeks, and thereafter a maintenance dose of 60,000 IU monthly for preventing recurrence of vitamin D deficiency.[2] Hence, it is not surprising that vitamin D sufficiency was not obtained in the treatment group at the end of the study (26.89 ± 12.23 ng/mL).[1] Only 41.2% of children in the intervention group had serum 25OHD >30 ng/mL at the end of the study.[1] Vitamin D is a fat-soluble vitamin, sequestrated in the adipose tissue, hence vitamin D deficiency is more common and more severe in obese individuals, who also require higher doses for optimal correction of vitamin D deficiency.[3],[4],[5]

Studies have consistently demonstrated that the non-bone mineral effects of vitamin D (pleiotropic benefits on cardiovascular system, glucose metabolism, nervous system, immune system, and cancers) are apparent at higher serum 25-hydroxy-vitamin D (25OHD) levels >30 ng/mL in contrast to >20 ng/mL which is considered to be sufficient to prevent adverse bone mineral outcomes.[6],[7],[8] Hence, it is likely that the authors did not document any meaningful impact of vitamin D supplementation on insulin resistance and CV risk factors, cause the majority of the children in the treatment group never attained vitamin D sufficiency (25OHD > 30 ng/mL) at the end of the study.

The D2d study, the largest blinded RCT published till date on impact of vitamin D on insulin resistance and prevention of prediabetes to diabetes progression showed that although there were no overall benefits after 2.5 years of vitamin D supplementation in people living with prediabetes who had a mean serum levels of vitamin D of 27 ng/mL at the start of the study.[9] However, subgroup analysis revealed that in a small cohort of 103 prediabetes individuals who had the most severe vitamin D deficiency (25OHD <12 ng/mL), vitamin D supplementation, and ensuring vitamin D sufficiency (25OHD >30 ng/mL) significantly reduced the hazard ratios of prediabetes progression to diabetes to 0.32 (95% CI 0.81–0.80) which is much better than the overall study rates of 0.92 (95% CI 0.78–1.08).[9] Dutta et al. demonstrated that vitamin D supplementation resulting in correction of vitamin D deficiency (25OHD levels improved from 17.04 ± 7.66 ng/mL to 35.47 ± 10.1 ng/mL) resulted in decreased prediabetes progression to diabetes and its increased reversal to normoglycemia, along with beneficial impact on insulin resistance and inflammatory cytokines, in a cohort of individuals from eastern India.[10] Another study from Kashmir showed similar results of the beneficial impact of vitamin D supplementation on reducing progression of prediabetes to diabetes with a reduction in fasting glucose, 2-hour plasma glucose, and HbA1c over a period of 1-year follow-up.[11]

The problem is that with rampant, unmonitored vitamin D supplementation (nutraceuticals; without medical supervision) both in India and the western world, which is, unfortunately, increasing the occurrence of vitamin D intoxication; the prevalence of severe vitamin D deficiency in the general population has gone down over the last few decades.[12]

It is very likely that these people who are living with the most severe form of vitamin D deficiency, are expected to get the maximal bone mineral and pleiotropic benefits of vitamin D supplementation once we ensure vitamin D sufficiency (25OHD >30 ng/mL). Therefore, further RCTs evaluating the pleiotropic benefits of vitamin D should primarily focus on them. Vitamin D is definitely not a panacea, and unmonitored prolonged vitamin D supplementation using supraphysiologic doses, especially parental, should be strongly discouraged.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Varshney S, Khadgawat R, Gahlot M, Khandelwal D, Oberoi AK, Yadav RK, et al. Effect of high-dose vitamin D supplementation on beta cell function in obese Asian-Indian children and adolescents: A randomized, double blind, active controlled study. Indian J Endocr Metab 2019;23:545-51.  Back to cited text no. 1
  [Full text]  
2.
Khadilkar A, Khadilkar V, Chinnappa J, Rathi N, Khadgawat R, Balasubramanian S, et al. From Indian Academy of Pediatrics 'Guideline for Vitamin D and Calcium in Children' Committee. Prevention and treatment of vitamin D and calcium deficiency in children and adolescents: Indian Academy of Pediatrics (IAP) guidelines. Indian Pediatr 2017;54:567-73.  Back to cited text no. 2
    
3.
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96:1911-30.  Back to cited text no. 3
    
4.
Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 2000;72:690-3.  Back to cited text no. 4
    
5.
Dutta D, Maisnam I, Shrivastava A, Sinha A, Ghosh S, Mukhopadhyay P, et al. Serum vitamin-D predicts insulin resistance in individuals with prediabetes. Indian J Med Res 2013;138:853-60.  Back to cited text no. 5
[PUBMED]  [Full text]  
6.
Ismailova K, Poudel P, Parlesak A, Frederiksen P, Heitmann BL. Vitamin D in early life and later risk of multiple sclerosis-A systematic review, meta-analysis. PLoS One 2019;14:e0221645.  Back to cited text no. 6
    
7.
Caprio M, Infante M, Calanchini M, Mammi C, Fabbri A. Vitamin D: Not just the bone. Evidence for beneficial pleiotropic extraskeletal effects. Eat Weight Disord 2017;22:27-41.  Back to cited text no. 7
    
8.
Yang J, Ou-Yang J, Huang J. Low serum vitamin D levels increase the mortality of cardiovascular disease in older adults: A dose-response meta-analysis of prospective studies. Medicine (Baltimore) 2019;98:e16733.  Back to cited text no. 8
    
9.
Pittas AG, Dawson-Hughes B, Sheehan P, Ware JH, Knowler WC, Aroda VR, et al. Vitamin D supplementation and prevention of type 2 diabetes. N Engl J Med 2019;381:520-30.  Back to cited text no. 9
    
10.
Dutta D, Mondal SA, Choudhuri S, Maisnam I, Reza AH, Bhattacharya B, et al. Vitamin-D supplementation in prediabetes reduced progression to type 2 diabetes and was associated with decreased insulin resistance and systemic inflammation: An open label randomized prospective study from Eastern India. Diabetes Res Clinical Pract 2014;103:e18-23.  Back to cited text no. 10
    
11.
Kuchay MS, Laway BA, Bashir MI, Wani AI, Misgar RA, Shah ZA. Effect of Vitamin D supplementation on glycemic parameters and progression of prediabetes to diabetes: A 1-year, open-label randomized study. Indian J Endocrinol Metab 2015;19:387-92.  Back to cited text no. 11
    
12.
Sharma LK, Dutta D, Sharma N, Gadpayle AK. The increasing problem of subclinical and overt hypervitaminosis D in India: An institutional experience and review. Nutrition 2017;34:76-81.  Back to cited text no. 12
    




 

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