Original articleEffects of vitamin D supplementation on body fat accumulation, inflammation, and metabolic risk factors in obese adults with low vitamin D levels — Results from a randomized trial
Introduction
Obesity is associated with metabolic risk factors such as insulin resistance, dyslipidemia and hypertension. Within the obese population, those with a central fat distribution are especially at risk of having insulin resistance and an adverse metabolic profile [1]. Although not fully elucidated, the link between obesity and insulin resistance may involve chronic low grade inflammation in the adipose tissue (AT) [2] as well as a disordered lipid metabolism which promotes ectopic fat accumulation within insulin sensitive tissues such as visceral adipose tissue (VAT), liver and skeletal muscle [3].
Low levels of 25-hydroxy-vitamin D (25OHD) are commonly seen in obesity, and the inverse association between 25OHD and adiposity has been confirmed in numerous studies [4]. Besides the inverse association to BMI and fat mass, higher plasma 25OHD has also been associated with lower amount of visceral (VAT) and subcutaneous (SAT) adipose tissue [5], [6], [7] and to reduced omental adipocyte size [5] suggesting a link between vitamin D (VD) status and fat distribution. This is further substantiated by reports of regulatory effects of VD on adipose tissue and lipid storage and by the fact that the vitamin D receptor (VDR) is expressed in adipocytes, and is dynamically up-regulated during adipogenesis [8]. Recently, adequate vitamin D status has been associated with less weight gain [9], and longitudinal observational studies have shown that plasma 25OHD is inversely related to the future development of the obesity complications such as hypertension, hyperglycemia, insulin resistance, dyslipidemia, metabolic syndrome and type II diabetes [10], [11], [12].
The strong epidemiological associations between plasma 25OHD and obesity and its complications, suggest that vitamin D supplementation could have beneficial effects on these metabolic aberrations. Supplementation with VD does not seem to affect body weight [13], but has been found to decrease insulin resistance [14], [15] and to decrease blood pressure [16], [17] in some studies, whereas other studies have shown negative results [14], [18].
Only few data are available on possible effects of vitamin D supplementation on body composition and ectopic lipid accumulation. One study showed that during a weight loss intervention, supplementation with 300 IU of vitamin D plus 1050 mg calcium decreased VAT compared to placebo [19].
In the present study, we hypothesized that an increase in circulating 25OHD levels would reduce ectopic lipid accumulation and thereby have beneficial effects on obesity complications such as chronic low-grade inflammation, insulin resistance, hypertension and dyslipidemia. This was tested in a double-blind, placebo-controlled study, in which obese subjects with low circulating levels of 25OHD were randomized to a daily dose of 7000 IU of cholecalciferol or placebo for 26 weeks.
Section snippets
Study population
Healthy adults aged 18–50 years with BMI > 30 kg/m2 and plasma 25OHD levels < 50 nmol/l were recruited through announcements in local newspapers. Eighty-eight subjects were assessed for eligibility at our out-patient clinic. We excluded subjects with a fasting plasma glucose > 7.0 mmol/l, hypercalcemia, impaired renal (plasma creatinine > 130 μmol/l) or hepatic function (alanine aminotransferase > 135 U/l), as well as subjects with history of diabetes, sarcoidosis, nephrolithiasis, osteomalacia, or alcohol or
Baseline characteristics
Fifty-five obese subjects with plasma 25OHD below 50 nmol/l were included in the trial. 71% of the subjects were female, and all female subjects were pre- or perimenopausal. Randomization was balanced with no significant differences between the two groups (Table 1). Thus, there were no significant differences in age (41.2 years vs. 39.5 years; P = 0.39), BMI (35.0 kg/m2 vs. 36.1 kg/m2; P = 0.27) or plasma 25OHD (34.6 nmol/l vs. 34.5 nmol/l; P = 0.96) between groups at baseline (Table 1).
Forty-three subjects
Discussion
In our randomized placebo-controlled trial, we investigated the effects of high-dose vitamin D supplementation in obese subjects with low baseline levels of 25OHD. The treatment for 26 weeks more than doubled the plasma 25OHD levels and had a minor but significant reduction on the level of PTH, but this treatment had no effect on body weight, body composition or on the amount of ectopic fat deposited in tissues such as VAT, skeletal muscle, and liver. Neither did we find any effect of VD
Learning points
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Plasma 25OHD is inversely associated to visceral and hepatic fat accumulation.
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Increasing plasma 25OHD in obese subjects with low plasma 25OHD does not decrease ectopic lipid accumulation.
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Vitamin D treatment in obese subjects does not affect metabolic or inflammatory risk factors.
Conflict of interests
The authors declare no conflicts of interests.
Acknowledgements
The authors thank the patients for their time and commitment while participating in this study, and the dieticians Berit Elgaard and Caroline Abild for their skillful assistance.
References (39)
- et al.
Vitamin-D receptor gene-expression is up-regulated by 1, 25-dihydroxyvitamin-D3 in 3t3-L1 preadipocytes
Biochem Biophys Res Commun
(1993) - et al.
Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers
Am J Clin Nutr
(2009) - et al.
Calcium and vitamin D supplementation is associated with decreased abdominal visceral adipose tissue in overweight and obese adults
Am J Clin Nutr
(2012) - et al.
Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study
Am J Clin Nutr
(2012) - et al.
High-throughput liquid–liquid extraction and LCMSMS assay for determination of circulating 25(OH) vitamin D3 and D2 in the routine clinical laboratory
Clin Chim Acta
(2010) - et al.
No effect of supplementation with cholecalciferol on cytokines and markers of inflammation in overweight and obese subjects
Cytokine
(2010) - et al.
Glucose tolerance and vitamin D: effects of treating vitamin D deficiency
Nutrition
(2008) - et al.
Complex role of the vitamin D receptor and its ligand in adipogenesis in 3T3-L1 cells
J Biol Chem
(2006) - et al.
Associations between serum 25-hydroxyvitamin D3 concentrations and liver histology in patients with non-alcoholic fatty liver disease
Nut Metab Cardiovasc Dis
(2007) - et al.
Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study
Circulation
(2007)