Vitamin D Intervention Trial in Healthy Chinese, Phase II
Condition: Vitamin D Deficiency
MeSH terms: Vitamin D Deficiency
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a double-blind, randomized, placebo-controlled trial. Based on inclusion and
      exclusion criteria, 400 eligible volunteers, who were 20-45 years, with 25-hydroxyvitamin D
      between 12.5-50 nmol/L and BMI between 18.5-28 kg/m2, were enrolled and randomly assigned to
      placebo or 2000 IU/d vitamin D3 arm, after taking placebo for one week. The study protocol
      was approved by the Ethics Committee of Huadong Hospital Affiliated to Fudan University,
      Shanghai and all participants provided written informed consents.In this 2-arm RCT we aimed
      to systematically investigate the effect of:

        1. vitamin D3 supplement on serum 25(OH)D levels and the modifying factors;

        2. genetic and non-genetic variants on vitamin D bioavailability;

        3. vitamin D3 supplementation on metabolic profiles and circulating bone-turnover markers
    

Detailed description: 
      At present time, the Recommended Dietary Allowance (RDA) and the tolerable upper intake level
      (UL) for vitamin D are 200 IU/day and 800 IU/day for Chinese aged 11-50 years, respectively.
      On the other hand, the RDA and UL for vitamin D for the same age group in USA are 600IU/day
      and 4000IU/day, respectively. Indeed, recent epidemiological studies suggested that serum
      25-hydroxyvitamin D [25(OH)D] concentration ≥75 nmol/L appeared to be optimal for preventing
      cardiometabolic diseases and improving bone health. To achieve this goal, a daily intake of
      1000 IU or equivalent amount from other sources, is needed, which is twice as much as the RDA
      recommended by Chinese Nutrition Society. Except for those individuals with hypersensitive
      conditions, daily intake less than 10,000 IU of vitamin D have not shown overt adverse
      effects based upon the studies conducted in Western populations.

      Since vitamin D metabolic rate and its relationship with health outcomes may vary across
      different ethnical groups and most available data so far were from Caucasians populations, it
      remains to be elucidated whether the findings from Western population could apply directly to
      Asian peoples like Chinese. Recently, our group has conducted the first relatively
      large-scale study in Asian to evaluate the association between 25(OH)D and risk of metabolic
      syndrome. It was found that the geometric mean of plasma 25(OH)D in these Chinese adults aged
      50-70 years from Beijing and Shanghai (n=3210) was 40.36 nmol/l and percentage of vitamin D
      deficiency [25(OH)D <50 nmol/l] and insufficiency (50 ≤ 25(OH)D < 75 nmol/l) were 69.2% and
      24.4%, respectively. Comparing the lowest with the highest 25(OH)D quintile (≤28.7 nmol/l vs.
      ≥57.7 nmol/l), the odds ratio for metabolic syndrome (MetS) was 1.52 (95% CI 1.17-1.98, P for
      trend = 0.0002), after multiple adjustment. Significant inverse associations also existed
      between 25(OH)D and most of MetS components, plus HbA1c. Moreover, low plasma 25(OH)D level
      was found to be associated with increased insulin resistance index (homeostasis model
      assessment of insulin resistance, HOMA-IR) in those overweight and obese individuals (BMI ≥24
      kg/m2),. (Lu et al., Diabetes Care, 2009). According to the data from 2002 China National
      Nutrition Survey, high prevalence of vitamin D deficiency also exited in Chinese children
      aged 1-3 years and approximate 82% of them had circulating 25(OH)D ≤ 50nmol/L. In consistent
      with our finding, a report from a population-based Korea study showed that the association
      between 25(OH)D and insulin resistance was modified by BMI status (Choi et al.,The Journal of
      Nutrition,2011).

      In our recent genetic study, it was found that genetic variants at GC and NADSYN1/DHCR7 were
      significantly associated with circulating 25(OH)D levels while marginal association between
      CYP2R1-rs2060793 and 25(OH)D levels was observed only in the Shanghai subpopulation (Lu et
      al., Human Genetics 2011). In addition, we developed a genetic risk score (GRS) to evaluate
      the combined effect of three SNPs (rs4588, rs1790349 and rs2060793) from GC, NADSYN1/DHCR7
      and CYP2R. Notably, the average plasma 25(OH)D concentration in individuals with 5-6 risk
      allele was 11.4 nmol/l lower than those without risk allele. Indeed, previous studies
      suggested that intake of 100 IU vitamin D could only raise circulating 25(OH)D by 2.5 nmol/l,
      implicating that 450 IU of extra vitamin D is required for these high risk individuals. The
      possible interpretations for such a high prevalence of poor vitamin D nutrition among Chinese
      may be due to the factors: (1) unlike United States and other Western countries, few, if any,
      vitamin D enriched or fortiﬁed foods are available in China; (2) Chinese, particularly women,
      like to have pale skin color, who therefore frequently utilize sunscreen and umbrella to
      prevent sun exposure. (3) approximate 318 million people are living in Heilongjiang, Shaanxi,
      Jilin, Shanxi, Liaoning, Qinghai, Gansu, Inner Mongolia, Xinjiang, and Hebei provinces, the
      areas with latitude N37°, which was previously showed to prevent skin synthesizing sufficient
      vitamin D during winter time. Collectively, all of these factors suggest that large
      proportions of Chinese may suffer vitamin D insufficiency or deficiency whereas the current
      RDA in China might be too low to provide adequate vitamin D for people's health. In order to
      fill up this gap, therefore, it is essential to study the bioavailability following vitamin D
      intervention and also identify the effects of genetic variants and other factors on vitamin D
      metabolism and associated health outcomes. Ultimately, the current study will provide
      important evidence for establishing optimal vitamin D requirement for Chinese people.
    

Intervention name(s): Placebo; Vitamin D3
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): placebo capsules have similar appearance and smell as 400 IU vitamin D3 capsules,; Vitamin D3 2000 IU per day
Intervention MeSH terms: Vitamin D; Cholecalciferol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Vitamin D3 supplementation; metabolite profile; SNPs; bone-turnover marker