In the news:Vitamin D May Benefit Prediabetics; Obesity Impairs Vitamin D Metabolsm

Vitamin D Cuts Diabetes Risk in Prediabetes

A new systemic review and meta-analysis(1) from researchers at Tufts Medical Center and published in the journal Annals of Internal Medicine has found that a higher vitamin D intake by individuals with prediabetes is associated with a 15% reduced risk of developing type 2 diabetes. People with prediabetes – estimated to be 1 of 3 Americans – have blood glucose levels higher than normal, but not high enough to be diagnosed with type 2.

Vitamin D also increased the likelihood of reverting back to normal glucose regulation by 30% - a finding with ophthalmic implications since an excess prevalence of retinopathy has been reported in prediabetes(2).

Three randomized trials were included that were specifically designed to test the effects of vitamin D vs. placebo on new-onset diabetes. The trials tested different vitamin D doses: 20,000 IU (500 mcg) cholecalciferol weekly; 4,000 IU (100 mcg) cholecalciferol daily; or 0.75 mcg eldecalcitol daily.

Vitamin D reduced the risk for diabetes by 15%, with a 3-year absolute risk reduction of 3.3%. The effect of vitamin D did not differ in prespecified subgroups.

For participants assigned to the vitamin D group who maintained a mean serum vitamin D level during the trial of at least 125 nmol/L compared with 50 to 74 nmol/L during follow-up, cholecalciferol reduced risk for diabetes by 76% with a 3-year absolute reduction of 18%.

In the analysis, no difference was seen in adverse events (including kidney stones, high blood or urine calcium levels) between those taking vitamin D and placebo takers. However, an accompanying editorial urges caution about high dose vitamin D in the general population.

According to the authors, the optimal level of vitamin D in the blood needed to reduce diabetes risk could be higher than the Institute of Medicine (IOM) committee recommendation of 400-800 IU daily.

The authors write that vitamin D blood levels needed to optimally reduce diabetes risk may be closer to the range corresponding to the tolerable upper intake level (UL) of 4,000 IU/d set for vitamin D. The benefit to risk ratio for vitamin D would depend on the target population and medical condition.

The investigators mention other strategies to combat prediabetes: Intensive lifestyle modification which has resulted in a 58% lower risk, and taking the drug metformin that has been shown to lower risk by 31%.

Obesity Impairs Response to Vitamin D

The large-scale VITAL Trial(3) overall showed no benefits to those randomized to receive 2,000 IU vitamin D vs. placebo in terms of primary endpoints of cancer or major cardiovascular disease outcomes. However, prespecified secondary analyses showed that normal weight individuals (BMI < 25 Kg/m2) did indeed benefit significantly from supplementation, with 24% lower cancer incidence, 42% lower cancer mortality, and 22% lower autoimmune disease incidence.

To clarify whether weight was really driving these disparate results, researchers analyzed baseline and follow-up vitamin D related serum biomarkers.

They found that serum vitamin D and other biomarkers were incrementally lower with higher BMI at baseline, and at 2 years of follow-up serum vitamin D levels were also significantly lower at high BMI categories (P < 0,001 for all treatment effect interactions).

The leading theory for why obesity would blunt the response to supplementation is that more adipose (fat) tissue and fat storage capacity results in greater removal of fat-soluble vitamin D from the circulation. More research is needed to determine what doses might be necessary to overcome this phenomenon.

References

1. Pittas AG, et al. Vitamin D and risk for type 2 diabetes in people with prediabetes. A systematic review and meta-analysis of individual participant data from 3 randomized trials. Ann Intern Med. Epub Feb 7, 2023.
2. Kirthi V, et al. The prevalence of retinopathy in prediabetes: A systematic review. Survey Ophthalmol. 67:1332-345, 2022.
3. Tobias TK, et al. Association of body weight with response to vitamin D supplementation and metabolism. Jama Network. Epub Jan. 17, 2023./li>