No link between vitamin D, omega-3 fatty acid supplements and improved kidney function

Supplementation with vitamin 3 or omega-3 fatty acids does not affect estimated glomerular filtration rate (eGFR) compared with placebo in patients with type 2 diabetes, a recent study found.

The VITAL-DKD study, a prespecified ancillary analysis of the Vitamin D and Omega-3 Trial (VITAL), included the 1,312 adult patients from VITAL who had type 2 diabetes and agreed to additional testing of kidney function and urinary albumin excretion at baseline and two and five years after randomization. They were randomly assigned to receive vitamin D₃, 2,000 IU/d, and omega-3 fatty acids, 1 g/d (n=370); vitamin D₃ and placebo (n=333); placebo and omega-3 fatty acids (n=289); or two placebos (n=320) for five years. Pharmacite LLC provided the vitamin D and placebo, ProNova provided the omega-3 fatty acids and placebo, and Quest Diagnostics provided diagnostic services. Change in eGFR from baseline to year five was the primary outcome measure. Patients were recruited from all U.S. states between November 2011 and March 2014, with follow-up completed in December 2017. Results of the study were published Nov. 8 by JAMA.

Of the 1,312 patients, 46% were women and 31% were racial or ethnic minorities. The mean age was 67.6 years. Nine hundred thirty-four patients (71%) completed the study. The mean eGFR at baseline was 85.8 mL/min/1.73 m². From baseline to year five, the mean change in eGFR was −12.3 mL/min/1.73 m² (95% CI, −13.4 to −11.2 mL/min/1.73 m²) with vitamin D compared to −13.1 mL/min/1.73 m² (95% CI, −14.2 to −11.9 mL/min/1.73 m²) with placebo (difference, 0.9 mL/min/1.73 m² [95% CI, −0.7 to 2.5 mL/min/1.73 m²]). With omega-3 fatty acids, the mean change in eGFR was −12.2 mL/min/1.73 m² (95% CI, −13.3 to −11.1 mL/min/1.73 m²) versus −13.1 mL/min/1.73 m² (95% CI, −14.2 to −12.0 mL/min/1.73 m²) with placebo (difference, 0.9 mL/min/1.73 m² [95% CI, −0.7 to 2.6 mL/min/1.73 m²]).

No significant interactions were seen between the two interventions, and none of three prespecified secondary outcomes (time to ≥40% decrease in eGFR from baseline, kidney failure, or death; time to ≥40% decrease in eGFR from baseline; and change in urine albumin-creatinine ratio from baseline to year five) differed by treatment assignment. Fifty-eight participants, 32 receiving vitamin D and 26 receiving placebo, developed kidney stones, and 45 participants, 28 receiving omega-3 fatty acids and 17 receiving placebo, developed gastrointestinal bleeding.

The researchers noted that the numbers of eGFR and urine albumin-to-creatinine ratio measurements collected per patient were “modest” and that not all of the patients returned a serum sample for calculation of the final eGFR at year five, among other limitations. They concluded that in relatively healthy adult patients with type 2 diabetes, vitamin D and omega-3 fatty acid supplements did not result in significant changes in eGFR versus placebo. “These findings do not support the use of vitamin D or omega-3 fatty acid supplementation for preserving kidney function in patients with type 2 diabetes,” they wrote.

An accompanying editorial focusing on vitamin D noted that although epidemiological studies have found an association between vitamin D deficiency and several adverse outcomes, these results have not been replicated in randomized clinical trials. “It now seems safe to conclude that many prior epidemiological associations between vitamin D deficiency and adverse health outcomes were driven by unmeasured residual confounding or reverse causality,” the editorialists wrote. “For many of the chronic conditions previously mapped to vitamin D deficiency, their preclinical stages likely contributed to the vitamin D deficiency that subsequently ‘predicted’ onset of overt clinical disease in observational studies rather than vice versa.”