Effect of Vitamin D and Omega-3 Fatty Acid Supplementation on Kidney Function in Patients With Type 2 Diabetes: A Randomized Clinical Trial

Abstract

Importance: Chronic kidney disease (CKD) is a common complication of type 2 diabetes that can lead to end-stage kidney disease and is associated with high cardiovascular risk. Few treatments are available to prevent CKD in type 2 diabetes.

Objective: To test whether supplementation with vitamin D3 or omega-3 fatty acids prevents development or progression of CKD in type 2 diabetes.

Design, setting, and participants: Randomized clinical trial with a 2 × 2 factorial design conducted among 1312 adults with type 2 diabetes recruited between November 2011 and March 2014 from all 50 US states as an ancillary study to the Vitamin D and Omega-3 Trial (VITAL), coordinated by a single center in Massachusetts. Follow-up was completed in December 2017.

Interventions: Participants were randomized to receive vitamin D3 (2000 IU/d) and omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid; 1 g/d) (n = 370), vitamin D3 and placebo (n = 333), placebo and omega-3 fatty acids (n = 289), or 2 placebos (n = 320) for 5 years.

Main outcomes and measures: The primary outcome was change in glomerular filtration rate estimated from serum creatinine and cystatin C (eGFR) from baseline to year 5.

Results: Among 1312 participants randomized (mean age, 67.6 years; 46% women; 31% of racial or ethnic minority), 934 (71%) completed the study. Baseline mean eGFR was 85.8 (SD, 22.1) mL/min/1.73 m2. Mean change in eGFR from baseline to year 5 was -12.3 (95% CI, -13.4 to -11.2) mL/min/1.73 m2 with vitamin D3 vs -13.1 (95% CI, -14.2 to -11.9) mL/min/1.73 m2 with placebo (difference, 0.9 [95% CI, -0.7 to 2.5] mL/min/1.73 m2). Mean change in eGFR was -12.2 (95% CI, -13.3 to -11.1) mL/min/1.73 m2 with omega-3 fatty acids vs -13.1 (95% CI, -14.2 to -12.0) mL/min/1.73 m2 with placebo (difference, 0.9 [95% CI, -0.7 to 2.6] mL/min/1.73 m2). There was no significant interaction between the 2 interventions. Kidney stones occurred among 58 participants (n = 32 receiving vitamin D3 and n = 26 receiving placebo) and gastrointestinal bleeding among 45 (n = 28 receiving omega-3 fatty acids and n = 17 receiving placebo).

Conclusions and relevance: Among adults with type 2 diabetes, supplementation with vitamin D3 or omega-3 fatty acids, compared with placebo, resulted in no significant difference in change in eGFR at 5 years. The 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.

Trial registration: ClinicalTrials.gov Identifier: NCT01684722.

Conflict of interest statement

Conflict of Interest Disclosures: Dr de Boer reported receipt of consulting fees from Boehringer Ingelheim and Ironwood and equipment and supplies for research from Medtronic and Abbott. Dr Thadhani reported holding a patent pending on measurement of bioavailable vitamin D and consulting for Fresenius Medical Care North America. Dr Glynn reported receipt of grants from Pfizer, Kowa, Novartis, AstraZeneca, and Amarin. Dr Buring reported that her spouse is a member of the scientific advisory board of Pharmavite, which provided the vitamin D pills and packaging for the trial. Dr Sesso reported receipt of grants from Pure Encapsulations. Dr Manson reported receipt of grants from the National Institutes of Health. No other disclosures were reported.

Figures

Figure 1.. Participant Flow in the Vitamin D and Omega-3 Trial to Prevent and Treat Diabetic Kidney Disease

eGFR indicates estimated glomerular filtration rate. aOf the 97 lost to follow-up, 1 was also missing baseline eGFR. bOf the 94 lost to follow-up, 1 was also missing baseline eGFR.

Figure 2.. Distributions of eGFR and Urine ACR Over the Course of the Study According to Treatment Assignment

ACR indicates urine albumin-creatinine ratio; eGFR, estimated glomerular filtration rate. The center horizontal line in each box indicates the median; top and bottom box borders indicate the first and third quartiles, respectively. Whiskers depict the most extreme observation within 1.5× the interquartile range (IQR) of the nearest quartile; circles show all points lying beyond 1.5× the IQR of the nearest quartile. Urine ACR plots are shown on a log scale. Numbers shown are participants contributing data at each time point.

Figure 3.. Effects of Vitamin D vs Placebo on Change in eGFR Among Participant Subgroups

ACR indicates urine albumin-creatinine ratio; eGFR, estimated glomerular filtration rate. Body mass index is calculated as weight in kilograms divided by height in meters squared. Estimates are differences in change in eGFR from baseline to year 5 comparing active treatment with placebo, adjusted for age, sex, and baseline urine ACR.

Figure 4.. Effects of Omega-3 Fatty Acids vs Placebo on Change in eGFR Among Participant Subgroups

ACR indicates urine albumin-creatinine ratio; DHA, docosahexaenoic acid; eGFR, estimated glomerular filtration rate; EPA, eicosapentaenoic acid; hsCRP, high-sensitivity C-reactive protein. Estimates are differences in change in eGFR from baseline to year 5 comparing active treatment with placebo, adjusted for age, sex, and baseline urine ACR.