Omega-3, vitamin D no help for kidney function: Time to shift attention

Supplementation with omega-3 fatty acids or vitamin D for up to 5 years has no effect on kidney function in adults with type 2 diabetes (T2D),  the VITAL-DKD* ancillary study has shown.

Reporting at ASN Kidney Week 2019, lead author Dr Ian H. de Boer, director, Kidney Research Institute, University of Washington, Seattle, US, said he had hoped that omega-3 fatty acids and vitamin D3 might help prevent kidney disease and its progression in patients with T2D, based on a plethora of studies suggesting benefits. “However, our study showed clearly that this was not the case. Neither supplement helped maintain kidney function in a broad population of patients with T2D. This provides a strong message that perhaps, it’s about time we turn our attention elsewhere to prevent and treat kidney disease.” [ASN Kidney Week 2019, abstract FR-OR138; JAMA 2019;doi:https://doi.org/10.1001/jama.2019.17380]

The VITAL-DKD ancillary study included 1,312 adults with T2D who were randomized to receive either vitamin D₃ 2000 IU daily plus omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) 1 gram daily), vitamin D₃ plus placebo, omega-3 fatty acids plus placebo, or two placebos, each for 5 years.

At baseline, the mean age of the participants was 67.6 years, with median diabetes duration of 6–10 years. Forty-six percent were female, 31 percent were of ethnic minority. Seventy-one percent completed the study.

The primary endpoint of mean change in eGFR from baseline to year 5 was −12.3 mL/min/1.73 m² with vitamin D3 vs −13.1 mL/min/1.73 m² with placebo, without significant difference.

As for omega-3 fatty acids, the mean eGFR change was −12.2 mL/min/1.73 m² vs −13.1 mL/min/1.73 m² with placebo.

At year 5, there was no significant difference in the change in eGFR by treatment (0.9 mL/min/1.73 m² for both vitamin D and omega-3 fatty acids vs placebo), and there was no significant interaction between treatment assignments (p=0.42).

Similarly, none of the three other prespecified outcomes differed significantly by treatment for either of the supplements.

The composite outcome of at least a 40 percent decline in eGFR, kidney failure, or death occurred in a total of 164 participants, with no difference by treatment (hazard ratios, 0.92 and 1.11 for vitamin D and omega-3 fatty acids, respectively, vs placebo).

Similarly, the secondary outcomes of at least a 40 percent decline in eGFR and change in urine albumin-creatinine by year 5 also did not differ significantly from placebo for either supplement.

Patients believe, but trials ‘disappointing’

“Patients believe in both vitamin D and omega-3 fatty acids, but clinical trials for both supplements have been generally disappointing. Now, how do we get through to patients? People take supplements when they like, but I think physicians and other healthcare providers need to make it clear that there is no evidence base for that,” de Boer said.

Drs Anika Lucas and Myles Wolf from the  Division of Nephrology at Duke University School of Medicine, Durham, North Carolina, US, in an accompanying editorial, were as forthright in their message. “Routine supplementation with vitamin D or omega-3 fatty acids have no role in primary prevention of incident CKD or slowing of eGFR loss.”

The contrast between the current VITAL-DKD results with the prior epidemiologic studies implicating vitamin D deficiency in various diseases “offers a stark lesson on the chasm between association and causation,” they added.

End of the road for vitamin D, omega-3?

The results of the parent VITAL trial, reported in 2018, showed no significant cardiovascular or cancer benefit with vitamin D or omega-3 fatty acids supplementation in 26,000 generally healthy individuals. [N Engl J Med 2019; 380:33-44; N Engl J Med 2019; 380:23-32]

“There was a signal that vitamin D might have benefit among subgroups of participants with low blood 25-hydroxyvitamin D concentrations or evidence of pre-existing kidney disease at baseline. It’s biologically plausible that these subgroups might benefit more from vitamin D, which is why we explored them in the ancillary study,” said de Boer. “But the subgroup effects were not statistically significant and hence, should be taken with a grain of salt.”