Effects of long-term vitamin D and n-3 fatty acid supplementation on inflammatory and cardiac biomarkers in patients with type 2 diabetes: secondary analyses from a randomised controlled trial

Abstract

Aims/hypothesis Interventions that reduce inflammation may delay progression of microvascular and macrovascular complications in diabetes. We examined the effects of vitamin D 3 and/or n-3 fatty acid supplementation vs placebo on 5 year changes in serum inflammatory and cardiac biomarkers in adults with type 2 diabetes. Methods This study reports pre-specified secondary outcomes of the Vitamin D and Omega-3 Trial to Prevent and Treat Diabetic Kidney Disease, in which 1312 US adults with type 2 diabetes and without known cardiovascular disease, malignancy, or endstage kidney disease were randomised using computer-generated random numbers in blocks of eight to vitamin D 3 (2000 IU/day) vs placebo and n-3 fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]; 1 g/day) vs placebo in a 2 × 2 factorial design. Participants, examiners, and researchers assessing outcomes were blinded to intervention assignment. We measured serum IL-6, high-sensitivity C-reactive protein (hsCRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline and after 2 and 5 years. Results A total of 333 participants were randomised to vitamin D 3 and placebo n-3 fatty acids, 289 to n-3 fatty acids and placebo vitamin D 3 , 370 to vitamin D 3 and n-3 fatty acids, and 320 to 2 placebos; 989 (75%) and 934 (71%) participants returned blood samples at 2 and 5 years, respectively. Participants had a mean age of 67.6 years (46% women). Overall, baseline geometric means of IL-6, hsCRP and NT-proBNP were 1.2 pg/ml, 1.9 mg/l and 262 ng/l, respectively. After 5 years, mean IL-6 and hsCRP remained within 6% of their baseline values while mean NT-proBNP increased by 55% overall. Compared with placebo, participants assigned to vitamin D 3 had a 1.24-fold greater increase in NT-proBNP over 5 years (95% CI 1.09, 1.41; p = 0.003), while IL-6 and hsCRP did not have a significant difference in change. Comparing n-3 fatty acids with placebo, there was no significant difference in change in IL-6, hsCRP or NT-proBNP. No heterogeneity was observed in subgroup analyses accounting for baseline eGFR, urine albumin to creatinine ratio, initial biomarker concentration, 25-hydroxyvitamin D level or EPA+DHA index.

Alterations in regulators of the renal-bone axis, inflammation and iron status in older people with early renal impairment and the effect of vitamin D supplementation

“…IL10 increased in both groups. These results are similar to the reported effects of pro-inflammatory and anti-inflammatory cytokines to vitamin D supplementation and/or VDR activation in in vitro models and in human studies mostly including participants with conditions associated with increased inflammation [ 25–27 , 30 , 31 , 50 , 51 ]. It has been suggested that an increase in iron status after vitamin D supplementation is mediated through a decline in IL6 and TNFα and an increase in IL10 [ 8 , 21 , 29 , 52 , 53 ].…”

Association between circulating 25-hydroxyvitamin D and cardiometabolic risk factors in adults in rural and urban settings

“…Our findings of an inverse association between vitamin D status and fasting glycemia and the null association with HOMA-IR suggest an effect via insulin secretion rather than insulin resistance. Most RCTs have consistently shown a null association between vitamin D supplementation and cardiometabolic endpoints, including a recent trial examining intermediate endpoints (highsensitivity CRP and N-terminal pro-B-type natriuretic peptide) [8,9,[38][39][40][41]. However, some of these trials were of small sample size and short duration [40], used a low dose of vitamin D [41], were only powered to detect large effect sizes [8], and were not designed to study cardiometabolic diseases as primary endpoints [41].…”

Association of marine PUFAs intakes with cardiovascular disease, all-cause mortality, and cardiovascular mortality in American adult male patients with dyslipidemia: The U.S. National Health and Nutrition Examination Survey, 2001 to 2016

“…In the OMEMI trial, the higher the EPA supplementation level was used in patients with recent acute myocardial infarction, the lower the risk of major cardiovascular events and the higher the risk of new atrial brillation (18). A secondary analysis of the STRENGTH test showed that Omega-3 fatty acid preparations had no effect on participants with high triglycerides and low HDL levels (19); The EPA and DHA interventions did not reduce the levels of in ammation or markers of heart failure in patients over ve years (20). In a population study, healthy subjects receiving EPA intervention increased the oxidative sensitivity of LDL, which may lead to atherosclerosis (21).…”