Effects of docosahexanoic acid supplementation on inflammatory and subcutaneous adipose tissue gene expression in HIV-infected patients on combination antiretroviral therapy (cART). A sub-study of a randomized, double-blind, placebo-controlled study.

BACKGROUND: Omega-3 fatty acids have the potential to decrease inflammation and modify gene transcription. Whether docosahexanoic acid (DHA) supplementation can modify systemic inflammatory and subcutaneous adipose tissue (SAT) gene expression in HIV-infected patients is unknown. METHODS: A randomized, double-blind, placebo-controlled trial that enrolled 84 antiretroviral-treated patients who had fasting TG levels from 2.26 to 5.65 mmol/l and received DHA or placebo for 48 weeks was performed (ClinicalTrials.gov, NCT02005900). Systemic inflammatory and SAT gene expression was assessed at baseline and at week 48 in 39 patients. RESULTS: Patients receiving DHA had a 43.9% median decline in fasting TG levels at week 4 (IQR: -31% to -56%), compared with -2.9% (-18.6% to 16.5%) in the placebo group (P < 0.0001). High sensitivity C reactive protein (hsCRP) and arachidonic acid levels significantly decreased in the DHA group. Adipogenesis-related and mitochondrial-related gene expression did not experience significant changes. Mitochondrial DNA (mtDNA) significantly decreased in the placebo group. SAT inflammation-related gene expression (Tumor necrosis factor alpha [TNF-α], and monocyte chemoattractant protein-1 [MCP-1]) significantly decreased in the DHA group. CONCLUSIONS: DHA supplementation down-regulated inflammatory gene expression in SAT. DHA impact on markers of systemic inflammation was restricted to hsCRP and arachidonic acid.

Effects of docosahexanoic acid on metabolic and fat parameters in HIV-infected patients on cART: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Hypertriglyceridemia is common in HIV-infected patients. Polyunsaturated fatty acids reduce fasting serum triglyceride (TG) levels in HIV-infected patients. It is not known whether docosahexanoic acid (DHA) supplementation can reduce hypertriglyceridemia and modify fat distribution in HIV-infected patients. METHODS: We conducted a randomized, double-blind, placebo-controlled trial with 84 antiretroviral-treated patients who had fasting TG levels from 2.26 to 5.65 mmol/l and were randomized to receive DHA or placebo for 48 weeks. TG levels were assessed at baseline, week 4 and every 12 weeks. Body composition was assessed at baseline and at week 48. Registered under ClinicalTrials.gov Identifier no. NCT02005900. RESULTS: Patients receiving DHA had a 43.9% median decline in fasting TG levels at week 4 (IQR: -31% to -56%), compared with -2.9% (-18.6% to 16.5%) in the placebo group (P < 0.0001). DHA levels and decrease in TG at week 4 in the DHA arm correlated significantly (r = 0.7110, P < 0.0001). The median reduction in TG levels in the DHA arm was -43.7% (-32.4% to -57.5%), and in the placebo arm +2.9% (-21.3% to +30.1%) at week 12. The difference remained statistically significant at week 48 (P = 0.0253). LDL cholesterol levels significantly increased at week 4 by 7.1% (IQR: -4.8% to +35.3%) in the DHA arm but not in the placebo group. No significant changes were observed in HDL cholesterol, insulin, and HOMA-IR during the study. Limb fat significantly increased in both arms, without statistically significant differences between groups (P = 0.3889). DHA was well tolerated; only 3 patients experienced treatment-limiting toxicity. CONCLUSIONS: Supplementation with DHA reduced fasting TG levels in antiretroviral-treated HIV-infected patients with mild hypertriglyceridemia. DHA was well tolerated with minor GI symptoms. Peripheral fat significantly increased in the DHA group but did not increase significantly compared with placebo.