The present randomized clinical trial (RCT) was conducted on Jordanian participants with vitamin D deficiency (VDD) with no other medical conditions, to evaluate the combined effect of 1,25-dihydroxy vitamin D 3 (Vit.D 3 ) and omega-3 fatty acid (n-3FA) supplements (D+) on oxidized low-density lipoprotein (Ox-LDL) and non-high-density lipoprotein cholesterol (non-HDL-C) levels as common predictors of cardiovascular diseases (CVDs). Participants were randomized into 4 groups as follows: a control group (C) that received no supplementations, a Vit.D 3 group that received 50,000 IU of Vit.D 3 every week, an n-3FA group that received 300 mg of omega-3 fatty acid every day, and a D+ group that received a combination of both supplements, with the same dosage administered by the previous groups but with a 4-6-hour time interval between Vit.D 3 and n-3FA administration to avoid any possible interaction. All supplementations were administered orally for 8 weeks. Forty-seven participants were allocated to each group. Twenty-six in the control group, 37 participants in the Vit.D 3 group, 37 participants in the n-3FA group, and 46 participants in the D+ group completed the study to the end. The D+ supplementations significantly increased non-HDL-C (118.99 ± 60.98 to 155.26 ± 43.36 mg/dL, P << 0.05) but decreased Ox-LDL-C levels (69.29 ± 37.69 to 52.81 ± 17.30 pg/mL, P = 0.03). The stepwise regression showed that the serum LDL-C level was the main independent variable involved in the elevation of non-HDL levels (R 2 = 0.837) observed at the end of the trial in the D+ group. The groups that were supplemented with either Vit.D 3 alone or n-3FA alone had an insignificant decrease in the level of Ox-LDL-C. In conclusion, despite the observed hyperlipidemic effect, the combination treatment is recommended by the research team because the decrease in Ox-LDL may offset the hyperlipidemic effect.
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