In the presented study, we enrolled 60 HD patients to study the effect of omega-3 supplementation after six months on the vascular calcification biomarkers fetuin-A and OPG. Serum levels of fetuin A and OPG were significantly increased after six months of omega-3 supplementation compared with baseline in the studied hemodialysis patients. These finding are in consistence with a previous study, conducted on 47 patients on dialysis, which concluded that increased fetuin-A levels after omega-3 FA supplementation for six months may work positively for dialysis patients in the aspects of nutrition, mortality, and VC [26].
The cardioprotective role of omega-3 in HD patients is owing to the decrease in the carotid intima-media thickness (CIMT) hindering the progression of atherosclerosis [27] or through the modulation of vascular calcification biomarkers such as fetuin-A [26] and the RANKL/RANK/OPG system in mice with metabolic syndrome [28]. In patients undergoing long-term HD, the VC process was found to be a very common adverse eventthat finally leads to CVD [29]. The leading cause of death in HD patients is atherogenesis which is interconnected with both VC and inflammation [30]. Fetuin-A glycoprotein is a calcium regulator that inhibits the precipitation of calcium phosphate and plays an important role in both calcification and inflammation processes [31]. Fetuin-A serum levels during acute inflammation are rapidly downregulated [32]. A previous cross-sectional study enrolled 312 hemodialysis patients demonstrated that fetuin-A serum levels were significantly lower in hemodialysis patients than in healthy controls. In addition, fetuin-A deficiency is associated with inflammation and links vascular calcification to mortality in patients on dialysis [8]. In consonance with our results, Ozyazgan et al., found that levels of fetuin-A were increased after omega-3 intake for two months in diabetic patients [33]. Other researchers found that levels of fetuin-A are positively associated with metabolic syndrome (MetS), the accumulation of visceral adipose tissue (VAT) and the insulin resistance in the normal healthy population [34; 35].
It was proved that fetuin-A inhibits in vitro vesicle-mediated VSMC that plays a beneficial role in CRF patients [36]. Furthermore, levels of fetuin-A are inversely related to valvular calcification in peritoneal dialysis patients [37]. In the early stages of calcification high levels of fetuin-A were found in children undergoing HD. This may be explained by its protective role against prolonged calcification and inflammatory environment [38]. The present study found a positive correlation between fetuin-A and OPG, this finding is in consistence with Koluman et al., study [39] who found that both biomarkers increased in diabetic patients. Additionally, this study found that the levels of OPG were significantly increased in patients after being supplemented with omega-3 compared with the control group. Consistently Kolahi et al., [40] illustrated that the levels of OPG were significantly increased in female patients suffering from rheumatoid arthritis after being supplemented with one gram fish oil per day for three months. Similarly, the OPG level was increased in hyperlipidemic patients who received 0.5 liter of fortified milk with fish oil, oleic acid, and vitamins per day for one year [41]. On the contrary, Zakaria et al., [42] found that serum OPG levels showed non-significant changes following the daily administration of the combined supplementation of fish oil with antioxidants such as wheat germ oil (WGO) for four months. Another study, conducted on 127 postmenopausal women with moderate cardiovascular risk, showed a decrease in total cholesterol, however, the levels of OPG were not changed after 12 months of consuming 40 mg/100 mL of EPA and DHA [43]. Our results from the ROC curves showed that fetuin-A levels followed by OPG levels could be used as predictor biomarkers in HD patients for VC progression and development after six months of omega-3 intake. In general, OPG is known to be a prognostic marker of mortality in ESRD because it plays a major role in the VC process [44]. Another study suggested that the measurement of OPG levels should be added to the routine biological follow up for HD patients. Results from another study, that followed up prospectively 185 HD patients for two yearsillustrated that the elevation of OPG level can be used as strong predictor of mortality in HD patients. this suggests that OPG is a vascular risk factor, particularly, in patients who have high C-reactive protein levels [45].
The presented study showed that omega-3 supplementation for six months did not affect the levels of serum creatinine, BUN, phosphorus, PTH and hemoglobin. Consistently the levels of PTH, phosphorus, and hemoglobin were not changed in 23 HD patients after receiving 3000 mg of Fish oil (omega-3 fatty acids withwheat germ oil) for four months [42]. Similarly, after ingestion of 1800mg of omega 3 fatty acids for four months , the levels of PTH were not significantly changed [46]. Furthermore, Vernaglione et al., [47] did not find a significant difference in hemoglobin after 12 months of omega-3 (2gram/daily) intake in HD patients. As opposed to our results, a study that used 2.4 gram per day for seven weeks in HD patients, revealed a slight increase in hemoglobin levels [18].
In our study calcium levels were significantly decreased in the omega-3 group, whereas there was a non-significant reduction in the control group. On the other hand, another a pervious study showed a slight increase in calcium levels after omega-3 supplementation for 12 weeks in peritoneal dialysis patients [48], and for four months HD patients [42]. The present study revealed that albumin levels were slightly increased after omega-3 supplementation compared with the control group. In agreement with our study, an earlier study conducted on HD patients, showed that albumin levels were slightly increased in patients who completed their omega-3 with protein supplementation regimen for six months [49]. Our study found that serum triglycerides levels were significantly decreased in the Omega 3 group and the control group as compared to the baseline, with no significant difference between both groups after six months of intervention. This may be attributed to the use of heparin in HD therapy, various therapy-related factors (such as statin, niacin and fibrate) which are thought to cause modifications in triglyceride and triglyceride-rich lipoproteins [50]. Some investigators have reported that dialysis using synthetic membranes with high-flux characteristics resulted in a reduction of triglyceride rich lipoproteins and an increase in HDL cholesterol and apoA1 levels [51].
This finding comes in agreement with another study that found a significant reduction in serum triglycerides compared with baseline after ten weeks of omega-3 intake in HD patients [52]. Omega-3 is a well-known hypotriglyceridemic agent because it works by inhibiting the fatty acid synthesis in the liver and hence it inhibits the synthesis of triglycerides [53; 54].