A randomized trial of fish oil omega-3 fatty acids on arterial health, inflammation, and metabolic syndrome in a young healthy population

Metabolic syndrome has become highly prevalent in the U.S. and has a strong impact on the development of future vascular ailments including Type II diabetes mellitus and cardiovascular diseases. This increase can be partially attributed to recent changes in the American diet that negatively affect body weight and arterial health [1].

Arterial stiffness is associated with metabolic syndrome and is a predictor of cardiovascular events [2]. Pulse wave velocity (PWV) and augmentation index (AIx) are measurements of arterial distensibility [3]. Reducing dietary saturated fats and increasing omega-3 polyunsaturated fats, especially from fish (O3), have long been known to improve vascular health and may improve measures of arterial stiffness [4]. Dangardt et al. reported supplementation with O3s improved vascular function and lowered the severity of inflammation among the obese [5]. However, Mackay, et al. found fish oil supplementation among those with or at risk of heart disease and receiving aspirin and statin therapy had no effect on pulse wave velocity [6]. O3s have also been found to improve obesity-induced metabolic syndrome through regulating chronic inflammation [7]. These include C-reactive protein (CRP), interleukin-6 (IL-6), and tumor-necrosis factor-α (TNF-α) [8].

While previous researchers have focused their studies on disease risk factors in older at-risk populations [9, 10], the present study sought to investigate the effects of O3 supplementation in a relatively overweight college-aged population. The pathologies of vascular diseases have been observed and recorded in the very young. Earlier intervention in those at early risk may show greater promise in longer-term benefits. Researchers have found that younger populations have responded favorably to O3 dosing during weight loss in reducing triglycerides, leptin, insulin, insulin resistance, and blood pressure and increasing ghrelin concentrations [11–14]. In addition, younger adults tend to consume relatively low amounts of fish and have relatively low levels of O3s in blood and tissues [15]. This might make this group especially responsive to the beneficial effects of even low doses of O3. Others have also found high PWV and Aix values among obese adolescents [16]. Thus, this study investigated whether O3s improved arterial health and inflammatory responses, both being indicators of risk for metabolic syndrome and ultimately, heart disease, diabetes, and stroke, in a healthy young relatively overweight population.

Of the 57 men and women who entered the study, 51 completed the intervention. Six participants did not return for the second clinical visit, four from the O3 group and two from the placebo group. Of those that completed the study, 41 returned the compliance check sheets, 19 from the placebo group and 22 from the fish oil group. Of those, 100% of the placebo participants consumed greater than 85% of their supplements while 86% of the fish oil participants consumed greater than 85% of their supplements.

Measurements were also taken four weeks later, after O3 supplementation. Figure 1 shows the effect of O3 dosing for four weeks on plasma phospholipid EPA and DHA. Plasma levels increased significantly (p < 0.001).

In this study we investigated the effect of O3 on relatively overweight but healthy young adults. We found no effect of 4 weeks of dosing with 1.7 grams per day on arterial hemodynamic measures, components of the metabolic syndrome, serum lipids, or measures of chronic inflammation. Yet, we were able to verify a change in O3 status in serum and red cell phospholipids with O3 dosing.

Emulsifying fish oils can enhance digestion and absorption of the fatty acids. Raatz, et al. investigated emulsified fish oil absorption compared with capsular triglyceride fish oil supplements in humans throughout a 48-hour observation period. A single dose (350 mg EPA and 230 mg DHA) of the emulsified product resulted in enhanced absorption of total O3 compared with the capsular supplement. Although we gave a relatively low dose, Raatz, et al. have shown that this material is absorbed more quickly and maybe more completely than fish oil in tablets [20]. Figure 1 shows that the O3 treatment increased plasma O3 EPA and DHA, despite four apparent non responders in the treatment group and two with increased EPA and DHA in the placebo group.

Arterial stiffness is associated with metabolic syndrome [2]. PWV and pulse pressure are measures positively associated with aortic stiffening, also measured by AIx [3, 21]. Sjoberg, et al. introduced 2 g, 4 g, and 6 g of fish oil supplementation per day into the diets of overweight or obese adults for 12 weeks. Improvement in arterial distensibility, as measured by PWV, was only found to be significant only at the highest dose of 6 g of fish oil per day [22]. Chong, et al. reported a significant improvement in PWV and AIx, in healthy adults immediately after a long chain O3 PUFA-rich meal containing 4.7 g of DHA and EPA [4]. However, Sanders, et al. recently found that 1.8 g of EPA and DHA daily over 12 months did not improve arterial stiffness among slightly overweight but relatively healthy middle aged subjects in England [23]. Thus, using a comparable dose over a greater duration than in our study within an older age group yielded similar outcomes.

A number of studies have been conducted on the association between O3 intake and the development of the metabolic syndrome. The present study found that fish oils did not have an effect on components of the metabolic syndrome in overweight young adults. Pederson, et al. found that supplementation with 1.5 g of O3 per day for 16 weeks significantly lowered systolic blood pressure and raised HDL cholesterol in overweight adolescents [24]. Also, supplementation with O3 over a 12-week period significantly lowered serum glucose levels [25].

Inflammation is also recognized as having a significant relationship with metabolic syndrome [26]. Dietary patterns poor in O3 may cause an excessive production of pro-inflammatory cytokines and CRP, while causing a lower production of anti-inflammatory cytokines, all recognized as contributing to the inflammation associated with metabolic syndrome and cardiovascular events [26, 27]. Dangardt, et al. executed an intervention of 1.2 g of O3 supplements per day on obese adolescents for 3 months having an average BMI of 33.8, compared to our group average BMI of 28.1. Results showed a significant decrease in TNF-α and IL-6 levels, but no significant change in the serum levels of CRP, IL-8 or IL-10 [5]. Low CRP levels have also been observed in Yup’ik Eskimos, a population who have mean daily intakes of DHA and EPA ranging from 2.4 to 3.7 g. In this population, CRP blood levels were inversely related to the intake of fish oils; however, there was no relationship found with IL-6 levels and fish oil intake [28]. Our results, in addition to those found in past studies, may further demonstrate the need for a longer intervention period, a higher treatment dose and an at-risk population selection for treatment to observe the desired results in inflammatory markers.

Overall, our present investigation found little effect of emulsified fish oil on components of the metabolic syndrome, inflammatory cytokines, or hemodynamic measures of arterial health. Other studies suggest that higher doses of fish oil coupled with a longer intervention period executed in a more unhealthy population may be needed to manifest positive and significant results from O3 intervention. Strengths of our study include the bioavailability of the emulsified supplement, clear evidence for incorporation of O3 doses into blood phospholipids, the young age of the participants, and the multiplicity of the endpoints, specifically the hemodynamic markers and the inflammatory cytokines. However, some limitations to the study are apparent. These include the short length in time of the dosing and the relatively low dose compared to other more recent studies.

The administration of a highly bioavailable emulsified preparation of fish oil O3 measurably increased plasma and red blood cells EPA and DHA in four weeks. However, no beneficial changes were observed in the markers that were measured for hemodynamic, metabolic syndrome, or inflammatory effects as a result in this relatively healthy overweight young adult cohort. More at-risk populations may benefit more from this intervention.