Fish oil and multivitamin supplementation reduces oxidative stress but not inflammation in healthy older adults: A randomised controlled trial

Abstract

The effects of daily fish oil supplementation, with and without multivitamins, on biochemical markers of health were examined. Healthy adults (N = 160) were randomised to receive 3 g of salmon oil with a multivitamin, 6 g of salmon oil with a multivitamin, 6 g of salmon oil in isolation or placebo in a double-blind fashion on a daily basis for 16 weeks. Relative to placebo, both 6 g salmon oil groups displayed significantly lower F₂-isoprostane levels at endpoint. Increases in red blood cell polyunsaturated fatty acids correlated with reductions in F₂-isoprostanes. Treatment had no effect on inflammatory cytokines, C-reactive protein, fibrinogen, cholesterol or triacylglycerol.

Introduction

Fish oil supplements containing the long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are one of the most popular dietary supplements in the western world (Morgan et al., 2012). Evidence suggests that higher intake of LC n-3 PUFA is related to better cardiovascular (Kris-Etherton, Harris, & Appel, 2002) and perhaps even neurological outcomes (Fotuhi et al, 2009, Tan et al, 2012). Fish oil supplements have been reported to improve the lipid profile, predominantly by lowering triacylglycerol levels (Harris, 1989), exerting vasodilatory effects (Xin, Wei, & Li, 2012) and by lowering blood pressure (Liu, Conklin, Manuck, Yao, & Muldoon, 2014).

LC n-3 PUFAs also play an important role in regulating inflammation (Calder, 2006b). The omega-6 (n-6) arachidonic acid (AA) has pro-inflammatory effects through the production of eicosanoids. Both AA and LC n-3 PUFA compete for space inside cell membrane phospholipids (Simopoulos, 2002). Increasing cellular levels of LC n-3 PUFA decreases the amount of AA in cell membranes thus limiting AA derived eicosanoids (Simopoulos, 2002). The ratio of LC n-3 PUFA to omega-6 fatty acid has thus been put forward as a measure of inflammation (Kalogeropoulos et al., 2010). Observational studies have reported that higher circulating levels of LC n-3 PUFA are associated with lower levels of pro-inflammatory cytokines and lower levels of C-reactive protein (CRP) (Farzaneh-Far et al, 2009, Ferrucci et al, 2006, Kalogeropoulos et al, 2010), which are known to be predictive of cardiovascular disease (CVD) (Ridker, Hennekens, Buring, & Rifai, 2000).

LC n-3 PUFAs may also have antioxidant effects. A study by Mori et al. (1999) reported that a daily fish meal for eight weeks reduced urinary F₂-isoprostane levels in sedentary subjects with non-insulin dependent diabetes. F₂-isoprostanes are lipid peroxidation products derived from the non-enzymatic free radical oxidation of AA in membrane lipids and are considered the most reliable biomarkers of in vivo lipid peroxidative damage (Milne, Yin, Hardy, Davies, & Roberts, 2011). Subsequent placebo controlled studies using purified EPA or DHA showed both fatty acids reduced urinary (Mori et al, 2000, Mori et al, 2003) and plasma (Mas et al., 2010) F₂-isoprostanes in type 2 diabetic patients, and in overweight mildly dyslipidaemic men, respectively. A recent double-blind, 4 month randomised, controlled trial (RCT) reported that LC n-3 PUFA supplementation reduced plasma F₂-isoprostane levels by approximately 15%, relative to placebo (Kiecolt-Glaser et al., 2013).

Multivitamin supplements, containing both vitamins and minerals, are commonly used among the general population (Radimer et al., 2004). Evidence suggests that the intake of a range of vitamins and minerals may interact with fatty acid metabolism influencing the overall levels of LC n-3 PUFA measured in vivo (Bertrandt et al, 2004, Durand et al, 1996, Pipingas et al, 2014, Stangl, Kirchgessner, 1998). There is thus a need to examine the combined effects of multivitamin supplements and LC n-3 PUFAs on all aspects of human health.

The present 16 week RCT was designed to investigate the effect of salmon oil supplementation, with and without the addition of a multivitamin supplement, on cardiovascular and cognitive health in healthy middle-aged and elderly subjects. To the best of our knowledge, this is the first RCT to investigate the combined effects of fish oils and multivitamins on human health. The results of supplementation on the cognitive, cardiovascular and omega-3 uptake into red bloods cells arising from this RCT have been published (Pase et al, 2014, Pipingas et al, 2014). This report examines the secondary outcomes from this study including the effects of supplementation on measures of inflammation, oxidative stress, serum lipids and liver function, in the same subjects. It was hypothesised that treatment with salmon oil would reduce markers of inflammation and oxidative stress as well as triacylglycerol levels. The study also had the novel aim of exploring whether combining salmon oil with a multivitamin would provide added benefits to human health.