Predicting the effects of supplemental EPA and DHA on the omega-3 index.

BACKGROUND: Supplemental long-chain omega-3 (n-3) fatty acids (EPA and DHA) raise erythrocyte EPA + DHA [omega-3 index (O3I)] concentrations, but the magnitude or variability of this effect is unclear. OBJECTIVE: The purpose of this study was to model the effects of supplemental EPA + DHA on the O3I. METHODS: Deidentified data from 1422 individuals from 14 published n-3 intervention trials were included. Variables considered included dose, baseline O3I, sex, age, weight, height, chemical form [ethyl ester (EE) compared with triglyceride (TG)], and duration of treatment. The O3I was measured by the same method in all included studies. Variables were selected by stepwise regression using the Bayesian information criterion. RESULTS: Individuals supplemented with EPA + DHA (n = 846) took a mean ± SD of 1983 ± 1297 mg/d, and the placebo controls (n = 576) took none. The mean duration of supplementation was 13.6 ± 6.0 wk. The O3I increased from 4.9% ± 1.7% to 8.1% ± 2.7% in the supplemented individuals ( P < 0.0001). The final model included dose, baseline O3I, and chemical formulation type (EE or TG), and these explained 62% of the variance in response (P < 0.0001). The model predicted that the final O3I (and 95% CI) for a population like this, with a baseline concentration of 4.9%, given 850 mg/d of EPA + DHA EE would be ∼6.5% (95% CI: 6.3%, 6.7%). Gram for gram, TG-based supplements increased the O3I by about 1 percentage point more than EE products. CONCLUSIONS: Of the factors tested, only baseline O3I, dose, and chemical formulation were significant predictors of O3I response to supplementation. The model developed here can be used by researchers to help estimate the O3I response to a given EPA + DHA dose and chemical form.

Red Blood Cell Docosapentaenoic Acid (DPA n-3) is Inversely Associated with Triglycerides and C-reactive Protein (CRP) in Healthy Adults and Dose-Dependently Increases Following n-3 Fatty Acid Supplementation.

The role of the long-chain omega-3 (n-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in lipid metabolism and inflammation has been extensively studied; however, little is known about the relationship between docosapentaenoic acid (DPA, 22:5 n-3) and inflammation and triglycerides (TG). We evaluated whether n-3 DPA content of red blood cells (RBC) was associated with markers of inflammation (interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and C-reactive protein (CRP) and fasting TG prior to n-3 supplementation in two studies (Study 1: n = 115, aged 20-44 years, body mass index (BMI) 20-30 kg/m2, TG = 34-176 mg/dL; Study 2: n = 28, aged 22-65 years, BMI 24-37 kg/m2, TG = 141-339 mg/dL). We also characterized the dose-response effects of n-3 fatty acid supplementation on RBC n-3 DPA after five months of supplementation with fish oil (Study 1: 0, 300, 600, 900, and 1800 mg/day EPA + DHA) and eight weeks of prescription n-3 ethyl esters (Study 2: 0, 850, and 3400 mg/day EPA + DHA). In Study 1, RBC n-3 DPA was inversely correlated with CRP (R2 = 36%, p < 0.001) and with fasting TG (r = -0.30, p = 0.001). The latter finding was replicated in Study 2 (r = -0.33, p = 0.04). In both studies, n-3 supplementation significantly increased RBC n-3 DPA dose-dependently. Relative increases were greater for Study 1, with increases of 29%-61% vs. 14%-26% for Study 2. The associations between RBC n-3 DPA, CRP, and fasting TG may have important implications for the prevention of atherosclerosis and chronic inflammatory diseases and warrant further study.

Effects of supplemental long-chain omega-3 fatty acids and erythrocyte membrane fatty acid content on circulating inflammatory markers in a randomized controlled trial of healthy adults.

The long-chain omega-3 polyunsaturated (n-3 PUFA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), may have anti-inflammatory effects. We evaluated the dose-response effect of EPA+DHA supplementation on circulating TNF-α, IL-6, and CRP and explored associations between red blood cell (RBC) membrane PUFA content and TNF-α, IL-6, and CRP. Young adults with low fish intake (n=116) received one of five doses (0, 300, 600, 900, or 1,800 mg/d EPA+DHA) for 5 months. There were no significant effects of supplemental EPA+DHA on IL-6 or CRP; however, there was a marginal treatment effect for TNF-α (p<0.08). At baseline, higher quartiles of RBC DHA were associated with lower TNF-α (p=0.001); higher quartiles of arachidonic acid were associated with higher TNF-α (p=0.005). EPA+DHA supplementation had no dose-response effect on TNF-α, IL-6, or CRP in healthy young adults; however, associations between inflammatory markers and RBC PUFA warrant further investigation.

Macronutrient replacement options for saturated fat: effects on cardiovascular health.

PURPOSE OF REVIEW: The purpose of this review is to discuss macronutrient replacement options for saturated fatty acids (SFAs) to optimize cardiovascular disease (CVD) risk reduction. RECENT FINDINGS: Dietary recommendations advise decreasing SFAs. There is convincing evidence that replacing SFAs with unsaturated fat, both omega-6 and omega-3 polyunsaturated fatty acids, reduces CVD risk. Monounsaturated fatty acid substitution for SFAs also decreases CVD risk. Replacing SFAs with refined carbohydrate does little to alter CVD risk, whereas whole-grain CHO or lean protein substitutions beneficially affect CVD risk. SUMMARY: Modifying the macronutrient composition of the diet by replacing SFAs with unsaturated fatty acids, as well as lean protein and carbohydrate from whole grains, all lower CVD risk. Research is needed to identify food sources of macronutrients that optimize CVD risk reduction.

Determinants of erythrocyte omega-3 fatty acid content in response to fish oil supplementation: a dose-response randomized controlled trial.

BACKGROUND: The erythrocyte membrane content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which constitutes the omega-3 index (O3I), predicts cardiovascular disease mortality. The amount of EPA+DHA needed to achieve a target O3I is poorly defined, as are the determinants of the O3I response to a change in EPA+DHA intake. The objective of this study was to develop a predictive model of the O3I response to EPA+DHA supplementation in healthy adults, specifically identifying factors that determine the response. METHODS AND RESULTS: A randomized, placebo-controlled, double-blind, parallel-group study was conducted in 115 healthy men and women. One of 5 doses (0, 300, 600, 900, 1800 mg) of EPA+DHA was given daily as placebo or fish oil supplements for ≈5 months. The O3I was measured at baseline and at the end of the study. There were no significant differences in the clinical characteristics between the groups at baseline. The O3I increased in a dose-dependent manner (P<0.0001), with the dose of EPA+DHA alone accounting for 68% (quadratic, P<0.0001) of the variability in the O3I response. Dose adjusted per unit body weight (g/kg) accounted for 70% (linear, P<0.0001). Additional factors that improved prediction of treatment response were baseline O3I, age, sex, and physical activity. Collectively, these explained 78% of the response variability (P<0.0001). CONCLUSIONS: Our findings validate the O3I as a biomarker of EPA+DHA consumption and identify additional factors, particularly body weight, that can be used to tailor EPA+DHA recommendations to achieve a target O3I.

Long-chain omega-3 fatty acids: time to establish a dietary reference intake.

The beneficial effects of consuming omega-3 polyunsaturated fatty acids (n-3 PUFAs), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on cardiovascular health have been studied extensively. To date, there is no dietary reference intake (DRI) for EPA and DHA, although many international authorities and expert groups have issued dietary recommendations for them. Given the substantial new evidence published since the last Institute of Medicine (IOM) report on energy and macronutrients, released in 2002, there is a pressing need to establish a DRI for EPA and DHA. In order to set a DRI, however, more information is needed to define the intakes of EPA and DHA required to reduce the burden of chronic disease. Information about potential gender- or race-based differences in requirements is also needed. Given the many health benefits of EPA and DHA that have been described since the 2002 IOM report, there is now a strong justification for establishing a DRI for these fatty acids.

Immunometabolic role of long-chain omega-3 fatty acids in obesity-induced inflammation.

Inflammation links obesity with the development of insulin resistance. Macrophages and phagocytic immune cells communicate with metabolic tissues to direct an inflammatory response caused by overnutrition and expanding adipose tissue. Marine-derived omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), modulate inflammatory signalling events, providing various anti-inflammatory and cardioprotective benefits. Moreover, EPA and DHA may improve insulin sensitivity by generating proresolving lipid mediators and promoting alternatively activated macrophages. This review will assess the role of EPA and DHA in ameliorating obesity-induced inflammation, evaluating clinical evidence and mechanisms of action. The pathophysiology of insulin resistance resulting from obesity-induced inflammation will be discussed, highlighting the relationship between metabolism and immunity, and in particular, how EPA and DHA work with both systems to modulate immunometabolic complications and chronic disease.

Diverse physiological effects of long-chain saturated fatty acids: implications for cardiovascular disease.

PURPOSE OF REVIEW: The purpose of this review is to discuss the metabolism of long-chain saturated fatty acids and the ensuing effects on an array of metabolic events. RECENT FINDINGS: Individual long-chain saturated fatty acids exhibit unique biological properties. Dietary saturated fat absorption varies depending on chain-length and the associated food matrix. The in-vivo metabolism of saturated fatty acids varies depending on the individual fatty acid and the nutritional state of the individual. A variety of fatty acid metabolites are formed, each with their own unique structure and properties that warrant further research. Replacing saturated fatty acids with unsaturated fatty acids improves the blood lipid profile and reduces cardiovascular disease risk, although the benefits depend on the specific saturated fatty acid(s) being replaced. SUMMARY: Acknowledging the complexity of saturated fatty acid metabolism and associated metabolic events is important when assessing their effects on cardiovascular disease risk. Investigating the biological effects of saturated fatty acids will advance our understanding of how they affect cardiovascular disease risk.