Harmonizing blood DHA levels in pregnancy studies: An interlaboratory investigation.

Recent trials in pregnant women on the effects of supplemental DHA on early preterm birth (ePTB) risk have shown that there is a maternal blood docosahexaenoic acid (DHA) level below which risk for ePTB was increased and supplemental DHA was effective at reducing risk. However, DHA levels were expressed in different terms across these trials making cross study comparisons impossible. The purposes of this study were 1) to report interlaboratory conversion factors from study-specific metrics to a common metric, red blood cell (RBC) DHA measured by OmegaQuant Analytics (OQA), and 2) to translate reported pre- and post-treatment DHA levels from these trials into a RBC DHA for comparison. Data from five published and one unpublished study are included. Across these studies, the effects on RBC DHA levels after supplementation with 0, 200, 600, 800 and 1000 mg of DHA were (as a% change from baseline): 0 mg, no change; 200 mg, 15-20% increase; 600 mg, 55-60% increase; 800 mg, 13-65% increase; and 1000 mg, 51% increase. Standardization of fatty acid analysis and reporting and a target omega-3 or DHA level for identifying those for which higher dose DHA supplementation is indicated to prevent ePTB are needed for clinical use.

Baseline red blood cell and breast milk DHA levels affect responses to standard dose of DHA in lactating women on a controlled feeding diet.

BACKGROUND: The importance of providing the newborn infant with docosahexaenoic acid (DHA) from breast milk is well established. However, women in the United States, on average, have breast milk DHA levels of 0.20%, which is below the worldwide average (and proposed target) of >0.32%. Additionally, the relationship between maternal red blood cell (RBC) and breast milk DHA levels may provide insight into the sufficiency of DHA recommendations during lactation. Whether the standard recommendation of at least 200 mg/day of supplemental DHA during lactation is sufficient for most women to achieve a desirable RBC and breast milk DHA status is unknown. METHODS: Lactating women (n = 27) at about 5 weeks postpartum were enrolled in a 10-12 week controlled feeding study that included randomization to 480 or 930 mg choline/d (diet plus supplementation). As part of the intervention, all participants were required to consume a 200 mg/d of microalgal DHA. RBC and breast milk DHA levels were measured by capillary gas chromatography in an exploratory analysis. RESULTS: Median RBC DHA was 5.0% (95% CI: 4.3, 5.5) at baseline and 5.1% (4.6, 5.4) after 10 weeks of supplementation (P = 0.6). DHA as a percent of breast milk fatty acids increased from 0.19% (0.18, 0.33) to 0.34% (0.27, 0.38) after supplementation (P<0.05). The proportion of women meeting the target RBC DHA level of >5% was unchanged (52% at baseline and week 10). The proportion of women achieving a breast milk DHA level of >0.32% approximately doubled from 30% to 56% (p = 0.06). Baseline RBC and breast milk DHA levels affected their responses to supplementation. Those with baseline RBC and breast milk DHA levels above the median (5% and 0.19%, respectively) experienced no change or a slight decrease in levels, while those below the median had a significant increase. Choline supplementation did not significantly influence final RBC or breast milk DHA levels. CONCLUSIONS: On average, the standard prenatal DHA dose of 200 mg/d did not increase RBC DHA but did increase breastmilk DHA over 10 weeks in a cohort of lactating women in a controlled-feeding study. Baseline DHA levels in RBC and breast milk affected the response to DHA supplementation, with lower levels being associated with a greater increase and higher levels with no change or a slight decrease. Additional larger, dose-response DHA trials accounting for usual intakes and baseline DHA status are needed to determine how to best achieve target breast milk DHA levels and to identify additional modifiers of the variable breast milk DHA response to maternal DHA supplementation.

Recent Clinical Trials Shed New Light on the Cardiovascular Benefits of Omega-3 Fatty Acids.

Three recent clinical trials have demonstrated the benefits of marine omega-3 fatty acids on cardiovascular disease end points. In the Vitamin D and Omega-3 Trial (VITAL), 840 mg/d of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) resulted in a 28% reduced risk for heart attacks, 50% reduced risk for fatal heart attacks, and 17% reduced risk for total coronary heart disease events. In the ASCEND trial (A Study of Cardiovascular Events in Diabetes), cardiovascular disease death was significantly reduced by 19% with 840 mg/d of EPA and DHA. However, the primary composite end points were not significantly reduced in either study. In REDUCE-IT (the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), there was a 25% decrease in the primary end point of major cardiovascular events with 4 g/d EPA (icosapent ethyl) in patients with elevated triglycerides (135-499 mg/dL) who also were taking a statin drug. For clinical practice, we now have compelling evidence of the cardiovascular benefits of omega-3 fatty acids. The findings of REDUCE-IT provide a strong rationale for prescribing icosapent ethyl for patients with hypertriglyceridemia who are on a statin. For primary prevention, the goal is to increase the population intake of omega-3 fatty acids to levels currently recommended, which translates to consuming at least one to two servings of fish/seafood per week. For individuals who prefer taking omega-3 fatty acid supplements, recent findings from clinical trials support the benefits for primary prevention.

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.

Comparing the serum TAG response to high-dose supplementation of either DHA or EPA among individuals with increased cardiovascular risk: the ComparED study.

Studies have shown that the reduction in serum TAG concentrations with long-chain n-3 fatty acid supplementation is highly variable among individuals. The objectives of the present study were to compare the proportions of individuals whose TAG concentrations lowered after high-dose DHA and EPA, and to identify the predictors of response to both modalities. In a double-blind, controlled, crossover study, 154 men and women were randomised to three supplemented phases of 10 weeks each: (1) 2·7 g/d of DHA, (2) 2·7 g/d of EPA and (3) 3 g/d of maize oil, separated by 9-week washouts. As secondary analyses, the mean intra-individual variation in TAG was calculated using the standard deviation from the mean of four off-treatment samples. The response remained within the intra-individual variation (±0·25 mmol/l) in 47 and 57 % of participants after DHA and EPA, respectively. Although there was a greater proportion of participants with a reduction >0·25 mmol/l after DHA than after EPA (45 υ. 32 %; P 0·25 mmol/l after both DHA and EPA had higher non-HDL-cholesterol, TAG and insulin concentrations compared with other responders at baseline (all P < 0·05). In conclusion, supplementation with 2·7 g/d DHA or EPA had no meaningful effect on TAG concentrations in a large proportion of individuals with normal mean TAG concentrations at baseline. Although DHA lowered TAG in a greater proportion of individuals compared with EPA, the magnitude of TAG lowering among them was similar.

Supplementation with high-dose docosahexaenoic acid increases the Omega-3 Index more than high-dose eicosapentaenoic acid.

BACKGROUND: Recent studies suggest that eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids have distinct effects on cardiometabolic risk factors. The Omega-3 Index (O3I), which is calculated as the proportion of EPA and DHA in red blood cell (RBC) membranes, has been inversely associated with the risk of coronary heart diseases and coronary mortality. The objective of this study was to compare the effects of EPA and DHA supplementation on the O3I in men and women with abdominal obesity and subclinical inflammation. METHODS: In a double-blind controlled crossover study, 48 men and 106 women with abdominal obesity and subclinical inflammation were randomized to a sequence of three treatment phases: 1-2.7g/d of EPA, 2-2.7g/d of DHA, and 3-3g/d of corn oil (0g of EPA+DHA). All supplements were provided as 3×1g capsules for a total of 3g/d. The 10-week treatment phases were separated by nine-week washouts. RBC membrane fatty acid composition and O3I were assessed at baseline and the end of each phase. Differences in O3I between treatments were assessed using mixed models for repeated measures. RESULTS: The increase in the O3I after supplementation with DHA (+5.6% compared with control, P<0.0001) was significantly greater than after EPA (+3.3% compared with control, P<0.0001; DHA vs. EPA, P<0.0001). Compared to control, DHA supplementation decreased (-0.8%, P<0.0001) while EPA increased (+2.5%, P<0.0001) proportion of docosapentaenoic acid (DPA) in RBCs (DHA vs. EPA, P<0.0001). The baseline O3I was higher in women than in men (6.3% vs. 5.8%, P=0.011). The difference between DHA and EPA in increasing the O3I tended to be higher in men than in women (+2.6% vs. +2.2% respectively, P for the treatment by sex interaction=0.0537). CONCLUSIONS: The increase in the O3I is greater with high dose DHA supplementation than with high dose EPA, which is consistent with the greater potency of DHA to modulate cardiometabolic risk factors. The extent to which such differences between EPA and DHA in increasing the O3I relates to long-term cardiovascular risk needs to be investigated in the future.

Breast milk DHA levels may increase after informing women: a community-based cohort study from South Dakota USA.

BACKGROUND: Docosahexaenoic acid (DHA), an omega-3 fatty acid found in breast milk, has many health benefits for both mother and baby. A 2007 meta-analysis found U.S. women had breast milk DHA levels (0.20% of total fatty acids) below the worldwide mean (0.32%). In 2008, international dietary recommendations were made for pregnant and lactating women to consume 200 mg of DHA per day. This community-based study aimed to define current milk DHA levels from upper Midwest USA lactating mothers and to determine if providing information about their own level along with dietary recommendations would incite changes to increase breast milk DHA content. METHODS: New mothers attending lactation classes or using hospital pumping rooms in Sioux Falls, South Dakota, USA participated by providing one drop of breast milk on a card for fatty acid analysis at baseline and 1 month after initial reporting. DHA levels were analyzed by gas chromatography. Mothers received a report of their own breast milk level along with dietary recommendations on DHA intake for lactating women. Median baseline and follow-up DHA levels were determined and differences were compared by Wilcoxon signed-rank test. RESULTS: At baseline, breast milk DHA content (n = 84) was highly variable (range 0.05 to 0.73%) with a median of 0.18% (IQR, 0.13, 0.28; mean ± SD, 0.22 ± 0.13%), well below the worldwide average (0.32%). Women who reported taking DHA supplements (n = 43) had higher levels than those who did not (0.23% vs. 0.15%, P < 0.0001). In a subset of 60 mothers who submitted a second sample, median breast milk DHA content increased from 0.19 to 0.22% (P < 0.01). CONCLUSIONS: Findings suggest that providing nursing mothers with their breast milk DHA level and education about DHA intake while breastfeeding motivates change to increase DHA levels.