Docosahexaenoic Acid Intake Research Articles

Omega-3 polyunsaturated fatty acid intake and plasma fatty acids of school going Indian children - a cross-sectional study

Long-chain omega-3 polyunsaturated fatty acids (PUFA) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) play an essential role in cognitive and behavioural changes among school going children. This study delineates the dietary omega-3 PUFA [alpha-Linolenic acid (ALA), DHA, and EPA] intake and plasma fatty acids levels among school-going children. This is a cross-sectional study purely observational in nature, wherein 625 apparently healthy boys and girls aged between 7 and 13 years were selected from five different schools of Hyderabad. Dietary information on omega-3 PUFA (ALA, DHA, and EPA) intake was collected using a food frequency questionnaire. Plasma fatty acid concentrations were measured in 34% of sub-sample using standard gas chromatography. The study revealed that the average dietary intakes of omega-3 PUFA, ALA, DHA, and EPA were 55.46, 15.82, 35.59, 4.06 mg/day, respectively. There was a significant difference in mean DHA intake among gender and age group [girls (38.64±1.45 mg/day), boys (31.80±1.38 mg/day) p < 0.001] and [7–10 years (31.75±1.38 mg/day), 11–13 years (38.07±1.40 mg/day) p < 0.01]. The mean plasma DHA and DPA levels of overall subjects were 0.98 nmol% and 0.18nmol% respectively which was comparable among different gender, age and BMI-for age groups. There was a positive correlation between dietary DHA intake and plasma DHA level [ρ=0.376 (p < 0.001)]. The current study demonstrated that the omega-3 PUFA intake in school going children was less and reinforces the importance of increasing the omega-3 PUFA intake through diet and supplements.

Association of prenatal factors and cord blood lead levels in China: A nested cohort cross-sectional study

BackgroundLead exposure all over the world has gradually declined. As fetuses are more prone to lead exposure, even to low levels of lead exposure, it is important to monitor blood lead levels (BLLs) in pregnancy. MethodsWe obtained data on BLLs in the third trimester of pregnancy from medical records and measured cord BLLs obtained from 121 mother-child pairs in Shenyang, China from September 2019 to February 2020. We also estimated relationships between socio-demographic, lifestyle and dietary factors during pregnancy as well as cord BLLs to identify the source of lead exposure during pregnancy. BLLs was estimated by atomic absorption spectrometry through graphite furnace ionization techniques. The data which obtained by questionnaires during pregnancy included maternal sociodemographic, lifestyle, dietary factors. We have established three multivariate logistic regression models in which the dichotomous BLLs was used as the dependent variable (cord BLLs ≥20 μg/L vs <20 μg/L). ResultsThe median and geometric mean of cord BLLs were 22.90 μg/L, 21.88 μg/L and BLLs in the third trimester of pregnancy were 25.29 μg/L, 24.66 μg/L, respectively. BLLs showed significant correlations between cord and the third trimester of pregnancy (r = 0.277, P = 0.012). Pregnant women who had not been exposed to passive smoking had lower OR (95 %) [0.43(0.19–0.94)] for cord BLLs ≥20 μg/L than pregnant women who had. Intake of docosahexaenoic acid (DHA) during third trimester of pregnancy presented an OR (95 %) [0.23(0.08–0.61)] for cord BLLs ≥20 μg/L. Consuming more whole grains (>3 times/week) and beverage (≥1 times/week) showed an OR (95%CI) for cord BLLs ≥20 μg/L of 0.09(0.02–0.53) and 0.19(0.06–0.69), respectively. ConclusionThis study showed the cord BLLs of Chinese are still higher than most developed countries. Passive smoking is a risk factor for cord BLLs ≥20 μg/L and supplement of DHA, whole grains and beverage consumption during pregnancy may act as a beneficial factor against having cord BLLs ≥20 μg/L.

Dried small fish provide nutrient densities important for the first 1000 days.

Inadequate nutrient intakes are prevalent among many populations in sub‐Saharan Africa and increasing fish consumption among pregnant/lactating women and children is one strategy to improve diets and address nutrient deficiencies. We report the nutrient content of two fish‐based recipes—fish powder and fish chutney—that contain dried small fish available in local markets in Zambia. The contribution of a serving of each recipe to the recommended daily intakes of iron, zinc, calcium and docosahexaenoic acid (DHA) for pregnant/lactating women and children 6–24 months was calculated because these nutrients are commonly deficient in African diets. We found that one 10‐g serving of fish powder provides 20% or more of the daily calcium recommendation and 37% or more of the daily DHA recommendation for both pregnant/lactating women and children. A 30‐g serving of fish chutney provides over 40% of the daily calcium recommendation for pregnant women and over 50% for lactating women. Additionally, we investigated the nutrient density (nutrients per kilocalorie) of the fish powder and compared it with the nutrient density of a small‐quantity lipid‐based nutrient supplement plus (SQ‐LNS‐plus). SQ‐LNS‐plus is designed to enhance children's diets by providing micronutrients and DHA. Fish powder is similar to SQ‐LNS‐plus in iron and zinc density and even higher in calcium and DHA density. Consuming dried small fish as part of a daily meal can be a viable strategy for combatting nutrient deficiencies in the first 1000 days.

Inadequate Content of Docosahexaenoic Acid (DHA) of Donor Human Milk for Feeding Preterm Infants: A Comparison with Mother's Own Milk at Different Stages of Lactation.

A cross-sectional single-center study was designed to compare the fatty acids profile, particularly docosahexaenoic acid (DHA) levels, between milk banking samples of donor human milk and mother’s own milk (MOM) for feeding preterm infants born before 32 weeks’ gestation. MOM samples from 118 mothers included colostrum (1–7 days after delivery), transitional milk (9–14 days), and mature milk (15–28 days and ≥29 days). In the n-3 polyunsaturated fatty acids (PUFAs) group, the levels of α-linolenic acid (C18:3 n3) and DHA (C22:6 n3) showed opposite trends, whereas α-linolenic acid was higher in donor human milk as compared with MOM, with increasing levels as stages of lactation progressed, DHA levels were significantly lower in donor human milk than in MOM samples, which, in turn, showed decreasing levels along stages of lactation. DHA levels in donor human milk were 53% lower than in colostrum. Therefore, in preterm infants born before 32 weeks’ gestation, the use of pasteurized donor human milk as exclusive feeding or combined with breastfeeding provides an inadequate supply of DHA. Nursing mothers should increase DHA intake through fish consumption or nutritional supplements with high-dose DHA while breastfeeding. Milk banking fortified with DHA would guarantee adequate DHA levels in donor human milk.

Associations of dietary fats intake and adipokines levels in obese women.

RBP4, Vaspin and omentin-1 are adipokines, which play an important role in the development of obesity-related complications. The main aim of this study was to investigate the effects of different kinds of fat intake on adipokine levels in obese women. A total of 272 obese women (BMI≥30) were included in the current cross-sectional study, according to the inclusion and exclusion criteria. Body composition was measured using a body composition analyzer. For the measurement of retinol binding protein 4 (RBP4), vaspin and omentin-1 serum concentrations, an enzyme-linked immunosorbent assay (ELISA) method was used. Dietary intake was assessed using a 3-day 24-h dietary recall. Statistically significant differences were found between polyunsaturated fatty acid (PUFAs) and linoleic acid intake and vaspin and omentin-1 levels. In addition, there were found statistically significant relationships between cholesterol, monounsaturated fatty acid (MUFAs) and total fat intakes with omentin-1 levels. Also, RBP4 and vaspin levels were different significant with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake. Moreover, the results revealed that there were statistically significant differences between RBP4 levels and α-linolenic acid and oleic acid intake. This study revealed that by examining RBP4, vaspin and omentin-1 as adipokines, a novel link between fat intakes and adipokine levels was found.

DHA and Its Metabolites Have a Protective Role against Methylmercury-Induced Neurotoxicity in Mouse Primary Neuron and SH-SY5Y Cells.

The consumption of fish now involves a risk of methylmercury (MeHg) exposure but also provides the benefit of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) such as docosahexaenoic acid (DHA). Some epidemiological studies have suggested that the intake of DHA can alleviate the neurotoxicity of MeHg, but the underlying mechanism is not known. Herein, we observed that pretreatment with 0.1–1 µM DHA suppressed MeHg-induced cytotoxicity in human neuroblastoma (SH-SY5Y) cells and mouse primary neuronal cells. These effects of DHA were canceled in the presence of the retinoid X receptor (RXR) antagonist UVI3003. An RXR agonist, bexarotene, suppressed the cytotoxicity of MeHg. DHA also suppressed the MeHg-induced production of reactive oxygen species (ROS) via an induction of antioxidant genes (catalase and SOD1). Pretreatment with DHA did not change the incorporation of MeHg. We showed previously that in the brain, the intake of DHA increased the level of 19,20-DHDP, which is the metabolite produced by cytochrome P450 and soluble epoxide hydrolase from DHA. In the present study, we observed that 19,20-DHDP also suppressed neurotoxicity from MeHg. These results indicate that DHA and its metabolites have a protective role in MeHg-induced neurotoxicity.

The association between dietary fatty acid intake and the risk of developing preeclampsia: a matched case\u2013control study

The association between dietary fat intake during pregnancy and the risk of developing preeclampsia has been examined in many epidemiological studies, but the results remain inconsistent. The aim of this study was to clarify this association in pregnant Chinese women. After conducting 1:1 matching, 440 pairs consisting of pregnant women with preeclampsia and hospital-based, healthy pregnant women matched by gestational week (± 1 week) and age (± 3 years) were recruited. A 79-item semi-quantitative food frequency questionnaire administered during face-to-face interviews was used to estimate the participants’ dietary intake of fatty acids. We found that the intakes of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were inversely associated with the risk of developing preeclampsia. Compared with the lowest quartile intake, the multivariate-adjusted odds ratios (95% confidence interval) of the highest quartile intake were 0.42 (0.26–0.68, p-trend < 0.001) for EPA, 0.52 (0.3–0.83, p-trend = 0.005) for DHA, and 0.41 (0.19–0.88, p-trend = 0.007) for AA. However, we did not observe any significant associations between the intake of total fatty acids, saturated fatty acids, and mono-unsaturated fatty acids and the risk of developing preeclampsia. Our results showed that the dietary intake of long-chain polyunsaturated fatty acids (i.e., EPA, DHA, and AA) may protect pregnant Chinese women against the development of preeclampsia.

Serum fatty acid synthase levels and n-3 fatty acid intake in patients with breast cancer.

Fatty acid synthase (FASN) is a key enzyme in fatty acid biosynthesis that is usually over-expressed in patients with breast cancer, but its relationship with the patient's dietary habit is not clear. A higher intake of n-3 polyunsaturated fatty acids is related to reduced breast carcinogenesis invitro and invivo. The aim of this study was to clinically investigate the association between serum FASN levels and fatty acid intake in women newly diagnosed with breast cancer. In a case-control cross-sectional study, with 18 breast cancer patients and 29 controls, we evaluated nutritional status, dietary intake, and serum FASN levels. Statistical analyses were carried out with parametric and non-parametric tests, according to the sample's normality distribution. The mean age of breast cancer group (n=18) and control group (n=29) was 46.8±9.7y and 44.4.±8.6y, respectively. Mean serum concentration of FASN in breast cancer group was significantly higher (132.51±95.05ng/mL) than in control group (36.88±20.87ng/mL) (p<0.0001). Among breast cancer group, serum FASN levels of premenopausal women were significantly higher than those of postmenopausal women (p=0.026). There was no significant difference between the early and late disease stages in regard to serum FASN levels in breast cancer group. Mean nutrient intake was similar and n-3 docosahexaenoic acid intake was low in both groups. We observed no association regarding fatty acid intake and serum FASN levels. These data suggest that dietary n-3 fatty acid has no association with serum FASN levels among newly diagnosed breast cancer patients.

Intake of marine n-3 polyunsaturated fatty acids and the risk of incident peripheral artery disease.

A high intake of marine n-3 polyunsaturated fatty acids (PUFAs) may lower the risk of coronary heart disease and ischemic stroke. The association between intake of marine n-3 PUFAs and development of peripheral artery disease (PAD), however, remains unexplored. We hypothesised that intake of marine n-3 PUFAs, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and the sum of EPA + DHA was associated with a lower risk of incident PAD. We used data from the Danish Diet, Cancer and Health cohort and investigated the associations between intake of EPA, DHA and EPA + DHA and development of PAD. Information on intake of n-3 PUFAs was obtained through a validated food frequency questionnaire. Potential PAD cases were identified through linkage to the Danish National Patient Register and subsequently, all cases were validated. Data were available from 55,248 participants and during a median of 13.6 years of follow-up, 950 cases of PAD were identified. Multivariate Cox regression analyses with adjustments for established risk factors showed no statistically significant associations between intake of EPA (p = 0.255), DHA (p = 0.071) or EPA + DHA (p = 0.168) and the rate of incident PAD. We did not confirm our hypothesis that intake of EPA, DHA or EPA + DHA was associated with a lower risk of incident PAD.

Intake of n-3 polyunsaturated fatty acids in childhood, FADS genotype and incident asthma.

Longitudinal evidence on the relation between dietary intake of n-3 (ω-3) very-long-chain polyunsaturated fatty acids, i.e. eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in mid-childhood and asthma risk is scarce. We aimed to investigate whether a higher intake of EPA and DHA from fish in childhood is associated with a lower risk of incident asthma.In the Avon Longitudinal Study of Parents and Children, dietary intakes of EPA and DHA from fish were estimated by food frequency questionnaire at 7 years of age. We used logistic regression, controlling for confounders, to analyse associations between intake of EPA and DHA (quartiles) and incidence of doctor-diagnosed asthma at age 11 or 14 years, and explored potential effect modification by a fatty acid desaturase (FADS) polymorphism (rs1535). Replication was sought in the Swedish BAMSE birth cohort.There was no evidence of association between intake of EPA plus DHA from fish and incident asthma overall (n=4543). However, when stratified by FADS genotype, the odds ratio comparing the top versus bottom quartile among the 2025 minor G allele carriers was 0.49 (95% CI 0.31–0.79; ptrend=0.006), but no inverse association was observed in the homozygous major A allele group (OR 1.43, 95% CI 0.83–2.46; ptrend=0.19) (pinteraction=0.006). This gene–nutrient interaction on incident asthma was replicated in BAMSE.In children with a common FADS variant, higher intake of EPA and DHA from fish in childhood was strongly associated with a lower risk of incident asthma up to mid-adolescence.

Dietary fatty acid intake, plasma fatty acid levels, and the risk of age-related macular degeneration (AMD): a dose-response meta-analysis of prospective cohort studies.

Previous population studies on the associations between dietary fatty acids (FAs), plasma FAs levels, and the risk of age-related macular degeneration (AMD) have yielded inconclusive results. Herein, we conducted a dose-response meta-analysis to quantitatively evaluate the associations between specific type of dietary FAs, plasma FAs on early and advanced AMD risk. PubMed, Web of Science, and EMBASE were systematically searched for observational cohort studies published through May 2020. For highest versus lowest comparison and dose-response analyses, the relative risk (RR) estimates with a 95% confidence interval (CI) were analyzed using random effects model. 11 studies with 167,581 participants were included in the meta-analysis. During the follow-up periods (ranging from 3 to 28years), 6,318 cases of AMD were recorded. Dietary intake of docosahexaenoic acid (DHA) and eicosatetraenoic acid (EPA) combined (per 1g/day increment) were found to be negatively associated with early AMD (RR: 0.67, 95% CI [0.51, 0.88]). Each 1g/day increment of DHA (RR: 0.50, 95% CI [0.32, 0.78]) and EPA (RR: 0.40, 95% CI [0.18, 0.87]) was associated with a 50% and 60% reduction of early AMD risk, respectively. Plasma DHA (RR: 0.72, 95% CI [0.55, 0.95]) and EPA (RR: 0.57, 95% CI [0.40, 0.81]) indicated significant negative relationship with advanced AMD. Increasing dietary intake of ω-3 polyunsaturated fatty acids (PUFAs), specifically DHA and EPA, were associated with a reduced risk of early subtype of AMD, while other types of FAs did not present significant results. Further research is warranted to explore the potential association between dietary FA, plasma FA levels, and advanced subtype of AMD.

Safety of oil from Schizochytrium limacinum (strain FCC-3204) for use in food supplements as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of Schizochytrium sp. oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Schizochytrium sp. is a single‐cell microalga. The strain FCC‐3204, used by the applicant (Fermentalg), belongs to the species Schizochytrium limacinum. The NF, an oil rich in docosahexaenoic acid (DHA), is obtained from microalgae after enzymatic lysis. The applicant proposed to increase the use level of the NF as a food supplement, from 250 mg DHA/day (currently authorised for the general population, excluding pregnant and lactating women) to 3 g DHA/day for adults, excluding pregnant and lactating women. S. limacinum was attributed the qualified presumption of safety (QPS) status with the qualification ‘for production purposes only’. Data provided by the applicant demonstrated the absence of viable cells in the NF. No toxicological studies were performed with the NF. However, based on the available toxicological data on oils derived from Schizochytrium sp., the QPS status of the source of the NF, the production process, the composition of the NF and the absence of viable cells in the NF, the Panel considers there are no concerns with regard to toxicity of the NF. The Panel considers that the data provided by the applicant are not sufficient to conclude on the safety of the NF at the proposed uses (3 g DHA/day as a food supplement) in adults. However, in 2012, the Panel concluded that supplemental intakes of DHA alone up to about 1 g/day do not raise safety concerns for the general population. The Panel concludes that the NF is safe for the use in food supplements at the maximum intake level of 1 g DHA/day for the target population (adults, excluding pregnant and lactating women).

Safety of oil from Schizochytrium limacinum (strain FCC-3204) for use in infant and follow-on formula as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of Schizochytrium sp. oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Schizochytrium sp. is a single‐cell microalga. The strain FCC‐ 3204, used by the applicant (Fermentalg), belongs to the species Schizochytrium limacinum. The NF, an oil rich in docosahexaenoic acid (DHA), is obtained from microalgae after enzymatic lysis. The applicant proposed to use the NF in infant formulae (IF) and follow‐on formulae (FOF). The use level defined by the applicant was derived from Regulation (EU) 2016/127, which states the mandatory addition of DHA to IF and FOF at the level of 20–50 mg/100 kcal. The intake of DHA resulting from the use of the NF in IF and FOF is not expected to pose safety concerns. S. limacinum was attributed the qualified presumption of safety (QPS) status with the qualification ‘for production purposes only’. Data provided by the applicant demonstrated the absence of viable cells in the NF. No toxicological studies were performed with the NF. However, based on the available toxicological data on oils derived from Schizochytrium sp., the QPS status of the source of the NF, the production process, the composition of the NF and the absence of viable cells in the NF, the Panel considers there are no concerns with regard to toxicity of the NF. The Panel concludes that the NF is safe under the proposed conditions of use.

Intake of Docosahexaenoic Acid-Enriched Milk Beverage Prevents Age-Related Cognitive Decline and Decreases Serum Bone Resorption Marker Levels.

The pathogenic mechanism of dementia is still unknown, and the fundamental treatment remains to be established. Thus, there is growing interest in preventing dementia through diet. One of the functional ingredients attracting attention is docosahexaenoic acid. We conducted a 12-month, randomized, double-blind, placebo-controlled clinical trial in healthy elderly Japanese individuals with a Mini-Mental State Examination score of 28 or higher at baseline using a docosahexaenoic acid-enriched milk beverage containing 297 mg docosahexaenoic acid and 137 mg eicosapentaenoic acid. Consumption of a docosahexaenoic acid-enriched milk beverage increased the fatty acid levels of docosahexaenoic acid and eicosapentaenoic acid in erythrocyte membranes, which was the primary outcome of this study. Moreover, intake of this beverage prevented age-related cognitive decline and decreased serum bone resorption marker levels. Our data demonstrate that, even at a low dose, long-term daily intake of docosahexaenoic acid prevents dementia and may show beneficial effect on bone health.

Protective effect and mechanism of docosahexaenoic acid on the cognitive function in female APP/PS1 mice.

Docosahexaenoic acid (DHA) has been studied for many years owing to its protective effect on the decline in brain function. DHA intake reduces the risk of Alzheimer's disease (AD) and decreases amyloid deposition; however, the underlying molecular mechanism has not been completed elucidated. In this study, the effect of DHA on the cognitive function of amyloid precursor protein (APP)/PS1 in wild-type mice and its related mechanism were investigated. Results from the Morris water maze test showed that DHA improved learning and memory function in mice. Moreover, DHA reduced neuronal damage in mice brains, as determined using Nissl staining. Unsaturated fatty acid levels in the brain of mice increased (p < 0.01) after DHA administration and saturated fatty acid levels decreased (p < 0.01). The deposition of amyloid-beta (Aβ) plaques and tau protein neurofibrillary tangles was significantly inhibited. The mechanism of action of DHA was attributed to the upregulation of the expression of β-secretase (BACE)2, which competed with BACE1 to cleave APP, thus decreasing the production of extracellular Aβ fragments (p < 0.01). The expression level of insulin-degrading enzyme was not significantly different. The expression of N-methyl-D-aspartate receptors was further downregulated and the phosphorylation of glycogen synthase kinase-3β and tau protein was inhibited (p < 0.01). These data indicated that DHA could protect cognitive function in mice by reducing Aβ plaque formation and decreasing tau phosphorylation levels.

Genetically modified plants are an alternative to oily fish for providing n-3 polyunsaturated fatty acids in the human diet: A summary of the findings of a Biotechnology and Biological Sciences Research Council funded project.

The n‐3 polyunsaturated fatty acids (PUFA) present primarily in oily fish, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are important components of cell membranes and that are needed for normal development and cell function. Humans have very limited capacity for EPA and DHA synthesis from α‐linolenic acid and so they must be obtained pre‐formed from the diet. However, perceived unpalatability of oily fish and fish oil concerns about contamination with environmental pollutants, dietary choices that exclude fish and animal products, and price limit the effectiveness of recommendations for EPA and DHA intakes. Moreover, marine sources of EPA and DHA are diminishing in the face of increasing demands. Therefore, an alternative source of EPA and DHA is needed that is broadly acceptable, can be upscaled and is sustainable. This review discusses these challenges and, using findings from recent nutritional trials, explains how they may be overcome by seed oils from transgenic plants engineered to produce EPA and DHA. Trials in healthy men and women assessed the acute uptake and appearance in blood over 8 hours of EPA and DHA from transgenic Camelina sativa compared to fish oil, and the incorporation of these PUFA into blood lipids after dietary supplementation. The findings showed that postprandial EPA and DHA incorporation into blood lipids and accumulation in plasma lipids after dietary supplementation was as good as that achieved with fish oil. The oil derived from this transgenic plant was well tolerated. This review also discusses the implications for human nutrition, marine ecology and agriculture.

DHA content in milk and biohydrogenation pathway in rumen: a review.

Docosahexaenoic acid (DHA) is an essential human nutrient that may promote neural health and development. DHA occurs naturally in milk in concentrations that are influenced by many factors, including the dietary intake of the cow and the rumen microbiome. We reviewed the literature of milk DHA content and the biohydrogenation pathway in rumen of dairy cows aim to enhance the DHA content. DHA in milk is mainly derived from two sources: α-linolenic acid (ALA) occurring in the liver and consumed as part of the diet, and overall dietary intake. Rumen biohydrogenation, the lymphatic system, and blood circulation influence the movement of dietary intake of DHA into the milk supply. Rumen biohydrogenation reduces DHA in ruminal environmental and limits DHA incorporation into milk. The fat-1 gene may increase DHA uptake into the body but this lacks experimental confirmation. Additional studies are needed to define the mechanisms by which different dietary sources of DHA are associated with variations of DHA in milk, the pathway of DHA biohydrogenation in the rumen, and the function of the fat-1 gene on DHA supply in dairy cows.

Refining omega‐3 supplementation trials in APOE4 carriers for dementia prevention

AbstractBackgroundDespite the observed association of the omega‐3s docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) intake or blood levels with Alzheimer’ disease (AD) incidence and cognitive outcomes, omega‐3 clinical trials have largely been negative. Carrying the APOE4 allele is the strongest genetic risk factor for AD. Therefore, identifying how APOE4 affects the response to omega‐3 supplementation can help refine newer and more personalized trials. DHA supplementation increases EPA levels and EPA has strong anti‐inflammatory effects. The ratio of EPA to arachidonic acid (EPA/AA) is a marker of tissue inflammation.MethodWe examined the effect of APOE4 on the change in plasma and cerebrospinal fluid (CSF) EPA/AA in two different clinical trials: the ADCS‐sponsored DHA trial in patients with mild AD (n=402), and the Brain DHA Delivery Pilot trial in cognitively normal participants (n=33). In both trials, participants were randomized to high doses of algal DHA (2 grams per day). A subset of the ADCS‐sponsored study underwent MRIs for measurement of hippocampal volumes (n=86).ResultPlasma EPA/AA was significantly lower in APOE4 carriers compared to non‐carriers after high dose DHA supplementation in both trials. CSF EPA/AA differed by APOE4 genotype in the Brain DHA Delivery Pilot, with APOE4 non‐carriers having two times greater increase in CSF EPA/AA than APOE4 carriers (30 vs. 14% increase, p=0.001) after supplementation. Greater increase in plasma EPA/AA was positively correlated with less decline in the right hippocampal volume (r=0.31, p=0.03) with APOE4 modifying this association (interaction p value, p=0.01, Figure 1).ConclusionAPOE4 appears to limit the conversion of DHA to EPA after DHA supplementation by promoting EPA’s mitochondrial oxidation. These changes start before the onset of dementia. We propose that the plasma EPA/AA can serve as a biomarker for DHA supplementation efficacy. Prospective validation of this biomarker can guide the development of more personalized omega‐3 interventions designed to reduce the increased AD risk with APOE4.

Changes in Erythrocyte Omega-3 Fatty Acids in German Employees upon Dietary Advice by Corporate Health.

Background: The erythrocyte ratio of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) over total fatty acids, the omega-3 index (O3I), has been suggested as an overall health marker and to motivate corporate health recommendations. We set out to assess the O3I status in a working population, the differences between normal and rotating shift employees, the consumption of omega-3 rich food and whether recommendations to increase intake of omega-3 rich foods can improve the O3I. Methods: Employees registered for their occupational health check-up were offered to participate in a pre-post study at the Ludwigshafen (Germany) site including an assessment of their O3I at baseline and after 4 months (follow-up) and two subsequent food frequency questionnaires. For those with O3I below 8%, a recommendation was provided to increase the intake of omega-3 fatty acid rich food and to take advantage of the employees’ catering service with its enhanced fatty seafood offer during the study period. Dietary intake of EPA and DHA, erythrocyte fatty acid profiles, clinical and lifestyle parameters were assessed. Results: In 500 employees (26.6% female, 21–64 years, median age: 47 years [IQR: 37–53]), at baseline the overall mean O3I was 4.1 ± 1.1% (99.6% of O3I assessed were below 8%), higher in women, in participants with “normal” body weight, upper employment grade, and non-smokers, but not different between regular and rotating shift workers. The three fifths of the cohort also participating in the follow-up increased their EPA and DHA intake by 0.1 g/d and their O3I by 0.5 percentage points. Conclusion: This study provides essential data on omega-3 erythrocyte concentrations in a clinically healthy German working population and the challenges of increasing the O3I with dietary recommendations even in study participants motivated to follow up on their omega-3 status.

Effect of Maternal Docosahexaenoic Acid (DHA) Supplementation on Offspring Neurodevelopment at 12 Months in India: A Randomized Controlled Trial.

Intake of dietary docosahexaenoic acid (DHA 22:6n-3) is very low among Indian pregnant women. Maternal supplementation during pregnancy and lactation may benefit offspring neurodevelopment. We conducted a double-blind, randomized, placebo-controlled trial to test the effectiveness of supplementing pregnant Indian women (singleton gestation) from ≤20 weeks through 6 months postpartum with 400 mg/d algal DHA compared to placebo on neurodevelopment of their offspring at 12 months. Of 3379 women screened, 1131 were found eligible; 957 were randomized. The primary outcome was infant neurodevelopment at 12 months, assessed using the Development Assessment Scale for Indian Infants (DASII). Both groups were well balanced on sociodemographic variables at baseline. More than 72% of women took >90% of their assigned treatment. Twenty-five serious adverse events (SAEs), none related to the intervention, (DHA group = 16; placebo = 9) were noted. Of 902 live births, 878 were followed up to 12 months; the DASII was administered to 863 infants. At 12 months, the mean development quotient (DQ) scores in the DHA and placebo groups were not statistically significant (96.6 ± 12.2 vs. 97.1 ± 13.0, p = 0.60). Supplementing mothers through pregnancy and lactation with 400 mg/d DHA did not impact offspring neurodevelopment at 12 months of age in this setting.