Doses Of DHA Research Articles

Thraustochytrids and Algae as Sustainable Sources of Long-Chain Omega-3 Fatty Acids for Aquafeeds

There is limited ability to biosynthesize long-chain omega-3 fatty acids such as EPA and DHA in food webs leading to humans. Seafood is the key source of ω3 LC-PUFA, with aquaculture expected to meet rising global demand; however, marine fish have a high dietary requirement for EPA and DHA themselves. This was traditionally met using unsustainable dietary fish oil and fish meal, but limited supply and environmental concerns have dictated research on replacements. Among the industrial sources of EPA and DHA, microalgae and especially thraustochytrids stand out as resources with high concentrations. Although unicellular, thraustochytrids are not microalgae as they are not photosynthetic but instead are microheterotrophs. This removes the light requirement and facilitates high yields of monoculture for the production of single-cell oils. The availability, in high concentrations, of usually one or the other essential fatty acid permits a calibration of the EPA and DHA dose, which is especially useful as their effects have mainly been considered together in medical and aquaculture research. EPA and DHA have different effects on cell function and are precursors of different bioactive compounds. Using thraustochytrids, microalgae, and heterotrophic dinoflagellates, the importance of DHA has been investigated. DHA was essential for optimizing the growth of the early life stages of scallops and finfish and was preferentially incorporated into fish membrane phospholipids. The production of microalgae and microheterotrophs can contribute to the treatment of wastewater and waste gas, further enhancing their sustainability and reducing the environmental costs of aquaculture.

Plasma levels of EPA and DHA after ingestion of a single dose of EPA and DHA ethyl esters

AbstractOmega‐3 polyunsaturated fatty acids (n3 PUFA), specifically eicosapentaenoic acid (EPA, 20:5n3), and docosahexaenoic acid (DHA, 22:6n3), are essential for maintaining health. To better understand their biology, it is important to define their bioavailability. The aim of this cross‐over study was to investigate and compare the acute effects on plasma EPA and DHA levels after single doses of EPA oil (99% pure) and DHA (97% pure) ethyl esters. Twelve men aged 20–40 years with a body‐mass‐index of 20–27 kg/m2 and low fish consumption were recruited. Several measures (e.g., 4‐week run‐in period, standardized diet, and blood collection protocols) were taken to reduce the inter‐individual variability of plasma fatty acids levels. Using a cross‐over design, the subjects received 2.2 g of EPA in the first test period and 2.3 g of DHA in the second. The test periods were separated by 2 weeks. Blood samples were taken before dosing and after 2, 4, 6, 8, 12, 24, 48, and 72 h. The mean ± SE maximum concentrations for EPA were higher than for DHA (115 ± 11 μg/mL vs. 86 ± 12 μg/mL; p = 0.05). The mean ± SE incremented area under the plasma concentration curve over 72 h for EPA (2461 ± 279 μg/mL) was 2.4 times higher (p < 0.001) than that for DHA (1021 ± 170 μg/mL). The mean ± SE half‐life was for EPA and DHA was 45 ± 8 and 66 ± 12 h. Our results indicate that EPA administration in single doses leads to higher circulating plasma levels of EPA compared to an effect of an equivalent dose of DHA on DHA plasma levels.

The Effect of Prenatal Docosahexaenoic Acid Supplementation on Offspring Fat Mass and Distribution at 24 Months Old

BackgroundExcessive gestational weight gain (GWG) is related to increased offspring fat accrual, and increased fat mass (FM) is related to obesity development. Prenatal DHA supplementation has been linked to lower levels of offspring FM; however, conflicting data exist. ObjectivesThis study aimed to determine if there is a protective effect of prenatal DHA supplementation on offspring fat accrual and adipose tissue deposition at 24 mo in offspring born to females who gain excessive weight compared with nonexcessive weight during pregnancy. We also explored if the effect of DHA dose on FM differed by offspring sex. MethodsInfants born to females who participated in the Assessment of DHA on Reducing Early Preterm Birth randomized controlled trial (ADORE) were recruited. In ADORE, females were randomly assigned to either a high or low prenatal DHA supplement. Offspring body composition and adipose tissue distribution were measured using dual-energy x-ray absorptiometry (DXA). GWG was categorized as excessive or not excessive based on clinical guidelines. ResultsFor total FM, there was a significant main effect for the DHA dose (P = 0.03); however, the dose by GWG status was nonsignificant (P = 0.44). Therefore, a higher prenatal DHA dose was related to greater offspring FM (622.9 g greater) and unrelated to GWG status. When investigating a DHA dose by sex effect, a significant main effect for DHA dose (P = 0.01) was detected for central FM. However, no interaction was detected (P = 0.98), meaning that both boys and girls had greater central FM if their mother was assigned to the higher DHA dose. ConclusionsGreater prenatal DHA supplementation was associated with greater offspring FM and adipose tissue distribution at 24 mo. It will be important to understand if these effects persist into childhood.This trial was registered at clinicaltrials.gov as NCT03310983.

A Preliminary Study on Hepatoprotective, Hypolipidemic and Aortic Morphometric Effects of Omega-3-Rich Fish Oil in Hypercholesterolemic Mice.

This study aims to evaluate the hepatoprotective, hypolipidemic and aortic morphometric effects of fish oil rich in omega-3 in hypercholesterolemic BALB/c mice. This is an experimental model that included 16 male BALB/c mice (Mus musculus) divided into three groups (G1 (standard commercial chow and 0.9% saline solution), G2 (hypercholesterolemic diet and 0.9% saline solution) and G3 (hypercholesterolemic diet and fish oil)) for 8 weeks. There was no significant difference in the treatment with omega-3-rich fish oil in the lipid profile (p > 0.05). In the histological analysis, group G2 detected the presence of hepatitis and liver tissue necrosis, but this was not observed in group G3. As for the morphometry in the light area of the vessel, the G1 group had a higher score (2.62 ± 0.36 mm2) when compared to G2 (2.10 ± 0.16 mm2) and G3 (2.26 ± 0.25 mm2) (p < 0.05). The vessel wall thickness did not differ between the groups (p > 0.05). It is concluded that supplementation with fish oil rich in omega-3 carried out in this study may have a protective effect on liver tissue, but it has not yet improved the lipid and morphometric profile. Despite this research being preliminary, it is a relevant study with future prospects for improving the doses of EPA and DHA in order to better elucidate the benefits of fish oil in models of dyslipidemia.

Effects of Varied Omega-3 Fatty Acid Supplementation on Postpartum Mental Health and the Association between Prenatal Erythrocyte Omega-3 Fatty Acid Levels and Postpartum Mental Health.

We investigated the postpartum mental health of women who had consumed perilla oil or fish oil containing various omega-3 fatty acids for 12 weeks starting in mid-pregnancy. The association between fatty acids in maternal erythrocytes and mental health risk factors was also examined. Healthy Japanese primiparas in mid-pregnancy (gestational weeks 18-25) were randomly divided into two groups and consumed approximately 2.0 g/day of omega-3 fatty acids in either perilla oil (the ALA dose was 2.4 g/day) or fish oil (the EPA + DHA dose was 1.7 g/day) for 12 weeks. Maternal mental health was assessed using the Edinburgh Postnatal Depression Scale (EPDS) as the primary measure and the Mother-to-Infant Bonding Scale (MIBS) as the secondary measure. Data from an observational study were used as a historical control. Maternal blood, cord blood, and colostrum samples were collected for fatty acid composition analysis. In addition, completers of the observational studies were enrolled in a case-control study, wherein logistic regression analysis was performed to examine the association between maternal fatty acids and EPDS score. The proportion of participants with a high EPDS score (≥9) was significantly lower in the perilla oil group (12.0%, p = 0.044) but not in the fish oil group (22.3%, p = 0.882) compared with the historical control (21.6%), while the proportions between the former groups also tended to be lower (p = 0.059). No marked effect of omega-3 fatty acid intake was observed from the MIBS results. In the case-control study of the historical control, high levels of α-linolenic acid in maternal erythrocytes were associated with an EPDS score of <9 (odds ratio of 0.23, 95% confidence interval: 0.06, 0.84, p = 0.018 for trend). The results of this study suggest that consumption of α-linolenic acid during pregnancy may stabilize postpartum mental health.

The effect of dietary docosahexaenoic acid (DHA; 22:6n-3) on photoreceptor abundance, rhodopsin expression and growth in developing gilthead sea bream (Sparus aurata) larvae

This study determined the effect of prey DHA on larval gilthead sea bream (GSB; Sparus aurata) photoreceptor abundance, rhodopsin expression, and growth performance. It was carried out in a twenty-eight 400 l conical tank system that was stocked with 100 viable GSB eggs/l/tank. This allowed the testing of 4 levels of rotifer DHA; 0.99 (Low; L), 1.9 (Intermediate low; I-L), 3.2 (Intermediate high; I-H) and 12.1(High; H) mg DHA/g DW rotifer, which were fed (10 rotifers/ml) to 3-16 DPH larvae. These rotifer diets continued to be offered to 17-34 DPH fish, although these larvae predominantly fed on 4 DHA enriched Artemia nauplii treatments that were offered at a concentration from 0.1 nauplii/ml to 4 nauplii/ml, depending on larval age. This resulted in 4 DHA rotifer-Artemia ranges: 0.99-0.0 (L), 1.9-2.6 (I-L), 3.2-7.2 (I-H), and 12.1-11.77 (H) mg DHA/g DW. The 4 DHA treatments and ranges were tested in replicates of 7 conical tanks per treatment. Increasing rotifer DHA significantly (P&lt;0.0001) improved TL, in an exponential manner, throughout larval rearing. DW in 34 DPH larvae was markedly (P&lt;0.05) enhanced with dietary DHA inclusion in the rotifers and Artemia. There was a significant (P &lt; 0.005) prey DHA dose dependent range effect on the abundance of photoreceptor cells in the retina of 34 DPH larvae. The gene expression of rhodopsin in GSB larvae was significantly (P&lt;0.05) upregulated with dietary DHA dose range and larval age (P&lt;0.0001). This study established a link between dietary DHA level with photoreceptor abundance and rhodopsin expression, which led to improved vision, prey acquisition, and growth in developing GSB larvae.

Equal bioavailability of omega-3 PUFA from Calanus oil, fish oil and krill oil: A 12-week randomized parallel study.

The bioavailability of long-chain omega-3 polyunsaturated fatty acids (n3 PUFA) can be affected by the form in which they are bound. An alternative source of n3 PUFA is Calanus finmarchicus oil (CO), which, unlike fish oil (FO) and krill oil (KO), contains fatty acids primarily bound as wax esters. Recent studies have shown that n3 PUFA from CO are bioavailable to humans, but CO has not been compared to other marine oils such as FO or KO. Therefore, the aim of this study was to investigate the influence of 12 weeks supplementation with CO, FO and KO on the long-term n3 PUFA status in healthy volunteers. The Omega-3 Index (O3I), defined as red blood cell EPA + DHA content as a percentage of total identified fatty acids, was used as a measure to assess n3 PUFA status. Sixty-two participants (mean ± standard deviation [SD] age: 29.7 ± 8.43 years) completed the randomized parallel group study (CO group: n=21, 4 capsules/day, EPA + DHA dose: 242 mg/day; FO group: n=22, 1 capsule/day, EPA + DHA dose: 248 mg/day; KO group: n=19, 2 capsules/day, EPA + DHA dose: 286 mg/day). At baseline, the three groups showed comparable (mean ± SD) O3I values (CO: 5.13 ± 1.12%, FO: 4.90 ± 0.57%, KO: 4.87 ± 0.77%). The post-interventional (mean ± SD) O3I increase was comparable between the three groups (CO: 1.09 ± 0.55%; FO: 1.0 ± 0.53%; KO: 1.15 ± 0.65%, all p < 0.001). The study confirms that CO can increase the n3 PUFA status comparable to FO and KO and is therefore an alternative marine source of bioavailable n3 PUFA, especially with regard to sustainability.

DHA Supplementation During Pregnancy Enhances Maternal Vagally Mediated Cardiac Autonomic Control in Humans

DHA is an essential omega-3 (ω-3; n-3) fatty acid that has well-established benefits for the fetus. DHA also has the potential to influence the health of the mother, but this area is understudied. The objective of this secondary analysis was to determine if DHA was related to maternal heart rate (HR) and heart rate variability (HRV) metrics in a large cohort of pregnant women. In the parent trial (1R01HD086001) eligible participants (≥18 y old, English speaking, carrying a singleton pregnancy, 12-20 wk of gestation) were randomly assigned to consume 200mg/d or 800mg/d DHA for the duration of their pregnancy (n=300). Weight, blood pressure, and magnetocardiograms (MCGs) were collected at 32 wk and 36 wk of gestation (n=221). Measures of HR and HRV in time-, frequency-, and nonlinear-domains were determined from the isolated maternal MCG. Treatment group and timepoint were examined as predictors in association with HR and HRV metrics using random-intercept mixed-effects ANOVA unadjusted and adjusted models accounting for weight and dietary DHA intake. Women receiving the higher dose of DHA (800mg/d) during pregnancy had lower HR, lower sympathetic index, higher vagally mediated HRV indices, and greater HRV complexity when compared with the women who received the lower dose (200mg/d; all P<0.05). All the dose relations remained significant even after controlling for the effect of time, maternal weight, and dietary DHA intake. DHA supplementation increases vagal tone in pregnant women. Longitudinal studies examining the potential link between DHA, enhanced vagal tone, and reported reduction in early preterm birth are warranted.

High doses of enteral docosahexaenoic acid omega-3 supplementation for prevention of bronchopulmonary dysplasia in very preterm infants: a protocol for a systematic review and meta-analysis

IntroductionDocosahexaenoic acid (DHA) supplementation in the neonatal period has been proposed to prevent bronchopulmonary dysplasia (BPD) in very preterm infants. We aim to determine the effects of an enteral supplementation...

Effects of maternal docosahexaenoic acid supplementation on brain development and neurodevelopmental outcomes of breastfed preterm neonates: protocol for a follow-up at preschool age of a randomised clinical trial (MOBYDIckPS)

IntroductionDocosahexaenoic acid (DHA), an omega-3 fatty acid, is important for brain development with possible implications in neurodevelopmental outcomes. In the two-arm, randomised, double-blind, placebo-controlled Maternal Omega-3 Supplementation to Reduce Bronchopulmonary...

Effect of Omega-3 Fatty Acids on Coronary Plaque Morphology - A Serial Computed Tomography Angiography Study.

Omega-3 fatty acids have been proposed to be useful in the prevention of cardiac events. High-risk plaque (HRP) and plaque progression on serial coronary computed tomography angiography (CTA) have been suggested to be the predecessor of acute coronary syndrome (ACS). The purpose of this study was to investigate whether addition of omega-3 fatty acids to statin therapy for secondary prevention would lead to change in plaque characteristics detected by using serial CTA. This study enrolled 210 patients with ACS: no eicosapentaenoic acid (EPA)/ docosahexaenoic acid (DHA; EPA/DHA), low-dose EPA+DHA, high-dose EPA+DHA, and high-dose EPA alone. HRP was significantly more frequent in patients with plaque progression (P=0.0001). There was a significant interaction between plaque progression and EPA dose regardless of the DHA dose; 20.3% in EPA-none (no EPA/DHA), 15.7% in EPA-low (low-dose EPA+DHA), and 5.6% in EPA-high (high-dose EPA+DHA and high-dose EPA alone). On multivariate logistic regression analysis, HRP (OR 6.44, P<0.0001), EPA-high (OR 0.13, P=0.0004), and Rosvastatin (OR 0.24, P=0.0079) were the independent predictors for plaque progression. In quantitative analyses (n=563 plaques), the interval change of low attenuation plaque (LAP) volume was significantly different based on EPA dose; LAP was significantly increased in the EPA-none group and significantly decreased in the EPA-high group. In patients with ACS, addition of high-dose EPA (EPA-high) to statin therapy, compared to statin therapy without EPA, was associated with a lower rate of plaque progression.

Dihydroartemisinin and artesunate inhibit aerobic glycolysis via suppressing c-Myc signaling in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) cells exhibit aberrant metabolism characterized by high glycolysis even in the presence of abundant oxygen. Inhibition of aerobic glycolysis remains challenging when identifying potential cancer-specific inhibitors while maintaining or even boosting the anti-cancer immunity. Artemisinin derivatives DHA and AS have shown excellent anti-tumor and immunoenhancing roles in numerous malignancies, but the molecular mechanism of DHA and AS in regulating cancer glucose metabolism is largely unknown. In this study, we proved that DHA and AS inhibit NSCLC growth via prohibiting cancer cell aerobic glycolysis through ERK/c-Myc pathway. First, we proved that DHA and AS have comparable anti-cancer growth roles in both NSCLC cell lines and mouse Lewis Lung Cancer model. Then, our data clearly showed that DHA and AS dose- and time-dependently reduce the uptake of glucose, the production of ATP, and the secretion of lactate, the expression of glucose transporter GLUT1 and two key glycolysis-related enzymes hexokinase and lactate dehydrogenase, as well as the level of c-Myc. Finally, we generated c-Mychigh stable-expressing NSCLC cell line and treated it with DHA or AS, respectively. Our data clearly showed that c-Myc overexpression can partially reverse the glycolysis-repressing role of DHA and AS which strongly supported our proposal that AS and DHA suppress aerobic glycolysis in a c-Myc-dependent manner in NSCLC cells. This study extends our knowledge of artemisinin derivatives in regulating tumor glucose metabolism and provides potential strategy in the therapy of lung cancer.

Oils Rich in α-Linolenic Acid or Docosahexaenoic Acid Have Distinct Effects on Plasma Oxylipin and Adiponectin Concentrations and on Monocyte Bioenergetics in Women with Obesity

BackgroundOmega-3 fatty acids, including DHA and α-linolenic acid (ALA), are proposed to improve metabolic health by reducing obesity-associated inflammation. Their effects are mediated in part by conversion to oxylipins. ALA is relatively understudied, and direct comparisons to other omega-3 fatty acids are limited. ObjectivesWe compared the effects of equal doses of ALA and DHA on plasma oxylipins and markers of metabolic health in women with obesity. MethodsWe carried out a randomized, double-blind, crossover clinical trial where women aged 20–51 with a BMI of 30–51 kg/m2 were supplemented with 4 g/day of ALA or DHA for 4 weeks in the form of ALA-rich flaxseed oil or DHA-rich fish oil. The primary outcome, the plasma oxylipin profile, was assessed at Days 0 and 28 of each phase by HPLC-MS/MS. Plasma fatty acids, inflammatory markers, and the monocyte glucose metabolism were key secondary outcomes. Data were analyzed using a mixed model. ResultsCompared to the baseline visit, there were higher plasma levels of nearly all oxylipins derived from DHA (3.8-fold overall; P < 0.001) and EPA (2.7-fold overall; P < 0.05) after 28 days of fish-oil supplementation, while there were no changes to oxylipins after flaxseed-oil supplementation. Neither supplement altered plasma cytokines; however, adiponectin was increased (1.1-fold; P < 0.05) at the end of the fish-oil phase. Compared to the baseline visit, 28 days of flaxseed-oil supplementation reduced ATP-linked oxygen consumption (0.75-fold; P < 0.05) and increased spare respiratory capacity (1.4-fold; P < 0.05) in monocytes, and countered the shift in oxygen consumption induced by LPS. ConclusionsFlaxseed oil and fish oil each had unique effects on metabolic parameters in women with obesity. The supplementation regimens were insufficient to reduce inflammatory markers but adequate to elicit increases in omega-3 oxylipins and adiponectin in response to fish oil and to alter monocyte bioenergetics in response to flaxseed oil. This trial was registered at clinicaltrials.gov as NCT03583281.

Bayesian EMAX model with a mixture of normal distributions for dose–response in clinical trials

When a dose–response relationship is monotonic, the EMAX model has been shown to provide a good empirical fit for designing and analyzing dose–response data across a wide range of pharmaceutical studies. However, the EMAX model has never been applied to a finite mixture distribution. Motivated by a proposal investigating DHA dose effect on preterm birth (PTB, <37 weeks gestation) rate, we developed a Bayesian EMAX mixture model incorporating the three normal components finite mixture model into the EMAX framework. The proposed Bayesian EMAX mixture model analyzes gestational age as a continuous variable, which allows for statistically efficient estimates of PTB rate using various cut point with the same parsimonious model. For example, we can estimate the rate of early PTB (ePTB, <34 weeks gestation), PTB (<37 weeks gestation), and late-term birth (>41 weeks gestation) using the same model. We compared our proposed EMAX mixture model with an EMAX logistic model and an independent doses logistic model for a dichotomized endpoint using extensive simulations. Across the scenarios under consideration, the EMAX mixture model achieved higher power than the EMAX logistic model and the independent doses logistic model in detecting the effect of DHA supplementation on the PTB rate. The EMAX mixture model also resulted in smaller mean squared errors (MSE) in PTB rate estimates.

APOE ε4 alters associations between docosahexaenoic acid and preclinical markers of Alzheimer's disease.

Docosahexaenoic acid is the main long-chain omega-3 polyunsaturated fatty acids in the brain and accounts for 30−40% of fatty acids in the grey matter of the human cortex. Although the influence of docosahexaenoic acid on memory function is widely researched, its association with brain volumes is under investigated and its association with spatial navigation is virtually unknown. This is despite the fact that spatial navigation deficits are a new cognitive fingerprint for symptomatic and asymptomatic Alzheimer’s disease. We investigated the cross-sectional relationship between docosahexaenoic acid levels and the major structural and cognitive markers of preclinical Alzheimer’s disease, namely hippocampal volume, entorhinal volume and spatial navigation ability. Fifty-three cognitively normal adults underwent volumetric magnetic resonance imaging, measurements of serum docosahexaenoic acid (DHA, including lysophosphatidylcholine DHA) and APOE ε4 genotyping. Relative regional brain volumes were calculated and linear regression models were fitted to examine DHA associations with brain volume. APOE genotype modulated serum DHA associations with entorhinal cortex volume and hippocampal volume. Linear models showed that greater serum DHA was associated with increased entorhinal cortex volume, but not hippocampal volume, in non APOΕ ε4 carriers. APOE also interacted with serum lysophosphatidylcholine DHA to predict hippocampal volume. After testing interactions between DHA and APOE on brain volume, we investigated whether DHA and APOE interact to predict spatial navigation performance on a novel virtual reality diagnostic test for Alzheimer’s disease in an independent population of APOE genotyped adults (n = 46). APOE genotype modulated DHA associations with spatial navigation performance, showing that DHA was inversely associated with path integration in APOE ε4 carriers only. This exploratory analysis suggests that interventions aiming to increase DHA blood levels to protect against cognitive decline should consider APOE ε4 carrier status. Future work should focus on replicating our initial findings and establishing whether a specific dose of supplementary DHA, at a particular time in the preclinical disease course can have a positive impact on Alzheimer’s disease progression in APOE ε4 carriers.

Omega-3 index in 2018/19.

The omega-3 index, the percentage of EPA plus DHA in erythrocytes (measured by standardised analysis), represents a human body's status in EPA and DHA. An omega-3 index is measured in many laboratories around the world; however, even small differences in analytical methods entail large differences in results. Nevertheless, results are frequently related to the target range of 8-11 %, defined for the original and scientifically validated method (HS-Omega-3 Index®), raising ethical issues, and calling for standardisation. No human subject has an omega-3 index <2 %, indicating a vital minimum. Thus, the absence of EPA and DHA cannot be tested against presence. Moreover, clinical events correlate with levels, less with the dose of EPA and DHA, and the bioavailability of EPA and DHA varies inter-individually. Therefore, the effects of EPA and DHA are difficult to demonstrate using typical drug trial methods. Recent epidemiologic data further support the relevance of the omega-3 index in the cardiovascular field, since total mortality, cardiovascular mortality, cardiovascular events such as myocardial infarction or stroke, or blood pressure all correlate inversely with the omega-3 index. The omega-3 index directly correlates with complex brain functions. Compiling recent data supports the target range for the omega-3 index of 8-11 % in pregnancy. Many other potential applications have emerged. Some, but not all health issues mentioned have already been demonstrated to be improved by increasing intake of EPA and DHA. Increasing the omega-3 index into the target range of 8-11 % with individualised doses of toxin-free sources for EPA and DHA is tolerable and safe.

Omega 3-DHA and Delta-Tocotrienol Modulate Lipid Droplet Biogenesis and Lipophagy in Breast Cancer Cells: the Impact in Cancer Aggressiveness.

Omega 3-docosahexaenoic acid (DHA) and vitamin E Delta-tocotrienol (Delta-T3) are extensively studied as protective nutrients against cancer development. Little is known about the biological mechanisms targeted by these bioactive molecules on lipid droplet (LD) biogenesis, an important breast cancer aggressiveness marker, and the occurrence of lipophagy in breast cancer cells. The aim of this study was to investigate the effect of DHA, Delta-T3 and DHA plus Delta-T3 co-treatment in LD biogenesis and lipophagy process in triple negative breast cancer cell line MDA-MB-231. Cells were treated with 50 μM DHA and/or 5 μM Delta-T3. Our results demonstrated that DHA can trigger an increase in LD biogenesis and co-treatment with Delta-T3 was able to reduce this LD biogenesis. In addition, we showed that a higher cytoplasmic LD content is associated with a higher breast cancer cells malignance and proliferation. Reduction of cytoplasmic LD content by silencing ADRP (adipose differentiation-related protein), a structural LD protein, also decreased cell proliferation in MDA-MB-231 cells. Treatment with DHA and Delta-T3 alone or co-treatment did not reduce cell viability. Moreover, we showed here that DHA can trigger lipophagy in MDA-MB-231 cells and DHA plus Delta-T3 co-treatment was able to enhance this lipophagy process. Our findings demonstrated that co-treatment with DHA plus Delta-T3 in MDA-MB-231 cells could reduce LD biogenesis and potentiate lipophagy in these cells, possibly having a positive impact to inhibit breast cancer malignancy. Therefore, suitable doses of DHA and Delta-T3 vitamin E isoform supplementation can be a prominent tool in therapeutic treatments against breast cancer.

Inhibitory Mechanisms of DHA/CQ on pH and Iron Homeostasis of Erythrocytic Stage Growth of Plasmodium falciparum

Malaria is an infectious disease caused by Plasmodium group. The mechanisms of antimalarial drugs DHA/CQ are still unclear today. The inhibitory effects (IC50) of single treatments with DHA/CQ or V-ATPase inhibitor Baf-A1 or combination treatments by DHA/CQ combined with Baf-A1 on the growth of Plasmodium falciparum strain 3D7 was investigated. Intracellular cytoplasmic pH and labile iron pool (LIP) were labeled by pH probe BCECF, AM and iron probe calcein, AM, the fluorescence of the probes was measured by FCM. The effects of low doses of DHA (0.2 nM, 0.4 nM, 0.8 nM) on gene expression of V-ATPases (vapE, vapA, vapG) located in the membrane of DV were tested by RT-qPCR. DHA combined with Baf-A1 showed a synergism effect (CI = 0.524) on the parasite growth in the concentration of IC50. Intracellular pH and irons were effected significantly by different doses of DHA/Baf-A1. Intracellular pH was decreased by CQ combined with Baf-A1 in the concentration of IC50. Intracellular LIP was increased by DHA combined with Baf-A1 in the concentration of 20 IC50. The expression of gene vapA was down-regulated by all low doses of DHA (0.2/0.4/0.8 nM) significantly (p < 0.001) and the expression of vapG/vapE were up-regulated by 0.8 nM DHA significantly (p < 0.001). Interacting with ferrous irons, affecting the DV membrane proton pumping and acidic pH or cytoplasmic irons homeostasis may be the antimalarial mechanism of DHA while CQ showed an effect on cytoplasmic pH of parasite in vitro. Lastly, this article provides us preliminary results and a new idea for antimalarial drugs combination and new potential antimalarial combination therapies.

Dietary docosahexaenoic acid contributes to increased bone mineral accretion and strength in young female Sprague-Dawley rats

Growing evidence suggests that docosahexaenoic acid (DHA: 22:6n-3) enhances bone mineral content (BMC) and bone mineral density (BMD) in adulthood and during aging, however the effects during and after sexual maturation are unclear. The aim of this study was to examine the dose-response of BMC, BMD and microarchitectural properties of bone to dietary DHA in healthy growing female rats during acquisition of peak bone mass (PBM). Female Sprague-Dawley rats (n = 12/diet) were randomized to receive a control diet (AIN-93 M, 60 g soybean oil/kg diet) or an experimental diet containing 0.1, 0.4, 0.8 and 1.2% DHA (w/w of total diet) for 10 weeks. Dietary DHA increased the whole body, lumbar spine and long bone BMC compared to the control, in addition to higher aBMD and also BMD. Additionally, an increase in cortical bone microarchitecture parameters of lumbar spine as well as peak force were observed in dietary DHA diet groups. Dietary DHA contributes to PBM when consumed during and after sexual maturation, however higher doses of DHA do not provide further benefits.

Accretion of Dietary Docosahexaenoic Acid in Mouse Tissues Did Not Differ between Its Purified Phospholipid and Triacylglycerol Forms.

Recent studies suggest that dietary krill oil leads to higher omega-3 polyunsaturated fatty acids (n-3 PUFA) tissue accretion compared to fish oil because the former is rich in n-3 PUFA esterified as phospholipids (PL), while n-3 PUFA in fish oil are primarily esterified as triacylglycerols (TAG). Tissue accretion of the same dietary concentrations of PL- and TAG-docosahexaenoic acid (22:6n-3) (DHA) has not been compared and was the focus of this study. Mice (n = 12/group) were fed either a control diet or one of six DHA (1%, 2%, or 4%) as PL-DHA or TAG-DHA diets for 4 weeks. Compared with the control, DHA concentration in liver, adipose tissue (AT), heart, and eye, but not brain, were significantly higher in mice consuming either PL- or TAG-DHA, but there was no difference in DHA concentration in all tissues between the PL- or TAG-DHA forms. Consumption of PL- and TAG-DHA at all concentrations significantly elevated eicosapentaenoic acid (20:5n-3) (EPA) in all tissues when compared with the control group, while docoshexapentaenoic acid (22:5n-6) (DPA) was significantly higher in all tissues except for the eye and heart. Both DHA forms lowered total omega-6 polyunsaturated fatty acids (n-6 PUFA) in all tissues and total monounsaturated fatty acids (MUFA) in the liver and AT; total saturated fatty acid (SFA) were lowered in the liver but elevated in the AT. An increase in the DHA dose, independent of DHA forms, significantly lowered n-6 PUFA and significantly elevated n-3 PUFA concentration in all tissues. Our results do not support the claim that the PL form of n-3 PUFA leads to higher n-3 PUFA tissue accretion than their TAG form.