n-3 Polyunsaturated Fatty Acids and Mechanisms to Mitigate Inflammatory Paracrine Signaling in Obesity-Associated Breast Cancer

Globally, the prevalence of obesity is increasing which subsequently increases the risk of the development of obesity-related chronic diseases. Low-grade chronic inflammation and dysregulated adipose tissue inflammatory mediator/adipokine secretion are well-established in obesity, and these factors increase the risk of developing inflammation-associated cancer. Breast cancer is of particular interest given that increased inflammation within the subcutaneous mammary adipose tissue depot can alter the local tissue inflammatory microenvironment such that it resembles that of obese visceral adipose tissue. Therefore, in obese women with breast cancer, increased inflammatory mediators both locally and systemically can perpetuate inflammation-associated pro-carcinogenic signaling pathways, thereby increasing disease severity. Herein, we discuss some of these inflammation-associated pro-carcinogenic mechanisms of the combined obese breast cancer phenotype and offer evidence that dietary long chain n-3 polyunsaturated fatty acids (PUFA) may have utility in mitigating the severity of obesity-associated inflammation and breast cancer.     

ω-3脂肪酸与冠状动脉性心脏病

ω-3多不饱和脂肪酸对冠状动脉性心脏病有潜在的预防和治疗作用，其保护心血管的可能作用机制包括：（1）抗心律失常；（2）调节脂代谢；（3）延缓动脉粥样硬化斑块的发展。     

Link between Omega 3 Fatty Acids Carried by Lipoproteins and Breast Cancer Severity

According to the International Agency for Research on Cancer (IARC) more than 10% of cancers can be explained by inadequate diet and excess body weight. Breast cancer is the most common cancer affecting women. The goal of our study is to clarify the relationship between ω3 fatty acids (FA) carried by different lipoproteins and breast cancer (BC) severity, according to two approaches: through clinic-biological data and through in vitro breast cancer cell models. The clinical study has been performed in sera from a cohort of BC women (n = 140, ICO, France) whose tumors differed by their hormone receptors status (HR− for tumors negative for estrogen receptors and progesterone receptors, HR+ for tumors positive for either estrogen receptors or progesterone receptors) and the level of proliferation markers (Ki-67 ≤ 20% Prolif− and Ki-67 ≥ 30% Prolif+). Lipids and ω3FA have been quantified in whole serum and in apoB-containing lipoproteins (Non-HDL) or free of it (HDL). Differences between Prolif− and Prolif+ were compared by Wilcoxon test in each sub-group HR+ and HR−. Results are expressed as median [25th–75th percentile]. Plasma cholesterol, triglycerides, HDL-cholesterol and Non-HDL cholesterol did not differ between Prolif− and Prolif+ sub-groups of HR− and HR+ patients. Plasma EPA and DHA concentrations did not differ either. In the HR− group, the distribution of EPA and DHA between HDL and Non-HDL differed significantly, as assessed by a higher ratio between the FA concentration in Non-HDL and HDL in Prolif− vs. Prolif+ patients (0.20 [0.15–0.36] vs. 0.04 [0.02–0.08], p = 0.0001 for EPA and 0.08 [0.04–0.10] vs. 0.04 [0.01–0.07], p = 0.04 for DHA). In this HR− group, a significant increase in Non-HDL EPA concentration was also observed in Prolif− vs. Prolif+ (0.18 [0.13–0.40] vs. 0.05 [0.02–0.07], p = 0.001). A relative enrichment on Non-HDL in EPA and DHA was also observed in Prolif− patients vs. Prolif+ patients, as assessed by a higher molar ratio between FA and apoB (0.12 [0.09–0.18] vs. 0.02 [0.01–0.05], p < 0.0001 for EPA and 1.00 [0.73–1.69 vs. 0.52 [0.14–1.08], p = 0.04 for DHA). These data were partly confirmed by an in vitro approach of proliferation of isolated lipoproteins containing EPA and DHA on MDA-MB-231 (HR−) and MCF-7 (HR+) cell models. Indeed, among all the studied fractions, only the correlation between the EPA concentration of Non-HDL was confirmed in vitro, although with borderline statistical significance (p = 0.07), in MDA-MB-231 cells. Non-HDL DHA, in the same cells model was significantly correlated to proliferation (p = 0.04). This preliminary study suggests a protective effect on breast cancer proliferation of EPA and DHA carried by apo B-containing lipoproteins (Non-HDL), limited to HR− tumors.     

Use of microencapsulated fish oil as a means of increasing n-3 polyunsaturated fatty acid intake

Background: The successful incorporation of fish oil into foods may provide a means of increasing intakes of n-3 polyunsaturated fatty acids (n-3 PUFA). The aim of the present study was to evaluate the bioavailability of n-3 PUFA in microencapsulatd fish oil compared with a fish oil capsule. Methods: Twenty-eight healthy volunteers were recruited to take part in this randomized controlled trial. Volunteers were supplemented with 0.9 g n-3 PUFA daily for 4 weeks, delivered either as microencapsulated fish oil in a milkshake or as a fish oil capsule. Plasma fatty acid composition and plasma total cholesterol levels were measured at baseline and after supplementation. In addition, volunteers completed a questionnaire on fish consumption, use of supplements and exercise. Results: Responses to the questionnaire indicated that the males who took part in this study took more physical exercise, consumed less fish and were less likely than the females to take supplements. Plasma n-3 PUFA concentrations were raised significantly and by a similar level by both fish oil supplements. Furthermore, no significant difference was observed in plasma n-3 PUFA concentrations following supplementation with either form of fish oil. Plasma total cholesterol levels were not significantly altered by n-3 PUFA supplementation in either group. The results of this study indicated that there was no difference in the bioavailability of n-3 PUFA given as microencapsulated fish oil compared with n-3 PUFA delivered as a fish oil capsule. Fortification of foodstuffs with microencapsulated fish oil therefore offers the potential to increase intakes of n-3 PUFA in line with current recommendations.     

The Role of FADS1/2 Polymorphisms on Cardiometabolic Markers and Fatty Acid Profiles in Young Adults Consuming Fish Oil Supplements

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 (n-3) fatty acids (FAs) known to influence cardiometabolic markers of health. Evidence suggests that single nucleotide polymorphisms (SNPs) in the fatty acid desaturase 1 and 2 (FADS1/2) gene cluster may influence an individual’s response to n-3 FAs. This study examined the impact of a moderate daily dose of EPA and DHA fish oil supplements on cardiometabolic markers, FA levels in serum and red blood cells (RBC), and whether these endpoints were influenced by SNPs in FADS1/2. Young adults consumed fish oil supplements (1.8 g total EPA/DHA per day) for 12 weeks followed by an 8-week washout period. Serum and RBC FA profiles were analyzed every two weeks by gas chromatography. Two SNPs were genotyped: rs174537 in FADS1 and rs174576 in FADS2. Participants had significantly reduced levels of blood triglycerides (−13%) and glucose (–11%) by week 12; however, these benefits were lost during the washout period. EPA and DHA levels increased significantly in serum (+250% and +51%, respectively) and RBCs (+132% and +18%, respectively) within the first two weeks of supplementation and remained elevated throughout the 12-week period. EPA and DHA levels in RBCs only (not serum) remained significantly elevated (+37% and +24%, respectively) after the washout period. Minor allele carriers for both SNPs experienced greater increases in RBC EPA levels during supplementation; suggesting that genetic variation at this locus can influence an individual’s response to fish oil supplements.     

Seasonal variability in intake of fish oil dietary supplements among inhabitants of Warsaw

The aim of this study was to estimate the rate of sale and intake level of dietary supplements containing fish oil among inhabitants of Warsaw. The survey was carried out during 25 months in the years 2004 to 2006 in 3 selected drugstores localized in the central areas of Warsaw. The amount of fish oil, level of ω-3 long-chain polyunsaturated fatty acids declared on the label, price and rate of sale of particular supplements, as well as the reasons why customers purchased the supplements were collected and analyzed. The rate of sale of fish oil supplements was low; however, it showed a tendency for increase during the time of evaluation. Strong seasonal variability of supplements sale and therefore intake were observed. The highest levels for these parameters occurred from October to February and the lowest from May to July. The most often purchased supplements were fish liver oil capsules. The main reason for fish oil supplement purchases was medical recommendations. The health benefits of fish liver oil were known among customers of drugstores; however, the term ω-3 was almost unknown.     

The Role for Dietary Omega-3 Fatty Acids Supplementation in Older Adults

Optimal nutrition is one of the most important determinants of healthier ageing, reducing the risk of disability, maintaining mental and physical functions, and thus preserving and ensuring a better quality of life. Dietary intake and nutrient absorption decline with age, thus increasing the risk of malnutrition, morbidity and mortality. Specific nutrients, particularly long-chain omega-3 polyunsaturated fatty acids (PUFAs), might have the potential of preventing and reducing co-morbidities in older adults. Omega-3 PUFAs are able to modulate inflammation, hyperlipidemia, platelet aggregation, and hypertension. Different mechanisms contribute to these effects, including conditioning cell membrane function and composition, eicosanoid production, and gene expression. The present review analyzes the influence of omega-3 PUFAs status and intake on brain function, cardiovascular system, immune function, muscle performance and bone health in older adults. Omega-3 FAs may have substantial benefits in reducing the risk of cognitive decline in older people. The available data encourage higher intakes of omega-3 PUFAs in the diet or via specific supplements. More studies are needed to confirm the role of omega-3 FAs in maintaining bone health and preventing the loss of muscle mass and function associated with ageing. In summary, omega-3 PUFAs are now identified as potential key nutrients, safe and effective in the treatment and prevention of several negative consequences of ageing.     

Omega-3 Polyunsaturated Fatty Acids Trigger Cell Cycle Arrest and Induce Apoptosis in Human Neuroblastoma LA-N-1 Cells

Omega-3 (n-3) fatty acids are dietary long-chain fatty acids with an array of health benefits. Previous research has demonstrated the growth-inhibitory effect of n-3 fatty acids on different cancer cell lines in vitro, yet their anti-tumor effects and underlying action mechanisms on human neuroblastoma LA-N-1 cells have not yet been reported. In this study, we showed that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) exhibited time- and concentration-dependent anti-proliferative effect on the human neuroblastoma LA-N-1 cells, but had minimal cytotoxicity on the normal or non-tumorigenic cells, as measured by MTT reduction assay. Mechanistic studies indicated that DHA and EPA triggered G₀/G₁ cell cycle arrest in LA-N-1 cells, as detected by flow cytometry, which was accompanied by a decrease in the expression of CDK2 and cyclin E proteins. Moreover, DHA and EPA could also induce apoptosis in LA-N-1 cells as revealed by an increase in DNA fragmentation, phosphatidylserine externalization and mitochondrial membrane depolarization. Up-regulation of Bax, activated caspase-3 and caspase-9 proteins, and down-regulation of Bcl-X_L protein, might account for the occurrence of apoptotic events. Collectively, our results suggest that the growth-inhibitory effect of DHA and EPA on LA-N-1 cells might be mediated, at least in part, via triggering of cell cycle arrest and apoptosis. Therefore, DHA and EPA are potential anti-cancer agents which might be used for the adjuvant therapy or combination therapy with the conventional anti-cancer drugs for the treatment of some forms of human neuroblastoma with minimal toxicity.     

Low level of n-3 polyunsaturated fatty acids in erythrocytes is a risk factor for both acute ischemic and hemorrhagic stroke in Koreans

Evidence suggesting an association between n-3 polyunsaturated fatty acids (PUFA) and stroke risk has been inconsistent, possibly because previous studies have not differentiated between different stroke types. The present study investigated the hypothesis that tissue levels of n-3 PUFA are positively associated with hemorrhagic stroke and negatively associated with ischemic stroke. We recruited 120 subjects for this case-control study, with 40 cases each of hemorrhagic stroke, ischemic stroke, and unaffected controls. Patients with a family history of hemorrhagic stroke had a significantly increased risk for hemorrhagic stroke. Omega-3 Index (20:5n3 + 22:6n3 in erythrocytes) and 22:6n3 were negatively (P < .01) associated with the risk of both hemorrhagic and ischemic stroke in multivariate analyses. Saturated fatty acids 16:0 and 18:0 were positively associated, whereas 18:2n6 and 18:3n6 were negatively (P < .05) associated with risk of ischemic stroke. Monounsaturated fatty acid, 18:1n9, increased (P = .03) the odds of hemorrhagic stroke. Omega-3 Index and docosahexaenoic acid were significantly lower in patients with both subtypes of hemorrhagic stroke, subarachnoid and intracerebral hemorrhage, but only in one subtype of ischemic stroke, small-artery occlusion. Saturated fatty acids 16:0 and 18:0 were significantly higher, but 20:4n6 was significantly lower, in patients with small-artery occlusion. Linoleic acid was significantly lower in patients with small-artery occlusion and large-artery atherosclerosis, whereas 18:1n9 was higher in both subgroups of hemorrhagic stroke. In conclusion, the results of our case-control study suggest that erythrocyte n-3 PUFA may protect against hemorrhagic stroke and ischemic stroke, particularly in the case of small-artery occlusion.     

Consequences of Essential Fatty Acids

Essential fatty acids (EFA) are nutrients that form an amazingly large array of bioactive mediators that act on a large family of selective receptors. Nearly every cell and tissue in the human body expresses at least one of these receptors, allowing EFA-based signaling to influence nearly every aspect of human physiology. In this way, the health consequences of specific gene-environment interactions with these nutrients are more extensive than often recognized. The metabolic transformations have similar competitive dynamics for the n-3 and n-6 homologs when converting dietary EFA from the external environment of foods into the highly unsaturated fatty acid (HUFA) esters that accumulate in the internal environment of cells and tissues. In contrast, the formation and action of bioactive mediators during tissue responses to stimuli tend to selectively create more intense consequences for n-6 than n-3 homologs. Both n-3 and n-6 nutrients have beneficial actions, but many common health disorders are undesired consequences of excessive actions of tissue n-6 HUFA which are preventable. This review considers the possibility of preventing imbalances in dietary n-3 and n-6 nutrients with informed voluntary food choices. That action may prevent the unintended consequences that come from eating imbalanced diets which support excessive chronic actions of n-6 mediators that harm human health. The consequences from preventing n-3 and n-6 nutrient imbalances on a nationwide scale may be very large, and they need careful evaluation and implementation to avoid further harmful consequences for the national economy.     

Effects of Omega-3 Fatty Acids on Muscle Mass,Muscle Strength and Muscle Performance among the Elderly: A Meta-Analysis

There is increasing evidence showing the role of fatty acids and their derived lipid intermediates in the regulation of skeletal muscle mass synthesis and function. However, the role of omega-3 fatty acids remains unclear. Therefore, we conducted a meta-analysis to evaluate the potential effects of omega-3 fatty acids on sarcopenia-related performances among the elderly. Eligible literature and reports of randomized controlled trials were comprehensively searched from the PubMed, Cochrane Library, ClinicalTrials.gov, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases until July 2018. A total of 10 articles were available for the meta-analysis. There were minor benefits for muscle mass gain (0.33 kg; 95% CI: 0.05, 0.62) and timed up and go performance (−0.30 s; 95% CI: −0.43, −0.17). Subgroup analyses regarding muscle mass and walk speed indicated that omega-3 fatty acid supplements at more than 2 g/day may contribute to muscle mass gain (0.67 kg; 95% CI: 0.16, 1.18) and improve walking speed, especially for those receiving more than 6 months of intervention (1.78 m/sec; 95% CI: 1.38, 2.17). Our findings provide some insight into the effects of omega-3 fatty acids on muscle mass, especially for those taking supplements at more than 2 g/day. We also observed that a long period of omega-3 fatty acids supplementation may improve walking speed.     

Duality of n-3 Polyunsaturated Fatty Acids on Mcp-1 Expression in Vascular Smooth Muscle: A Potential Role of 4-Hydroxy Hexenal

N-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have protective effects against atherosclerosis. Monocyte chemotactic protein (MCP)-1 is a major inflammatory mediator in the progression of atherosclerosis. However, little is known about the regulation of Mcp-1 by DHA and EPA in vessels and vascular smooth muscle cells (VSMCs). In this study, we compared the effect of DHA and EPA on the expression of Mcp-1 in rat arterial strips and rat VSMCs. DHA, but not EPA, suppressed Mcp-1 expression in arterial strips. Furthermore, DHA generated 4-hydroxy hexenal (4-HHE), an end product of n-3 polyunsaturated fatty acids (PUFAs), in arterial strips as measured by liquid chromatography-tandem mass spectrometry. In addition, 4-HHE treatment suppressed Mcp-1 expression in arterial strips, suggesting 4-HHE derived from DHA may be involved in the mechanism of this phenomenon. In contrast, Mcp-1 expression was stimulated by DHA, EPA and 4-HHE through p38 kinase and the Keap1-Nuclear factor erythroid-derived 2-like 2 (Nrf2) pathway in VSMCs. In conclusion, there is a dual effect of n-3 PUFAs on the regulation of Mcp-1 expression. Further study is necessary to elucidate the pathological role of this phenomenon.     

Direct Determinations of the Fatty Acid Composition of Daily Dietary Intakes Incorporating Nutraceuticals and Functional Food Strategies to Increase n-3 Highly Unsaturated Fatty Acids

Objective: North American diets are low in eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA). This investigation aims to assess the ability to increase EPA and DHA in the Canadian diet using traditional whole food, functional food or nutraceutical strategies.

Methods: A typical Canadian diet (TC) was compared to four diets enriched with EPA and DHA but with similar caloric and macronutrient composition: a nutraceutical fish oil capsule diet (FO), an EPA + DHA-enriched functional foods diet (ED), a traditional whole foods (fish) diet (TW) and a comprehensive diet combining fish with functional foods (FF) containing EPA + DHA and α-linolenic acid. Direct biochemical quantitations were performed for energy, protein, carbohydrate (proximate analysis) and fat (gas chromatography). Costs of each diet and EPA + DHA source were assessed.

Results: The FO (1.03 ± 0.01g EPA + DHA), ED (0.59 ± 0.02g), TW (3.23 ± 0.09g) and FF (3.15 ± 0.06g) diets provided significantly higher amounts of EPA + DHA compared to the TC diet (0.08 ± 0.01g). Using the TC diet as a baseline, the daily cost increase for each revised diet was $0.53 (FO), $0.82 (TW), $0.93 (ED) and $1.62 (FF). The cost per gram of EPA + DHA was lowest for fish oil nutraceuticals ($0.53/g), followed by fish (～$1.05/g).

Conclusions: The EPA and DHA content of daily diets can be increased significantly and cost effectively using nutraceuticals, functional foods and whole foods. Several North American EPA + DHA recommendations for healthy individuals can be met using these strategies and American Heart Association recommendations for secondary coronary heart disease prevention can be met via traditional whole food, nutraceutical or combination approaches.     

Omega-3 Fatty Acids and Their Interaction with the Gut Microbiome in the Prevention and Amelioration of Type-2 Diabetes

Type-2 diabetes mellitus (T2DM) is often linked with hyperglycemia, disturbed lipid profiles, inflammation, and gut dysbiosis. Omega-3 fatty acid supplementation has a vital role in the management of T2DM. As a result, a better understanding of the potential role of omega-3 fatty acids in the development and progression of T2DM by influencing the intestinal microflora will help to improve the therapeutic intervention for T2DM and related complications. Focusing on the molecular mechanisms and signaling pathways induced by omega-3 fatty acids, this paper attempts to comprehensively review and discuss the putative associations between omega-3 fatty acids, gut dysbiosis, and the pathophysiology of T2DM and its related comorbidities. In addition, we contemplate the importance of gut microbiota in T2DM prevention and treatment and ponder the role of omega-3 fatty acids in T2DM by positively modulating gut microbiota, which may lead to discovery of novel targets and therapeutic strategies thereby paving way for further comprehensive, mechanistic, and clinical studies.     

Low Levels of Omega-3 Long-Chain Polyunsaturated Fatty Acids Are Associated with Bone Metastasis Formation in Premenopausal Women with Breast Cancer: A Retrospective Study

In the present study, we investigated various biochemical, clinical, and histological factors associated with bone metastases in a large cohort of pre- and postmenopausal women with breast cancer. Two hundred and sixty-one consecutive women with breast cancer were included in this study. Breast adipose tissue specimens were collected during surgery. After having established the fatty acid profile of breast adipose tissue by gas chromatography, we determined whether there were differences associated with the occurrence of bone metastases in these patients. Regarding the clinical and histological criteria, a majority of the patients with bone metastases (around 70%) had tumors with a luminal phenotype and 59% of them showed axillary lymph node involvement. Moreover, we found a negative association between the levels of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in breast adipose tissue and the development of bone metastases in premenopausal women. No significant association was observed in postmenopausal women. In addition to a luminal phenotype and axillary lymph node involvement, low levels of n-3 LC-PUFA in breast adipose tissue may constitute a risk factor that contributes to breast cancer bone metastases formation in premenopausal women.     

Polyunsaturated Fatty Acid Composition of Maternal Diet and Erythrocyte Phospholipid Status in Chilean Pregnant Women

Chilean diets are characterized by a low supply of n-3 polyunsaturated fatty acids (n-3 PUFA), which are critical nutrients during pregnancy and lactation, because of their role in brain and visual development. DHA is the most relevant n-3 PUFA in this period. We evaluated the dietary n-3 PUFA intake and erythrocyte phospholipids n-3 PUFA in Chilean pregnant women. Eighty healthy pregnant women (20–36 years old) in the 3rd–6th month of pregnancy were included in the study. Dietary assessment was done applying a food frequency questionnaire, and data were analyzed through the Food Processor SQL^® software. Fatty acids of erythrocyte phospholipids were assessed by gas-liquid chromatography. Diet composition was high in saturated fat, low in mono- and PUFA, high in n-6 PUFA (linoleic acid) and low in n-3 PUFA (alpha-linolenic acid and DHA), with imbalance in the n-6/n-3 PUFA ratio. Similar results were observed for fatty acids from erythrocyte phospholipids. The sample of Chilean pregnant women showed high consumption of saturated fat and low consumption of n-3 PUFA, which is reflected in the low DHA content of erythrocyte phospholipids. Imbalance between n-6/n-3 PUFA could negatively affect fetal development. New strategies are necessary to improve n-3 PUFA intake throughout pregnancy and breast feeding periods. Furthermore, it is necessary to develop dietary interventions to improve the quality of consumed foods with particular emphasis on n-3 PUFA.     

Linseed oil and marine oil as sources of (n-3) fatty acids in rat heart

Rats were fed a fat mixture containing a low level of (n-3) polyunsaturated fatty acids, linseed oil or marine oil. The arachidonic acid in cardiac tissue was depressed by (n-3) linolenic acid and further depressed by (n-3) polyunsaturated fatty acids of marine oil. Docosahexaenoic acid was the principal replacement for arachidonic acid.     

Plasma Phospholipid n-3/n-6 Polyunsaturated Fatty Acids and Desaturase Activities in Relation to Moderate-to-Vigorous Physical Activity through Pregnancy: A Longitudinal Study within the NICHD Fetal Growth Studies

Maternal plasma phospholipid polyunsaturated fatty acids (PUFAs) play critical roles in maternal health and fetal development. Beyond dietary factors, maternal moderate-to-vigorous physical activity (MVPA) has been linked to multiple health benefits for both the mother and offspring, but studies investigating the influence of maternal MVPA on maternal PUFA profile are scarce. The objective of present study was to examine the time-specific and prospective associations of MVPA with plasma PUFA profile among pregnant women. This study included 321 participants from the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies–Singletons cohort. Maternal plasma phospholipid PUFAs and MPVA were measured at four visits during pregnancy (10–14, 15–26, 23–31, and 33–39 gestational weeks (GW)). Associations of maternal MVPA with individual plasma PUFAs and desaturase activity were examined using generalized linear models. Maternal MVPA was associated inversely with plasma phospholipid linoleic acid, gamma-linolenic acid, and Δ6-desaturase in late pregnancy (23–31 or 33–39 GW), independent of maternal age, race, education, parity, pre-pregnancy body mass index, and dietary factors. Findings from this longitudinal study indicate that maternal habitual MVPA may play a role on PUFAs metabolism, particular by alerting plasma n-6 subclass and desaturase activity in late pregnancy. These associations are novel and merit confirmation in future studies.     

Randomized Controlled Trial Examining the Effects of Fish Oil and Multivitamin Supplementation on the Incorporation of n-3 and n-6 Fatty Acids into Red Blood Cells

The present randomized, placebo-controlled, double-blind, parallel-groups clinical trial examined the effects of fish oil and multivitamin supplementation on the incorporation of n-3 and n-6 fatty acids into red blood cells. Healthy adult humans (n = 160) were randomized to receive 6 g of fish oil, 6 g of fish oil plus a multivitamin, 3 g of fish oil plus a multivitamin or a placebo daily for 16 weeks. Treatment with 6 g of fish oil, with or without a daily multivitamin, led to higher eicosapentaenoic acid (EPA) composition at endpoint. Docosahexaenoic acid (DHA) composition was unchanged following treatment. The long chain LC n-3 PUFA index was only higher, compared to placebo, in the group receiving the combination of 6 g of fish oil and the multivitamin. Analysis by gender revealed that all treatments increased EPA incorporation in females while, in males, EPA was only significantly increased by the 6 g fish oil multivitamin combination. There was considerable individual variability in the red blood cell incorporation of EPA and DHA at endpoint. Gender contributed to a large proportion of this variability with females generally showing higher LC n-3 PUFA composition at endpoint. In conclusion, the incorporation of LC n-3 PUFA into red blood cells was influenced by dosage, the concurrent intake of vitamin/minerals and gender.