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Concept: Omega-3 fatty acid

536

Over the last century, intakes of omega-6 (ω-6) fatty acids in Western diets have dramatically increased, while omega-3 (ω-3) intakes have fallen. Resulting ω-6/ω-3 intake ratios have risen to nutritionally undesirable levels, generally 10 to 15, compared to a possible optimal ratio near 2.3. We report results of the first large-scale, nationwide study of fatty acids in U.S. organic and conventional milk. Averaged over 12 months, organic milk contained 25% less ω-6 fatty acids and 62% more ω-3 fatty acids than conventional milk, yielding a 2.5-fold higher ω-6/ω-3 ratio in conventional compared to organic milk (5.77 vs. 2.28). All individual ω-3 fatty acid concentrations were higher in organic milk-α-linolenic acid (by 60%), eicosapentaenoic acid (32%), and docosapentaenoic acid (19%)-as was the concentration of conjugated linoleic acid (18%). We report mostly moderate regional and seasonal variability in milk fatty acid profiles. Hypothetical diets of adult women were modeled to assess milk fatty-acid-driven differences in overall dietary ω-6/ω-3 ratios. Diets varied according to three choices: high instead of moderate dairy consumption; organic vs. conventional dairy products; and reduced vs. typical consumption of ω-6 fatty acids. The three choices together would decrease the ω-6/ω-3 ratio among adult women by ∼80% of the total decrease needed to reach a target ratio of 2.3, with relative impact “switch to low ω-6 foods” > “switch to organic dairy products” ≈ “increase consumption of conventional dairy products.” Based on recommended servings of dairy products and seafoods, dairy products supply far more α-linolenic acid than seafoods, about one-third as much eicosapentaenoic acid, and slightly more docosapentaenoic acid, but negligible docosahexaenoic acid. We conclude that consumers have viable options to reduce average ω-6/ω-3 intake ratios, thereby reducing or eliminating probable risk factors for a wide range of developmental and chronic health problems.

Concepts: Nutrition, Fatty acid, Fatty acids, Omega-3 fatty acid, Butter, Eicosapentaenoic acid, Omega-6 fatty acid, Linoleic acid

272

This article describes the nutrient and elemental composition, including residues of herbicides and pesticides, of 31 soybean batches from Iowa, USA. The soy samples were grouped into three different categories: (i) genetically modified, glyphosate-tolerant soy (GM-soy); (ii) unmodified soy cultivated using a conventional “chemical” cultivation regime; and (iii) unmodified soy cultivated using an organic cultivation regime. Organic soybeans showed the healthiest nutritional profile with more sugars, such as glucose, fructose, sucrose and maltose, significantly more total protein, zinc and less fibre than both conventional and GM-soy. Organic soybeans also contained less total saturated fat and total omega-6 fatty acids than both conventional and GM-soy. GM-soy contained high residues of glyphosate and AMPA (mean 3.3 and 5.7 mg/kg, respectively). Conventional and organic soybean batches contained none of these agrochemicals. Using 35 different nutritional and elemental variables to characterise each soy sample, we were able to discriminate GM, conventional and organic soybeans without exception, demonstrating “substantial non-equivalence” in compositional characteristics for ‘ready-to-market’ soybeans.

Concepts: Nutrition, Fatty acid, Glucose, Omega-3 fatty acid, Fat, Soybean, Saturated fat, Sucrose

235

Omega-3 fatty acids are dietary essentials, and the current low intakes in most modern developed countries are believed to contribute to a wide variety of physical and mental health problems. Evidence from clinical trials indicates that dietary supplementation with long-chain omega-3 may improve child behavior and learning, although most previous trials have involved children with neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD) or developmental coordination disorder (DCD). Here we investigated whether such benefits might extend to the general child population.

Concepts: Psychology, Nutrition, Fatty acid, Fatty acids, Omega-3 fatty acid, Mental disorder, Eicosapentaenoic acid, Docosahexaenoic acid

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BACKGROUND: Given that acne is a rare condition in societies with higher consumption of omega-3 (n-3) relative to omega-6 (n-6) fatty acids, supplementation with n-3 may suppress inflammatory cytokine production and thereby reduce acne severity. METHODS: 13 individuals with inflammatory acne were given three grams of fish oil containing 930 mg of EPA to their unchanged diet and existing acne remedies for 12 weeks. Acne was assessed using an overall severity grading scale, total inflammatory lesion counts, and colorimetry. FINDINGS: There was no significant change in acne grading and inflammatory counts at week 12 compared to baseline. However, there was a broad range of response to the intervention on an individual basis. The results showed that acne severity improved in 8 individuals, worsened in 4, and remained unchanged in 1. Interestingly, among the individuals who showed improvement, 7 were classified as having moderate to severe acne at baseline, while 3 of the 4 whose acne deteriorated were classified as having mild acne. CONCLUSION: There is some evidence that fish oil supplementation is associated with an improvement in overall acne severity, especially for individuals with moderate to severe acne. Divergent responses to fish oil in our pilot study indicates that dietary and supplemental lipids are worthy of further investigation in acne.

Concepts: Nutrition, Fatty acid, Essential fatty acid, Omega-3 fatty acid, Fat, Eicosapentaenoic acid, Omega-6 fatty acid, Fish oil

183

Walnuts are rich in omega-3 fatty acids, phytochemicals and antioxidants making them unique compared to other foods. Consuming walnuts has been associated with health benefits including a reduced risk of heart disease and cancer. Dysbiosis of the gut microbiome has been linked to several chronic diseases. One potential mechanism by which walnuts may exert their health benefit is through modifying the gut microbiome. This study identified the changes in the gut microbial communities that occur following the inclusion of walnuts in the diet. Male Fischer 344 rats (n=20) were randomly assigned to one of two diets for as long as 10 weeks: (1) walnut (W), and (2) replacement ® in which the fat, fiber, and protein in walnuts were matched with corn oil, protein casein, and a cellulose fiber source. Intestinal samples were collected from the descending colon, the DNA isolated, and the V3-V4 hypervariable region of 16S rRNA gene deep sequenced on an Illumina MiSeq for characterization of the gut microbiota. Body weight and food intake did not differ significantly between the two diet groups. The diet groups had distinct microbial communities with animals consuming walnuts displaying significantly greater species diversity. Walnuts increased the abundance of Firmicutes and reduced the abundance of Bacteriodetes. Walnuts enriched the microbiota for probiotic-type bacteria including Lactobacillus, Ruminococcaceae, and Roseburia while significantly reducing Bacteroides and Anaerotruncus. The class Alphaproteobacteria was also reduced. Walnut consumption altered the gut microbial community suggesting a new mechanism by which walnuts may confer their beneficial health effects.

Concepts: Bacteria, Gut flora, Nutrition, Fatty acid, Microbiology, Ribosomal RNA, Omega-3 fatty acid, 16S ribosomal RNA

179

Early randomized controlled trials (RCTs) demonstrated the health benefits of omega-3 fatty acids (n-3), whereas recent RCTs were negative. We now address the issue, focusing on the temporal changes having occurred: most patients in recent RCTs are no longer n-3 deficient and the vast majority are now treated with statins. Recent RCTs testing n-3 against arrhythmias suggest that n-3 reduce the risk only in patients not taking a statin. Other recent RCTs in secondary prevention were negative although, in a post-hoc analysis separating statin users and non-users, non-significant protection of n-3 was observed among statin non-users whereas statin users had no effect. Recent RCTs testing statins - after the implementation of the New Clinical Trial Regulation in 2007 - are negative (or flawed) suggesting that the lack of effect of n-3 cannot be attributed to a parallel protection by statins. Finally, statins favor the metabolism of omega-6 fatty acids (n-6), which in turn inhibits n-3 and, contrary to n-3, they increase insulin resistance and the risk of diabetes.Thus, n-3 and statins are counteractive at several levels and statins appear to inhibit n-3.

Concepts: Nutrition, Fatty acid, Triglyceride, Essential fatty acid, Omega-3 fatty acid, Clinical research, Omega-6 fatty acid, Omega-9 fatty acid

175

Traumatic brain injury (TBI) has long been recognized as the leading cause of traumatic death and disability. Tremendous advances in surgical and intensive care unit management of the primary injury, including maintaining adequate oxygenation, controlling intracranial pressure, and ensuring proper cerebral perfusion pressure, have resulted in reduced mortality. However, the secondary injury phase of TBI is a prolonged pathogenic process characterized by neuroinflammation, excitatory amino acids, free radicals, and ion imbalance. There are no approved therapies to directly address these underlying processes. Here, we present a case that was intentionally treated with substantial amounts of omega-3 fatty acids (n-3FA) to provide the nutritional foundation for the brain to begin the healing process following severe TBI. Recent animal research supports the use of n-3FA, and clinical experience suggests that benefits may be possible from substantially and aggressively adding n-3FA to optimize the nutritional foundation of severe TBI patients and must be in place if the brain is to be given the opportunity to repair itself to the best possible extent. Administration early in the course of treatment, in the emergency department or sooner, has the potential to improve outcomes from this potentially devastating public health problem.

Concepts: Nutrition, Fatty acid, Traumatic brain injury, Intracranial pressure, Omega-3 fatty acid, Neurology, Cerebral perfusion pressure, Neurotrauma

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OBJECTIVE: To assess whether three novel interventions, formulated based on a systems medicine therapeutic concept, reduced disease activity in patients with relapsing-remitting multiple sclerosis (MS) who were either treated or not with disease-modifying treatment. DESIGN: A 30-month randomised, double-blind, placebo-controlled, parallel design, phase II proof-of-concept clinical study. SETTINGS: Cyprus Institute of Neurology and Genetics. PARTICIPANTS: 80 participants were randomised into four groups of 20 each. A total of 41 (51%) patients completed the 30-month trial. The eligibility criteria were an age of 18-65; a diagnosis of relapsing-remitting MS according to the McDonald criteria; a score of 0.0-5.5 on the Expanded Disability Status Scale (EDSS); MRI showing lesions consistent with MS; at least one documented clinical relapse and either receiving or not a disease-modifying treatment within the 24-month period before enrolment in the study. Patients were excluded because of a recent (<30 days) relapse, prior immunosuppressant or monoclonal antibody therapy, pregnancy or nursing, other severe disease compromising organ function, progressive MS, history of recent drug or alcohol abuse, use of any additional food supplements, vitamins or any form of polyunsaturated fatty acids, and a history of severe allergic or anaphylactic reactions or known specific nutritional hypersensitivity. INTERVENTIONS: The first intervention (A) was composed of Ω-3 and Ω-6 polyunsaturated fatty acids at 1:1 wt/wt. Specifically, the Ω-3 fatty acids were docosahexaenoic acid and eicosapentaenoic acid at 3:1 wt/wt, and the Ω-6 fatty acids were linoleic acid and γ-linolenic acid at 2:1 wt/wt. This intervention also included minor quantities of other specific polyunsaturated, monounsaturated and saturated fatty acids as well as vitamin A and vitamin E (α-tocopherol). The second intervention (B, PLP10) was a combination of A and γ-tocopherol. The third intervention (C) was γ-tocopherol alone. The fourth group of 20 participants received placebo. The interventions were administered per os (by mouth) once daily, 30 min before dinner for 30 months. MAIN OUTCOME MEASURES: The primary end point was the annualised relapse rate (ARR) of the three interventions versus the placebo at 2 years. The secondary end point was the time to confirmed disability progression at 2 years. RESULTS: A total of 41 (51%) patients completed the 30-month trial. Overall, for the per-protocol analysis of the 2-year primary end point, eight relapses were recorded in the PLP10 group (n=10; 0.40 ARR) versus 25 relapses in the placebo group (n=12; 1.04 ARR), representing a 64% adjusted relative rate reduction for the PLP10 group (RRR 0.36, 95% CI 0.15 to 0.87, p=0.024). In a subgroup analysis that excluded patients on monoclonal antibody (natalizumab) treatment, the observed adjusted RRR became stronger (72%) over the 2 years (RRR 0.28, 95% CI 0.10 to 0.79, p=0.016). The per-protocol analysis for the secondary outcome at 2 years, the time to disability progression, was significantly longer only for PLP10. The cumulative probability of disability progression at 2 years was 10% in the PLP10 group and 58% in the placebo group (unadjusted log-rank p=0.019). In a subgroup analysis that excluded patients on natalizumab, the cumulative probability of progression was 10% for the 10 patients in the PLP10 group and 70% for the 12 patients in the placebo group, representing a relative 86% decrease in the risk of the sustained progression of disability in the PLP10 group (unadjusted log-rank p=0.006; adjusted HR, 0.11; 95% CI 0.01 to 0.97, p=0.047). No adverse events were reported. Interventions A (10 patients) and C (9 patients) showed no significant efficacy. CONCLUSIONS: In this small proof-of-concept, randomised, double-blind clinical trial; the PLP10 treatment significantly reduced the ARR and the risk of sustained disability progression without any reported serious adverse events. Larger studies are needed to further assess the safety and efficacy of PLP10. TRIAL REGISTRATION: International Standard Randomised Controlled Trial, number ISRCTN87818535.

Concepts: Clinical trial, Nutrition, Fatty acid, Fatty acids, Essential fatty acid, Omega-3 fatty acid, Multiple sclerosis, Linoleic acid

173

Microalgae are a promising feedstock for renewable fuels, and algal metabolic engineering can lead to crop improvement, thus accelerating the development of commercially viable biodiesel production from algae biomass. We demonstrate that protein-protein interactions between the fatty acid acyl carrier protein (ACP) and thioesterase (TE) govern fatty acid hydrolysis within the algal chloroplast. Using green microalga Chlamydomonas reinhardtii (Cr) as a model, a structural simulation of docking CrACP to CrTE identifies a protein-protein recognition surface between the two domains. A virtual screen reveals plant TEs with similar in silico binding to CrACP. Employing an activity-based crosslinking probe designed to selectively trap transient protein-protein interactions between the TE and ACP, we demonstrate in vitro that CrTE must functionally interact with CrACP to release fatty acids, while TEs of vascular plants show no mechanistic crosslinking to CrACP. This is recapitulated in vivo, where overproduction of the endogenous CrTE increased levels of short-chain fatty acids and engineering plant TEs into the C. reinhardtii chloroplast did not alter the fatty acid profile. These findings highlight the critical role of protein-protein interactions in manipulating fatty acid biosynthesis for algae biofuel engineering as illuminated by activity-based probes.

Concepts: Algae, Photosynthesis, Protein, Fatty acid, Plant, Water, Omega-3 fatty acid, Hydrolysis

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n-3 polyunsaturated fatty acids, namely docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), reduce the risk of cardiovascular disease and can ameliorate many of obesity-associated disorders. We hypothesised that the latter effect will be more pronounced when DHA/EPA is supplemented as phospholipids rather than as triglycerides.

Concepts: Nutrition, Fatty acid, Fatty acids, Essential fatty acid, Omega-3 fatty acid, Eicosapentaenoic acid, Docosahexaenoic acid, Polyunsaturated fatty acid