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A previous report showed that 12-week lowering of dietary omega-6 linoleic acid (LA) coupled with increased omega-3 polyunsaturated fatty acid (PUFA) intake (H3-L6 diet) reduced headache frequency and improved quality of life in patients with chronic daily headaches (CDHs) compared to dietary LA reduction alone (L6 diet). The trial also showed that targeted dietary manipulation alters PUFA-derived lipid mediators and endocannabinoids. However, several additional classes of lipid mediators associated with pain in preclinical models were not measured. The current secondary analysis investigated whether the clinical benefits of the H3-L6 diet were related to changes in plasma unesterified PUFA-derived lipid mediators known to be involved in nociception, including prostanoids. Lipid mediators were measured by ultra-high-pressure liquid chromatography coupled with tandem mass-spectrometry. Compared to baseline, dietary LA lowering with or without added omega-3 fatty acids did not alter unesterified n-6 PUFA-derived lipid mediators, although several species derived from LA, di-homo-gamma-linolenic acid, and arachidonic acid were positively associated with headache frequency and intensity, as well as mental health burden. Alpha-linolenic acid (ALA)-derived metabolites were also associated with increased headache frequency and intensity, although they did not change from the baseline in either dietary group. Compared to baseline, docosahexaenoic acid (DHA)-derived epoxides were more elevated in the H3-L6 group compared to the L6 group. Diet-induced elevations in plasma DHA-epoxides were associated with reduced headache frequency, better physical and mental health, and improved quality of life (p < 0.05). Prostanoids were not detected, except for PGF2-alpha, which was not associated with any outcomes. This study demonstrates that diet-induced changes in DHA-epoxides were associated with pain reduction in patients with chronic headaches, whereas n-6 PUFA and ALA metabolites were associated with nociception. Lipid mediator associations with mental health and quality of life paralleled pain management outcomes in this population. The findings point to a network of multiple diet-modifiable lipid mediator targets for pain management in individuals with CDHs.

Omega-3 and omega-6 fatty acids are precursors of bioactive lipid mediators posited to modulate both physical pain and psychological distress. In a randomized trial of 67 subjects with severe headaches, we recently demonstrated that targeted dietary manipulation-increasing omega-3 fatty acids with concurrent reduction in omega-6 linoleic acid (the H3-L6 intervention)-produced major reductions in headache compared with an omega-6 lowering (L6) intervention. Because chronic pain is often accompanied by psychological distress and impaired health-related quality of life (HRQOL), we used data from this trial to examine whether the H3-L6 intervention favorably impacted these domains. Additionally, we examined the effect of the interventions on the number of cases with substantial physical or mental impairments as defined by cutoff values in the Brief Symptom Inventory (BSI-18), Medical Outcomes Study Short Forms 12 (SF-12), Headache Impact Test (HIT-6), and the number of headache days per month. In the intention-to-treat analysis, participants in the H3-L6 group experienced statistically significant reductions in psychological distress (BSI-18 mean difference: -6.56; 95% confidence interval [CI]: -11.43 to -1.69) and improvements in SF-12 mental (mean difference: 6.01; 95% CI: 0.57 to 11.45) and physical (mean difference: 6.65; 95% CI: 2.14 to 11.16) health summary scores. At 12 weeks, the proportion of subjects experiencing substantial impairment according to cutoff values in the BSI-18, SF-12 physical, HIT-6, and headache days per month was significantly lower in the H3-L6 group. Dietary manipulation of n-3 and n-6 fatty acids, previously shown to produce major improvements in headache, was found to also reduce psychological distress and improve HRQOL and function.

BackgroundDietary linoleic acid (LA, 18:2n-6) lowering in rats reduces n-6 polyunsaturated fatty acid (PUFA) plasma concentrations and increases n-3 PUFA (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) concentrations.ObjectiveTo evaluate the extent to which 12 weeks of dietary n-6 PUFA lowering, with or without increased dietary n-3 PUFAs, alters unesterified and esterified plasma n-6 and n-3 PUFA concentrations in subjects with chronic headache.DesignSecondary analysis of a randomized trial. Subjects with chronic headache were randomized for 12 weeks to (1) average n-3, low n-6 (L6) diet; or (2) high n-3, low n-6 LA (H3-L6) diet. Esterified and unesterified plasma fatty acids were quantified at baseline (0 weeks) and after 12 weeks on a diet.ResultsCompared to baseline, the L6 diet reduced esterified plasma LA and increased esterified n-3 PUFA concentrations (nmol/ml), but did not significantly change plasma arachidonic acid (AA, 20:4n-6) concentration. In addition, unesterified EPA concentration was increased significantly among unesterified fatty acids. The H3-L6 diet decreased esterified LA and AA concentrations, and produced more marked increases in esterified and unesterified n-3 PUFA concentrations.ConclusionDietary n-6 PUFA lowering for 12 weeks significantly reduces LA and increases n-3 PUFA concentrations in plasma, without altering plasma AA concentration. A concurrent increase in dietary n-3 PUFAs for 12 weeks further increases n-3 PUFA plasma concentrations and reduces AA.

Choline is an essential nutrient for humans that is used to synthesize membrane phospholipids and the neurotransmitter acetylcholine. Betaine, a metabolite of choline, functions as a methyl-group donor in the conversion of homocysteine to methionine, and is important for renal function. Accurate analysis of choline intake was previously not possible because the choline content of most foods was not known. Using new and recently published data on the concentrations of choline in common foods, we measured the choline content of diets consumed ad libitum by healthy adult volunteers housed in a clinical research center and compared these with estimates of choline intake derived from 3-d food records kept by subjects immediately before study enrollment. Mean choline intake in this subject population met or slightly exceeded the current Adequate Intake (AI) of 7 mg/(kg x d) set by the Institute of Medicine. Men and women consumed similar amounts of choline per day (8.4 and. 6.7 mg/kg, respectively; P = 0.11). Choline intakes estimated from the 3-d food records were significantly lower than this (when expressed as mg/kg, or as total mg, but not when normalized to energy intake), suggesting underreporting of food intake. Intake of betaine, which may spare choline utilization as a methyl-group donor, was 5.3 mg/(kg x d) in men and 4.7 mg/(kg x d)in women. Intake of folate, vitamin B-12, and methionine + cysteine, were similar and sufficient in all subjects. The current recommended Al for choline seems to be a good approximation of the actual intake of this nutrient. KEY WORDS: * choline * lecithin * betaine * folate * humans

Objective: To investigate the preliminary efficacy of a high n‐3 plus low n‐6 (H3‐L6) dietary intervention in improving mood stability in Bipolar Disorder (BD) when compared to dietary intervention with usual U.S. levels of n‐6 and n‐3 polyunsaturated fatty acid (PUFA) intakes (control diet, CD). Methods: This 2‐arm, parallel‐group, randomized, modified double‐blind, controlled 48‐week study of 12‐week intensive diet intervention in subjects with BD was conducted at a single suburban‐rural site in the mid‐Atlantic region. Participants with DSM‐IV TR BD I or II with hypomanic or depressive symptoms were randomized, stratified on gender (N = 82). The intervention included the provision of group‐specific study foods and dietary counseling. Variability of mood symptoms was measured by a twice‐daily, 12‐week ecological momentary analysis (EMA) paradigm, and group differences were analyzed using multilevel models. Circulating n‐3 and n‐6 fatty acids were measured at baseline and after 4, 8, and 12 weeks of diet exposure. Results: All 82 randomized participants were included in biochemical analyses. Seventy participants completed at least 2 EMA surveys and were included in primary EMA analyses. Variability in mood, energy, irritability, and pain as measured using EMA was reduced in the H3‐L6 group compared to the CD group. No significant differences in mean ratings of mood symptoms, or any other symptom measures, were detected. The dietary intervention effect on target PUFAs significantly differed by the group over time. Conclusions: A dietary intervention adjunctive to usual care showed preliminary efficacy in improving variability in mood symptoms in participants with BD. Trial Registration: ClinicalTrials.Gov NCT02272010. [ABSTRACT FROM AUTHOR]

Background: Gaps in hospital‐based nutrition care practices and opportunities to improve care of patients at risk of malnutrition or malnourished have been demonstrated by several US hospitals implementing quality improvement (QI) projects. This study examined the impact of nutrition care process improvements focused on better documentation of identification and diagnosis of malnutrition in 5 hospital services and differences between nutritionally targeted vs nontargeted services. Methods: Data on malnutrition risk screening, nutrition assessment, malnutrition diagnosis, and nutrition care plan delivery were collected from 32,723 hospital encounters for patients admitted to the intensive care unit, pulmonology, oncology, urology, and general medicine services (targeted) as well as the rest of the nontargeted hospital services between 2017 and 2019. Results: Higher rates of morbidity in targeted service patients compared with those in the patient population admitted in the nontargeted services were observed, including higher rates of malnutrition risk (37.43% vs 19.16%, P <.001), higher rates of moderate and severe malnutrition first identified by a registered dietitian nutritionist (20.27% vs 9.67%, P <.001), and malnutrition diagnosis confirmed by an admitting physician (16.72% vs 6.74%, P <.001). Conclusions: The findings suggest sustained improvements in confirmed rates of malnutrition identification and diagnosis are achievable. Targeting malnutrition QI efforts to hospital services with higher patient morbidity is an effective method for improving malnutrition diagnosis, in particular in hospitals with limited resources, which in turn can result in improved nutrition care delivery. [ABSTRACT FROM AUTHOR]

Abstract Background Targeted analgesic dietary interventions are a promising strategy for alleviating pain and improving quality of life in patients with persistent pain syndromes, such as chronic daily headache (CDH). High intakes of the omega-6 (n-6) polyunsaturated fatty acids (PUFAs), linoleic acid (LA) and arachidonic acid (AA) may promote physical pain by increasing the abundance, and subsequent metabolism, of LA and AA in immune and nervous system tissues. Here we describe methodology for an ongoing randomized clinical trial comparing the metabolic and clinical effects of a low n-6, average n-3 PUFA diet, to the effects of a low n-6 plus high n-3 PUFA diet, in patients with CDH. Our primary aim is to determine if: A) both diets reduce n-6 PUFAs in plasma and erythrocyte lipid pools, compared to baseline; and B) the low n-6 plus high n-3 diet produces a greater decline in n-6 PUFAs, compared to the low n-6 diet alone. Secondary clinical outcomes include headache-specific quality-of-life, and headache frequency and intensity. Methods Adults meeting the International Classification of Headache Disorders criteria for CDH are included. After a 6-week baseline phase, participants are randomized to a low n-6 diet, or a low n-6 plus high n-3 diet, for 12 weeks. Foods meeting nutrient intake targets are provided for 2 meals and 2 snacks per day. A research dietitian provides intensive dietary counseling at 2-week intervals. Web-based intervention materials complement dietitian advice. Blood and clinical outcome data are collected every 4 weeks. Results Subject recruitment and retention has been excellent; 35 of 40 randomized participants completed the 12-week intervention. Preliminary blinded analysis of composite data from the first 20 participants found significant reductions in erythrocyte n-6 LA, AA and %n-6 in HUFA, and increases in n-3 EPA, DHA and the omega-3 index, indicating adherence. Trial Registration ClinicalTrials.gov (NCT01157208)