Toxicity of oxidized fish oil in pregnancy: a dose-response study in rats.

Fish oil (FO) supplements are consumed during pregnancy to increase dietary omega-3. However, FO is often oxidized past recommended limits. In rats, a large dose of highly oxidized FO substantially increased newborn mortality, but the effects of human-relevant doses of less oxidized oil are unknown. A dose-response study in rats was conducted to estimate the safe level of oxidation during pregnancy. Sprague-Dawley rat dams were mated, then individually housed and provided with a gel treatment on each day of pregnancy. Treatment groups differed only in the FO content of the gel; control (no oil), PV5, PV10, and PV40 [0.05 mL of FO oxidized to a peroxide value (PV) of 5, 10, or 40 meq/kg], or PV40(1 mL) (1 mL of PV40). A subset of dams was culled on gestational day 20 to enable sampling, and the remainder were allowed to give birth. Newborn mortality was recorded. Offspring were sampled on postnatal days 2 and 21, and dams on day 21. There were no signs of unwellness during pregnancy. However, there was markedly increased neonatal mortality affecting the PV40(1 mL) (12.8%) and PV40 (6.3%) groups, but not the control, PV5, or PV10 groups (1%-1.4%). Dietary-oxidized FO altered the expression of placental genes involved in antioxidant pathways and the production of free radicals. Highly oxidized FO was toxic in rat pregnancy leading to a marked increase in mortality even at a human-relevant dose. We observed no toxic effects of FOs with PV ≤10 meq/kg, suggesting that this is an appropriate maximum limit.

Plant-based dietary patterns are associated with lower body weight, BMI and waist circumference in older Australian women.

OBJECTIVE: To investigate the association between plant-based diets (PBD) and overweight/obesity compared to regular meat eaters in older women. DESIGN: Cross-sectional analysis. SETTING: 1946-1951 birth cohort of the Australian Longitudinal Study on Women's Health (ALSWH). PBD were categorised as vegan, lacto-ovo vegetarian, pesco-vegetarian, semi-vegetarian and regular meat eaters. Outcomes included body weight (BW), BMI and waist circumference (WC). PARTICIPANTS: Women who completed Survey 7 (n 9102) with complete FFQ data. RESULTS: Compared to regular meat eaters, BW, BMI and WC were significantly lower in pesco-vegetarians (-10·2 kg (95 % CI -5·1, -15·2); -3·8 kg/m2 (95 % CI -2·0, -5·6); -8·4 cm (95 % CI -3·9, -12·9)) and BW and BMI lower in lacto-ovo vegetarians (-7·4 kg (95 % CI -1·2, -13·6); -2·9 kg/m2 (95 % CI -0·6, -5·1)). In regular meat eaters, individuals consuming meat daily or multiple times/d had significantly higher BW, BMI and WC compared to those consuming meat >2 times/week but 1 but ≤2 times/week (6·8 kg (95 % CI 1·8, 11·8); 2·1 kg/m2 (95 % CI 0·3, 4·0) and 6·0 cm (95 % CI 1·7, 10·4)). This association was dose-dependent such that for every increase in category of weekly meat intake (i.e. >1 time/week but ≤2 times/week; >2 times/week but less than daily, and daily or multiple times/d), an associated 2·6 kg (95 % CI 1·8, 3·4) increase in BW, 0·9 kg/m2 (95 % CI 0·6, 1·2) increase in BMI and 2·3 cm (95 % CI 1·6, 3·0) increase in WC was reported. CONCLUSIONS: BW, BMI and WC are lower in women following PBD and positively associated with increasing meat consumption. Results were robust to adjustment for confounders including physical activity levels, smoking status, habitual alcohol intake, use of supplements, and hormone replacement therapy.

The relationship between oxytocin, dietary intake and feeding: A systematic review and meta-analysis of studies in mice and rats.

The neuropeptide oxytocin has been associated with food intake and feeding behaviour. This systematic review aimed to investigate the impact of oxytocin on dietary intake and feeding behaviour in rodent studies. Six electronic databases were searched to identify published studies to April 2018. Preclinical studies in mice and rats were included if they reported: (1) a dietary measure (i.e. food or nutrient and/or behaviour (2) an oxytocin measure, and (3) relationship between the two measures. A total of 75 articles (n = 246 experiments) were included, and study quality appraised. The majority of studies were carried out in males (87%). The top three oxytocin outcomes assessed were: exogenous oxytocin administration (n = 126), oxytocin-receptor antagonist administration (n = 46) and oxytocin gene deletion (n = 29). Meta-analysis of exogenous studies in mice (3 studies, n = 43 comparisons) and rats (n = 8 studies, n = 82 comparisons) showed an overall decrease in food intake with maximum effect shown at 2 h post-administration.

GlucoTRIG: a novel tool to determine the nutritional quality of foods and meals in general population.

BACKGROUND: This study aimed to develop a novel criterion, GlucoTRIG, to rank meals for healthiness, that considers both glycaemic (serum insulin) and lipaemic (serum triglycerides) responses. METHODS: Healthy volunteers (n = 10) were recruited with the aim of deriving a standard GlucoTRIG value for a reference meal. Volunteers consumed the reference meal (2 regular slices of wholemeal bread; 250 mL chocolate flavoured milk; 7 g butter and 11 g peanut butter) comprising of carbohydrate, fat and protein (41, 40 and 16% energy respectively) on three different occasions with a minimum washout period of 3 days. The GlucoTRIG value was determined as the difference between the product of insulin and triglyceride obtained from venous blood samples at baseline and the product of insulin and triglyceride at 180 min. RESULTS: There were no significant differences in the participants' dietary intakes and their metabolic parameters between three visits (P > 0.005). The GlucoTRIG value obtained from three mean values of the reference meal was found to be 19 ± 3.5. There were no significant (P = 0.2303) differences observed between the GlucoTRIG values for the three visits. CONCLUSION: GlucoTRIG, consisting of both glycaemic and lipaemic responses, may be a physiologically relevant tool to rank foods and meals for reducing the risk of metabolic diseases. TRIAL REGISTRATION: ACTRN12619000973112.

Curcumin and/or omega-3 polyunsaturated fatty acids supplementation reduces insulin resistance and blood lipids in individuals with high risk of type 2 diabetes: a randomised controlled trial.

BACKGROUND: Lowering insulin resistance and dyslipidaemia may not only enhance glycaemic control but also preserve the ß-cell function, reducing the overall risk of developing type 2 diabetes (T2D). The current study was aimed to evaluate the effects of curcumin and/or long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) supplementation on glycaemic control and blood lipid levels in individuals at high risk of developing T2D. METHODS: This was a 2 × 2 factorial, randomised, double-blinded, placebo-controlled study. Participants were allocated to either double placebo (PL) or curcumin plus placebo matching for LCn-3PUFA (CC), or LCn-3PUFA plus placebo matching for curcumin (FO), or curcumin plus LCn-3PUFA (CC-FO) for twelve weeks. Primary outcome of the trial was glycaemic indices (HbA1C, fasting glucose and insulin). Insulin resistance and sensitivity is measured using homeostatic model assessment model. RESULTS: A total of sixty-four participants (PL, n = 16; CC, n = 15; FO, n = 17, CC-FO, n = 16) were included in the final analysis. Post-intervention, HbA1c and fasting glucose remained unchanged across all the groups. Insulin sensitivity was significantly improved in the CC supplemented group (32.7 ± 10.3%) compared to PL (P = 0.009). FO and CC-FO tended to improve insulin sensitivity by 14.6 ± 8.5% and 8.8 ± 7.7% respectively, but the difference did not reach significance. Triglyceride levels were further increased in the PL (26.9 ± 7.4%), however, CC and CC-FO supplementation reduced the triglycerides, FO resulted in the greatest reduction in triglycerides (- 16.4 ± 4.5%, P < 0.001). CONCLUSION: Reduction in insulin resistance and triglycerides by curcumin and LCn-3PUFA appears to be attractive strategies for lowering the risk of developing T2D. However, this study failed to demonstrate complimentary benefits of curcumin and LCn-3PUFA on glycaemic control. TRAIL REGISTRATION: ACTRN12615000559516 .

Omega-3 polyunsaturated fatty acids status and cognitive function in young women.

BACKGROUND: Research indicates that low omega-3 polyunsaturated fatty acid (n-3 PUFA) may be associated with decreased cognitive function. This study examined the association between n-3 PUFA status and cognitive function in young Australian women. METHODS: This was a secondary outcome analysis of a cross-sectional study that recruited 300 healthy women (18-35 y) of normal weight (NW: BMI 18.5-24.9 kg/m2) or obese weight (OB: BMI ≥30.0 kg/m2). Participants completed a computer-based cognition testing battery (IntegNeuro™) evaluating the domains of impulsivity, attention, information processing, memory and executive function. The Omega-3 Index (O3I) was used to determine n-3 PUFA status (percentage of EPA (20:5n-3) plus DHA (22:6n3) in the red cell membrane) and the participants were divided into O3I tertile groups: T1 < 5.47%, T2 = 5.47-6.75%, T3 > 6.75%. Potential confounding factors of BMI, inflammatory status (C-reactive Protein), physical activity (total MET-min/wk), alpha1-acid glycoprotein, serum ferritin and hemoglobin, were assessed. Data reported as z-scores (mean ± SD), analyses via ANOVA and ANCOVA. RESULTS: Two hundred ninety-nine women (26.9 ± 5.4 y) completed the study (O3I data, n = 288). The ANOVA showed no overall group differences but a significant group × cognition domain interaction (p < 0.01). Post hoc tests showed that participants in the low O3I tertile group scored significantly lower on attention than the middle group (p = 0.01; ES = 0.45 [0.15-0.74]), while the difference with the high group was borderline significant (p = 0.052; ES = 0.38 [0.09-0.68]). After confounder adjustments, the low group had lower attention scores than both the middle (p = 0.01) and high (p = 0.048) groups. These findings were supported by univariate analyses which found significant group differences for the attention domain only (p = 0.004). CONCLUSIONS: Cognitive function in the attention domain was lower in women with lower O3I, but still within normal range. This reduced but normal level of cognition potentially provides a lower baseline from which cognition would decline with age. Further investigation of individuals with low n-3 PUFA status is warranted.

LipSpin: A New Bioinformatics Tool for Quantitative 1H NMR Lipid Profiling.

The structural similarity among lipid species and the low sensitivity and spectral resolution of nuclear magnetic resonance (NMR) have traditionally hampered the routine use of 1H NMR lipid profiling of complex biological samples in metabolomics, which remains mostly manual and lacks freely available bioinformatics tools. However, 1H NMR lipid profiling provides fast quantitative screening of major lipid classes (fatty acids, glycerolipids, phospholipids, and sterols) and some individual species and has been used in several clinical and nutritional studies, leading to improved risk prediction models. In this Article, we present LipSpin, a free and open-source bioinformatics tool for quantitative 1H NMR lipid profiling. LipSpin implements a constrained line shape fitting algorithm based on voigt profiles and spectral templates from spectra of lipid standards, which automates the analysis of severely overlapped spectral regions and lipid signals with complex coupling patterns. LipSpin provides the most detailed quantification of fatty acid families and choline phospholipids in serum lipid samples by 1H NMR to date. Moreover, analytical and clinical results using LipSpin quantifications conform with other techniques commonly used for lipid analysis.

Postprandial lipemia: factoring in lipemic response for ranking foods for their healthiness.

One of the limitations for ranking foods and meals for healthiness on the basis of the glycaemic index (GI) is that the GI is subject to manipulation by addition of fat. Postprandial lipemia, defined as a rise in circulating triglyceride containing lipoproteins following consumption of a meal, has been recognised as a risk factor for the development of cardiovascular disease and other chronic diseases. Many non-modifiable factors (pathological conditions, genetic background, age, sex and menopausal status) and life-style factors (physical activity, smoking, alcohol and medication use, dietary choices) may modulate postprandial lipemia. The structure and the composition of a food or a meal consumed also plays an important role in the rate of postprandial appearance and clearance of triglycerides in the blood. However, a major difficulty in grading foods, meals and diets according to their potential to elevate postprandial triglyceride levels has been the lack of a standardised marker that takes into consideration both the general characteristics of the food and the food's fat composition and quantity. The release rate of lipids from the food matrix during digestion also has an important role in determining the postprandial lipemic effects of a food product. This article reviews the factors that have been shown to influence postprandial lipemia with a view to develop a novel index for ranking foods according to their healthiness. This index should take into consideration not only the glycaemic but also lipemic responses.

Oxidized fish oil in rat pregnancy causes high newborn mortality and increases maternal insulin resistance.

Fish oil is commonly taken by pregnant women, and supplements sold at retail are often oxidized. Using a rat model, we aimed to assess the effects of supplementation with oxidized fish oil during pregnancy in mothers and offspring, focusing on newborn viability and maternal insulin sensitivity. Female rats were allocated to a control or high-fat diet and then mated. These rats were subsequently randomized to receive a daily gavage treatment of 1 ml of unoxidized fish oil, a highly oxidized fish oil, or control (water) throughout pregnancy. At birth, the gavage treatment was stopped, but the same maternal diets were fed ad libitum throughout lactation. Supplementation with oxidized fish oil during pregnancy had a marked adverse effect on newborn survival at day 2, leading to much greater odds of mortality than in the control (odds ratio 8.26) and unoxidized fish oil (odds ratio 13.70) groups. In addition, maternal intake of oxidized fish oil during pregnancy led to increased insulin resistance at the time of weaning (3 wks after exposure) compared with control dams (HOMA-IR 2.64 vs. 1.42; P = 0.044). These data show that the consumption of oxidized fish oil is harmful in rat pregnancy, with deleterious effects in both mothers and offspring.

Sex-dependent association between erythrocyte n-3 PUFA and type 2 diabetes in older overweight people.

The association between n-3 PUFA intake and type 2 diabetes (T2D) is unclear, and studies relating objective biomarkers of n-3 PUFA consumption to diabetic status remain limited. The aim of this study was to determine whether erythrocyte n-3 PUFA levels (n-3 index; n-3I) are associated with T2D in a cohort of older adults (n 608). To achieve this, the n-3I (erythrocyte %EPA+%DHA) was determined by GC and associated with fasting blood glucose; HbA1c; and plasma insulin. Insulin resistance (IR) was assessed using the homeostatic model assessment of insulin resistance (HOMA--IR). OR for T2D were calculated for each quartile of n-3I. In all, eighty-two type 2 diabetic (46·3 % female; 76·7 (sd 5·9) years) and 466 non-diabetic (57·9 % female; 77·8 (sd 7·1) years) individuals were included in the analysis. In overweight/obese (BMI≥27 kg/m2), the prevalence of T2D decreased across ascending n-3I quartiles: 1·0 (reference), 0·82 (95 % CI 0·31, 2·18), 0·56 (95 % CI 0·21, 1·52) and 0·22 (95 % CI 0·06, 0·82) (P trend=0·015). A similar but non-significant trend was seen in overweight men. After adjusting for BMI, no associations were found between n-3I and fasting blood glucose, HbA1c, insulin or HOMA-IR. In conclusion, higher erythrocyte n-3 PUFA status may be protective against the development of T2D in overweight women. Further research is warranted to determine whether dietary interventions that improve n-3 PUFA status can improve measures of IR, and to further elucidate sex-dependent differences.

Efficacy of the Omega-3 Index in predicting non-alcoholic fatty liver disease in overweight and obese adults: a pilot study.

Non-alcoholic fatty liver disease (NAFLD) is an independent predictor of CVD in otherwise healthy individuals. Low n-3 PUFA intake has been associated with the presence of NAFLD; however, the relationship between a biomarker of n-3 status - the Omega-3 Index - and liver fat is yet to be elucidated. A total of eighty overweight adults (fifty-six men) completed the anthropometric and biochemical measurements, including the Omega-3 Index, and underwent proton magnetic resonance spectroscopy assessment of liver fat. Bivariate correlations and multiple regression analyses were performed with reference to prediction of liver fat percentage. The mean Omega-3 Index was high in both NAFLD (intrahepatic lipid concentration≥5·5 %) and non-NAFLD groups. The Omega-3 Index, BMI, waist circumference, glucose, insulin, TAG, high-sensitive C-reactive protein (hsCRP) and alanine aminotransferase (ALT) were positively correlated, and HDL and erythrocyte n-6:n-3 ratio negatively correlated with liver fat concentration. Regression analysis found that simple anthropometric and demographic variables (waist, age) accounted for 31 % of the variance in liver fat and the addition of traditional cardiometabolic blood markers (TAG, HDL, hsCRP and ALT) increased the predictive power to 43 %. The addition of the novel erythrocyte fatty acid variable (Omega-3 Index) to the model only accounted for a further 3 % of the variance (P=0·049). In conclusion, the Omega-3 Index was associated with liver fat concentration but did not improve the overall capacity of demographic, anthropometric and blood markers to predict NAFLD.

Determinants of weight loss success utilizing a meal replacement plan and/or exercise, in overweight and obese adults with asthma.

BACKGROUND AND OBJECTIVE: While weight loss has been shown to reduce obesity-related comorbidity, many weight loss treatments fail. Factors that enhance weight loss success are unknown, particularly in those with asthma. The aim of the study was to identify patient characteristics that predict weight loss success in adults with asthma. METHODS: Baseline and change in asthma characteristics and eating behaviours were investigated for relationships with weight loss and fat loss using multiple linear regression, in 38 overweight and obese adults with asthma randomized to dietary, exercise or combined interventions targeting weight loss for 10 weeks. RESULTS: Mean ± standard deviation weight loss was 6.6 ± 5.1 kg. Greater %weight loss and %fat loss was achieved in those with poorer asthma-related quality of life at baseline ((rs = 0.398, P = 0.015) and (rs = 0.455, P = 0.005) respectively), with 1.7% greater absolute weight loss at week 10 corresponding to each one unit reduction in the asthma-related quality of life score at baseline. Furthermore, a lower baseline forced expiratory volume in 1 s/forced vital capacity correlated with greater weight loss (rs = 0.398, P = 0.015). Male sex was associated with a 3.6 kg greater weight loss (P = 0.087). Reducing emotional eating during the programme was associated with greater weight loss in women (rs = 0.576, P = 0.010). CONCLUSIONS: This study demonstrates that individuals with more severe asthma at baseline are more successful in achieving weight loss, which could be a consequence of greater motivation and could be used as a motivational tool within the clinical setting. Gender tailoring of weight loss programmes may be useful to enhance weight loss success. Future studies are urgently needed to establish predictors of long-term weight loss maintenance in those with asthma.

Diet quality score is a predictor of type 2 diabetes risk in women: the Australian Longitudinal Study on Women's Health.

The present study aimed to determine the ability of two diet quality scores to predict the incidence of type 2 diabetes in women. The study population comprised a nationally representative sample of 8370 Australian middle-aged (45-50 years) women participating in the ALSWH (Australian Longitudinal Study on Women's Health), who were free of diabetes and completed FFQ at baseline. The associations between the Australian Recommended Food Score (ARFS) and Dietary Guideline Index (DGI) with type 2 diabetes risk were assessed using multiple logistic regression models, adjusting for sociodemographic characteristics, lifestyle factors and energy intake. During 6 years of follow-up, 311 incident cases of type 2 diabetes were reported. The DGI score was inversely associated with type 2 diabetes risk (OR comparing the highest with the lowest quintile of DGI was 0·51; 95% CI 0·35, 0·76; P for trend = 0·01). There was no statistically significant association between the ARFS and type 2 diabetes risk (OR comparing the highest with the lowest quintile of ARFS was 0·99; 95% CI 0·68, 1·43; P for trend = 0·42). The results of the present prospective study indicate that the DGI score, which assesses compliance with established dietary guidelines, is predictive of type 2 diabetes risk in Australian women. The risk of type 2 diabetes among women in the highest quintile of DGI was approximately 50% lower than that in women in the lowest quintile. The ARFS was not significantly predictive of type 2 diabetes.

Macronutrient intake and type 2 diabetes risk in middle-aged Australian women. Results from the Australian Longitudinal Study on Women's Health.

OBJECTIVE: To investigate the association between macronutrient intake and type 2 diabetes risk in middle-aged Australian women. DESIGN: A prospective cohort study, with 6 years (2002-2007) of follow up. Dietary intake was assessed with a validated FFQ. Relative risks with 95 % confidence intervals were used to examine risk associations. SETTING: Australian Longitudinal Study on Women's Health, Australia. SUBJECTS: Australian women (n 8370) from the Australian Longitudinal Study on Women's Health aged 45-50 years and free of type 2 diabetes at baseline. RESULTS: After 6 years of follow-up, 311 women developed type 2 diabetes. After adjusting for sociodemographic, lifestyle and other dietary risk factors, MUFA, total n-3 PUFA, α-linolenic acid and total n-6 PUFA intakes were positively associated with the incidence of type 2 diabetes. The relative risks for type 2 diabetes for the highest compared with the lowest quintiles were 1·64 (95 % CI 1·06, 2·54), P = 0·04 for MUFA; 1·55 (95 % CI 1·03, 2·32), P = 0·01 for n-3 PUFA; 1·84 (95 % CI 1·25, 2·71), P < 0·01 for α-linolenic acid; and 1·60 (95 % CI 1·03, 2·48), P = 0·04 for n-6 PUFA. Other dietary macronutrients were not significantly associated with diabetes risk. CONCLUSIONS: The data indicate that consumption of MUFA, n-3 PUFA and n-6 PUFA may influence the risk of developing type 2 diabetes in women.

Acute effects of feeding fructose, glucose and sucrose on blood lipid levels and systemic inflammation.

BACKGROUND: Recent studies have demonstrated a relationship between fructose consumption and risk of developing metabolic syndrome. Mechanisms by which dietary fructose mediates metabolic changes are poorly understood. This study compared the effects of fructose, glucose and sucrose consumption on post-postprandial lipemia and low grade inflammation measured as hs-CRP. METHODS: This was a randomized, single blinded, cross-over trial involving healthy subjects (n=14). After an overnight fast, participants were given one of 3 different isocaloric drinks, containing 50 g of either fructose or glucose or sucrose dissolved in water. Blood samples were collected at baseline, 30, 60 and 120 minutes post intervention for the analysis of blood lipids, glucose, insulin and high sensitivity C-reactive protein (hs-CRP). RESULTS: Glucose and sucrose supplementation initially resulted in a significant increase in glucose and insulin levels compared to fructose supplementation and returned to near baseline values within 2 hours. Change in plasma cholesterol, LDL and HDL-cholesterol (measured as area under curve, AUC) was significantly higher when participants consumed fructose compared with glucose or sucrose (P<0.05). AUC for plasma triglyceride levels however remained unchanged regardless of the dietary intervention. Change in AUC for hs-CRP was also significantly higher in subjects consuming fructose compared with those consuming glucose (P<0.05), but not sucrose (P=0.07). CONCLUSION: This study demonstrates that fructose as a sole source of energy modulates plasma lipids and hsCRP levels in healthy individuals. The significance of increase in HDL-cholesterol with a concurrent increase in LDL-cholesterol and elevated hs-CRP levels remains to be delineated when considering health effects of feeding fructose-rich diets. REGISTRATION NUMBER FOR CLINICAL TRIALS: ACTRN12614000431628.

Cardiovascular Disease Risk in Individuals Following Plant-Based Dietary Patterns Compared to Regular Meat-Eaters.

Plant-based diets (PBDs) have been associated with a lower risk of cardiovascular disease (CVD). The aim was to investigate the predicted 5-year and 10-year risk of developing CVD in individuals following PBDs compared to regular meat-eating diets. This cross-sectional study included n = 240 middle-aged adults habitually consuming dietary patterns for ≥6 months: vegan, lacto-ovo vegetarian (LOV), pesco-vegetarian (PV), semi-vegetarian (SV) or regular meat-eater (RME) (n = 48 per group). Predicted 5-year and 10-year CVD risks were quantified using the Framingham Risk Equation and the Australian Absolute CVD risk calculator, respectively. Multivariable regression analysis was used to adjust for age, sex, smoking status, physical activity, alcohol use and BMI. Over three-quarters of the participants were women, mean age of 53.8 yrs. After adjustments for potential confounders, there was no difference in the predicted risk of CVD between regular-meat diets and PBDs, although crude analyses revealed that vegans had a lower 5-year and 10-year predicted risk of CVD compared to RMEs. SVs, PVs and LOVs had lower CVD risk scores, however, not significantly. Vegans had a favourable cardiometabolic risk profile including significantly lower serum lipid levels, fasting blood glucose and dietary fats and higher dietary fibre intake compared to RMEs. This was the first study to purposefully sample Australians habitually following PBDs. We found that PBDs do not independently influence the predicted risk of CVD, although PBDs tended to have lower risk and vegans had significantly lower cardiometabolic risk factors for CVD.

Eicosapentaenoic and docosahexaenoic acid supplementations reduce platelet aggregation and hemostatic markers differentially in men and women.

Although long-chain n3 polyunsaturated fatty acids [n3 PUFAs; eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] have been reported to reduce platelet aggregation, the available evidence on this is equivocal. We previously demonstrated that the acute effects of n3 PUFA supplementation on platelet aggregation are sex specific. We aimed to determine if this gender bias is maintained during long-term n3 PUFA supplementation and whether this translates to other hemostatic markers. A double-blinded, randomized, placebo controlled trial was conducted in 94 healthy men and women. Platelet aggregation, thromboxane (TX) B2, P-selectin (P-sel), von Willebrand factor (vWF), and plasminogen activator inhibitor-1 were measured at baseline and 4 wk postsupplementation with EPA-rich (1000 mg EPA:200 mg DHA) or DHA-rich (200 mg EPA:1000 mg DHA) oil capsules daily. The effects of n3 PUFA on platelet activity were compared between men and women. In men and women combined, EPA and DHA reduced platelet aggregation following 4 wk of supplementation relative to placebo (-11.8%, P = 0.016; and -14.8%, P = 0.001, respectively). In subgroup analyses, in men, only the EPA treatment reduced platelet aggregation by -18.4% compared with placebo (P = 0.005) and women (P = 0.011). In contrast, in women, only the DHA treatment reduced platelet aggregation (-18.9%) compared with placebo (P = 0.001) and men (P = 0.017). Significant sex × treatment interactions were also observed on hemostatic markers and uptake of n3 PUFAs. The significant interactions between sex and specific, supplemental, long-chain n3 PUFAs result in platelet aggregation being differentially affected in men and women. With respect to thrombotic disease risk, men are more likely to benefit from supplementation with EPA, whereas women are more responsive to DHA.

Omega-3 polyunsaturated fatty acids and vegetarian diets.

While intakes of the omega-3 fatty acid α-linolenic acid (ALA) are similar in vegetarians and non-vegetarians, intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are low in vegetarians and virtually absent in vegans. Plasma, blood and tissue levels of EPA and DHA are lower in vegetarians than in non-vegetarians, although the clinical significance of this is unknown. Vegetarians do not exhibit clinical signs of DHA deficiency, but further research is required to ascertain whether levels observed in vegetarians are sufficient to support optimal health. ALA is endogenously converted to EPA and DHA, but the process is slow and inefficient and is affected by genetics, sex, age and dietary composition. Vegetarians can take practical steps to optimise conversion of ALA to EPA and DHA, including reducing intake of linoleic acid. There are no official separate recommendations for intake of fatty acids by vegetarians. However, we suggest that vegetarians double the current adequate intake of ALA if no direct sources of EPA and DHA are consumed. Vegetarians with increased needs or reduced conversion ability may receive some advantage from DHA and EPA supplements derived from microalgae. A supplement of 200-300 mg/day of DHA and EPA is suggested for those with increased needs, such as pregnant and lactating women, and those with reduced conversion ability, such as older people or those who have chronic disease (eg, diabetes).

Altered expression of histone and synaptic plasticity associated genes in the hippocampus of streptozotocin-induced diabetic mice.

Accumulating evidence indicates that hyper-glycaemia is deleterious to brain function, in particular to the hippocampus. It is thought this hippocampal dysfunction may contribute to hyperglycaemia related cognitive impairment, such as that which manifests with diabetes. In the present study, we investigated the effects of diabetes-related hyperglycaemia on hippocampal gene expression, in order to identify potential mechanisms that might be associated with the cognitive dysfunction that develops with diabetes mellitus. Genome-wide gene expression profiling was carried out on the hippocampi from streptozotocin (STZ)-induced diabetic mice, and from vehicle treated control mice. Genes of interest that satisfied expression fold-change and statistical criteria, and that were considered to be potentially associated with cognitive function, were further tested by real time, quantitative polymerase chain reaction (qPCR) analysis. We found that STZ-induced diabetes resulted in decreased hippocampal expression of genes involved in epigenetic regulation and synaptic plasticity, for example, histone deacetylases and glycogen synthase kinase 3 beta (HDACs and GSK3ß). We also found increased expression of genes involved in signalling cascades related to cell growth, cell survival and energy metabolism, such as neurotropic tyrosine kinase receptor type 2, apolipoprotein E, and protein tyrosine phosphatase receptor type (Ntrk2, APOE, PTPRT). To our knowledge this is the first study to demonstrate a gene expression profile implicating epigenetic modifications and alterations of synaptic plasticity associated genes in diabetes mellitus. The present study will improve our understanding of the neural mechanisms that might underpin diabetes-related cognitive dysfunction.

Plant-Based Dietary Patterns and Cardiovascular Disease Risk in Australians: Protocol for a Cross-Sectional Study.

Plant-based diets (PBDs) emphasise higher intakes of plant foods and lower intakes of animal foods, and they have been associated with reduced cardiovascular morbidity/mortality and lower cardiovascular disease (CVD) risk factors. Evidence is limited regarding the dietary profile, diet quality, and nutritional adequacy of PBDs, including their impact on CVD risk compared with traditional meat-eating diets in Australians. The PBD Study (PBDS) is a cross-sectional study that will recruit 240 adults from the Hunter region (NSW) without known CVD who are habitually consuming vegan (no animal flesh/animal products), lacto-ovo vegetarian (dairy and/or eggs only), pesco-vegetarian (fish/seafood only), or semi-vegetarian (minimal animal flesh) diets or are a regular meat-eater. To investigate dietary profile, diet quality, nutritional adequacy, and CVD risk, questionnaires (medical history, demographics, and physical activity), blood samples (biomarkers), physical measures (anthropometry, blood pressure, body composition, and bone density), and dietary intake (food frequency questionnaire and diet history) will be collected. One-way ANOVA and Kruskal-Wallis tests will compare the CVD risk and other quantitative measures, and Chi-square or Fisher's Exact tests will be used for qualitative data. Directed acyclic graphs will determine the confounding variables, and linear regression and mediation analyses will account for the confounders and estimate the effect of dietary patterns on CVD risk. p-values will be adjusted using the Benjamini-Hochberg method to control the False Discovery Rate to 5%.