Dietary fatty acids and colorectal cancer risk in men: A report from the Shanghai Men's Health Study and a meta-analysis.

Evidence from animal models suggests that dietary fatty acids have both anticancer and tumor-promoting effects. Whether dietary fatty acids are associated with colorectal cancer (CRC) in humans remains inconclusive. We investigated associations between dietary fatty acids and risk of CRC among 59 986 men who participated in the Shanghai Men's Health Study (SMHS), an ongoing population-based prospective cohort study. We identified 876 incident CRC cases in the SMHS during a mean follow-up of 9.8 years. Associations between dietary fatty acid intake and CRC risk were evaluated by Cox proportional hazard regression analyses. Consumption of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) was not significantly associated with CRC risk. Multivariate hazard ratios (HRs) and respective 95% confidence intervals (CIs) for Quartile 4 vs Quartile 1 were 0.92 (0.74-1.14; Ptrend = 0.47) for SFA, 0.95 (0.79-1.16; Ptrend = 0.74) for MUFA and 1.18 (0.95-1.46; Ptrend = 0.21) for PUFA. No significant associations were found for total n-6 PUFA or total n-3 PUFA. Additionally, we performed a meta-analysis to summarize results from the present study and 28 reports from 26 additional cohorts, which supported the overall null association between dietary fatty acid intake and CRC risk among men. Docosahexanoic acid and eicosapentaenoic acid were associated with 11% to 12% reduced risk, and linoleic acid a 19% increased risk, of CRC in the meta-analysis of combined sexes. In conclusion, this population-based prospective study and meta-analysis of cohort studies found little evidence that dietary fatty acid intake was associated with risk of CRC in men.

Association between dietary fat and fat subtypes with the risk of breast cancer in an Iranian population: a case-control study.

AIM: To examine the relationship between dietary fat intake and breast cancer (BC) development. METHOD: This case-control study included 473 women with breast cancer (pathologically confirmed) and 501 healthy subjects matched by age and residency. Dietary intakes of different types and sources of fatty acids were assessed using a validated food frequency questionnaire. The association between dietary fats and odds of BC was assessed using a logistic regression model in crude and multivariable-adjusted models. P values below 0.05 were regarded as statistically significant. RESULTS: Participants' age and body mass index were 44.0 ± 10.8 years and 28.4 ± 5.6 kg/m2, respectively. Individuals with the highest quartile of total fat intake and polyunsaturated fatty acid (PUFA) intake were 1.50 times more at risk to develop BC than others. A positive significant association was observed between animal fat (Q4 vs. Q1, OR = 1.89, 95 % CI = 0.93-3.81), saturated fatty acid (SFA) (Q4 vs. Q1, OR = 1.70, 95 % CI = 0.88-3.30), monounsaturated fatty acid (MUFA) (Q4 vs. Q1 OR = 1.85, 95 % CI = 0.95-3.61) and PUFA intake (Q4 vs. Q1, OR = 2.12, 95 % CI = 1.05-4.27) with BC risk in postmenopausal women. However, there was no association in premenopausal women. CONCLUSIONS: Total dietary fat and its subtypes might increase the risk of BC, especially in postmenopausal women. This observational study confirms the role of dietary fat in breast cancer development. Intervention studies involving different estrogen receptor subgroups are needed.

Dietary Fat Intake and the Risk of Skin Cancer: A Systematic Review and Meta-Analysis of Observational Studies.

We conducted a meta-analysis to evaluate the association between fat intake and the risk of three major types of skin cancer including basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and cutaneous malignant melanoma (CMM). A comprehensive search of PubMed and EMBASE was performed to identify all relevant observational studies published up to December 1, 2018. Specific odds ratio (OR) or relative risk (RR) estimates for the highest versus the lowest intake of dietary fat and 95% confidence intervals (CI) from the included studies were pooled using random effect model. Three prospective cohort studies (175,675 participants and 30,915 BCC cases, 4,106 SCC cases and 1,638 CMM cases) and nine case-control studies (328 BCC cases, 493 SCC cases, 1,547 CMM cases and 2,660 controls) were identified. The pooled results indicated that dietary consumption of total fat and saturated fat were not associated with three major types of skin cancer. High consumption of monounsaturated fat was significantly associated with a decreased risk of BCC (RR: 0.90, 95% CI: 0.85-0.96) and high level of polyunsaturated fat intake was potentially positively associated with SCC (RR: 1.19, 95% CI: 1.06-1.33). Our findings should be confirmed by further evidence from well-designed and large-scale prospective cohort studies.

Polyunsaturated fatty acids and risk of melanoma: A Mendelian randomisation analysis.

Melanoma is the deadliest form of skin cancer, mainly affecting populations of European ancestry. Some observational studies suggest that particular diets reduce melanoma risk, putatively through an increase in polyunsaturated fatty acid (PUFA) consumption. However, interpretation of these observational findings is difficult due to residual confounding or reverse causality. To date, a randomized controlled trial has not been carried out to examine the relationship between PUFAs and melanoma. Hence, we performed a Mendelian randomisation (MR) study to evaluate the link between PUFAs and melanoma. To perform MR, we used summary results from the largest risk genome-wide association study (GWAS) meta-analysis of melanoma, consisting of 12,874 cases and 23,203 controls. As instrumental variables we selected SNPs associated with PUFA levels from a GWAS meta-analysis of PUFA levels, from the CHARGE consortium. We used the inverse variance weighted method to estimate a causal odds ratio. To aid interpretation, we established a benchmark "large" predicted change in PUFAs in which, for example, an increase in docosahexaenoic acid (DPA) of 0.17 units (equal to 1 standard deviation) moves a person from the 17th percentile to the median. Raising PUFA levels by a large amount (increasing DPA by 0.17 units) only negligibly changed melanoma risk: odds ratio [OR] = 1.03 (95% confidence interval [CI] = 0.96-1.10). Other PUFAs yielded similar results as DPA. Our MR analysis suggests that the effect of PUFA levels on melanoma risk is either zero or very small.

Ground flaxseed reverses protection of a reduced-fat diet against Citrobacter rodentium-induced colitis.

Flaxseed is high in ω-3 polyunsaturated fatty acids, fiber, and lignans known to lower cholesterol levels. However, its use for prevention or treatment of inflammatory bowel diseases has yielded mixed results, perhaps related to dietary interactions. In this study, we evaluated the impact of ground flaxseed supplementation on the severity of Citrobacter rodentium-induced colitis in the setting of either a high-fat (HF, ~36%kcal) or reduced-fat (RF, ~12%kcal) diet. After weaning, C57BL/6 mice ( n = 8-15/treatment) were fed ground flaxseed (7 g/100 g diet) with either HF (HF Flx) or RF (RF Flx) diets for 4 wk before infection with C. rodentium or sham gavage. Weight changes, mucosal inflammation, pathogen burden, gut microbiota composition, tissue polyunsaturated fatty acids, and cecal short-chain fatty acids were compared over a 14-day infection period. The RF diet protected against C. rodentium-induced colitis, whereas the RF Flx diet increased pathogen burden, exacerbated gut inflammation, and promoted gut dysbiosis. When compared with the RF diet, both HF and HF Flx diets resulted in more severe pathology in response to C. rodentium infection. Our findings demonstrate that although an RF diet protected against C. rodentium-induced colitis and associated gut dysbiosis in mice, beneficial effects were diminished with ground flaxseed supplementation. NEW & NOTEWORTHY Our results demonstrate a strong protective effect of a reduced-fat diet against intestinal inflammation, dysbiosis, and pathogen burden during Citrobacter rodentium-induced colitis. However, ground flaxseed supplementation in the setting of a reduced-fat diet exacerbated colitis despite higher levels of intestinal n-3 polyunsaturated fatty acids and cecal short-chain fatty acids.

Polyunsaturated fatty acids for the primary and secondary prevention of cardiovascular disease.

BACKGROUND: Evidence on the health effects of total polyunsaturated fatty acids (PUFA) is equivocal. Fish oils are rich in omega-3 PUFA and plant oils in omega-6 PUFA. Evidence suggests that increasing PUFA-rich foods, supplements or supplemented foods can reduce serum cholesterol, but may increase body weight, so overall cardiovascular effects are unclear. OBJECTIVES: To assess effects of increasing total PUFA intake on cardiovascular disease and all-cause mortality, lipids and adiposity in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase to April 2017 and clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform to September 2016, without language restrictions. We checked trials included in relevant systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing higher with lower PUFA intakes in adults with or without cardiovascular disease that assessed effects over 12 months or longer. We included full texts, abstracts, trials registry entries and unpublished data. Outcomes were all-cause mortality, cardiovascular disease mortality and events, risk factors (blood lipids, adiposity, blood pressure), and adverse events. We excluded trials where we could not separate effects of PUFA intake from other dietary, lifestyle or medication interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts, assessed trials for inclusion, extracted data, and assessed risk of bias. We wrote to authors of included trials for further data. Meta-analyses used random-effects analysis, sensitivity analyses included fixed-effects and limiting to low summary risk of bias. We assessed GRADE quality of evidence. MAIN RESULTS: We included 49 RCTs randomising 24,272 participants, with duration of one to eight years. Eleven included trials were at low summary risk of bias, 33 recruited participants without cardiovascular disease. Baseline PUFA intake was unclear in most trials, but 3.9% to 8% of total energy intake where reported. Most trials gave supplemental capsules, but eight gave dietary advice, eight gave supplemental foods such as nuts or margarine, and three used a combination of methods to increase PUFA.Increasing PUFA intake probably has little or no effect on all-cause mortality (risk 7.8% vs 7.6%, risk ratio (RR) 0.98, 95% confidence interval (CI) 0.89 to 1.07, 19,290 participants in 24 trials), but probably slightly reduces risk of coronary heart disease events from 14.2% to 12.3% (RR 0.87, 95% CI 0.72 to 1.06, 15 trials, 10,076 participants) and cardiovascular disease events from 14.6% to 13.0% (RR 0.89, 95% CI 0.79 to 1.01, 17,799 participants in 21 trials), all moderate-quality evidence. Increasing PUFA may slightly reduce risk of coronary heart disease death (6.6% to 6.1%, RR 0.91, 95% CI 0.78 to 1.06, 9 trials, 8810 participants) andstroke (1.2% to 1.1%, RR 0.91, 95% CI 0.58 to 1.44, 11 trials, 14,742 participants, though confidence intervals include important harms), but has little or no effect on cardiovascular mortality (RR 1.02, 95% CI 0.82 to 1.26, 16 trials, 15,107 participants) all low-quality evidence. Effects of increasing PUFA on major adverse cardiac and cerebrovascular events and atrial fibrillation are unclear as evidence is of very low quality.Increasing PUFA intake slightly reduces total cholesterol (mean difference (MD) -0.12 mmol/L, 95% CI -0.23 to -0.02, 26 trials, 8072 participants) and probably slightly decreases triglycerides (MD -0.12 mmol/L, 95% CI -0.20 to -0.04, 20 trials, 3905 participants), but has little or no effect on high-density lipoprotein (HDL) (MD -0.01 mmol/L, 95% CI -0.02 to 0.01, 18 trials, 4674 participants) or low-density lipoprotein (LDL) (MD -0.01 mmol/L, 95% CI -0.09 to 0.06, 15 trials, 3362 participants). Increasing PUFA probably causes slight weight gain (MD 0.76 kg, 95% CI 0.34 to 1.19, 12 trials, 7100 participants).Effects of increasing PUFA on serious adverse events such as pulmonary embolism and bleeding are unclear as the evidence is of very low quality. AUTHORS' CONCLUSIONS: This is the most extensive systematic review of RCTs conducted to date to assess effects of increasing PUFA on cardiovascular disease, mortality, lipids or adiposity. Increasing PUFA intake probably slightly reduces risk of coronary heart disease and cardiovascular disease events, may slightly reduce risk of coronary heart disease mortality and stroke (though not ruling out harms), but has little or no effect on all-cause or cardiovascular disease mortality. The mechanism may be via lipid reduction, but increasing PUFA probably slightly increases weight.

Polyunsaturated fatty acids for the primary and secondary prevention of cardiovascular disease.

BACKGROUND: Evidence on the health effects of total polyunsaturated fatty acids (PUFA) is equivocal. Fish oils are rich in omega-3 PUFA and plant oils in omega-6 PUFA. Evidence suggests that increasing PUFA-rich foods, supplements or supplemented foods can reduce serum cholesterol, but may increase body weight, so overall cardiovascular effects are unclear. OBJECTIVES: To assess effects of increasing total PUFA intake on cardiovascular disease and all-cause mortality, lipids and adiposity in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase to April 2017 and clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform to September 2016, without language restrictions. We checked trials included in relevant systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing higher with lower PUFA intakes in adults with or without cardiovascular disease that assessed effects over 12 months or longer. We included full texts, abstracts, trials registry entries and unpublished data. Outcomes were all-cause mortality, cardiovascular disease mortality and events, risk factors (blood lipids, adiposity, blood pressure), and adverse events. We excluded trials where we could not separate effects of PUFA intake from other dietary, lifestyle or medication interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts, assessed trials for inclusion, extracted data, and assessed risk of bias. We wrote to authors of included trials for further data. Meta-analyses used random-effects analysis, sensitivity analyses included fixed-effects and limiting to low summary risk of bias. We assessed GRADE quality of evidence. MAIN RESULTS: We included 49 RCTs randomising 24,272 participants, with duration of one to eight years. Eleven included trials were at low summary risk of bias, 33 recruited participants without cardiovascular disease. Baseline PUFA intake was unclear in most trials, but 3.9% to 8% of total energy intake where reported. Most trials gave supplemental capsules, but eight gave dietary advice, eight gave supplemental foods such as nuts or margarine, and three used a combination of methods to increase PUFA.Increasing PUFA intake probably has little or no effect on all-cause mortality (risk 7.8% vs 7.6%, risk ratio (RR) 0.98, 95% confidence interval (CI) 0.89 to 1.07, 19,290 participants in 24 trials), but probably slightly reduces risk of coronary heart disease events from 14.2% to 12.3% (RR 0.87, 95% CI 0.72 to 1.06, 15 trials, 10,076 participants) and cardiovascular disease events from 14.6% to 13.0% (RR 0.89, 95% CI 0.79 to 1.01, 17,799 participants in 21 trials), all moderate-quality evidence. Increasing PUFA may slightly reduce risk of coronary heart disease death (6.6% to 6.1%, RR 0.91, 95% CI 0.78 to 1.06, 9 trials, 8810 participants) andstroke (1.2% to 1.1%, RR 0.91, 95% CI 0.58 to 1.44, 11 trials, 14,742 participants, though confidence intervals include important harms), but has little or no effect on cardiovascular mortality (RR 1.02, 95% CI 0.82 to 1.26, 16 trials, 15,107 participants) all low-quality evidence. Effects of increasing PUFA on major adverse cardiac and cerebrovascular events and atrial fibrillation are unclear as evidence is of very low quality.Increasing PUFA intake probably slightly decreases triglycerides (by 15%, MD -0.12 mmol/L, 95% CI -0.20 to -0.04, 20 trials, 3905 participants), but has little or no effect on total cholesterol (mean difference (MD) -0.12 mmol/L, 95% CI -0.23 to -0.02, 26 trials, 8072 participants), high-density lipoprotein (HDL) (MD -0.01 mmol/L, 95% CI -0.02 to 0.01, 18 trials, 4674 participants) or low-density lipoprotein (LDL) (MD -0.01 mmol/L, 95% CI -0.09 to 0.06, 15 trials, 3362 participants). Increasing PUFA probably has little or no effect on adiposity (body weight MD 0.76 kg, 95% CI 0.34 to 1.19, 12 trials, 7100 participants).Effects of increasing PUFA on serious adverse events such as pulmonary embolism and bleeding are unclear as the evidence is of very low quality. AUTHORS' CONCLUSIONS: This is the most extensive systematic review of RCTs conducted to date to assess effects of increasing PUFA on cardiovascular disease, mortality, lipids or adiposity. Increasing PUFA intake probably slightly reduces risk of coronary heart disease and cardiovascular disease events, may slightly reduce risk of coronary heart disease mortality and stroke (though not ruling out harms), but has little or no effect on all-cause or cardiovascular disease mortality. The mechanism may be via TG reduction.

The relationship between early pregnancy dietary intakes and subsequent birthweight and neonatal adiposity.

Background: Maternal nutrition intakes may influence neonatal birthweight and adiposity; however, inconsistencies within the literature exist. The relationships between maternal dietary intakes in early pregnancy and both birthweight and neonatal adiposity requires elucidation. This study examined the relationship between early pregnancy dietary intakes and subsequent birthweight and neonatal adiposity. Methods: Women were recruited at their convenience after sonographic confirmation of a singleton pregnancy. Women completed a Willet food frequency questionnaire evaluating habitual food and nutrient intakes at their first antenatal visit. Neonatal body composition was measured using air-displacement plethysmography. Results: Of the 385 mother-neonate dyads, mean maternal age was 30.8 ± 5.3 years, mean Body Mass Index (BMI) was 24.5 ± 4.8 kg/m2 and 41.8% (n = 161) were nulliparous. There were no relationships between maternal food intakes and birthweight (P > 0.05) (n = 385). On multivariable analysis there was a positive relationship between polyunsaturated fat and neonatal fat mass index (FMI) (beta = 0.015, 95% CI = 0.002-0.028, P = 0.04) (n = 80). Conclusion: Dietary intakes of polyunsaturated fat in early pregnancy are positively associated with neonatal FMI at birth on multivariable analysis. Further longitudinal studies need to explore this association and the long-term implications for the neonate.

No effect of adding dairy lipids or long chain polyunsaturated fatty acids on formula tolerance and growth in full term infants: a randomized controlled trial.

BACKGROUND: When breastfeeding is not possible, infants are fed formulas in which lipids are usually of plant origin. However, the use of dairy fat in combination with plant oils enables a lipid profile in formula closer to breast milk in terms of fatty acid composition, triglyceride structure and cholesterol content. The objectives of this study were to investigate the impact on growth and gastrointestinal tolerance of a formula containing a mix of dairy lipids and plant oils in healthy infants. METHODS: This study was a monocentric, double-blind, controlled, randomized trial. Healthy term infants aged less than 3 weeks whose mothers did not breastfeed were randomly allocated to formula containing either: a mix of plant oils and dairy fat (D), only plant oils (P) or plant oils supplemented with long-chain polyunsaturated fatty acids (PDHA). Breastfed infants were included in a reference group (BF). Anthropometric parameters and body composition were measured after 2 and 4 months. Gastrointestinal tolerance was evaluated during 2 day-periods after 1 and 3 months thanks to descriptive parameters reported by parents. Nonrandomized BF infants were not included in the statistical analysis. RESULTS: Eighty eight formula-fed and 29 BF infants were enrolled. Gains of weight, recumbent length, cranial circumference and fat mass were similar between the 3 formula-fed groups at 2 and 4 months and close to those of BF. Z-scores for weight, recumbent length and cranial circumference in all groups were within normal ranges for growth standards. No significant differences were noted among the 3 formula groups in gastrointestinal parameters (stool frequency/consistency/color), occurrence of gastrointestinal symptoms (abdominal pain, flatulence, regurgitation) or infant's behavior. CONCLUSIONS: A formula containing a mix of dairy lipids and plant oils enables a normal growth in healthy newborns. This formula is well tolerated and does not lead to abnormal gastrointestinal symptoms. Consequently, reintroduction of dairy lipids could represent an interesting strategy to improve lipid quality in infant formulas. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01611649 , retrospectively registered on May 25, 2012.

Enterocytozoon bieneusi Microsporidiosis in Stem Cell Transplant Recipients Treated with Fumagillin

Enterocytozoon bieneusi microsporidiosis is an emerging disease in immunocompromised patients. We report 2 cases of this disease in allogeneic hematopoietic stem cell transplant patients successfully treated with fumagillin. Thrombocytopenia occurred but without major adverse events. Modifications of immunosuppression could be avoided when E. bieneusi is rapidly identified and fumagillin therapy is started promptly.

Intake of dietary fat and fat subtypes and risk of premenstrual syndrome in the Nurses' Health Study II.

Approximately 8-20 % of reproductive-aged women experience premenstrual syndrome (PMS), substantially impacting quality of life. Women with PMS are encouraged to reduce fat intake to alleviate symptoms; however, its role in PMS development is unclear. We evaluated the association between dietary fat intake and PMS development among a subset of the prospective Nurses' Health Study II cohort. We compared 1257 women reporting clinician-diagnosed PMS, confirmed by premenstrual symptom questionnaire and 2463 matched controls with no or minimal premenstrual symptoms. Intakes of total fat, subtypes and fatty acids were assessed via FFQ. After adjustment for age, BMI, smoking, Ca and other factors, intakes of total fat, MUFA, PUFA and trans-fat measured 2-4 years before were not associated with PMS. High SFA intake was associated with lower PMS risk (relative risk (RR) quintile 5 (median=28·1 g/d) v. quintile 1 (median=15·1 g/d)=0·75; 95 % CI 0·58, 0·98; P trend=0·07). This association was largely attributable to stearic acid intake, with women in the highest quintile (median=7·4 g/d) having a RR of 0·75 v. those with the lowest intake (median=3·7 g/d) (95 % CI 0·57, 0·97; P trend=0·03). Individual PUFA and MUFA, including n-3 fatty acids, were not associated with risk. Overall, fat intake was not associated with higher PMS risk. High intake of stearic acid may be associated with a lower risk of developing PMS. Additional prospective research is needed to confirm this finding.

A systematic review of the effect of dietary saturated and polyunsaturated fat on heart disease.

AIMS: Over the last 7 years there has been intense debate about the advice to reduce saturated fat and increase polyunsaturated fat to reduce CVD risk. The aim of this review was to examine systematic reviews and meta-analyses since 2010 on this topic plus additional cohort studies and interventions not included in these reviews. DATA SYNTHESIS: High saturated and trans fat intake (which elevates LDL like saturated fat) in the Nurses and Health Professional Follow-Up Studies combined is associated with an 8-13% higher mortality and replacement of saturated fat with any carbohydrate, PUFA and MUFA is associated with lower mortality with PUFA being more effective than MUFA (19% reduction versus 11%). With CVD mortality only PUFA and fish oil replacement of saturated fat lowers risk with a 28% reduction in CVD mortality per 5% of energy. Replacing saturated fat with PUFA or MUFA is equally effective at reducing CHD events and replacement with whole grains will lower events while replacement with sugar and starch increases events. Replacement of saturated fat with carbohydrate has no effect on CHD events or death. Only PUFA replacement of saturated fat lowers CHD events and CVD and total mortality. Replacing saturated fat with linoleic acid appears to be beneficial based on the Hooper Cochrane meta-analysis of interventions although other analyses with fewer studies have shown no effect. CONCLUSIONS: Reducing saturated fat and replacing it with carbohydrate will not lower CHD events or CVD mortality although it will reduce total mortality. Replacing saturated fat with PUFA, MUFA or high-quality carbohydrate will lower CHD events.

Effects of Saturated Fat, Polyunsaturated Fat, Monounsaturated Fat, and Carbohydrate on Glucose-Insulin Homeostasis: A Systematic Review and Meta-analysis of Randomised Controlled Feeding Trials.

BACKGROUND: Effects of major dietary macronutrients on glucose-insulin homeostasis remain controversial and may vary by the clinical measures examined. We aimed to assess how saturated fat (SFA), monounsaturated fat (MUFA), polyunsaturated fat (PUFA), and carbohydrate affect key metrics of glucose-insulin homeostasis. METHODS AND FINDINGS: We systematically searched multiple databases (PubMed, EMBASE, OVID, BIOSIS, Web-of-Knowledge, CAB, CINAHL, Cochrane Library, SIGLE, Faculty1000) for randomised controlled feeding trials published by 26 Nov 2015 that tested effects of macronutrient intake on blood glucose, insulin, HbA1c, insulin sensitivity, and insulin secretion in adults aged ≥18 years. We excluded trials with non-isocaloric comparisons and trials providing dietary advice or supplements rather than meals. Studies were reviewed and data extracted independently in duplicate. Among 6,124 abstracts, 102 trials, including 239 diet arms and 4,220 adults, met eligibility requirements. Using multiple-treatment meta-regression, we estimated dose-response effects of isocaloric replacements between SFA, MUFA, PUFA, and carbohydrate, adjusted for protein, trans fat, and dietary fibre. Replacing 5% energy from carbohydrate with SFA had no significant effect on fasting glucose (+0.02 mmol/L, 95% CI = -0.01, +0.04; n trials = 99), but lowered fasting insulin (-1.1 pmol/L; -1.7, -0.5; n = 90). Replacing carbohydrate with MUFA lowered HbA1c (-0.09%; -0.12, -0.05; n = 23), 2 h post-challenge insulin (-20.3 pmol/L; -32.2, -8.4; n = 11), and homeostasis model assessment for insulin resistance (HOMA-IR) (-2.4%; -4.6, -0.3; n = 30). Replacing carbohydrate with PUFA significantly lowered HbA1c (-0.11%; -0.17, -0.05) and fasting insulin (-1.6 pmol/L; -2.8, -0.4). Replacing SFA with PUFA significantly lowered glucose, HbA1c, C-peptide, and HOMA. Based on gold-standard acute insulin response in ten trials, PUFA significantly improved insulin secretion capacity (+0.5 pmol/L/min; 0.2, 0.8) whether replacing carbohydrate, SFA, or even MUFA. No significant effects of any macronutrient replacements were observed for 2 h post-challenge glucose or insulin sensitivity (minimal-model index). Limitations included a small number of trials for some outcomes and potential issues of blinding, compliance, generalisability, heterogeneity due to unmeasured factors, and publication bias. CONCLUSIONS: This meta-analysis of randomised controlled feeding trials provides evidence that dietary macronutrients have diverse effects on glucose-insulin homeostasis. In comparison to carbohydrate, SFA, or MUFA, most consistent favourable effects were seen with PUFA, which was linked to improved glycaemia, insulin resistance, and insulin secretion capacity.

Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study.

BACKGROUND: Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations. METHODS AND FINDINGS: Plasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study across eight European countries. Country-specific hazard ratios (HRs) were estimated using Prentice-weighted Cox regression and pooled by random-effects meta-analysis. We also systematically reviewed published prospective studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct. In EPIC-InterAct, among long-chain n-3 PUFAs, α-linolenic acid (ALA) was inversely associated with T2D (HR per standard deviation [SD] 0.93; 95% CI 0.88-0.98), but eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not significantly associated. Among n-6 PUFAs, linoleic acid (LA) (0.80; 95% CI 0.77-0.83) and eicosadienoic acid (EDA) (0.89; 95% CI 0.85-0.94) were inversely related, and arachidonic acid (AA) was not significantly associated, while significant positive associations were observed with γ-linolenic acid (GLA), dihomo-GLA, docosatetraenoic acid (DTA), and docosapentaenoic acid (n6-DPA), with HRs between 1.13 to 1.46 per SD. These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to nine studies including between 71 to 2,499 T2D cases. Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs. CONCLUSIONS: These large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA (ALA) but no convincing association of marine-derived n3 PUFAs (EPA and DHA) with T2D. Moreover, they highlight that the most abundant n6-PUFA (LA) is inversely associated with T2D. The detection of associations with previously less well-investigated PUFAs points to the importance of considering individual fatty acids rather than focusing on fatty acid class.

Fat intake and breast milk fatty acid composition in farming and nonfarming women and allergy development in the offspring.

BACKGROUND: Children growing up on small family farms are at much lower risk of developing allergy than other children. We hypothesized that low intake of margarine and polyunsaturated fats among farming families could contribute to this protection. METHODS: Twenty-eight mother-infant pairs living on small dairy farms and 37 nonfarm rural resident pairs were recruited in the FARMFLORA birth cohort. Food items expected to affect dietary fat composition were recorded by food frequency questionnaires during pregnancy and by 24-h recalls followed by 24-h food diaries during lactation. Allergy was diagnosed by doctors, using strict predefined criteria. Maternal diet and breast milk fat composition were compared between farming and nonfarming mothers and related to children's allergy at age 3 y. RESULTS: Farming mothers consumed more butter, whole milk, saturated fat, and total fat than nonfarming mothers, who consumed more margarine, oils, and low-fat milk. Farming mothers' breast milk contained higher proportions of saturated and lower proportions of polyunsaturated fat. Allergy was eight times more common in nonfarm children. Mothers of allergic children consumed more margarine and oils than mothers of nonallergic children. CONCLUSION: Low maternal consumption of margarine and vegetable oils might contribute to the allergy-preventive effect of growing up on small dairy farms.

Clinical safety evaluation of marine oil derived from Calanus finmarchicus.

Marine oils are rich in polyunsaturated fatty acids (PUFAs), including docosahexaenoic and eicosapentaenoic acid. These PUFAs are associated with health benefits and additional sustainable sources of marine oils are desirable. One of the source organisms is Calanus finmarchicus, a copepod endemic to the North Atlantic. PUFAs in the lipid fraction of this organism are largely in the form of wax esters. To assess the safety of these wax esters as a source of PUFAs, a randomized, double-blinded, placebo-controlled clinical trial was conducted whereby 64 subjects consumed 2 g Calanus oil in capsule form daily for a period of one year. A group of 53 subjects consumed placebo capsules. At baseline, 6-, and 12-months, series of evaluations were conducted, including: vital signs, clinical chemistry and hematological evaluations, and adverse event reporting. Food intake and physical exercise were controlled by means of a questionnaire. There were no effects on Calanus oil treatment on any of the safety parameters measured. A slight increase in the incidence of eczema was reported in the Calanus oil group, but the response was minor in nature, not statistically significant after controlling for multiple comparisons, and could not be attributed to treatment.

Early fatty acid exposure and later obesity risk.

PURPOSE OF REVIEW: The impact of fatty acids in early nutrition on later body composition and obesity risk remains elusive. Aim of this review was to summarize and discuss recent studies on the role of early supply with long-chain polyunsaturated fatty acids (LCPUFAs) through maternal nutrition during pregnancy and lactation for later offspring obesity. RECENT FINDINGS: Recent human studies, either interventional or observational, investigating the role of dietary fatty acids, in particular of LCPUFAs, on body composition and later obesity risk provide inconsistent results concerning BMI as well as fat mass development in the offspring. A recent meta-analysis of randomized controlled trials found no significant effect of maternal supplementation with n-3 LCPUFA on BMI in both preschool and school-aged children. SUMMARY: There is currently no conclusive evidence that dietary intervention to modify fat intake during pregnancy and lactation is a reasonable strategy to prevent childhood obesity in humans, but more research is clearly needed to address this issue.

Dietary fatty acids and risk of coronary heart disease in men: the Kuopio Ischemic Heart Disease Risk Factor Study.

OBJECTIVE: The epidemiological evidence of the role of dietary saturated fatty acids (SFA) in the development of coronary heart disease (CHD) is inconsistent. We investigated the associations of dietary fatty acids with the risk of CHD and carotid atherosclerosis in men with high SFA intake and high rates of CHD. APPROACH AND RESULTS: In total, 1981 men from the population-based Kuopio Ischemic Heart Disease Risk Factor Study (KIHD), aged 42 to 60 years and free of CHD at baseline in 1984 to 1989, were investigated. Food consumption was assessed with 4-day food recording. Multivariate nutrient-density models were used to analyze isocaloric replacement of nutrients. CHD events were ascertained from national registries. Carotid atherosclerosis was assessed by ultrasonography of the common carotid artery intima-media thickness in 1015 men. During the average follow-up of 21.4 years, 183 fatal and 382 nonfatal CHD events occurred. SFA or trans fat intakes were not associated with CHD risk. In contrast, monounsaturated fat intake was associated with increased risk and polyunsaturated fat intake with decreased risk of fatal CHD, whether replacing SFA, trans fat, or carbohydrates. The associations with carotid atherosclerosis were broadly similar, whereas the associations with nonfatal CHD were weaker. CONCLUSIONS: Our results suggest that SFA intake is not an independent risk factor for CHD, even in a population with higher ranges of SFA intake. In contrast, polyunsaturated fat intake was associated with lower risk of fatal CHD, whether replacing SFA, trans fat, or carbohydrates. Further investigation on the effect of monounsaturated fat on the CHD risk is warranted.

Fat and starch as additive risk factors for milk fat depression in dairy diets containing corn dried distillers grains with solubles.

Two experiments were conducted to evaluate the additive effects of starch and fat as risk factors associated with milk fat depression in dairy diets containing corn dried distillers grains with solubles. In experiment 1, 4 multiparous ruminally cannulated Holstein cows, averaging 114±14 d in milk and 662±52 kg of body weight, were randomly assigned to 4 treatments in a 4×4 Latin square to determine the effect of these risk factors on rumen fermentation and milk fatty acid profile. In each 21-d period, cows were assigned to 1 of 4 dietary treatments: a control diet (CON; ether extract 5.2%, starch 19%); CON with added oil (OL; ether extract 6.4%, starch 18%); CON with added starch (STR; ether extract 5.5%, starch 22%); and CON with added oil and starch (COMBO; ether extract 6.5%, starch 23%). After completion of experiment 1, milk production response was evaluated in a second experiment with a similar approach to diet formulation. Twenty Holstein cows, 12 primiparous and 8 multiparous, averaging 117±17 d in milk and 641±82 kg, were used in replicated 4×4 Latin squares with 21-d periods. Results from experiment 1 showed that ruminal pH was not affected by treatment averaging 5.87±0.08. Molar proportion of propionate in rumen fluid was greatest on the COMBO diet, followed by OL and STR, and lowest for CON. The concentration of trans-10,cis-12 conjugated linoleic acid in milk fat increased with the COMBO diet. Adding oil, starch, or a combination of both resulted in lower concentration and yield of fatty acids<16 carbons. Compared with the control, OL and STR resulted in 13% lower concentration, whereas the COMBO diet resulted in a 27% reduction; similarly yield was reduced by 24% with the OL and STR treatments and 54% with the COMBO diet. In experiment 2, milk yield, milk protein percentage, and milk protein yield were similar across treatments, averaging 26.6±1.01 kg/d, 3.2±0.05%, and 0.84±0.03 kg/d, respectively. Fat-corrected milk was greatest for CON, 26.5±1.12 kg/d; no differences were detected among the remaining treatments, which averaged 23.5±1.12 kg/d. Milk fat percentage was greatest when cows consumed CON, 3.3±0.15%; OL and STR averaged 3.0±0.15% and COMBO resulted in the lowest milk fat percentage, 2.73±0.15%. Milk fat yield was 0.25±0.05 kg/d greater for the CON diet compared with the other 3 treatments, which were similar. These results suggest that fat and starch are additive risk factors that will likely induce milk fat depression in diets containing high inclusion of dried distillers grains with solubles.

Effectiveness and tolerance of anti-inflammatory drugs' add-on therapy in major mental disorders: a systematic qualitative review.

OBJECTIVE: To provide a systematic review of the literature regarding the efficacy of anti-inflammatory drugs in three major mental disorders [major depressive disorder (MDD), schizophrenia and bipolar disorders]. METHOD: Four databases were explored, without any year or language restrictions. The baseline search paradigm was limited to open-labelled clinical and randomized controlled trials (RCTs). RESULTS: Four major classes of anti-inflammatory drugs were identified, namely polyunsaturated fatty acids (PUFAs), cyclooxygenase (COX) inhibitors, anti-TNFalpha and minocycline. Effectiveness and benefit/risk ratio of each class in MDD, bipolar disorders and schizophrenia was detailed when data were available. Several meta-analyses indicated effectiveness of PUFAs in MDD with a good tolerance profile. One meta-analysis indicated that COX-2 specific inhibitors showed effectiveness in schizophrenia. Anti-TNFalpha showed important effectiveness in resistant MDD with blood inflammatory abnormalities. Minocycline showed effectiveness in schizophrenia. CONCLUSION: Polyunsaturated fatty acids seem to have the best benefit/risk ratio profile but proved their effectiveness only in MDD. A number of anti-inflammatory drugs are available as adjunct treatment for treatment-resistant patients with MDD, schizophrenia and bipolar disorder. If used with caution regarding their possible side-effects, they may be reasonable therapeutic alternatives for resistant symptomatology.