Role of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease: Pooled De Novo Results From 15 Observational Studies.

BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium. METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction. RESULTS: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; P=0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions. CONCLUSIONS: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD.

n-3 Fatty Acid Biomarkers and Incident Type 2 Diabetes: An Individual Participant-Level Pooling Project of 20 Prospective Cohort Studies.

OBJECTIVE: Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis. RESEARCH DESIGN AND METHODS: For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed in each cohort following a prespecified protocol, and cohort-specific associations were pooled using inverse variance-weighted meta-analysis. RESULTS: A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per interquintile range (difference between the 90th and 10th percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% CIs of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89), and 0.81 (0.75, 0.88), respectively (all P < 0.001). ALA was not associated with T2D (HR 0.97 [95% CI 0.92, 1.02]) per interquintile range. Associations were robust across prespecified subgroups as well as in sensitivity analyses. CONCLUSIONS: Higher circulating biomarkers of seafood-derived n-3 fatty acids, including EPA, DPA, DHA, and their sum, were associated with lower risk of T2D in a global consortium of prospective studies. The biomarker of plant-derived ALA was not significantly associated with T2D risk.

Postpartum Diet Quality: A Cross-Sectional Analysis from the Australian Longitudinal Study on Women's Health.

Reproductive-aged women are at high risk of developing obesity, and diet quality is a potential modifiable risk factor. There is limited research exploring diet quality and its association with time since childbirth. Using data from the Australian Longitudinal Study on Women's Health (ALSWH) survey 5 (2009) of women born between 1973-1978, who reported having previously given birth, we investigated the association between time since childbirth and diet quality, and differences in energy, macronutrients, micronutrient intake, and diet quality assessed by the dietary guideline index (DGI) in women stratified by time from last childbirth, early (0-6 months; n = 558) and late (7-12 months; n = 547), and all other women with children (>12 months post childbirth n = 3434). From this cohort, 8200 participants were eligible, of which 4539 participants completed a food frequency questionnaire (FFQ) and were included in this analysis. Overall, diet quality was higher in early and late postpartum women (mean DGI score 89.8 (SD 10.5) and mean DGI score 90.0 (SD 10.2), respectively) compared to all other women with children (>12 months post childbirth), mean DGI score 85.2 (SD 11.7), p < 0.001. Factors positively associated with diet quality included higher education, physical activity, health provider support, and vitamin and/or mineral supplement use. Conversely, increasing time from childbirth (>12 months), smoking compared with non-smoking and medium income level compared with no income was negatively associated with diet quality. A lower diet quality in women greater than 12 months post childbirth may be reflective of increased pressures, balancing childrearing and return to work responsibilities. This highlights the need to support women beyond the postpartum period to improve modifiable factors associated with weight gain, including diet quality, to optimize health and reduce chronic disease risk.

Is high vitamin B12 status a cause of lung cancer?

Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer etiology via direct measurements of pre-diagnostic circulating vitamin B12 concentrations in a nested case-control study, complemented with a Mendelian randomization (MR) approach in an independent case-control sample. We used pre-diagnostic biomarker data from 5183 case-control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls. Exposures included directly measured circulating vitamin B12 in pre-diagnostic blood samples from the nested case-control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study. Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations. We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 [ORlog2B12 ] = 1.15, 95% confidence interval (95%CI) = 1.06-1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 [ORSD ] = 1.08, 95%CI = 1.00-1.16). Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer.

Circulating concentrations of biomarkers and metabolites related to vitamin status, one-carbon and the kynurenine pathways in US, Nordic, Asian, and Australian populations.

Background: Circulating concentrations of biomarkers that are related to vitamin status vary by factors such as diet, fortification, and supplement use. Published biomarker concentrations have also been influenced by the variation across laboratories, which complicates a comparison of results from different studies.Objective: We robustly and comprehensively assessed differences in biomarkers that are related to vitamin status across geographic regions.Design: The trial was a cross-sectional study in which we investigated 38 biomarkers that are related to vitamin status and one-carbon and tryptophan metabolism in serum and plasma from 5314 healthy control subjects representing 20 cohorts recruited from the United States, Nordic countries, Asia, and Australia, participating in the Lung Cancer Cohort Consortium. All samples were analyzed in a centralized laboratory.Results: Circulating concentrations of riboflavin, pyridoxal 5'-phosphate, folate, vitamin B-12, all-trans retinol, 25-hydroxyvitamin D, and α-tocopherol as well as combined vitamin scores that were based on these nutrients showed that the general B-vitamin concentration was highest in the United States and that the B vitamins and lipid soluble vitamins were low in Asians. Conversely, circulating concentrations of metabolites that are inversely related to B vitamins involved in the one-carbon and kynurenine pathways were high in Asians. The high B-vitamin concentration in the United States appears to be driven mainly by multivitamin-supplement users.Conclusions: The observed differences likely reflect the variation in intake of vitamins and, in particular, the widespread multivitamin-supplement use in the United States. The results provide valuable information about the differences in biomarker concentrations in populations across continents.

ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies.

IMPORTANCE: The role of ω-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. OBJECTIVE: To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5ω-3), docosapentaenoic acid (DPA; 22:5ω-3), and docosahexaenoic acid (DHA; 22:6ω-3) and plant-derived α-linolenic acid (ALA; 18:3ω-3) for incident CHD. DATA SOURCES: A global consortium of 19 studies identified by November 2014. STUDY SELECTION: Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ω-3 biomarkers and ascertained CHD. DATA EXTRACTION AND SYNTHESIS: Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, ω-6 levels, and FADS desaturase genes. MAIN OUTCOMES AND MEASURES: Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). RESULTS: The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with ω-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the ω-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. CONCLUSIONS AND RELEVANCE: On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived ω-3 fatty acids are associated with a modestly lower incidence of fatal CHD.

Plasma phospholipids fatty acids, dietary fatty acids, and breast cancer risk.

PURPOSE: This study prospectively investigates associations between fatty acids assessed in plasma phospholipids (PPL) and diet, and breast cancer risk, including subgroups defined by hormone receptor status. METHODS: We performed a case-cohort analysis within the Melbourne Collaborative Cohort Study using a random sample of 2,021 women and 470 breast cancer cases. At baseline, fatty acids were assessed in PPL and estimated from diet using a 121-item food frequency questionnaire. Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using Cox regression. RESULTS: Breast cancer risk was positively associated with %PPL saturated fatty acids (SFA); HRQ5vsQ1 = 1.64 (95 % CI 1.17-2.30); p trend = 0.004. Positive associations were found for ER+ or PR+ tumors for %PPL SFA and palmitic acid and for ER-/PR- tumors for %PPL n-6 polyunsaturated fatty acid (PUFA), TFA, TFA 16:1, and TFA 18:1n-7 (all p homogeneity <0.05). Breast cancer risk was inversely associated with dietary docosapentaenoic acid (DPA); HRQ5vsQ1 = 0.57 (95 % CI 0.40-0.82); p trend = 0.001 [with similar inverse associations observed for dietary docosahexaenoic (DHA) and eicosapentaenoic acid (EPA)] and positively associated with dietary n-6:n-3 PUFA. Inverse associations for ER-/PR- tumors were found for dietary dihomo-γ-linolenic acid (DGLA) for older women (p homogeneity = 0.04). CONCLUSIONS: Breast cancer risk was positively associated with %PPL SFA and the ratio of dietary n-6 to n-3 PUFA and inversely associated with dietary long-chain n-3 PUFA intake. Some associations between fatty acids and breast cancer varied by age and tumor phenotype defined by hormone receptor status. Increased intake of fish and other foods rich in long-chain n-3 PUFAs and reduced n-6 PUFA intake might reduce breast cancer risk.

Dietary α-Linolenic Acid and Total ω-3 Fatty Acids Are Inversely Associated with Abdominal Aortic Calcification in Older Women, but Not in Older Men.

BACKGROUND: Associations of α-linolenic acid (ALA), eicosapentaenoic acid (EPA) plus decosahexaenoic acid (DHA), and total omega-3 (n-3) fatty acid (FA) intakes with abdominal aortic calcification (AAC) are not well understood. OBJECTIVE: This study explored the associations between baseline and long-term changes in ω-3 FA consumption and AAC severity among community-dwelling older men and women. METHODS: The present study used a subset of the Melbourne Collaborative Cohort Study in which participants were interviewed in 1990-1994 and again in 2010-2011. Dietary intake was evaluated at both baseline and follow-up with use of food-frequency questionnaires. AAC severity was assessed by both lateral thoraco-lumbar radiography and dual-energy X-ray absorptiometry (DXA) at follow-up. RESULTS: A total of 312 participants aged 45-64 y old at baseline were followed for a duration of (mean ± SD) 18 ± 1 y. Baseline energy-adjusted ALA intake tended to be inversely associated with AAC severity by radiography [OR (95% CI) for tertile 3 vs. tertile 1: 0.49 (0.23, 1.02), P-trend: 0.06] and was inversely associated with AAC severity by DXA [OR (95% CI) for tertile 3 vs. tertile 1: 0.37 (0.16, 0.83)] in women, after adjustment for confounders. Women in the third tertile of total ω-3 FA intake had significantly lower AAC severity by radiography [OR (95% CI): 0.33 (0.16, 0.71)] and DXA [OR (95% CI): 0.27 (0.12, 0.62)] than those in the first tertile. Changes in tertile of ω-3 FA intake over 18 y were not found to be associated with AAC severity in either men or women. CONCLUSION: The results of our study suggest that dietary ALA and total ω-3 FA intakes are both important predictors of the development of AAC in older women, but not in older men.

Dietary intake of B vitamins and methionine and breast cancer risk.

PURPOSE: We investigated prospectively the relationship between dietary intakes of methionine and B vitamins associated with one-carbon metabolism and breast cancer risk, including modification by age, hormone receptor status and alcohol consumption. Interactions between different B vitamins and methionine were also examined. METHODS: During follow-up of 20,756 women from the Melbourne Collaborative Cohort Study for an average of 16 years, we ascertained 936 incident breast cancers. Dietary intakes were estimated using a 121-item food frequency questionnaire. Hazard ratios (HR) and 95 % confidence intervals were estimated using Cox regression. RESULTS: We found weak evidence for an inverse association between breast cancer risk and riboflavin intake (fourth versus first quartile, HR Q4 vs. Q1 = 0.84 (0.69, 1.01); p linear trend = 0.05) and a positive association for vitamin B12 (HR Q4 vs. Q1 = 1.21 (1.00, 1.46); p linear trend = 0.06). We did not find any significant interactions between alcohol consumption and any of the B vitamins or methionine intake (all p interaction > 0.17) or between methionine or folate intake and any other B vitamins (all p interaction > 0.07). No association varied by tumor hormone receptor status (all p homogeneity > 0.14). CONCLUSIONS: We found weak evidence of an inverse association between breast cancer risk and riboflavin intake and a positive association with vitamin B12.

Fat consumption and its association with age-related macular degeneration.

OBJECTIVE: To evaluate associations between past dietary fat intake and the prevalence of age-related macular degeneration (AMD). METHODS: Six thousand seven hundred thirty-four participants aged 58 to 69 years in 1990-1994 took part in this cohort study. Participants' nutrient intakes were estimated from a food frequency questionnaire at baseline. At follow-up from 2003 to 2006, digital macula photographs of both eyes were evaluated for early and late AMD signs. Logistic regression was used to estimate odds ratios, with adjustment for age, smoking, and other potential confounders. RESULTS: Higher trans-unsaturated fat intake was associated with an increased prevalence of late AMD; the odds ratio comparing the highest with the lowest quartile of trans fat was 1.76 (95% confidence interval, 0.92-3.37; P = .02). Higher omega-3 fatty acid intake (highest quartile vs lowest quartile) was inversely associated with early AMD (odds ratio, 0.85; 95% confidence interval, 0.71-1.02; P = .03). Olive oil intake (> or =100 mL/week vs <1 mL/week) was associated with decreased prevalence of late AMD (odds ratio, 0.48; 95% confidence interval, 0.22-1.04; P = .03). No significant associations with AMD were observed for intakes of fish, total fat, butter, or margarine. CONCLUSION: A diet low in trans-unsaturated fat and rich in omega-3 fatty acids and olive oil may reduce the risk of AMD.

Can the Mediterranean diet prevent prostate cancer?

Prostate cancer is the second most common cancer in men worldwide. Despite the global importance of this cancer, until recently little was known about risk factors apart from the well-established factors: age, family history and country of birth. The large worldwide variation in prostate cancer risk and increased risk in migrants moving from low to high risk countries provides strong support for modifiable environmental factors. We have based our review on the findings of a systematic review undertaken by an expert panel on behalf of the World Cancer Research Fund and the American Institute for Cancer Research, and new data since then, linking identified foods and nutrients with prostate cancer. Evidence indicates that foods containing lycopene, as well as selenium and foods containing it, probably protect against prostate cancer, and excess consumption of foods or supplements containing calcium are a probable cause of this cancer. The expert panel also concluded that it is unlikely that beta-carotene (whether from foods or supplements) has a substantial effect on the risk of this cancer. A recent review on environmental factors in human prostate cancer also found that there were protective effects of vitamin E, pulses, soy foods and high plasma 1,25-dihydroxyvitamin D levels. The Mediterranean diet is abundant in foods that may protect against prostate cancer and is associated with longevity and reduced cardiovascular and cancer mortality. Compared with many Western countries Greece has lower prostate cancer mortality and Greek migrant men in Australia have retained their low risk for prostate cancer. Consumption of a traditional Mediterranean diet, rich in bioactive nutrients, may confer protection to Greek migrant men, and this dietary pattern offers a palatable alternative for prevention of this disease.

Dietary lutein, zeaxanthin, and fats and the progression of age-related macular degeneration.

BACKGROUND: To estimate the effect of dietary intake of lutein and zeaxanthin (L/Z) and fats on the progression of age-related macular degeneration (AMD). METHODS: Two hundred and fifty-four subjects identified with early age-related macular degeneration (AMD) were re-examined to determine 7-year AMD progression. Intakes of L/Z and fatty acids were estimated from food frequency questionnaires. Progression was defined by 3 different definitions, 2 quantitative and 1 qualitative, which varied in the stringency of the change required for the AMD to be deemed to have progressed. Covariates included age, smoking, AMD family history, source study, and follow-up duration. RESULTS: Energy-adjusted L/Z intake as a continuous variable was associated with AMD progression in the worse affected eye when defined by the most stringent criterion (odds ratio [OR] = 2.65, 95% confidence interval [CI] 1.13-6.22, p = 0.02). Similar associations were observed for the 2 other progression definitions (p = 0.18 and p = 0.13). Energy-adjusted omega-3 fatty acid intake modelled as a quintile median was associated with AMD progression only in the side-by-side assessment (OR = 2.56, 95% CI 1.11-5.91, p = 0.03), with borderline significance in the other 2 definitions (p = 0.05 and p = 0.08). No association of AMD progression was observed with the intake of either total fat or other subgroups: saturated, polyunsaturated, or monounsaturated fats; trans fatty acids; or omega-6 fatty acids. INTERPRETATION: The findings of the study are counterintuitive, suggesting that increased intakes of dietary L/Z and omega-3 fatty acids are associated with progression of AMD. These results may indicate that too much of a good thing might be harmful. It is possible that in this study participants adopted a more healthy diet, having been aware of their AMD status at the beginning of the study. This healthy diet was then reflected in the dietary questionnaire completed at the end of study. However, this explanation may not adequately explain why those whose AMD had progressed, on the basis of fundus signs and not symptoms such as visual acuity decline, adopted a healthier lifestyle more aggressively than those without progression.