Biomarker Of Fatty Acid Intake Research Articles

Biomarkers of fatty acid intake are independently associated with preclinical atherosclerosis in individuals with type 1 diabetes.

Information on the association between diet and cardiovascular disease (CVD) in type 1 diabetes (T1D) is scarce. We assessed the association between biomarkers of fatty acid (FA) intake and the presence of carotid plaques (a surrogate marker of future CVD events) in this high-risk population. Cross-sectional study in 167 consecutive T1D patients without CVD and with at least one of the following: ≥ 40years, diabetic nephropathy, or ≥ 10years of T1D duration with another CVD risk factor. The FA profile of erythrocyte membranes was determined by gas chromatography, and the number of carotid plaques (intima-media thickness ≥ 1.5mm) was assessed by ultrasonography. Regression models were constructed adjusting for classical (age, gender, blood pressure, smoking habit, LDL-cholesterol, body mass index and statins) and T1D-specific risk factors (diabetes duration, HbA1c and chronic complications). A total of 58.7% were men (mean age 48.3 ± 10.3years, T1D duration 27.2 ± 10.1years). Sixty-one patients (36.5%) showed carotid plaque. Linoleic acid decreased and all-C18:1trans increased with the number of carotid plaques (none, 1-2, ≥ 3 plaques; p for trend < 0.05). In multivariate regression models, linoleic acid remained inversely associated with the presence of plaque [1% increase of total FAs; OR 0.71 (0.53-0.95), p = 0.021] and ≥ 2 plaques [OR 0.70 (0.51-0.98), p = 0.039]; whereas, all-C18:1trans was positively associated with ≥ 3 plaques (0.1% increase of total FAs; OR 1.51 [1.05-2.16], p = 0.026). Erythrocyte FA composition, as a biomarker of FA intake, was independently associated with preclinical atherosclerosis in T1DM. Our data support the potential role of an unfavorable pattern of fat intake and CVD risk in this population.

Comparison of the Utility of Total Plasma Fatty Acids Versus those in Cholesteryl Ester, Phospholipid, and Triglyceride as Biomarkers of Fatty Acid Intake.

Total plasma fatty acids or those in cholesteryl ester and phospholipids are often used to reflect fatty acid intake in epidemiological studies, but their relative performance as biomarkers of intake has not been clearly evaluated within a single population. The assessment of fatty acids in plasma fractions is more labor intensive. Thus, their use as biomarkers of dietary intake needs to be justified. Dietary intake was assessed in 200 population-based controls from a case-control study of diet and heart disease in Costa Rica by a validated food frequency questionnaire (FFQ). Fatty acids in fasting whole plasma and plasma fractions (cholesteryl ester, phospholipid, and triglyceride + free fatty acid) were measured in the 200 controls by the same laboratory using gas chromatography with flame ionization detection (GC-FID). We compared the plasma and plasma fractions data with the FFQ and adipose fatty acid profile using partial Spearman correlations to assess utility as biomarkers of intake and exposure. We found that whole plasma was equally or more strongly correlated with the FFQ and adipose fatty acid profile than either cholesteryl ester or phospholipid in most of the established markers of dietary intake, including dairy (15:0 and 17:0) and seafood (eicosapentaenoic acid and docosahexaenoic acid). Of the three plasma fractions, only fatty acids in the plasma triglyceride + free fatty acid fraction had stronger correlations with dietary intake than whole plasma. In our study population, fatty acids measured in fasting whole plasma perform as good as or better than those measured in plasma fractions as biomarkers for dietary fatty acid intake. Thus, the fractionation of plasma to evaluate long-term fatty acid intake may not be warranted.

Baseline patterns of adipose tissue fatty acids and long-term risk of breast cancer: a case-cohort study in the Danish cohort Diet, Cancer and Health

The evidence regarding fatty acids and breast cancer risk is inconclusive. Adipose tissue fatty acids can be used as biomarkers of fatty acid intake and of endogenous fatty acid exposure. Fatty acids in adipose tissue are correlated owing to common dietary sources and shared metabolic pathways, which group fatty acids into naturally occurring patterns. We aimed to prospectively investigate associations between adipose tissue fatty acid patterns and long-term risk of total breast cancer and breast cancer subtypes characterised by oestrogen and progesterone receptor status (ER and PR). This case-cohort study was based on data from the Danish cohort Diet, Cancer and Health. At baseline, a fat biopsy and information on lifestyle and reproductive factors were collected. From the 31 original fatty acids measured, patterns of fatty acids were identified using the treelet transform. During a median follow-up of 5.3 years, 474 breast cancer cases were identified. Hazard ratios and 95% confidence intervals of risk of total breast cancer and of subtypes according to quintiles of factor score were determined by weighted Cox proportional hazards regression. After adjustment for potential confounders, factor scores for the seven patterns identified by the treelet transform were not associated with risk of total breast cancer, nor with risk of ER+, ER-, PR+ or PR- tumours. No clear associations between the patterns of fatty acids at baseline and long-term risk of total breast cancer or ER+, ER-, PR+ or PR- tumours were observed.

Plasma Fatty Acid Composition and Incident Ischemic Stroke in Middle-Aged Adults: The Atherosclerosis Risk in Communities (ARIC) Study

Background: The association of individual fatty acids with ischemic stroke has not been thoroughly studied, and results have been inconsistent. Few prospective studies have systematically explored the association of biomarkers of fatty acid intake with stroke. The aim of this study was to explore which individual plasma fatty acids would be associated with higher risk of ischemic stroke among whites. Methods: We studied 3,870 white men and women from the Minneapolis field center of the Atherosclerosis Risk in Communities (ARIC) Study, aged 45-64 years at baseline (1987-1989), who had plasma cholesterol ester (CE) and phospholipid (PL) fatty acids measured. Participants were followed through 2008 for incident ischemic stroke. Hazard ratios (HRs) with 95% confidence intervals (CIs) across quartiles of each fatty acid, measured as the percentage of total fatty acids, were calculated using the Cox proportional hazards model. Results: During a maximum of 22 years of follow-up, we identified 168 cases of ischemic stroke. After adjustment for age and sex, plasma levels of saturated fatty acids were associated positively: HR (95% CI) of the highest versus the lowest quartile for CE fraction was 1.93 (1.23-3.04, p for trend = 0.01) and that for PL fraction was 1.64 (1.05-2.57, p for trend = 0.03). There was also a positive linear association with monounsaturated fatty acids, especially with palmitoleic acid: HR (95% CI) of the highest versus the lowest quartile for CE fraction was 1.86 (1.20-2.87, p for trend = 0.003) and that for PL fraction was 1.52 (0.99-2.34, p for trend = 0.005). No associations of ω-3 and ω-6 polyunsaturated fatty acids with ischemic stroke were observed, but linoleic acid was inversely and nonlinearly associated with ischemic stroke: HR (95% CI) of the highest versus the lowest quartile for CE fraction was 0.64 (0.43-0.97, p for trend = 0.13) and that for PL fraction was 0.69 (0.45-1.05, p for trend = 0.24). These associations were generally unchanged after adjustment for cardiovascular risk factors. Conclusions: In this US cohort of whites, we found significant positive associations of plasma saturated and monounsaturated fatty acids, especially of palmitoleic acid, with ischemic stroke. We also found an inverse nonlinear association between linoleic acid and ischemic stroke.

Trans–fatty acid levels in sperm are associated with sperm concentration among men from an infertility clinic

We measured the sperm fatty acid composition using gas chromatography in anonymized semen samples of 33 men undergoing infertility evaluation at an academic medical center. Trans-fatty acids were present in human sperm and were related inversely to sperm concentration (r = -0.44).

Abstract 896: Pre-diagnostic blood fatty acid levels and prostate cancer mortality

Abstract Purpose: Fatty acid metabolism, particularly de novo lipogenesis, may be an important determinant of prostate cancer progression and mortality. However, epidemiologic data regarding the role of circulating fatty acids, as biomarkers of fatty acid intake and metabolism, on prostate cancer progression and mortality is scarce. Methods: We conducted a prospective cohort study among 582 Physicans’ Health Study participants who provided a blood sample in 1982 and who were later diagnosed with prostate cancer, between 1982 and 2006. Blood samples were kept frozen until they were assayed. Men were followed from the date of prostate cancer diagnosis until death or the end of follow-up (March 31, 2009). Blood levels of major types of fatty acids were measured using gas chromatography and expressed as percentage of total fatty acids. Men were categorized according to quintiles of blood fatty acid levels. Proportional hazards regression was used to estimate the relative risk (RR) and 95% confidence interval (95% CI) of prostate cancer specific mortality in a given quintile of fatty acid level in relation to the lowest quintile. Results: During 7,414 person-years of follow-up, 94 men died of prostate cancer. The median time between diagnosis and prostate cancer death was 14 years. The median time between blood draw and prostate cancer diagnosis was 9.5 years. Blood levels of all the mono-unsaturated, n-6 polyunsaturated and n-3 polyunsaturated fatty acids examined were unrelated to prostate cancer mortality. However, compared to men in the lowest quintile, the RRs (95% CIs) of prostate cancer mortality for men in increasing quintiles of blood stearic acid (18:0) levels were 1.90 (0.81-4.50), 3.61 (1.55-8.42), 2.29 (0.96-5.43) and 4.96 (2.10-11.7) (P, trend &amp;lt;0.001) after adjusting for age at diagnosis, race, body mass index, smoking status, clinical stage and tumor grade at diagnosis, and time between blood draw and prostate cancer diagnosis. Blood levels of the remaining saturated fatty acids examined were unrelated to prostate cancer mortality. Conclusions: Pre-diagnostic blood levels of stearic acid, a saturated fatty acid, are positively related to prostate cancer mortality. Since blood stearic acid levels are usually unrelated to diet, these data suggest that differences in fatty acid metabolism might be responsible for this association. It remains to be determined whether this finding is due to between-person differences in the activity of de novo lipogenesis enzymes or other metabolic factors that result in higher blood levels of stearic acid. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 896.

Adipose Tissue Fatty Acids in Breast Cancer Patients versus Healthy Control Women from Crete

Background: Few studies have implemented biomarkers of fatty acid intake in relation to breast cancer. Aims: To examine possible differences in adipose tissue fatty acid composition between breast cancer patients and healthy control women. The relationship between tumor promotion and adipose tissue fatty acid synthesis was also investigated. Methods: The study was conducted at the University of Crete. Subjects included 94 women with clinically diagnosed cancer of the breast and 131 healthy control women. Histological tumor grading and breast cancer staging were assessed. Fatty acids were determined by gas chromatography in gluteal adipose tissue. Results: Conditional logistic regression analysis controlling for potential confounders indicated that elevated adipose monounsaturated fatty acids and oleic acid are associated with reduced odds of breast cancer [OR (T2 vs. T1) 0.15; 95% CI 0.03–0.64, and OR (T2 vs. T1) 0.18; 95% CI 0.04–0.71, respectively]. Adipose myristic acid was associated with an increase in breast cancer risk [OR (T3 vs. T1) 5.66; 95% CI 1.3–23.9]. Conclusions: Adipose oleic acid is inversely related, whereas adipose myristic acid is positively related to breast cancer risk. These relations could be mediated by Her-2/neu and FAS oncogenes.

Association between serum trans-monounsaturated fatty acids and breast cancer risk in the E3N-EPIC Study.

The authors assessed the association between serum phospholipid fatty acids as biomarkers of fatty acid intake and breast cancer risk among women in the E3N Study (1989-2002), the French component of the European Prospective Investigation into Cancer and Nutrition. During an average of 7 years of follow-up, 363 cases of incident invasive breast cancer were documented among 19,934 women who, at baseline (1995-1998), had completed a diet history questionnaire and provided serum samples. Controls were randomly matched to cases by age, menopausal status at blood collection, fasting status at blood collection, date, and collection center. Serum phospholipid fatty acid composition was assessed by gas chromatography. Adjusted odds ratios for risk of breast cancer with increasing levels of fatty acids were calculated using conditional logistic regression. An increased risk of breast cancer was associated with increasing levels of the trans-monounsaturated fatty acids palmitoleic acid and elaidic acid (highest quintile vs. lowest: odds ratio = 1.75, 95% confidence interval: 1.08, 2.83; p-trend = 0.018). cis-Monounsaturated fatty acids were unrelated to breast cancer risk. A high serum level of trans-monounsaturated fatty acids, presumably reflecting a high intake of industrially processed foods, is probably one factor contributing to increased risk of invasive breast cancer in women.

Comparison between plasma and erythrocyte fatty acid content as biomarkers of fatty acid intake in US women

Background: Erythrocyte fatty acids may be superior to plasma fatty acids for reflecting long-term fatty acid intake because of less sensitivity to recent intake and a slower turnover rate.Objective: The objective was to compare the fatty acid content of erythrocytes with that of plasma with respect to their abilities to reflect usual fatty acid intake.Design: Fatty acids in plasma and erythrocytes were measured by capillary gas-liquid chromatography in 306 US women aged 43–69 y. Fatty acid intake was assessed with a food-frequency questionnaire, which was validated for measuring intakes of various fatty acids.Results: Docosahexaenoic acid (DHA, 22:6n−3) in erythrocytes and plasma provided the strongest correlations with its intake, but erythrocyte DHA concentrations [Spearman's partial correlation coefficient (rs) = 0.56] were better than plasma DHA concentrations (rs = 0.48) as a biomarker. Total trans fatty acids (rs = 0.43) and total 18:1 trans isomers (rs = 0.42) in erythrocytes were also more strongly correlated with intake than were those in plasma (rs = 0.30 and rs = 0.29, respectively). Moderate correlations were observed for linoleic acid (18:2n−6; erythrocytes, rs = 0.24; plasma, rs = 0.25), α-linolenic acid (18:3n−3; erythrocytes, rs = 0.18; plasma, rs = 0.23), and eicosapentaenoic acid (20:5n−3; erythrocytes, rs = 0.38; plasma, rs = 0.21). For polyunsaturated and trans fatty acids, correlations between intakes and biomarkers improved moderately when average intakes over previous years were used.Conclusion: Erythrocyte n−3 fatty acids of marine origin and trans fatty acid content are suitable biomarkers for long-term intake.

Biomarkers of dietary fatty acid intake and the risk of breast cancer: a meta-analysis.

The use of the fatty acid composition of adipose tissue, erythrocyte membranes, serum and plasma as biological markers of fatty acid intake was recently introduced in epidemiological studies. The biomarkers of fatty acid intake have the advantage of providing quantitative measurement independent of energy intake and of the subject's memory. We performed a meta-analysis of published results of epidemiological studies of the composition of fatty acids in biological samples and breast cancer risk. The analysis was based on 3 cohort and 7 case-control studies including 2,031 cases and 2,334 controls. The summary statistic used was the average of the relative risk estimated for each level of the fatty acid on study, weighted by the inverse of its variance. Random effect models were assumed when the test for heterogeneity was significant. Overall relative risks were estimated for studies including pre- and post-menopausal breast cancer and separately for post-menopausal women. In cohort studies, a significant protective effect was found for total n-3 polyunsaturated fatty acids, while total monounsaturated fatty acids, oleic acid (C18:1 n-9c) and palmitic acid (C16:0) were significantly associated with an increase of breast cancer risk. Total saturated fatty acids were significantly associated with breast cancer risk in cohort studies only in postmenopausal women. For case-control studies, the only finding was for alpha linolenic acid (C18:3, n-3), which showed an inverse association bordering on statistical significance. The findings of cohort studies fit well with hypotheses derived from experimental animal studies. More epidemiological cohort studies that integrate biological markers of dietary fatty acid intake are needed in order to determine the contribution of different types of fatty acids in the etiology of breast cancer.

Adipose tissue biomarkers of fatty acid intake

Biomarkers can provide a more accurate measure of long-term intake than can dietary questionnaires. The objective was to identify which adipose tissue fatty acids are suitable biomarkers of intake as assessed with a validated food-frequency questionnaire. Costa Rican men with a mean (+/- SD) age of 56 +/- 11 y (n = 367) and women aged 60 +/- 10 y (n = 136) completed a 135-item food-frequency questionnaire and provided an adipose tissue sample. Fifty fatty acids were identified by capillary gas chromatography. Correlation coefficients were calculated after adjustment for age, sex, body mass index, and smoking status. The best adipose tissue marker for total intake of saturated fatty acids was 15:0 + 17:0 (r = 0.18). Both 15:0 and 17:0 were also the best correlates of dairy product intake (r = 0.31 for each). The diet-adipose tissue correlations for n-3 fatty acids were r = 0.34 for 18:3, r = 0.15 for 20:5, and r = 0.18 for 22:6. Fish intake correlated significantly with these adipose tissue n-3 fatty acids. Dietary and adipose tissue n-6 fatty acids were highly correlated: 18:2 (r = 0.58) and 18:3 (r = 0.24). The best indicators of total trans fatty acid intake were ct18:2n-6 and tc18:2n-6 (r = 0.58 for each); total 18:1 trans fatty acid (r = 0.45) and 16:1 trans fatty acid (r = 0.16) were the next best indicators. Adipose tissue is a suitable biomarker of dietary fatty acid intake, particularly for n-3 and n-6 cis polyunsaturated fatty acids and trans fatty acids. Ideally, adipose tissue and dietary questionnaires should complement, rather than substitute for, each other in epidemiologic studies.

Fatty acid composition of serum cholesterol esters as a reflector of low‐saturated‐fat, low‐cholesterol diet in young children: the STRIP project

STRIP (the Special Turku coronary Risk factor Intervention Project) is an ongoing intervention trial which aims at a permanent reduction in the intake of saturated fat and cholesterol starting in childhood. A total of 75 intervention and 63 control children was studied consecutively at the ages of 7 and 13 mo, and 2, 3 and 5 y to evaluate the influence of such intervention on serum cholesterol ester (CE) fatty acid composition, a widely used biomarker of fatty acid intake. Analysis of 4‐d food records showed that total intake of fat and of saturated fat increased with age in both groups of children but was constantly lower in intervention than in control children, e.g. at the age of 5 y the mean intakes of total fat and of saturated fatty acids were 31.1 E% and 33.9 E% and 12.1 E% and 14.6E% in intervention and control children, respectively (p = 0.009 and 0.0001, respectively). Serum CE fatty acid compositions did not differ between the 2 groups at any age; the mean proportion of CE linoleic acid was 52.4% and 52.0% in 5‐y‐old intervention and control children, respectively. Correlation analysis showed, however, that the percentage of linoleic acid and of polyunsaturated fatty acids in CE reflected well the respective dietary intakes (r= 0.36; p = 0.0001 for both coefficients).In conclusion, CE fatty acid composition did not differ between the intervention and control groups, whereas CE linoleic and total polyunsaturated fatty acids reflected well the differences in their intakes at the individual level.