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BACKGROUND: An altered plasma fatty acid (FA) profile and desaturase activities have been associated with several metabolic diseases, including the MetS, but studies in the general populations are lacking, and only few studies have investigated a broad spectrum of FA in plasma phospholipids (PL). OBJECTIVE: We investigated, cross-sectionally, the relationship of the FA profile and desaturase activities in plasma PL with the prevalence of MetS in a general population in The Netherlands. METHODS: Baseline characteristic data from 850 participants (Male: 50.2%) aged 38-68 years recruited in the Lifelines Cohort study were obtained. The FA profile was determined in fasting plasma PL, and desaturase activities were estimated from product/precursor ratios. The MetS was defined according to International Diabetes Federation. Logistic regressions were used to examine the relation of the FA profile with the prevalence of MetS, and Bonferroni correction was applied to account for multiple testing. RESULTS: 151 participants (17.7%) had the MetS. After adjustment for several confounders and Bonferroni correction, higher tertiles of C18 : 0 (the early precursor of de novo lipogenesis pathway), C18 : 3n6 and C20 : 3n6 (both consistent with a high Δ 6 desaturase (D6D) activity), and D6D activity itself were associated with a higher prevalence of MetS, while higher tertiles of C18 : 1n7, C24 : 0, and C24 : 1n9 (very-long-chain FA) as well as stearoyl-CoA desaturase (SCD)-18 were inversely associated with the MetS. CONCLUSIONS: This study shows that a wide-ranging plasma PL FA profile and estimated desaturase activities were different between adults with and without the MetS in a general representative population and implicates the importance of monitoring individual FAs and desaturase activities as novel modifiable biomarkers for the MetS.

OBJECTIVES: Determine whether plasma omega-7 cis-vaccenic acid and palmitoleic acid levels are related to all-cause mortality in a general population. METHODS: Plasma phospholipids (PL) and triglycerides (TG) fatty acids were measured by gas chromatography with polar column and detected with a flame ionization detector in the Lifelines fatty acids cohort study participants (n = 864). Associations with all-cause mortality were analyzed by Cox proportional hazards regression with adjustment for conventional risk factors. RESULTS: During a median follow-up of 9.3 years, 33 (3.9%) participants died. Adjusting for typical risk factors, high levels of plasma PL and TG cis-vaccenic acid, and TG palmitoleic acid were found to be associated with all-cause mortality. A 1-SD increase in PL cis-vaccenic acid, TG cis-vaccenic acid, and TG palmitoleic acid was associated with increased risk of all-cause mortality with HRs (95% CI) of 1.69 (1.17–2.46), 1.54 (1.03–1.15), and 1.44 (1.08–1.92), respectively. Compared to the lowest tertile, the HRs (95% CI, p-trend) for the highest tertile of PL cis-vaccenic acid, TG cis-vaccenic acid, and TG palmitoleic acid were 3.0 (1.05–8.56, 0.03), 2.25 (0.87–5.85), and 3.39 (1.24–9.28, 0.02), respectively. CONCLUSIONS: Elevated levels of plasma cis-vaccenic acid and palmitoleic acid are risk factors for all-cause mortality. FUNDING SOURCES: The data analyses from the Lifelines Cohort that were carried out in this paper were funded by Friesl and Campina. The funders had no role in study design, data collection and analysis, manuscript preparation and decision to publish.

Dairy fat intake, reflected by the biomarkers C14:0, C15:0, C17:0, trans-C16:1 (n-7), trans-C18:1 (n-7) and CLA, may have beneficial effects on cardiovascular health. It has, however, been questioned whether this association is genuine, since C15:0 and C17:0 are also biomarkers from fish. We investigated whether the above biomarkers are reliable markers for dairy fat intake in 864 healthy subjects. Subsequently, we explored the association between these biomarkers and cardiovascular risk factors. Intakes of dairy and fish were determined by Food Frequency Questionnaires FFQs. Fatty acids were analyzed in plasma triglycerides (TG) and phospholipids (PL). Median intakes of dairy and fish fat were 12.3 (8.4&ndash, 17.4) g/day and 1.14 (0.53&ndash, 1.75) g/day. All fatty acids, except TG C17:0, were associated with dairy fat (std.&beta, range TG: 0.12 for C14:0 till 0.25 for C15:0 and Trans-C18:1 (n-7), and std.&beta, range PL: 0.12 for C17:0 and Trans-C16:1 (n-7) till 0.24 for Trans-C18:1 (n-7) and CLA, p &lt, 0.001). TG C17:0 was associated with fish fat (std.&beta, = 0.08, p = 0.03), whereas PL C17:0 was not. Associations remained after adjustment for fish/dairy fat intake. Strongest inverse associations with biological variables were found with PL C17:0 and Trans-C18:1 (n-7) (Std.&beta, s: waist circumference: &minus, 0.18, p &lt, 0.001 and &minus, 0.10, p &lt, 0.05, BMI: &minus, 0.17, p &lt, 0.001, &minus, 0.11, p &lt, 0.01, glucose: &minus, 0.01 and &minus, 0.08, p &lt, high sensitive C-reactive protein (hs-CRP): &minus, 0.22, p &lt, 0.16, p &lt, uric acid: &minus, 0.27, p &lt, 0.24, p &lt, 0.001). In conclusion, fatty acid biomarkers, except plasma TG C17:0, were associated with dairy fat intake, independent of fish fat intake. PL C17:0 and trans-C18:1 (n-7) were inversely associated with adiposity, diabetes, inflammation and uric acid.

Supplementation withn-3 fatty acids may improve long-term outcomes of renal transplant recipients (RTR). Recent evidence suggests that EPA and DHA have different outcomes compared withα-linolenic acid (ALA). We examined the prospective associations of EPA–DHA and ALA intakes with graft failure and all-cause mortality in 637 RTR. During 3·1 years (interquartile range 2·7, 3·8) of follow-up, forty-one developed graft failure and sixty-seven died. In age- and sex-adjusted analyses, EPA–DHA and ALA intakes were not associated with graft failure. EPA–DHA intake was not significantly associated with mortality (hazard ratio (HR) 0·79; 95% CI 0·54, 1·15 per 0·1 energy% difference). ALA intake was significantly associated with mortality (HR 1·17; 95% CI 1·04, 1·31 per 0·1 energy% difference). This association remained following adjustments for BMI, proteinuria and intakes of fat, carbohydrate and protein. RTR in the highest tertile of ALA intake exhibited about 2-fold higher mortality risk (HR 2·21; 95% CI 1·23, 3·97) compared with the lowest tertile. In conclusion, ALA intake may be associated with increased mortality in RTR. Future RCT are needed to confirm these results.

Background: C14:0, C15:0, C17:0 and trans-C16:1(n-7) are often used as biomarkers for dairy fat intake. Trans-C18:1(n-7) and CLA, two fatty acids which are also present in dairy, have hardly been explored. We investigated whether trans-C18:1(n-7) and CLA can enrich the existing biomarker portfolio. Methods: Data were obtained from Lifelines (n = 769). Dairy fat intake was determined by FFQ. Fatty acids were measured in fasting plasma triglycerides (TG), phospholipids (PL) and cholesterol esters (CE). Results: Median (25th–75th percentile) intakes of dairy and dairy fat were 322(209–447) and 12.3(8.4–17.4) g/d respectively. A pilot study showed that trans-C18:1(n-7) and CLA were only detectable in TG and PL. Of the established markers, TG C15:0 was most strongly associated with dairy fat intake (standardized β (std.β) = 0.286, R2 = 0.111). Of the less established markers, TG trans-C18:1(n-7) was most strongly associated with dairy fat intake (Std.β = 0.292, R2 = 0.115), followed by PL CLA (Std.β = 0.272, R2 = 0.103) and PL trans-C18:1(n-7) (Std.β = 0.269, R2 = 0.099). In TG, a combination of C15:0 and trans-C18:1(n-7) performed best (R2 = 0.128). In PL, a combination of C14:0, C15:0, trans-C18:1(n-7) and CLA performed best (R2 = 0.143). Conclusion: Trans-C18:1(n-7) and CLA can be used as biomarkers of dairy fat intake. Additionally, combining established with less established markers allowed even stronger predictions for dairy fat intake.

The main goal of this thesis was to explore commonly (C14:0, C15:0, C17:0 and Trans-C16:1(n-7)) and less commonly (Trans-C18:1(n-7) and Conjugated linoleic acid (CLA)) investigated fatty acid biomarkers for dairy and dairy fat intake in the general population. We therefore developed a new method, with which we would be able to measure all potential biomarkers. We also explored whether the association between dairy fat biomarkers and dairy fat intake was independent of fish fat intake, since it has been suggested that C15:0 and C17:0 might also be biomarkers for fish intake. It appeared that C14:0, C15:0, C17:0, trans-C16:1(n-7), trans-C18:1(n-7) and CLA are useful biomarkers of dairy fat intake for the general population. Moreover, we found that a combination of commonly and less commonly fatty acids was the best predictor for dairy fat intake. Associations of dairy biomarkers with dairy fat intake were independent of fish fat. C15:0, trans-C18:1(n-7) and CLA were found to be inversely associated with cardiovascular risk factors. Literature shows that the marine-derived omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid are also inversely related to cardiovasclular risk factors. This thesis shows that this is might also be true in a renal transplant recipients. In contrast, in this population, the plant-derived omega-3 fatty acid alpha-linolenic acid may be associated with an increased risk of mortality.

Context: Dairy intake in humans is commonly assessed using questionnaires, but the data collected are often biased. As a result, there is increasing interest in biomarkers of dairy fat. To date, there has been no overview of the fatty acids suitable for use as biomarkers of dairy fat intake.Objective: This systematic review and meta-analysis of observational studies was performed to identify circulating fatty acids as biomarkers of total dairy and dairy fat intakes in the general population.Data Sources: MEDLINE, Embase, and Web of Knowledge databases were searched for eligible studies published until June 2017.Study Selection: Articles were included when a correlation between circulating dairy fatty acids and intakes of total dairy and dairy fat was found, as measured by dietary assessment tools.Data Extraction: Two authors extracted data independently and assessed the risk of bias. An adapted form of the Newcastle-Ottawa Scale was used for quality assessment.Results: Data were pooled using the random-effects model. Meta-analysis revealed that the fatty acids in plasma/serum were significantly correlated with intakes of total dairy (C14:0 [r = 0.15; 95%CI, 0.11 - 0.18], C15:0 [r = 0.20; 95%CI, 0.13 - 0.27], and C17:0 [r = 0.10; 95%CI, 0.03 - 0.16] and dairy fat (C14:0 [r = 0.16; 95%CI, 0.10 - 0.22], C15:0 [r = 0.33; 95%CI, 0.27 - 0.39], C17:0 [r = 0.19; 95%CI, 0.14 - 0.25], and trans-C16:1n-7 [r = 0.21; 95%CI, 0.14 - 0.29).Conclusions: C14:0, C15:0, C17:0, and trans-C16:1n-7 were identified as biomarkers of total dairy and dairy fat intakes in the general population. In light of the suboptimal measurement techniques used in some studies, correlations with trans-C18:1n-7 and conjugated linoleic acid require further investigation.

Glucocorticoid treatment decreases liver insulin sensitivity and may modify fatty acid metabolism. We investigated the influence of oral prednisolone on indices for de novo lipogenesis (DNLi), stearoyl-CoA desaturase (SCDi) and Δ6-desaturase (D6Di) activity in healthy males. In addition, we explored whether the changes may be associated with prednisolone-induced changes in glucose and lipid metabolism and insulin sensitivity. Thirty-two healthy young males (mean ± SD age 22 ± 3 years, BMI 22.4 ± 1.7 kg/m2) were allocated to receive prednisolone 7.5 mg/day (PRED7.5; n = 12), prednisolone 30 mg/day (PRED30; n = 12), or placebo (n = 8) in a randomized double-blind fashion for 2 weeks. Fatty acid compositions of plasma cholesteryl esters (CE), phospholipids (PL) and triglycerides (TG) were measured at baseline and on day 14. DNLi, SCDi and D6Di were estimated from product/precursor ratios in CE, with DNLi primary deriving from 16:1ω7/18:2ω6, SCDi from 16:1ω7/16:0 and D6Di from 22:6ω3/20:5ω3. Ratios were also assessed in PL and TG. In CE, PRED30 increased DNLi by 51.2 [95%CI 14.8; 87.6]%, increased SCDi by 48.6 [18.7; 78.5]%, and decreased D6Di by 57.7 [-91.8; -23.5]% (p ≤ 0.01 for all, compared to placebo). The prednisolone-induced increases in DNLi and SCDi were positively correlated with insulin sensitivity (r = 0.35 and 0.50, respectively). Similar results were found in PL and TG. Prednisolone dose-dependently increases DNLi and SCDi and decreases D6Di in plasma CE, PL and TG in healthy males after 2 weeks. The observed unfavorable effects on fatty acid metabolism were related to the induction of glucocorticoid-induced insulin resistance.

The effect of marine-derived omega-3 polyunsaturated fatty acids (n-3 PUFA) on long-term outcome in renal transplant recipients (RTR) remains unclear. We investigated whether marine-derived n-3 PUFA intake is associated with all-cause and cardiovascular (CV) mortality in RTR. Intake of eicosapentaenoic acid plus docosahexaenoic acid (EPA-DHA) was assessed using a validated Food Frequency Questionnaire. Cox regression analyses were performed to evaluate the associations of EPA-DHA intake with all-cause and CV mortality. We included 627 RTR (age 53 +/- 13 years). EPA-DHA intake was 102 (42-215) mg/day. During median follow-up of 5.4 years, 130 (21%) RTR died, with 52 (8.3%) due to CV causes. EPA-DHA intake was associated with lower risk of all-cause mortality (Hazard Ratio (HR) 0.85; 95% confidence interval (95% CI) 0.75-0.97). Age (p = 0.03) and smoking status (p = 0.01) significantly modified this association, with lower risk of all-cause and CV mortality particularly in older (HR 0.75, 95% CI 0.61-0.92; HR 0.68, 95% CI 0.48-0.95) and non-smoking RTR (HR 0.80, 95% CI 0.68-0.93; HR 0.74, 95% CI 0.56-0.98). In conclusion, marine-derived n-3 PUFA intake is inversely associated with risk of all-cause and CV mortality in RTR. The strongest associations were present in subgroups of patients, which adds further evidence to the plea for EPA-DHA supplementation, particularly in elderly and non-smoking RTR.