Very Long Chain Saturated Fatty Acids Research Articles

Association of circulation very long chain saturated fatty acids with depression in NHANES 2011–2014

BackgroundRecent studies have shown that elevated levels of medium and long chain saturated fatty acids are associated with an increased risk of depression. However, little is known about the effect of very long chain saturated fatty acids (VLSFAs) on depression. Therefore, our study aimed to examine the association between VLSFAs and depression in the US adult population. MethodsA total of 2706 participants with serum VLSFAs detection from NHANES 2011–2014 were included in the study. Logistic regression models were used to evaluate the association between quartile levels of serum VLSFAs (20:0, 22:0, 23:0, 24:0, and total VLSFA) and depression. ResultsAfter adjusting for multiple variables, we found that increased circulating levels of 22:0, 23:0, 24:0 and total VLSFA were linearly associated with a reduced risk of depression (model 3, Q4 OR: 0.658, 95 % CI: 0.438–0.989, P-trend = 0.023; OR: 0.515, 95 % CI: 0.339–0.782, P-trend<0.001; OR: 0.556, 95 % CI: 0.370–0.835, P-trend = 0.003; OR: 0.652, 95 % CI: 0.435–0.976, P-trend = 0.021, respectively). Additionally, individuals with the highest serum ratios of 22:0/16:0, 23:0/16:0, 24:0/16:0 and total VLSFA/16:0 also had a lower risk of depression after adjusting for multiple variables compared to the group with the lowest serum VLSFAs/16:0 (P-trend = 0.001, <0.001, 0.001 and 0.004, respectively). Moreover, the decreasing trend of depression associated with increased VLSFAs/18:0 remained significant. ConclusionIn conclusion, our findings suggest that increased circulating levels of 22:0, 23:0, 24:0 and total VLSFA may have a protective effect against the risk of depression.

Association between the circulating very long-chain saturated fatty acid and cognitive function in older adults: findings from the NHANES

BackgroundAge-related cognitive decline has a significant impact on the health and longevity of older adults. Circulating very long-chain saturated fatty acids (VLSFAs) may actively contribute to the improvement of cognitive function. The objective of this study was to investigate the associations between arachidic acid (20:0), docosanoic acid (22:0), tricosanoic acid (23:0), and lignoceric acid (24:0) with cognitive function in older adults.MethodsThis study used a dataset derived from the 2011–2014 National Health and Nutrition Examination Survey (NHANES). A total of 806 adults (≥ 60 years) were included who underwent comprehensive cognitive testing and plasma fatty acid measurements. Multivariable linear regression, restricted cubic spline (RCS), and interaction analyses were used to assess associations between VLSFAs and cognitive function. Partial Spearman’ s correlation analysis was used to examine the correlations between VLSFAs and palmitic acid (16:0), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglycerides, systemic inflammatory markers, and dietary nutrients.ResultsMultivariable linear regression analysis, adjusting for sociodemographic, clinical conditions, and lifestyle factors, showed that 22:0 and 24:0 levels were positively associated with better global cognitive function (β = 0.37, 95% confidence interval [CI] = 0.01, 0.73; β = 0.73, 95% CI = 0.29, 1.2, respectively) as well as better CEARD-DR Z-score (β = 0.82, 95% CI = 0.36, 1.3 and β = 1.2, 95% CI = 0.63, 1.8, respectively). RCS analysis showed linear associations between higher 22:0 and 24:0 levels and better cognitive performance in both global cognitive function and CERAD-DR tests.ConclusionsThe study suggests that higher levels of 22:0 and 24:0 are associated with better global cognitive function in older adults. 22:0 and 24:0 may be important biomarkers for recognizing cognitive impairment, and supplementation with specific VLSFAs (22:0 and 24:0) may be an important intervention to improve cognitive function. Further studies are needed to elucidate the underlying biological mechanisms between VLSFAs and cognitive function.

C15:0 and C17:0 partially mediate the association of milk and dairy products with bladder cancer risk

The relationship between saturated fatty acids (SFA) and bladder cancer (BC) risk has been conflicting. Our aim was to investigate the relationship between erythrocyte membrane SFA and BC risk. A total of 404 participants were enrolled in the study (including 112 cases and 292 controls). A validated food frequency questionnaire was used to assess the food intake. The constitutive composition of fatty acids in the erythrocyte membrane was measured by gas chromatography. After adjustment for BC risk factors, SFA had no significant association with BC risk. However, C18:0 was positively linked with BC risk with an odds ratio (OR; 95% CI) of 2.99 (1.37-6.53). In contrast, very-long-chain saturated fatty acids (VLCSFA), especially C24:0, were negatively related to BC risk with an OR (95% CI) of 0.28 (0.12-0.65) for VLCSFA and 0.33 (0.15-0.75) for C24:0. Higher total odd-chain SFA (C15:0 and C17:0) were associated with a lower risk of BC with OR (95% CI) of 0.18 (0.076-0.44), 0.18 (0.068-0.47), 0.34 (0.14-0.81), respectively. After subgroup analysis, the protective effects C15:0 and C17:0 were still remained. Receiver operating characteristic analysis displayed that the combination of C15:0 and C17:0 indexes increased the accurate predictive rate of BC risk. Further mediation effect analysis showed that C15:0 and C17:0 could be used as partial mediation effectors for milk and dairy products and bladder carcinogenesis. Overall, the combination of odd-chain SFA (C15:0 and C17:0) in the erythrocyte membrane could serve as a reliable mediator and predictor, indicating a relationship between a high intake of milk and dairy products and a lower risk of BC.

Association of Circulating Very Long-Chain Saturated Fatty Acids With Cardiovascular Mortality in NHANES 2003-2004, 2011-2012.

Limited studies have shown a protective effect of very long-chain saturated fatty acids (VLSFAs) on healthy aging, diabetes, heart failure, and risk factors related to cardiovascular disease (CVD), but the role of VLSFAs on mortality risk is unclear. We aimed to investigate the association of serum docosanoic acid (C22:0) and serum lignoceric acid (C24:0) with all-cause and disease-specific mortality and to confirm the effect of VLSFAs on mortality risk in the whole, hyperlipidemia, and hypertensive populations. A total of 4132 individuals from the 2003-2004, 2011-2012 National Health and Nutrition Examination Survey (NHANES) were included in this study. There were 1326 and 1456 participants in the hyperlipidemia and hypertensive population, respectively. Mortality information was confirmed using the National Death Index (NDI). Multiple model calibration was performed using Cox regression analysis for known risk factors to explore the association between circulating VLSFAs and all-cause or CVD or coronary heart disease (CHD) mortality. In the whole population, individuals with higher circulating C22:0 and C24:0 as a percentage of total serum fatty acid levels reduced the risks of mortality of all-cause (C22:0: HR = .409; 95% CI, 0.271-0.618; C24:0: HR = 0.430; 95% CI, 0.283-0.651), CVD (C22:0: HR = 0.286; 95% CI, 0.134-0.612; C24:0: HR = 0.233; 95% CI, 0.101-0.538), and CHD (C22:0: HR = 0.401; 95% CI, 0.187-0.913; C24:0: HR = 0.263; 95% CI, 0.082-0.846). Similar to the whole population, individuals with higher circulating C22:0 and C24:0 as a percentage of total serum fatty acid levels in the hyperlipidemia and hypertensive populations were also protective for all-cause, CHD, and CVD mortality. Our results confirm the protective effect of high levels of circulating VLSFAs (C22:0 and C24:0) on CVD, CHD, and all causes of death in the whole, hyperlipidemia, and hypertensive populations.

Association of Serum Very-Long-Chain Saturated Fatty Acids With Changes in Insulin Sensitivity and β-Cell Function: The Prospective Metabolism and Islet Cell Evaluation (PROMISE) Cohort.

A unique group of circulating very long-chain saturated fatty acids (VLCSFA), including arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0), have been associated with lower risk of type 2 diabetes, although associations with early metabolic risk phenotypes preceding type 2 diabetes have received limited study. We aimed to examine the associations of VLCSFA with longitudinal changes in insulin sensitivity and beta-cell function in a cohort at risk of type 2 diabetes. VLCSFA in the four main serum pools (phospholipid, triacylglycerol, cholesteryl ester, and non-esterified fatty acid) were extracted from fasting baseline samples (n=467). Generalized Estimating Equations were used to determine the associations between VLCSFA and changes over 9 years in validated indices of insulin sensitivity (HOMA2-%S and ISI) and beta-cell function (IGI, IGI/IR and ISSI-2). Associations of VLCSFA with outcomes were strongest in the triacylglycerol lipid pool: 20:0 was positively associated with both insulin sensitivity and beta-cell function (5.01% increase in HOMA2-%S and 4.01-6.28% increase in IGI/IR and ISSI-2 per SD increase in 20:0); 22:0 was positively associated with insulin sensitivity with 6.55% increase in HOMA2-%S and a 5.80% increase in ISI per SD increase in 22:0. Lastly, 24:0 was positively associated with insulin sensitivity and beta-cell function (7.94-8.45% increase in HOMA2-%S and ISI, and 4.61-6.93% increase in IGI/IR and ISSI-2 per SD increase in 24:0). Fewer significant associations were observed in the cholesteryl ester and non-esterified pools. Overall, our results indicate positive longitudinal associations of VLCSFA with insulin sensitivity and beta-cell function, especially within the triacylglycerol pool.

A novel ELOVL4 variant, L168S, causes early childhood-onset Spinocerebellar ataxia-34 and retinal dysfunction: a case report

Spinocerebellar ataxia 34 (SCA34) is an autosomal dominant inherited disease characterized by age-related cerebellar degeneration and ataxia caused by mutations in the Elongation of Very Long Chain Fatty Acid-4 (ELOVL4) gene. The ELOVL4 enzyme catalyzes the biosynthesis of both very long chain saturated fatty acids (VLC-SFA) and very long chain polyunsaturated fatty acids (VLC-PUFA) that are important for neuronal, reproductive, and skin function. Several variants in ELOVL4 have been shown to cause different tissue-specific disorders including SCA34 with or without Erythrokeratodermia Variabilis (EKV), a skin condition characterized by dry, scaly skin, Autosomal Dominant Stargardt-Like Macular Dystrophy (STGD3), and seizures associated with neuro-ichthyotic disorders. What is puzzling is how different mutations in the same gene seem to cause different tissue-specific disorders. To date, no SCA34 patients have presented with both SCA34 and STGD3 pathology that is caused by ELOVL4 variants that cause truncation of ELOVL4. Here, we report a novel case of an early childhood onset and rapidly progressive cerebellar degeneration and retinal dysfunction in a Belgian-Italian girl who developed severe dysarthria and gait problems starting at about 3.5 years of age and progressed to immobility by 4.5 years of age. Brain magnetic resonance imaging (MRI) revealed progressive vermian, cerebellar, cortical atrophy, progressive corpus callosum slimming, and hot cross bun sign visible on the MRI. Ophthalmological examinations also revealed progressive macular dysfunction as measured by electroretinography. Using exome sequencing, we identified a novel heterozygous ELOVL4 variant, c.503 T > C (p. L168S) in the patient. To understand the enzymatic function of this novel ELOVL4 variant and how it alters the levels of VLC-PUFA and VLC-SFA biosynthesis to contribute to cerebellar and retinal dysfunction, we expressed wild-type ELOVL4 or the L168S ELOVL4 variant in cell culture and supplemented the cultures with VLC-PUFA or VLC-SFA precursors. We showed that the L168S ELOVL4 variant is deficient in the biosynthesis of VLC-SFA and VLC-PUFA. Our work suggests that differential depletion of these fatty acids may be a contributing factor to the pathogenic mechanism of SCA34 with or without EKV. Further studies will help further define how the different ELOVL4 variants cause different tissue-specific disorders with variable ages of onset.

Serum Saturated Fatty Acids including Very Long-Chain Saturated Fatty Acids and Colorectal Cancer Risk among Chinese Population.

The association between circulating saturated fatty acids (SFAs) including very long-chain SFAs (VLCSFAs) and colorectal cancer (CRC) risk has not been clearly established. To investigate the association between serum SFAs and CRC risk in Chinese population, 680 CRC cases and 680 sex and age-matched (5-year interval) controls were recruited in our study. Serum levels of SFAs were detected by gas chromatography. Unconditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between serum SFAs and CRC risk. Results showed that total SFAs were positively associated with the risk of CRC (adjusted OR quartile 4 vs. 1 = 2.64, 95%CI: 1.47-4.74). However, VLCSFAs were inversely associated with CRC risk (adjusted OR quartile 4 vs. 1 = 0.51, 95%CI: 0.36-0.72). Specifically, lauric acid, myristic acid, palmitic acid, heptadecanoic acid, and arachidic acid were positively associated with CRC risk, while behenic acid and lignoceric acid were inversely associated with CRC risk. This study indicates that higher levels of total serum SFAs and lower levels of serum VLCSFAs were associated with an increased risk of CRC in Chinese population. To reduce the risk of CRC, we recommend reducing the intake of foods containing palmitic acid and heptadecanoic acid such as animal products and dairy products, and moderately increasing the intake of foods containing VLCSFAs such as peanuts and canola oil.

Lifestyle Factors Associated with Circulating Very Long-Chain Saturated Fatty Acids in Humans: A Systematic Review of Observational Studies.

Recent observational studies have documented inverse associations of circulating very long-chain saturated fatty acids (VLCSFAs), namely arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0), with cardiometabolic outcomes. In addition to their endogenous production, it has been suggested that dietary intake or an overall healthier lifestyle may influence VLCSFA concentrations; however, a systematic review of the modifiable lifestyle contributors to circulating VLCSFAs is lacking. Therefore, this review aimed to systematically assess the effects of diet, physical activity, and smoking on circulating VLCSFAs. Following registration on PROSPERO (International Prospective Register of Systematic Reviews) (ID: CRD42021233550), a systematic search of observational studies was conducted in MEDLINE, EMBASE, and The Cochrane databases up to February 2022. A total of 12 studies consisting of mostly cross-sectional analyses were included in this review. The majority of the studies documented the associations of dietary intake with total plasma or red blood cell VLCSFAs, in which a range of macronutrients and food groups were examined. Two cross-sectional analyses showed a consistent positive association between total fat and peanut intake with 22:0 and 24:0 and an inverse association between alcohol intake and 20:0 and 22:0. Furthermore, a moderate positive association between physical activity and 22:0 and 24:0 was observed. Lastly, there were conflicting results on the effects of smoking on VLCSFA. Although most studies had a low risk of bias; the findings of this review are limited by the bi-variate analyses presented in the majority of the included studies, therefore, the impact of confounding is unclear. In conclusion, although the current observational literature examining lifestyle determinants of VLCSFAs is limited, existing evidence suggests that circulating 22:0 and 24:0 may be influenced by higher total and saturated fat consumption and nut intake.

Abstract 11634: Fatty Acid Length Dictates Association of Sphingomyelins With Sudden Cardiac Death

Background: Sudden cardiac death (SCD) is a leading cause of mortality worldwide and is precipitated primarily by ventricular tachyarrhythmias related to coronary artery disease. Sphingolipids, composed of ceramides and sphingomyelins, may influence the pathophysiology and risk of SCD through multiple biological activities. Whether the length of the fatty acid conjugated to the sphingolipid species is associated with SCD risk is not known. Methods and Results: Among 4612 Cardiovascular Health Study participants, we identified 215 patients who experienced SCD over a median follow up of 10.2 years. We examined 8 sphingolipids: ceramide and sphingomyelin species containing palmitic acid and species containing, respectively, the very-long-chain saturated fatty acids (VLSFA) arachidic, behenic, and lignoceric acids. In adjusted Cox regression analyses, ceramides and sphingomyelins with palmitic acid were associated with increased SCD risk per standard deviation log difference (ceramide with palmitic acid: hazard ratio 1.34, 95% CI 1.12-1.59; sphingomyelin with palmitic acid: hazard ratio 1.37, 95% CI 1.12-1.67). In contrast, one sphingomyelin with a VLSFA trended towards an association with reduced SCD risk (sphingomyelin with arachidic acid: hazard ratio 0.83, 95% CI 0.71-0.98). Associations were weakened when adjusted for C-reactive protein (CRP), B-type natriuretic peptide, and troponin-T, but did not differ significantly by age, sex, race, body-mass index, or history of coronary heart disease. In comparison, ceramide with palmitic acid was associated with higher risk of nonfatal myocardial infarction, and ceramide with the VLSFA lignoceric acid trended towards lower risk. Conclusions: Our results suggest associations between sphingolipid species and SCD, differing by the length of the acylated saturated fatty acid. Palmitic acid-containing sphingolipids were strongly associated with increased SCD risk, whereas VLSFA-containing sphingomyelins trended toward reduced SCD risk. The study indicates that plasma sphingolipids may influence the risk of SCD, independent of traditional cardiovascular risk factors. Our findings may provide further insight into the pathogenesis of SCD and enhance risk stratification tools.

Saturated Fatty Acid Blood Levels and Cardiometabolic Phenotype in Patients with HFpEF: A Secondary Analysis of the Aldo-DHF Trial.

Background: Circulating long-chain (LCSFAs) and very long-chain saturated fatty acids (VLSFAs) have been differentially linked to risk of incident heart failure (HF). In patients with heart failure with preserved ejection fraction (HFpEF), associations of blood SFA levels with patient characteristics are unknown. Methods: From the Aldo-DHF-RCT, whole blood SFAs were analyzed at baseline in n = 404 using the HS-Omega-3-Index® methodology. Patient characteristics were 67 ± 8 years, 53% female, NYHA II/III (87%/13%), ejection fraction ≥50%, E/e’ 7.1 ± 1.5; and median NT-proBNP 158 ng/L (IQR 82–298). Spearman´s correlation coefficients and linear regression analyses, using sex and age as covariates, were used to describe associations of blood SFAs with metabolic phenotype, functional capacity, cardiac function, and neurohumoral activation at baseline and after 12-month follow-up (12 mFU). Results: In line with prior data supporting a potential role of de novo lipogenesis-related LCSFAs in the development of HF, we showed that baseline blood levels of C14:0 and C16:0 were associated with cardiovascular risk factors and/or lower exercise capacity in patients with HFpEF at baseline/12 mFU. Contrarily, the three major circulating VLSFAs, lignoceric acid (C24:0), behenic acid (C22:0), and arachidic acid (C20:0), as well as the LCSFA C18:0, were broadly associated with a lower risk phenotype, particularly a lower risk lipid profile. No associations were found between cardiac function and blood SFAs. Conclusions: Blood SFAs were differentially linked to biomarkers and anthropometric markers indicative of a higher-/lower-risk cardiometabolic phenotype in HFpEF patients. Blood SFA warrant further investigation as prognostic markers in HFpEF. One Sentence Summary: In patients with HFpEF, individual circulating blood SFAs were differentially associated with cardiometabolic phenotype and aerobic capacity.

Circulating saturated fatty acids and risk of gestational diabetes mellitus: A cross-sectional study and meta-analysis.

BackgroundPrevious studies have analyzed the associations between the circulating saturated fatty acids (SFAs) and gestational diabetes mellitus (GDM), but no consistent conclusions have been reached. The aim of this study was to evaluate whether plasma SFAs were in correlation with GDM risks in our in-house women cross-sectional study and to better define their associations on the clinical evidence available to date by a dose-response meta-analysis.MethodsWe carried out a cross-sectional study of 807 pregnant women in 2018–2019 (Shanghai, China). GDM was defined according to the criteria of the International Association of Diabetes and Pregnancy Study Groups (IADPSG). Gas chromatography was used to determine the plasma fatty acids (FAs) in the 24–28 gestational weeks. The SFAs levels of non-GDM and GDM participants were compared by Mann–Whitney test, and the association between SFAs and GDM was explored by multivariate logistic models. Further, the potential diagnostic value of plasma SFAs was evaluated using the method of receiver operating characteristic (ROC) analysis. For meta-analysis, five databases were systematically searched from inception to March 2022, and we included 25 relevant studies for calculating pooled standard mean differences (SMDs) and 95% CI to describe the differences in SFAs profiles between non-GDM and GDM women. Study-specific, multivariable-adjusted ORs and 95% CI were also pooled using a fixed-effect model or random-effects model according to the heterogeneity to evaluate the associations between circulating SFAs and GDM prevalence.ResultsIn our cross-sectional study, we found plasma proportion of palmitic acid (C16:0) was positively associated (aOR: 1.10 per 1% increase; 95% CI: 1.04, 1.17), while plasma stearic acid (C18:0) (aOR: 0.76 per 1% increase; 95% CI: 0.66, 0.89), arachidic acid (C20:0) (aOR: 0.92 per 0.1% increase; 95% CI: 0.87, 0.97), behenic acid (C22:0) (aOR: 0.94 per 0.1% increase; 95% CI: 0.92, 0.97), and lignoceric acid (C24:0) (aOR: 0.94 per 0.1% increase; 95% CI: 0.92, 0.97) were inversely associated with GDM. The area under the receiver operative characteristic curve increased from 0.7503 (the basic diagnostic model) to 0.8178 (p = 0.002) after adding total very-long-chain SFAs (VLcSFAs). A meta-analysis from 25 studies showed the circulating levels of three individual SFAs of GDM women were different from those of normal pregnant women. The summarized ORs for GDM was 1.593 (95% CI: 1.125, 2.255, p = 0.009), 0.652 (95% CI: 0.472, 0.901, p = 0.010) and 0.613 (95% CI: 0.449, 0.838, p = 0.002), respectively, comparing the highest vs. lowest quantile of the concentrations of C16:0, C22:0, and C24:0.ConclusionOur results, combined with the findings from meta-analysis, showed that women with GDM had a particular circulating SFA profile, characterized by higher levels of palmitic acid, and lower levels of VLcSFAs. Alterations in the chain lengths of blood SFA profile were shown to be associated with the occurrence of GDM.

Effect of Crushing Peanuts on Fatty Acid and Phenolic Bioaccessibility: A Long-Term Study.

Background: Peanuts are consumed worldwide and have been linked to multiple health benefits. Processing may affect the bioavailability of peanut bioactive compounds. Therefore, we aim to evaluate the effects of crushing peanuts on the bioavailability of fatty acids and phenolic compounds in healthy adults. Methods: 44 participants from the ARISTOTLE study consumed 25 g/day of whole peanuts (WP) or 32 g/day of peanut butter (PB) for 6 months. Fatty acids and phenolic compounds in peanut products and biological samples were assessed by gas chromatography coupled to flame ionization detection and liquid chromatography coupled to high resolution mass spectrometry, respectively. Results: Plasma concentrations of very long chain saturated fatty acids (VLCSFAs) increased significantly after 6 months of WP or PB intake (p < 0.001 in both cases). Participants in the WP group excreted twice as many VLCSFAs in feces as those in the PB group (p = 0.012). The most abundant polyphenols found in WP and PB were p-coumaric and isoferulic acids. Urinary excretion of isoferulic acid increased after the intake of WP and PB (p = 0.032 and p = 0.048, respectively), with no significant difference observed between interventions. Conclusion: The crushing step in peanut butter production seems to enhance the bioavailability of bioactive compounds.

Very long-chain saturated fatty acids and diabetes and cardiovascular disease.

Purpose of reviewIn contrast to other saturated fatty acids, very long-chain saturated fatty acids (VLSFAs) have received limited attention The purpose of this review is to summarize the associations of VLSFAs, including arachidic acid, behenic acid, and lignoceric acid, with cardiovascular disease outcomes and type 2 diabetes; to discuss the findings implications; and to call for future studies of the VLSFAs.Recent findingsIncreased levels of circulating VLSFAs have been found associated with lower risks of incident heart failure, atrial fibrillation, coronary heart disease, mortality, sudden cardiac arrest, type 2 diabetes, and with better aging. The VLSFA associations are paralleled by associations of plasma ceramide and sphingomyelin species carrying a VLSFA with lower risks of heart failure, atrial fibrillation, and mortality, suggesting VLSFAs affect the biological activity of ceramides and sphingomyelins thereby impacting health. For diabetes, there is no such parallel and the associations of VLSFAs with diabetes may be confounded or mediated by triglyceride and circulating palmitic acid, possible biomarkers of de novo lipogenesis.SummaryIn many ways, the epidemiology has preceded our knowledge of VLSFAs biology. We hope this review will spur interest from the research community in further studying these potentially beneficial fatty acids.

Low Circulating Concentrations of Very Long Chain Saturated Fatty Acids Are Associated with High Risk of Mortality in Kidney Transplant Recipients.

Kidney transplant recipients (KTR) are at increased risk of mortality, particularly from infectious diseases, due to lifelong immunosuppression. Although very long chain saturated fatty acids (VLSFA) have been identified as crucial for phagocytosis and clearance of infections, their association with mortality in immunocompromised patient groups has not been studied. In this prospective cohort study we included 680 outpatient KTR with a functional graft ≥1 year and 193 healthy controls. Plasma VLSFA (arachidonic acid (C20:0), behenic acid (C22:0) and lignoceric acid (C24:0)) were measured by gas chromatography coupled with a flame ionization detector. Cox regression analyses was used to prospectively study the associations of VLSFA with all-cause and cause-specific mortality. All studied VLSFA were significantly lower in KTR compared to healthy controls (all p < 0.001). During a median (interquartile range) follow-up of 5.6 (5.2–6.3) years, 146 (21%) KTR died, of which 41 (28%) died due to infectious diseases. In KTR, C22:0 was inversely associated with risk of all-cause mortality, with a HR (95% CI) per 1-SD-increment of 0.79 (0.64–0.99), independent of adjustment for potential confounders. All studied VLSFA were particularly strongly associated with mortality from infectious causes, with respective HRs for C20:0, C22:0 and C24:0 of 0.53 (0.35–0.82), 0.48 (0.30–0.75), and 0.51 (0.33–0.80), independent of potential confounders. VLSFA are inversely associated with infectious disease mortality in KTR after adjustment, including HDL-cholesterol. Further studies are needed to assess the effect of VLSFA-containing foods on the risk of infectious diseases in immunocompromised patient groups.

Consumption of peanut products improves memory and stress response in healthy adults from the ARISTOTLE study: A 6-month randomized controlled trial

Peanuts are rich in bioactive compounds that may have a positive impact on memory and stress response. To evaluate the effect of regular consumption of peanut products on cognitive functions and stress response in healthy young adults. A three-arm parallel-group randomized controlled trial was conducted in 63 healthy young adults that consumed 25g/day of skin roasted peanuts (SRP, n=21), 32g/d of peanut butter (PB, n=23) or 32g/d of a control butter made from peanut oil (free of phenolic compounds and fiber) (CB, n=19) for six months. Polyphenol intake, cognitive functions, and anxiety and depression scores were evaluated using validated tests. Fecal short-chain fatty acids (SCFAs) and plasma and fecal fatty acids were assessed by chromatographic methods. Urinary cortisol was quantified by an enzymatic method. Comparing the two interventions with the control, a significant reduction in anxiety scores was observed in the SRP compared to the CB group. After the intervention, consumers of SRP and PB had an improved immediate memory (p=0.046 and p=0.011). Lower anxiety scores were associated with SRP and PB (p<0.001 and p=0.002, respectively) and lower depression scores with SRP, PB and CB (p=0.007, p=0.003 and p=0.032, respectively). Memory functions and stress response were significantly correlated with polyphenol intake, fecal SCFAs, plasma and fecal very long chain saturated fatty acids (VLCSFAs). Regular peanut and peanut butter consumption may enhance memory function and stress response in a healthy young population. These effects seem to be associated with the intake of peanut polyphenols, increased levels of fecal SCFAs, and unexpectedly, VLCSFAs, which were also present in the control product.

Assessment of Plasma Phospholipid Very-Long-Chain Saturated Fatty Acid Levels and Healthy Aging

Identifying novel factors that protect against age-related diseases and promote healthy aging is critical to public health. Higher levels of circulating very-long-chain saturated fatty acids (VLSFAs) are integrated biomarkers of diet and metabolism shown to have beneficial associations in cardiovascular disease and total mortality, but whether they are associated with overall healthy aging is unknown. To examine the association of circulating levels of 3 VLSFAs with unhealthy aging events, including incident chronic disease (cardiovascular disease, cancer, lung disease or severe kidney disease), physical dysfunction, and cognitive decline. This cohort study used 1992 to 2014 data from the Cardiovascular Health Study (CHS). The CHS is a multicenter, population-based study of cardiovascular disease among older adults. Among the 4559 CHS participants with available fatty acid data, 1879 participants who had an age-related event before their first measurement were excluded. Data analysis was performed in 2020. Plasma phospholipid VLSFA levels were measured by thin-layer chromatography followed by gas chromatography. The main outcome was the hazard ratio (HR) of an incident unhealthy aging event associated with serial measures of plasma arachidic acid, behenic acid, and lignoceric acid. Among the 2680 study participants (976 men [36.4%]), the mean (SD) age was 74.7 (4.8) years old at entry. During a median (interquartile range) of 6.4 (2.9-12.9) years of follow-up, 2484 participants experienced an unhealthy event. Compared with the lowest quintile, levels of behenic acid in the highest quintile of the fatty acid distribution were associated with 15% lower risk of an unhealthy event (HR, 0.85; 95% CI, 0.74-0.97; P for trend = .01) after adjustment for demographic characteristics, lifestyle factors, and clinical conditions. In analogous comparisons, levels of lignoceric acid were similarly associated with 16% lower risk of an unhealthy event (HR, 0.84; 95% CI, 0.73-0.95; P for trend = .001). These findings suggest that higher levels of circulating behenic acid and lignoceric acid are associated with lower risk of unhealthy aging events. These results highlight the need to explore determinants of circulating VLSFAs for potential novel efforts to promote healthy aging.

Circulating Very-Long-Chain Saturated Fatty Acids Were Inversely Associated with Cardiovascular Health: A Prospective Cohort Study and Meta-Analysis.

Saturated fatty acids with different chain lengths have different biological activities, but little is known about very-long-chain saturated fatty acids (VLCSFAs). This study investigated the associations between the circulating VLCSFAs and cardiovascular health. This community-based cohort study included 2198 adults without carotid artery plaques (CAPs) at baseline. The percentage of baseline erythrocyte VLCSFA (arachidic acid (C20:0), behenic acid (C22:0), and lignoceric acid (C24:0)) was measured by gas chromatography. The presence of CAPs was determined at baseline and every 3 years thereafter by ultrasound examination. A meta-analysis was conducted to summarize the pooled associations between circulating VLCSFAs and the risk of cardiovascular diseases (CVDs). During a median of 7.2 years of follow-up, 573 women (35.1%) and 281 men (49.6%) were identified as CAP incident cases. VLCSFAs were inversely related with CAP risk in women (all p-trend <0.05) but not in men. Multivariate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of CAPs for the highest (vs. lowest) quartile were 0.80 (0.63–1.01) for C20:0, 0.71 (0.56–0.89) for C22:0, 0.75 (0.59–0.94) for C24:0, and 0.69 (0.55–0.87) for total VLCSFAs in women. The pooled HRs (95% CIs) of CVDs for the highest (vs. lowest) circulating VLCSFAs from seven studies including 8592 participants and 3172 CVD events were 0.67 (0.57–0.79) for C20:0, 0.66 (0.48–0.90) for C22:0, and 0.57 (0.42–0.79) for C24:0, respectively. Our findings suggested that circulating VLCSFAs were inversely associated with cardiovascular health.

Genome-Wide Identification of Peanut KCS Genes Reveals That AhKCS1 and AhKCS28 Are Involved in Regulating VLCFA Contents in Seeds

The peanut (Arachis hypogaea L.) is an important oilseed crop worldwide. Compared to other common edible vegetable oils, peanut oil contains a higher content of saturated fatty acids (SFAs), approximately 20–40% of which are very long chain fatty acids (VLCFAs). To understand the basis for this oil profile, we interrogated genes for peanut β-ketoacyl-CoA synthase (KCS), which is known to be a key enzyme in VLCFA biosynthesis. A total of 30 AhKCS genes were identified in the assembled genome of the peanut. Based on transcriptome data, nine AhKCS genes with high expression levels in developing seeds were cloned and expressed in yeast. All these AhKCSs could produce VLCFAs but result in different profiles, indicating that the AhKCSs catalyzed fatty acid elongation with different substrate specificities. Expression level analysis of these nine AhKCS genes was performed in developing seeds from six peanut germplasm lines with different VLCFA contents. Among these genes, the expression levels of AhKCS1 or AhKCS28 were, 4–10-fold higher than that of any other AhKCS. However, only the expression levels of AhKCS1 and AhKCS28 were significantly and positively correlated with the VLCFA content, suggesting that AhKCS1 and AhKCS28 were involved in the regulation of VLCFA content in the peanut seed. Further subcellular localization analysis indicated that AhKCS1 and AhKCS28 were located at the endoplasmic reticulum (ER). Overexpression of AhKCS1 or AhKCS28 in Arabidopsis increased the contents of VLCFAs in the seed, especially for very long chain saturated fatty acids (VLCSFAs). Taken together, this study suggests that AhKCS1 and AhKCS28 could be key genes in regulating VLCFA biosynthesis in the seed, which could be applied to improve the health-promoting and nutritional qualities of the peanut.

Abstract P414: Biomarkers of Very Long-chain Saturated Fatty Acids and Incident Coronary Heart Disease: Prospective Evidence From 15 Cohorts in the Fatty Acids and Outcomes Research Consortium

Background: Biomarker levels of very long-chain saturated fatty acids (VLCSFAs) have been found to be favorably associated with cardiovascular risk factors including lower risk of diabetes and reduced triglycerides. Few studies have examined the association between VLCSFAs and coronary heart disease (CHD). Aims: To assess the association of circulating arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) with incident total, fatal, and nonfatal CHD. Methods: We used data from the Fatty Acids and Outcomes Research Consortium consisting of 15 prospective cohorts worldwide which included adults (age≥18 years) who were free of cardiovascular disease and had blood measurements of 20:0, 22:0, and 24:0 at baseline. A study protocol with standardized definitions of exposures, disease outcomes, and covariates was developed, for which each cohort conducted individual participant-level analysis. Cohort-specific associations were pooled using inverse variance-weighted meta-analysis to calculate the overall relative risk (RR) per interquintile range (difference between the 90 th and 10 th percentiles) and 95% confidence interval (CI). Results: Among 33,083 participants, 6,165 cases of total CHD were ascertained. The overall pooled RR and 95% CI were 0.96 (0.89, 1.02) for 20:0, 1.01 (0.92, 1.11) for 22:0, 0.94 (0.86, 1.02) for 24:0, and 0.96 (0.89, 1.04) for 20:0 + 22:0 + 24:0 ( Figure 1 ). However, we noted heterogeneity by lipid compartments, with significant inverse associations for higher 22:0 [0.77 (0.62, 0.96)], 24:0 [0.61 (0.49, 0.77)], and 20:0 + 22:0 + 24:0 [0.73 (0.60, 0.89)] in the total plasma/serum compartment but not in the phospholipid compartment. Similar associations were observed for fatal and nonfatal CHD and when using a random-effects model. Conclusion: Higher circulating VLCSFAs were not associated with total CHD in a global consortium of prospective studies. The finding of an inverse association with total CHD for VLCSFAs in the total plasma/serum compartment warrants further research.

Abstract P492: Circulating Sphingolipids and Risk of Mortality: The Cardiovascular Health Study

Introduction: Recent studies suggest that the type of saturated fatty acid bound to sphingolipids influences sphingolipid activity, and that associations of ceramides (Cer) and sphingomyelins (SM) with cardiovascular outcomes may differ by lipid species. The purpose of this study was to assess associations of Cer and SM species with mortality among 4,612 older adults from the Cardiovascular Health Study, a population-based prospective study of adults aged ≥65 y who were followed from 1992-2015. Hypothesis: Higher levels of circulating Cer and SM with palmitic acid (Cer-16) are associated with a higher risk of mortality (i.e., deaths from cardiovascular disease (CVD) and non-cardiovascular causes) while higher levels of Cer and SM with very-long chain saturated fatty acids arachidic acid (Cer-20 and SM-20), behenic acid (Cer-22 and SM-22), and lignoceric acid (Cer-24 and SM-24) are associated with a lower risk. Methods: The associations of each sphingolipid with mortality were assessed using Cox proportional hazards models. Models adjusted for age, sex, self-reported race, geographic area, education, smoking, alcohol use, BMI, activities of daily living, HDL and LDL cholesterol, triglycerides, systolic blood pressure, physical activity, use of hypertension or lipid-lowering drugs, self-reported health status, prevalent diabetes, CVD, heart failure (HF), and other sphingolipids species. Results: During a median follow-up of 10.2 years (range 0-23 years), 4,099 deaths occurred. At each time, higher levels of Cer-16 and SM-16 were associated with a higher risk of mortality, while higher levels of Cer-22, Cer-24, SM-20, SM-22, and SM-24 were associated with a lower risk of mortality (Figure). Models that did not adjust for diabetes, CVD, and HF produced similar results. Conclusions: These findings suggest that the associations of Cer and SM with the risk of death differ according to the length of their acylated saturated fatty acid, and support the need for future studies to explore mechanisms underlying these relations.