Alter Disease Risk Research Articles

Soil-Transmitted Helminth Prevalence and Infection Intensity Among Geographically and Economically Distinct Shuar Communities in the Ecuadorian Amazon

Soil-transmitted helminth (STH) infections can result in a variety of negative health outcomes (e.g., diarrhea, nutritional deficiencies). Market integration (MI; participation in market-based economies) has been suggested to alter levels of STH exposure due to associated changes in diet, sanitation, and behavior, but the effects are complicated and not well understood. Some effects of economic development result in decreased exposure to certain pathogens, and other factors can lead to higher pathogen exposure. With geographic location used as a proxy, the present study investigates the effects of economic development on parasite load among an indigenous population at multiple points along the spectrum of MI. This research has many implications for public health, including an increased understanding of how social and economic changes alter disease risk around the world and how changing parasite load affects other health outcomes (i.e., allergy, autoimmunity). Specifically, this study examines the prevalence of intestinal helminths among the Shuar, an indigenous group in the Morona-Santiago region of Ecuador, from 2 geographically/economically separated areas, with the following objectives: (1) report STH infection prevalence and intensity among Shuar; (2) explore STH infection prevalence and intensity as it relates to age distribution in the Shuar population; (3) compare STH infection patterns in geographically and economically separated Shuar communities at different levels of MI. Kato-Katz thick smears were made from fresh stool samples and examined to determine STH presence/intensity. Results indicate that 65% of the 211 participants were infected with at least 1 STH. Twenty-five percent of the sample had coinfections with at least 2 species of helminth. Infection was more common among juveniles (<15 yr) than adults. Infection prevalence and intensity was highest among more isolated communities with less market access. This study documents preliminary associations between STH infection and exposure to MI, with implications for public health research and interventions.

Association of selenium and copper with lipids in umbilical cord blood.

Altered levels of selenium and copper have been linked with altered cardiovascular disease risk factors including changes in blood triglyceride and cholesterol levels. However, it is unclear whether this can be observed prenatally. This cross-sectional study includes 274 singleton births from 2004 to 2005 in Baltimore, Maryland. We measured umbilical cord serum selenium and copper using inductively coupled plasma mass spectrometry. We evaluated exposure levels vis-à-vis umbilical cord serum triglyceride and total cholesterol concentrations in multivariable regression models adjusted for gestational age, birth weight, maternal age, race, parity, smoking, prepregnancy body mass index, n-3 fatty acids and methyl mercury. The percent difference in triglycerides comparing those in the highest v. lowest quartile of selenium was 22.3% (95% confidence interval (CI): 7.1, 39.7). For copper this was 43.8% (95% CI: 25.9, 64.3). In multivariable models including both copper and selenium as covariates, copper, but not selenium, maintained a statistically significant association with increased triglycerides (percent difference: 40.7%, 95% CI: 22.1, 62.1). There was limited evidence of a relationship of increasing selenium with increasing total cholesterol. Our findings provide evidence that higher serum copper levels are associated with higher serum triglycerides in newborns, but should be confirmed in larger studies.

Identification of New Genetic Susceptibility Loci for Breast Cancer Through Consideration of Gene‐Environment Interactions

Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10(-07)), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m(2) (OR = 1.26, 95% CI 1.15-1.38) but not in women with a BMI of 30 kg/m(2) or higher (OR = 0.89, 95% CI 0.72-1.11, P for interaction = 3.2 × 10(-05)). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci.

The role of nutrition on epigenetic modifications and their implications on health

Nutrition plays a key role in many aspects of health and dietary imbalances are major determinants of chronic diseases including cardiovascular disease, obesity, diabetes and cancer. Adequate nutrition is particularly essential during critical periods in early life (both pre- and postnatal). In this regard, there is extensive epidemiologic and experimental data showing that early sub-optimal nutrition can have health consequences several decades later. The hypothesis that epigenetic mechanisms may link such nutritional imbalances with altered disease risk has been gaining acceptance over recent years. Epigenetics can be defined as the study of heritable changes in gene expression that do not involve alterations in the DNA sequence. Epigenetic marks include DNA methylation, histone modifications and a variety of non-coding RNAs. Strikingly, they are plastic and respond to environmental signals, including diet. Here we will review how dietary factors modulate the establishment and maintenance of epigenetic marks, thereby influencing gene expression and, hence, disease risk and health.

Health consequences of exercise and inactivity: The endurance athlete: high aerobic capacity and improved longevity

Adaptations to the cardiovascular, pulmonary and skeletal muscle systems allow endurance athletes to perform exercise for prolonged periods and delay the onset of fatigue. These adaptations explain why the current men's marathon world record holder can run 42.195 km (26.2 miles) in a little over 2 hours at an average speed of over 20 km/h. The adaptations which enable sustained endurance performance also offer protection against many chronic diseases and increase average lifespan. For example, former cyclists who competed in the Tour de France before 1964 demonstrated a 17% increase in average longevity compared with the general population1. Therefore studying the elite endurance athlete can give us clues as to how partaking in regular physical activity, or failure to do so, alters disease risk and life expectancy.

Statistical colocalization of monocyte gene expression and genetic risk variants for type 1 diabetes

One mechanism by which disease-associated DNA variation can alter disease risk is altering gene expression. However, linkage disequilibrium (LD) between variants, mostly single-nucleotide polymorphisms (SNPs), means it is not sufficient to show that a particular variant associates with both disease and expression, as there could be two distinct causal variants in LD. Here, we describe a formal statistical test of colocalization and apply it to type 1 diabetes (T1D)-associated regions identified mostly through genome-wide association studies and expression quantitative trait loci (eQTLs) discovered in a recently determined large monocyte expression data set from the Gutenberg Health Study (1370 individuals), with confirmation sought in an additional data set from the Cardiogenics Transcriptome Study (558 individuals). We excluded 39 out of 60 overlapping eQTLs in 49 T1D regions from possible colocalization and identified 21 coincident eQTLs, representing 21 genes in 14 distinct T1D regions. Our results reflect the importance of monocyte (and their derivatives, macrophage and dendritic cell) gene expression in human T1D and support the candidacy of several genes as causal factors in autoimmune pancreatic beta-cell destruction, including AFF3, CD226, CLECL1, DEXI, FKRP, PRKD2, RNLS, SMARCE1 and SUOX, in addition to the recently described GPR183 (EBI2) gene.

Early childhood socioeconomic status is associated with circulating interleukin-6 among mid-life adults

It is proposed that socioeconomic conditions in early childhood effect immune programming, with poorer conditions resulting in adult phenotypes that are prone to inflammation. Recent evidence supports this possibility, showing an inverse association of childhood SES with adult markers of systemic inflammation. In this study, we further investigate this association, extending prior studies to include an examination of multiple indices of SES across distinct periods of childhood. Subjects were 112 men and women, 40-60 years of age (88.6% Caucasian). Childhood SES was indexed by a composite of three indicators of parental wealth (parental home and vehicle ownership, and number of bedrooms per child in the family home) averaged across 2 year periods of childhood between 1 and 18 years old. Higher adult serum concentrations of interleukin (IL)-6 were associated with lower SES in early childhood (years 1-2) (β=-.05, p<.05), associations that were independent of adult age, personal income, educational attainment, gender, race, body mass index, and physical activity. These associations support recent suggestions that the early environment may program immune phenotypes that contribute to disease risk.

Interaction of the inflammasome genes CARD8 and NLRP3 in abdominal aortic aneurysms

ObjectiveCholesterol crystals have been shown to cause inflammation, and ultimately atherosclerotic lesions through the activation of the NLRP3 inflammasome. As cholesterol crystals have also been found in the walls of patients with abdominal aortic aneurysms (AAA), it is possible that the NLRP3 inflammasome is involved in AAA and genetic variability within this protein complex could alter disease risk. The primary objective of this study was to assess whether there is genetic evidence for a role of the NLRP3 inflammasome in AAA by testing for association of AAA with functional single nucleotide polymorphisms (SNPs) in the CARD8 and NLRP3 genes. MethodsAAA patients (n=1151) and controls (n=727) were genotyped for CARD8 SNP rs2043211 and NLRP3 SNP rs35829419 using TaqMan SNP assays. IL1-β, C-reactive protein (CRP), and lipoprotein (a) [Lp(a)] were measured in the plasma of a subset of study participants. The Kruskal–Wallis Rank test was conducted to test for differences in mean concentration of IL1-β, CRP and Lp(a). Logistic regression was used to test for interaction between CARD8 and NLRP3. ResultsSignificantly higher mean concentration of plasma IL1-β was observed in study participants who were homozygous for the common C allele of NLRP3 rs35829419 (p=0.010). Interaction between rs2043211 and rs35829419 was observed in this dataset (χ2=6.22; p=0.044), which strengthened when adjusted for age, gender, smoking, diabetes, hypertension, and dyslipidemia (χ2=14.75; p=0.012); and separately for NOD2 genotype (χ2=14.06; p=0.015). ConclusionOur finding suggests genetic variability within the NLRP3 inflammasome may be important in the pathophysiology of AAA.

Diet induced epigenetic changes and their implications for health

Dietary exposures can have consequences for health years or decades later and this raises questions about the mechanisms through which such exposures are 'remembered' and how they result in altered disease risk. There is growing evidence that epigenetic mechanisms may mediate the effects of nutrition and may be causal for the development of common complex (or chronic) diseases. Epigenetics encompasses changes to marks on the genome (and associated cellular machinery) that are copied from one cell generation to the next, which may alter gene expression, but which do not involve changes in the primary DNA sequence. These include three distinct, but closely inter-acting, mechanisms including DNA methylation, histone modifications and non-coding microRNAs (miRNA) which, together, are responsible for regulating gene expression not only during cellular differentiation in embryonic and foetal development but also throughout the life-course. This review summarizes the growing evidence that numerous dietary factors, including micronutrients and non-nutrient dietary components such as genistein and polyphenols, can modify epigenetic marks. In some cases, for example, effects of altered dietary supply of methyl donors on DNA methylation, there are plausible explanations for the observed epigenetic changes, but to a large extent, the mechanisms responsible for diet-epigenome-health relationships remain to be discovered. In addition, relatively little is known about which epigenomic marks are most labile in response to dietary exposures. Given the plasticity of epigenetic marks and their responsiveness to dietary factors, there is potential for the development of epigenetic marks as biomarkers of health for use in intervention studies.

Prenatal Tobacco Smoke Exposure and Genomewide Methylation in Adulthood

Abstract Genomic DNA demethylation, including demethylation of repetitive elements (which comprise 45% of the human genome), has been linked to increased risk of breast and other cancers. Genomic DNA methylation can be altered prenatally and throughout life and may be a mechanism through which the environment alters disease risk. There is evidence that prenatal tobacco smoke exposure has a persistent impact on genomic DNA methylation; however, no study to date has assessed the association between prenatal smoke exposure and adult repetitive element methylation. We measured repetitive element methylation of Alu, LINE-1, and Sat2 using MethyLight in 92 members of the New York Women's Birth Cohort, a follow-up of former female participants of the New York site of the U.S. National Collaborative Perinatal Project (mean age at blood draw = 43.5, SD = 1.8). Prenatal smoke exposure was reported prospectively. We estimated associations using multivariable linear regression, and used the natural log of Alu, LINE-1, and Sat2 methylation level. Thirty-one (36%) participants were exposed to prenatal smoke. These participants were more likely to smoke at the time of interview (P &amp;lt; 0.01). Prenatal smoke exposure was inversely associated with genomic DNA methylation of Sat2 and Alu, adjusted for age, childhood environmental tobacco smoke exposure (ETS) and adult smoking status (exposed vs. unexposed to prenatal smoke: Sat2: β = −0.20, 95% CI = −0.39, −0.02; Alu: β = −0.09, 95% CI = −0.26, 0.08). In multivariable models, childhood ETS had a positive, borderline significant association with Sat2 methylation (β = 0.17, 95% CI −0.02, 0.37). If replicated in larger studies, these results suggest that prenatal smoke exposure may have a persistent impact on genomic DNA demethylation of Sat2 and Alu in adulthood, and thus may be a pathway through which prenatal smoke exposure impacts adult disease. Results are strengthened by the fact that prenatal smoke exposure data were collected prospectively in the early 1960s, before there was a stigma associated with maternal smoking during pregnancy. These results are consistent with the one study assessing this relation in children. Further studies are needed to confirm this finding and to investigate the underlying biological mechanism.

Epigenetics and Prenatal Influences on Asthma and Allergic Airways Disease

Uterine life is arguably the most critical time in developmental programming, when environmental exposures may have the greatest potential to influence evolving fetal structure and function. There has been substantial progress in understanding the epigenetic mechanisms through which environmental exposures can permanently alter the expression of fetal genes and contribute to the increasing propensity for many complex diseases. These concepts of "developmental origins" of disease are being applied across virtually all fields of medicine, and emerging epigenetic paradigms are the likely mechanism behind the environment-driven epidemic of asthma and allergic disease. Here, we examine the epigenetic regulation of immune development and the early immune profiles that contribute to allergic risk. In particular we review new evidence that key environmental exposures, such as microbial exposure, dietary changes, tobacco smoke, and pollutants, can induce epigenetic changes in gene expression and alter disease risk. Although most of these factors have already been clearly implicated in epidemiologic studies of asthma and allergic disease, new studies investigating the mechanisms of these effects may provide new avenues for using these pathways for disease prevention.

Polymorphisms in the selenoprotein S and 15-kDa selenoprotein genes are associated with altered susceptibility to colorectal cancer

Selenium (Se), a dietary trace metal essential for human health, is incorporated into~25 selenoproteins including selenoprotein S (SelS) and the 15-kDa selenoprotein (Sep15) both of which have functions in the endoplasmic reticulum protein unfolding response. The aim of this study was to investigate whether genetic variants in such selenoprotein genes are associated with altered risk of colorectal cancer (CRC). A Korean population of 827 patients with CRC and 733 healthy controls was genotyped for 7 SNPs in selenoprotein genes and one SNP in the gene encoding manganese superoxide dismutase using Sequenom technology. Multivariate logistic regression analysis showed that after adjustment for lifestyle factors three SNP variants were associated with altered disease risk. There was a mean odds ratio of 2.25 [95% CI 1.13,4.48] in females homozygous TT for rs34713741 in SELS with the T variant being associated with higher risk of rectal cancer, and odds ratios of 2.47 and 2.51, respectively, for rs5845 and rs5859 in SEP15 with the minor A and T alleles being associated with increased risk of male rectal cancer. The data indicate that the minor alleles for rs5845, rs5859 and rs34713741 are associated with increased rectal cancer risk and that the effects of the three SNPs are dependent on gender. The results highlight potential links between Se, the function of two selenoproteins involved in the protein unfolding response and CRC risk. Further studies are required to investigate whether the effects of the variants on CRC risk are also modulated by dietary Se intake.

The plastic human

AbstractDevelopmental plasticity is the process by which environmental cues in early life influence the nature of the phenotype. The near‐universal capacity for plasticity evolved because it allows the organism to maintain or enhance its fitness, either at the time of the challenge (by allowing survival) or later in life. Importantly, developmental plasticity operates over the normative range of environmental experiences. Studies of the long‐term consequences of different developmental environments for human health and disease have shown that growth restriction (altered birth size) is not a prerequisite for altered disease risk and that there is a graded effect across the whole range of fetal milieu. Thus, the emerging consensus is that ‘fetal programming’ reflects the maladaptive consequences of developmental plasticity, arising from discordance between the triggering and later environments. Such discordance is increasingly likely, both because of demographic shifts and because of the rapid change in the nutritional and social environments experienced after weaning. Copyright © 2010 John Wiley &amp; Sons, Ltd.

Chia seed does not promote weight loss or alter disease risk factors in overweight adults

The objective of this study was to assess the effectiveness of chia seed (Salvia hispanica L) in promoting weight loss and altering disease risk factors in overweight adults. The hypothesis was that the high dietary fiber and alpha-linolenic (ALA) contents of chia seed would induce a small but significant decrease in body weight and fat and improve disease risk factors. Subjects were randomized to chia seed (CS) and placebo (P) groups, and under single-blinded procedures, ingested 25 g CS or P supplements mixed in 0.25 L water twice daily before the first and last meal for 12 weeks. Ninety nondiseased, overweight/obese men and women between the ages of 20 and 70 years were recruited into the study, with 76 subjects (n = 39 CS, n = 37 P) completing all phases of the study. Pre- and poststudy measures included body mass and composition (dual energy x-ray absorptiometry), inflammation markers from fasting blood samples (C-reactive protein, interleukin 6, monocyte chemoattractant protein 1, and tumor necrosis factor alpha), oxidative stress markers (trolox equivalent antioxidant capacity and plasma nitrite), blood pressure, and a serum lipid profile. Plasma ALA increased 24.4% compared to a 2.8% decrease in CS and P, respectively (interaction effect, P = .012). No group differences were measured for changes in plasma eicosapentaenoic acid and docosahexaenoic acid (interaction effects, P = .420 and .980, respectively). Pre-to-post measures of body composition, inflammation, oxidative stress, blood pressure, and lipoproteins did not differ between CS and P for both sexes. In conclusion, ingestion of 50 g/d CS vs P for 12 weeks by overweight/obese men and women had no influence on body mass or composition, or various disease risk factor measures.

Genome-wide association meta-analysis for total serum bilirubin levels

Variation in serum bilirubin is associated with altered cardiovascular disease risk and drug metabolism. We aimed to identify genetic contributors to variability in serum bilirubin levels by combining results from three genome-wide association studies (Framingham heart study, n = 3424; Rotterdam study, n = 3847; Age, Gene, Environment and Susceptibility-Reykjavik, n = 2193). Meta-analysis showed strong replication for a genetic influence on serum bilirubin levels of the UGT1A1 locus (P < 5 x 10(-324)) and a 12p12.2 locus. The peak signal in the 12p12.2 region was a non-synonymous SNP in SLCO1B1 (rs4149056, P = 6.7 x 10(-13)), which gives rise to a valine to alanine amino acid change leading to reduced activity for a hepatic transporter with known affinity for bilirubin. There were also suggestive associations with several other loci. The top variants in UGT1A1 and SLCO1B1 explain approximately 18.0 and approximately 1.0% of the variation in total serum bilirubin levels, respectively. In a conditional analysis adjusted for individual genotypes for the top UGT1A1 variant, the top SLCO1B1 variant remained highly significant (P = 7.3 x 10(-13)), but no other variants achieved genome-wide significance. In one of the largest genetic studies of bilirubin to date (n = 9464), we confirm the substantial genetic influence of UGT1A1 variants, consistent with past linkage and association studies, and additionally provide strong evidence of a role for allelic variation in SLCO1B1. Given the involvement of bilirubin in a number of physiological and disease processes, and the roles for UGT1A1 and SLCO1B1 in drug metabolism, these genetic findings have potential clinical importance. In analyses for association with gallbladder disease or gallstones, top bilirubin SNPs in UGT1A1 and SLCO1B1 were not associated.

Chronic Exposure to Arsenic in the Drinking Water Alters the Expression of Immune Response Genes in Mouse Lung

BackgroundChronic exposure to drinking water arsenic is a significant worldwide environmental health concern. Exposure to As is associated with an increased risk of lung disease, which may make it a unique toxicant, because lung toxicity is usually associated with inhalation rather than ingestion.ObjectivesThe goal of this study was to examine mRNA and protein expression changes in the lungs of mice exposed chronically to environmentally relevant concentrations of As in the food or drinking water, specifically examining the hypothesis that As may preferentially affect gene and protein expression related to immune function as part of its mechanism of toxicant action.MethodsC57BL/6J mice fed a casein-based AIN-76A defined diet were exposed to 10 or 100 ppb As in drinking water or food for 5–6 weeks.ResultsWhole genome transcriptome profiling of animal lungs revealed significant alterations in the expression of many genes with functions in cell adhesion and migration, channels, receptors, differentiation and proliferation, and, most strikingly, aspects of the innate immune response. Confirmation of mRNA and protein expression changes in key genes of this response revealed that genes for interleukin 1β, interleukin 1 receptor, a number of toll-like receptors, and several cytokines and cytokine receptors were significantly altered in the lungs of As-exposed mice.ConclusionsThese findings indicate that chronic low-dose As exposure at the current U.S. drinking-water standard can elicit effects on the regulation of innate immunity, which may contribute to altered disease risk, particularly in lung.

Effects of the removal of large herbivores on fleas of small mammals

The removal of large herbivorous mammals can cause dramatic increases in the densities of small mammals. These small mammals are hosts for a variety of ectoparasites, many of which are important pathogens of human diseases such as plague and murine typhus. It is thus valuable from a human health perspective to understand if large herbivore removals can indirectly affect ectoparasite numbers and thus potentially alter disease risk. To make this determination, we experimentally excluded large herbivores and measured the number of fleas present on the numerically dominant small mammal, the pouched mouse, Saccostomus mearnsi. Removing large herbivores nearly doubled S. mearnsi density, while the percentage of mice infested with fleas (prevalence) and the average number of fleas per sampled mouse (intensity) remained constant. The net effect of doubling the number of mice via the removal of large herbivores was a near doubling in the number of fleas present in the study habitat. Because these fleas also parasitize humans and can serve as disease vectors, this work empirically demonstrates a potential mechanism by which ecosystem alterations could affect human risk for zoonotic diseases.

Natriuretic peptides and asthma: is there a connection?

Natriuretic peptides and asthma: is there a connection?

Comment on the Nanoparticle Conclusions in Crüts et al. (2008), "Exposure to diesel exhaust induces changes in EEG in human volunteers"

A recent publication in this journal reported interesting changes in electroencephalographic (EEG) waves that occurred in 10 young, male volunteers following inhalation for one hour of elevated levels of diesel-engine exhaust fumes [1]. The authors then proposed a chain of causal events that they hypothesized underlay their observed EEG changes. Their reasoning linked the observed results to nanoparticles in diesel-engine exhaust (DEE), and went on to suggest that associations between changes in ambient particulate matter (PM) levels and changes in health statistics might be due to the effects of diesel-engine exhaust (DEE) nanoparticles on EEG. We suggest that the extrapolations of the Crüts et al. EEG findings to casual mechanisms about how ambient levels of DEE particulate might affect electrical signals in the brain, and subsequently to how DEE particulate might alter disease risk, are premature.

Artificial rearing with docosahexaenoic acid and n-6 docosapentaenoic acid alters rat tissue fatty acid composition

Docosahexaenoic acid (DHA; 22:6n-3) and n-6 docosapentaenoic acid (DPAn-6; 22:5n-6) are components of enriched animal feed and oil derived from Schizochytrium species microalgae. A one generation, artificial rearing model from day 2 after birth onward (AR) and a dam-reared control group (DAM) were used to examine DPAn-6 feeding on the fatty acid composition of various rat tissues at 15 weeks of age. Four AR diets were based on an n-3 fatty acid-deficient, 18:2n-6-based artificial milk with 22:6n-3 and/or 22:5n-6 added: AR-LA, AR-DHA, AR-DPAn-6, and AR-DHA+DPAn-6. The 22:6n-3 levels for the DAM, AR-DHA, and AR-DHA+DPAn-6 groups tended to be similar and higher than in the AR-LA and AR-DPAn-6 groups. The levels of 22:5n-6 tended to be higher only in the absence of dietary 22:6n-3. Adipose levels of 22:5n-6 was the only exception, as 22:5n-6 was significantly higher in AR-DHA+DPAn-6 than was observed in either the DAM or the AR-DHA group. There were no differences in 20:4n-6 levels within the tissues examined. In conclusion, 22:5n-6 replaces 22:6n-3 in the absence of 22:6n-3 only and does not appear to compete with 22:6n-3 in the presence of dietary 22:6n-3, suggesting that oils containing 22:5n-6 and 22:6n-3 may be a good dietary source of 22:6n-3.