Children's erythrocyte fatty acids are associated with the risk of islet autoimmunity.

Our aim was to investigate the associations between erythrocyte fatty acids and the risk of islet autoimmunity in children. The Environmental Determinants of Diabetes in the Young Study (TEDDY) is a longitudinal cohort study of children at high genetic risk for type 1 diabetes (n = 8676) born between 2004 and 2010 in the U.S., Finland, Sweden, and Germany. A nested case-control design comprised 398 cases with islet autoimmunity and 1178 sero-negative controls matched for clinical site, family history, and gender. Fatty acids composition was measured in erythrocytes collected at the age of 3, 6, and 12 months and then annually up to 6 years of age. Conditional logistic regression models were adjusted for HLA risk genotype, ancestry, and weight z-score. Higher eicosapentaenoic and docosapentaenoic acid (n - 3 polyunsaturated fatty acids) levels during infancy and conjugated linoleic acid after infancy were associated with a lower risk of islet autoimmunity. Furthermore, higher levels of some even-chain saturated (SFA) and monounsaturated fatty acids (MUFA) were associated with increased risk. Fatty acid status in early life may signal the risk for islet autoimmunity, especially n - 3 fatty acids may be protective, while increased levels of some SFAs and MUFAs may precede islet autoimmunity.

Food and Nutrient Intake and Nutritional Status of Finnish Vegans and Non-Vegetarians.

BACKGROUND: Vegetarian and vegan diets have become more popular among adolescents and young adults. However, few studies have investigated the nutritional status of vegans, who may be at risk of nutritional deficiencies. OBJECTIVE: To compare dietary intake and nutritional status of Finnish long-term vegans and non-vegetarians. METHODS: Dietary intake and supplement use were estimated using three-day dietary records. Nutritional status was assessed by measuring biomarkers in plasma, serum, and urine samples. Vegans' (n = 22) data was compared with those of sex- and age-matched non-vegetarians (n = 19). RESULTS: All vegans adhered strictly to their diet; however, individual variability was marked in food consumption and supplementation habits. Dietary intakes of key nutrients, vitamins B12 and D, were lower (P < 0.001) in vegans than in non-vegetarians. Nutritional biomarker measurements showed lower concentrations of serum 25-hydroxyvitamin D3 (25(OH)D3), iodine and selenium (corrected for multiple comparisons, P < 0.001), Vegans showed more favorable fatty acid profiles (P < 0.001) as well as much higher concentrations of polyphenols such as genistein and daidzein (P < 0.001). Eicosapentaenoic acid proportions in vegans were higher than expected. The median concentration of iodine in urine was below the recommended levels in both groups. CONCLUSIONS: Long-term consumption of a vegan diet was associated with some favorable laboratory measures but also with lowered concentrations of key nutrients compared to reference values. This study highlights the need for nutritional guidance to vegans.

Vegetable and fruit consumption, education and plasma vitamin C concentration in Russian and Finnish Karelia, 1992-2002.

OBJECTIVE: To examine (i) whether the consumption of fresh vegetables, fruit and berries is associated with plasma vitamin C concentration and (ii) educational differences in plasma vitamin C concentration in two neighbouring areas in Russia and Finland. DESIGN: Cross-sectional risk factor surveys in 1992, 1997 and 2002. Logistic regression analysis was applied to examine the associations of consumption of selected foods and education with plasma vitamin C concentration. SETTING: District of Pitkäranta in the Republic of Karelia, Russia and North Karelia, Finland. SUBJECTS: Adults aged 25-64 years: 579 men and 612 women in Pitkäranta; 974 men and 642 women in North Karelia. RESULTS: The plasma vitamin C concentration was strikingly low in Pitkäranta, Russia across the study years. During the 10 years of monitoring, the mean plasma vitamin C concentration among men ranged from 2·5 to 8·0 µmol/l in Pitkäranta, Russia and from 27·1 to 53·9 µmol/l in North Karelia, Finland. In both areas, daily consumption of fruit was most strongly associated with plasma vitamin C, while the association of fresh vegetable consumption with plasma vitamin C was less consistent. Consumption of berries was less important in explaining plasma vitamin C. In Pitkäranta, the plasma vitamin C concentration was lower among respondents in the lowest education group. CONCLUSIONS: Differences in the consumption of fresh vegetables and fruit resulted in notable differences in vitamin C status between Pitkäranta and North Karelia in spring. In comparative settings, knowledge of local food culture and validation pilots are important before conducting large population surveys.

The effect of proatherogenic pathogens on adipose tissue transcriptome and fatty acid distribution in apolipoprotein E-deficient mice.

BACKGROUND: Chronic infections have been demonstrated to maintain low-grade systemic inflammation and associate with atherosclerosis. We studied the inflammation- and lipid homeostasis-related effects of Aggregatibacter actinomycetemcomitans (Aa) and Chlamydia pneumoniae (Cpn) infections on the epididymal and inguinal adipose tissue (AT) transcriptomes and fatty acid distribution in apolipoprotein (apo) E-deficient mice. Chow-fed apoE-deficient mice were exposed to 1) chronic intranasal infection with C. pneumoniae (Cpn group), 2) recurrent intravenous infection with A. actinomycetemcomitans (Aa group), 3) a combination of both types of infection (Cpn + Aa group), or 4) infection with the vehicle (control group). Epididymal and inguinal AT gene expression was analyzed using an Illumina Mouse WG-6 v2.0 platform and quantitative PCR (QPCR). Microarray data were analyzed using Gene Ontology enrichment analysis. AT fatty acid analysis was performed using gas-liquid chromatography. RESULTS: The transcriptomics data revealed significant enrichment in inflammation-associated biological pathways in both AT depots derived from the Aa and Cpn + Aa treated mice compared with the control group. The proportion of saturated fatty acids was higher in the inguinal AT in Aa (p = 0.027) and Cpn + Aa (p = 0.009) groups and in the epididymal AT in Aa group (p = 0.003). The proportion of polyunsaturated fatty acids was significantly lower among all Aa-infected groups in both depots. Chronic Cpn infection displayed only minor effects on transcriptomics and fatty acids of the AT depots. CONCLUSIONS: Systemic infection with A. actinomycetemcomitans activates inflammation-related biological pathways and modulates cellular lipid homeostasis. The adverse changes in adipose tissues during chronic infection may promote atherosclerosis.

Fatty acids in serum and diet--a canonical correlation analysis among toddlers.

Fatty acid concentrations in blood are potential biomarkers of dietary fat intake, but methodological studies among children are scarce. The large number of fatty acids and their complex interrelationships pose a special challenge in research on fatty acids. Our target was to assess the interrelationships between the total fatty acid profiles in diet and serum of young children. The study subjects were healthy control children from the birth cohort of the Type 1 Diabetes Prediction and Prevention Study. A 3-day food record and a frozen serum sample were available from 135 children at the age of 1 year, from 133 at 2 years, and from 92 at 3 years. The relationship between dietary and serum fatty acid profiles was analysed using canonical correlation analysis. The consumption of fatty milk correlated positively with serum fatty acids, pentadecanoic acid, palmitic acid and conjugated linoleic acid (CLA) at all ages. Correlations between dietary and serum eicosapentaenoic and/or docosahexaenoic acid were observed at 2 and 3 years of age. Serum linoleic acid was positively associated with the consumption of infant formula at the age of 1 year, and with the consumption of vegetable margarine at 2 and 3 years. The results indicate a high quality of the 3-day food records kept by parents and other caretakers of the children, and suitability of non-fasting, un-fractioned serum samples for total fatty acid analyses. The correlation between intake of milk fat and serum proportion of CLA is a novel finding.

Chlamydial and periodontal pathogens induce hepatic inflammation and fatty acid imbalance in apolipoprotein E-deficient mice.

Periodontitis and Chlamydia pneumoniae infection are independent risk factors for cardiovascular diseases. The aim of this study was to investigate the effect of C. pneumoniae and Aggregatibacter actinomycetemcomitans infection on hepatic inflammation and lipid homeostasis of apolipoprotein E-deficient mice. Mice were infected with viable C. pneumoniae intranasally three times for chronic infection or once for acute infection. Viable A. actinomycetemcomitans was administered 10 times intravenously alone or in concert with C. pneumoniae. Hepatic alterations were assessed by histochemistry, lipid quantification, and fatty acid profile analysis. The RNA expression levels and the presence of pathogens in the livers and lungs were detected by quantitative real-time PCR. Both pathogens were detected in the livers of the infected animals. Chronic C. pneumoniae infection induced marked changes in hepatic lipid homeostasis. A. actinomycetemcomitans infection resulted in inflammatory cell infiltration into the liver, accompanied by elevated hepatic RNA expression levels of inflammation-related genes and higher serum amyloid A and lipopolysaccharide concentrations. Our results indicate that proatherogenic pathogens infect the liver, causing proinflammatory alterations and lipid disturbances. This infection may maintain chronic systemic inflammation attributable to atherogenesis.

Plasma ascorbic acid preparation and storage for epidemiological studies using TCA precipitation.

OBJECTIVES: To introduce a procedure to validate an ascorbic acid method using trichloroacetic acid (TCA) for plasma stabilization at different storage temperatures. METHODS: EDTA and heparin plasma were precipitated with TCA (1:5) containing 0.54 mol/L EDTA, or without. Samples were stored at -20 degrees C and -70 degrees C and their stability was tested at room temperature for 24 h. RESULTS: A significant 40% loss (p<0.001) of plasma ascorbic acid was found when EDTA samples with added EDTA were stored at -20 degrees C for 2-4 weeks compared with storage at -70 degrees C. Ascorbic acid in heparin plasma without added EDTA was most unstable and samples left at room temperature for 24 h lead to almost a total loss of ascorbic acid. Addition of EDTA to the TCA solution improved stability of samples of both plasma types at room temperature. CONCLUSION: The recommended procedure for ascorbic acid determination in plasma stabilized with TCA is immediate storage at -70 degrees C and inclusion of EDTA into the TCA solution.

Effects of a flaxseed mixture and plant oils rich in alpha-linolenic acid on the adenoma formation in multiple intestinal neoplasia (Min) mice.

Flaxseed is a dietary source of possible chemopreventive compounds such as lignans and alpha-linolenic acid (ALA). To study the effects of a flaxseed mixture on adenoma formation in multiple intestinal neoplasia mice, the mice were fed a diet containing 2.7 % flaxseed, 4.5 % fibre and 3.7 % ALA. To elucidate the effect of oils of the mixture we also composed a diet without flaxseed but with the same oil composition. The median number of adenomas in the small intestine was fifty-four for the control group, and thirty-seven (P=0.023) and forty-two (P=0.095) for flaxseed and oil groups, respectively. Compared with controls (1.2 mm), the adenoma size was smaller in the flaxseed (0.9 mm; P=0.002) and oil (1.0 mm; P=0.012) groups. Both diets changed the proportions of n-3 and n-6 fatty acids in the colonic mucosa. Membrane beta-catenin and protein kinase C (PKC)-zeta levels were reduced in the adenoma v. mucosa (P<0.05), and an inverse association was found between the membrane PKC-zeta in the mucosa and the adenoma number (r -0.460, P=0.008, n 32). Only the flaxseed diet increased lignan levels in the caecum (P=0.002) and in plasma (P=0.002) but they were not associated with tumour formation. The results suggest that the preventive effect of flaxseed on colon carcinogenesis may be due to the oil part of flaxseed, and the loss of beta-catenin and PKC-zeta from the membranes of the mucosal tissue may play a permissive role in intestinal tumour development.

Dietary fat content modifies liver fat in overweight nondiabetic subjects.

BACKGROUND: Fat accumulation in the liver has been shown to be closely correlated with hepatic insulin resistance and features of insulin resistance, even independent of body weight. The reason for interindividual variation in liver fat content is unknown. Cross-sectional data suggest that dietary fat content may influence liver fat, but this possibility has not been directly tested in humans. DESIGN AND METHODS: Liver fat (proton spectroscopy), intraabdominal and sc fat (magnetic resonance imaging), and markers of insulin sensitivity (insulin, free fatty acids, and lipids) were determined in 10 normal, obese women (age, 43 +/- 5 yr, mean +/- sd; body mass index, 33 +/- 4 kg/m2; range, 27-38 kg/m2) at baseline and after two 2-wk isocaloric periods containing either 16% (low-fat diet) or 56% (high-fat diet) of total energy as fat. RESULTS: Liver fat at baseline averaged 10 +/- 7%. It decreased by 20 +/- 9% during the low-fat diet and increased by 35 +/- 21% during the high-fat diet (P = 0.014 for liver fat after low- vs. high-fat diets; P = 0.042 for change in liver fat by the low- vs. high-fat diet). Fasting serum insulin averaged 70 +/- 41 pmol/liter at baseline. It decreased to 60 +/- 24 pmol/liter during the low-fat diet (P = 0.007 vs. before low-fat diet) and increased to 81 +/- 44 pmol/liter during the high-fat diet (P = 0.040 vs. before high-fat diet; P = 0.005 for change in serum insulin during low- vs. high-fat diet). Serum lipids, free fatty acids, and intraabdominal and sc fat masses were unchanged. CONCLUSION: These data suggest that the amount of dietary fat influences liver fat content.

Effects of equal weight loss with orlistat and placebo on body fat and serum fatty acid composition and insulin resistance in obese women.

BACKGROUND: Dietary fat has been reported to influence insulin sensitivity. OBJECTIVE: The objective of the study was to determine how identical weight loss (target: loss of 8% of body weight over 3-6 mo) in women taking orlistat or placebo combined with a hypocaloric diet influences body composition and insulin sensitivity. DESIGN: Forty-seven obese women [body mass index (in kg/m(2)): 32.1 +/- 0.4] were randomly assigned to receive either orlistat (120 mg 3 times daily; n = 23) or placebo (n = 24) with a hypocaloric diet. Whole-body insulin sensitivity (insulin clamp technique), serum fatty acids, and body composition (magnetic resonance imaging) were measured before and after weight loss. RESULTS: The groups did not differ significantly at baseline with respect to age, body weight, intraabdominal and subcutaneous fat volumes, or insulin sensitivity. Weight loss did not differ significantly between the orlistat (7.3 +/- 0.2 kg, or 8.3 +/- 0.1%) and placebo (7.4 +/- 0.2 kg, or 8.2 +/- 0.1%) groups. Insulin sensitivity improved significantly (P < 0.001) and similarly after weight loss in the orlistat (from 4.0 +/- 0.3 to 5.1 +/- 0.3 mg x kg fat-free mass(-1) x min(-1)) and placebo (from 4.4 +/- 0.4 to 5.4 +/- 0.4 mg x kg fat-free mass(-1) x min(-1)) groups. Intraabdominal fat and subcutaneous fat decreased significantly in both groups, but the ratio of the 2 decreased significantly only in the orlistat group. The proportion of dihomo-gamma-linolenic acid (20:3n-6) in serum phospholipids was inversely related to insulin sensitivity both before (r = -0.48, P < 0.001) and after (r = -0.46, P < 0.001) weight loss, but it did not change significantly in either group. CONCLUSIONS: Weight loss rather than inhibition of fat absorption enhances insulin sensitivity. A decrease in fat absorption by orlistat appears to favorably influence the ratio between intraabdominal and subcutaneous fat, which suggests that exogenous fat or its composition influences fat distribution.

Fatty acids and risk of prostate cancer in a nested case-control study in male smokers.

There is some evidence that alpha-linolenic acid might be positively related to prostate cancer risk. Associations between serum fatty acid composition as well as fatty acid intakes and prostate cancer risk were examined in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The cohort included 29,133 male smokers aged 50-69 years. During 5-8 years of follow-up, 246 prostate cancer cases were diagnosed. One control was selected and matched by age (+/- 1 month) for each case from the cohort subjects alive and free of prostate cancer at the time the case was diagnosed. This study included 198 case-control pairs with baseline serum sample available for both. Fatty acids of serum cholesterol esters were measured as a percentage of total fatty acids, using capillary gas chromatography. Intakes of fatty acids were assessed from a validated self-administered dietary questionnaire. Serum and dietary fatty acids had no consistent association with prostate cancer risk. Serum alpha-linolenic acid was not related to prostate cancer risk. Twofold risk was found in the highest quartile of serum myristic acid compared with the lowest quartile (odds ratio, 1.93; 95% confidence interval, 1.02-3.64). alpha-Tocopherol supplementation modified the association between serum linoleic acid and prostate cancer risk (P for interaction 0.03); odds ratio was 0.17 (95% confidence interval, 0.04-0.68) in the highest quartile of serum linoleic acid compared with the lowest quartile in men who received alpha-tocopherol, whereas no association was found in men who did not receive alpha-tocopherol. In conclusion, we found no overall association between serum or dietary alpha-linolenic acid or any other unsaturated fatty acid and prostate cancer risk, but high serum linoleic acid was associated with lower risk in men supplemented with alpha-tocopherol. High serum myristic acid associated with an increased risk of prostate cancer.

Serum fatty acids and breast cancer incidence.

Fatty acid composition of the diet may be essential to the development of breast cancer. We studied the ability of several fatty acids of serum total lipids to predict breast cancer incidence in a case-control study nested within a longitudinal population study. The proportions of fatty acids in serum total lipids were determined from stored serum samples collected at baseline for 127 incident breast cancer cases and 242 matched controls. Women with a higher proportion of total polyunsaturated fatty acids (PUFAs) in serum had a reduced risk of breast cancer. The odds ratio (OR) between the highest and lowest tertiles of serum PUFA was 0.31 (95% confidence interval, CI = 0.12-0.77). This association was mainly due to n-6 PUFAs and especially to linoleic acid. The ORs were 0.35 (CI = 0.14-0.84) and 0.29 (CI = 0.12-0.73), respectively. Of the monounsaturated fatty acids (MUFAs), higher trans-11-18:1 levels were related to an increased breast cancer risk (OR = 3.69, CI = 1.35-10.06). The association was stronger in postmenopausal than in premenopausal women. The present study suggests that higher serum proportions of the n-6 PUFA linoleic acid and lower proportions of the MUFA trans-11-18:1 fatty acid predict a reduced incidence of breast cancer.

Adenoma growth stimulation by the trans-10, cis-12 isomer of conjugated linoleic acid (CLA) is associated with changes in mucosal NF-kappaB and cyclin D1 protein levels in the Min mouse.

Conjugated linoleic acid (CLA) is a term used to describe the different conjugated isomers of linoleic acid. CLA has been found to be anticarcinogenic in mammary cancer, but its effects on colon carcinogenesis are still inconclusive. In this study, the isomer-specific effects of the cis-9, trans-11 and trans-10, cis-12 CLA isomers were investigated in the Min mouse model for intestinal carcinogenesis. The Min mice (n = 10/group) were fed either an AIN-93G control diet or a diet containing 1 g/100 g cis-9, trans-11 or trans-10, cis-12 CLA for 8 wk. The number and size of adenomas were measured and the proteins from the small intestinal tissues extracted for immunoblotting analysis. The number of adenomas did not differ, but the size of the adenomas was greater in the distal part of the small intestine in mice fed the trans-10, cis-12 isomer than in controls (1.19 +/- 0.16 vs. 0.94 +/- 0.21 mm, mean +/- SD, P < 0.01). The same isomer caused an increase in lipid peroxidation, measured as urinary 8-iso-prostaglandin (PG)F(2alpha). Nuclear p65 protein of the mucosal tissue was not detectable in the trans-10, cis-12 group, which differed (P < 0.05) from the control group. Cyclin D1, a target for the nuclear factor (NF)-kappaB pathway, was elevated in the trans-10, cis-12 group compared with the control group (P < 0.01), but cyclooxygenase-2 levels were not higher. There was no difference in beta-catenin protein levels between the groups. The results indicate that the trans-10, cis-12 isomer of CLA can act as a cancer promoter in colon carcinogenesis possibly through pathways affecting NF-kappaB and cyclin D1.

High intakes of vegetables, berries, and apples combined with a high intake of linoleic or oleic acid only slightly affect markers of lipid peroxidation and lipoprotein metabolism in healthy subjects.

BACKGROUND: A high consumption of vegetables and fruit is associated with decreased risk of ischemic heart disease and several cancers. The pathophysiology of these diseases involves free radical mechanisms. Diet may either enhance or diminish oxidative stress in the body. OBJECTIVE: We studied the effects of high and low intakes of vegetables, berries, and apples on markers of lipid peroxidation and lipoprotein metabolism in subjects consuming diets high in linoleic or oleic acid. DESIGN: For 6 wk, healthy men and women (n = 77; aged 19-52 y) consumed 1 of 4 controlled isoenergetic diets rich in either linoleic acid (11% of energy) or oleic acid (12% of energy) and containing either 815 or 170 g vegetables, berries, and apples/10 MJ. Nineteen healthy volunteers served as control subjects. Several markers of dietary compliance (plasma fatty acids, vitamin C, carotenoids, and quercetin), lipid peroxidation [ex vivo LDL oxidation, plasma and LDL thiobarbituric acid-reactive substances, paraoxonase (EC 3.1.8.1), and urinary 8-iso-prostaglandin F(2)(alpha)], and lipoprotein metabolism (plasma lipids, apolipoproteins, and lipid transfer protein activities) were measured from samples collected before and at the end of the experimental period. RESULTS: Plasma fatty acid composition and antioxidant concentrations showed that compliance with the diets was good. However, there were no significant differences between the diets in the markers of lipid peroxidation and lipoprotein metabolism. CONCLUSIONS: In healthy volunteers with adequate vitamin intakes, 6-wk diets differing markedly in the amounts of linoleic and oleic acid and vegetables, berries, and apples did not differ in their effects on lipid peroxidation or lipoprotein metabolism.

Effect of alpha-linolenic acid-rich Camelina sativa oil on serum fatty acid composition and serum lipids in hypercholesterolemic subjects.

Camelina sativa-derived oil (camelina oil) is a good source of alpha-linolenic acid. The proportion of alpha-linolenic acid in serum fatty acids is associated with the risk of cardiovascular diseases. We studied the effects of camelina oil on serum lipids and on the fatty acid composition of total lipids in comparison to rapeseed and olive oils in a parallel, double-blind setting. Sixty-eight hypercholesterolemic subjects aged 28 to 65 years were randomly assigned after a 2-week pretrial period to 1 of 3 oil groups: camelina oil, olive oil, and rapeseed oil. Subjects consumed daily 30 g (actual intake, approximately 33 mL) of test oils for 6 weeks. In the camelina group, the proportion of alpha-linolenic acid in fatty acids of serum lipids was significantly higher (P <.001) compared to the 2 other oil groups at the end of the study: 2.5 times higher compared to the rapeseed oil group and 4 times higher compared to the olive oil group. Respectively the proportions of 2 metabolites of alpha-linolenic acid (eicosapentaenoic and docosapentaenoic acids) increased and differed significantly in the camelina group from those in other groups. During the intervention, the serum low-density lipoprotein (LDL) cholesterol concentration decreased significantly by 12.2% in the camelina oil group, 5.4% in the rapeseed oil group, and 7.7% in the olive oil group. In conclusion, camelina oil significantly elevated the proportions of alpha-linolenic acid and its metabolites in serum of mildly or moderately hypercholesterolemic subjects. Camelina oil's serum cholesterol-lowering effect was comparable to that of rapeseed and olive oils.

Bioconversion of vaccenic acid to conjugated linoleic acid in humans.

BACKGROUND: Vaccenic acid (11-trans octadecenoic acid; VA), a major trans fatty acid in the fat of ruminants, is produced in the rumen and converted in tissues to rumenic acid (9-cis, 11-trans octadecenoic acid; RA), an isomer of conjugated linoleic acid, by Delta(9)-desaturase. There are indications that this conversion also occurs in humans. OBJECTIVE: The aim of this controlled intervention was to study the conversion of VA to RA in humans after consumption of diets with increasing amounts of VA. DESIGN: Thirty healthy subjects consumed a baseline diet rich in oleic acid for 2 wk. The subjects were then divided into 3 groups (n = 10 per group) and provided a diet containing 1.5, 3.0, or 4.5 g VA/d for 9 d. All diets contained equal amounts of macronutrients and differed only in their fatty acid compositions. The fats were mixed into conventional foods, and nearly all food was provided during the study. RESULTS: The proportion of VA in serum total fatty acids increased 94%, 307%, and 620% above baseline with the 1.5-, 3.0-, and 4.5-g diets, respectively. This was associated with a linear increase in the proportion of RA. The conversion rate was 19% on average, with significant interindividual differences with all 3 intakes of VA. The urinary excretion of 8-iso-prostaglandin F(2alpha) increased in all groups (P < 0.001). CONCLUSIONS: The results quantify the desaturation of VA to RA in humans. Conversion is likely to contribute significantly to the amount of RA available to the body, and dietary intakes of VA should thus be taken into account when predicting RA status.