Irma Salminen

The Risk to Develop NIDDM Is Related to the Fatty Acid Composition of the Serum Cholesterol Esters

This investigation was undertaken to study whether the risk to develop non-insulin-dependent diabetes mellitus (NIDDM) among 50-year-old men during a 10-year follow-up period was related to the fatty acid composition of their serum cholesterol esters. There were highly significant differences in the initial health survey between the fatty acid composition in serum in subjects who remained normoglycemic (w = 1,753) and in those who later developed NIDDM (n = 75). The main differences were that the latter had higher proportions of saturated fatty acids and palmitoleic acid (16:ω-7), a low proportion of linoleic acid (18:2ω-6), and a relatively high content of γ-linolenic (18:3ω-6) and dihomo-γ-linolenic (20:3ω-6) acids in the serum cholesterol esters. The picture was similar also after adjusting for differences in body mass index. In a logistic model, a high proportion of dihomo-γ-linolenic acid remained a significant contributor to the development of diabetes, along with the height of the insulin index, the blood glucose concentration at 60 min, and the fasting insulin concentration. The increased risk to develop NIDDM related to the serum cholesterol ester fatty acid composition may be mediated by diet and/or genetic factors.

Adipose tissue isomeric trans fatty acids and risk of myocardial infarction in nine countries : the EURAMIC study

Dietary isomeric trans fatty acids-mainly produced by hydrogenation of oils-are suspected of increasing the risk of coronary heart disease. Dietary trans fatty acid intake is reflected in the fatty acid composition of adipose tissue. In an international multicentre study in eight European countries and Israel (EURAMIC), adipose tissue aspiration samples were obtained from 671 men with acute myocardial infarction (AMI), aged 70 years or less, and 717 men without a history of AMI (controls). The proportion of fatty acids, including isomeric trans monoenoic fatty acids with 18 carbon atoms (C18:1), was determined by gas chromatography. Although there were considerable differences between countries in mean (SD) proportion of adipose tissue C18:1 trans fatty acids, there was no overall difference between cases (1.61 [0.92]%) and the controls (1.57 [0.86]%). The risk of AMI did not differ significantly from 1.0 over quartiles of adipose C18:1 trans fatty acids: the multivariate odds ratio was 0.97 (95% CI 0.56-1.67) for the highest versus lowest quartile. After exclusion of subjects from Spanish centres because they had far lower proportions of adipose trans fatty acids than subjects from other countries, there was a tendency to increased risk of AMI in the upper quartiles of C18:1 trans; however, the trend was not statistically significant. Our results reflect considerable differences between countries in dietary intake of trans fatty acids but do not suggest a major overall effect of C18:1 trans fatty acids on risk of AMI. We cannot exclude the possibility that trans fatty acids have a significant impact on risk of AMI in populations with high intake.

Omega-3 Fatty Acids in Adipose Tissue and Risk of Myocardial Infarction The EURAMIC Study

Omega-3 fatty acids have potential antiatherogenic, antithrombotic, and antiarrhythmic properties, but their role in coronary heart disease remains controversial. To evaluate the association of omega-3 fatty acids in adipose tissue with the risk of myocardial infarction in men, a case-control study was conducted in eight European countries and Israel. Cases (n=639) included patients with a first myocardial infarction admitted to coronary care units within 24 hours from the onset of symptoms. Controls (n=700) were selected to represent the populations originating the cases. Adipose tissue levels of fatty acids were determined by capillary gas chromatography. The mean (+/-SD) proportion of alpha-linolenic acid was 0.77% (+/-0.19) of fatty acids in cases and 0.80% (+/-0.19) of fatty acids in controls (P=0.01). The relative risk for the highest quintile of alpha-linolenic acid compared with the lowest was 0.42 (95% confidence interval [CI] 0.22 to 0.81, P-trend=0.02). After adjusting for classical risk factors, the relative risk for the highest quintile was 0.68 (95% CI 0.31 to 1.49, P-trend=0.38). The mean proportion of docosahexaenoic acid was 0.24% (+/-0.13) of fatty acids in cases and 0.25% (+/-0.13) of fatty acids in controls (P=0. 14), with no evidence of association with risk of myocardial infarction. In this large case-control study we could not detect a protective effect of docosahexaenoic acid on the risk of myocardial infarction. The protective effect of alpha-linolenic acid was attenuated after adjusting for classical risk factors (mainly smoking), but it deserves further research.

Dietary trans fatty acids increase conjugated linoleic acid levels in human serum

Conjugated linoleic acid (CLA), fatty acids with 18 carbon atoms and two conjugated cis/trans double bonds, have shown anticarcinogenic effects in experimental studies. We determined the proportion of CLA (the sum of cis-9, trans-11 and trans-9, cis-11 CLA) of total fatty acids in the diets and serum samples of healthy subjects who consumed for 5 weeks a diet high in saturated fatty acids mainly from dairy fat, followed by 5 weeks on a diet high (8.7% of energy, en%) in trans fatty acids from partially hydrogenated vegetable oil (40 subjects) or a similar diet high in stearic acid (9.3 en%, 40 subjects). All diets contained equal amounts of fat and cis-monounsaturated and cis-polyunsaturated fatty acids. The fatty acid compositions of the pooled diets and fasting serum samples drawn at the end of the diet periods were analyzed by gas chromatography, and CLA was identified by comparison with a standard of C18:2 conjugated dienes. The proportions of CLA in the dairy fat, trans fatty acid, and stearic acid diets were 0.37, 0.04, and 0.10% of total methylated fatty acids, respectively. The corresponding mean (SD) proportions in serum were 0.33 (0.07)% after the dairy fat diet, higher, 0.43 (0.12)%, P < 0.001, after the trans fatty acid diet, and lower, 0.17 (0.06)%, P < 0.001, after the stearic acid diet. The difference between dairy fat and stearic acid diets was explained by different dietary intakes but increased amounts of CLA not present in the diet were incorporated into serum lipids during the trans fatty acid diet. CLA in human tissues is partly derived from the diet but part of it may be formed by conversion from dietary trans fatty acids.

The serum cholesterol ester fatty acid composition but not the serum concentration of alpha tocopherol predicts the development of myocardial infarction in 50-year-old men: 19 years follow-up

A low serum tocopherol concentration and a low proportion of linoleic acid in plasma cholesterol esters have been reported to be associated with coronary heart disease. This study was undertaken to evaluate the predictive importance of the serum cholesterol ester fatty acid composition and serum tocopherol concentration in addition to established risk factors for myocardial infarction. The study comprised 2322 fifty-year-old men who participated in a health survey in 1970-1973 regarding risk factors for coronary heart disease. The proportions of myristic, palmitic, palmitoleic, and dihomogammalinolenic acid were significantly higher in 1970-1973 in subjects who suffered myocardial infarction during the following 19 years, while the proportion of linoleic acid was lower, than in those who remained healthy. Serum tocopherol did not differ significantly between the groups. LDL/HDL ratio, systolic blood pressure, and arachidonic acid/dihomogammalinolenic acid ratio were significant independent discriminators between cases and controls in a stepwise logistic regression analysis. This study suggests that middle-aged men who later develop a myocardial infarction are characterized not only by conventional risk factors but also by an altered fatty acid composition of serum cholesterol esters, with a low arachidonic to dihomogammalinolenic acid ratio, indicating reduced delta 5 desaturase activity. This may imply that changes in the quality of dietary fat intake, or an altered capacity to metabolize fatty acids in the body, could precede the development of coronary heart disease.

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.

Effects of a flaxseed mixture and plant oils rich in α-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.

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.

Chlamydial and Periodontal Pathogens Induce Hepatic Inflammation and Fatty Acid Imbalance in Apolipoprotein E-Deficient Mice

ABSTRACT 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.

Serum fatty acids and risk of advanced β-cell autoimmunity: a nested case–control study among children with HLA-conferred susceptibility to type I diabetes

Background/Objectives:N-3 (omega-3) fatty acids have been reported to decrease the risk for development of β-cell autoimmunity and clinical type I diabetes. We set out to examine whether different serum fatty acids are associated with the development of advanced β-cell autoimmunity in children carrying human leukocyte antigen DQ β-1 (HLA-DQB1)-conferred susceptibility to type I diabetes.Subjects/Methods:Within a cohort, serum total fatty acid composition of 108 children with advanced β-cell autoimmunity and of 216 matched persistently autoantibody-negative controls was analyzed using gas chromatography. Non-fasting serum samples were obtained annually at the ages of 1–6 years. Conditional logistic regression was applied to analyze the associations between advanced β-cell autoimmunity and serum fatty acids.Results:The serum fatty acid profile of myristic acid (odds ratio (OR) 1.48, 95% confidence interval (CI) 1.09–2.00, P=0.011), pentadecanoic acid (OR 1.65, 95% CI 1.19–2.28, P=0.003), palmitoleic acid isomers 16:1 n-7 (omega-7) (OR 1.41, 95% CI 1.03–1.92, P=0.030) and 16:1 n-9 (omega-9) (OR 1.45, 95% CI 1.05–2.01, P=0.026) and conjugated linoleic acid (OR 1.67, 95% CI 1.16–2.41, P=0.006) closest to the time of the appearance of multiple autoantibodies were positively associated with the risk of advanced β-cell autoimmunity after adjustment for potential confounding factors. Serum linoleic acid showed inverse, marginal association with the end point.Conclusions:Serum biomarkers of milk and ruminant meat fat consumption are directly associated and linoleic acid is inversely associated with advanced β-cell autoimmunity in children with HLA-conferred susceptibility to type I diabetes.