Eva Warensjö

Fatty acid composition of serum lipids predicts the development of the metabolic syndrome in men

Aims/hypothesisTypes of dietary fat have been related to components of the metabolic syndrome. Serum fatty acid composition mainly reflects dietary fat intake, but also endogenous fatty acid synthesis catalysed by Δ-desaturases. It is not known whether alterations of fatty acid composition or desaturase activities predict metabolic syndrome.Materials and methodsWe prospectively evaluated fatty acid composition in serum cholesteryl esters and estimated desaturase activities in 1,558 50-year-old men taking part in a population-based cohort study. The follow-up time was 20 years. Stearoyl-CoA desaturase (SCD-1), Δ6 (D6D) and Δ5 (D5D) desaturases were estimated as precursor to fatty acid ratios.ResultsHigh activity of estimated SCD-1 (odds ratio=1.29, p<0.05) and D6D (odds ratio=1.35, p<0.05), as well as low estimated D5D activity (odds ratio=0.71, p<0.001) predicted the development of metabolic syndrome (as defined by the National Cholesterol Education Program). The predictive value of D5D activity was independent of lifestyle factors (smoking, BMI and physical activity), whereas the risk associated with higher SCD-1 and D6D activities was mainly explained by obesity. Among those developing metabolic syndrome (119 out of 706) during follow-up, the proportions of fatty acids 14:0, 16:0, 16:1 (n−7), 18:1 (n−9), 18:3 (n−6) and 20:3 (n−6) were increased at baseline, while 18:2 (n−6) was decreased (p<0.05 for all).Conclusions/interpretationSerum fatty acid composition predicts the long-term development of the metabolic syndrome, and D5D activity may be particularly important in this process. Our results suggest a role of dietary fat quality in the development of metabolic syndrome, but the possibility that altered fatty acid composition, partly secondary to genetic or hormonal factors, should also be considered.

Associations between estimated fatty acid desaturase activities in serum lipids and adipose tissue in humans: links to obesity and insulin resistance

Fatty acid composition of serum lipids and adipose tissue triacylglycerols (AT-TAG) partly reflect dietary fatty acid intake. The fatty acid composition is, besides the diet, also influenced by desaturating enzymes that can be estimated using product-to-precursor fatty acid ratios. The interrelationships between desaturase indices derived from different serum lipid fractions and adipose tissue are unclear, as well as their associations with obesity and insulin resistance. We aimed to investigate cross-sectional correlations between desaturase indices as measured in serum lipid fractions (phospholipids; PL and free fatty acids; FFA) and in adipose tissue (AT-TAG). In a population-based sample of 301 healthy 60-year-old men various desaturase indices were assessed: stearoyl-CoA-desaturase (16:1n-7/16:0; SCD-16 and 18:1n-9/18:0; SCD-18, respectively), delta-6-desaturase (20:3n-6/18:2n-6; D6D) and delta-5-desaturase (20:4n-6/20:3n-6; D5D). Correlations with BMI and insulin resistance (HOMA-IR) were also examined. SCD-16 and D5D were significantly correlated between fractions and tissues (all r > 0.30), whereas SCD-18 and D6D were not. Desaturase indices in serum FFA and AT-TAG were significantly correlated; SCD-16 (r = 0.63), SCD-18 (r = 0.37), and D5D (r = 0.43). In phospholipids, SCD-16 was positively correlated to BMI (r = 0.15), while D5D negatively to both BMI (r = -0.30) and HOMA-IR (r = -0.31), all p < 0.01. D6D in both phospholipids and AT-TAG was positively correlated to HOMA-IR and BMI (all p < 0.01). In conclusion, SCD-1 and D5D activity indices showed overall strong correlations between lipid pools. SCD-1 activity index in adipose tissue is best reflected by 16:1/16:0-ratio in serum FFA, but associations with obesity and insulin resistance differ between these pools. D5D in PL was inversely related to obesity and insulin resistance, whereas D6D index showed positive associations.

Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study.

Objective To investigate associations between long term dietary intake of calcium and risk of fracture of any type, hip fractures, and osteoporosis. Design A longitudinal and prospective cohort study, based on the Swedish Mammography Cohort, including a subcohort, the Swedish Mammography Cohort Clinical. Setting A population based cohort in Sweden established in 1987. Participants 61 433 women (born between 1914 and 1948) were followed up for 19 years. 5022 of these women participated in the subcohort. Main outcome measures Primary outcome measures were incident fractures of any type and hip fractures, which were identified from registry data. Secondary outcome was osteoporosis diagnosed by dual energy x ray absorptiometry in the subcohort. Diet was assessed by repeated food frequency questionnaires. Results During follow-up, 14 738 women (24%) experienced a first fracture of any type and among them 3871 (6%) a first hip fracture. Of the 5022 women in the subcohort, 1012 (20%) were measured as osteoporotic. The risk patterns with dietary calcium were non-linear. The crude rate of a first fracture of any type was 17.2/1000 person years at risk in the lowest quintile of calcium intake, and 14.0/1000 person years at risk in the third quintile, corresponding to a multivariable adjusted hazard ratio of 1.18 (95% confidence interval 1.12 to 1.25). The hazard ratio for a first hip fracture was 1.29 (1.17 to 1.43) and the odds ratio for osteoporosis was 1.47 (1.09 to 2.00). With a low vitamin D intake, the rate of fracture in the first calcium quintile was more pronounced. The highest quintile of calcium intake did not further reduce the risk of fractures of any type, or of osteoporosis, but was associated with a higher rate of hip fracture, hazard ratio 1.19 (1.06 to 1.32). Conclusion Gradual increases in dietary calcium intake above the first quintile in our female population were not associated with further reductions in fracture risk or osteoporosis.

Factor analysis of fatty acids in serum lipids as a measure of dietary fat quality in relation to the metabolic syndrome in men

BACKGROUND A specific fatty acid (FA) composition in plasma lipid esters is related to the metabolic syndrome (MetS) and may influence the development of the MetS. OBJECTIVE The objective was to define and study FA factors as measures of dietary fat quality and endogenous FA metabolism in relation to MetS. DESIGN Principal factor analysis was performed to define specific FA factors in men participating in a population-based cohort study-the Uppsala Longitudinal Study of Adult Men. The factors were generated at ages 50 (n = 2009) and 70 (n = 576) y, and relations between FA factors and MetS (National Cholesterol Education Program) were studied in cross-sectional and prospective (20 y) analyses. RESULTS The factor analysis generated 3 major FA factors: a low-linoleic acid (LA) factor, a dietary saturated FA factor, and an n-3 polyunsaturated FA (PUFA) factor. All factors differed between those subjects with MetS (n = 281 of 2009) and those without MetS at age 50 y; only the low-LA factor differed at age 70 y, which suggests an association between MetS and fat quality. The low-LA factor (odds ratio: 1.51; 95% CI: 1.28, 1.79; P < 0.0001) and the n-3 PUFA factor (0.76; 0.64, 0.90; P < 0.001) predicted MetS development over 20 y, independent of smoking habits, physical activity, and BMI. CONCLUSIONS The generated FA factors, which presumably represent dietary fat quality and endogenous FA metabolism, may be important in the development of MetS. This finding supports current dietary recommendations to increase PUFA intakes and restrict saturated FA intakes.

Effects of saturated and unsaturated fatty acids on estimated desaturase activities during a controlled dietary intervention

BACKGROUND AND AIMS Direct measurement of desaturase activities are difficult to obtain in humans. Consequently, surrogate measures of desaturase activity (estimated desaturase activities) have been frequently used in observational studies, and estimated Delta(9)- (or stearoyl-CoA-desaturase (SCD)), Delta(6)- and Delta(5)-desaturase activities have been associated with cardiometabolic disease. Data on how the markers of desaturase activities are modified by changes in dietary fat quality are lacking and therefore warrant examination. METHODS AND RESULTS In a two-period (three weeks) strictly controlled cross-over study, 20 subjects (six women and 14 men) consumed a diet high in saturated fat (SAT-diet) and a rapeseed oil diet (RO-diet), rich in oleic acid (OA), linoleic acid (LA) and alpha-linolenic acid (ALA). Estimated desaturase activities were calculated as precursor to product FA ratios in serum cholesteryl esters and phospholipids. The estimated SCD [16:1 n-7/16:0] and Delta(6)-desaturase [20:3 n-6/18:2 n-6] was significantly higher while Delta(5)-desaturase [20:4 n-6/20:3 n-6] was significantly lower in the SAT-diet (P<0.001 for all), compared to the RO-diet. The serum proportions of palmitic, stearic, palmitoleic and dihomo-gamma-linolenic acids were significantly higher in the SAT-diet while the proportions of LA and ALA were significantly higher in the RO-diet. CONCLUSION This is the first study to demonstrate that surrogate measures of desaturase activities change as a consequence of an alteration in dietary fat quality. Both the [16:1/16:0]-ratio and 16:1 seem to reflect changes in saturated fat intake and may be useful markers of saturated fat intake in Western countries.

Biomarkers of milk fat and the risk of myocardial infarction in men and women: a prospective, matched case-control study

BACKGROUND High intakes of saturated fat have been associated with cardiovascular disease, and milk fat is rich in saturated fat. OBJECTIVE The objective of this study was to investigate the association between the serum milk fat biomarkers pentadecanoic acid (15:0), heptadecanoic acid (17:0), and their sum (15:0+17:0) and a first myocardial infarction (MI). DESIGN The study design was a prospective case-control study nested within a large population-based cohort in Sweden. Included in the study were 444 cases (307 men) and 556 controls (308 men) matched on sex, age, date of examination, and geographic region. Clinical, anthropometric, biomarker fatty acid, physical activity, and dietary data were collected. The odds of a first MI were investigated by using conditional logistic regression. RESULTS In women, proportions of milk fat biomarkers in plasma phospholipids were significantly higher (P < 0.05) in controls than in cases and were, in general, negatively, albeit weakly, correlated with risk factors for metabolic syndrome. The crude standardized odds ratios of becoming an MI case were 0.74 (95% CI: 0.58, 0.94) in women and 0.91 (95% CI: 0.77, 1.1) in men. After multivariable adjustment for confounders, the inverse association remained in both sexes and was significant in women. In agreement with biomarker data, quartiles of reported intake of cheese (men and women) and fermented milk products (men) were inversely related to a first MI (P for trend < 0.05 for all). CONCLUSIONS Milk fat biomarkers were associated with a lower risk of developing a first MI, especially in women. This was partly confirmed in analysis of fermented milk and cheese intake. Components of metabolic syndrome were observed as potential intermediates for the risk relations.

Mediterranean and carbohydrate-restricted diets and mortality among elderly men: a cohort study in Sweden

BACKGROUND Comparative studies on dietary patterns and long-term mortality are sparse. OBJECTIVE The objective was to examine the relations between 10-y mortality and adherence to the World Health Organization dietary guidelines [Healthy Diet Indicator (HDI)], a Mediterranean-like diet, and a carbohydrate-restricted (CR) diet in elderly Swedish men. DESIGN Dietary habits were determined by 7-d dietary records in a population-based longitudinal study of 924 Swedish men (age: 71 ± 1 y). The HDI score (-1 to 8 points), the Mediterranean Diet Score (MDS; 0-8 points), and the CR score (2-20 points) were calculated for each participant. Nonadequate reporters of energy intake were identified (n = 413). Mortality was registered during a median follow-up of 10.2 y. Cox proportional hazards regression, with multivariable adjustments, was used to determine the effects of adherence to each dietary pattern. RESULTS Two hundred fifteen and 88 subjects died of all-cause and cardiovascular disease, respectively. In all individuals, risk relations to mortality for each SD increment in the scores were observed for only MDS, with an adjusted hazard ratio (HR) of 0.83 (95% CI: 0.70, 0.99). Among adequate dietary reporters (n = 511), adjusted HRs for each SD increment in scores were enhanced for MDS (ie, 0.71; 95% CI: 0.55, 0.92) for all-cause mortality and 0.63 (95% CI: 0.42, 0.96) for cardiovascular mortality. Corresponding HRs for CR diet score were 1.19 (95% CI: 0.97, 1.45) for all-cause mortality and 1.44 (95% CI: 1.03, 2.02) for cardiovascular mortality. CONCLUSION Adherence to a Mediterranean-like dietary pattern reduced mortality, whereas adherence to a CR dietary pattern appeared to increase mortality in elderly Swedish men, especially when only adequate dietary reporters were considered.

Polymorphisms in the SCD1 Gene: Associations With Body Fat Distribution and Insulin Sensitivity

Objective: Obesity and insulin resistance are major risk factors for metabolic diseases and are influenced by lifestyle and genetics. The lipogenic enzyme, stearoyl‐coenzyme A‐desaturase (SCD), is related to obesity. Further, SCD1‐deficent mice are protected against obesity and insulin resistance. We hypothesized that genetic polymorphisms in the SCD1 gene would be associated with obesity, insulin sensitivity, and estimated SCD activity in humans.

Stroke and plasma markers of milk fat intake - a prospective nested case-control study

BackgroundDairy products are high in saturated fat and are traditionally a risk factor for vascular diseases. The fatty acids 15:0 and 17:0 of plasma lipids are biomarkers of milk fat intake. The aim of the present study was to evaluate the risk of a first-ever stroke in relation to the plasma milk fat biomarkers.MethodsA prospective case-control study was nested within two population based health surveys in Northern Sweden. Among 129 stroke cases and 257 matched controls, plasma samples for fatty acid analyses were available in 108 cases and 216 control subjects. Proportions of 15:0 and 17:0 of plasma lipids, weight, height, blood lipids, blood pressures, and lifestyle data were employed in conditional logistic regression modelling.ResultsThe proportions of fatty acids 17:0 and 15:0+17:0 of total plasma phospholipids were significantly higher in female controls than cases, but not in men. 17:0 and 15:0+17:0 were significantly and inversely related to stroke in the whole study sample as well as in women. The standardised odds ratio (95% CI) in women to have a stroke was 0.41 (0.24–0.69) for 17:0 in plasma phospholipids. Adjustment for traditional cardiovascular risk factors, physical activity and diet had marginal effects on the odds ratios. A similar, but non-significant, trend was seen in men.ConclusionIt is hypothesised that dairy or milk fat intake may be inversely related to the risk of a first event of stroke. The intriguing results of this study should be interpreted with caution. Follow up studies with greater power, and where intakes are monitored both by dietary recordings and fatty acid markers are needed.

Short term effects of energy restriction and dietary fat sub-type on weight loss and disease risk factors

BACKGROUND AND AIMS Decreasing energy intake relative to energy expenditure is the indisputable tenet of weight loss. In addition to caloric restriction modification of the type of dietary fat may provide further benefits. The aim of the present study was to examine the effect of energy restriction alone and with dietary fat modification on weight loss and adiposity, as well as on risk factors for obesity related disease. METHODS AND RESULTS One-hundred and fifty overweight men and women were randomized into a 3month controlled trial with four low fat (30% energy) dietary arms: (1) isocaloric (LF); (2) isocaloric with 10% polyunsaturated fatty acids (LF-PUFA); (3) low calorie (LF-LC) (-2MJ); (4) low calorie with 10% PUFA (LF-PUFA-LC). Primary outcomes were changes in body weight and body fat and secondary outcomes were changes in fasting levels of leptin, insulin, glucose, lipids and erythrocyte fatty acids. Changes in dietary intake were assessed using 3day food records. One-hundred and twenty-two participants entered the study and 95 completed the study. All groups lost weight and body fat (P<0.0001 time effect for both), but the LC groups lost more weight (P=0.026 for diet effect). All groups reduced total cholesterol levels (P<0.0001 time effect and P=0.017 intervention effect), but the LC and PUFA groups were better at reducing triacylglycerol levels (P=0.056 diet effect). HDL increased with LF-LC and LF-PUFA but not with LF-PUFA-LC (0.042 diet effect). The LF and LF-LC groups reported greater dietary fat reductions than the two PUFA groups (P=0.043). CONCLUSION Energy restriction has the most potent effect on weight loss and lipids, but fat modification is also beneficial when energy restriction is more modest.