Achievement of dietary fatty acid intakes in long-term controlled intervention studies: approach and methodology

Objective: To describe the calculations and approaches used to design experimental diets of differing saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) compositions for use in a long-term dietary intervention study, and to evaluate the degree to which the dietary targets were met. Design, setting and subjects: Fifty-one students living in a university hall of residence consumed a reference (SFA) diet for 8 weeks followed by either a moderate MUFA (MM) diet or a high MUFA (HM) diet for 16 weeks. The three diets were designed to differ only in their proportions of SFA and MUFA, while keeping total fat, polyunsaturated fatty acids (PUFA), trans-fatty acids, and the ratio of palmitic to stearic acid, and n-6 to n-3 PUFA, unchanged. Results: Using habitual diet records and a standardised database for food fatty acid compositions, a sequential process of theoretical fat substitutions enabled suitable fat sources for use in the three diets to be identified, and experimental margarines for baking, spreading and the manufacture of snack foods to be designed. The dietary intervention was largely successful in achieving the fatty acid targets of the three diets, although unintended differences between the original target and the analysed fatty acid composition of the experimental margarines resulted in a lower than anticipated MUFA intake on the HM diet, and a lower ratio of palmitic to stearic acid compared with the reference or MM diet. Conclusions: This study has revealed important theoretical considerations that should be taken into account when designing diets of specific fatty acid composition, as well as practical issues of implementation.

Comparison of dietary fat and fatty acid intake estimated by the duplicate diet collection technique and estimated dietary records

Introduction A high saturated fatty acid intake is a well recognized risk factor for coronary heart disease development. More recently a high intake of n-6 polyunsaturated fatty acids (PUFA) in combination with a low intake of the long chain n-3 PUFA, eicosapentaenoic acid and docosahexaenoic acid has also been implicated as an important risk factor. Aim To compare total dietary fat and fatty acid intake measured by chemical analysis of duplicate diets with nutritional database analysis of estimated dietary records, collected over the same 3-day study period. Methods Total fat was analysed using soxhlet extraction and subsequently the individual fatty acid content of the diet was determined by gas chromatography. Estimated dietary records were analysed using a nutrient database which was supplemented with a selection of dishes commonly consumed by study participants. Results Bland & Altman statistical analysis demonstrated a lack of agreement between the two dietary assessment techniques for determining dietary fat and fatty acid intake. Conclusion The lack of agreement observed between dietary evaluation techniques may be attributed to inadequacies in either or both assessment techniques. This study highlights the difficulties that may be encountered when attempting to accurately evaluate dietary fat intake among the population.

Effects of dietary fat modification on skeletal muscle fatty acid handling in the metabolic syndrome

Objective: In the metabolic syndrome (MetS), increased fat storage in ‘nonadipose’ tissues such as skeletal muscle may be related to insulin resistance (‘lipid overflow’ hypothesis). The objective of this study was to examine the effects of dietary fat modification on the capacity of skeletal muscle to handle dietary and endogenous fatty acids (FAs). Subjects and Methods: In total, 29 men with the MetS were randomly assigned to one of four diets for 12 weeks: a high-fat saturated fat diet (HSFA, n=6), a high-fat monounsaturated fat diet (HMUFA, n=7) and two low-fat high-complex carbohydrate diets supplemented with (LFHCCn−3, n=8) or without (LFHCC, n=8) 1.24 g per day docosahexaenoic and eicosapentaenoic acid. Fasting and postprandial skeletal muscle FA handling was examined by measuring arteriovenous concentration differences across the forearm muscle. [2H2]-palmitate was infused intravenously to label endogenous triacylglycerol (TAG) and free fatty acids in the circulation and subjects received a high-fat mixed meal (2.6 MJ, 61 energy% fat) containing [U-13C]-palmitate to label chylomicron-TAG. Results: Postprandial circulating TAG concentrations were significantly lower after dietary intervention in the LFHCCn−3 group compared to the HSFA group (ΔiAUC −139±67 vs 167±70 μmol l−1 min−1, P=0.009), together with decreased concentrations of [U-13C]-labeled TAG, representing dietary FA. Fasting TAG clearance across forearm muscle was decreased on the HSFA diet, whereas no differences were observed in postprandial forearm muscle FA handling between diets. Conclusion: Chronic manipulation of dietary fat quantity and quality did not affect forearm muscle FA handling in men with the MetS. Postprandial TAG concentrations decreased on the LFHCCn−3 diet, which could be (partly) explained by lower concentration of dietary FA in the circulation.

Is fatty acid intake a predictor of arterial stiffness and blood pressure in men? Evidence from the Caerphilly Prospective Study

Background and aims: Arterial stiffness is an independent predictor of cardiovascular disease (CVD) events and all-cause mortality and may be differentially affected by dietary fatty acid (FA) intake. The aim of this study was to investigate the relationship between FA consumption and arterial stiffness and blood pressure in a community-based population. Methods and results: The Caerphilly Prospective Study recruited 2398 men, aged 45-59 years, who were followed up at 5-year intervals for a mean of 17.8-years (n 787). A semi-quantitative food frequency questionnaire estimated intakes of total, saturated, mono- and poly-unsaturated fatty acids (SFA, MUFA, PUFA). Multiple regression models investigated associations between intakes of FA at baseline with aortic pulse wave velocity (aPWV), augmentation index (AIx), systolic and diastolic blood pressure (SBP, DBP) and pulse pressure after a 17.8-year follow-up - as well as cross-sectional relationships with metabolic markers. After adjustment, higher SFA consumption at baseline was associated with higher SBP (P = 0.043) and DBP (P = 0.002) and after a 17.8-year follow-up was associated with a 0.51 m/s higher aPWV (P = 0.006). After adjustment, higher PUFA consumption at baseline was associated with lower SBP (P = 0.022) and DBP (P = 0.036) and after a 17.8-year follow-up was associated with a 0.63 m/s lower aPWV (P = 0.007). Conclusion: This study suggests that consumption of SFA and PUFA have opposing effects on arterial stiffness and blood pressure. Importantly, this study suggests that consumption of FA is an important risk factor for arterial stiffness and CVD.

Seasonal variation in the fatty acid composition of milk available at retail in the United Kingdom and implications for dietary intake

Milk and dairy products are major sources of fat in the human diet, but there are few detailed reports on the fatty acid composition of retail milk, trans fatty acids in particular, and how these change throughout the year. Semi-skimmed milk was collected monthly for one year from five supermarkets and analysed for fatty acid composition. Relative to winter, milk sold in the summer contained lower total saturated fatty acid (SFA; 67 vs 72 g/100 g fatty acids) and higher cis-monounsaturated fatty acid (MUFA; 23 vs 21 g/100 g fatty acids) and total trans fatty acid (6.5 vs 4.5 g/100 g fatty acids) concentrations. Concentrations of most trans-18:1 and -18:2 isomers also exhibited seasonal variation. Results were applied to national dietary intakes, and indicated that monthly variation in the fatty acid composition of milk available at retail has limited influence on total dietary fatty acid consumption by UK adults.

Development of a food-exchange model to replace saturated fat with MUFAS and n-6 PUFAS in adults at moderate cardiovascular risk

The recommendation to reduce saturated fatty acid (SFA) consumption to ≤10% of total energy (%TE) is a key public health target aimed at lowering cardiovascular disease (CVD) risk. Replacement of SFA with unsaturated fats may provide greater benefit than replacement with carbohydrates, yet the optimal type of fat is unclear. The aim was to develop a flexible food-exchange model to investigate the effects of substituting SFAs with monounsaturated fatty acids (MUFAs) or n-6 (ω-6) polyunsaturated fatty acids (PUFAs) on CVD risk factors. In this parallel study, UK adults aged 21-60 y with moderate CVD risk (50% greater than the population mean) were identified using a risk assessment tool (n = 195; 56% females). Three 16-wk isoenergetic diets of specific fatty acid (FA) composition (%TE SFA:%TE MUFA:%TE n-6 PUFA) were designed using spreads, oils, dairy products, and snacks as follows: 1) SFA-rich diet (17:11:4; n = 65); 2) MUFA-rich diet (9:19:4; n = 64); and 3) n-6 PUFA-rich diet (9:13:10; n = 66). Each diet provided 36%TE total fat. Dietary targets were broadly met for all intervention groups, reaching 17.6 ± 0.4%TE SFA, 18.5 ± 0.3%TE MUFA, and 10.4 ± 0.3%TE n-6 PUFA in the respective diets, with significant overall diet effects for the changes in SFA, MUFA, and n-6 PUFA between groups (P < 0.001). There were no differences in the changes of total fat, protein, carbohydrate, and alcohol intake or anthropometric measures between groups. Plasma phospholipid FA composition showed changes from baseline in the proportions of total SFA, MUFA, and n-6 PUFA for each diet group, with significant overall diet effects for total SFA and MUFA between groups (P < 0.001). In conclusion, successful implementation of the food-exchange model broadly achieved the dietary target intakes for the exchange of SFA with MUFA or n-6 PUFA with minimal disruption to the overall diet in a free-living population. This trial was registered at clinicaltrials.gov as NCT01478958.

Endothelial function and insulin sensitivity during acute non-esterified fatty acid elevation: effects of fat composition and gender

Background and Aims: We have reported that adverse effects on flow-mediated dilation of an acute elevation of non-esterified fatty acids rich in saturated fat (SFA) are reversed following addition of long-chain (LC) n-3 polyunsaturated fatty acids (PUFA), and hypothesised that these effects may be mediated through alterations in insulin signalling pathways. In a subgroup, we explored the effects of raised NEFA enriched with SFA, with or without LC n-3 PUFA, on whole body insulin sensitivity (SI) and responsiveness of the endothelium to insulin infusion. Methods and Results: Thirty adults (mean age 27.8 y, BMI 23.2 kg/m2) consumed oral fat loads on separate occasions with continuous heparin infusion to elevate NEFA between 60-390 min. For the final 150 min, a hyperinsulinaemic-euglycaemic clamp was performed, whilst FMD and circulating markers of endothelial function were measured at baseline, pre-clamp (240 min) and post-clamp (390 min). NEFA elevation during the SFA-rich drinks was associated with impaired FMD (P=0.027) whilst SFA+LC n-3 PUFA improved FMD at 240 min (P=0.003). In males, insulin infusion attenuated the increase in FMD with SFA+LC n-3 PUFA (P=0.049), with SI 10% greater with SFA+LC n-3 PUFA than SFA (P=0.041). Conclusion: This study provides evidence that NEFA composition during acute elevation influences both FMD and SI, with some indication of a difference by gender. However our findings are not consistent with the hypothesis that the effects of fatty acids on endothelial function and SI operate through a common pathway. Trial registered at clinicaltrials.gov, NCT01351324.

Replacement of saturated with unsaturated fats had no impact on vascular function but beneficial effects on lipid biomarkers, E-selectin and blood pressure: results from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study

Background: Public health strategies to lower cardiovascular disease (CVD) risk involve reducing dietary saturated fatty acid (SFA) intake to ≤10% of total energy (%TE). However, the optimal type of replacement fat is unclear. Objective: We investigated the substitution of 9.5-9.6%TE dietary SFA with either monounsaturated (MUFA) or n-6 polyunsaturated fatty acids (PUFA) on vascular function and other CVD risk factors. Design: Using a randomized, controlled, single-blind, parallel group dietary intervention, 195 men and women aged 21-60 y with moderate CVD risk (≥50% above the population mean) from the United Kingdom followed one of three 16-wk isoenergetic diets (%TE target compositions, total fat:SFA:MUFA:n-6 PUFA): SFA-rich (36:17:11:4, n = 65), MUFA-rich (36:9:19:4, n = 64) or n-6 PUFA-rich (36:9:13:10, n = 66). The primary outcome measure was flow-mediated dilatation (%FMD); secondary outcome measures included fasting serum lipids, microvascular reactivity, arterial stiffness, ambulatory blood pressure, and markers of insulin resistance, inflammation and endothelial activation. Results: Replacing SFA with MUFA or n-6 PUFA did not significantly impact on %FMD (primary endpoint) or other measures of vascular reactivity. Of the secondary outcome measures, substitution of SFA with MUFA attenuated the increase in night systolic blood pressure (-4.9 mm Hg, P = 0.019) and reduced E-selectin (-7.8%, P = 0.012). Replacement with MUFA or n-6 PUFA lowered fasting serum total cholesterol (TC; -8.4% and -9.2%, respectively), low-density lipoprotein cholesterol (-11.3% and -13.6%) and TC to high-density lipoprotein cholesterol ratio (-5.6% and -8.5%) (P ≤ 0.001). These changes in low-density lipoprotein cholesterol equate to an estimated 17-20% reduction in CVD mortality. Conclusions: Substitution of 9.5-9.6%TE dietary SFA with either MUFA or n-6 PUFA did not impact significantly on %FMD or other measures of vascular function. However, the beneficial effects on serum lipid biomarkers, blood pressure and E-selectin offer a potential public health strategy for CVD risk reduction.

Neutrophil fatty acid composition: effect of a single session of exercise and glutamine supplementation

The fatty acid composition of immune cells appears to contribute to variations of cell function. The independent and combined effects of a single session of exercise (SSE) and glutamine supplementation (GS) on neutrophil fatty acid composition were investigated. Compared to control (no treatment given - i.e. neither SSE or GS), single session of exercise decreased myristic, palmitic and eicosapentaenoic (EPA) acids, and increased lauric, oleic, linoleic, arachidonic (AA) and docosahexaenoic (DHA) acids whereas glutamine supplementation combined with SSE (GS+SSE) increased oleic acid. Polyunsaturated/saturated fatty acid ratio and Unsaturation index were higher in neutrophils from the SSE and GS groups as compared with control. These findings support the proposition that SSE and GS may modulate neutrophil function through alterations in fatty acid composition.

The role of proliferator-activated receptor gamma coactivator-1 alpha in the fatty-acid -dependent transcriptional control of interleukin-10 in hepatic cells of rodents

Interleukin-10 (IL-10) is an endogenous factor that restrains hepatic insulin resistance in diet-induced steatosis Reducing IL-10 expression increases proinflammatory activity in the steatotic liver and worsens insulin resistance As the transcriptional coactivator proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) plays a central role in dysfunctional hepatocytic activity in diet-induced steatosis, we hypothesized that at least part of the action of PGC-1 alpha could be mediated by reducing the transcription of the IL-10 gene Here, we used immunoblotting, real-time polymerase chain reaction, immunocytochemistry, and chromatin immunoprecipitation assay to investigate the role of PGC-1 alpha in the control of IL-10 expression in hepatic cells First, we show that, in the intact steatotic liver, the expressions of IL-10 and PGC-1 alpha are increased Inhibiting PGC-1 alpha expression by antisense oligonucleotide increases IL-10 expression and reduces the steatotic phenotype. In cultured hepatocytes, the treatment with saturated and unsaturated fatty acids increased IL-10 expression. This was accompanied by increased association of PGC-1 alpha with c-Maf and p50-nuclear factor (NF) kappa B, 2 transcription factors known to modulate IL-10 expression In addition, after fatty acid treatment. PGC-1 alpha, c-Maf, and p50-NF kappa B migrate from the cytosol to the nuclei of hepatocytes and bind to the IL-10 promoter region Inhibiting NF kappa B activation with salicylate reduces IL-10 expression and the association of PGC-1 alpha with p50-NF kappa B Thus, PGC-1 alpha emerges as a potential transcriptional regulator of the inflammatory phenomenon taking place in the steatotic liver (C) 2010 Elsevier Inc All rights reserved

Comparison of fatty acid composition in nine organs of the sympatric Antarctic teleost fish species Notothenia coriiceps and Notothenia rossii (Perciformes: Nototheniidae)

Fatty acid (FA) composition of nine organs from two closely related Antarctic fish species, Notothenia codiceps and Notothenia rossii, was determined through gas chromatography with flame ionization detection. A data set for each species was obtained using major FA profiles from specimens caught in the sea waters of Admiralty Bay during the summer season. The FA profiles for both species are overall similar, but organ peculiarities have been found, which could reflect metabolic specificities and feeding habits between species. With the exception of liver, the most abundant FA in organs was the n-3 polyunsaturated FA. The total n-6 polyunsaturated FAs were minor components in all evaluated organs. Palmitic acid was identified as the major saturated FA, whereas oleic acid was the most represented of the monounsaturated FA in almost all assessed organs of both species. The n-3/n-6 ratios of all organs were higher than 3.5. Differences in individual FA and FA metabolic profiles of some organs observed between N. coriiceps and N. rossii suggest specific requirements in the mobilization, transport, incorporation, and/or catabolism of lipids that were reinforced by differences on some FA ratios expressing the activity coefficient of enzymes implicated on the FA pathway flux. (C) 2009 Elsevier Inc. All rights reserved.

Lipid and selenium sources on fatty acid composition of intramuscular fat and muscle selenium concentration of Nellore steers

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Lipid and selenium sources on fatty acid composition of intramuscular fat and muscle selenium concentration of Nellore steers

The objective of this study was to evaluate the effect of lipid and selenium sources in diets for finishing Nellore steers on the fatty acid composition and selenium concentration of the longissimus muscle. Fifty Nellore steers (body weight = 458 +/- 39 kg) were assigned to one of six dietary treatments: 1) diet containing sunflower seed and inorganic selenium; 2) sunflower seed and organic selenium; 3) whole cottonseed and inorganic selenium; 4) whole cottonseed and organic selenium; 5) soybeans and inorganic selenium; and 6) soybeans and organic selenium. Diets were formulated with the same amount of nitrogen and calories and supplied once daily to steers in collective pens, with three animals per pen, for 120 d. At the end of the trial, steers were slaughtered and samples of the longissimus muscle were collected for fatty acid and selenium analysis. Effect of selenium sources was detected for selenium concentration in the longissimus muscle. Organic selenium had higher concentrations in the meat compared with inorganic selenium. The total saturated, monounsaturated and polyunsaturated fatty acids did not differ between the sources of lipids and selenium. For selenium sources, no differences were observed between the concentrations of polyunsaturated fat. Also, no differences in C18:2 cis-9 trans-11 concentrations were noted; however, steers fed sunflower seed presented greater proportions of this fatty acid in the meat. The results indicated that the use of sunflower seed, cottonseed or soybeans and organic or inorganic selenium in feedlot diets to Nellore cattle does not alter the great part of the fatty acid profile of the longissimus muscle. However, the inclusion of sunflower seed in the diet increases the meat CLA cis-9, trans-11, which is desirable and beneficial for the health of consumers.

Trans fatty acid intake is associated with insulin sensitivity but independently of inflammation

High saturated and trans fatty acid intake, the typical dietary pattern of Western populations, favors a proinflammatory status that contributes to generating insulin resistance (IR). We examined whether the consumption of these fatty acids was associated with IR and inflammatory markers. In this cross-sectional study, 127 non-diabetic individuals were allocated to a group without IR and 56 to another with IR, defined as homeostasis model assessment-IR (HOMA-IR) >2.71. Diet was assessed using 24-h food recalls. Multiple linear regression was employed to test independent associations with HOMA-IR. The IR group presented worse anthropometric, biochemical and inflammatory profiles. Energy intake was correlated with abdominal circumference and inversely with adiponectin concentrations (r = -0.227, P = 0.002), while saturated fat intake correlated with inflammatory markers and trans fat with HOMA-IR (r = 0.160, P = 0.030). Abdominal circumference was associated with HOMA-IR (r = 0.430, P < 0.001). In multiple analysis, HOMA-IR remained associated with trans fat intake (beta = 1.416, P = 0.039) and body mass index (beta = 0.390, P < 0.001), and was also inversely associated with adiponectin (beta = -1.637, P = 0.004). Inclusion of other nutrients (saturated fat and added sugar) or other inflammatory markers (IL-6 and CRP) into the models did not modify these associations. Our study supports that trans fat intake impairs insulin sensitivity. The hypothesis that its effect could depend on transcription factors, resulting in expression of proinflammatory genes, was not corroborated. We speculate that trans fat interferes predominantly with insulin signaling via intracellular kinases, which alter insulin receptor substrates.

Sleep duration in elderly obese patients correlated negatively with intake fatty

Study objectives: The purpose of the present study was to evaluate the relationship between sleep duration and dietary habits in elderly obese patients treated at an institute of cardiology. Methods: The fifty-eight volunteers were elderly patients with obesity (classified as obese according to BMI) of both genders, between 60 and 80 years of age. All participants were subjected to assessments of food intake, anthropometry, level of physical activity, and duration of sleep. Results: The men had significantly greater weight, height, and waist circumference than women. Sleep durations were correlated with dietary nutrient compositions only in men. We found a negative association between short sleep and protein intake (r = -0.43; p = 0.02), short sleep and monounsaturated fatty acids intake (r = -0.40; p = 0.03), and short sleep and cholesterol dietary intake (r = -0.50; p = 0.01). Conclusions: We conclude that mainly in men, volunteers that had short sleep duration showed a preference for high energy-density as fatty food, at least in part, may explain the relationship between short sleep duration and the development of metabolic abnormalities.