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Effect of a dietary intervention including minimal and unprocessed foods, high in natural saturated fats, on the lipid profile of children, pooled evidence from randomized controlled trials and a cohort study.
Hendriksen, RB, van der Gaag, EJ
PloS one. 2022;(1):e0261446
Abstract
AIM: To study the possible effects of a dietary intervention with minimal and unprocessed foods, high in natural saturated fats on the lipid profile and body mass index of children. METHOD This study combines three intervention studies; one non-randomized retrospective cohort study and two randomized controlled trials, to a pooled analysis. The intervention group received a dietary intervention of minimal and unprocessed foods for three to six months, consisting of five times per week green vegetables, three times per week beef, daily 200-300 mL whole cow's milk (3.4% fat) and whole dairy butter (80% fat) on each slice of bread. The control group continued their usual dietary habits. Raw data of the three intervention studies where combined into one single dataset for data analysis, using mixed effects analysis of covariance to test the effects of the dietary advice on the main study outcomes, which are measurements of the lipid profile. RESULTS In total, 267 children aged 1 to 16 years were followed. 135 children were included in the intervention group and 139 children in the control group. Characteristics (age, gender and follow-up period) were equally distributed between the groups at baseline. In the intervention group HDL-cholesterol increased significantly from 1.22 mmol/L, 95% confidence interval (CI) 1.14-1.32 to 1.42 mmol/L 95% CI 1.30-1.65 (p = 0.007). The increase over time in HDL cholesterol in the intervention group was significantly different compared to the increase in the control group (from 1.26 mmol/L, 95% CI 1.19-1.35, to 1.30 mmol/L, 95% CI 1.26-1.37) (p = 0.04). Due to the increased HDL concentration in the intervention group, the total cholesterol/HDL cholesterol ratio decreased significantly from 3.70 mmol/L, 95% CI 3.38-3.87, to 3.25 mmol/L, 95% CI 2.96-3.31 (p = 0.05). CONCLUSION Consumption of minimal and unprocessed foods (high in natural saturated fats) has favourable effects on HDL cholesterol in children. Therefore, this dietary advice can safely be recommended to children.
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Effects of Dietary Fat and Protein on Glucoregulatory Hormones in Adolescents and Young Adults With Type 1 Diabetes.
Harray, AJ, Binkowski, S, Keating, BL, Horowitz, M, Standfield, S, Smith, G, Paramalingam, N, Jones, T, King, BR, Smart, CEM, et al
The Journal of clinical endocrinology and metabolism. 2022;(1):e205-e213
Abstract
CONTEXT Dietary fat and protein impact postprandial hyperglycemia in people with type 1 diabetes, but the underlying mechanisms are poorly understood. Glucoregulatory hormones are also known to modulate gastric emptying and may contribute to this effect. OBJECTIVE Investigate the effects of fat and protein on glucagon-like peptide (GLP-1), glucagon-dependent insulinotropic polypeptide (GIP) and glucagon secretion. METHODS 2 crossover euglycemic insulin clamp clinical trials at 2 Australian pediatric diabetes centers. Participants were 12-21 years (n = 21) with type 1 diabetes for ≥1 year. Participants consumed a low-protein (LP) or high-protein (HP) meal in Study 1, and low-protein/low-fat (LPLF) or high-protein/high-fat (HPHF) meal in Study 2, all containing 30 g of carbohydrate. An insulin clamp was used to maintain postprandial euglycemia and plasma glucoregulatory hormones were measured every 30 minutes for 5 hours. Data from both cohorts (n = 11, 10) were analyzed separately. The main outcome measure was area under the curve of GLP-1, GIP, and glucagon. RESULTS Meals low in fat and protein had minimal effect on GLP-1, while there was sustained elevation after HP (80.3 ± 16.8 pmol/L) vs LP (56.9 ± 18.6), P = .016, and HPHF (103.0 ± 26.9) vs LPLF (69.5 ± 31.9) meals, P = .002. The prompt rise in GIP after all meals was greater after HP (190.2 ± 35.7 pmol/L) vs LP (152.3 ± 23.3), P = .003, and HPHF (258.6 ± 31.0) vs LPLF (151.7 ± 29.4), P < .001. A rise in glucagon was also seen in response to protein, and HP (292.5 ± 88.1 pg/mL) vs LP (182.8 ± 48.5), P = .010. CONCLUSION The impact of fat and protein on postprandial glucose excursions may be mediated by the differential secretion of glucoregulatory hormones. Further studies to better understand these mechanisms may lead to improved personalized postprandial glucose management.
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Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle.
Sarabhai, T, Koliaki, C, Mastrototaro, L, Kahl, S, Pesta, D, Apostolopoulou, M, Wolkersdorfer, M, Bönner, AC, Bobrov, P, Markgraf, DF, et al
Diabetologia. 2022;(2):301-314
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Abstract
AIMS/HYPOTHESIS Energy-dense nutrition generally induces insulin resistance, but dietary composition may differently affect glucose metabolism. This study investigated initial effects of monounsaturated vs saturated lipid meals on basal and insulin-stimulated myocellular glucose metabolism and insulin signalling. METHODS In a randomised crossover study, 16 lean metabolically healthy volunteers received single meals containing safflower oil (SAF), palm oil (PAL) or vehicle (VCL). Whole-body glucose metabolism was assessed from glucose disposal (Rd) before and during hyperinsulinaemic-euglycaemic clamps with D-[6,6-2H2]glucose. In serial skeletal muscle biopsies, subcellular lipid metabolites and insulin signalling were measured before and after meals. RESULTS SAF and PAL raised plasma oleate, but only PAL significantly increased plasma palmitate concentrations. SAF and PAL increased myocellular diacylglycerol and activated protein kinase C (PKC) isoform θ (p < 0.05) but only PAL activated PKCɛ. Moreover, PAL led to increased myocellular ceramides along with stimulated PKCζ translocation (p < 0.05 vs SAF). During clamp, SAF and PAL both decreased insulin-stimulated Rd (p < 0.05 vs VCL), but non-oxidative glucose disposal was lower after PAL compared with SAF (p < 0.05). Muscle serine1101-phosphorylation of IRS-1 was increased upon SAF and PAL consumption (p < 0.05), whereas PAL decreased serine473-phosphorylation of Akt more than SAF (p < 0.05). CONCLUSIONS/INTERPRETATION Lipid-induced myocellular insulin resistance is likely more pronounced with palmitate than with oleate and is associated with PKC isoforms activation and inhibitory insulin signalling. TRIAL REGISTRATION ClinicalTrials.gov .NCT01736202. FUNDING German Federal Ministry of Health, Ministry of Culture and Science of the State North Rhine-Westphalia, German Federal Ministry of Education and Research, European Regional Development Fund, German Research Foundation, German Center for Diabetes Research.
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Dietary stearic acid and palmitic acid do not differently affect ABCA1-mediated cholesterol efflux capacity in healthy men and postmenopausal women: A randomized controlled trial.
van Rooijen, MA, Plat, J, Blom, WAM, Zock, PL, Mensink, RP
Clinical nutrition (Edinburgh, Scotland). 2021;(3):804-811
Abstract
BACKGROUND The saturated fatty acid stearic acid (C18:0) lowers HDL cholesterol compared with palmitic acid (C16:0). However, the ability of HDL particles to promote cholesterol efflux from macrophages (cholesterol efflux capacity; CEC) may better predict coronary heart disease (CHD) risk than HDL cholesterol concentrations. OBJECTIVE We examined effects of exchanging dietary palmitic acid for stearic acid on ATP-binding cassette transporter A1 (ABCA1)-mediated CEC, and other conventional and emerging cardiometabolic risk makers. DESIGN In a double-blind, randomized, crossover study with two 4-week isocaloric intervention periods, 34 healthy men and postmenopausal women (61.5 ± 5.7 years, BMI: 25.4 ± 2.5 kg/m2) followed diets rich in palmitic acids or stearic acids. Difference in intakes was 6% of daily energy. ABCA1-mediated CEC was measured from J774 macrophages to apolipoprotein (apo)B-depleted serum. RESULTS Compared with the palmitic-acid diet, the stearic-acid diet lowered serum LDL cholesterol (-0.14 mmol/L; p = 0.010), HDL cholesterol (-0.09 mmol/L; p=<0.001), and apoA1 (-0.05 g/L; p < 0.001). ABCA1-mediated CEC did not differ between diets (p = 0.280). Cholesteryl ester transfer protein (CETP) mass was higher on stearic acid (0.11 mg/L; p = 0.003), but CETP activity was comparable. ApoB100 did not differ, but triacylglycerol concentrations tended to be higher on stearic acid (p = 0.100). Glucose concentrations were comparable. Effects on insulin and C-peptide were sex-dependent. In women, the stearic-acid diet increased insulin concentrations (1.57 μU/mL; p = 0.002), while in men, C-peptide concentrations were lower (-0.15 ng/mL; p = 0.037). Interleukin 6 (0.15 pg/mL; p = 0.039) and tumor necrosis factor alpha (0.18 pg/mL; p = 0.005), but not high-sensitivity C-reactive protein, were higher on stearic acid. Soluble intracellular adhesion molecule (9 ng/mL; p = 0.033), but not soluble vascular cell adhesion molecule and endothelial-selectin concentrations decreased after stearic-acid consumption. CONCLUSIONS As expected, stearic-acid intake lowered LDL cholesterol, HDL cholesterol, and apoA1. Insulin sensitivity in women and low-grade inflammation might be unfavorably affected by stearic-acid intake. However, palmitic-acid and stearic-acid intakes did not differently affect ABCA1-mediated CEC. CLINICAL TRIAL REGISTRY This trial was registered at clinicaltrials.gov as NCT02835651.
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Low-fat dietary pattern and breast cancer mortality by metabolic syndrome components: a secondary analysis of the Women's Health Initiative (WHI) randomised trial.
Pan, K, Aragaki, AK, Neuhouser, ML, Simon, MS, Luo, J, Caan, B, Snetselaar, L, Mortimer, JE, Manson, JE, Kroenke, C, et al
British journal of cancer. 2021;(3):372-379
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BACKGROUND In the Women's Health Initiative (WHI) dietary modification (DM) randomised trial, the low-fat dietary intervention reduced deaths from breast cancer (P = 0.02). Extending these findings, secondary analysis examined dietary intervention influence on breast cancer mortality by metabolic syndrome (MS) components. METHODS In total, 48,835 postmenopausal women with no prior breast cancer were randomised to a low-fat dietary intervention or comparison groups. Four MS components were determined at entry in 45,833 participants: (1) high waist circumference, (2) high blood pressure, (3) high cholesterol and (4) diabetes history. Forest plots of hazard ratios (HRs) were generated with P-values for interaction between randomisation groups and MS component score. Primary outcome was death from breast cancer by metabolic syndrome score. RESULTS HRs and 95% confidence intervals (CI) for dietary intervention influence on death from breast cancer were with no MS components (n = 10,639), HR 1.09, 95% CI 0.63-1.87; with 1-2 MS components (n = 30,948), HR 0.80, 95% CI 0.62-1.02; with 3-4 MS components (n = 4,246), HR 0.31, 95% CI 0.14-0.69 (interaction P = 0.01). CONCLUSIONS While postmenopausal women with 3-4 MS components were at higher risk of death from breast cancer, those randomised to a low-fat dietary intervention more likely had reduction in this risk. REGISTRY ClinicalTrials.gov (NCT00000611).
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Causal effects of relative fat, protein, and carbohydrate intake on chronic kidney disease: a Mendelian randomization study.
Park, S, Lee, S, Kim, Y, Lee, Y, Kang, MW, Kim, K, Kim, YC, Han, SS, Lee, H, Lee, JP, et al
The American journal of clinical nutrition. 2021;(4):1023-1031
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BACKGROUND The effects of specific macronutrients on kidney function independent of total calorie intake have rarely been studied, although the composition of macronutrient intake has been reported to affect health outcomes. OBJECTIVES We aimed to investigate the effects of macronutrient intake ratios on the risk of chronic kidney disease (CKD) by Mendelian randomization (MR) analysis. METHODS The study was an observational cohort study mainly based on the UK Biobank and including MR analysis. First, we evaluated the relative baseline macronutrient composition-that is, the number of calories from each macronutrient divided by total calorie intake-of the diets of UK Biobank participants, and we used Cox regression to assess the incidence of end-stage kidney disease (ESKD) in 65,164 participants with normal kidney function [estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2]. We implemented a genetic instrument for relative fat, protein, and carbohydrate intake developed by a previous genome-wide association study (GWAS) and performed MR analysis. Two-sample MR was performed with the summary statistics from independent CKDGen GWAS for kidney function traits (n = 567,460), including CKD (eGFR <60 mL/min/1.73 m2) and log-transformed eGFR. RESULTS The median relative macronutrient intake composition at baseline was 35% fats, 15% protein, and 50% carbohydrates. Higher relative protein intake in subjects with normal kidney function was significantly associated with a lower risk of incident ESKD (HR: 0.54; 95% CI: 0.30, 0.95) in the observational investigation. Two-sample MR indicated that increased relative fat intake causally increased the risk of kidney function impairment [CKD (OR: 1.94; 95% CI: 1.39, 2.71); log eGFR (β: -0.036; 95% CI: -0.048, -0.024)] and that higher relative protein intake was causally linked to a lower CKD risk [CKD (OR: 0.50; 95% CI: 0.35, 0.72); log eGFR (β: 0.044; 95% CI: 0.030, 0.058)]. CONCLUSIONS A desirable macronutrient composition, including high relative protein intake and low relative fat intake, may causally reduce the risk of CKD in the general population.
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Egg and saturated fat containing breakfasts have no acute effect on acute glycemic control in healthy adults: a randomized partial crossover trial.
Dhanasekara, CS, Dawson, JA, Binks, M, Childress, A, Dhurandhar, NV
Nutrition & diabetes. 2021;(1):34
Abstract
BACKGROUND/OBJECTIVES High egg consumption is associated with poor glycemic control. Considering the widespread consumption of eggs, it is crucial to determine causality in this association. We tested if egg consumption acutely alters glucose disposal in the absence or presence of saturated fat, which is frequently consumed with eggs. SUBJECTS/METHODS In a randomized partial crossover clinical trial, 48 subjects (consuming ≥ 1 egg/week) received two of four isocaloric, macronutrient-matched breakfasts. The groups were defined based on the main ingredient of the breakfasts offered: eggs (EB); saturated fat (SB); eggs and saturated fat (ES); and control, which included a cereal based breakfast (CB). The breakfasts were offered in two testing sessions spaced seven days apart. Six blood samples (pre breakfast (fasting); 30, 60, 90, 120, and 180 minutes post breakfast) were collected to measure glucose and insulin levels. Area under the curves (AUC) were analyzed controlling for the baseline concentrations using mixed-effects models accounting for within-subject dependencies to compare these across breakfast assignments. RESULTS Forty-eight patients (46% males, age 25.8 ± 7.7 years, BMI 25.7 ± 4.6 kg/m2) were included. Neither EB, SB nor ES was associated with a significant difference in AUC of glucose or insulin compared to CB (p > 0.1). CONCLUSIONS Acutely, consumption of egg breakfast with or without accompanying saturated fat does not adversely affect glucose disposal in healthy adults. While this is reassuring for continued egg consumption, a long-term evaluation of egg intake with or without saturated fat would be the next step.
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Small Amounts of Dietary Medium-Chain Fatty Acids Protect Against Insulin Resistance During Caloric Excess in Humans.
Lundsgaard, AM, Fritzen, AM, Sjøberg, KA, Kleinert, M, Richter, EA, Kiens, B
Diabetes. 2021;(1):91-98
Abstract
Medium-chain fatty acids (MCFAs) have in rodents been shown to have protective effects on glucose homeostasis during high-fat overfeeding. In this study, we investigated whether dietary MCFAs protect against insulin resistance induced by a hypercaloric high-fat diet in humans. Healthy, lean men ingested a eucaloric control diet and a 3-day hypercaloric high-fat diet (increase of 75% in energy, 81-83% energy [E%] from fat) in randomized order. For one group (n = 8), the high-fat diet was enriched with saturated long-chain FAs (LCSFA-HFD), while the other group (n = 9) ingested a matched diet, but with ∼30 g (5E%) saturated MCFAs (MCSFA-HFD) in substitution for a corresponding fraction of the saturated long-chain fatty acids (LCFAs). A hyperinsulinemic-euglycemic clamp with femoral arteriovenous balance and glucose tracer was applied after the control and hypercaloric diets. In LCSFA-HFD, whole-body insulin sensitivity and peripheral insulin-stimulated glucose disposal were reduced. These impairments were prevented in MCSFA-HFD, accompanied by increased basal fatty acid oxidation, maintained glucose metabolic flexibility, increased nonoxidative glucose disposal related to lower starting glycogen content, and increased glycogen synthase activity, together with increased muscle lactate production. In conclusion, substitution of a small amount of dietary LCFAs with MCFAs rescues insulin action in conditions of lipid-induced energy excess.
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Additional Insulin Is Required in Both the Early and Late Postprandial Periods for Meals High in Protein and Fat: A Randomized Trial.
Keating, B, Smart, CEM, Harray, AJ, Paramalingam, N, Smith, G, Jones, TW, King, BR, Davis, EA
The Journal of clinical endocrinology and metabolism. 2021;(9):e3611-e3618
Abstract
CONTEXT The pattern and quantity of insulin required for high-protein high-fat (HPHF) meals is not well understood. OBJECTIVE This study aimed to determine the amount and delivery pattern of insulin required to maintain euglycemia for 5 hours after consuming a HPHF meal compared with a low-protein low-fat (LPLF) meal. METHODS This randomized crossover clinical trial, conducted at 2 Australian pediatric diabetes centers, included 10 patients (12-21 years of age) with type 1 diabetes for ≥ 1 year. Participants were randomized to HPHF meal (60 g protein, 40 g fat) or LPLF meal (5 g protein, 5 g fat) with identical carbohydrate content (30 g). A modified insulin clamp technique was used to determine insulin requirements to maintain postprandial euglycemia for 5 hours. Total mean insulin requirements over 5 hours were measured. RESULTS The total mean insulin requirements for the HPHF meal were significantly greater than for the LPLF meal (11.0 [CI 9.2, 12.8] units vs 5.7 [CI 3.8, 7.5] units; P = 0.001). Extra intravenous insulin was required for HPHF 0 to 2 hours (extra 1.2 [CI 0.6, 1.6] units/h), 2 to 4 hours (extra 1.1 [CI 0.6, 1.6] units/h), and 4 to 5 hours (extra 0.6 [CI 0.1, 1.1] units/h) after the meal. There were marked inter-individual differences in the quantity of additional insulin (0.3 to 5 times more for HPHF) and the pattern of insulin delivery (0%-85% of additional insulin required in the first 2 hours). CONCLUSION The addition of protein and fat to a standardized carbohydrate meal almost doubled the mean insulin requirement, with most participants requiring half of the additional insulin in the first 2 hours.
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Dietary Intake of trans Fatty Acids in the Slovenian Population.
Zupanič, N, Hribar, M, Hristov, H, Lavriša, Ž, Kušar, A, Gregorič, M, Blaznik, U, Koroušić Seljak, B, Golja, P, Vidrih, R, et al
Nutrients. 2021;(1)
Abstract
Consumption of trans fatty acids (TFAs) has been unequivocally linked to several adverse health effects, with the increased risk of cardiovascular disease being one of the most well understood. To reduce TFA-related morbidity and mortality, several countries have imposed voluntary or mandatory measures to minimize the content of industrial TFAs (iTFAs) in the food supply. In 2018, Slovenia introduced a ban on iTFAs on top of preceding voluntary calls to industry to reduce its use of partially hydrogenated oils (PHOs) as the main source of iTFAs. To investigate the consumption of TFAs, data available from the nationally representative dietary survey SI.Menu were analyzed. The survey consisted of two 24-h non-consecutive day recalls from 1248 study participants from three age groups (10-17, 18-64, 65-74 years old), combined with socio-demographic, socio-economic, and lifestyle parameters. The analyses demonstrated that, on average, TFAs accounted for 0.38-0.50% of total energy intake (TEI). However, 13% of adolescents, 29.4% of adults, and 41.8% of the elderly population still consumed more than 0.50% TEI with TFAs. The main sources of TFAs in the diet were naturally present TFAs from butter, meat dishes, and meat products, regardless of the age group. Results indicate that following the reformulation activities, the major sources of TFAs in the diets of the Slovenian population now represent foods which are natural sources of TFAs.