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Randomized Controlled Trial
. 2024 Mar 4;15(5):2733-2750.
doi: 10.1039/d3fo05324e.

Postprandial lipid and vascular responses following consumption of a commercially-relevant interesterified palmitic acid-rich spread in comparison to functionally-equivalent non-interesterified spread and spreadable butter: a randomised controlled trial in healthy adults

Wendy L Hall  1 , Aseel Alkoblan  1   2   3 , Philippa S Gibson  1 , Maria D'Annibale  1 , Astrid Coekaerts  1 , Mathilde Bauer  1 , Johanna H Bruce  4 , Beryle Lecomte  5 , Armelle Penhoat  5 , Fabienne Laugerette  5 , Marie-Caroline Michalski  5 , Louise J Salt  6 , Peter J Wilde  6 , Sarah E Berry  1
Affiliations
Randomized Controlled Trial

Postprandial lipid and vascular responses following consumption of a commercially-relevant interesterified palmitic acid-rich spread in comparison to functionally-equivalent non-interesterified spread and spreadable butter: a randomised controlled trial in healthy adults

Wendy L Hall et al. Food Funct. .

Abstract

Background: Interesterification is an industrial processing technique used widely where hard fats are essential for functionality and consumer acceptability, e.g. margarines and lower fat spreads. Objective: The aim of this study was to compare acute cardiovascular effects of functionally equivalent spreads (similar solid fat content) made with interesterified (IE) or non-IE palm-based fats, or spreadable butter. Methods: A randomised, controlled, 4-armed crossover, double-blind study (25 men, 25 women; 35-75 years; healthy; mean BMI 24.5, SD 3.8), compared effects of mixed nutrient meals containing 50 g fat from functionally equivalent products [IE spread, non-IE spread and spreadable butter (SB), with rapeseed oil (RO) as a reference treatment: with 16.7%, 27.9%, 19.3% and 4% palmitic acid, respectively] on 8 h postprandial changes in plasma triacylglycerol (TAG) and endothelial dysfunction (flow-mediated dilatation; FMD). Circulating reactive oxygen species (estimated using a neutrophil oxidative burst assay), glucose, insulin, NEFA, lipoprotein particle profiles, inflammatory markers (glycoprotein acetylation (Glyc-A) and IL-6), and biomarkers of endotoxemia were measured. Results: Postprandial plasma TAG concentrations after test meals were similar. However following RO versus the 3 spreads, there were significantly higher postprandial apolipoprotein B concentrations, and small HDL and LDL particle concentrations, and lower postprandial extra-large, large, and medium HDL particle concentrations, as well as smaller average HDL and LDL particle sizes. There were no differences following IE compared to the other spreads. Postprandial FMD% did not decrease after high-fat test meals, and there were no differences between treatments. Postprandial serum IL-6 increased similarly after test meals, but RO provoked a greater increase in postprandial concentrations of glycoprotein acetyls (GlycA), as well as 8 h sCD14, an endotoxemia marker. All other postprandial outcomes were not different between treatments. Conclusions: In healthy adults, a commercially-available IE-based spread did not evoke a different postprandial triacylglycerol, lipoprotein subclass, oxidative stress, inflammatory or endotoxemic response to functionally-equivalent, but compositionally-distinct alternative spreads. Clinical trial registry number: NCT03438084 (https://ClinicalTrials.gov).

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Conflict of interest statement

SB and WH are consultants to ZOE Ltd and SB also receives options in ZOE Ltd, but this is not related to the present study. JB is employed by a multinational agrochemical company (ADM) which manufactures vegetable oils including interesterified fats. M-CM received research funding from CNIEL, Sodiaal-Candia R&I and Danone Nutricia Research and has a research partnership with ITERG, which are not related to the present study. All other authors declared they had no conflicts of interest.

Figures

Fig. 1
Fig. 1. Study design. FMD, flow-mediated dilatation; TAG, triacylglycerol; PFA, plasma fatty acids; NEFA, non-esterified fatty acids.
Fig. 2
Fig. 2. Solid fat content of test fats at temperatures 10–40 °C. Solid fat contents of spreads and their respective hardstocks (in the case of spreadable butter, compared to the pure, unblended butter), prior to blending with rapeseed oil, at temperatures from 10 to 40 °C. All fats contained 5% or less solid fat content at body temperature. IE, interesterified.
Fig. 3
Fig. 3. Flow diagram of the progress through the phases of the trial. FMD, flow-mediated dilatation; iAUC, incremental area under the curve; IE, interesterified; RO, rapeseed oil; SB, spreadable butter; TAG, triacylglycerol.
Fig. 4
Fig. 4. Postprandial serum fatty acid concentrations following a commercially available interesterified (IE) spread, a functionally equivalent non-IE spread, and spreadable butter, relative to a reference rapeseed oil (RO). Serum total MUFA, PUFA, SFA, n-6 PUFA, n-3 PUFA, and palmitic acid as percentages of total serum fatty acids (mol%). Data are mean (SEM), n = 44–46. Treatment, time and treatment × time interaction effects were all highly statistically significant P < 0.001. MUFA, PUFA, SFA, n-6 PUFA, n-3 PUFA analysed by NMR spectroscopy and palmitic acid by GC. MUFA, monounsaturated; PUFA, polyunsaturated; SFA, saturated.
Fig. 5
Fig. 5. Postprandial serum triacylglycerol (TAG) concentrations, flow-mediated dilatation (FMD), and serum GlycA and interleukin-6 (IL-6) concentrations following a commercially available interesterified (IE) spread, a functionally equivalent non-IE spread, and spreadable butter, relative to a reference rapeseed oil (RO). Serum TAG (n = 45) concentrations, FMD (n = 46), and serum GlycA (n = 45) and IL-6 (n = 45) concentrations following a test meal containing 50 g fat from 3 different spreads (one commercially available containing IE palm oil fractions, palm kernel oil and RO; one, a non-IE equivalent from mid-fraction palm oil, palm kernel oil, and RO; and the other a spreadable butter (made with butter and RO) relative to a reference RO). Data are geometric means with 95% confidence intervals. Comparison of test fats by linear mixed-model analysis (dependent variable postprandial values, fixed factors of treatment, time, period, treatment × time interaction, treatment × period interaction; random effect participant; covariate baseline, and sex where significant) showed no significant treatment or treatment × time effects for plasma TAG, FMD and IL-6. Significant treatment effect for GlycA (P < 0.001) and treatment × time interaction for GlycA (P < 0.001). * Bonferroni-adjusted post hoc pairwise comparisons showed that postprandial GlycA concentrations were significantly higher following RO consumption compared to IE (mean difference 0.082 mmol L−1, 95% CI 0.048, 0.116), non-IE (mean difference 0.092 mmol L−1, 95% CI 0.058, 0.126) and SB (mean difference 0.095 mmol L−1, 95% CI 0.061, 0.129); all P < 0.001. There were significant time effects for TAG, GlycA, and IL-6 (P < 0.001).
Fig. 6
Fig. 6. Postprandial serum apolipoprotein concentrations, lipoprotein particle sizes, and lipoprotein subclass particle concentrations following a commercially available interesterified (IE) spread, a functionally equivalent non-IE spread, and spreadable butter, relative to a reference rapeseed oil (RO). Serum apolipoprotein and lipoprotein concentrations, and average lipoprotein particle sizes (n = 44–46) following a test meal containing 50 g fat from 3 different spreads (one commercially available containing IE palm oil fractions, palm kernel oil and RO; one, a non-IE equivalent from mid-fraction palm oil, palm kernel oil, and RO; and the other, a spreadable butter made with butter and RO) relative to a reference RO. Data are geometric means with 95% confidence intervals for ApoB, ApoA1, ApoB : ApoA1 ratio, large LDL particle concentrations, and small LDL particle concentrations, and means with standard errors for average HDL, LDL and VLDL particle sizes and small HDL particle concentrations. Comparison of test fats by linear mixed-model analysis (dependent variable postprandial values; fixed factors of treatment, time, period, treatment × time interaction, treatment × period interaction; random effect participant; covariate baseline) showed significant treatment effects for ApoB (P < 0.001), ApoA1 (P < 0.05), ApoB : ApoA1 ratio (P < 0.001), average HDL particle size (P < 0.001), average LDL particle size (P < 0.001), small HDL particle concentration (P < 0.05), large LDL particle concentrations (P < 0.05), and small LDL particle concentrations (P = 0.001). ApoA1, apolipoprotein A1; ApoB, apolipoprotein B; HDL, high-density lipoprotein; LDL, low-density lipoprotein; VLDL, very low-density lipoprotein.
Fig. 7
Fig. 7. Postprandial plasma concentrations of endotoxin biomarkers following a commercially available interesterified (IE) spread, a functionally equivalent non-IE spread, and spreadable butter, relative to a reference rapeseed oil (RO). Changes from baseline in plasma lipopolysaccharide-binding protein (LBP) concentrations, soluble cluster of differentiation 14 (sCD14) concentrations, and LBP : sCD14 ratio (n = 31–40 per treatment/time point) concentrations following a test meal containing 50 g fat from 3 different spreads (one commercially available containing interesterified (IE) palm oil fractions, palm kernel oil and rapeseed oil; one a non-IE equivalent from mid-fraction palm oil, palm kernel oil, and rapeseed oil; and the other a spreadable butter made with butter and rapeseed oil) relative to a reference rapeseed oil. Data are means with standard errors. Comparison of test fats by linear mixed-model analysis (dependent variable postprandial values, fixed factors of treatment, time, period, treatment × time interaction, treatment × period interaction; random effect participant; covariate baseline) showed no significant treatment or time effects. There was a treatment × time interaction (P = 0.031) and a significant sex effect (P = 0.031) for sCD14; there was a tendency for sCD14 to decrease postprandially in males and increase in females.
Fig. 8
Fig. 8. Postprandial plasma glucose concentrations, and serum insulin, C-peptide and non-esterified fatty acid (NEFA) concentrations following a commercially available interesterified (IE) spread, a functionally equivalent non-IE spread, and spreadable butter, relative to a reference rapeseed oil (RO). Mean (SE) plasma glucose concentrations (n = 44–45 per treatment/time point), geometric mean (95% CI) serum insulin and c-peptide concentrations (n = 43–45 per treatment/time point), and mean (SE) serum NEFA concentrations (n = 44–45 per treatment/time point) following a test meal containing 50 g fat from 3 different spreads (one commercially available containing interesterified (IE) palm oil fractions, palm kernel oil and rapeseed oil; one a non-IE equivalent from mid-fraction palm oil, palm kernel oil, and rapeseed oil; and the other a spreadable butter made with butter and rapeseed oil) relative to a reference rapeseed oil. Comparison of test fats by linear mixed-model analysis (dependent variable postprandial values, fixed factors of treatment, time, period, treatment × time interaction, treatment × period interaction; random effect participant; covariate baseline) showed significant time effects (P < 0.001 for all) but no significant treatment effects or treatment × time interactions for glucose, insulin and C-peptide. Significant treatment effects for NEFA iAUC (0–4 h) and iAUC (0–8 h) (P = 0.014 and P = 0.002 respectively) were observed; post hoc tests with Bonferroni adjustment showed that the decrease in NEFA up to 4 hours was significantly greater following RO compared to non-IE (mean difference −0.13 mmol L−1 h−1, 95% CI −0.25, −0.02, P = 0.015), and up to 8 hours was significantly greater following TO compared to SB, IE and non-IE (mean difference RO-SB was −0.29 mmol L−1 h−1, 95% CI −0.57, −0.00, P = 0.048, mean difference RO-IE was −0.30 mmol L−1 h−1, 95% CI −0.54, −0.06, P = 0.008, and mean difference RO-non-IE was −0.41 mmol L−1 h−1, 95% CI −0.69, −0.13, P = 0.001).
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