Abstract
Background: Interesterified (IE) fats rich in palmitic acid (16:0) and stearic acid (18:0) are widely used hard fats. Comparative effects of commercially relevant palmitic or stearic acid-rich IE fat blends on cardiometabolic disease (CMD) risk markers remain unclear. It was hypothesized that functionally matched palmitic and stearic acid-rich fats would have equivalent effects on plasma total:high-density lipoprotein (HDL) cholesterol ratio within a predefined equivalence margin of ±0.09. Objectives: This study aimed to compare the effects of diets enriched in palmitic or stearic acid, delivered as commercially relevant IE fats and incorporated at realistic levels of dietary intake, on plasma lipid concentrations and other CMD risk markers in healthy participants. Methods: In a randomized, crossover trial at 2 centers, 51 healthy participants (aged 35–65 y) consumed diets with either palmitic acid-rich or stearic acid-rich IE fats (10% energy intake) for 6 wk per arm, with a 4-wk washout. IE fats were incorporated into muffins and margarine spreads. The primary outcome was total:HDL cholesterol ratio; secondary outcomes included HDL and low-density lipoprotein cholesterol and fasting and postprandial triacylglycerol, lipoproteins, apolipoproteins, insulin sensitivity, vascular endothelial function, inflammation markers, and fasting liver fat (via proton magnetic resonance spectroscopy, subgroup). Linear mixed models were used to assess intervention effects. Results: Forty-seven participants (51% female, mean age 52 ± 8 y; body mass index 25.2 ± 2.8 kg/m 2) completed the study. No significant differences were observed in total:HDL cholesterol ratio between interventions (stearic compared with palmitic mean difference: 0.05; 95% confidence interval [CI]: −0.08, 0.18). Interleukin-10 concentration decreased after consuming palmitic relative to stearic acid-rich IE fats (−0.14 ng/L; 95% CI: −0.23, −0.06 ng/L). No effects were observed on other outcomes. Conclusions: Commercially relevant palmitic acid-rich IE fats consumed at 10% energy for a 6-wk period do not adversely affect total:HDL cholesterol ratio or other CMD risk markers compared with stearic acid-rich fats. Long-term effects could not be determined from this trial. This trial was registered at clinicaltrials.gov as NCT04418102.
| Original language | English |
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| Journal | The American Journal of Clinical Nutrition |
| Early online date | 18 Sept 2025 |
| DOIs | |
| Publication status | E-pub ahead of print - 18 Sept 2025 |
Data Availability Statement
Data described in the manuscript, code book, and analytic code will be made available upon request pending application and approval.Funding
A key strength of this study is the use of commercially relevant, functionally equivalent fats delivered at realistic dietary doses, exceeding current population-level exposures in the United Kingdom [46]. However, some limitations must be noted. Although the study was adequately powered for equivalence testing using a margin of ±0.09 on the primary outcome (total:HDL cholesterol ratio) and for differences in the secondary outcome (peak postprandial TAG), it may have been underpowered for other endpoints. Furthermore, whereas total:HDL cholesterol ratio is historically regarded as one of the strongest predictors of CVD risk [14,26] and more recently has been shown to remain discriminatory at lower LDL cholesterol and non-HDL cholesterol concentrations [15], causal evidence supports LDL cholesterol and triglyceride-rich lipoproteins (components of non-HDL cholesterol) as direct mediators of atherosclerotic risk [48]. Although HDL cholesterol is inversely associated with CVD risk, interventions and genetic studies have not demonstrated a causal effect of raising HDL cholesterol. Therefore, results based on the total:HDL cholesterol ratio should be interpreted alongside findings for LDL cholesterol and non-HDL cholesterol, which were consistent in supporting equivalence of the two interventions. The sample size was insufficient to stratify analyses by sex, menopause status, age, or BMI—factors that influence individual cardiometabolic responses to dietary fat. Males and females may respond differently to dietary interventions; therefore, we cannot exclude the possibility of sex-specific effects, which should be further explored in future studies. Although factors such as genetic variation, ω-3 status, gut microbiota, and physical activity may modulate individual responses, the randomized crossover design helped control interindividual variability. The study was conducted in healthy participants in the United Kingdom and The Netherlands within a specific age range, and therefore, the results cannot be extrapolated to those with CMDs or other population groups. A key limitation is the relatively short 6-week intervention period. Although this duration has previously been sufficient to detect changes in lipid and vascular markers [ 49–51], longer-term effects remain unknown. Finally, dietary fatty acid intakes from other meals were not controlled. However, a tightly controlled metabolic feeding study would not have been feasible for a total duration of 18 weeks.The authors’ responsibilities were as follows – WLH, HAS: conducted statistical analysis; SEB, WLH: wrote the initial manuscript draft and finalized the submitted version; SEB, RPM: conceptualized the study and acquired funding; SEB, RPM, WLH, PJJ: supervised research activity planning and execution, designed the trials, interpreted data, and reviewed and edited subsequent versions of the manuscript; EW, PJJ, AC, TM: conducted the clinical trial and collected the data; JHB: formulated the test fats and spreads, provided test fat compositional data, and provided advice on the design of the dietary intervention; and all authors: commented on the initial manuscript draft and read and approved the final manuscript.This research was funded by a research grant from the Malaysian Palm Oil Board. The funders were not involved in the study design; collection, analysis, and interpretation of data; writing of the report; or restrictions regarding publication.Sarah Berry reports financial support was provided by Malaysian Palm Oil Board. Harry Smith reports a relationship with Zoe Ltd that includes: equity or stocks. Sarah Berry reports a relationship with Zoe Ltd that includes: consulting or advisory, equity or stocks, and travel reimbursement. Wendy Hall reports a relationship with Zoe Ltd that includes: consulting or advisory. Alice Creedon reports a relationship with Zoe Ltd that includes: employment. Wendy Hall reports a relationship with Almond Board of California that includes: funding grants. Johanna Bruce reports a relationship with ADM Ltd that includes: employment. Peter Joris reports a relationship with Peanut Institute Foundation that includes: funding grants. Ronald Mensink reports a relationship with Peanut Institute Foundation that includes: funding grants. Peter Joris reports a relationship with Wild Blueberry Association of North America that includes: funding grants. Peter Joris reports a relationship with Cosun Nutrition Center that includes: funding grants. Peter Joris reports a relationship with California Walnut Commission that includes: funding grants. Co-author was previously employed by Zoe Ltd (HAS). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
| Funders | Funder number |
|---|---|
| Malaysian Palm Oil Board |
Keywords
- cardiovascular risk factors
- dietary fats
- endothelial function
- inflammation
- interesterified fats
- lipids
- palmitic acid
- postprandial metabolism
- randomized controlled trial
- stearic acid
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Nutrition and Dietetics