J Clin Lipidol. 2026 Jul 15:S1933-2874(26)00447-2. doi: 10.1016/j.jacl.2026.07.019. Online ahead of print.
ABSTRACT
BACKGROUND: Changes in macronutrient intake are associated with alterations in serum lipid profiles, which may contribute to dyslipidemia, a well-established risk factor for cardiovascular disease. However, the potential associations of isocaloric macronutrient substitution with lipid profiles remain insufficiently studied in Middle Eastern populations.
OBJECTIVE: Using isocaloric substitution models, we investigated how substituting one macronutrient for another was associated with lipid profiles among apparently healthy Iranian adults.
METHODS: This cross-sectional analysis used data from 3329 apparently healthy adults participating in the Amol Cohort Study, a population-based study conducted in Iran. We employed multivariable linear regression with a leave-one-out analytical approach to assess the associations between isocaloric macronutrient substitutions, calculated per 100 kcal/d, and lipid profile status.
RESULTS: Isocaloric replacement of carbohydrate with total fat was associated with reduced triglyceride levels. A reduction in both total cholesterol and low-density lipoprotein cholesterol (LDL-C) was observed when replacing carbohydrate or fat with protein. Regarding fatty acid substitutions, replacing carbohydrate with monounsaturated fatty acids, as well as replacing either carbohydrate or protein with saturated fatty acids (SFAs), each led to lower triglycerides. Replacement of protein or carbohydrate with SFAs and polyunsaturated fatty acids was not associated with any change in the serum lipid profile.
CONCLUSION: In conclusion, substitution of carbohydrate or fat with protein lowers total cholesterol and LDL-C, whereas reduced carbohydrate intake-whether replaced by protein or fat-lowers triglycerides. Furthermore, the association of replacing carbohydrates with fat on triglycerides was dependent on the type of fatty acid. Confirming these findings through a cohort study would strengthen evidence that the balance of dietary macronutrients plays a key role in reducing cardiovascular risk factors.
PMID:42722581 | DOI:10.1016/j.jacl.2026.07.019