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. 2025 Apr 14;11(1):76.
doi: 10.1186/s40795-025-01062-w.

The effect of low-carbohydrate diets, based on changes in intake of dietary saturated fats on circulating TNF-α and interleukin- 6 levels in adults: a systematic review and meta-analysis of randomized controlled trials

Mahdieh Khodarahmi  1 , Fatemeh Pourteymour Fard Tabrizi  2 , Gholamreza Askari  3
Affiliations

The effect of low-carbohydrate diets, based on changes in intake of dietary saturated fats on circulating TNF-α and interleukin- 6 levels in adults: a systematic review and meta-analysis of randomized controlled trials

Mahdieh Khodarahmi et al. BMC Nutr. .

Abstract

Background: Low-carbohydrate diets (LCDs) have been associated with inflammation while there is still conflicting evidence regarding the effects of this type of diet on inflammatory markers and the clinical benefit of them remains uncertain. So, we aimed to ascertain the effects of LCDs on serum concentrations of tumor necrosis factor alpha (TNF-α) and interleukin- 6 (IL- 6) by performing a systematic review and meta-analysis of randomized clinical trials (RCTs).

Methods: The online databases PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science, and Scopus were comprehensively searched up to February 2024, to find pertinent RCTs. Pooled weighted mean difference (WMD) with 95% confidence intervals (CIs) were calculated using the random-effects model.

Results: This meta-analysis of 33 studies assessed a total of 2106 adults irrespective of their health status. Compared with control group, participants on LCDs experienced a decline in IL- 6 levels (WMD: - 0.31 pg/mL; 95% CI: - 0.49 to - 0.12; P = 0.001). However, no significant effect was revealed for TNF-α (WMD: - 0.02 pg/mL; 95% CI: - 0.08 to - 0.03; P = 0.449). Stratification analyses indicated that beneficial effects of LCDs on inflammatory cytokines (WMD: - 0.28 pg/mL; 95% CI: - 0.47 to - 0.10; P = 0.003, WMD: - 0.26 pg/mL; 95% CI: - 0.48 to - 0.03; P = 0.027, for TNF-α and IL- 6, respectively) were stronger when carbohydrate intake was < 10%. The results of Meta-regression analyses suggested that baseline level of both markers remained as a strong predictor of the effect size (P = 0.038 and P = 0.001 for TNF-α and IL- 6, respectively).

Conclusion: Adherence to LCDs appeared to be effective at improving inflammatory cytokines particularly, when carbohydrate intake was restricted to less than 10% of total energy. Nevertheless, further rigorously designed clinical trials considering factors such as race and genetic, the sources and quality of dietary carbohydrates, protein, and fat are required to gain a deeper understanding of the impact of LCDs on inflammatory markers.

Trial registration: PROSPERO, registration no: CRD42023387452.

Keywords: Carbohydrate restriction; Inflammation; Interleukin- 6; Low-carbohydrate diet; Meta-analysis; TNF-α.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram for study selection process
Fig. 2
Fig. 2
Funnel plot for assessment of publication bias in the studies evaluating the influence of low carbohydrate diets on IL- 6
See this image and copyright information in PMC

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