The Effects of Different Degrees of Carbohydrate Restriction and Carbohydrate Replacement on Cardiometabolic Risk Markers in Humans—A Systematic Review and Meta-Analysis
Open accessAbstract
Low-carbohydrate diets (LCDs) often differ in their diet composition, which may lead to conflicting results between randomized controlled trials. Therefore, we aimed to compare the effects of different degrees of carbohydrate (CHO) restriction on cardiometabolic risk markers in humans. The experimental LCDs of 37 human trials were classified as (1) moderate-low CHO diets (<45–40 E%, n = 13), (2) low CHO diets (<40–30 E%, n = 16), and (3) very-low CHO diets (<30–3 E%; n = 8). Summary estimates of weighted mean differences (WMDs) in selected risk markers were calculated using random-effect meta-analyses. Differences between the LCD groups were assessed with univariate meta-regression analyses. Overall, the LCDs resulted in significant weight loss, reduced diastolic blood pressure BP, and increased total cholesterol and high-density lipoprotein cholesterol (HDL-C), without significant differences between the three LCD groups. Higher low-density lipoprotein cholesterol (LDL-C) concentrations were found with the very-low CHO diets compared to the moderate-low CHO diets. Decreases in triacylglycerol (TAG) concentrations were more pronounced with the low and very-low CHO diets, compared to the moderate-low CHO diets. Substitution of CHO by mainly saturated fatty acids (SFAs) increased total cholesterol, LDL-C, and HDL-C concentrations. Except for LDL-C and TAGs, effects were not related to the degree of CHO restriction. Potential effects of nutrient exchanges should be considered when following LCDs.
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The reduction in triglycerides was greatest for the very low-carbohydrate (<10% of calories from carbohydrates) diet: −24 mg/dL (95% CI: −38 to −9 mg/dL) when combined with weight loss (−1.62 kg).
“The reduction in triglycerides was greatest for the very low-carbohydrate (<10% of calories from carbohydrates) diet: −24 mg/dL (95% CI: −38 to −9 mg/dL) when combined with weight loss (−1.62 kg) (65).”
From 2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia (2021) · cites this paper as [65]
Section 3.3 reports a triglyceride (TAG) reduction of −0.27 mmol/L (95% CI −0.43 to −0.10), approximately −24 mg/dL (−38 to −9), and greater weight loss of −1.62 kg for its very-low-carbohydrate group. Section 3.4 shows this group had the largest triglyceride reduction. But Methods §2.3 defines the group as 3% to less than 30% of energy from carbohydrates, not exclusively less than 10%. (LLM, conf=0.90)
Experimental — accuracy not yet measuredIn a systematic review and meta-analysis, all carbohydrate-restricted diets resulted in significant and similar weight loss from baseline but had different triglyceride-lowering effects.
“In a systematic review and meta-analysis of the effect of different levels of carbohydrate restriction on body weight and cardiometabolic risk markers (65), all carbohydrate-restricted diets resulted in significant and similar weight loss from baseline but had different triglyceride-lowering effects.”
From 2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia (2021) · cites this paper as [65]
Sections 3.4.1 and 3.4.4 report no statistically significant weight-loss differences among carbohydrate-restriction groups, but significant differences in triglyceride reductions. The weight-loss estimates compare restricted diets with moderate-carbohydrate diets; they do not establish that every diet produced significant weight loss from baseline. Section 3.2 notes that only six studies in its low-carbohydrate group showed significant weight loss. (LLM, conf=0.87)
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Virani, S. S., Morris, P. B., Agarwala, A., Ballantyne, C. M., Birtcher, K. K., Kris-Etherton, P. M., Ladden-Stirling, A. B., Miller, M., Orringer, C. E., & Stone, N. J. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.06.011 · Cited by 341 · see citing works
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Blumenthal, R. S., Morris, P. B., Gaudino, M., Johnson, H. M., Anderson, T. S., Bittner, V. A., Blankstein, R., Brewer, L. C., Cho, L., de Ferranti, S. D., et al. (2026) · JACC · doi:10.1016/j.jacc.2025.11.016 · Cited by 304 · see citing works
Writing Committee Members, Blumenthal, R. S., Morris, P. B., Gaudino, M., Johnson, H. M., Anderson, T. S., Bittner, V. A., Blankstein, R., Brewer, L. C., Cho, L., et al. (2026) · Circulation · doi:10.1161/cir.0000000000001423 · Cited by 122 · see citing works
The Effect of Ketogenic Diet on Shared Risk Factors of Cardiovascular Disease and Cancer
Mohammadifard, N., Haghighatdoost, F., Rahimlou, M., Rodrigues, A., Gaskarei, M. A. K., Okhovat, P., de Oliveira, C., Silveira, É. A., & Sarrafzadegan, N. (2022) · Nutrients · doi:10.3390/nu14173499 · Cited by 62 · see citing works
Dietary patterns to promote cardiometabolic health
Pagidipati, N. J., Taub, P. R., Ostfeld, R. J., & Kirkpatrick, C. F. (2024) · Nature Reviews Cardiology · doi:10.1038/s41569-024-01061-7 · Cited by 43 · see citing works
“…a significant reduction in plasma triglyceride levels with carbohydrate-restricted dietary interventions compared with higher carbohydrate intake in participants with overweight or obesity, with or without prediabetes or type 2 diabetes, at both short-term and long-term follow-up 42,43,56,57 .”
Adherence to Low-Carbohydrate Diets in Patients with Diabetes: A Narrative Review
Kumar, N., Merrill, J., Carlson, S. M., German, J. C., & Yancy, W. (2022) · Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy · doi:10.2147/dmso.s292742 · Cited by 39 · see citing works
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Sukhato, K., Akksilp, K., Dellow, A., Vathesatogkit, P., & Anothaisintawee, T. (2020) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqaa252 · Cited by 38 · see citing works
Benefits of low carbohydrate diets: a settled question or still controversial?
Landry, M. J., Crimarco, A., & Gardner, C. D. (2021) · Current Obesity Reports · doi:10.1007/s13679-021-00451-z · Cited by 31 · see citing works
Novel Therapeutic Approaches in the Management of Chronic Kidney Disease
Dąbek, B., Dybiec, J., Frąk, W., Fularski, P., Lisińska, W., Radzioch, E., Młynarska, E., Rysz, J., & Franczyk, B. (2023) · Biomedicines · doi:10.3390/biomedicines11102746 · Cited by 29 · see citing works
“Furthermore, KD is associated with an increased risk of dyslipidemia and hyperlipidemia, as well as its link to increased mortality risks, according to observational studies [38,39].”
BackgroundStorz, M. A., & Ronco, A. L. (2023) · British Journal of Nutrition · doi:10.1017/s0007114522001908 · Cited by 27 · see citing works
“with regard to carbohydrate quality), which may also lead to conflicting results in clinical studies(5).”
ResultTian, W.-D., Cao, S., Guan, Y.-X., Zhang, Z.-H., Liu, Q., Ju, J., Xi, R.-X., & Bai, R. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1516086 · Cited by 26 · see citing works
Zinöcker, M., Svendsen, K., & Dankel, S. (2021) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqaa322 · Cited by 22 · see citing works
Mårtensson, A., Stomby, A., Tellström, A., Ryberg, M., Waling, M., & Otten, J. (2021) · Nutrients · doi:10.3390/nu13030969 · Cited by 14 · see citing works
“In our study, we hypothesized that the lower carbohydrate intake in part explains the lower triglyceride levels [31].”
BackgroundTerakawa, A., Bouchi, R., Kodani, N., Hisatake, T., Sugiyama, T., Matsumoto, M., Ihana-Sugiyama, N., Ohsugi, M., Ueki, K., & Kajio, H. (2022) · Journal of Diabetes Investigation · doi:10.1111/jdi.13758 · Cited by 12
Carbohydrates: Separating fact from fiction
Blaak, E. E., Riccardi, G., & Cho, L. (2021) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2021.03.025 · Cited by 16 · see citing works
Fasting diets: what are the impacts on eating behaviors, sleep, mood, and well-being?
Hosseini, E., Ammar, A., Josephson, J., Gibson, D. L., Askari, G., Bragazzi, N. L., Trabelsi, K., Schöllhorn, W., & Mokhtari, Z. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1256101 · Cited by 11 · see citing works
Dankel, S., Bjørndal, B., Lindquist, C., Grinna, M. L., Rossmann, C., Bohov, P., Nygård, O., Hallström, S., Strand, E., & Berge, R. (2021) · Journal of NutriLife · doi:10.1093/jn/nxab178 · Cited by 11 · see citing works
“Several studies have since confirmed a dose-dependent TG-lowering effect of lower carbohydrate intake (6).”
BackgroundResultda Silva, I. V., Gullette, S., Florindo, C., Huang, N. K., Neuberger, T., Ross, A., Soveral, G., & Castro, R. (2022) · Biomedicines · doi:10.3390/biomedicines10051159 · Cited by 10 · see citing works
“The impact of a KD on cardiometabolic and vascular health is still a subject under intense debate [10,11].”
BackgroundNorgren, J., Sindi, S., Sandebring-Matton, A., Ngandu, T., Kivipelto, M., & Kåreholt, I. (2023) · Current Developments in Nutrition · doi:10.1016/j.cdnut.2023.100096 · Cited by 9 · see citing works
“Macronutritional composition may influence factors related to cognitive health, for example, blood pressure, lipids, insulin, and weight [1,17].”
BackgroundKivrak, H., Er, O. F., Ozok, O., Çelik, S., & Kıvrak, A. (2022) · Materials Chemistry and Physics · doi:10.1016/j.matchemphys.2022.125951 · Cited by 9
Weinstein, S., Maor, E., Kaplan, A., Hod, T., Leibowitz, A., Grossman, E., & Shlomai, G. (2024) · Nutrients · doi:10.3390/nu16040486 · Cited by 8 · see citing works
“The effects of different dietary patterns on the lipid profile, particularly on the TG/HDL-C ratio, have been previously explored [29–35].”
BackgroundSalcedo, A. C., Yun, J., Carter, C. S., & Hart, E. (2023) · Nutrients · doi:10.3390/nu15173760 · Cited by 8 · see citing works
“Other studies indicate that, while balancing the LDL and cholesterol elevations, low-carbohydrate diets improve metabolic markers such as triglycerides, HDL, and weight [57,58].”
Background2024 KSoLA Consensus on Secondary Dyslipidemia
Won, H., Bae, J., Lim, H., Kang, M.-J., Kim, M., & Lee, S.-H. (2024) · Journal of Lipid and Atherosclerosis · doi:10.12997/jla.2024.13.3.215 · Cited by 7 · see citing works
2024 KSoLA consensus on secondary dyslipidemia
Won, H., Bae, J., Lim, H., Kang, M.-J., Kim, M., & Lee, S.-H. (2024) · The Korean Journal of Internal Medicine · doi:10.3904/kjim.2024.156 · Cited by 7 · see citing works
“LDL-C levels increase as carbohydrate intake decreases [21].”
BackgroundBreeze, P. R., Sworn, K., McGrane, E., Abraham, S., & Cantrell, A. J. (2024) · BMJ Nutrition Prevention & Health · doi:10.1136/bmjnph-2023-000666 · Cited by 9 · see citing works
Volek, J., Clinthorne, J. F., & Yancy, W. S. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1141859 · Cited by 6 · see citing works
Approach to patients with hypertriglyceridemia
Chait, A., & Feingold, K. R. (2022) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2022.101659 · Cited by 8 · see citing works
Mousavi, S. M., Ejtahed, H., Marvasti, F. E., Taghavi, M., Siadat, S., Hasani-Ranjbar, S., Larijani, B., & Esmaillzadeh, A. (2023) · Clinical Therapeutics · doi:10.1016/j.clinthera.2023.02.002 · Cited by 5 · see citing works
Salehi, N., & Walters, M. (2022) · British Journal of Nutrition · doi:10.1017/s0007114522001854 · Cited by 5 · see citing works
“, blood glucose, blood pressure, TAG, insulin levels, weight gain and an improvement in lipid profiles)(7,19).”
BackgroundInfluentialBorsi, E., Șerban, C., Potre, C., Potre, O., Putnoky, S., Samfireag, M., Tudor, R., Ioniţă, I., & Ioniță, H. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18105444 · Cited by 4 · see citing works
Nevoit, G., Stankuvienė, A., Jaruševičius, G., McCraty, R., Landauskas, M., Potyazhenko, M., Bumblyte, I. A., & Vainoras, A. (2024) · KIDNEYS · doi:10.22141/2307-1257.13.1.2024.438 · Cited by 3 · see citing works
Gao, Q., Li, Y., & Wang, L. (2026) · Food Reviews International · doi:10.1080/87559129.2026.2642794 · Cited by 1 · see citing works
“[164] Similar findings were reported in a meta-analysis of 11 RCTs, with greater weight loss (2.17 kg), lower triglycerides (0.26 mmol/L), and higher HDL-C (0.14 mmol/L) at six months.”
InfluentialChiang, W.-L., Yusof, B. M. M., & Azlan, A. (2021) · International Journal of Academic Research in Business and Social Sciences · doi:10.6007/ijarbss/v11-i19/11743 · Cited by 2 · see citing works
“Restricting dietary carbohydrate intake induced fat loss and weight loss, which reduced the CMR-related complications (Fechner et al., 2020; Timóteo, 2018).”
BackgroundSun, Y., Yin, M., & Zhou, L.-B. (2026) · Journal of Health, Population and Nutrition · doi:10.1186/s41043-025-01220-7 · Cited by 1 · see citing works
“Excessive or prolonged adherence has been associated with elevated lipid levels, impaired renal function, and increased cardiovascular risk in susceptible individuals [25, 26].”
Evolving dietary strategies in the management of obesity: a narrative review
Kim, M. (2026) · Journal of Korean Medical Association · doi:10.5124/jkma.25.0116 · Cited by 1 · see citing works
Aloraini, G. F., McKeown, N. M., Rogers, G. T., Das, S. K., Lichtenstein, A. H., & Jacques, P. F. (2025) · Nutrix Journal · doi:10.1186/s12937-025-01194-6 · Cited by 1 · see citing works
“The observed positive association between LCDSs and a greater annual increase in WC contradicts evidence from longer-term RCTs (> 6 months–2 y), which reported equivalent [1, 2, 33–35], or greater [4, 36–40] weight reduction in LCDs compared to low-fat diets.”
Lee, S. H., Kim, S. H., & Park, S. C. (2024) · Korean Journal of Gastroenterology · doi:10.4166/kjg.2024.004 · Cited by 4 · see citing works
Strategies for Long-Term Weight Loss and Maintenance
Seo, Y. (2023) · Korean Journal of Family Practice · doi:10.21215/kjfp.2023.13.3.128 · Cited by 1 · see citing works
Viljoen, A., Yu, K., Witchell, E., & Conklin, A. (2023) · BMJ Nutrition, Prevention & Health · doi:10.1136/bmjnph-2022-000532 · Cited by 1 · see citing works
Kowalski, C., Dustin, D., Johnson, L., Belury, M., & Conrad, Z. (2022) · Current Developments in Nutrition · doi:10.1016/j.cdnut.2022.100019 · Cited by 1 · see citing works
“Variability of fat quantity and fat class in restricted carbohydrate diets may affect their association with CMD [11, 16].”
BackgroundEgyptian practical guidance in hypertriglyceridemia management 2021
Taha, H. S. E. D., Kandil, H., Farag, N., Oraby, A., Sharkawy, M. E. E., Fawzy, F., Mahrous, H., Bahgat, J., Samy, M., Aboul, M., et al. (2021) · Egyptian Heart Journal · doi:10.1186/s43044-021-00235-9 · Cited by 1 · see citing works
“The reduction in TG was greater for the very low carbohydrate regimens (in which carbohydrates represent < 10% of calories) [37].”
BackgroundDietary Interventions for Hypertriglyceridemia
Kirkpatrick, C. F., Petersen, K. S., Kris-Etherton, P. M., & Maki, K. C. (2026) · Current Atherosclerosis Reports · doi:10.1007/s11883-026-01444-w
“Results of meta-analyses of RCTs show that very-low-and low-carbohydrate diets lower TGs, compared to higher-carbohy-drate, low-fat diets ( 30% TDE fat) [ 59, 75, 76].”
Saeed, A. A. M., Faragb, H. A. M., & Rasul, N. H. (2026) · Kurdistan Journal of Applied Research · doi:10.24017/science.2026.1.10
Khodarahmi, M., Mehrabani, S., & Askari, G. (2026) · International Journal of Environmental Health Research · doi:10.1080/09603123.2026.2650506
“LCDs encompass a spectrum of dietary approaches, ranging from moderately carbohydrate-restricted to very-low-carbohydrate diets, which may elicit different metabolic and inflammatory responses (Fechner et al. 2020).”
Wang, H.-Q., Wang, Q., Chen, J., Chen, Y., & Tang, Y.-H. (2026) · Journal of Diabetes Research · doi:10.1155/jdr/7230214
“CCR reduces post-prandial glycemic load and insulin demand while promoting fat oxidation, thereby directly mitigating glucotoxicity and supporting β -cell rest [7, 10].”
Low-carbohydrate diets in diabetes mellitus: A clinical case report and a brief literature review
Hudiakova, N. V., Khudyakov, Y. S., Pchelin, I. Y., Stojanovich, S., Radoičić, D., Semigolovskii, N. Y., Мазуренко, С. О., & Смирнов, В. В. (2025) · Meditsinskiy sovet = Medical Council · doi:10.21518/ms2025-458
Gogga, P., Szulc, P., & Janczy, A. (2025) · Nutrients · doi:10.3390/nu17213381
“…with lower concentrations of this lipoprotein, in line with earlier reports suggesting that diets higher in carbohydrates tend to have a more positive impact on LDL-C levels compared to higher intake of other macronutrients, highlighting that their dietary source is of key importance [49,50].”
2024 KSoLA Consensus on the Management of Secondary Dyslipidemia
Won, H., Bae, J., Lim, H., Kang, M.-J., Kim, M., & Lee, S.-H. (2025) · Korean Journal of Medicine · doi:10.3904/kjm.2025.100.1.5
“C 수치 는 높아진다 [21”
Tramontt, C., Mouti, S., Vale, M. R. L. D., Li, X.-H., Golubic, R., & Ray, S. (2023) · BMJ Nutrition, Prevention & Health · doi:10.1136/bmjnph-2022-000551
“Substitution of carbohydrate by saturated fatty acids has been associated with increased total cholesterol, LDL and HDL concentrations, 9 yet there is little to no evidence on the impact of saturated fat intake on HDL and triglycerides, and only small reductions total cholesterol and LDL…”
BackgroundResultInfluentialStudy on food nutrition and association with Diabetes Mellitus
Wan, S. (2020) · IOP Conference Series Earth and Environmental Science · doi:10.1088/1755-1315/615/1/012109 · Cited by 2 · see citing works
“According to many studies, low carbohydrate diet shows significant effect, including weight loss, reducing diastolic blood pressure, and increasing total cholesterol and high-density lipoprotein cholesterol[22].”
Background
- Authors
- Fechner, E., Smeets, E., Schrauwen, P., & Mensink, R.
- Affiliations
- Maastricht University Medical Centre (NL)
- Corresponding author
- Mensink, Ronald
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2020-04-02
- Volume
- 12
- Issue
- 4
- Pages
- 991
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC7230871
- OpenAlex
- W3014552459
- Cited by
- 64
- References
- 74
- Citations by year
- 2026: 10 · 2025: 6 · 2024: 9 · 2023: 9 · 2022: 13 · 2021: 13 · 2020: 4
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Physiology › Diet and metabolism studies
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Keywords
- low-carbohydrate diet, carbohydrate restriction, very low carbohydrate diet, cardiometabolic risk markers, weight loss, blood pressure, cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, saturated fatty acids, fat replacement, nutrient exchange
- MeSH terms
- Cardiovascular Diseases, Cholesterol, Dietary Carbohydrates, Humans, Triglycerides, Diet, Carbohydrate-Restricted
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