Cholesterol and cardiovascular risk: for the heart, a low-sugar diet

Initial note: This article was originally published in the past and has been updated according to scientific and informative criteria. The text is for informational purposes only and does not replace medical advice.

In brief

• Cholesterol is an essential substance, but excessive amounts of certain forms (especially LDL and apoB-containing particles) increase the risk of cardiovascular disease.
• Evidence from genetic, observational, and clinical studies indicates a dose-duration relationship between LDL exposure and atherosclerosis risk.
• Low carb diets tend to improve triglycerides and HDL, but can increase LDL in some individuals; the effect depends on fat composition and metabolic context.
• Glycation and modifications of lipoproteins (for example, in conditions of hyperglycemia) can reduce their functionality and contribute to vascular damage.
• For the general population, reducing simple sugar intake and preferring higher quality carbohydrates is a plausible strategy to improve many cardiometabolic biomarkers.

Abstract: what does science say?

Cholesterol is a fundamental biological component for cell membranes and hormone synthesis. However, when the concentration of apolipoprotein B-rich lipoproteins—particularly LDL—is high and/or prolonged over time, the risk of atherosclerosis and cardiovascular events increases. Various lines of evidence (genetic studies, observational studies, and clinical trials) show a dose-response relationship between cumulative LDL exposure and cardiovascular risk. Low carb diets and interventions that improve insulin sensitivity tend to reduce triglycerides and increase HDL; the effect on LDL is variable and depends on the fat composition and individual characteristics. Biochemical modifications of lipoproteins, such as glycation and oxidation, worsen HDL function and the fate of LDL in the arterial wall. Current limitations include heterogeneity of dietary studies, limited duration of trials, and the frequent use of surrogate biomarkers instead of long-term clinical events.

Cholesterol and cardiovascular risk

Evidence of causality and clinical outcomes

The scientific community has evaluated the relationship between LDL and cardiovascular disease through multiple approaches: genetic studies, prospective cohorts, and LDL-lowering trials. The overall picture shows a consistent and dose- and time-dependent relationship: longer and greater exposure to LDL is associated with a higher risk of atherosclerosis and cardiovascular events. This consistency has emerged from both genetic analyses (Mendelian randomization) and clinical studies showing that lowering LDL with drugs that act on LDL receptors reduces cardiovascular events proportionally to the reduction itself [1].

Meta-analyses of trials with statins and other pharmacological interventions have shown significant reductions in myocardial infarction and cardiovascular death in at-risk populations when LDL is consistently lowered [2]. These results consolidate the concept that, in addition to total cholesterol measurement alone, LDL concentration and duration of exposure matter.

Biological mechanisms: accumulation, oxidation, and glycation

Atherogenesis begins when cholesterol-rich lipoproteins penetrate and remain in the arterial wall; there they undergo modifications such as oxidation and glycation that increase their pro-atherogenicity. HDL, normally involved in reverse cholesterol transport, can lose some of its function if it undergoes post-translational modifications, for example, in conditions of chronic hyperglycemia; this loss of function is linked to a reduced ability to remove cholesterol from the vascular intima [4][3][5]. Chemical modifications of lipoprotein proteins contribute to local inflammation and endothelial dysfunction, promoting the progression of atherosclerotic plaque [4].

Carbohydrates, sugars, and dietary patterns: what studies show

Evidence from controlled trials and meta-analyses

Numerous randomized trials and meta-analyses have compared low carb diets with low-fat diets. Overall, carbohydrate-restricted diets tend to improve triglycerides and increase HDL, while the effect on LDL is heterogeneous: in some studies, LDL remains stable, in others it increases slightly, especially if caloric replacement involves an increase in saturated fatty acids [6][8]. In subjects with type 2 diabetes, some reviews document benefits on glycemic control and certain cardiometabolic biomarkers, but evidence on long-term cardiovascular events is limited [7].

Quality and quantity: why composition matters

Not all carbohydrates are equivalent: simple sugars and starches with a high glycemic index are associated with worse glycemic profiles and an increase in triglycerides. Reducing added sugars and choosing higher quality carbohydrates (whole grains, rich in dietary fiber) reduces post-prandial glycemia and can limit processes such as glycation of plasma proteins that worsen lipoprotein function. Furthermore, the effect of a low carb diet on LDL cholesterol depends heavily on the nature of the fats that replace them: unsaturated fats (mono- and polyunsaturated, including omega-3) tend to yield more favorable results compared to an increase in saturated fatty acids [6][3].

What it means in practice

For the general population, evidence indicates that the most prudent strategy is to aim for a complete and balanced diet that limits simple sugars and favors complex carbohydrates and fiber sources. Reducing the consumption of sugary drinks and refined sugar products has beneficial effects on triglycerides, glycemic control, and cardiometabolic risk markers. When considering a low carb diet, it is important to evaluate the quality of increasing fats: preferring unsaturated fats (olive oil, omega-3 rich fish, nuts) and limiting the increase in saturated fats can mitigate the risk of increased LDL. Furthermore, the effect of diet varies based on individual circumstances (presence of diabetes, dyslipidemia, family history of cardiovascular disease), so any significant dietary change should be discussed with a doctor or a nutrition professional.

Regular physical activity, smoking cessation, and blood pressure and glycemia control remain pillars of cardiovascular prevention; dietary intervention is one of the integrated components in a multifactorial strategy [6][7].

Key takeaways

• Elevated LDL and cumulative LDL exposure increase the risk of atherosclerosis and cardiovascular events [1].
• Reducing simple sugars and high glycemic index carbohydrates improves triglycerides, insulin sensitivity, and some cardiometabolic biomarkers [6][7].
• Low carb diets tend to increase HDL and reduce triglycerides, but the effect on LDL is variable and depends on replacement fats [6][8].
• Glycation and oxidation of lipoproteins reduce HDL functionality and can increase the pro-atherogenicity of LDL [3][4][5].
• Dietary decisions should consider the individual risk profile and the overall quality of the diet.

Limitations of the evidence

It is important to distinguish between observational studies and evidence of causality: associations found in cohorts do not always imply direct effects, and many questions require long-term trials with clinical outcomes. Meta-analyses of diets currently show improvements in biomarkers (triglycerides, HDL, sometimes LDL), but often include studies with heterogeneity in duration, adherence, and macronutrient composition. Furthermore, many reviews are based on surrogate endpoints (cholesterol, triglycerides) rather than long-term cardiovascular events; for the latter, longer studies with adequate statistical power are needed [6][8].

Another limitation: individual response to dietary change varies due to genetics, gut microbiota, body composition, and comorbidities; therefore, the average results reported by meta-analyses may not reflect the experience of every single person. Finally, some biochemical modifications of lipoproteins (such as glycation) are better documented in populations with hyperglycemia or diabetes, and their relevance in normoglycemic individuals requires further investigation [3][4][5].

Editorial conclusion

The relationship between cholesterol, carbohydrates, and cardiovascular risk is complex but clearly relevant to public health. Available evidence supports the causal role of LDL in atherosclerosis and shows that dietary modifications can improve some cardiovascular risk factors. Reducing simple sugars and favoring quality carbohydrates, along with an active lifestyle and regular clinical check-ups, is a reasonable strategy for prevention. Specific choices regarding diet composition—and the eventual use of pharmacological therapies—must be personalized and discussed with competent healthcare professionals.

Editorial note

Article originally published in the past and updated in light of the most recent relevant reviews and meta-analyses. The update followed criteria of clarity, transparency, and verification of primary sources. The content is for informational purposes only and does not replace individual medical evaluations.

SCIENTIFIC RESEARCH

1. Ference BA, Ginsberg HN, Graham I, Ray KK, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. European Heart Journal. 2017. https://doi.org/10.1093/eurheartj/ehx144
2. Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010. https://doi.org/10.1016/S0140-6736(10)61350-5
3. Godfrey KM, et al. Arginine-directed glycation and decreased HDL plasma concentration and functionality. Nutrition & Diabetes. 2014. https://doi.org/10.1038/nutd.2014.31
4. Itabe H, Sawada N, Makiyama T, Obama T. Structure and dynamics of oxidized lipoproteins in vivo: roles of high-density lipoprotein. Biomedicines. 2021. https://doi.org/10.3390/biomedicines9060655
5. Korach-André M, et al. Glycation reduces the stability of apoA-I and increases HDL dysfunction in diet-controlled type 2 diabetes. Journal of Clinical Endocrinology & Metabolism. 2018. https://doi.org/10.1210/jc.2017-01551
6. O’Connor LE, et al. Effects of carbohydrate-restricted diets on low-density lipoprotein cholesterol levels in overweight and obese adults: a systematic review and meta-analysis. Nutrition Reviews. 2019. https://doi.org/10.1093/nutrit/nuy049
7. Goldenberg JZ, Day A, Brinkworth GD, et al. Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission: systematic review and meta-analysis. BMJ. 2021. https://doi.org/10.1136/bmj.m4743
8. Yang Q, Lang X, Li W, Liang Y, et al. The effects of low-fat, high-carbohydrate diets vs. low-carbohydrate, high-fat diets: systematic review and meta-analysis. European Journal of Clinical Nutrition. 2022. https://doi.org/10.1038/s41430-021-00927-0