What is cholesterol?
Routine laboratory tests measure three main fractions:
- Total cholesterol – the sum of all fractions
- LDL cholesterol (low-density lipoprotein) – carries cholesterol from the liver to peripheral cells
- HDL cholesterol (high-density lipoprotein) – transports excess cholesterol back to the liver for breakdown
The earlier simplification labelled LDL as “bad” and HDL as “good.” The modern perspective is more nuanced: both fractions perform physiological functions, and the problem begins when LDL particles undergo oxidation, i.e. become damaged.1
The takeaway in one sentence
It is not the LDL level alone that is the primary driver of atherosclerosis, but rather the extent to which LDL particles are exposed to oxidative damage. High LDL together with oxidative stress poses the real risk.
How does atherosclerosis develop? – The modern view
A 2024 review in the Journal of Advanced Research frames atherosclerosis not simply as “fat deposition” but as a chronic inflammatory disease. We present the steps of the process in three main stages.1
LDL particles circulating in the bloodstream are continuously exposed to oxidative stress. Sources of oxidative stress are multifactorial: chronic high blood glucose and insulin resistance, smoking, air pollution, trans fat intake, physical inactivity, chronic inflammation, and aging. If the body's antioxidant capacity cannot neutralize free radicals, LDL is converted into oxidized LDL (oxLDL). The immune system treats oxLDL as a foreign substance.
oxLDL penetrates the endothelial layer of the vessel wall and accumulates in the subendothelial space. Macrophages engulf oxLDL and transform into so-called foam cells. These foam cells form the backbone of the growing plaque. The plaque gradually narrows the vessel lumen, and this process can remain asymptomatic for decades.1,2
Chronic inflammatory processes develop within the plaque: T cells, cytokines and inflammatory mediators appear. An so-called unstable plaque can rupture – platelets adhere to the lesion and a thrombus forms. This causes myocardial infarction, ischemic stroke or peripheral arterial occlusion.
This model explains why a person can still suffer cardiovascular events despite a seemingly normal LDL value. The degree of oxidative stress, biomarkers (ApoB, Lp(a)), and inflammatory parameters (hs-CRP) together provide a fuller picture.
What cholesterol values are considered high?
Hungarian and European (ESC/EAS 2019, 2021 update) guidelines use the following thresholds for the general population. Stricter targets may apply for higher-risk individuals (diabetes, prior myocardial infarction, strong family history).
| Parameter | Optimal | Borderline | High |
|---|---|---|---|
| Total cholesterol | < 5.2 mmol/l | 5.2–6.2 mmol/l | > 6.2 mmol/l |
| LDL cholesterol | < 2.6 mmol/l | 2.6–3.4 mmol/l | > 3.4 mmol/l |
| HDL cholesterol (male) | > 1.0 mmol/l | 0.9–1.0 mmol/l | < 0.9 mmol/l (unfavorable) |
| HDL cholesterol (female) | > 1.2 mmol/l | 1.0–1.2 mmol/l | < 1.0 mmol/l (unfavorable) |
| Fasting triglyceride | < 1.7 mmol/l | 1.7–2.3 mmol/l | > 2.3 mmol/l |
Important context
The value alone says little. An LDL of 4.0 mmol/l means something different in a young, non-smoking, normotensive athlete with low abdominal fat than in a 60‑year‑old diabetic, hypertensive smoker. A comprehensive cardiovascular risk assessment (SCORE2 or ESC calculator) provides the true picture.
What complications can untreated high cholesterol lead to?
High LDL together with oxidative stress can, over years to decades, cause significant vascular damage. The following complications are demonstrably associated with persistently elevated LDL levels:
Rupture of a coronary plaque leads to thrombus formation, occluding blood supply to part of the heart muscle. Prevention includes LDL reduction alongside blood pressure control and smoking cessation, which all carry similar weight.
Occlusion of carotid or cerebral arteries by plaque can cause acute cessation of blood supply to brain tissue.
Stenosis of the leg arteries causes walking pain (intermittent claudication), chronic circulatory impairment, in severe cases wound-healing problems and risk of amputation.
Stenosis of the renal arteries can lead to deterioration of kidney function and difficult-to-control high blood pressure.
How can we influence cholesterol levels? – Two main paths
The modern approach identifies two main strategies for treating high cholesterol, which are not mutually exclusive but rather complementary:
- Lifestyle and dietary changes – address the cause
- Drug therapy (primarily statins) – mitigate the consequence
The question is not which approach is “right,” but rather who needs which. A 50‑year‑old recently identified person with borderline LDL and low other risk factors requires a different approach than a 65‑year‑old diabetic who has already had a myocardial infarction.
Statins – what does the latest evidence say?
Statins (atorvastatin, rosuvastatin, simvastatin, pravastatin, etc.) are the most commonly prescribed cholesterol-lowering drugs today. Their efficacy and safety assessment has become more nuanced in recent years: it is worth understanding both sides correctly.
What can statins do? – The efficacy side
Statins inhibit hepatic cholesterol synthesis (by blocking the HMG-CoA reductase enzyme) and thereby lower LDL. Clinical trials show statins reduce the risk of cardiovascular events, particularly in those who have already had myocardial infarction, stroke or who are at high risk (secondary prevention). In primary prevention the absolute benefit, however, is smaller than many assume.
2022 JAMA Internal Medicine meta-analysis (Byrne et al.)
Combined analysis of 21 randomized controlled trials (statin and control arms together included over 130,000 participants). Statin therapy produced modest absolute risk reductions across primary and secondary prevention:3
- All-cause mortality: ARR 0.8% (relative risk reduction 9%)
- Myocardial infarction: ARR 1.3% (relative risk reduction 29%)
- Stroke: ARR 0.4% (relative risk reduction 14%)
In other words: 1 fewer death per 100 people treated, which is important for individual decision-making. This does not mean statins are useless, but that the individual's baseline risk determines whether treatment is warranted.
2022 BMJ systematic review (Cai et al.)
62 trials, 120,456 participants in primary prevention with an average follow-up of 3.9 years. Statins reduced the risk of major cardiovascular events and, in the trial populations, benefits outweighed harms.4
What to watch for? – Side effects and long-term risks
Statins have several side effects and potential long-term consequences worth knowing. From the latest evidence we highlight the following:
Muscle symptoms – CTT Collaboration 2022 (Lancet)
Individual participant data from 19 placebo-controlled trials (123,940 participants, average follow-up 4.3 years). Reported frequency of muscle pain or weakness was 27.1% in the statin group vs. 26.6% in the placebo group. The difference is small (RR 1.03) and is most apparent in the first year. The authors estimate that only about one-fifteenth of reported muscle symptoms are actually caused by statins; the remainder is attributable to the nocebo effect – symptoms triggered by expectation.5
This does not mean muscle pain “doesn’t exist” — rather that true statin-induced muscle symptoms are less common than previously thought. Severe rhabdomyolysis (muscle breakdown) is very rare but remains a potential risk requiring urgent medical attention.
New-onset diabetes – CTT Collaboration 2024 (Lancet Diabetes & Endocrinology)
This 2024 analysis was the most detailed to date, using individual data from 19 placebo-controlled trials:6
- Low/moderate-intensity statin: new-onset diabetes incidence 1.3% per year vs. 1.2% with placebo – relative risk increase 10%
- High-intensity statin: new-onset diabetes incidence 4.8% per year vs. 3.5% with placebo – relative risk increase 36%
Most new diabetes cases (62%) occurred among people whose baseline glucose parameters were already near the diabetes threshold. In other words: in those with prediabetes, high-dose statin therapy is more likely to “tip” them into diagnosable diabetes.
Other harms in primary prevention – BMJ 2021
The Cai et al. analysis reported that in primary prevention statins increased the following non-cardiovascular risks per 10,000 patients per year:4
- Liver function abnormality: +8 cases (OR 1.33)
- Kidney function deterioration: +12 cases (OR 1.14)
- Eye disorders (e.g., cataract): +14 cases (OR 1.23)
- Self-reported muscle symptoms: +15 cases (OR 1.06)
The authors conclude these excess risks did not outweigh cardiovascular benefit in the trial populations, but they require individual discussion.
What does this mean in practice?
Statins are neither demonic nor miraculous. They are a tool with well-defined clinical benefits and a documented side-effect profile. The decision is always individual and should consider the full risk profile (age, blood pressure, smoking, family history, blood glucose, abdominal circumference). The decision to start or stop a statin should always be made together with the treating physician.
Lifestyle approach vs. medication – what does recent research say?
Notably, recent evidence shows that certain structured dietary programs in primary prevention deliver absolute benefits at least comparable to statins — and in some cases may even surpass them.
2024 Mediterranean diet meta-analysis (Sebastian et al., Curr Probl Cardiol)
4 large RCTs, 10,054 participants, 2–7 years follow-up. Compared with control diets, the Mediterranean diet:7
- Major adverse cardiovascular events (MACE): OR 0.52 (48% relative risk reduction)
- Myocardial infarction: OR 0.62
- Stroke: OR 0.63
- Cardiovascular mortality: OR 0.54
2023 BMJ network meta-analysis – comparing dietary programs (Karam et al.)
40 RCTs, 35,548 participants, comparing seven structured dietary programs. The Mediterranean and low-fat diets showed the largest reductions in mortality and events:8
- Mediterranean diet – mortality: OR 0.72 (17 fewer deaths per 1,000 over 5 years)
- Mediterranean diet – cardiovascular mortality: OR 0.55
- Mediterranean diet – stroke: OR 0.65
- Mediterranean diet – non-fatal myocardial infarction: OR 0.48
Since 2021 ESC/EAS guidelines emphasize that lifestyle intervention is the cornerstone of any cardiovascular prevention strategy. Drug therapy complements, but does not replace, lifestyle measures.
What can you do? – Practical steps
Diet
My advice – change your diet!
A Mediterranean-style diet: plenty of vegetables, legumes, fish, extra virgin olive oil, nuts, and moderate whole grains. Reduce refined carbohydrates (sugary drinks, pastries, white flour) and trans fats (margarine, many industrial baked goods). Reducing saturated fats (butter, fatty red meats) alone does not solve everything but can contribute to a favorable lipid profile when combined with overall healthy eating.
Exercise
WHO and ESC guidelines recommend a minimum of 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity aerobic activity per week, supplemented by resistance training twice weekly.
- Aerobic exercise – walking, jogging, cycling, swimming – can improve HDL and lower triglycerides
- Strength training – increases muscle mass and improves insulin sensitivity
- Yoga, tai chi – can complement aerobic training through stress reduction
Other lifestyle factors
- Smoking cessation – one of the single most impactful cardiovascular protective measures
- Stress management – chronic stress contributes to oxidative load. Details about chronic stress →
- Sleep quality – regular nightly sleep of 7–9 hours improves metabolism
- Reduce abdominal circumference – desirable targets: men < 94 cm, women < 80 cm
- Alcohol consumption – based on the 2018 Lancet and the WHO 2023 position, there is no safe level of alcohol from a cardiovascular perspective. Earlier “moderate red wine” recommendations do not hold up in light of newer evidence.
Natural support – what do recent meta-analyses say?
Dietary supplements and herbal remedies do not replace lifestyle changes or necessary medications, but recent meta-analyses suggest some may contribute to a more favorable lipid profile. Important: effect sizes are generally modest, and results from trial populations (metabolic syndrome, diabetes) may not generalize to everyone.
| Ingredient | Meta-analysis | Observed effect |
|---|---|---|
| Garlic | Fu et al. 2023, 19 RCTs9 | Significant reductions in TC, LDL and triglycerides in metabolic syndrome |
| Turmeric/curcumin | Dehzad et al. 2023, 64 RCTs11 | TC –3.99 mg/dl, LDL –4.89 mg/dl, HDL +1.80 mg/dl (low certainty) |
| Ginger | Salih et al. 202312 | Significant reductions in TC and triglycerides; no significant effect on LDL |
| Flaxseed / ALA | Musazadeh et al. 202513, Yin et al. 2023 | Triglyceride reduction in diabetes; inconsistent effect on LDL |
Realistic expectations
No single spice or supplement replaces a comprehensive lifestyle approach. Meta-analyses show effects are usually modest, and it is unrealistic to expect that garlic or turmeric alone will normalize a high LDL. They are better viewed as beneficial adjuncts to diet and lifestyle rather than stand-alone therapies.
When is medical consultation and drug consideration absolutely necessary?
There are situations where lifestyle change alone is insufficient and initiating a statin (or other lipid-lowering therapy) may be clearly indicated. Omitting drug therapy in these cases carries significant risk.
Situations when medication should be seriously considered
- Prior myocardial infarction, stroke or revascularization – statins are proven to reduce recurrence risk in secondary prevention
- Diabetes over age 40 with additional risk factors
- Familial hypercholesterolemia – genetic, very high LDL (often > 5 mmol/l)
- High calculated 10-year cardiovascular risk (based on SCORE2)
- Chronic kidney disease stage 3 or worse
- Prior PAD or proven coronary calcification (high CAC score)
Home support – tools that can help with control
Reducing cardiovascular risk is a long-term project in which regular self-monitoring and tracking activity can provide substantial help.
Blood pressure monitors
Alongside cholesterol, blood pressure control is the second pillar of cardiovascular prevention. Home blood pressure monitoring gives a more accurate picture than office measurements (avoiding the white coat effect). Validated upper-arm devices are recommended.
Activity trackers and heart rate monitors
Useful for tracking the recommended 150 minutes of moderate activity per week and monitoring target heart rate zones. Visual feedback can support long-term routine formation.
When should you be particularly cautious?
Certain situations require medical supervision when intervening to lower cholesterol. Do not start medications, new supplements or a strict diet on your own in the following circumstances:
- Pregnancy and breastfeeding – statins and certain supplements are contraindicated
- Active liver disease – statins can affect liver function; careful monitoring is required
- Severe kidney disease – some statins require dose adjustment
- History of rhabdomyolysis or elevated muscle enzymes – restarting statin should only be under medical supervision
- Concurrent anticoagulant therapy with high-dose garlic or ginger supplements – combined blood-thinning effects possible
- Diabetes (especially prediabetes) – high-dose statin may increase the risk of new-onset diabetes; individual weighing is required
Important note
The information in this article is for guidance and does not replace individual medical consultation. If you take a statin, do not stop it on your own – always consult your treating physician. If you plan to add a new supplement while on regular medication, ask your doctor or pharmacist about possible interactions.
Frequently asked questions
Atherosclerosis most often develops silently over years to decades. Unfortunately, the first symptom is often myocardial infarction or stroke. High LDL alone does not determine outcome, but it increases risk. Assessing the full risk profile (age, blood pressure, blood glucose, smoking, family history) with your physician is recommended.
Discuss this with your treating physician! Lifestyle approaches are often effective, especially in primary prevention and in lower-risk individuals. In high-risk cases (prior myocardial infarction, established coronary disease, familial hypercholesterolemia) dietary change alone is insufficient. A compromise can be to attempt 3–6 months of intensive lifestyle measures with re-evaluation of blood values thereafter.
Both play physiological roles. LDL becomes problematic when it is oxidized, and high blood levels provide more substrate for this process. HDL does have protective functions, but a high HDL alone does not guarantee full protection. Particle size, particle number and the oxidative environment all matter.
There is no one-size-fits-all answer. Recent meta-analyses suggest limiting refined carbohydrates (sugary drinks, white flour, pastries) can improve the metabolic profile. Very strict ketogenic diets can paradoxically raise LDL in some individuals – therefore a gradual, sustainable transition and periodic lab monitoring is the most useful strategy. Dietitian guidance for individualized plans is advised.
Meta-analyses suggest these spices can favorably influence the lipid profile, but effect sizes are generally modest (a few mg/dl LDL reduction). They can be useful as part of a healthy diet, but in cases of high LDL or elevated risk they do not replace a comprehensive lifestyle approach or necessary medical treatment.
Do not stop on your own! Talk to your treating physician. Recent data indicate much of the muscle pain reported by statin users is not caused by the statin. Your doctor can consider dose reduction, switching to a different statin, a temporary drug holiday, or measuring CK. Sudden discontinuation, especially in secondary prevention, may increase the risk of cardiovascular events.
Summary – Quick overview
References
- Xing Y, Lin X (2024). Challenges and advances in the management of inflammation in atherosclerosis. Journal of Advanced Research, 71:317-335. PubMed: 38909884 | DOI
- Gianopoulos I, Daskalopoulou SS (2024). Macrophage profiling in atherosclerosis: understanding the unstable plaque. Basic Research in Cardiology, 119(1):35-56. PubMed: 38244055 | DOI
- Byrne P, Demasi M, Jones M, et al. (2022). Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment: A Systematic Review and Meta-analysis. JAMA Internal Medicine, 182(5):474-481. PubMed: 35285850 | DOI
- Cai T, Abel L, Langford O, et al. (2021). Associations between statins and adverse events in primary prevention of cardiovascular disease: systematic review with pairwise, network, and dose-response meta-analyses. BMJ, 374:n1537. PubMed: 34261627 | DOI
- Cholesterol Treatment Trialists' (CTT) Collaboration (2022). Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials. Lancet, 400(10355):832-845. PubMed: 36049498 | DOI
- Cholesterol Treatment Trialists' (CTT) Collaboration (2024). Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials. The Lancet Diabetes & Endocrinology, 12(5):306-319. PubMed: 38554713 | DOI
- Sebastian SA, Padda I, Johal G (2024). Long-term impact of mediterranean diet on cardiovascular disease prevention: A systematic review and meta-analysis of randomized controlled trials. Current Problems in Cardiology, 49(5):102509. PubMed: 38431146 | DOI
- Karam G, Agarwal A, Sadeghirad B, et al. (2023). Comparison of seven popular structured dietary programmes and risk of mortality and major cardiovascular events in patients at increased cardiovascular risk: systematic review and network meta-analysis. BMJ, 380:e072003. PubMed: 36990505 | DOI
- Fu Z, Lv J, Gao X, et al. (2023). Effects of garlic supplementation on components of metabolic syndrome: a systematic review, meta-analysis, and meta-regression of randomized controlled trials. BMC Complementary Medicine and Therapies, 23(1):260. PubMed: 37481521 | DOI
- Bashiri S, TaghipourSheshdeh F, Foshati S, et al. (2025). The Effect of Aged Garlic Supplementation on Blood Pressure and Lipid Profile: A Dose-Response Grade-Assessed Systematic Review and Meta-Analysis of Randomized Controlled Trials. Phytotherapy Research, 39(12):5669-5694. PubMed: 40628369 | DOI
- Dehzad MJ, Ghalandari H, Amini MR, Askarpour M (2023). Effects of curcumin/turmeric supplementation on lipid profile: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials. Complementary Therapies in Medicine, 75:102955. PubMed: 37230418 | DOI
- Salih AK, Alwan AH, Khadim M, et al. (2023). Effect of ginger (Zingiber officinale) intake on human serum lipid profile: Systematic review and meta-analysis. Phytotherapy Research, 37(6):2472-2483. PubMed: 36786398 | DOI
- Musazadeh V, Nezamoleslami S, Faghfouri AH, Shidfar F, Aryaeian N (2025). The effect of flaxseed supplementation on anthropometric indices, blood pressure, and lipid profile in diabetic patients: A GRADE-assessed systematic review and meta-analysis of randomized controlled trials. Diabetes & Metabolic Syndrome, 19(5):103241. PubMed: 40499336 | DOI
