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Cholesterol

Everything in the library studied for it, medical and holistic together. Within each kind, what was shown to help comes first, strongest evidence first. What was tested and not shown to help stays on the list.

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Medication9 Peptides and SARMs1 Supplements25 Therapies1 Practices6 Daily life1 Food and drink9 Diets14 Devices and wearables1 Lab markers31

Medication

Ezetimibe and fenofibrateStrong

Ezetimibe: LDL cholesterol and ApoB

Shown to lower LDL cholesterol about 18% more than placebo when taken alone, with ApoB about 16% lower, and to lower LDL further when added to a statin.

Compared with placebo [1][2]; a statin or fenofibrate alone [3][4]

The numbers and sources

Effect: Across 8 placebo-controlled 12-week trials, ezetimibe 10 mg lowered LDL cholesterol 18.58% more than placebo (95% CI 17.48 to 19.67), total cholesterol 13.46% more and triglycerides 8.06% more, and raised HDL cholesterol 3.00% [1]. In two label trials, LDL cholesterol fell 18% and ApoB 16% on ezetimibe against a 1% rise and 2% fall on placebo [2]. Added to a statin or fenofibrate, ezetimibe lowered LDL cholesterol, total cholesterol and triglycerides further and likely raised HDL [3]. After an acute coronary syndrome, time-averaged LDL was 53.7 mg/dL on simvastatin with ezetimibe against 69.5 mg/dL on simvastatin alone [4].
Population: 2,722 people with primary hypercholesterolemia in 8 trials [1]; 1,719 adults in two trials [2]; 23,499 people in 26 trials [3]; 18,144 patients [4].
Sources: [1], [2], [3], [4]
Caveats: Lipid trials alone lasted 12 weeks [1]. Heterogeneity was substantial in the combination analyses [3].

OrlistatStrong

Cholesterol and blood lipids

Shown to lower total and LDL cholesterol slightly, by about 0.3 mmol/L, with larger drops when more weight was lost.

The numbers and sources

Effect: Orlistat lowered total cholesterol by 0.30 mmol/L and LDL cholesterol by 0.27 mmol/L. HDL cholesterol fell 0.034 mmol/L and triglycerides 0.09 mmol/L. Lipoprotein(a) did not change. LDL lowering was larger with more weight loss and shorter treatment [3]. An earlier systematic review also found greater falls in total and LDL cholesterol than with control [5].
Population: 33 RCTs [3]; 28 RCTs, 17 of them with 10,041 patients over a year [5].
Sources: [3], [5]
Caveats: The changes are small. The reviews do not separate the drug from the weight lost.

Ezetimibe and fenofibrateModerate

Ezetimibe added to a statin: heart attacks and strokes

Shown to lower heart attacks, strokes and related events about 6% when added to a statin, 267 against 284 per 1,000, mostly in people with recent heart disease.

Compared with a statin alone or with placebo [3][4]

The numbers and sources

Effect: Adding ezetimibe to a statin lowered major cardiovascular events (RR 0.94, 95% CI 0.90 to 0.98), from 284 to 267 per 1,000, nonfatal heart attack (RR 0.88, 105 to 92 per 1,000) and nonfatal stroke (RR 0.83, 32 to 27 per 1,000) [3]. In the largest trial, the 7-year event rate was 32.7% on simvastatin with ezetimibe and 34.7% on simvastatin alone (HR 0.936, 95% CI 0.89 to 0.99), an absolute difference of 2.0 points [4].
Population: 21,727 people in 10 trials, mostly with established heart disease [3]; 18,144 patients within 10 days of an acute coronary syndrome, median follow-up 6 years [4].
Sources: [3], [4]
Caveats: The pooled result is driven by one trial, which carried 41.5% to 98.4% of the weight [3]. That trial was funded by the maker [4]. Evidence for people without heart disease and for ezetimibe alone is limited [3].

Ezetimibe and fenofibrateModerate

Fenofibrate: triglycerides, HDL and LDL cholesterol

Shown to lower triglycerides about 29% and LDL cholesterol 21% and to raise HDL 11% against placebo, with triglycerides 46% to 55% lower in severe high triglycerides.

Compared with placebo [7]

The numbers and sources

Effect: In four placebo-controlled trials of 3 to 6 months, fenofibrate at the 145 mg dose changed triglycerides by -28.9% against +7.7% on placebo, LDL cholesterol by -20.6% against -2.2%, total cholesterol by -18.7% against -0.4%, and HDL by +11.0% against +0.7%. ApoB fell 25.1% against a 2.4% rise. In severe high triglycerides, triglycerides fell 46.2% (baseline 432 mg/dL) and 54.5% (baseline 726 mg/dL) against -0.5% and +7.2% on placebo, while LDL cholesterol rose in both groups [7].
Population: 646 adults with high cholesterol or mixed dyslipidemia in 4 trials, and 147 adults with high triglycerides in 2 trials of 8 weeks [7].
Sources: [7]
Caveats: Label trials, short-term. The label reports rare severe paradoxical drops in HDL, listed under Risks [7].

StatinsModerate

LDL cholesterol lowering

Shown to lower LDL cholesterol by about 51 to 56 mg/dL with atorvastatin and rosuvastatin, and triglycerides by about 25 to 32 mg/dL.

The numbers and sources

Effect: Pooled across studies, atorvastatin lowered LDL cholesterol by 51.49 mg/dL (95% CI 42.75 to 60.23) and rosuvastatin by 55.66 mg/dL (95% CI 46.32 to 65.00). Triglycerides fell by 24.76 and 31.98 mg/dL, and HDL rose by 1.85 and 3.87 mg/dL [3].
Population: Studies of atorvastatin and rosuvastatin from 2003 to 2025 [3].
Sources: [3]
Caveats: The abstract does not give study counts, doses or the comparison used. The heart attack and stroke results above are expressed per unit of LDL lowered [1].

Ezetimibe and fenofibrateLimited

Ezetimibe alone in adults 75 and older

One open-label trial found ezetimibe lowered heart events about a third against usual care in Japanese adults 75 or older without heart disease, with no change in deaths or strokes.

Compared with usual care with dietary counseling [5]

The numbers and sources

Effect: The composite of sudden cardiac death, heart attack, coronary revascularization or stroke was lower on ezetimibe 10 mg (HR 0.66, 95% CI 0.50 to 0.86), with fewer cardiac events (HR 0.60) and revascularizations (HR 0.38). Stroke, all-cause mortality and adverse events did not differ [5].
Population: 3,796 adults aged 75 or older in Japan with raised LDL and no coronary disease, 3,411 analyzed, median follow-up 4.1 years [5].
Sources: [5]
Caveats: Open-label, stopped early, with follow-up problems and 10% excluded after randomization, which the authors say call for caution [5].
Why limited: This rests on one trial, of 3,796 people. Strength counts independent studies that agree, so one trial is limited at any size.

Ezetimibe and fenofibrateLimited

Ezetimibe with a moderate statin against a high-dose statin

One trial found a moderate statin with ezetimibe matched a high-intensity statin on heart events over 3 years, 9.1% against 9.9%, with fewer people stopping for intolerance.

Compared with high-intensity statin alone, rosuvastatin 20 mg [6]

The numbers and sources

Effect: The 3-year composite of cardiovascular death, major cardiovascular events or nonfatal stroke was 9.1% on rosuvastatin 10 mg with ezetimibe and 9.9% on rosuvastatin 20 mg, meeting the trial's noninferiority margin. LDL below 70 mg/dL was reached by 72% to 75% against 55% to 60%, and drug stopping or dose cuts for intolerance were 4.8% against 8.2% [6].
Population: 3,780 patients with atherosclerotic heart disease at 26 centers in South Korea [6].
Sources: [6]
Caveats: Open-label, a noninferiority design, and funded by a manufacturer [6].
Why limited: This rests on one trial, of 3,780 people. Strength counts independent studies that agree, so one trial is limited at any size.

Ezetimibe and fenofibrateModerate

Fenofibrate and fibrates: heart attacks and strokes

Mixed results: pooled fibrate trials showed about 10% fewer major heart events and 13% fewer coronary events, but fenofibrate's main trial missed its coronary goal and deaths did not fall.

Compared with placebo [8][9]; placebo or usual care [10]

The numbers and sources

Effect: In people with type 2 diabetes, coronary events were 5.2% on fenofibrate and 5.9% on placebo (HR 0.89, 95% CI 0.75 to 1.05), not significant. Total cardiovascular events fell from 13.9% to 12.5% (HR 0.89, 95% CI 0.80 to 0.99), with 24% fewer nonfatal heart attacks and a nonsignificant rise in coronary deaths (HR 1.19) [8]. Across 18 fibrate trials, major cardiovascular events fell 10% (95% CI 0 to 18), coronary events 13%, and stroke, cardiovascular death and all-cause death did not change [9]. In primary prevention, fibrates lowered cardiovascular death, heart attack or stroke (RR 0.84, 95% CI 0.74 to 0.96), with absolute reductions under 1% [10]. The fenofibrate label states it was not shown to reduce coronary heart disease illness and death in type 2 diabetes [7].
Population: 9,795 adults aged 50 to 75 with type 2 diabetes, 5 years [8]; 45,058 people in 18 trials [9]; 16,135 people in 6 primary prevention trials [10].
Sources: [8], [9], [10], [7]
Caveats: [9] and [10] pool fibrates as a class, including gemfibrozil and bezafibrate, not fenofibrate alone. More placebo patients started statins in [8], which the authors say may have masked a benefit.

Ezetimibe and fenofibrateModerate

Fenofibrate added to a statin

Not shown to lower heart attacks, strokes or heart deaths when fenofibrate was added to simvastatin in type 2 diabetes, 2.2% against 2.4% a year.

Compared with simvastatin with placebo [11]; statins alone [10]

The numbers and sources

Effect: The annual rate of nonfatal heart attack, nonfatal stroke or cardiovascular death was 2.2% on fenofibrate with simvastatin and 2.4% on simvastatin with placebo (HR 0.92, 95% CI 0.79 to 1.08), and no secondary outcome differed. Annual deaths were 1.5% and 1.6%. A subgroup with high triglycerides and low HDL suggested possible benefit, and results differed by sex [11]. In the Cochrane review, the two trials of fibrates on top of statins showed no benefit [10].
Population: 5,518 patients with type 2 diabetes, mean follow-up 4.7 years [11]; 2 trials [10].
Sources: [11], [10]
Caveats: Subgroup findings were prespecified but not confirmed [11].

Peptides and SARMs

TesamorelinModerate

Triglycerides and cholesterol

Shown to lower triglycerides about 12% more than placebo in adults with HIV. These are lab changes, and long-term heart effects are not established.

The numbers and sources

Effect: At 26 weeks, triglycerides changed by -50 mg/dL on tesamorelin and +9 mg/dL on placebo, and the total to HDL cholesterol ratio by -0.31 against +0.21 [1]. Pooled across both trials, triglycerides changed by -37 against +6 mg/dL, a treatment effect of -12.3% [3].
Population: As above [1][3].
Sources: [1], [3]
Caveats: Laboratory changes only. The label states that long-term cardiovascular safety has not been established [6].

Supplements

Apple cider vinegarStrong

Cholesterol

Shown to lower total cholesterol by about 6 mg/dL in adults, with no change in LDL or HDL.

The numbers and sources

Effect: ACV lowered total cholesterol by 6.06 mg/dL (95% CI -10.95 to -1.17) with no significant effect on LDL or HDL [2]. A 2025 meta-analysis of 25 trials found total cholesterol 6.72 mg/dL lower (95% CI -12.91 to -0.53, I² 50.8%), with no significant change in LDL, HDL or triglycerides [4].
Population: Adults in 9 studies [2]. 1,320 adults in 25 trials [4].
Sources: [2], [4]
Caveats: Triglyceride reductions appeared only in subgroups [2][4].

BerberineStrong

Cholesterol and triglycerides

Shown to lower LDL by about 0.46 mmol/L and lower triglycerides in adults, in trials mostly from China and Hong Kong.

The numbers and sources

Effect: In 18 placebo-controlled trials (1,788 participants), berberine lowered LDL by 0.46 mmol/L (95% CI -0.62 to -0.30), total cholesterol by 0.48 mmol/L and triglycerides by 0.34 mmol/L, and raised HDL by 0.06 mmol/L. The HDL rise was seen in women and not in men [8]. A 27-trial meta-analysis found berberine combined with lipid drugs lowered cholesterol more than the drugs alone [4].
Population: Adults, mostly in mainland China and Hong Kong, for 4 to 24 weeks [8].
Sources: [4], [8]
Caveats: 15 of the 18 trials were in mainland China or Hong Kong [8].

Beta-glucanStrong

LDL cholesterol (oat beta-glucan)

Shown to lower LDL by about 0.2 to 0.25 mmol/L in adults at 3 g a day or more of oat beta-glucan.

The numbers and sources

Effect: In 28 trials, 3 g a day or more of oat beta-glucan lowered LDL by 0.25 mmol/L (95% CI 0.20 to 0.30) and total cholesterol by 0.30 mmol/L, with no change in HDL or triglycerides. Dose (3.0 to 12.4 g a day) and duration (2 to 12 weeks) did not change the result [1]. In 58 trials (3,974 people), a median 3.5 g a day lowered LDL by 0.19 mmol/L (95% CI 0.14 to 0.23), non-HDL by 0.20 mmol/L and apoB by 0.03 g/L [2].
Population: Adults, mostly with normal to raised cholesterol [1][2].
Sources: [1], [2]
Caveats: LDL heterogeneity was high in [2] (I² 79%). [1] was supported by DSM Nutritional Products and searched in-house reports at CreaNutrition, a subsidiary of an oat fiber company. FDA's health claim rests on 3 g a day or more from whole oats or barley [3].

Black seed oilStrong

Cholesterol and triglycerides

Shown to lower LDL by about 14 mg/dL and triglycerides by about 21 mg/dL in adults. HDL did not change overall.

The numbers and sources

Effect: In 17 RCTs, Nigella sativa lowered total cholesterol by 15.65 mg/dL (95% CI -24.67 to -6.63), LDL by 14.10 mg/dL and triglycerides by 20.64 mg/dL. HDL did not change overall (0.28 mg/dL, 95% CI -1.96 to 2.53) and rose only with seed powder. Oil lowered total and LDL cholesterol more than powder [1]. A 2025 review of 82 RCTs (5,026 participants) also reported improved total cholesterol, LDL, HDL and triglycerides [2].
Population: Adults in placebo-controlled RCTs [1]. Trials of 1 to 48 weeks [2].
Sources: [1], [2]
Caveats: The 2025 abstract lists outcomes without effect sizes [2]. Neither review measured heart attacks or strokes.

Fiber supplementsStrong

LDL cholesterol

Shown to lower LDL cholesterol by about 0.33 mmol/L with about 10 g of psyllium a day in adults with or without high cholesterol.

The numbers and sources

Effect: Across 28 trials (1,924 participants), a median 10.2 g of psyllium a day lowered LDL cholesterol by 0.33 mmol/L (95% CI -0.38 to -0.27), non-HDL cholesterol by 0.39 mmol/L and apoB by 0.05 g/L (95% CI -0.08 to -0.03) [1]. A 2025 meta-analysis of 41 RCTs (2,049 participants) found LDL cholesterol 8.55 mg/dL lower (95% CI -12.92 to -4.19) and total cholesterol 9.05 mg/dL lower. Triglycerides and HDL did not change significantly [2].
Population: Adults with or without high cholesterol in RCTs of 3 weeks or longer [1]; adults in 41 RCTs [2].
Sources: [1], [2]
Caveats: LDL and non-HDL estimates were graded moderate quality because of inconsistency, and apoB high quality [1]. Heterogeneity in the 2025 review was considerable (I² 88% for LDL), and dose and duration did not explain it [2].

Fish oilStrong

Triglycerides

Shown to lower triglycerides by about 15% in adults, more at higher doses.

The numbers and sources

Effect: Increasing long-chain omega-3 reduced triglycerides by about 15% in a dose-dependent way (high-certainty evidence). It had little or no effect on other blood lipids, adiposity or blood pressure [1]. In 23 RCTs of people with coronary heart disease, omega-3 lowered triglycerides (SMD -0.25, 95% CI -0.38 to -0.11), with a linear dose-response [2]. Across 21 trials in mixed populations, triglycerides fell 16.95 mg/dL (95% CI -23.25 to -10.66) [3]. In 9 trials of people with fatty liver disease, they fell 13.81 mg/dL (95% CI -24.56 to -3.06), with no significant effect in those who also had type 2 diabetes [4]. In 21 trials of metabolic syndrome, reductions ranged from about 25 to 57 mg/dL, largest above 2,000 mg a day [5].
Population: 86 RCTs with 162,796 adults at varying cardiovascular risk, lasting 12 to 88 months, mostly capsule supplements [1]; 2,061 patients with coronary heart disease [2]; 2,043 adults in 24 studies [3]; 528 patients with fatty liver disease [4]; about 1,950 adults with metabolic syndrome or its components [5].
Sources: [1], [2], [3], [4], [5]
Caveats: The Cochrane abstract reports the triglyceride effect as a percentage without a confidence interval [1]. The metabolic syndrome review reports subgroup reductions about three times the size of the other pooled estimates, from dose and duration subgroups rather than one overall estimate [5].

GarlicStrong

Cholesterol

Shown to lower total cholesterol about 10 to 17 mg/dL and LDL about 6 to 9 mg/dL in adults, more in those with high cholesterol.

The numbers and sources

Effect: Across 39 trials, garlic lowered total cholesterol by 17 ± 6 mg/dL and LDL by 9 ± 6 mg/dL in people with total cholesterol above 200 mg/dL, when taken for longer than 2 months. HDL rose slightly and triglycerides did not change significantly [3]. A 2026 meta-analysis of 108 trials (7,137 adults) found total cholesterol fell 10.21 mg/dL (95% CI -13.69 to -6.74), LDL 5.90 mg/dL, and triglycerides 5.82 mg/dL, while HDL rose 2.18 mg/dL [4].
Population: Adults in 39 trials, effects reported in those with elevated cholesterol [3]. Adults in 108 trials [4].
Sources: [3], [4]
Caveats: The abstract of [3] describes earlier meta-analyses on this question as conflicting. The authors of [4] report larger effects in adults with unfavorable baseline risk factors and call for larger, longer, more rigorous trials. The two reviews disagree on triglycerides.

GlucomannanStrong

LDL cholesterol

Shown to lower LDL cholesterol by about 10%, about 16 mg/dL, in adults and children. Changes were not significant in adults with insulin resistance.

The numbers and sources

Effect: Across 14 studies with 531 participants, glucomannan lowered total cholesterol 19.28 mg/dL (95% CI -24.30 to -14.26), LDL 15.99 mg/dL (95% CI -21.31 to -10.67) and triglycerides 11.08 mg/dL (95% CI -22.07 to -0.09), with no change in HDL [1]. Across 12 studies with 370 participants, LDL fell 0.35 mmol/L (95% CI -0.46 to -0.25) and non-HDL cholesterol 0.32 mmol/L, about 10% and 7%. Apolipoprotein B did not change in 6 trials [2].
Population: Adults and children in RCTs [1][2].
Sources: [1], [2]
Caveats: Trials were small and short, with follow-up of at least 3 weeks in [2]. In 11 trials restricted to adults with insulin resistance-related conditions, lipid changes were not significant overall, with LDL and total cholesterol lower only in subgroups above 3,000 mg a day or at 4 weeks or less [3].

Green tea extractStrong

LDL cholesterol

Shown to lower LDL cholesterol slightly, about 2 mg/dL, and total cholesterol about 7 mg/dL in adults, with no HDL change.

The numbers and sources

Effect: Across 14 RCTs (1,136 subjects), green tea beverages or extracts lowered total cholesterol by 7.20 mg/dL (95% CI -8.19 to -6.21) and LDL cholesterol by 2.19 mg/dL (95% CI -3.16 to -1.21). HDL did not change [3]. Across 13 studies, LDL fell by 0.16 mmol/L (95% CI -0.22 to -0.09) [4].
Population: Adults in RCTs [3][4].
Sources: [3], [4]
Caveats: Both reviews pooled beverages with extracts.

TaurineStrong

Blood sugar and blood lipids

Shown to lower fasting glucose about 6 mg/dL and triglycerides about 14 to 18 mg/dL, mostly in people with obesity, diabetes or metabolic syndrome. HDL did not change.

The numbers and sources

Effect: Fasting glucose fell by 5.9 mg/dL (95% CI -10.7 to -1.0) and triglycerides by 18.3 mg/dL (95% CI -25.6 to -11.0). HDL cholesterol did not change [4]. A second meta-analysis found fasting glucose 5.9 mg/dL lower, HbA1c 0.21% lower, triglycerides 14.4 mg/dL lower and LDL cholesterol 5.1 mg/dL lower [5].
Population: 25 RCTs, 1,024 participants [4]; 34 RCTs [5].
Sources: [4], [5]
Caveats: Most trials were short and enrolled people with obesity, diabetes or metabolic syndrome. Neither review measured hard outcomes such as heart attacks or diabetes onset.

TurmericStrong

Cholesterol and triglycerides

Shown to lower triglycerides about 13 mg/dL and LDL about 6 mg/dL in adults with metabolic conditions. Smaller reviews found no significant LDL change.

The numbers and sources

Effect: An umbrella review re-pooled 72 RCTs. Curcumin lowered LDL cholesterol by 5.84 mg/dL (95% CI -11.63 to -0.05), triglycerides by 13.15 mg/dL (95% CI -17.31 to -8.98) and total cholesterol by 7.76 mg/dL, and raised HDL by 2.4 mg/dL [10]. In 27 RCTs in prediabetes and diabetes, triglycerides fell 13.73 mg/dL, total cholesterol 5.24 mg/dL and LDL 5.72 mg/dL (95% CI -8.62 to -2.82), and HDL rose 2.14 mg/dL [11]. In 11 RCTs (662 people with metabolic disease), triglycerides and total cholesterol fell, while LDL and HDL did not change significantly under random-effects models [12]. With piperine added, 16 RCTs (1,038 participants) showed lower triglycerides and total cholesterol and no significant LDL change [13].
Population: Adults with noncommunicable diseases, with larger effects in type 2 diabetes [10]; adults with prediabetes or diabetes [11]; adults with metabolic disorders [12][13].
Sources: [10], [11], [12], [13]
Caveats: I² was 94% to 98% in the umbrella review [10] and above 80% in the diabetes review, which rated certainty low for every outcome [11]. The LDL drop did not reach significance in two smaller reviews [12][13]. The umbrella review found the total cholesterol and HDL changes smaller than their minimal clinically important differences [10].

AstaxanthinModerate

Blood sugar and blood lipids

Shown to lower fasting glucose by about 16 mg/dL and triglycerides in people with prediabetes or type 2 diabetes. Reviews disagree on LDL and total cholesterol.

The numbers and sources

Effect: In prediabetes and type 2 diabetes, astaxanthin lowered fasting glucose by 16.1 mg/dL (95% CI -29.0 to -3.3), HbA1c by 0.34 points, triglycerides by 20.9 mg/dL, total cholesterol by 12.2 mg/dL and LDL by 9.4 mg/dL, and raised HDL by 3.0 mg/dL. HOMA-IR, weight and BMI did not change [4]. At 6 to 20 mg a day, a second meta-analysis found higher HDL and lower triglycerides, with no change in LDL or total cholesterol [5]. In adults at risk of metabolic syndrome, effects on total cholesterol and systolic pressure were marginal, and LDL fell [6].
Population: 403 patients in 9 RCTs [4]; 8 studies with 11 results [5]; 321 adults in 7 RCTs [6].
Sources: [4], [5], [6]
Caveats: The reviews disagree on LDL and total cholesterol. All pooled small trials.

Beta-glucanModerate

LDL cholesterol (barley beta-glucan)

Shown to lower LDL by about 0.25 mmol/L in adults on a median 6.5 g a day of barley beta-glucan.

The numbers and sources

Effect: In 14 trials (615 people), a median 6.5 g a day of barley beta-glucan for 4 weeks lowered LDL by 0.25 mmol/L (95% CI 0.20 to 0.30) and non-HDL by 0.31 mmol/L. ApoB did not change [4].
Population: Adults in trials of 3 weeks or longer [4].
Sources: [4]
Caveats: Non-HDL heterogeneity was high (I² 98%) [4].

FenugreekModerate

Blood lipids

Shown to lower total cholesterol and triglycerides and raise HDL in controlled trials, more in people with diabetes. Sources disagree on LDL.

The numbers and sources

Effect: Across 15 RCTs, fenugreek lowered total cholesterol (-1.13, 95% CI -1.88 to -0.37), LDL (-1.26, 95% CI -2.09 to -0.43) and triglycerides (-1.07) and raised HDL (0.70, 95% CI 0.07 to 1.34) compared with control. Effects were larger in people with diabetes [3]. The 2023 diabetes meta-analysis reported lower total cholesterol and triglycerides, higher HDL, and no change in LDL [2].
Population: 281 people on fenugreek and 255 controls in controlled trials [3].
Sources: [2], [3]
Caveats: The sources disagree on LDL. The abstract of [3] does not state the units of its pooled estimates.

Fisetin and quercetin (senolytics)Moderate

Liver enzymes and lipids in fatty liver disease (quercetin alone)

Shown to lower liver enzymes, LDL and triglycerides with quercetin alone in people with fatty liver disease, at very low to moderate certainty.

The numbers and sources

Effect: A 2025 meta-analysis of 7 RCTs (540 patients) with metabolic dysfunction-associated steatotic liver disease found that quercetin lowered ALT, AST, GGT, direct bilirubin and C-reactive protein, lowered total cholesterol, LDL and triglycerides, and raised HDL. BMI, body fat, kidney function and TNF-α did not change [10].
Population: 540 patients with fatty liver disease in 7 RCTs [10].
Sources: [10]
Caveats: GRADE certainty ranged from very low to moderate. Dose, baseline BMI and age may explain heterogeneity. The abstract gives no pooled effect sizes [10]. None of the trials measured senescent cells.

Garcinia cambogiaModerate

Cholesterol and triglycerides

Shown to lower triglycerides about 24 mg/dL and raise HDL slightly in adults, with no LDL change. One 10-week trial found no lipid change.

The numbers and sources

Effect: Across 14 trials with 623 subjects, total cholesterol fell 6.76 mg/dL (95% CI -12.39 to -0.59), triglycerides fell 24.21 mg/dL (95% CI -37.84 to -10.58) and HDL rose 2.95 mg/dL (95% CI 2.01 to 3.89). LDL did not change (-1.15 mg/dL, 95% CI -16.08 to 13.78). Changes were larger in trials longer than 8 weeks [5]. In the 10-week Korean trial, garcinia extract did not change triglycerides or total cholesterol compared with placebo [4].
Population: Adults in 14 RCTs [5]; 86 overweight adults [4].
Sources: [4], [5]
Caveats: Interventions were short and heterogeneity was significant [5].

InositolModerate

Weight, blood sugar and lipids

Shown to lower BMI slightly, about 0.6 kg/m², and glucose, triglycerides and blood pressure in adults across several conditions, at low certainty for some.

The numbers and sources

Effect: In 18 RCTs (898 participants) of at least 4 weeks, inositol lowered BMI by 0.57 kg/m² (95% CI -1.10 to -0.03), waist circumference by 2.36 cm, glucose by 7.25 mg/dL, HOMA-IR by 1.21, triglycerides by 29.80 mg/dL, LDL cholesterol by 5.15 mg/dL, and systolic and diastolic pressure by 5.34 and 6.12 mm Hg [11].
Population: Adults in RCTs across several conditions [11].
Sources: [11]
Caveats: Certainty was low to very low for BMI, waist and blood pressure, and moderate for glucose, insulin and HOMA-IR. Heterogeneity was high for most outcomes, and the authors note a high risk of bias in the trials [11].

NiacinModerate

Blood lipids

Shown to raise HDL and lower triglycerides and LDL in people with vascular disease on statins, though events did not fall.

The numbers and sources

Effect: At 2 years in AIM-HIGH, median HDL rose from 35 to 42 mg/dL, triglycerides fell from 164 to 122 mg/dL and LDL fell from 74 to 62 mg/dL on 1,500 to 2,000 mg a day of extended-release niacin [1]. In HPS2-THRIVE, LDL averaged 10 mg/dL lower and HDL 6 mg/dL higher than placebo [2].
Population: 3,414 people with cardiovascular disease on simvastatin [1]; 25,673 adults with vascular disease on statin-based therapy [2].
Sources: [1], [2]
Caveats: Lipid changes did not translate into fewer events in these trials (see next block).

Fish oilModerate

LDL and HDL cholesterol

Mixed results: most reviews found little or no change in LDL or HDL, while subgroups saw LDL fall in some groups and rise in others.

The numbers and sources

Effect: The Cochrane review found little or no effect on blood lipids other than triglycerides [1]. In coronary heart disease, LDL and HDL did not change significantly, and total cholesterol fell slightly (SMD -0.12) [2]. Across mixed populations, HDL rose 1.55 mg/dL (95% CI 0.69 to 2.42), and LDL fell only in subgroups of women and of people with polycystic ovary syndrome [3]. In metabolic syndrome trials, LDL rose in low-dose subgroups (7.04 mg/dL short term, 35.5 mg/dL long term) [5].
Population: Trial participants in the four reviews above [1][2][3][5].
Sources: [1], [2], [3], [5]
Caveats: The reviews differ on direction in subgroups. The LDL rise in [5] came from few studies per subgroup.

ResveratrolModerate

Inflammation and blood lipids

Mixed results: reviews disagree on whether CRP falls, and most found no change in LDL or triglycerides.

The numbers and sources

Effect: One meta-analysis found no change in CRP (WMD -0.144 mg/L, 95% CI -0.968 to 0.680), total cholesterol, LDL, triglycerides or glucose. HDL fell slightly (WMD -4.18 mg/dL, 95% CI -6.54 to -1.82) [4]. A later meta-analysis found lower TNF-α (WMD -0.44, 95% CI -0.71 to -0.16) and hs-CRP (WMD -0.27, 95% CI -0.5 to -0.02), with no change in IL-6 [6]. In 25 RCTs in metabolic disorders, CRP fell (SMD -0.18, 95% CI -0.33 to -0.03), and IL-6 and TNF-α did not change significantly [7]. In 6 RCTs in type 2 diabetes (533 participants), CRP fell (SMD -1.40, 95% CI -2.60 to -0.21) [8]. Apolipoprotein B (WMD 2.11 mg/dL, 95% CI -1.53 to 5.75) and apolipoprotein A-I did not change in 7 RCTs [9]. An umbrella review rated as high certainty a 0.19 mmol/L drop in total cholesterol in adults with overweight (95% CI 0.06 to 0.32) [5].
Population: 10 RCTs [4]; 17 RCTs with 736 adults [6]; adults with metabolic disorders [7]; adults with type 2 diabetes [8]; 7 RCTs [9]; meta-analyses of RCTs [5].
Sources: [4], [6], [7], [8], [9], [5]
Caveats: The reviews disagree on CRP, and the CRP effect in [8] is several times the size of that in [7]. Heterogeneity in [6] was about 50%. Evidence in [8] was low certainty. CRP is a marker, not a clinical outcome [7].

Grape seed extractLimited

Cholesterol

Limited evidence: a 50-trial review found lower total and LDL cholesterol and triglycerides, while an earlier review found no effect on lipids.

The numbers and sources

Effect: Across 50 trials, grape seed extract lowered total cholesterol (WMD -6.03, 95% CI -9.71 to -2.35), LDL cholesterol (WMD -4.97) and triglycerides (WMD -6.55). HDL did not change [5]. An earlier meta-analysis of 9 RCTs found no significant effect on lipid levels [2].
Population: Adults in RCTs [5][2].
Sources: [5], [2]
Caveats: The two reviews disagree.

Tart cherryStrong

Blood pressure and cardiometabolic markers

Not shown to change blood pressure, cholesterol or body fat in adults. Fasting glucose and CRP fell very slightly.

The numbers and sources

Effect: Across 10 RCTs, tart cherry juice did not change blood pressure, cholesterol, triglycerides or body fat. Fasting glucose fell by 0.51 mg/dL [4]. Across 21 trials, blood pressure, heart rate, hs-CRP and IL-6 did not change, while CRP fell by 0.39 mg/L (95% CI -0.74 to -0.05, moderate certainty) [5]. A 3-month trial in 50 middle-aged adults found no change in vascular or metabolic measures [6].
Population: Adults across 10 to 21 RCTs [4][5]; middle-aged adults, 30 mL concentrate twice a day [6].
Sources: [4], [5], [6]
Caveats: A 0.51 mg/dL glucose change is very small. The 3-month trial was funded by the Cherry Research Committee [6].

ChromiumModerate

Blood sugar in people without diabetes

Not shown to change glucose or lipid metabolism in people without diabetes.

The numbers and sources

Effect: Chromium did not change glucose or lipid metabolism in people without diabetes [1].
Population: Trials of people without diabetes within a 41-trial review [1].
Sources: [1]
Caveats: The review notes no consensus on how to measure chromium status [1].

NMNModerate

Insulin sensitivity and metabolic markers

Not shown to change weight, glucose, HbA1c or lipids across trials. One small trial found better insulin sensitivity in women with prediabetes.

The numbers and sources

Effect: In women with prediabetes and overweight or obesity, insulin-stimulated glucose disposal measured by clamp rose after 10 weeks of NMN and did not change on placebo [7]. Across 15 trials, NMN did not change body weight, BMI, fasting glucose, HbA1c or lipids. HOMA-IR showed a downward trend that was not significant [8]. In the 60-day dose trial, HOMA-IR did not differ from placebo [1].
Population: Postmenopausal women with prediabetes [7]; 15 RCTs at 250 to 2,000 mg a day for 14 days to 24 weeks [8]; 80 middle-aged adults [1].
Sources: [7], [8], [1]
Caveats: The clamp result comes from a single small trial in one population [7]. The pooled trials were short [8].

ReishiModerate

Blood sugar, cholesterol and blood pressure

Not shown to change HbA1c, fasting glucose, cholesterol or blood pressure against placebo, with one spore oil trial finding lower lipids.

The numbers and sources

Effect: In a Cochrane review of 5 trials (398 participants), 1.4 to 3 g a day for 12 to 16 weeks did not change HbA1c (WMD -0.10%, 95% CI -1.05 to 0.85), total cholesterol, LDL or BMI against placebo. Fasting glucose, blood pressure and triglycerides did not differ. Post-meal glucose results were inconsistent [2]. A 2025 meta-analysis of 17 RCTs (971 participants) at 200 to 11,200 mg a day for 1 to 24 weeks found no effect on blood pressure, fasting glucose or the lipid profile. BMI fell by 0.43 (95% CI 0.10 to 0.77) and heart rate by 3.92 beats a minute (95% CI 0.40 to 7.45) [3]. In 110 adults with dyslipidemia, a spore oil extract for 12 weeks lowered total cholesterol, triglycerides and LDL and raised HDL compared with placebo. The abstract gives no effect sizes [4].
Population: Adults with type 2 diabetes in the analyzed trials [2]. Healthy, at-risk and chronically ill adults [3]. Adults with dyslipidemia [4].
Sources: [2], [3], [4]
Caveats: Data in [2] came from 3 small trials, and risk of bias was unclear in 4 of 5 [2]. The 2025 review rated the certainty of evidence very low for every outcome [3]. The spore oil trial tested a different product and disagrees with both reviews on lipids [4].

Therapies

CuppingLimitedStudied in men

LDL cholesterol, wet cupping

One small trial found LDL cholesterol fell after wet cupping in 47 healthy young men, with no significant change in total cholesterol, HDL or triglycerides.

Compared with no treatment [12]

The numbers and sources

Effect: Over 3 weeks after one wet cupping session, LDL cholesterol and the LDL to HDL ratio fell in the treated group against untreated controls (p < 0.0001). Triglycerides did not change, and total cholesterol (7% lower) and HDL (3% higher) did not differ significantly [12].
Population: 47 healthy men aged 18 to 25 [12].
Sources: [12]
Caveats: One small trial in young men without high cholesterol, with no sham. Wet cupping removes blood, and the authors compare it with phlebotomy [12].

Practices

Tai chi and qigongModerate

Blood fats in hypertension

Shown in two meta-analyses to lower LDL cholesterol and triglycerides in people with hypertension. HDL cholesterol results differed between them.

Compared with control groups the source abstract does not describe [5]; no intervention [6]

The numbers and sources

Effect: Tai chi was associated with lower total cholesterol (WMD -0.49), triglycerides (WMD -0.49, 95% CI -0.92 to -0.07) and LDL cholesterol (WMD -0.86), and no significant effect on HDL cholesterol (P = 0.16) [5]. Baduanjin lowered triglycerides and LDL cholesterol and raised HDL cholesterol against no intervention [6].
Population: Adults with essential hypertension [5][6].
Sources: [5], [6]
Caveats: The first abstract gives no units, and its HDL interval does not contain its own point estimate [5]. The second gives no sizes for blood fats [6].

Whole-body cryotherapyModerate

Cholesterol and triglycerides

Shown to lower triglycerides in a meta-analysis of 7 studies. Total and LDL cholesterol were lower only after single studies were removed.

The numbers and sources

Effect: Pooled data from 7 studies showed significantly lower triglycerides after a series of sessions. Total cholesterol and LDL were significantly lower only in sensitivity analyses that removed single studies. Lower baseline body mass index was associated with larger changes [12].
Population: Participants in 7 studies [12].
Sources: [12]
Caveats: The authors urge caution because of the low number of studies and considerable differences in methods [12]. The abstract reports no effect sizes.

YogaModerate

Stress hormones, heart rate and blood fats, against active controls

Shown in one meta-analysis to lower cortisol, ambulatory systolic pressure, resting heart rate, fasting glucose and LDL cholesterol more than active control activities.

Compared with active control interventions [11]

The numbers and sources

Effect: Across 42 trials, practices including yoga postures were associated with lower evening and waking cortisol, ambulatory systolic blood pressure, resting heart rate, fasting blood glucose, cholesterol and LDL cholesterol, and higher high-frequency heart rate variability, compared with active controls [11].
Population: Participants in 42 randomized trials in various populations [11].
Sources: [11]
Caveats: The abstract gives no effect sizes and describes the interventions as heterogeneous. Some included mindfulness-based stress reduction alongside postures [11].

YogaModerate

Blood sugar and blood fats in type 2 diabetes

Shown in one meta-analysis to lower HbA1c by 0.47 points and fasting glucose by 24 mg/dL in adults with type 2 diabetes, with high heterogeneity.

Compared with control groups including usual care or standard treatment [12]

The numbers and sources

Effect: Pooled differences were -23.72 mg/dL for fasting blood glucose (95% CI -37.78 to -9.65, I² 82%), -0.47% for HbA1c (95% CI -0.87 to -0.07, I² 82%), -17.38 mg/dL for glucose after meals, -18.50 mg/dL for total cholesterol, +4.30 mg/dL for HDL cholesterol and -12.95 mg/dL for LDL cholesterol. Triglycerides did not differ (-12.57 mg/dL, 95% CI -29.91 to 4.76) [12].
Population: 864 adults with type 2 diabetes in 12 trials [12].
Sources: [12]
Caveats: The authors note limited methods and heterogeneity, and long-term effects were not studied [12].

SaunaLimited

Cholesterol

Mixed results: 4 trials in adults under 60 found lower total and LDL cholesterol with hot spring or sauna use, and 3 trials in older adults found no change.

The numbers and sources

Effect: A systematic review of 7 RCTs found reductions in total and LDL cholesterol in 4 trials with a mean age under 60, and no significant lipid changes in 3 trials with a mean age of 60 or more [22]. In sedentary adults, total cholesterol fell 19 mg/dL more (95% CI -35 to 0) with exercise plus sauna than with exercise alone over 8 weeks [3].
Population: Adults in 7 RCTs of hot spring or sauna use, alone or with exercise [22]. 47 sedentary adults [3].
Sources: [22], [3]
Caveats: The review pools hot springs with saunas and reports no pooled effect size [22]. The confidence interval in [3] reaches zero.

Infrared saunaLimited

Cholesterol

Limited evidence: a 2009 review of 9 far-infrared sauna papers found consistent fair evidence against a cholesterol-lowering effect.

The numbers and sources

Effect: The review concluded there was consistent fair evidence to refute claims regarding cholesterol reduction [14].
Population: 9 papers on far-infrared sauna in humans, 4 in heart failure and 5 in people with coronary risk factors [14].
Sources: [14]
Caveats: A review by a single author, searched to 2009, with no pooled numbers in the abstract.

Daily life

Physical activityStrong

Blood fats

Shown to lower triglycerides in pooled trials of aerobic training, with HDL cholesterol rising modestly in two reviews and not changing overall in a third.

Compared with control groups in randomized trials [8][9]; no exercise, or diet alone [10]

The numbers and sources

Effect: HDL cholesterol rose by 2.53 mg/dL against controls, from a minimum of about 120 minutes of exercise a week, and rose more with longer sessions [8]. In sedentary adults with metabolic syndrome factors, aerobic training lowered triglycerides by 0.17 to 0.18 mmol/L, total cholesterol by 0.19 to 0.29 mmol/L and LDL cholesterol by 0.12 to 0.20 mmol/L, and raised HDL cholesterol by 0.05 to 0.10 mmol/L [9]. In adults with overweight or obesity, aerobic exercise lowered triglycerides and did not change total, HDL or LDL cholesterol overall [10].
Population: 25 randomized trials [8]. 2,990 participants in 48 data sets of trials of at least 12 weeks [9]. 619 adults with overweight or obesity in 9 trials [10].
Sources: [8], [9], [10]
Caveats: Changes were modest. The populations differed across reviews, which may explain the HDL difference.

Food and drink

NutsStrong

LDL cholesterol and ApoB

Shown to lower LDL cholesterol by about 4.8 mg/dL per daily ounce of tree nuts, and by 10.2 mg/dL at about 67 g a day, along with ApoB.

Compared with control arms without nuts [4]; control diets the abstract does not describe [5]

The numbers and sources

Effect: Per 1 oz (28.4 g) serving a day, tree nuts lowered total cholesterol by 4.7 mg/dL (95% CI 4.0 to 5.3), LDL cholesterol by 4.8 mg/dL (95% CI 4.2 to 5.5), ApoB by 3.7 mg/dL (95% CI 2.3 to 5.2) and triglycerides by 2.2 mg/dL (95% CI 0.5 to 3.8). HDL cholesterol, apolipoprotein A1 and blood pressure did not change significantly. Effects were stronger at 60 g a day or more and did not differ by nut type. ApoB fell more in people with type 2 diabetes (11.5 mg/dL) than in healthy people (2.5 mg/dL) [4]. Pooled individual data from 25 trials found a mean 67 g a day lowered total cholesterol by 10.9 mg/dL (5.1%) and LDL cholesterol by 10.2 mg/dL (7.4%). Triglycerides fell 20.6 mg/dL in people starting at 150 mg/dL or higher and not in others [5].
Population: 2,582 adults without cardiovascular disease in 61 trials of 3 to 26 weeks [4]. 583 adults with normal or high cholesterol not on lipid-lowering drugs, in 25 trials in 7 countries [5].
Sources: [4], [5]
Caveats: Trials were short and many are shared between the two analyses. Effects were largest in people with higher starting LDL cholesterol and lower body mass index [5].

Soy foodsStrong

LDL cholesterol

Shown to lower LDL cholesterol by about 4.8 mg/dL, 3% to 4%, at a median 25 g of soy protein a day against non-soy protein, in pooled trials.

Compared with non-soy protein [4]; control groups the abstract does not describe [5]

The numbers and sources

Effect: Across 41 trials identified by the FDA, soy protein at a median 25 g a day for a median 6 weeks lowered LDL cholesterol by 4.76 mg/dL (95% CI -6.71 to -2.80) and total cholesterol by 6.41 mg/dL (95% CI -9.30 to -3.52), with no dose-response or publication bias. About 75% of trials showed a fall, though few were individually significant [4]. In 23 trials of soy protein with its isoflavones intact, total cholesterol fell 3.77%, LDL cholesterol 5.25% and triglycerides 7.27%, and HDL cholesterol rose 3.03%. Falls were larger in men and in people with high cholesterol. Tablets of extracted isoflavones did not lower total cholesterol [5].
Population: Adults with baseline LDL cholesterol of 110 to 201 mg/dL in 43 trials [4]. 23 randomized trials published 1995 to 2002 [5].
Sources: [4], [5]
Caveats: Heterogeneity was moderate (I² 55% for LDL) [4]. Most trials lasted weeks. The FDA has proposed revoking the soy protein heart claim [1], which the review authors attribute to a perceived lack of consistent LDL reduction in trials [4].

Whole grainsStrong

LDL cholesterol

Shown to lower LDL cholesterol slightly, by 0.09 mmol/L, against refined-grain control foods in pooled trials, with whole-grain oats lowering cholesterol most.

Compared with non-whole-grain control foods [8]; refined grains or placebo [9]

The numbers and sources

Effect: Whole grain intake lowered LDL cholesterol by 0.09 mmol/L (about 3.5 mg/dL, 95% CI -0.15 to -0.03) and total cholesterol by 0.12 mmol/L (95% CI -0.19 to -0.05), with no effect on HDL cholesterol. Triglycerides tended to fall (-0.04 mmol/L, 95% CI -0.08 to 0.01). Oats had the largest effect on total cholesterol (-0.17 mmol/L) [8]. In a second review, whole-grain oats improved total cholesterol (SMD -0.54, 95% CI -0.95 to -0.12) and LDL cholesterol (SMD -0.57, 95% CI -0.84 to -0.31), and whole-grain rice improved triglycerides [9].
Population: 24 randomized trials in apparently healthy adults [8]. 25 randomized trials of 2 to 16 weeks in adults with or without cardiovascular risk factors [9].
Sources: [8], [9]
Caveats: Small changes over weeks. The second review found the LDL effect for oats, not for all whole grains combined [9]. Beta-glucan from oats is on its own page.

AlcoholModerate

HDL cholesterol in trials

Shown to raise HDL cholesterol by about 0.09 mmol/L in trials of adults without heart disease, with no change in triglycerides.

Compared with periods without alcohol [9]

The numbers and sources

Effect: Alcohol raised HDL cholesterol (mean difference 0.094 mmol/L, 95% CI 0.064 to 0.123), apolipoprotein A1 (0.101 g/L, 95% CI 0.073 to 0.129) and adiponectin, with a dose-response for HDL. It lowered fibrinogen (-0.20 g/L) and did not change triglycerides. Results were similar for wine, beer and spirits [9].
Population: 44 interventional studies of 13 markers in adults without known cardiovascular disease [9].
Sources: [9]
Caveats: These are blood markers, not heart attacks. The review calls them indirect support for a protective effect [9], while genetic studies of heart disease found none (see above).

Green teaModerate

Cholesterol

Shown to lower total cholesterol by 2.8 mg/dL in trials of catechin-enriched green tea drinks. LDL, HDL and triglycerides did not change significantly in those trials.

Compared with water or other placebo drinks, no intervention, or green tea drinks low in catechins [4]

The numbers and sources

Effect: In the 9 trials that gave green tea as a drink, total cholesterol fell by 2.80 mg/dL (95% CI 0.16 to 5.43). LDL changed by -2.61 mg/dL (95% CI -5.49 to 0.27), HDL by -0.84 mg/dL and triglycerides by -0.77 mg/dL, none significant. Across all 31 trials of drinks and capsules, LDL fell by 4.55 mg/dL (95% CI 2.80 to 6.31) [4].
Population: 3,321 participants in 31 randomized trials, 9 of them using a green tea drink [4].
Sources: [4]
Caveats: The drinks in these trials were green tea beverages made with extract, carrying 400 to 928 mg of catechins a day, not ordinary brewed tea. Meta-regression found no significant difference between drinks and capsules [4]. Capsule trials are on the green tea extract page.

EggsStrong

HDL cholesterol and the cholesterol ratio

Shown to raise HDL cholesterol slightly in feeding trials. The ratio of LDL or total cholesterol to HDL rose in two of three pooled analyses.

Compared with diets differing only in dietary cholesterol or number of eggs [2]; control groups eating fewer eggs [3][4]

The numbers and sources

Effect: Each extra 100 mg of dietary cholesterol a day raised HDL by 0.3 mg/dL (95% CI 0.2 to 0.4), total cholesterol by 2.2 mg/dL and the total to HDL cholesterol ratio by 0.020 units (95% CI 0.010 to 0.030) [2]. Across 66 trials, eggs raised HDL and apolipoprotein A1 along with total and LDL cholesterol, with no change in the LDL to HDL ratio [4]. Across 17 trials in healthy people, eating more eggs raised the LDL to HDL ratio by 0.14 (P = 0.001) [3].
Population: 556 participants in 17 controlled feeding studies of at least 14 days [2]. 3,185 participants in 66 randomized trials [4]. Healthy participants in 17 randomized trials [3].
Sources: [2], [4], [3]
Caveats: The pooled analyses disagree on the ratio. Trials ran weeks to months and measured blood lipids, not heart events.

Olive oilModerate

Cholesterol

Shown to raise HDL cholesterol slightly in trials. LDL fell with high-polyphenol olive oil, but other plant oils lowered LDL more than olive oil did.

Compared with other plant oils [9]; low-polyphenol olive oil [10][11]

The numbers and sources

Effect: Against other plant oils, olive oil raised HDL more (1.37 mg/dL, 95% CI 0.4 to 2.36) and lowered total cholesterol (by 6.27 mg/dL), LDL (by 4.2 mg/dL, 95% CI 1.4 to 7.01) and triglycerides (by 4.31 mg/dL) less. Apolipoproteins A1 and B did not differ [9]. Against low-polyphenol olive oil, high-polyphenol oil lowered total cholesterol by 4.5 mg/dL and raised HDL by 2.37 mg/dL [10]. A later pooling found higher HDL (1.13 mg/dL, 95% CI 0.45 to 1.80), lower LDL only at the highest polyphenol level (-4.28 mg/dL) and no change in total cholesterol [11].
Population: 1,089 participants in 27 randomized trials [9]. 26 randomized trials [10]. 10 randomized trials, mostly crossover, in mostly healthy Europeans [11].
Sources: [9], [10], [11]
Caveats: The changes are a few mg/dL. The comparison decides the direction: olive oil looks favorable against low-polyphenol olive oil and less favorable for LDL against other plant oils.

Red meat and processed meatModerate

Cholesterol and blood pressure in trials

Not shown to change cholesterol or blood pressure against all comparison diets combined. Against plant proteins, LDL fell less on red meat. Against fish, it fell more.

Compared with diets replacing red meat with legumes, soy or nuts, fish, poultry, mixed animal protein, refined carbohydrates or the usual diet [4]

The numbers and sources

Effect: Against all comparison diets combined, red meat made no significant difference to total, LDL or HDL cholesterol, apolipoproteins A1 and B, or blood pressure, and gave a smaller fall in triglycerides (0.065 mmol/L). Against high-quality plant proteins, total cholesterol fell 0.264 mmol/L less and LDL 0.198 mmol/L less. Against fish, LDL fell 0.173 mmol/L more and HDL 0.065 mmol/L more. Against refined carbohydrates, triglycerides fell 0.181 mmol/L more [4].
Population: 1,803 participants in 36 randomized trials [4].
Sources: [4]
Caveats: The result depends on what replaced the red meat. Trials measured blood markers, not heart events.

GrapefruitLimited

Cholesterol

Mixed results: one trial found HDL cholesterol rose with grapefruit against a water preload, while another found no difference in blood lipids against a control diet.

Compared with a control diet low in fruits and vegetables [4]; a water preload matched for weight and calories [5]

The numbers and sources

Effect: Over 12 weeks, HDL cholesterol changed by +6.2% with grapefruit and +8.2% with grapefruit juice preloads, against -3.7% with water (significant) [5]. Over 6 weeks, lipids did not differ between the grapefruit and control groups, though total cholesterol fell 11.7 mg/dL and LDL cholesterol 18.7 mg/dL from baseline in the grapefruit group [4].
Population: 85 obese adults on calorie restriction [5]. 74 overweight adults [4].
Sources: [5], [4]
Caveats: Two small trials with different comparisons. Changes from baseline within one group do not show an effect of grapefruit when the control group is not different [4].

Diets

Keto dietStrong

Triglycerides and HDL cholesterol

Shown to lower triglycerides by about 0.2 to 0.3 mmol/L and raise HDL cholesterol more than comparison diets in adults.

Compared with diets that did not restrict carbohydrates to the level of ketosis

The numbers and sources

Effect: Against low-fat diets over 12 months or more, triglycerides fell 0.18 mmol/L more (95% CI 0.08 to 0.27) and HDL rose 0.09 mmol/L more (95% CI 0.06 to 0.12) [1]. Across 27 RCTs, triglycerides fell 0.20 mmol/L (95% CI 0.11 to 0.29) and HDL rose 0.16 mmol/L (95% CI 0.09 to 0.23) against control diets [2]. In 62 studies, triglycerides fell 19.96 mg/dL (95% CI 13.81 to 26.10) and HDL rose 3.61 mg/dL (95% CI 1.44 to 5.57) [5]. In pre-diabetes and type 2 diabetes, triglycerides were 0.28 mmol/L lower at 12 months (95% CI 0.11 to 0.44) [6].
Population: Adults with and without obesity or type 2 diabetes [1][2][5][6].
Sources: [1], [2], [5], [6]
Caveats: Heterogeneity was 72.2% for triglycerides and 86.7% for HDL in [2]. The same reviews found LDL cholesterol rose (see Risks).

Low-fat dietStrong

LDL cholesterol

Shown to lower LDL cholesterol slightly more than higher-fat and low-carbohydrate diets, by about 0.07 to 0.16 mmol/L.

Compared with diets with more fat

The numbers and sources

Effect: Against higher-fat diets in people not trying to lose weight, LDL fell 0.13 mmol/L (95% CI 0.05 to 0.21) and total cholesterol 0.23 mmol/L [1]. Against low-carbohydrate diets, LDL was lower on low-fat diets by 0.16 mmol/L (95% CI 0.003 to 0.33) [4], by 0.07 mmol/L at 6 to 12 months (95% CI 0.02 to 0.12) [5] and by 0.14 mmol/L at 6 months (95% CI 0.03 to 0.26) [8]. In postmenopausal women, LDL fell 3.55 mg/dL more than in the comparison group [9].
Population: Adults in the trials above [1][4][5]; 447 adults with BMI 25 or more in 5 trials [8]; 48,835 postmenopausal women [9].
Sources: [1], [4], [5], [8], [9]
Caveats: The differences are about 0.1 mmol/L, or about 4 mg/dL. In [8], the low-fat diets restricted energy and the low-carbohydrate diets did not. LDL is a risk marker, not a heart event.

Nordic dietStrong

LDL and total cholesterol

Shown to lower LDL cholesterol about 0.26 to 0.30 mmol/L against usual diets in adults with cardiometabolic risk factors.

Compared with control groups the source does not describe [1]; a usual or habitual Nordic diet, a usual Western diet or general healthy eating advice [2]; the participants' usual Western diet, in Swedish adults [3]; an average Nordic diet with the same calories [4]

The numbers and sources

Effect: In 5 RCTs (513 participants), a Nordic diet lowered total cholesterol by 0.38 mmol/L (95% CI -0.76 to -0.01) and LDL by 0.30 mmol/L (95% CI -0.54 to -0.06), with no change in HDL or triglycerides [1]. In 6 RCTs (717 participants), LDL fell 0.26 mmol/L (95% CI -0.52 to -0.00), with reductions in non-HDL cholesterol and apolipoprotein B [2]. In NORDIET, LDL fell 21% and HDL 5% over 6 weeks against usual diets [3]. In SYSDIET, non-HDL cholesterol fell 0.18 mmol/L (95% CI -0.35 to -0.01) against an average Nordic diet [4].
Population: Adults, mostly in Nordic countries, with raised cholesterol, metabolic syndrome or central obesity [1][2]; 88 Swedish adults with mild high cholesterol [3]; 200 adults with metabolic syndrome features [4].
Sources: [1], [2], [3], [4]
Caveats: Both meta-analyses pooled largely the same few trials. Heterogeneity was high (I² 89%) and certainty low for LDL in [2]. NORDIET lowered HDL along with LDL [3].

Paleo dietStrong

Cholesterol and triglycerides

Shown to lower total and LDL cholesterol and triglycerides more than comparison diets in adults, though some pooled results depended on single trials.

Compared with control diets the source does not describe [1], [3]; a diet following the Nordic Nutrition Recommendations [4]; a control group the source does not describe [5]

The numbers and sources

Effect: In people with metabolic disorders, total cholesterol fell 0.32 mmol/L (95% CI 0.15 to 0.49), triglycerides 0.29 mmol/L (95% CI 0.16 to 0.42) and LDL 0.35 mmol/L (95% CI 0.03 to 0.67) more than on control diets [5]. In 19 RCTs, total cholesterol fell 0.15, LDL 0.24 and triglycerides 0.16 more, in units the abstract does not state [3]. A third review found lower total cholesterol, triglycerides and LDL and higher HDL [1]. Triglycerides fell more than on a Nordic guideline diet at 6 and 24 months [4].
Population: Adults with metabolic disorders [5]; adults in 19 RCTs [3]; adults in 8 RCTs [1]; postmenopausal women with obesity [4].
Sources: [1], [3], [4], [5]
Caveats: In [1], lipid results changed when single studies were removed.

Vegan dietStrong

LDL cholesterol

Shown to lower LDL cholesterol about 0.24 to 0.30 mmol/L against omnivorous or control diets in adults.

Compared with the participants' habitual diet, unchanged, in 3 trials in US and New Zealand adults, and in 8 trials a National Cholesterol Education Program diet, American Diabetes Association and Korean Diabetes Association diets, a portion-controlled diet, a Mediterranean diet, a low-fat diet, a healthy omnivorous diet or a high-carbohydrate lacto-ovo vegetarian diet [1]; an omnivorous diet [3]

The numbers and sources

Effect: Vegan diets lowered total cholesterol by 0.30 mmol/L and LDL by 0.24 mmol/L (95% CI -0.40 to -0.07), with no change in HDL or triglycerides [1]. In 30 RCTs of vegetarian or vegan diets, LDL fell 0.30 mmol/L (95% CI -0.40 to -0.19) and apolipoprotein B 12.92 mg/dL, with similar effects across intervention diet types [3].
Population: Adults with overweight or type 2 diabetes [1]; adults in 30 RCTs [3].
Sources: [1], [3]
Caveats: The larger review pooled vegan and vegetarian diets [3].

Vegetarian dietStrong

LDL cholesterol

Shown to lower LDL cholesterol about 0.3 mmol/L against omnivorous diets in adults. HDL also fell slightly in one review.

Compared with control diets the source does not describe [2]; an omnivorous control diet containing meat and dairy products [3]; an omnivorous diet [4]

The numbers and sources

Effect: In 11 trials, vegetarian diets lowered total cholesterol by 0.36 mmol/L, LDL by 0.34 mmol/L (95% CI -0.57 to -0.11) and HDL by 0.10 mmol/L (95% CI -0.14 to -0.06), with no triglyceride change [3]. In 30 RCTs, vegetarian or vegan diets lowered LDL by 0.30 mmol/L (95% CI -0.40 to -0.19) and apolipoprotein B by 12.92 mg/dL, with similar effects across intervention diet types and no triglyceride change [4]. In people with diabetes, LDL fell 0.12 mmol/L (95% CI -0.20 to -0.04) [2].
Population: Adults in randomized trials [3][4]; adults with diabetes [2].
Sources: [2], [3], [4]
Caveats: The reviews pooled lacto-ovo and vegan diets, though [4] found effects similar across diet types.

Alternate-day fastingModerate

Cholesterol

Shown to lower total cholesterol by about 8 mg/dL against control in adults with overweight, mostly in trials under 6 months.

Compared with control diets the source does not describe [1]; eating freely every day or keeping the present lifestyle [2]; no change in eating times [5]; time-restricted eating [6]

The numbers and sources

Effect: Total cholesterol fell 8.14 mg/dL (95% CI -14.59 to -1.69) against control [1]. Total cholesterol, LDL and triglycerides fell against control in a second review, which reported p values only [2]. Alternate-day fasting lowered total cholesterol, triglycerides and non-HDL cholesterol more than time-restricted eating [6]. Non-HDL cholesterol fell against control over 4 weeks [5].
Population: 728 participants in 8 trials [1]; 269 in 7 trials [2]; 99 trials [6]; 76 adults [5].
Sources: [1], [2], [5], [6]
Caveats: In a year-long trial, LDL cholesterol ended higher on alternate-day fasting than on daily calorie restriction (see Risks) [3].

Atkins dietModerate

Triglycerides and HDL cholesterol

Shown in two trials to lower triglycerides more than higher-carbohydrate diets in adults with overweight, while a third found similar heart risk changes across four diets.

Compared with the Zone, LEARN and Ornish diets [7]; the Zone, Weight Watchers and Ornish diets [8]; a conventional low-calorie, high-carbohydrate, low-fat diet [9]; a high-carbohydrate, high-fibre diet and the high-protein Zone diet [11]

The numbers and sources

Effect: HDL rose and triglycerides fell more on Atkins than on a conventional diet through most of a year, with no difference in total or LDL cholesterol after 3 months [9]. Triglycerides fell 0.30 mmol/L more than on a high-carbohydrate diet in insulin-resistant women [11]. At 12 months, Atkins secondary outcomes, including lipids, were comparable with or more favorable than Zone, LEARN and Ornish [7]. In another trial, each of four diets lowered the LDL to HDL ratio by about 10%, with no significant change in blood pressure or glucose [8].
Population: Adults with obesity [9]; insulin-resistant women [11]; premenopausal women [7]; adults with cardiac risk factors [8].
Sources: [7], [8], [9], [11]
Caveats: Small trials with high dropout. Blood markers, not heart attacks or strokes.

DASH dietModerate

LDL and total cholesterol

Shown to lower LDL cholesterol slightly in adults, by 0.10 mmol/L across trials and 0.28 mmol/L in the original feeding trial.

Compared with control diets the source does not describe [3]; the DASH trial's control diet [6]; usual, low-fat and low-antioxidant diets, behavioral programs alone and usual gestational diabetes care [7]

The numbers and sources

Effect: Across 20 trials, DASH lowered total cholesterol by 0.20 mmol/L (95% CI -0.31 to -0.10) and LDL by 0.10 mmol/L (95% CI -0.20 to -0.01) [3]. In the 8-week DASH feeding trial, total cholesterol fell 0.35 mmol/L (13.7 mg/dL) and LDL 0.28 mmol/L (10.7 mg/dL) against control, with no triglyceride change. LDL fell 11.2 mg/dL more in men than in women [6]. An umbrella review reported the same pooled figures as [3], with no effect on HDL or triglycerides [7].
Population: Adults in 20 trials of 2 to 24 weeks [3]; 436 adults with total cholesterol of 6.7 mmol/L or less, mean age 44.6, 60% African American [6].
Sources: [3], [6], [7]
Caveats: The umbrella review drew its lipid figures from the same meta-analysis, so the two are not independent [3][7]. The umbrella review rated most secondary outcomes very low to moderate certainty [7].

Mediterranean dietModerate

Blood pressure, cholesterol and blood sugar markers

Shown to lower blood pressure about 3/2 mmHg and LDL cholesterol and HbA1c slightly in adults, at low to moderate certainty.

Compared with no or minimal intervention, and another dietary intervention the abstract does not name [2]; a low-fat diet, a low-carbohydrate diet and the American Diabetes Association diet [7]; control diets the source does not describe [10]

The numbers and sources

Effect: Against no or minimal intervention, systolic blood pressure fell 2.99 mmHg (95% CI -3.45 to -2.53) and diastolic 2.0 mmHg (95% CI -2.29 to -1.71) at moderate quality, with little or no effect on LDL or HDL. Against other diets, LDL fell 0.15 mmol/L (95% CI -0.27 to -0.02) and triglycerides 0.09 mmol/L, with little or no effect on blood pressure [2]. In 9 RCTs (1,337 people at raised risk of diabetes or heart disease), HbA1c fell 0.18 points (95% CI -0.35 to -0.01), LDL 0.10 mmol/L and triglycerides 0.20 mmol/L. Fasting glucose, insulin, insulin resistance and HDL did not change [10]. Over 12 months or more, blood pressure and lipids changed about as much as on comparator diets [7].
Population: Healthy adults and adults at high cardiovascular risk [2]; adults at increased risk of type 2 diabetes and heart disease [10]; adults with overweight or obesity [7].
Sources: [2], [7], [10]
Caveats: The Cochrane review rated the lipid evidence low or very low quality for most comparisons [2]. The changes are small next to drug effects.

Carnivore dietLimited

Triglycerides

Limited evidence: triglycerides fell in all 6 followers who started above 130 mg/dL, in a study of 24 people sharing blood tests.

Compared with no comparison group [1]; before the diet, in the same people [3]

The numbers and sources

Effect: All 6 participants with triglycerides above 130 mg/dL before the diet had lower levels on it [3]. Survey respondents who reported current lipids had a triglyceride level of 68 mg/dL [1].
Population: 24 German followers, median age 46, on the diet at least 1 month [3]; a subset of survey respondents [1].
Sources: [1], [3]
Caveats: No control group. The survey reported current values, not change [1].

Flexitarian dietLimited

Heart disease

Limited evidence: in a review of 4 trials in healthy adults, replacing part of animal protein with plant protein lowered LDL and total cholesterol. No study measured heart disease itself.

Compared with diets with a higher share of animal protein foods [9]

The numbers and sources

Effect: A 2026 systematic review found 4 dietary interventions, reported in 7 articles, that partially replaced animal protein foods with plant protein foods in healthy adults. LDL cholesterol, total cholesterol and body weight improved in those eating the higher share of plant protein. Vitamin B12 status fell on the diets with the most plant protein [9].
Population: Healthy adults with a mean or median age of 18 to 65 in randomized trials, 3 of 7 articles at low risk of bias [9].
Sources: [9]
Caveats: The abstract gives no pooled sizes of effect [9]. Cholesterol is a risk marker, not heart disease. No cohort or trial of flexitarian eating and heart attacks or heart deaths was located.

High-protein dietModerate

Blood pressure and triglycerides

Mixed results: triglycerides fell more on higher-protein diets in two meta-analyses, while blood pressure fell slightly in one and did not differ in another.

Compared with diets with less protein

The numbers and sources

Effect: Across 74 trials, higher-protein diets lowered systolic (SMD -0.21, 95% CI -0.32 to -0.09) and diastolic blood pressure (SMD -0.18, 95% CI -0.29 to -0.06) and triglycerides (SMD -0.51, 95% CI -0.78 to -0.24). Total and LDL cholesterol, C-reactive protein and HbA1c did not change [6]. In energy-restricted trials, triglycerides fell 0.23 mmol/L more (95% CI 0.12 to 0.33), and blood pressure and total, LDL and HDL cholesterol did not differ [1].
Population: Adults in 74 trials [6] and in 24 weight-loss trials [1].
Sources: [1], [6]
Caveats: Restricting to studies at lower risk of bias reduced the triglyceride effect [6]. In type 2 diabetes, blood pressure changes were not significant [8].

Low-carb dietModerate

Heart risk factors

Mixed results: triglycerides and cholesterol ratio improved in some trials, while a Cochrane review found little to no difference in LDL or blood pressure over 1 to 2 years.

Compared with diets with more carbohydrate

The numbers and sources

Effect: Over 1 to 2 years, diastolic blood pressure and LDL cholesterol showed little to no difference from balanced-carbohydrate diets, with and without type 2 diabetes [1]. Over 2 years, the ratio of total to HDL cholesterol fell 20% on a low-carbohydrate diet and 12% on a low-fat diet [5]. In type 2 diabetes, triglycerides improved substantially at 6 months and less at 12 months. LDL cholesterol worsened at 12 months by an amount judged clinically important but not statistically significant [6].
Population: Adults with overweight or obesity [1][5]; adults with type 2 diabetes [6].
Sources: [1], [5], [6]
Caveats: Mean baseline LDL and diastolic pressure were in the normal range across the Cochrane trials [1]. No trial here measured heart attacks or strokes.

Devices and wearables

Wrist heart rate and calorie estimatesStrong

Blood pressure, cholesterol and blood sugar

Mixed results: effects of activity trackers on blood pressure, cholesterol and HbA1c across systematic reviews were typically small and often not statistically significant.

The numbers and sources

Effect: Effects of activity trackers on blood pressure, cholesterol and glycosylated hemoglobin were typically small and often non-significant, as were effects on quality of life and pain [18].
Population: Participants in 39 systematic reviews and meta-analyses [18].
Sources: [18]
Caveats: The abstract gives no pooled figures for these outcomes [18].

Lab markers

Apolipoprotein A1 (ApoA1)Strong

Coronary heart disease in cohort studies

Linked to more coronary heart disease at lower levels, about 62% more in the lowest than the highest third across 21 prospective studies.

The numbers and sources

Effect: In a meta-analysis of prospective studies in general populations, people in the bottom third of ApoA1 had a relative risk of coronary heart disease of 1.62 (95% CI 1.43 to 1.83) against those in the top third [8]. In a pooled analysis of individual records, ApoA1 and HDL cholesterol had very similar shape and size of association with coronary heart disease, and the authors concluded that either cholesterol levels or apolipoproteins can be measured for risk assessment [9]. In 27,673 initially healthy US women, the hazard ratio for cardiovascular disease in the top against the bottom fifth of ApoA1 was 0.63 (95% CI 0.52 to 0.77), against 0.52 (0.42 to 0.64) for HDL cholesterol [10]. Among patients on statins in 8 trials, each standard deviation higher ApoA1 went with a hazard ratio for major cardiovascular events of 0.79 (95% CI 0.72 to 0.82), including in those with LDL cholesterol below 50 mg/dL [11].
Population: 6,333 coronary heart disease cases in 21 studies [8]. 91,307 participants with 4,499 cases in the 22 studies with apolipoproteins measured, within 302,430 people in 68 studies [9]. 27,673 women followed 11 years, 1,015 events [10]. 38,153 trial participants allocated to a statin, 5,387 with a major cardiovascular event [11].
Sources: [8], [9], [10], [11]
Caveats: Observational, including the analysis within statin trials. The literature-based meta-analysis found heterogeneity between studies that study characteristics only partly explained [8].

Apolipoprotein A1 (ApoA1)Strong

Heart attack and the ApoB to ApoA1 ratio

Linked to more heart attacks at a higher ApoB to ApoA1 ratio, about 59% higher odds per standard deviation in a 52-country case-control study.

The numbers and sources

Effect: In the INTERHEART study, the ApoB to ApoA1 ratio had an odds ratio for acute myocardial infarction of 1.59 per standard deviation (95% CI 1.53 to 1.64) and a population-attributable risk of 54%, against 32% for the ratio of total to HDL cholesterol [15]. In pooled prospective studies, the hazard ratio for coronary heart disease per standard deviation was 1.49 (95% CI 1.39 to 1.60) for the ApoB to ApoA1 ratio and 1.50 (1.38 to 1.62) for the ratio of non-HDL to HDL cholesterol [9]. A literature-based meta-analysis found a relative risk of 1.86 (95% CI 1.55 to 2.22) for the top against the bottom third of the ratio [8]. In a Swedish cohort, the ratio was strongly related to fatal myocardial infarction in men and women, and ApoA1 was noted to be protective [16].
Population: 12,461 cases and 14,637 controls in 52 countries, with blood samples from 9,345 cases and 12,120 controls [15]. 91,307 participants in 22 prospective studies [9]. 3,730 coronary cases in 7 studies [8]. 175,553 people followed a mean of about 65 months, with 1,223 fatal myocardial infarctions [16].
Sources: [15], [9], [8], [16]
Caveats: Observational, and the largest study is a case-control study, which cannot show that the ratio was raised before the heart attack [15]. The ratio is a different quantity from ApoA1 and has no unit, so this page places no typed result against it. One Finnish study put its reference interval at 0.3 to 1.0 in men and 0.3 to 0.8 in women [5], and a European guideline describes such ratios as useful for risk estimation and not for diagnosis or as treatment targets [2].

Apolipoprotein B (ApoB)Strong

Heart attack and other cardiovascular events

Linked to more cardiovascular events at higher levels, about 43% more per standard deviation in pooled cohorts, a stronger link than for LDL cholesterol.

The numbers and sources

Effect: A meta-analysis of 12 reports found a standardized relative risk of fatal or nonfatal ischemic cardiovascular events of 1.43 for ApoB (95% CI 1.35 to 1.51), 1.34 for non-HDL cholesterol (1.24 to 1.44) and 1.25 for LDL cholesterol (1.18 to 1.33) [9]. In UK Biobank adults not taking lipid-lowering drugs, ApoB, non-HDL cholesterol and triglycerides were each associated with a first heart attack. When they were assessed together, only ApoB remained associated (adjusted HR 1.27 per standard deviation, 95% CI 1.15 to 1.40), and the same was found in statin-treated trial patients with atherosclerosis [10]. In 68 prospective studies, the hazard ratio for coronary heart disease per standard deviation was 1.49 (95% CI 1.39 to 1.60) for the ratio of ApoB to apolipoprotein A-I and 1.50 (1.38 to 1.62) for the ratio of non-HDL to HDL cholesterol [11].
Population: 233,455 people with 22,950 events in 12 reports [9]. 389,529 UK Biobank participants followed a median 11.1 years, and 40,430 trial patients followed a median 2.5 years [10]. 302,430 people without vascular disease in 68 studies, a subset of whom had apolipoproteins measured [11].
Sources: [9], [10], [11]
Caveats: Observational. ApoB, LDL cholesterol and non-HDL cholesterol are highly correlated, which makes their separate contributions hard to tell apart [12]. The largest pooled analysis reported ApoB only as a ratio to apolipoprotein A-I [11].

Apolipoprotein B (ApoB)Strong

Cardiovascular events and death in trials that lowered ApoB

Shown in trials: each 10 mg/dL lowered went with about 7% fewer major cardiovascular events, except with drugs that act outside the LDL receptor.

The numbers and sources

Effect: Across 29 randomized trials, each 10 mg/dL decrease in ApoB went with a relative risk of 0.93 for major adverse cardiovascular events (95% CI 0.90 to 0.97), 0.93 for cardiovascular death (0.88 to 0.98) and 0.95 for death from any cause (0.92 to 0.99). For major events the relative risk was 0.88 (0.83 to 0.93) with statins and 0.96 (0.94 to 0.99) with non-statin drugs that clear ApoB through the LDL receptor. Drugs that lower ApoB by other routes (CETP inhibitors, fibrates, niacin, omega-3 fatty acids) showed no reduction (1.02, 0.81 to 1.30), and the reduction in death from any cause was limited to statins [14]. An earlier analysis of 25 trials found each 10 mg/dL decrease went with 9% less coronary heart disease, 6% less major cardiovascular disease and no decrease in stroke. Across all drug classes, the fall in ApoB did not consistently predict risk better than the fall in LDL or non-HDL cholesterol [15].
Population: 332,912 patients in 29 trials of at least 1,000 people and 1 year [14]. 131,134 participants in 25 trials: 12 of statins, 4 of fibrates, 5 of niacin and 4 others [15].
Sources: [14], [15]
Caveats: Both analyses compare averages between trials, not individuals within them. None of the trials behind current treatment thresholds enrolled people by ApoB, and ApoB was often measured in only part of a trial population [2].

HDL cholesterol (HDL-C)Strong

Coronary heart disease in cohort studies

Linked to less coronary heart disease at higher levels, about 22% less for each 15 mg/dL higher across 68 pooled cohorts.

The numbers and sources

Effect: In 68 prospective studies, coronary heart disease rates per 1,000 person-years were 6.4 in the bottom third and 2.4 in the top third of HDL cholesterol. The adjusted hazard ratio was 0.78 (95% CI 0.74 to 0.82) per 15 mg/dL higher HDL cholesterol [8]. A separate pooled observational analysis found an odds ratio for heart attack of 0.62 (95% CI 0.58 to 0.66) per standard deviation higher [9].
Population: 302,430 people without vascular disease in 68 prospective studies, mostly in Europe and North America [8].
Sources: [8], [9]
Caveats: Observational. Low HDL cholesterol travels with high triglycerides, obesity, smoking and type 2 diabetes, so an association does not show that HDL cholesterol itself is protective [2].

LDL cholesterol (LDL-C)Strong

Heart attack, stroke and other artery disease

Linked to more atherosclerotic cardiovascular disease across over 200 cohort, genetic and trial studies, with risk rising with the level and the years of exposure.

The numbers and sources

Effect: A European Atherosclerosis Society consensus panel reviewed separate meta-analyses of over 200 prospective cohort studies, Mendelian randomization studies and randomized trials. It reported a consistent, dose-dependent, log-linear association between LDL cholesterol and atherosclerotic cardiovascular disease that grows with duration of exposure, and concluded that LDL causes the disease [9]. In a pooled analysis of prospective studies, directly measured LDL cholesterol had a hazard ratio for coronary heart disease of 1.38 per 33 mg/dL higher (95% CI 1.09 to 1.73) [10]. In Mendelian randomization analyses, each 1 mmol/L (38.7 mg/dL) lower lifelong LDL cholesterol went with a 54.5% lower risk of coronary heart disease (95% CI 48.8 to 59.5), about 3 times the reduction per unit seen with a statin started later in life [11].
Population: More than 2 million participants with over 150,000 cardiovascular events [9]. 302,430 people without vascular disease in 68 prospective studies, a subset of whom had LDL cholesterol measured directly [10]. 312,321 participants in genetic studies of 9 variants in 6 genes [11].
Sources: [9], [10], [11]
Caveats: The cohort findings are observational. The consensus states that the benefit of lowering holds when the fall in LDL cholesterol is matched by a fall in LDL particle number and the treatment has no offsetting harms [9].

LDL cholesterol (LDL-C)Strong

Cardiovascular events in trials that lowered LDL cholesterol

Shown in trials: each 1 mmol/L (39 mg/dL) lowered cut major vascular events about 22% with statins, and similarly with other drugs acting through the LDL receptor.

The numbers and sources

Effect: In 26 statin trials, each 1.0 mmol/L reduction in LDL cholesterol lowered major vascular events with a rate ratio of 0.78 (95% CI 0.76 to 0.80), including in people whose LDL cholesterol was already below 2 mmol/L [12]. Across 49 trials of 9 kinds of LDL-lowering treatment, the relative risk per 1 mmol/L (38.7 mg/dL) was 0.77 for statins (95% CI 0.71 to 0.84) and 0.75 for diet, bile acid sequestrants, ileal bypass and ezetimibe (95% CI 0.66 to 0.86). CETP inhibitors produced less risk reduction than their LDL lowering predicted (observed 1.01 against an expected 0.90) [13]. In populations starting at a median of 70 mg/dL or less, the relative risk per 1 mmol/L was 0.79 (95% CI 0.71 to 0.87) for statins and non-statins combined [14].
Population: About 170,000 participants in 26 trials, median follow-up about 5 years [12]. 312,175 participants in 49 trials [13]. A low-LDL subgroup of the statin trials plus 50,627 patients in 3 trials of non-statin drugs added to statins [14].
Sources: [12], [13], [14]
Caveats: Effects are expressed per unit of LDL cholesterol lowered, over about 5 years of treatment. The same fall in LDL cholesterol did not bring the same benefit with every drug class [13].

Lipoprotein(a)Strong

Heart attack and stroke in cohort studies

Linked to more heart attacks and strokes at higher levels, about 11% more cardiovascular disease for each 50 nmol/L higher in 460,506 UK adults.

The numbers and sources

Effect: In 36 prospective studies, the risk ratio for coronary heart disease was 1.13 (95% CI 1.09 to 1.18) per 3.5-fold higher usual lipoprotein(a) after adjustment for lipids and other risk factors, and 1.10 (1.02 to 1.18) for ischemic stroke. It was 1.01 (0.98 to 1.05) for death from nonvascular causes [10]. In the UK Biobank, the relationship with atherosclerotic cardiovascular disease appeared linear, with a hazard ratio of 1.11 (95% CI 1.10 to 1.12) per 50 nmol/L. Median levels were 19, 31, 75 and 16 nmol/L in white, South Asian, black and Chinese participants, and the risk per 50 nmol/L was similar across groups. A level of 150 nmol/L or above was found in 12.2% of people without cardiovascular disease and went with a hazard ratio of 1.50 (95% CI 1.44 to 1.56) [11].
Population: 126,634 participants in 36 prospective studies, 1.3 million person-years [10]. 460,506 middle-aged UK Biobank participants, median follow-up 11.2 years, 22,401 events [11].
Sources: [10], [11]
Caveats: Observational. The pooled cohorts used many different assays [10]. A European panel states that risk rises continuously, with no level at which it begins [4].

Lipoprotein(a)Strong

Coronary heart disease in genetic studies

Shown in genetic studies to track coronary heart disease: variants that raise lipoprotein(a) raised risk, about 22% more heart attacks for each doubling.

The numbers and sources

Effect: In Danish studies, genetically elevated lipoprotein(a) went with a hazard ratio for heart attack of 1.22 (95% CI 1.09 to 1.37) per doubling, against 1.08 (1.03 to 1.12) for measured levels [12]. Two variants at the LPA gene had odds ratios for coronary disease of 1.70 and 1.92. Carrying one variant gave an odds ratio of 1.51 (95% CI 1.38 to 1.66) and two or more 2.57 (1.80 to 3.67), and the association disappeared after adjustment for the lipoprotein(a) level [13]. In a Mendelian randomization analysis, each 10 mg/dL lower genetically predicted lipoprotein(a) went with 5.8% lower coronary heart disease risk (OR 0.942, 95% CI 0.933 to 0.951). A difference of 101.5 mg/dL (95% CI 71.0 to 137.0) carried the same risk difference as 38.67 mg/dL of LDL cholesterol [14].
Population: 8,637, 29,388 and 2,461 white Danish participants in three studies [12]. 3,145 cases and 3,352 controls, replicated in 4,846 cases and 4,594 controls [13]. 20,793 coronary heart disease cases and 27,540 controls with individual data, plus summary data on 62,240 cases and 127,299 controls, all of European ancestry [14].
Sources: [12], [13], [14]
Caveats: Genetic studies estimate the effect of lifelong differences, which may not match what lowering later in life does. Participants were of European ancestry [12][14].

Non-HDL cholesterol (non-HDL-C)Strong

Heart attack, stroke and other cardiovascular disease in cohort studies

Linked to more cardiovascular disease at higher levels, about 50% more coronary heart disease for each 43 mg/dL higher across 68 pooled cohorts.

The numbers and sources

Effect: In 68 prospective studies, coronary heart disease rates per 1,000 person-years were 2.3 in the bottom third and 6.7 in the top third of non-HDL cholesterol. The adjusted hazard ratio per 43 mg/dL higher was 1.50 (95% CI 1.39 to 1.61) for coronary heart disease and 1.12 (1.04 to 1.20) for ischemic stroke [8]. In a consortium of 38 cohorts, 30-year cardiovascular event rates rose from 7.7% at non-HDL cholesterol below 2.6 mmol/L (about 100 mg/dL) to 33.7% at 5.7 mmol/L (about 220 mg/dL) or above in women, and from 12.8% to 43.6% in men [9]. A meta-analysis of 9 prospective studies found a relative risk of coronary heart disease of 1.79 (95% CI 1.68 to 1.91) for the highest against the lowest category [10]. Across 12 reports, the standardized relative risk of ischemic cardiovascular events was 1.34 (95% CI 1.24 to 1.44) for non-HDL cholesterol, between that of LDL cholesterol (1.25, 1.18 to 1.33) and ApoB (1.43, 1.35 to 1.51) [11].
Population: 302,430 people without vascular disease in 68 prospective studies [8]. 398,846 people in 38 cohorts, median follow-up 13.5 years, 54,542 cardiovascular events [9]. 448,732 people in 9 prospective studies [10]. 233,455 people with 22,950 events in 12 reports [11].
Sources: [8], [9], [10], [11]
Caveats: Observational. In the pooled cohorts the hazard ratios were at least as strong in participants who did not fast as in those who did [8]. Each study in the category comparison defined its own highest and lowest groups [10].

Non-HDL cholesterol (non-HDL-C)Strong

Cardiovascular events in trials that lowered non-HDL cholesterol

Shown in trials: each 1 mmol/L (39 mg/dL) of non-HDL cholesterol lowered went with about 21% fewer major vascular events across 49 trials.

The numbers and sources

Effect: In a meta-regression of 24 trials of non-statin drugs and 25 statin trials, the risk ratio for major vascular events was 0.79 (95% CI 0.76 to 0.82) per 1 mmol/L reduction in non-HDL cholesterol [12]. In an earlier analysis of 30 trials, each 1% decrease in non-HDL cholesterol with a statin went with a 4.5-year relative risk of coronary heart disease of 0.99 (95% Bayesian interval 0.98 to 1.00), and the fibrate trials did not differ from the statin trials [13]. Across 7 placebo-controlled statin trials, coronary risk fell 20.0% (95% CI 15.2 to 24.7) per standard deviation decrease in non-HDL cholesterol, 20.1% for LDL cholesterol and 24.4% for ApoB [14]. Among patients on statins in 8 trials, each standard deviation higher on-treatment non-HDL cholesterol went with a hazard ratio of 1.16 (95% CI 1.12 to 1.19) for major cardiovascular events, against 1.13 (1.10 to 1.17) for LDL cholesterol, a significant difference [15].
Population: 374,358 patients in 49 trials, with 46,180 major cardiovascular events [12]. 14 statin trials (100,827 people), 7 fibrate trials (21,647), 6 niacin trials (4,445) and 3 others [13]. 7 placebo-controlled statin trials [14]. 62,154 patients in 8 statin trials, of whom 38,153 were allocated to a statin [15].
Sources: [12], [13], [14], [15]
Caveats: The meta-regressions compare trials with each other, not people within a trial, and cover drugs that lower non-HDL cholesterol in different ways [12][13]. The niacin trials did not follow the pattern of the statin trials, with inconsistent results in five small trials of niacin combined with other drugs [13].

Total cholesterolStrong

Death from coronary heart disease and total cholesterol

Linked to more coronary heart disease deaths at higher levels: each 1 mmol/L (39 mg/dL) lower total cholesterol went with a third fewer at ages 50 to 69.

The numbers and sources

Effect: In a meta-analysis of 61 prospective studies, each 1 mmol/L lower usual total cholesterol went with lower death from ischemic heart disease in both sexes: hazard ratio 0.44 (95% CI 0.42 to 0.48) at ages 40 to 49, 0.66 (0.65 to 0.68) at ages 50 to 69 and 0.83 (0.81 to 0.85) at ages 70 to 89, with no apparent threshold. The ratio of total to HDL cholesterol predicted these deaths more than twice as informatively as total cholesterol alone [5].
Population: Almost 900,000 adults without previous disease in 61 prospective studies, mostly in western Europe or North America, with more than 55,000 vascular deaths [5].
Sources: [5]
Caveats: Observational. The proportional difference in risk was smaller at older ages and at higher blood pressure [5].

Total cholesterolStrong

Cardiovascular disease and non-HDL cholesterol

Linked to more cardiovascular disease at higher non-HDL cholesterol, about 50% more coronary heart disease for each 43 mg/dL higher across 68 pooled cohorts.

The numbers and sources

Effect: In 68 prospective studies, coronary heart disease rates per 1,000 person-years were 2.3 in the bottom third and 6.7 in the top third of non-HDL cholesterol, and the adjusted hazard ratio was 1.50 (95% CI 1.39 to 1.61) per 43 mg/dL higher [6]. In a consortium of 38 cohorts, 30-year cardiovascular event rates rose from 7.7% at non-HDL cholesterol below 2.6 mmol/L (about 100 mg/dL) to 33.7% at 5.7 mmol/L (about 220 mg/dL) or above in women, and from 12.8% to 43.6% in men. Adjusted hazard ratios for the highest against the lowest category were 1.9 (95% CI 1.6 to 2.2) in women and 2.3 (2.0 to 2.5) in men [7].
Population: 302,430 people without vascular disease in 68 prospective studies [6]. 398,846 people in 38 cohorts, median follow-up 13.5 years, 54,542 cardiovascular events [7].
Sources: [6], [7]
Caveats: Observational. In the pooled cohorts the hazard ratios were at least as strong in participants who did not fast as in those who did [6].

Total cholesterolStrong

Cardiovascular events in trials that lowered non-HDL cholesterol

Shown in trials: each 1 mmol/L (39 mg/dL) of non-HDL cholesterol lowered went with about 21% fewer major vascular events across 49 trials.

The numbers and sources

Effect: In a meta-regression of 24 trials of non-statin drugs and 25 statin trials, the risk ratio for major vascular events was 0.79 (95% CI 0.76 to 0.82) per 1 mmol/L reduction in non-HDL cholesterol [8]. Among patients on statins in 8 trials, each standard deviation higher on-treatment non-HDL cholesterol went with a hazard ratio of 1.16 (95% CI 1.12 to 1.19) for major cardiovascular events, against 1.13 (1.10 to 1.17) for LDL cholesterol, a significant difference [9]. Statin trials found that each 1.0 mmol/L reduction in LDL cholesterol lowered major vascular events with a rate ratio of 0.78 (95% CI 0.76 to 0.80) [10].
Population: 374,358 patients in 49 trials, with 46,180 major cardiovascular events [8]. 62,154 patients in 8 statin trials, of whom 38,153 were allocated to a statin [9]. About 170,000 participants in 26 statin trials [10].
Sources: [8], [9], [10]
Caveats: The meta-regression compares trials with each other, not people within a trial, and covers drugs that lower non-HDL cholesterol in different ways [8].

Apolipoprotein B (ApoB)Moderate

Coronary heart disease in genetic studies

Shown to track coronary heart disease in genetic studies, with about 23% lower odds for each 10 mg/dL lower lifelong ApoB.

The numbers and sources

Effect: In Mendelian randomization analyses, gene variants that lower triglycerides (in LPL) and gene variants that lower LDL cholesterol (in LDLR) were associated with the same lower odds of coronary heart disease per 10 mg/dL lower ApoB: OR 0.771 (95% CI 0.741 to 0.802) and 0.773 (0.747 to 0.801). After adjusting for ApoB, the associations of triglycerides and of LDL cholesterol with coronary heart disease became null [13]. A second multivariable analysis found that only ApoB kept a robust effect (OR 1.92 per standard deviation higher, 95% CI 1.31 to 2.81), while the LDL cholesterol estimate reversed (OR 0.85, 95% CI 0.57 to 1.27) [12].
Population: 654,783 participants in 63 cohort or case-control studies, including 91,129 with coronary heart disease [13]. Genetic data from up to 441,016 UK Biobank participants, applied to 60,801 coronary cases and 123,504 controls [12].
Sources: [13], [12]
Caveats: Gene variants act from birth, so these estimates describe lifelong differences, not a change made later in life. The authors of one analysis note that lipid traits are highly correlated, which limits conclusions about any single one [12].

LDL particle number (LDL-P)Moderate

Heart attack, stroke and other cardiovascular disease in cohort studies

Linked to more cardiovascular disease at higher levels, about 2.5 times the rate in the top against the bottom fifth of 27,673 US women.

The numbers and sources

Effect: In initially healthy US women, the adjusted hazard ratio for cardiovascular disease in the top against the bottom fifth was 2.51 (95% CI 1.91 to 3.30) for LDL particle number, 2.57 (1.98 to 3.33) for ApoB, 2.52 (1.95 to 3.25) for non-HDL cholesterol and 1.74 (1.40 to 2.16) for LDL cholesterol. Adding LDL particle number to a model with the total to HDL cholesterol ratio and other risk factors reclassified essentially no one, and the authors called its prediction comparable but not superior to standard lipids or apolipoproteins [4]. In a multi-ethnic US cohort, the hazard ratio per standard deviation was 1.32 (95% CI 1.19 to 1.47) for LDL particle number and 1.20 (1.08 to 1.34) for LDL cholesterol [5]. In a later analysis of that cohort, the top against the bottom quarter had a hazard ratio for coronary heart disease of 1.77 (95% CI 1.21 to 2.58), which weakened after adjustment for the standard lipid panel [8]. A laboratory medicine working group reviewed 25 studies with 85 outcomes in which both markers were measured, and found LDL particle number and ApoB each significantly associated with the outcome in 50 comparisons and neither in 17 [3].
Population: 27,673 women followed 11 years, 1,015 events [4]. Participants in a cohort of 6,814 adults aged 45 to 84, 319 events over 5.5 years [5]. 4,679 participants of the same cohort [8]. 25 clinical studies [3].
Sources: [4], [5], [8], [3]
Caveats: Observational. None of the studies here assigned treatment by LDL particle number, so they do not show what happens to events when it is lowered. The multi-ethnic cohort analysis was written with employees of the company that ran the test [5].

LDL particle number (LDL-P)Moderate

Heart disease when LDL particle number and LDL cholesterol disagree

Linked to coronary events when the two disagree: women with low LDL cholesterol and high LDL particle number had about 2.3 times the risk of women low on both.

The numbers and sources

Effect: Among 27,533 healthy women split at the medians, 24.3% had LDL particle number and LDL cholesterol on opposite sides. Among women with LDL cholesterol below the median of 121 mg/dL, those with LDL particle number at or above its median had an age-adjusted hazard ratio for coronary events of 2.32 (95% CI 1.88 to 2.85) against women low on both. Among women with LDL cholesterol at or above the median, those with a low LDL particle number had a hazard ratio of 0.42 (0.33 to 0.53). The same pattern held for ApoB (2.48 and 0.34) and non-HDL cholesterol (2.92 and 0.40) [9]. In a multi-ethnic cohort, among people whose two values differed by 12 percentile points or more, LDL particle number was associated with cardiovascular events (HR 1.45 per standard deviation, 95% CI 1.19 to 1.78) and LDL cholesterol was not (1.07, 0.88 to 1.30) [5]. In the Framingham Offspring cohort, people below the 25th percentile of LDL particle number had 59 events per 1,000 person-years, against 81 for those equally low on LDL cholesterol [10].
Population: 27,533 women, median follow-up 17.2 years, 1,070 coronary events [9]. Participants in a cohort of 6,814 adults, 319 events [5]. 3,066 middle-aged white adults followed a median 14.8 years, 531 events [10].
Sources: [9], [5], [10]
Caveats: Observational. High and low were defined by each cohort's own medians or percentiles, not by a fixed cut point. After adjustment for HDL cholesterol, triglycerides and other factors, risk in the women's cohort remained under or overestimated by about 20% to 50% [9].

Non-HDL cholesterol (non-HDL-C)Moderate

Type 2 diabetes

Linked to more new type 2 diabetes at higher levels, 16% more in the higher than the lower non-HDL cholesterol group across 8 cohort studies.

The numbers and sources

Effect: In a meta-analysis of cohort studies in the general population, the pooled effect size for type 2 diabetes was 1.16 (95% CI 1.079 to 1.251) for higher against lower non-HDL cholesterol. The result did not change with region, share of men, sample size or adjustment for body mass index, hypertension, waist circumference and family history of diabetes [19].
Population: 251,672 participants in 8 cohort studies [19].
Sources: [19]
Caveats: Observational, and the authors describe earlier studies as inconsistent and call for large prospective cohorts to confirm the finding. Each study defined its own higher and lower groups [19].

TriglyceridesModerate

Coronary heart disease in genetic studies

Shown in genetic studies to track coronary heart disease, an effect that followed the number of ApoB-carrying particles more than triglycerides themselves.

The numbers and sources

Effect: Each copy of a variant in the APOA5 gene went with 16.0% higher triglycerides (95% CI 12.9 to 18.7) and an odds ratio for coronary heart disease of 1.18 (95% CI 1.11 to 1.26), in line with the hazard ratio of 1.10 seen for the same triglyceride difference in cohorts [13]. Across 185 common variants, the strength of a variant's effect on triglycerides correlated with its effect on coronary artery disease after accounting for LDL and HDL cholesterol [14]. In a Mendelian randomization analysis, triglyceride-lowering LPL variants and LDL-lowering LDLR variants went with the same lower risk per 10 mg/dL lower ApoB (odds ratios 0.771 and 0.773). After adjustment for ApoB, the association of triglycerides with coronary heart disease was null (OR 1.014, 95% CI 0.965 to 1.065) [15].
Population: 20,842 coronary heart disease patients and 35,206 controls [13]. Variants mapped in genome-wide studies of plasma lipids [14]. 654,783 participants, including 91,129 coronary heart disease cases, in 63 studies [15].
Sources: [13], [14], [15]
Caveats: Variants that change triglycerides also change other lipoproteins. The APOA5 variant went with lower HDL cholesterol and higher ApoB [13]. The authors of the largest analysis concluded that the benefit of lowering triglycerides may be proportional to the change in ApoB [15].

Total cholesterolStrong

Stroke

Mixed results: higher total cholesterol went with fewer bleeding strokes in pooled cohorts, and higher non-HDL cholesterol with slightly more ischemic strokes.

The numbers and sources

Effect: In a meta-analysis of 23 prospective studies, the relative risk of hemorrhagic stroke was 0.69 (95% CI 0.59 to 0.81) for high against low total cholesterol and 0.85 (0.80 to 0.91) per 1 mmol/L higher [11]. In 61 prospective studies, total cholesterol showed no independent positive association with death from stroke, and at ages 70 to 89 and at systolic blood pressure above about 145 mm Hg it was negatively related to death from hemorrhagic and total stroke [5]. In 68 pooled cohorts, the hazard ratio for ischemic stroke was 1.12 (95% CI 1.04 to 1.20) per 43 mg/dL higher non-HDL cholesterol [6].
Population: 1,430,141 participants with 7,960 hemorrhagic strokes [11]. Almost 900,000 adults with about 12,000 stroke deaths [5]. 302,430 people with 2,534 ischemic strokes [6].
Sources: [11], [5], [6]
Caveats: Observational. The authors of the largest analysis call the absence of a positive link with stroke death unexplained, and note that statin trials reduce total stroke rates [5].

TriglyceridesStrong

Coronary heart disease in cohort studies

Mixed results: pooled cohorts linked higher triglycerides to more coronary heart disease, but in the largest analysis the link disappeared after adjustment for other risk factors.

The numbers and sources

Effect: In a meta-analysis of 29 Western prospective studies, people in the top third of usual triglyceride values had an adjusted odds ratio for coronary heart disease of 1.72 (95% CI 1.56 to 1.90) against the bottom third. The authors noted that adjustment for established risk factors substantially weakened the association [10]. In 68 prospective studies, coronary heart disease rates per 1,000 person-years were 2.6 in the bottom third and 6.2 in the top third of triglycerides. After adjustment for several conventional factors, the hazard ratio per standard deviation higher triglycerides was 0.99 (95% CI 0.94 to 1.05), and the authors concluded that vascular risk can be assessed without regard to triglyceride [11]. In a Danish cohort followed for a mean 26 years, multifactorially adjusted hazard ratios for heart attack at non-fasting triglycerides of 5 mmol/L (442.5 mg/dL) or more, against below 1 mmol/L, were 5.4 in women and 2.4 in men [12].
Population: 262,525 participants with 10,158 coronary heart disease cases in 29 studies [10]. 302,430 people without vascular disease in 68 prospective studies [11]. 7,587 women and 6,394 men aged 20 to 93 in Copenhagen [12].
Sources: [10], [11], [12]
Caveats: Observational. Triglycerides travel with low HDL cholesterol, obesity and diabetes, so how much of the link belongs to triglycerides themselves depends on what an analysis adjusts for [10][11].

TriglyceridesStrong

Cardiovascular events in trials that lowered triglycerides

Mixed results: fibrates cut cardiovascular events 10% in pooled trials and icosapent ethyl 25% in one, while pemafibrate lowered triglycerides 26% without fewer events.

The numbers and sources

Effect: Across 18 trials, fibrates reduced major cardiovascular events by 10% (95% CI 0 to 18) and coronary events by 13% (95% CI 7 to 19), with no effect on death from any cause [16]. Icosapent ethyl, 4 g a day, reduced a composite of cardiovascular events against placebo (17.2% against 22.0%, HR 0.75, 95% CI 0.68 to 0.83) in statin-treated patients with triglycerides of 135 to 499 mg/dL [17]. A different omega-3 formulation, 4 g a day against corn oil, made no difference (HR 0.99, 95% CI 0.90 to 1.09) and the trial was stopped early [18]. Pemafibrate lowered triglycerides by 26.2% against placebo and did not reduce cardiovascular events (HR 1.03, 95% CI 0.91 to 1.15), while ApoB rose 4.8% [19]. In a meta-regression of 49 trials, each 1 mmol/L reduction in triglycerides went with a risk ratio of 0.84 (95% CI 0.75 to 0.94) for major vascular events after accounting for LDL cholesterol. With the icosapent ethyl trial removed, the risk ratio was 0.91 (95% CI 0.81 to 1.006) [20].
Population: 45,058 participants in 18 fibrate trials [16]. 8,179 patients followed a median 4.9 years [17]. 13,078 statin-treated patients at high cardiovascular risk [18]. 10,497 patients with type 2 diabetes, triglycerides of 200 to 499 mg/dL and low HDL cholesterol, followed a median 3.4 years [19]. 374,358 patients in 49 trials [20].
Sources: [16], [17], [18], [19], [20]
Caveats: A marker that tracks risk is not always one whose lowering changes it. The meta-regression's authors concluded that the benefit of high-dose eicosapentaenoic acid appeared to exceed its lipid-lowering effect [20]. The icosapent ethyl and pemafibrate trials were funded by the drugs' makers [17][19].

LDL cholesterol (LDL-C)Moderate

Death from any cause

Mixed results: one Danish cohort found more deaths at both low and high LDL cholesterol, while statin trials found 10% fewer deaths per 1 mmol/L lowered.

The numbers and sources

Effect: In 108,243 Danish adults, the association with death from any cause was U-shaped. Compared with 132 to 154 mg/dL, the adjusted hazard ratio was 1.25 (95% CI 1.15 to 1.36) below 70 mg/dL and 1.15 (1.05 to 1.27) above 189 mg/dL. The level with the lowest risk was 140 mg/dL overall and 89 mg/dL in people on lipid-lowering treatment. The pattern held for cancer and other deaths and not for cardiovascular deaths, and any increase in LDL cholesterol went with more heart attacks [15]. Across 26 statin trials, death from any cause fell 10% per 1.0 mmol/L reduction (RR 0.90, 95% CI 0.87 to 0.93), with no significant effect on deaths from cancer or other non-vascular causes [12].
Population: 108,243 people aged 20 to 100 in the Copenhagen General Population Study, median follow-up 9.4 years, 11,376 deaths [15]. About 170,000 participants in 26 statin trials [12].
Sources: [15], [12]
Caveats: The cohort finding is observational, and illness that lowers LDL cholesterol before death (reverse causation) cannot be ruled out. The trials tested lowering with a statin in people selected for trials, over about 5 years.

LDL cholesterol (LDL-C)Moderate

Bleeding stroke at low levels

Mixed results: one cohort linked LDL cholesterol below 70 mg/dL to more bleeding strokes, while pooled trials lowering it to very low levels found no increase.

The numbers and sources

Effect: In a cohort with repeated LDL cholesterol measurements, people averaging below 70 mg/dL had more intracerebral hemorrhage than those at 70 to 99 mg/dL: adjusted HR 1.65 (95% CI 1.32 to 2.05) at 50 to 69 mg/dL and 2.69 (2.03 to 3.57) below 50 mg/dL. Risk at 100 mg/dL or above was similar to that at 70 to 99 [16]. In a meta-analysis of trials in populations starting at a median of 70 mg/dL or less and reaching a median as low as 21 mg/dL, LDL lowering was not associated with an increased risk of hemorrhagic stroke [14]. Statin trials found no significant effect on deaths due to stroke (RR 0.96, 95% CI 0.84 to 1.09) [12].
Population: 96,043 adults, mean age 51, free of stroke, heart attack and cancer at baseline, 753 hemorrhages over 9 years [16]. 50,627 patients in 3 trials of non-statin drugs plus a statin trial subgroup [14].
Sources: [16], [14], [12]
Caveats: The cohort is observational and cannot show that low LDL cholesterol caused the hemorrhages. The trials ran for a few years, so they say little about decades at very low levels.

Lipoprotein(a)Moderate

Cardiovascular events in trials that lowered lipoprotein(a)

Mixed results: a trial designed to test lowering took lipoprotein(a) from 236 to 64 nmol/L with no fewer cardiovascular events, while PCSK9 inhibitor trial analyses tied lowering to fewer.

The numbers and sources

Effect: In a placebo-controlled trial of monthly pelacarsen in patients with cardiovascular disease and lipoprotein(a) of at least 70 mg/dL, the median baseline level was 236 nmol/L. At 12 months it was 64.4 nmol/L on pelacarsen and 233.4 nmol/L on placebo. Over a median 4.7 years, a major adverse cardiovascular event occurred in 12.3% and 12.1% (HR 1.02, 95% CI 0.90 to 1.15). Among patients starting at 90 mg/dL or above the hazard ratio was 1.00 (0.87 to 1.15) [17]. Further analyses by treatment exposure, by the level reached at 3 months and by subgroup also found no association with fewer events [18]. Adding niacin to a statin lowered lipoprotein(a) 21% and did not reduce cardiovascular events [19]. Evolocumab lowered lipoprotein(a) by a median 26.9%, and reduced coronary events by 23% (HR 0.77, 95% CI 0.67 to 0.88) in patients with baseline levels above the median against 7% (HR 0.93, 0.80 to 1.08) at or below it, an interaction with a P value of 0.07 [20]. With alirocumab, each 1 mg/dL reduction in lipoprotein(a) went with a hazard ratio of 0.994 (95% CI 0.990 to 0.999) for major cardiovascular events, independent of the fall in LDL cholesterol [21].
Population: 8,350 patients with cardiovascular disease randomized and 8,322 analyzed, mean age 59.7, 27.0% women [17]. Patients with cardiovascular disease and low HDL cholesterol in a niacin trial [19]. 25,096 patients with cardiovascular disease, median follow-up 2.2 years [20]. 18,924 patients after an acute coronary syndrome, median follow-up 2.8 years [21].
Sources: [17], [18], [19], [20], [21]
Caveats: A marker that tracks risk is not always one whose lowering changes it. The pelacarsen trial enrolled people who already had cardiovascular disease, was funded by Novartis and was published in November 2026 [17]. The PCSK9 inhibitor findings are secondary analyses of drugs that mainly lower LDL cholesterol [20][21]. The sources for this page include no outcome results for other drugs built to lower lipoprotein(a).

Non-HDL cholesterol (non-HDL-C)Moderate

Death from any cause

Mixed results: higher non-HDL cholesterol went with more deaths in people with heart disease or on statins, while pooled general-population studies found no clear link with cardiovascular death.

The numbers and sources

Effect: In statin-treated Danish adults, non-HDL cholesterol above the median with LDL cholesterol below it had hazard ratios of 1.18 for death from any cause (95% CI 1.02 to 1.36) and 1.78 for heart attack (1.35 to 2.34), compared with both below the median. ApoB above the median with non-HDL cholesterol below it had a hazard ratio for death of 1.21 (1.03 to 1.41) [16]. In a meta-analysis of people with coronary heart disease, high baseline non-HDL cholesterol went with a risk ratio for death of 1.24 (95% CI 1.05 to 1.46) [17]. In a meta-analysis of observational studies, elevated non-HDL cholesterol was not associated with cardiovascular death in the general population (RR 1.64, 95% CI 0.96 to 2.80) or in people with type 2 diabetes (RR 1.08, 0.57 to 2.07), while it was associated with cardiovascular disease in both (RR 1.59 and 1.99) [18].
Population: 13,015 statin-treated adults in the Copenhagen General Population Study, median follow-up 8 years [16]. 11,057 people with coronary heart disease in 6 studies followed 18 to 148 months [17]. 156,381 people in 13 studies [18].
Sources: [16], [17], [18]
Caveats: Observational. High and low were defined by each cohort's own median or categories [16][17]. The confidence intervals for cardiovascular death are wide [18].

Total cholesterolModerate

Death from any cause

Mixed results: a Korean cohort of 12.8 million linked both low and high total cholesterol to more deaths, while statin trials found 10% fewer deaths per 1 mmol/L lowered.

The numbers and sources

Effect: In 12.8 million Korean adults, the association with death from any cause was U-shaped. Below 200 mg/dL, each 39 mg/dL higher total cholesterol went with 23% lower mortality (95% CI 23 to 24). From 200 mg/dL upward, each 39 mg/dL higher went with 7% higher mortality (6 to 7). The levels with the lowest mortality were 210 to 249 mg/dL in most age and sex groups, and lower in men aged 18 to 34 (180 to 219 mg/dL) and women aged 18 to 34 (160 to 199 mg/dL) [12]. Across 26 statin trials, death from any cause fell 10% per 1.0 mmol/L reduction in LDL cholesterol (RR 0.90, 95% CI 0.87 to 0.93) [10].
Population: 12,815,006 Korean adults who had routine health examinations in 2001 to 2004, followed until 2013, with 694,423 deaths [12]. About 170,000 participants in 26 statin trials [10].
Sources: [12], [10]
Caveats: The cohort finding is observational, and illness that lowers cholesterol before death (reverse causation) cannot be ruled out. The trials tested lowering with a statin in people selected for trials, over about 5 years.

HDL cholesterol (HDL-C)Strong

Heart attack and death in trials of drugs that raised HDL cholesterol

Not shown to cut heart attacks or deaths when raised by drugs: pooled trials of niacin, fibrates and CETP inhibitors in 117,411 patients found no reduction on statins.

The numbers and sources

Effect: In a meta-analysis of 39 trials, no significant effect on death from any cause was seen for niacin (OR 1.03, 95% CI 0.92 to 1.15), fibrates (0.98, 0.89 to 1.08) or CETP inhibitors (1.16, 0.93 to 1.44). Niacin reduced non-fatal heart attack in trials run before statins (OR 0.69, 95% CI 0.56 to 0.85) and not in trials where statins were taken (0.96, 0.85 to 1.09) [10]. A meta-regression of 108 trials found no association between the change in HDL cholesterol a treatment produced and coronary events or deaths, once the change in LDL cholesterol was accounted for [11]. Among CETP inhibitors, torcetrapib raised HDL cholesterol 72.1% and increased cardiovascular events (HR 1.25, 95% CI 1.09 to 1.44) and death from any cause (HR 1.58, 95% CI 1.14 to 2.19) [12]. Dalcetrapib raised it 31 to 40% with no effect on events (HR 1.04, 95% CI 0.93 to 1.16) [13]. Evacetrapib raised it 133.2% and lowered LDL cholesterol 31.1% with no effect on events (HR 1.01, 95% CI 0.91 to 1.11) [14]. Anacetrapib raised it by 43 mg/dL, lowered non-HDL cholesterol by 17 mg/dL and reduced major coronary events (rate ratio 0.91, 95% CI 0.85 to 0.97) [15]. Adding niacin to a statin raised HDL cholesterol from 35 to 42 mg/dL in one trial (HR 1.02, 95% CI 0.87 to 1.21) and by 6 mg/dL in another (rate ratio 0.96, 95% CI 0.90 to 1.03), without fewer events in either [16][17].
Population: 117,411 patients in 39 trials [10]. 299,310 participants in 108 trials [11]. 15,067, 15,871, 12,092 and 30,449 patients at high cardiovascular risk in the four CETP inhibitor trials [12][13][14][15]. 3,414 and 25,673 patients with vascular disease in the two niacin trials [16][17].
Sources: [10], [11], [12], [13], [14], [15], [16], [17]
Caveats: A marker that tracks risk is not always one whose raising changes it. Torcetrapib also raised blood pressure, an effect its investigators considered off-target [12]. The one trial with fewer events also lowered non-HDL cholesterol [15]. Niacin with laropiprant increased serious adverse events [17].

Apolipoprotein A1 (ApoA1)Moderate

Coronary heart disease in genetic studies

Not shown to protect against coronary disease in genetic studies: gene variants that raise ApoA1 did not go with less disease once ApoB was accounted for.

The numbers and sources

Effect: In a Mendelian randomization analysis using a variant in the APOA1 gene region, each standard deviation higher ApoA1 had an odds ratio for coronary artery disease of 1.13 (95% CI 0.98 to 1.30), while the observational hazard ratio in the same paper was 0.81 (0.75 to 0.88) [12]. In a second analysis, the odds ratio per standard deviation higher ApoA1 was 0.83 (95% CI 0.77 to 0.89) when ApoA1 was analyzed alone and 0.94 (0.76 to 1.17) after adjustment for ApoB, which itself kept an odds ratio of 1.68 (1.54 to 1.84) [13].
Population: Genetic data on 20,370 Finnish participants combined with an earlier genome-wide study, applied to 122,733 coronary cases, and 918 incident cases among 11,535 people for the observational estimate [12]. Genetic data from up to 441,016 UK Biobank participants, applied to 60,801 coronary cases and 123,504 controls [13].
Sources: [12], [13]
Caveats: Gene variants act from birth, so these estimates describe lifelong differences, not a change made later in life. The authors of one analysis note that its single-trait estimates weakened under methods more robust to variants that act through several traits [13].

HDL cholesterol (HDL-C)Moderate

Heart attack in genetic studies

Not shown to protect against heart attack in genetic studies: gene variants that raise HDL cholesterol alone did not lower risk.

The numbers and sources

Effect: Carriers of a variant in the endothelial lipase gene had HDL cholesterol 0.14 mmol/L higher, with other risk factors similar. That difference predicted a 13% lower risk of heart attack (OR 0.87), and the observed odds ratio was 0.99 (95% CI 0.88 to 1.11). A one standard deviation rise in HDL cholesterol from a 14-variant genetic score was also not associated with heart attack (OR 0.93, 95% CI 0.68 to 1.26). The same method applied to LDL cholesterol gave an odds ratio of 2.13 (95% CI 1.69 to 2.69) per standard deviation, in line with the observational estimate [9].
Population: 20,913 heart attack cases and 95,407 controls in 20 studies for the single variant, and up to 12,482 cases and 41,331 controls for the genetic score [9].
Sources: [9]
Caveats: One Mendelian randomization study. Its authors concluded that some genetic mechanisms that raise HDL cholesterol do not seem to lower risk, which does not rule out a role for other properties of HDL particles [9].

Apolipoprotein A1 (ApoA1)Limited

Heart attack, stroke and cardiovascular death in a trial that infused ApoA1

One trial found four weekly infusions of human ApoA1 after a heart attack did not significantly lower heart attack, stroke or cardiovascular death against placebo.

The numbers and sources

Effect: In the AEGIS-II trial, the composite of heart attack, stroke or cardiovascular death occurred in 4.8% of patients given ApoA1 (CSL112) and 5.2% given placebo at 90 days (HR 0.93, 95% CI 0.81 to 1.05, P = 0.24). At 180 days it was 6.9% against 7.6% (HR 0.91, 0.81 to 1.01), and at 365 days 9.8% against 10.5% (HR 0.93, 0.85 to 1.02). Adverse events were similar, with more hypersensitivity events reported with ApoA1 [14]. In a meta-analysis of people on statins, a rise in ApoA1 after starting treatment went with fewer major cardiovascular events (HR 0.93 per standard deviation, 95% CI 0.90 to 0.97), while a rise in HDL cholesterol did not (0.98, 0.94 to 1.01) [11].
Population: 18,219 patients with acute myocardial infarction, multivessel coronary disease and other risk factors, given four weekly infusions of 6 g or placebo [14]. 38,153 trial participants allocated to a statin [11].
Sources: [14], [11]
Caveats: The trial tested a short course of infused ApoA1 soon after a heart attack and was funded by the maker of the product. It did not test a lasting rise in a person's own ApoA1 [14]. The statin finding compares people within trials and is observational [11].
Why limited: This rests on one trial, of 18,219 people. Strength counts independent studies that agree, so one trial is limited at any size.