The role of cholesterol and saturated fat in chronic disease risk has been overstated

Since Ancel Keys popularized the lipid-heart hypothesis in the mid-20th century, animal fat has been criticized for its potential to increase total and LDL cholesterol (LDL-C). However, the proposed mechanism—that dietary cholesterol and saturated fat raise serum cholesterol, which then leads to heart disease—is simplistic and has been contradicted by numerous systematic reviews, meta-analyses, and expert opinions. Foundational studies supporting the hypothesis have come under scrutiny for methodological flaws, inconsistencies, and/or reliance on (very) low-certainty evidence with very low absolute risk reductions.

Collectively, this body of evidence casts doubt on the validity of dietary guidelines that continue to advocate for further reductions in saturated fat intake. It raises concerns about biases and conflicts of interest that keep on perpetuating these recommendations. More importantly, such debates risk diverting attention from the true drivers of the current public health crisis: hyperinsulinemia and chronic inflammation fueled by nutrient-poor diets dominated by ultra-processed foods.

Evidence from randomized controlled trials (RCTs) on the impact of reducing saturated fat intake remains contentious due to concerns over methodological flaws. A prominent 2020 Cochrane meta-analysis found no significant reduction in myocardial infarction, stroke, or mortality. It did, however, report a modest decrease in the more subjective outcome of ‘combined cardiovascular events’. Yet, this finding has faced criticism for being biased and losing statistical significance in sensitivity analysis.

Other meta-analyses have suggested that replacing saturated fats with polyunsaturated fats may improve health outcomes, but these conclusions have been questioned for selective inclusion of trials and a lack of clinical endpoints. Indeed, RCTs often focus excessively on a narrow range of biomarkers, particularly LDL-C, while neglecting broader systemic metabolic factors that can be adversely affected by replacing saturated fats with carbohydrates, trans fats, or linoleic acid.

Upon discarding inadequate trials, a 2017 meta-analysis of rigorous RCTs concluded that substituting omega-6 polyunsaturated fatty acids for saturated fats does not reduce coronary heart disease events or mortality. Similarly, a 2024 preprint meta-analysis of RCTs found insufficient evidence to broadly recommend reducing dietary saturated fat to prevent cardiovascular disease or mortality.

The effects of saturated fat and cholesterol on health depend on various factors, including variation in individual responses and the type of saturated fat consumed. While saturated fat can increase LDL-C in most people, this response may be 'normal' and related to cholesterol homeostasis. However, inflammation-driven metabolic disorders can disrupt this balance, increasing cardiovascular risk. 

Notably, the increase in LDL-C associated with saturated fat intake predominantly involves large, buoyant LDL particles, which are minimally associated—or not associated at all—with atherosclerosis. In contrast, small, dense LDL particles are formed with high intake levels of fructose and other refined carbohydrates. These particles are more prone to oxidation, making them highly atherogenic and less efficiently cleared from the bloodstream by the liver. The oxidized state of these LDL particles depends on the presence of systemic inflammation, insulin resistance, and dietary oxidized lipids.

The effects of different types of saturated fatty acids also vary. Stearic acid, common in animal fat, may be associated with lower cardiovascular and cancer risk, helping to reduce visceral fat and promote healthier metabolism. Short- to medium-chain saturated fatty acids, especially those from dairy, have been linked to reduced risks of ischemic heart disease, while other saturated fats like lauric and palmitic acids showed no such associations. Furthermore, very long-chain saturated fatty acids, found in nuts and seeds, may have protective effects on cardiovascular health, whereas pentadecanoic acid, a saturated fat from butter, is being explored as a potential essential fatty acid with health benefits.

Traditional dietary guidance, often focusing on individual nutrients like saturated fat, tends to overlook the complexities of the food matrix. This reductionist approach has led to recommendations to restrict whole-fat dairy in favour of low-fat versions. However, these claims are not supported by evidence.

Studies have shown that whole-fat dairy, as opposed to reduced-fat dairy, does not lead to increased body fat or worsen cardiometabolic markers in children. In fact, regular-fat dairy has sometimes been linked to a lower risk of obesity. Moreover, the Framingham Offspring Study found that males with higher intakes of dairy-derived saturated fats exhibited a less atherogenic profile.

Even though some studies have suggested a link between dairy consumption and cardiovascular risk, these associations do not hold across all types of dairy products, which vary widely in their nutritional composition. A meta-analysis has shown that even butter has negligible associations with all-cause mortality, no links to cardiovascular disease, and an inverse association with diabetes.

This body of evidence suggests that whole-fat dairy offers benefits and should not be dismissed based on its saturated fat content. The PURE diet score, based on a well-controlled global dataset, supports the inclusion of whole-fat dairy as a protective food, recommending up to 14 servings per week.

Eggs, often discouraged due to their cholesterol content, do not typically raise serum cholesterol levels, except in hyperresponders. While research in the US found a weak association between egg cholesterol and increased mortality, studies in Asia have reported the opposite effect, which may reflect culture-dependent 'healthy user' biases. Similarly, the effects of egg intake on type-2 diabetes vary by region. 

On a global scale, no significant associations have been found between egg consumption and blood lipids, mortality, or major cardiovascular disease events. Higher egg consumption is even associated with a better healthy diet score, as shown by data from the PURE cohort. 

Therefore, and contrary to common concerns, egg consumption is not generally associated with risk, and may even be linked to protective outcomes.