[#481: Why Saturated Fat Really Does Impact Heart Disease Risk | Sigma Nutrition](https://sigmanutrition.com/episode481/) tl;dr: The podcast examines the association between saturated fat intake and cardiovascular disease, scrutinizing several influencing factors such as thresholds, nutrient replacements, and study designs. The main points discussed include the importance of substituting one type of fat with another, adjusting for blood cholesterol levels, and the fact that observational studies may show a risk reduction with a higher recommended saturated fat intake than the current 10% threshold. Several influential studies (e.g., The Seven Country Study and the Siri Torino meta-analysis) are examined, but their limitations and methodological issues are highlighted. Overall, there is sufficient evidence to suggest a causal relationship between saturated fat intake, blood lipids, and heart disease, but further consideration should be given to factors such as inter-individual variability and methodology in future research. Notes: - The podcast episode addresses the claim that reducing saturated fat intake doesn't lead to a decrease in cardiovascular disease or mortality. - There are concerns about the validity of evidence showing associations between saturated fat intake and cardiovascular disease. - One commonly cited study is the 2010 meta-analysis by Siri-Torino and colleagues, which looked at 16 prospective cohort studies. - The Siri-Torino study had issues with dietary assessment and adjustment for potential covariates and mediating factors. - Over-adjustment was a key issue in the Siri-Torino study, as almost half of the statistical weight was derived from studies that had controlled for blood cholesterol levels, which mediates the relationship between saturated fat intake and cardiovascular disease. - The overall analysis in the Siri-Torino study did not distinguish between fatal cardiovascular disease and events, which is important in assessing mortality risk. - In a follow-up editorial by Jeremiah Stamler, an analysis confined to 11 studies reporting on fatal cardiovascular disease showed a 32% higher risk for mortality related to saturated fat intake. - A second paper from the same author later in the year acknowledged Stamler's findings and also showed an 18% higher risk of heart disease mortality in a subgroup analysis of seven studies reporting only on heart disease mortality. - The Chowdhury meta-analysis found no association between saturated fat intake and coronary heart disease, and looked at both dietary and circulating levels of individual fatty acids. - One issue with the meta-analysis was a failure to account for food source of monounsaturated fats, which could erroneously suggest an association with heart disease. - The meta-analysis also did not account for individual variation in response to saturated fat intake, making it harder to detect a relationship. - Biomarkers in nutritional epidemiology were not well accounted for, and the analysis suggested that circulating saturated fatty acid levels were weakly associated with a relative risk of about 6%. - Several meta-analyses have been conducted to investigate the relationship between saturated fat and cardiovascular disease. - The Siri Torino meta-analysis and the Chowdhury meta-analysis both had methodological issues, including over-adjustment and the use of unreliable biomarkers. - The de Souza meta-analysis also had methodological issues, including using risk estimates from the Siri Torino paper and not conducting substitution analysis to determine what was being replaced with saturated fat intake. - The PURE trial suggested that higher levels of carbohydrate intake increase the risk for mortality while higher levels of saturated fat intake are protective, but this interpretation is flawed because the study was conducted in populations with very narrow ranges of saturated fat intake that make it difficult to detect meaningful differences in risk. - The PURE study is often cited as evidence that reducing saturated fat intake may not improve health outcomes, but there are limitations in the study design and the range of intake levels studied. - The Seven Country Study is a useful study for examining the association between saturated fat intake and cardiovascular disease. - The Seven Country Study has been criticized for being an ecological comparison instead of measuring diet in every individual, but it had a representative subgroup in each cohort. - The study found a strong association between saturated fat intake and cardiovascular disease, with populations that had higher saturated fat intake having higher rates of cardiovascular disease. - The study also found a strong inverse association between the intake of polyunsaturated fatty acids and cardiovascular disease. - The Seven Countries Study was a study that compared the intake of animal and vegetable fats in different populations. - It showed a linear association between saturated fat intake and coronary heart disease mortality. - The study provided a contrast in the average population cholesterol levels in each cohort, allowing for meaningful comparisons. - The correlation between saturated fat intake and coronary heart disease was 0.88, a strong correlation for an epidemiological study. - The study used multivariate models including adjustment for factors like smoking and physical activity. - Saturated fat intake explained 73% of the association between factors and coronary heart disease. - The Seven Countries Study had limitations but it was a useful illustration of the causal chain between saturated fat intake, blood lipids, and heart disease mortality. - The impact of saturated fat intake on blood lipids has been observed in metabolic ward feeding studies. - There is a chain of relationship between saturated fat as a percentage of energy, blood cholesterol levels, and heart disease risk. - The impact of different types of fats on blood cholesterol levels has been extensively studied. - The Keyes equation shows that saturated fats have twice the cholesterol raising effect as the cholesterol lowering effect of polyunsaturated fats, but dietary cholesterol must also be taken into account. - Substitution effects must be considered when changing levels of saturated fat in the diet and what nutrients are taking its place. - Meta-analyses of metabolic ward studies have shown that the greatest reduction in total and LDL cholesterol levels come from replacing saturated fat with polyunsaturated fat. - Core trials, such as the LA Veterans Study, the Oslo Diet Heart Study, the Finnish Mental Hospital Study, and the UK Medical Research Council Study, have shown significant effects in reducing the risk of myocardial infarction and sudden cardiac death when specific replacement of saturated fat with polyunsaturated fats is achieved. - RCTs show no effect of X on Y, but often lack meaningful comparison - Thresholds and levels of intake are crucial in discussions on heart disease risk - Evidence from epidemiology, intervention trials, and substitution analyses show consistent effect of replacing saturated fat with polyunsaturated fat - Magnitude of achieved lowering of saturated fat is important, with minimum of 4% reduction and ideally 4-8% or over 8% achieved - Cumulative effect of elevated blood lipids is important in atherosclerosis risk - Reduction in saturated fat intake needs to be of a great enough magnitude and for long enough to have an impact on reducing blood lipids and cardiovascular disease risk - Thresholds and levels of intake have always been crucial in discussions on heart disease risk, and the actual percentages are important in interpreting evidence from intervention trials and epidemiology. - There is an association between saturated fat and heart disease. - The association depends on the levels of intake that are being compared. - The nutrient that replaces saturated fat in the diet also matters. - Adjusting for blood cholesterol levels can affect the results of a study. - There needs to be categorical stratification for more meaningful comparisons in nutrition research. - Population studies show a pronounced risk at over 16-18% of energy intake from saturated fat. - There are limitations to epidemiology and meta-analyses that can lead to inconsistent findings. - There is sufficient evidence to support a causal chain between saturated fat intake, blood lipids, LDL in particular, and atherosclerosis driving dietary contributor to coronary heart disease. - The graph from the Hooper paper has interesting modeling of cutoff points but methodology limitations. - We should not view the cutoff points as concrete but think critically about them. - Inter-individual differences in responsiveness to saturated fatty acid intake exist. - Observational studies show potential benefits of a wider range of intake beyond under 10%. - There are key factors to consider in accurately looking at the levels of intake, nutrient replacement, and adjustment in studies. - Detailed study notes and a transcript are available for Sigma Nutrition premium subscribers.