From saturated fat to arterial plaque: cholesterol and beyond

This article is a work in progress and regularly updated as I study this topic.

Cardiovascular diseases (CVDs) are still the leading cause of death globally (OWID), but vary markedly by demographics and in relation to various lifestyle factors. In particular, in the second half of the 20^th century, the seminal Seven Countries Study illuminated associations with diet, especially saturated fatty acids (SFAs), which at 50-year follow-up remain strongly associated with coronary heart disease mortality (n=16 cohorts, r=0.92) ¹. Many other studies have further probed this relationship, and while some inconsistency emerged, so has context. For instance, some prospective cohort studies and meta-analyses thereof fail to find independent associations with SFA intake ²; however, studies performing substitution analyses generally report that replacing SFAs (mainly from animals) with unsaturated fatty acids (UFAs; from plants and fish) or complex carbohydrates (from whole grains) lowers CVD risk and mortality (e.g. US ^3–8, Europe ^9–11 and pooled ^12,13). Importantly, in the US it was also revealed that SFAs are typically replaced by refined grains and added sugars, which are also associated with CVD, potentially explaining prior null findings ⁴. In addition, dietary SFAs are also highly correlated with animal-sourced MUFAs (r=>0.8), which may have obscured favourable associations seen only with plant sources ^7,8.

Solid vs. liquid fat—a biophysical perspective

As reviewed previously, dietary fats have differential effects on the body in relation to various mechanisms. This post explores why from a more fundamental perspective.

The body is largely an aqueous environment, compartmentalised by amphipathic lipid barriers/membranes containing specific hydrophobic fatty acids; and similarly, lipids are transported in amphipathic lipoproteins and metabolised by water-soluble enzymes (e.g. lipases). However, dietary fats have diverse structures and physiochemical properties. Foremost, unsaturated fatty acids (UFAs) are liquid at body temperature (37°C), while saturated fatty acids (SFAs) have higher melting points, which increase with chain length, resulting in short–medium chain fatty acids (e.g. C3–11:0) being liquid and longer chains solid; with a parallel relationship to water insolubility (Wiki). Could these basic characteristics underlie some of their differential effects?

Reversal of CVD with diet and lifestyle

Among the ocean of research, I’m very interested in natural interventions which have reversed common diseases, since they help reveal basic ecology. Here’s a mini-review based around my initial reading of such CVD trials.

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, accounting for 31% of all deaths (WHO). The most common forms are coronary artery and cerebrovascular diseases (affecting heart and brain, respectively) driven by atherosclerosis (i.e. plaque build-up) ^1,2. Further, CVD and intracranial atherosclerosis are also linked to dementia ^3,4, another leading cause of death (e.g. Dementia Hub).

Autonomic dysfunction in ME/CFS: a role for the immune system?

Autonomic dysfunction (dysautonomia) is a major feature of ME/CFS ^1–4. The autonomic nervous system regulates many organs and things of relevance (e.g. blood flow, heart rate, immune function and energy metabolism) ⁵, so could contribute to multi-system dysfunction.