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?

Differential effects of fats on gut–host health

Dietary fats are ubiquitous and essential, while their quantity and quality modulate health. Recently, effects on the gut microbiome are being revealed. This post explores their differential effects on the gut–host dialog and underlying mechanisms relevant to many diseases.

Dietary fats appear to differentially affect human physiology; and perhaps most notoriously in the case of cardiovascular disease (CVD), the leading cause of death globally. For instance, in large observational studies, substitution analyses suggest opposing effects of saturated vs. monounsaturated and polyunsaturated fatty acids (i.e. SFAs vs. MUFAs and PUFAs, respectively) on CVD ^1–3; a relationship tested and supported by meta-analyses of randomised controlled trials (RCTs) ⁴, and referenced in many dietary guidelines. Further, in 3–4 week RCTs on healthy adults, adjusting the habitual palmitate/oleate ratio (i.e. the most abundant SFA/MUFA) affects blood/tissue lipids, alongside energy metabolism, immune activity and brain function ^5–11. And even single meals with different fats can have markedly different effects on postprandial cardiometabolic biomarkers ¹².

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).

Homocysteine on the brain: many paths to many problems

2019 – end edit and update.

Homocysteine might be important in many neurological disorders, especially cognitive decline. I’ve been reading about potential mechanisms—there are a lot! Here’s an attempt to arrange some things of interest as a mini-review.

Homocysteine is a sulfur-containing amino acid, derived from the metabolism of dietary methionine. Homocysteine exists in various forms ¹ and is metabolised via two main pathways: remethylation and transsulfuration. Homocysteine remethylation to methionine maintains levels of SAM, the major methyl-donor, required in over 50 methylation reactions to DNA/RNA, proteins, phospholipids and other metabolites ². Whereas homocysteine catabolism via the transsulfuration pathway yields many other important sulfur metabolites (e.g. cysteine/glutathione, H₂S and taurine). Both of these pathways depend upon B vitamin-derived substrates/cofactors and are regulated by various physiological processes.