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.

Oxidative ageing: from proximate to ultimate causes

Oxidative stress seems really important in age-related decline and disease—but what causes it? Here I’ve tried to express a broadening perspective, by exploring its core, context and ultimate causes; and largely anchored in human studies where possible.

We all die—what matters is how. While human life expectancy has increased, non-communicable diseases are now the major cause of disability and death globally (WHO and OWID). These are mostly age-related diseases (e.g. CVD, cancer, COPD, dementia, etc.), which develop slowly over time, and coexist as multimorbidity (e.g. most people >65 in US/UK ^1,2); resulting in functional decline/frailty and socioeconomic burden (i.e. ↓ productivity, ↑ sick care). This situation is growing globally, as populations are ageing, and diseases occur earlier—so we may live longer but sicker ¹. Moreover, this invisible epidemic underlies susceptibility to (communicable) infectious diseases, such as COVID-19 ³, elevating chronic disease to acute threat.

Synthetic vs. organic B12 metabolism—is cyanocobalamin inferior?

Cyanocobalamin is a common synthetic form of vitamin B₁₂ used in supplements and fortified foods—how does it compare to natural forms?

Vitamin B₁₂ (cobalamin, Cbl) has the most complex structure of all vitamins, which consists of a central cobalt atom bound to a corrin ring, a displaceable lower (a) ligand (5,6-dimethylbenzimidazole, DMBI) and a variable upper (b) ligand (e.g. cyano-, methyl-, 5’-deoxyadenosyl-, etc.) ¹ (see).

Cbl was originally isolated as cyanocobalamin (CNCbl), which was later recognised as an artefact arising from extraction methods ². Further advances led to identification of natural forms in microbes, animals and humans ^2–5, where methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl) serve as vital coenzymes for methionine synthase (MS) and methylmalonyl-CoA mutase (MCM), respectively.

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.

Sulfur in CFS: signals in the noise?

Some findings presented at a recent CFS conference got me interested in sulfur again. What is the current picture? How does it fit with everything else? Here’s a mini-review of my reading.

Sulfur is the 7th most abundant element in the body ¹. Most has been presumed to come from dietary proteins, specifically the two sulfur-containing amino acids: methionine and cysteine. However, a substantial amount also comes from other organosulfur compounds in plants (e.g. allium and cruciferous veg) and inorganic sulphates (i.e. water and food) ².

Many things influence hydrogen sulfide metabolism

Some time ago hydrogen sulphide (H₂S) was suggested to play a role in ME/CFS ^1,2. Since then the general research literature has continued to forge ever more intricate and compelling links between H₂S, health and disease. Gone are the days of H₂S being exclusively viewed as an environmental toxicant; H₂S is now widely recognised as a major biological mediator (even in mitochondria! ³). Recently H₂S was even found to mediate the beneficial effects of dietary restriction on stress resistance and lifespan ⁴.