Chocolate vs. CFS: flavanols and beyond

There have now been several preliminary studies testing the effects of phytochemical-rich plants in ME/CFS, some of which show benefit (discussed later). Of these, I find the 2010 trial with chocolate particularly intriguing ¹.

This was a very small pilot trial (UK, n=10 CFS, Fukuda criteria + severe fatigue; no mood disorders, no drugs) to test the effect of polyphenol-rich chocolate for 8 weeks on symptoms. It had a double-blind, placebo-controlled, crossover design (8–2–8), with several subjective outcomes; and high methodological quality in a recent systematic review ². The active treatment arm had an improvement in fatigue, anxiety, depression and disability (pre–post effect: –35%, –37%, –45% and +31%, respectively); anecdotally, 2 people with short illness duration even returned to work ¹. For reference, this is a greater reduction in fatigue, depression and anxiety than over a year of CBT or GET in the large PACE trial (UK, n=641 CFS, multiple criteria), which used some of the same outcome measures ³.

Is NAD low in CFS?

Nicotinamide adenine dinucleotide (NAD) performs central roles in metabolism as a redox cofactor and enzyme substrate. NAD is synthesised via several pathways; in essence from tryptophan (i.e. de novo pathway) or vitamin B₃ precursors (i.e. Preiss-Handler and salvage pathways), with addition of ribose-phosphate (from PRPP) and AMP (from ATP), and amidation to form NAD ¹. Several enzymes (e.g. sirtuins, PARPs and CD38) catabolise NAD by removing the whole ADP-ribose portion releasing nicotinamide (NAM), which can be recycled to NAD in the salvage pathway, or methylated (via NNMT) and excreted.

NAD metabolism is regulated by circadian rhythms ² and daily activities ³, while levels may decline with ageing ^4,5 and disease ⁶. Several authors have also suggested NAD may be low in ME/CFS, based on suspected pathophysiology ^7–10. Currently, there are scarce studies in this area, but below are some preliminary findings I’ve scraped together.

Redox in CFS: to what do we owe this electron flow?

Oxidative stress has long been implicated in CFS. Here are some data summary tables from a draft paper on redox in CFS written around this time. They generally show how an oxidative redox status may affect many molecules and tissues, and associate with many symptoms.

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.

Why is there autoimmunity in ME/CFS?

Several lines of evidence suggest autoimmunity is involved in ME/CFS.

Firstly, there are similarities in both the demography (e.g. female dominance) and general immunological milieu of ME/CFS with established autoimmune conditions ^1–4. Secondly, a large array of autoantibody responses to various signaling molecules, cell-surface receptors and intracellular molecules have long been reported in ME/CFS ^1,5,6. Note however, the number of people with these autoantibody responses varies widely, and their functional significance is not yet clear ⁷. Thirdly, several preliminary trials have shown that Rituximab (CD20 antibody which depletes peripheral B cells) can induce a moderate-major remission in around 60% of people (followed by relapse). The delayed response (2-7 months) seems consistent with the gradual removal of existing antibodies ^8,9, and autoantibodies to autonomic receptors do decline with clinical response ⁶.

However, why is there even autoimmunity at all? Why would the body start attacking itself? Bad luck, or system failure? Here is a little exploration of just that.

Is ME/CFS an immunodeficiency disorder?

ME/CFS has long been associated with infections. A large variety of viral ,bacterial and even protozoan infections have been implicated as triggers ^1–4 . There is also some evidence for persisting chronic infections - elevated antibody responses to several viruses are found in at least some CFS subsets ^1,2,5,6, and increased viral presence has been found in blood cells, muscle tissue and the GI tract ^7–10. CFS patients also appear to have an increased rate of upper respiratory tract infections (URTIs), as recently confirmed by objective virology and antibody levels ¹¹.

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.