Anyone who has experience with ME/CFS is likely to have gained a significant appreciation for the symptoms associated with “crashing” and Post Exertional Malaise (PEM).

A daily fear that too much activity will “crash” you and leave you with fatigue / malaise, flu-like symptoms and often tinnitus. A further fear that this may persist for days / weeks / months.

A hypothesis surrounding the mechanisms involved in PEM is being described in the upcoming paper, however the work-in-progress diagrams are available on the Born Free website.

Unfortunately, due to the trauma surrounding PEM, some people choose to severely limit their activity. This unfortunately has an impact on the capabilities of their immune system to deal with chronic infection.

One of the primary tools the innate immune system can use against microbial challenges is creating reactive oxygen species (ROS) to oxidise these pathogens. IFN-γ inhibits Complex I, which means that NADH generated by the TCA cycle can be diverted towards elevating NADPH, also powering NADPH oxidase (NOX) and nitric oxide synthase, which then (like xanthine oxidase, which uses NAD⁺ instead) create reactive oxygen species to oxidise pathogens, damaging your cells in the process. This can also lead to fungal die-off symptoms.

Excess NADPH / low NADP with elevated NADH / low NAD⁺ can be observed / inferred by elevated cholesterols, impaired glucose metabolism, elevated cortisol / inverted diurnal release profile, low aldosterone, low testosterone, low BH4, impaired methylation and various other compensations.

For optimal immune response and hormones, “pacing” should always be attempted – testing the appropriate upper threshold for activity, each day, unless that threshold has been exceeded already. Over sufficient time, inactivity leads to “rotting”, which is wholly undesirable, as the immune response is expected to be insufficient for maintaining resilience against pathogens.

The combination of supplements here should help improve the exertion threshold and buffer against “crashing”. However, you may have already noticed that fungal “die-off” symptoms share some common features with PEM and crashing, as does any immune activity. This will add some challenges for identifying your upper limits for exertion / glycogen synthesis rate.

Note the upper limit for exertion will be artificially reduced when IFN-γ is elevated and Complex I is inhibited, during any intense immune response. Increasing temperature elevates IFN-γ levels potentially ten-fold. Spirulina, schisandra and curcumin modify this pathway, favourably, by inhibiting NOX.

Proceed carefully, however the age-old phrase “no pain, no gain” absolutely applies here.