2.2.9 PEM prevention and recovery

One of the hallmark symptoms of ME/CFS, Long COVID / Long Haulers and various other named syndromes is post-exertional malaise (PEM).

The disease model shows that exertion promotes IFN-γ and oxidative stress, which further inhibits glycolysis, fatty acid oxidation, methylation and other key energy metabolism. Simultaneously, histamine is released during exertion, signalling for liver glycogen to be redistributed to muscle tissue.

Part of the glycolysis impairment relates to inhibited liver glycogenesis (glycogen synthesis). This is acutely influenced by epinephrine in response to the energy crisis, however there are additional "background" influences from elevated microbiome-related acetaldehyde and various cofactor + nutrient deficiencies. This part of the disease cascade is described as a reversible liver glycogen storage disease.

Glycolysis insufficiency is frequently accompanied by tinnitus, vision reduction, dizziness, reduced mobility / muscle activation, muscle spasms / tremors, tachycardia and nausea.

The protocol addresses these upstream influences and the glucose uptake and glycolysis rate has been shown to improve / revert, however some daily variability around glycogen usage will exist relative to your exertion and immune activity levels.

During increased exertion and/or (downstream) immune activity, energy consumption also increases and creates oxidative stress, hence your carbohydrate and protein intake may need to be increased to match your glycogen expenditure. This would normally be additional carbohydrates, protein as additional small meals over the day, and a large additional intake of vitamin C and/or other antioxidants.

However, in a crash / PEM, the priority is restoring liver glycogen (and sodium) levels. Spoonfuls of NZ Manuka honey are one of the least risky sources for simple carbohydrates, as it has an antimicrobial profile thought to be related to the methylglyoxal content and various phenols. H1 antagonists like doxylamine succinate can also be helpful, especially before sleep - as they normally cause drowsiness.

You can also target restoration of energy availability and glycogen synthesis via alternative pathways, if they are functioning. These pathways may include (non-exhaustive):

• Branched-chain amino acids (BCAAs) catabolism. BCAAs are found in dietary protein sources. BCAA catabolism requires sufficiency of manganese, Vitamin B1 (as thiamine pyrophosphate), P5P, biotin and Vitamin B12 (as adenosylcobalamin, for 2 of the BCAAs - L-leucine has a different pathway). Assuming you are supporting these co-factors with the protocol, you can simply take 5-10g of BCAAs or L-leucine alone to rapidly help initial recovery and then increase carbohydrates and/or protein to prevent reoccurence.
  https://www.bulksupplements.com/search?q=bcaa
  
  
• Ketogenesis - supplying beta-hydroxybutyrate (BHB). This pathway requires phosphatidylcholine (PC) and NAD⁺ sufficiency. Assuming you are supporting phosphatidylcholine and NAD⁺ biosynthesis and redox with the protocol, you can also take 10–20g of a BHB supplement, as needed to help recovery and then increase carbohydrates and / or protein to prevent reoccurrence.
  https://www.bulksupplements.com/search?q=hydroxybutyrate
  
  

If you have an asthma inhaler (salbutamol), it can be very helpful to increase catabolic activity and provide emergency energy availability for a period of time, but may also inhibit glycogen storage, where insulin is not elevated (between meals), so should not be used frequently.