In a fabulous review on Acelylcholine the following sentence sticked out to me: "Consistent with a potenetial role of ACh in coordianting caloric need with food-seeking behaviours. long term maintenance on a high-fat/high-sugar diet significantly downregulated levels of AChE in a number of brain areas that was particularly pronounced in the hyothalamus (Kaizer et al. 2004)." "Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Functions and Behaviour"; Picciotto, Highley et al. 2012, page 122, the original source: "Diet-induced changes in AChE activity after long-term exposure"; Kaizer, da Silva et al. 2004 Abstract: In the present study we investigated a potential mechanism by which high sugar (HS) and high fat (HF) diets could affect acetylcholinesterase (AChE) activity. The treatment with HS and HF diet was done for six months on male and female rats. The results showed decreased hippocampal AChE activity in male and females receiving HS and HF diets (HS 24% and 36%; HF 38% and 32%, males and females, respectively; P < 0.05). The activity in the cerebral cortex was reduced in males (49 and 40%) and females (19 and 17%) (P < 0.05) on HS and HF diets, respectively. In the hypothalamus AChE activity was decreased on HS diet in males (46%) and female (25%) (P < 0.05) and also on HF diet in males (34%) and females (21%) (P < 0.05). However, in the cerebellum no changes in AChE activity were observed. These results indicate that HS and HF diets produced mainly inhibition in acetylcholine degradation. It probably indicates a chronic alteration induced by these diets on the cholinergic system. A lot of us report effects from choline. A dysregulation of the "choline-carnetine pathway" could be pointed out by the fabulous announcement "Insights into myalgic encephalomyelitis/chronic fatique syndrom phenotypes through comprehensive metabolomics" 2018 (the Lipkin paper) on p.3. A good effect by choline intake could indicate both, to less ACh (which would be helped) and to much ACh (wich would steadily cause a defiency). A bad effect might indicate at least high ACh (which would become even higher). ACh autoantibodies are sometimes found. They might be a counteraction on to much ACh or the cause for to less ACh, Is there any detailed research already? Dr Phair and Fred I think have come up with the idea of a trap. I don´t know if it would be possible here that high ACh then would lead to low ACh which would not be wise to elevate. This might be not to be found out without any doctor. I personally think that ACh would be to high, and that an influence from the immunesystem on ACh exists (iNOS), beside a possible influence from ACh on the immunesystem (eg hypothalamus). It might be a circuit. Maybe it´s a significiant influence on our disease on the long run?