Why some people with ME/CFS react more strongly to medications

[Kitty]

I think my reactions are fairly normal. Many things are okay-ish and a few really aren't.

Worst reactions were to methotrexate (taken off it due to toxicity) and antidepressants (which used to be prescribed to people with no depressive symptoms in the hope of improving ME/CFS).

The only unusual one is severe alcohol intolerance. It makes me feel so awful so quickly that I'm not sure I've ever drunk enough to be over the limit for driving. Definitely never achieved a hangover.

 

[Turtle]

There have been several metabolomics studies where glucose was detectable—one or two found just slightly higher glucose compared to controls (still well below even pre-diabetes range, iirc), and several other studies did not replicate this.

If anything it might be a comorbidity that comes up sometimes, but not a robust feature of ME/CFS. After some googling I’m not seeing anything to suggest insulin resistance would be relevant to alcohol or drug intolerance anyways, more likely the other way round where higher alcohol intake could be a risk factor for developing insulin resistance

The Beentjes 2025 paper does mention insuline resistance several times.

 

[NelliePledge]

Some medications we get prescribed have common side effects eg I’ve posted before about pregabalin, I found it very sedating but it also gave me internal tremor which was so scary I stopped taking it. Some years later chatting with a sibling who doesn’t have ME but had also been prescribed pregabalin for pain I discovered they had also experienced scary tremor and stopped taking the medication. Tremor is listed on the information sheet as a common side effect.

 

[jnmaciuch]

The Beentjes 2025 paper does mention insuline resistance several times.

Yup it's mentioned as a speculation for slightly elevated blood glucose, not as proof of insulin resistance. The armstrong (2015) paper and the same groups re-analysis of the same UK biobank data also found slightly elevated blood glucose compared to HC. In all cases the fold change is less than what you would expect for random glucose measurements between control and even pre-diabetic insulin resistance. In contrast, Hanson and naviaux studies did not report glucose as a significant finding. The Fluge/mella/tronstad study showed normal average random glucose. So where abnormal glucose was found it was only weakly elevated, and it did not replicate.

Random glucose levels would not completely rule out insulin resistance on the individual level. But to consider it an important feature in ME/CFS we would need reason to rule it in, which we don't have for ME/CFS as a whole (either from metabolomics studies, or clinical symptoms, or other routine lab tests that have been checked in many studies).

 

[Amw66]

They’re pretty multi-purpose enzymes used in a bunch of endogenous processes like steroid synthesis. It’s mostly that they handle several fundamental chemical conversions for compounds that traffic through the liver (which ends up including a lot of things in the circulation) and those conversions also happen to be very important in drug metabolism

Hydrocortisone ( oral) and cocodamol wreak havoc.
Drugs / products with synthetic vit E cause issues ( it has a distinctly different molecular shape )
It may be the " getting rid of" aspect that is the issue .

 

[mariovitali]

I went through the thread quickly and just wanted to share that one of the things I found during analysing my symptoms and interventions through machine learning, one of the key factors appeared to be P450 inhibitors.

With regard to foods, for instance, the machine learning analysis suggested that a fat-free diet, whey protein, iron-rich, and foods containing gluten were problematic while zinc-rich and cholesterol-rich foods were helpful. Weather changes were also clearly affecting me and any abrupt weather changes (e.g. increase in humidity, drop in temperature) would increase my symptoms.

Another finding was that substances that were negatively affecting the cytochrome P450 system – which is related to the liver – such as bioperine and grapefruit would greatly induce my symptoms.

The results suggested that the following supplements might be helpful: Any supplement providing methyl groups such as methylcobalamin, MSM, 5-methyltetrahydrofolate, and Zinc.

Source : https://www.healthrising.org/blog/2023/10/02/efthymios-artificial-intelligence-chronic-fatigue-syndrome-recovery/