Dysregulated Provision of Oxidisable Substrates to the Mitochondria in ME/CFS Lymphoblasts, 2021, Missailidis et al

I'm curious about how anyone would find out they were sensitive to proline, since it is an amino acid prevalent in a wide range of foods.

 

What do you mean by "sensitive to proline", sensitive to the amount we get from a regular diet or some supplement?

 

Glutamine and glutamate can be drastically altered by dietary changes in otherwise healthy humans (I've seen around 1.5 fold increase in glutamine, with a similar reduction in glutamate, by changing diet alone), and reduced glutamine with increased glutamate is seen in many conditions.

 

@DMissa, nice to see another paper out. What is up next for you and the team? Do you have funding?

 

A really nice background - it can be hard to get it right, but this one nails it, I think.
Background

Page 3 typo

 

A bloodsample. In this case, it was a change from a "standard" diet to a diet following that country's specific dietary guidelines (these are pretty much the same all over the world: increase intake of whole foods, fiber-rich foods such as fruits/vegetables/legumes/grains, eat high quality protein and fats). But as I said, this was otherwise healthy humans, it might be different once someone has a disease. The reason for the change glutamine/glutamate values may also be different.

But I feel better...

Diet as a treatment in other disease is also for the most part in the "science is not there yet", except in the cases of nutrient deficiency diseases and celiac disease. There are cool results for inflammatory bowel disease, where certain dietary approaches can induce remission of inflammation in the gut, but I guess that's about it. Or, low-FODMAP or IBS might be included here, even if there are some questions about how it works.

There's impairment of the integrity of the intestinal wall ("leaky gut") and changes in gut microbiome composition in several diseases, and we know certain foods/dietary approaches (and other lifestyle approaches) that can improve things, but if that influences the state of the disease is more uncertain. In the case of the gut microbiome we don't know what the ideal microbiome should look like for anyone. That said, for any disease not meeting your nutrient requirements is an unnecessary strain on your body that has enough to deal with already.

Edit: Forgot inborn errors of metabolism.

 

So, if those differences are there between ME/CFS and controls, in both non-immortalised PBMCs and lymphoblasts, what does that tell us about what is causing the differences? The lymphoblasts will have been frozen, and presumably washed, and cultured, and treated with the EBV, umm, treatment that immortalises them. And presumably new cells are being made by the lymphoblasts, with the new cells also showing the differences. So, what is perpetuating the difference from controls, in the lymphocytes taken from the patients all the way through to new generations of lymphoblast cells?

Is it epigenetic changes? Could it be bits of virus?
(Sorry, I've run out of energy, so haven't read much of the last bit of the paper.)

There are quite big differences between patient lymphoblasts and control lymphoblasts in gender (88% female vs 45% female) and age (53 years vs 30 years). No significant effect of age or gender was found, but it's less than ideal. I guess Covid may have made blood collection difficult in 2020 - but perhaps Emerge could help with control recruitment, to try to get better matched control samples going forward?