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Myalgic Encephalomyelitis, ME, aka Chronic Fatigue Syndrome, CFS

A client of mine asked me about research connections to Vitamin A toxicity on this topic.  There isn't anything directly connecting the two, so I'm going to lay out the trail of research here for you to follow.

Chronic fatigue syndrome.  Let's focus on the word "fatigue" for a second, and don't forget the "chronic"!.

Chronic Hypervitaminosis A in an Adult

Fatigue, musculoskeletal symptoms, skin changes, anorexia, weight loss, and hepatomegaly are the major manifestations of chronic hypervitaminosis A.

Already it looks like we're onto something here!

Now let's head into Myalgic Encephalomyelitis.  First, "myalgic".  Myalgia means pain in a muscle or group of muscles.  Myalgia is an effect of Vitamin A toxicity, and goes along with "musculoskeletal symptoms" from the paper already quoted above.

In addition, oral isotretinoin has reportedly been associated with muscular adverse effects that most frequently manifest as myalgia and stiffness and, in rare cases, as true myopathy or rhabdomyolysis.

Next, encephalomyelitis.  Encephalomyelitis means inflammation of the brain and spinal cord.  Let's break this into encephalitis (inflammation of the brain) and myelitis (inflammation of the spinal cord).

Regarding encephalitis, Vitamin A toxicity has been documented to cause it:


Regarding myelitis, Vitamin A toxicity has been documented to cause impaired myelination in rats, which could look to researchers like myelin was being "destroyed" when in actuality it simply wasn't being formed (the end product is the same, a lack of myelin sheath):

Impaired Myelination in rats given excess vitamin A postnatally.

Let's do some more associating.

There is hypothalamic-pituitary-adrenal hypofunction (low function, or underfunction) in ME/CFS:

Hypothalamic-pituitary-adrenal hypofunction in Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) as a consequence of activated immune-inflammatory and oxidative and nitrosative pathways.

There is evidence that immune-inflammatory and oxidative and nitrosative stress (O&NS) pathways play a role in the pathophysiology of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). There is also evidence that these neuroimmune diseases are accompanied by hypothalamic-pituitary-adrenal (HPA) axis hypoactivity as indicated by lowered baseline glucocorticoid levels. 

So from the above paper, ME/CFS is associated with a lowered, or hypofunctioning, HPA axis. What about if HPA function was directly impacted in rat studies by retinol levels (Poison/"Vitamin A")?

Vitamin A regulates hypothalamic–pituitary–adrenal axis status in LOU/C rats

The aim of this study was to explore the involvement of retinoids in the hypoactivity and hyporeactivity to stress of the hypothalamic–pituitary–adrenal (HPA) axis in LOU/C rats.
Interestingly, under control conditions, we measured a higher plasma concentration of retinol in LOU/C than in Wistar rats, which could contribute to the lower basal activity of the HPA axis in LOU/C rats. Vitamin A deficiency induced an increased HPA axis activity in LOU/C rats, normalized by RA administration.
The high vitamin A status of LOU/C rats could contribute to their low HPA axis activity/reactivity and to a protective effect against 11β-HSD1-mediated deleterious action on cognitive performances during ageing.

Higher blood retinol aka Poison/"Vitamin A" was associated with lower HPA activity.  Low HPA activity is associated with ME/CFS.  Note that a "Vitamin A deficiency" INCREASED the HPA activity, which is exactly what would help an ME/CFS person!

You want a mechanism?  How about mitochondria?  Here we go:

Mitochondrial dysfunctions in Myalgic Encephalomyelitis/chronic fatigue syndrome explained by activated immuno-inflammatory, oxidative and nitrosative stress pathways

Does Vitamin A toxicity cause mitochondrial problems/dysfunctions/TOXICITY? Yes.

Vitamin A and Retinoids as Mitochondrial Toxicants

If it looks like a duck, swims like a duck, and quacks like a duck, then it probably is a duck. If Vitamin A toxicity has been shown to cause every single issue that a disease is named for, there's probably massive Vitamin A toxicity going on as the CAUSE of that disease.


Dr. Garrett Smith, the "Nutrition Detective"
Licensed Naturopathic Physician (NMD) in Arizona
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