Fatigue — candidate cause: Hypoxia

This is a summary of items that may be the cause. This assumes that a lack of oxygen getting to tissue (or the brain) is the cause. Note that if the brain is tired(oxygen starved), that there may be false signals saying the body is exhausted because the brain does not have the energy to manage the body. The sources are typically from Chronic Fatigue Syndrome. Some of these may be related to the microbiome (lack of studies). It is suspected that many people are borderline (have no apparent issues) and then some event pushes them over the edge into fatigue.

This is intended as a checklist to review with your medical professional. Items should be objectively excluded by actual tests and not subjectively excluded (often a response if the professional does not know how to test). See Hypoxia[2022] and Hypoxia (medical)

Coagulation Issues

The typical scenario seems to be an inherited or acquired (epigenetic — sometimes from a virus infection) coagulation defect. Some step of the coagulation cascade gets “constipated” with the result being what is often called “sticky blood”. It only takes one step.

If the blood gets thick, it gets slow and hence less oxygen gets to the body and the brain.

Most “blood thinners” only impacts one of these steps (with heparin being the main exception). Taking excessive supplements that impacts the same step may result in long bleeding time or easy bruising.

Note: We are talking about sub-clinical (i.e. not having a stroke or blood clot) levels. The lab levels may not be abnormal, just low (or high).

Low Iron Or Impaired Heme

Hemoglobin is the iron-containing oxygen-transportmetalloprotein in the red blood cells of all vertebrates  Hemoglobin in the blood carries oxygen from the respiratory organs (lungs or gills) to the rest of the body (i.e. the tissues). There it releases the oxygen to permit aerobic respiration to provide energy to power the functions of the organism in the process called metabolism. [wikipedia]. Hemogloblin can be inhibited by some chemicals (Carbon Monoxide [2022] and the pH of the blood (Bohr effect [2021]) are the most common. pH is influenced by the microbiome.

Iron insufficiency and hypovitaminosis D in adolescents with chronic fatigue and orthostatic intolerance. Restless leg syndrome (RLS) is  negatively correlated with ferritin / iron [2012] and RLS is also co-morbid with CFS (i.e. the less iron, the more likely you will have RLS).

For example, Staphylococcus aureus is known to adversely impact iron [2022]

Malformed Red Blood Cells

Back in 1997, Dr. Les Simpson in New Zealand wrote “Myalgic Encephalomyelitis (ME): A Haemorheological Disorder Manifested as Impaired Capillary Blood Flow” observed this in CFS patients. “So it has been proposed – first at the Cambridge Symposium on ME in 1990 and in another article in 1998, that ME is a dysfunctional state resulting from reduced rates of capillary blood flow due to the presence of shape-changed, poorly-deformable red cells” [source]

It should be noted that SPECT scans show the expected effects of shape-
changed, poorly deformable red cells in reducing cerebral blood flow in
regions which by chance have smaller than usual capillaries.

TheBMJ, Chronic fatigue syndrome or myalgic encephalomyelitis [2007]

Inflammatory hypoxia

Hypoxia and inflammation are frequently co-incidental microenvironmental features of sites of concentrated physiological or pathological immune activity.

Hypoxia activates hypoxia-inducible factor, which is a major regulator of multiple aspects of immune cell function. Consequently, hypoxia plays a key role in the regulation of immunity and inflammation.

The impact of hypoxia on immunity and inflammation is site-specific and cell type-specific.

Pharmacological hydroxylase inhibition, which activates hypoxia-sensitive pathways, is profoundly protective in multiple models of inflammation.

Regulation of immunity and inflammation by hypoxia in immunological niches [2017]

Low Blood Volume

David Bell, M.D. did a study in 1995 (twenty years ago) finding about low blood volume. Cort Johnson has an 2015 update by Dr. Bell that is worth reading. “In contrast, ME patients have a volume that can be as low as 50% of normal.”

Small Heart Size

“A considerable number of CFS patients have a small heart. Small heart syndrome may contribute to the development of CFS as a constitutional factor predisposing to fatigue, and may be included in the genesis of CFS.” [2008]

” Echocardiographic examination revealed that CFS patients with “small heart” had an actually small LV chamber and poor cardiac performance. Cardiac functional changes evaluated by repeated examinations appeared to be directly associated with the severity of their symptoms. Small heart syndrome with impaired cardiac function may contribute to the development of CFS through low cardiac output as a constitutional factor.” [2009]

Enzymes and thus Microbiome

“We’ve discovered that the muscles regulate oxygen consumption in a very precise way using the oxygen-sensitive enzyme FIH,”

How muscles regulate their oxygen consumption [2018]

” cytochrome P450 (CYP), monoamine oxygenase (MAO), and cyclooxygenase (COX). CYP enzymes are central players.. are important for therapeutic intervention and treatment of neurological and inflammatory diseases”

Analysis of activity and inhibition of oxygen-dependent enzymes by optical respirometry on the LightCycler system [2010]

Obstructive Sleep Apnea

Note that blood platelets activation is part of the coagulation cascade above.

Snoring, collapse of upper airways and intermittent hypoxia are main causes of smoldering systemic inflammation in patients suffering from obstructive sleep apnea. The systematic inflammation is considered one of the key mechanisms leading to significant cardiovascular complications. Blood platelets, formerly not even recognized as cells, are currently gaining attention as crucial players in the immune continuum. Platelet surface is endowed with receptors characteristic for cells classically belonging to the immune system, which enables them to recognize pathogens, immune complexes, and interact in a homo- and heterotypic aggregates.

Obstructive Sleep Apnea: From Intermittent Hypoxia to Cardiovascular Complications via Blood Platelets [2018]

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