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Biotin Deficiency : Impairs Heme Synthesis, Loss of Function Of Mitochondrial Complex IV and The Electron Transport Chain, and Triggered Oxidative Damage .......Links To Candida

This article is not medical advice. Before starting any health related regimen, seek the advice of your Primary Care Physician, or an M.D.


Heme is fundamental in many of the body's basic systems. (See earlier blog articles on the Heme Pathway / Porphyria):

  • Hemoglobin

  • Glutathione Peroxidase Enzymes GPX1-8

  • Catalase

  • CYP 450 Enzymes

  • Synthesis of Tryptophan and thus NAD

  • Processing of sulfur

  • and many more


It is common place that i see low biotin status in cases where candida levels are elevated. Its common in typical american diets, common in immune compromise and common in folks on ketogenic diets (candida can use ketones for fuel). In fact the most severe cases of candida i have seen have been with folks who have been on ketogenic diets for some significant time. Candida will deplete both biotin and b5 (pantothenic acid). But before i go into details with how candida effects the body overall, some details on biotin and heme:


Biotin's Connection To Heme:

"Four of the 5 biotin-dependent carboxylases (BDC) are in the mitochondria. BDC replace intermediates in the Krebs [tricarboxylic acid (TCA)] cycle that are regularly removed for the synthesis of key metabolites such as heme or amino acids. Heme, unlike amino acids, is not recycled to regenerate these intermediates, is not utilized from the diet, and must be synthesized in situ. We studied whether biotin deficiency (BD) lowers heme synthesis and whether mitochondria would be disrupted. Biotin-deficient medium was prepared by using bovine serum stripped of biotin with charcoal/dextran or avidin. Biotin-deficient primary human lung fibroblasts (IMR90) lost their BDC and senesced before biotin-sufficient cells. BD caused heme deficiency; there was a decrease in heme content and heme synthesis, and biotin-deficient cells selectively lost mitochondrial complex IV, which contains heme-a. Loss of complex IV, which is part of the electron transport chain, triggered oxidant release and oxidative damage, hallmarks of heme deficiency. Restoring biotin to the biotin-deficient medium prevented the above changes. Old cells were more susceptible to biotin shortage than young cells. These findings highlight the biochemical connection among biotin, heme, and iron metabolism, and the mitochondria, due to the role of biotin in maintaining the biochemical integrity of the TCA cycle. The findings are discussed in relation to aging and birth defects in humans."[1]


Candida interferes with the MTHFR, NAD, catecholamine, and aldehyde pathways.  Aldehydes produced by candida slow down MTHFR-related pathways like glutathione and methionine synthase. The processing of aldehydes deplete NAD, consume B2 (needed for so many things like recycling glutathione, clearing histamine, etc), and consume molybdenum (needed to process sulfur).   As NAD levels drop we lose tryptophan to make serotonin and melatonin because the body tries to make more NAD from tryptophan.  Depression can result from low serotonin.  Low NAD will cause significant fatigue. Sulfur sensitivity, high oxidative stress (low glutathione), and impaired methylation (build up of histamine) can all result.


Have you ever wondered why getting really stressed out leaves you feeling drained, foggy and out of touch like you have been drinking?  Excess stress can raise catecholamines (dopamine) by-products that turn into alcohol in our brains. If this is not cleared (and they require vitamins like B3 and others to properly detoxify) then the neurons become damaged.  This leads to neural degeneration effects.


The ALR (aldehyde reductase), ALDH (aldehyde dehydrogenase) and ADH (alcohol dehydrogenase) enzymes are all necessary to detoxify and get rid of excessive stress chemicals like dopamine, norepinephrine and epinephrine. High levels of candida can overload these detoxification genes trying to deal with the alcohol and aldehydes from the gut and result in a buildup of toxic stress chemicals from catecholamines in the brain. This will amplify the effects of stress and can lead to – anxiety, insomnia, chronic pain, brain fog, memory issues, depression, etc. Histamine is also detoxified through the aldehyde system as well as the MTHFR related pathways. As MTHFR pathways get overloaded you can see why these folks have histamine intolerance issues, energy deficits, and other GI related issues. It is common in folks with candida issues, to have high dopamine (high stress), food / histamine intolerance symptoms. The presence of Yeast in the GI tract diverts pyruvate away from its preferred metabolic pathway (Krebs cycle), which can also lead to fatigue.


High aldehydes can also deplete B5 (pantethene - preferred form), B5 is needed for the NAT2 gene - which supports acetylation of fatty acids, and detoxification. B5 is also needed for the production of cortisol which helps manage PLA2/ Arachadonic Acid (into the ALOX12 pathway / ALOX5 pathway), and also is involved in gut motility. Further - mutations in SLC5A6 - the multivitamin sodium dependent transporter for (ALA, B7, B5) can further compromise both B7 status (candida consumes B7), as well as B5 status. So, here we see that high levels of candida deplete b5, which is needed to process fats (think keto diets) and to produce cortisol which is needed inhibit platelet activation (PLA2) also known as micro clotting. Micro clotting results in low blood oxygen levels = fatigue, and cognitive impairment.


B5 can also get depleted in high phenol diets (think berries, coffees/teas, and herbs) - so folks who enjoy significant amounts of fruit, teas, coffees may want to consider testing as well.


And finally, for those who have read my earlier Heme / Porphyria blog articles, you may recall how anti fungals inhibit the heme cycle - its how they are designed to work - to stop the heme cycle in fungus. Well, for those of you who are eating lots of non organic fruits - you are exposed to another level of heme cycle inhibition through the anti fungal herbicides on these fruits - which are generously loaded on fruits like Strawberries.


The cascade of symptoms and issues from candida overgrowth can be significant as shown above. The simplest markers to monitor candida are on Organic Acids Tests, which are urine based and can be ordered consumer direct from places like MyMedLab or MyLabsForLife. Functional B5, B2 and B7 status markers are also on the Organic Acids test, although these are far from perfect.


References

  1. Biotin Deficiency Inhibits Heme Synthesis and Impairs Mitochondria in Human Lung Fibroblasts. By Atamna Hani, Newberry Justin, et. al. The Journal of Nutrition Volume 137, Issue 1, January 2007, Pages 25-30. https://doi.org/10.1093/jn/137.1.25


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I find your blog interesting, but stating hypothesis as fact undermines your efforts. For example, you state "Depression can result from low serotonin."


The serotonin hypothesis was categorically refuted with the 2022 publication "The serotonin theory of depression: a systematic umbrella review of the evidence." (Moncrieff, J., Cooper, R.E., Stockmann, T. et al. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01661-0).


They state, "Our comprehensive review of the major strands of research on serotonin shows there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity. Most studies found no evidence of reduced serotonin activity in people with depression compared to people without, and methods…


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