Acetaldehyde Subhypothesis

Acetaldehyde Subhypothesis

The acetaldehyde subhypothesis suggests that acetaldehyde, a byproduct of sugar fermentation by Candida albicans (Marttila et al. 2013; Reddy, Kakodkar, and Nayanar 2022), plays a crucial role in inducing various symptoms, including brain fog and fatigue. These effects include neurotoxicity and mitochondrial dysfunction (Yan et al. 2022). Acetaldehyde is produced endogenously by Candida albicans in the gut rather than being ingested directly as alcohol.

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Mechanisms of Action

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Acetaldehyde is highly reactive and has been linked to the impairment of brain function (Correa et al. 2012). It induces neurotoxicity through mechanisms involving excessive Drp1 phosphorylation and mitochondrial fragmentation, mediated by ROS and Ca2+-dependent signaling pathways (Yan et al. 2022).

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Acetaldehyde exerts its harmful effects via multiple mechanisms (Yan and Zhao 2020; Yan et al. 2022). It elevates reactive oxygen species (ROS) levels, leading to cellular damage and activation of stress response pathways. Additionally, acetaldehyde induces mitochondrial damage, promoting mitophagy and reducing mitochondrial mass, which results in energy deficits in cells. Furthermore, acetaldehyde can alter gene expression through oxidative stress and other pathways, contributing to neurodegeneration.

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Role of Candidalysin

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Recent research has highlighted the damaging effects of candidalysin (Moyes et al. 2016; Ho et al. 2021), a peptide toxin secreted by Candida albicans, on the integrity of the intestinal barrier (Allert et al. 2018). Candidalysin plays a crucial role in compromising the intestinal epithelial cells, leading to the condition often referred to as leaky gut (Christovich and Luo 2022). This increased intestinal permeability allows a variety of substances, including toxins and microbial byproducts, to pass through the intestinal wall and enter the bloodstream. Among these substances is acetaldehyde, a toxic byproduct produced during the fermentation of sugars by Candida albicans. The presence of acetaldehyde in the bloodstream can lead to broader systemic effects, contributing to inflammation and a range of neurological and metabolic issues (Correa et al. 2012).

Neurological and Systemic Symptoms

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Acetaldehyde, being neuroactive (Correa et al. 2012; Hunt 1996), is hypothesized to contribute to fatigue and brain fog observed in various syndromes, similar to the aftereffects of alcohol consumption. This is consistent with the auto-brewery syndrome (Dinis-Oliveira 2021; Malik et al. 2019), where individuals suffering from this condition exhibit neurological symptoms due to the fermentation byproducts of Candida albicans accumulating in their bloodstream. This aligns with the hypothesis that the byproducts of Candida albicans fermentation, including acetaldehyde, can induce significant neurological symptoms.

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