Arabinitol: Why It Is More Reliable Than Arabinose for Identifying Yeast Overgrowth

Biomarkers for Yeast Overgrowth

Many species of fungi live in healthy humans and are considered commensal. The balance of yeast can change due to several factors leading to yeast overgrowth, and in some cases can become invasive. Candida infections are often studied because they can be serious in immunocompromised individuals. C. albicans is one of the few fungal species causing disease in humans. The "gold standard" for the diagnosis of invasive candidiasis has long been positive cultures, though its low sensitivity has led to the development of non-cultural methods.¹ Clinicians have long proposed the need for early identification of yeast/fungi imbalances in populations not necessarily at risk for invasive overgrowth but that could still impact health. Elevations of serum and urinary arabinitol have been used to screen for yeast overgrowth. Early research of arabinitol found that both the serum and urinary arabinitol/creatinine ratios in animals with invasive C. albicans infection rose directly in proportion to total arabinitol appearance and to C. albicans colony counts.^2,3

Siew Fah Yeo, et.al. (2002) concluded that "the excess arabinitol observed in the body fluids in invasive candidiasis was produced by C. albicans and that arabinitol is a quantitative diagnostic marker for invasive candidiasis." ⁴

Arabinitol vs. Arabinose

Though arabinitol and arabinose assessment in urine have been noted as able to identify yeast overgrowth, a recent review of PubMed articles does not support utilizing arabinose. Arabinitol is known to identify yeast overgrowth, while arabinose is a 5-carbon sugar, largely derived from the diet, that yeast can metabolize to arabinitol.^3,5

In an additional 2022 article on the diagnosis and treatment of Candida, the authors reviewed Candida metabolites and again noted that arabinitol and not arabinose was associated with levels of Candida, with the exception of C. krusei and C. Glabrata.⁷ Though some older research noted possible benefits of testing arabinose, newer research and a better understanding of the pathways does not support its use. Much of the early research was based on a case study done almost twenty years ago that was not repeated, had significant conflicts of interest, and has been brought into question by other laboratories and researchers.^6,7,5

Research studies have shown that yeast and fungi produce several metabolites. Arabinose is found in nature as a component of hemicellulose and pectin, and a derivative of dietary fiber. There are two different arabinose utilization pathways in nature: bacterial and fungal. While the bacterial pathway converts arabinose into xylulose-5-P, the fungal pathway converts arabinose into arabinitol. The most efficient native yeast strains produce arabinitol from arabinose. Though arabinitol is primarily produced from arabinose, it can also be produced from glucose and glycerol. Native yeast strains, Candida, and others can biotransform arabinose, glucose, or glycerol into arabinitol.^8,2

Fermentation Production of Arabinitol⁸

From Arabinose:

• Multiple Candida strains (primary metabolizer of arabinose)
• A few Debaryomyces strains (found in mouse guts with Crohn's disease)⁹
• Rhodotorula mucilaginosa (intestinal colonization is rather common)¹⁰

From Glucose:

• Two Pichia strains (common in the human gut)¹¹
• Debaryomyces nepalensis (primarily from rotten fruit)¹²

From Glycerol:

• Debaryomyces hansenii (found in human gut; a rare human fungal pathogen)^13,14
• Two Candida strains
• Hansenula anomala (a possible human fungal pathogen)¹⁵

 

D-Arabinitol vs. L-Arabinitol

Arabinitol, along with mannitol, erythritol, D-threitol, xylitol, galactitol, and sorbitol are polyols (sugar alcohols) that have diverse functions in fungi. Arabinitol comes in two forms, D-arabinitol and L-arabinitol. In addition to endogenous production, arabinitol is used in the food and pharmaceutical industries as a natural sweetener, a dental-caries reducer, and a sugar substitute for diabetic patients due to its low-caloric (only 0.2 kcal g^-1), low-glycemic, low-insulinemic, anticariogenic, and prebiotic effects).^16,17,18 The normal level of D-arabinitol in urine is around 10 μg mL-1, which is significantly higher than serum which is around 0.2 μg mL-1.⁸ The levels of D-arabinitol in serum and urine increases as Candida proliferates and can identify a concern of invasive candidiasis. L-arabinitol is found in nature but not produced by fungus.

Though some research has noted the need to evaluate the ratio of D- and L-arabinitol, it can be difficult to accurately separate which may give false values. It was primarily only developed to account for those with poor kidney function. An evaluation of total urine arabinitol can be used as a screen for possible fungal/candidiasis imbalance or overgrowth. A negative or low arabinitol result can confirm a lack of fungal overgrowth.

Treatment and Testing for (Yeast/Candida) Overgrowth

While A low urine arabinitol can help to rule out candida overgrowth, an elevated value can indicate concern for overgrowth. Depending on the level, clinicians may want to rule out if the patient is using dental caries reducers, sugar substitute or has an elevated glucose value. Treatment recommendations vary depending on other findings such as autoimmune conditions, intake of glucose or glycerol, level of symptoms, as well as other markers such as increased inflammation, poor commensal bacterial status, kidney function or fecal candida findings. Treatment for an elevated urine arabinitol may include supporting good commensal bacteria, probiotics, changes in diet, and further testing.

Urine arabinitol may identify if there is a general yeast imbalance or overgrowth and its level. It does not identify location. Urine arabinitol and fecal fungal rtPCR assessments (GI-MAP) are not expected to correlate at low or moderate overgrowth levels. An elevated arabinitol level identifies a yeast metabolite that could be anywhere within the body, while fecal rtPCR identifies a specific yeast and its quantity within the gastrointestinal tract.^19,20

 

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REFERENCES

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