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Serum folate

Updated 15/12/2022

What is measured?

Synonym: s-Folate.
Biologically active folate species in serum/plasma. The prevailing folate form in serum/plasma is 5-methyltetrahydrofolate.
Method(s): Microbiological assay, using a chloramphenicol-resistant strain of Lactobacillus casei (1). The assay has been adapted to a microtiter plate format and is carried out by a robotic workstation. Notably, samples containing antibiotic(s) that inhibit(s) the growth of Lactobacillus casei may cause assay interference.

Indication(s)

Assessment of folate status (2).

Specimen, collection and processing

Patient/subject: Serum folate increases after at folate rich meal, and the concentration reflects (in contrast to erythrocyte folate) short-term folate status. Some antibiotics may inhibit growth of Lactobacillus casei, and may cause artificial, low folate levels.
Matrix: Serum is preferred. Folate is one of few biomarkers that degrade faster in EDTA plasma than in serum.
Volume: Minimum volume is 100 µL, but 250 µL is optimal and allows reanalysis.
Preparation: The serum concentration of mTHF increases markedly in hemolytic samples, which is explained by release of high amounts of cellular folate into the serum/plasma fraction. Optimal procedure for sample handling involves addition of ascorbic acid and rapid freezing at -80 °C.

Transportation

Frozen, on dry ice. (for general instruction on transportation, click here.)

Reported values

Reported values: > 7.5 nmol/L.
Intraclass correlation coefficient (ICC): 0.56.

Literature

1. Molloy, A.M., and Scott, J.M. (1997). Microbiological assay for serum, plasma, and red cell folate using cryopreserved, microtiter plate method. Methods Enzymol 281, 43-53.
2. Bailey, L.B., Stover, P.J., McNulty, H., Fenech, M.F., Gregory, J.F., Mills, J.L., Pfeiffer, C.M., Fazili, Z., Zhang, M., Ueland, P.M., et al. (2015). Biomarkers of nutrition for development-folate review. J Nutr 145, 1636S-680S.

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Amino acids, amino acid catabolites, acylcarnitines, TCA metabolites, ketone bodies, AGEs

Kynurenines, proteins, ratio-derived metabolites



SCFAs, indoles, choline metabolites, amino acid derived



B-vitamins, functional markers, and methyl donors, fat-soluble vitamins, essential amino acids, meat & fish intake, tobacco use & coffee intake
Biomarkers
65
18
20
41
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Amino acids: Alanine, Arginine, Asparagine, Aspartic acid, Glutamic acid, Glutamine, Glycine, Histidine, Isoleucine, Kynurenine, Leucine, Lysine, Methionine, Ornithine, Phenylalanine, Proline, Sarcosine, Serine, Threonine, Total cysteine, Tryptophan, Tyrosine, Valine

Amino acids and catabolites: 2-Aminoadipic acid, 2-Hydroxybutyrate, 3-Hydroxysiobutyrate, α-Hydroxyglutaric acid, β-Alanine, β-Aminoisobutyrate, β-Hydroxy B-methylbutyric acid, Phenylacetylglutamine

Acylcarnities: BB, C0, C2, C3, C3, DC, C4, C4-OH , C4-DC , iC5 , C5-DC, C5:1 , C6 , C8, C10, C12, C14 , C14-OH, C16, C16-OH, C18 , C18-OH, C18:1, C18:2

TCA metabolites: α-Ketoglutarate, Citrate, Fumarate, Isocitrate, Lactate, Malate, Pyruvate, Ketone bodies, 3-Hydroxybutyrate, Acetoacetate

AGEs: Carboxyethyllysine, Carboxymethyllysine

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Kynurenines: Kynurenine, Kynurenic acid, Quinaldic acid, Anthranilic acid, 3-Hydroxykynurenine, Xanthurenic acid, 3-Hydroxyanthranilic acid, Picolinic acid, Quinolinic acid, Nicotinic acid, Nicotinamide, N1-methylnicotinamide

Neopterin

Proteins: C-Reactive protein, Calprotectin, Serum Amyloid A

Ratio-derived: Kynurenine/tryptophan ratio, PAr index (PLP, PL, PA)

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SCFAs: Acetate, Butyrate, Formate, Isobutyrate, Isovalerate, Propionate, Valerate, α-Methylbutyrate

Indoles: 3-Indoxyl sulfate, Imidazole propionate, Indole-3-acetamide, Indole-3-acetate, Indole-3-aldehyde, Indole-3-lactate, Indole-3-propionate

Choline metabolites: Choline ,Betaine, DMG, TMAO

Amino acid derived: Phenylacetylglutamine

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B-vitamins, functional markers, and methyl donors: 4-Pyridoxic acid, Betaine, Choline, Cobalamin, Flavin mononucleotide, Folate, Methylmalonic acid, N1-methylnicotinamide, Nicotinamide, Nicotinic acid, Pyridoxal, Pyridoxal 5-phosphate, Pyridoxine, Riboflavin, Thiamine, Thiamine monophosphate, Total homocysteine

Fat-soluble vitamins: 25-hydroxy vitamin D2, 25-hydroxy vitamin D3, α-Tocopherol (Vit. E), All-trans retinol (Vit. A), Phylloquinone (Vit. K1), y-Tocopherol (Vit. E)

Essential amino acids: Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine

Meat and fish intake: 1-Methylhistidine, 3-Methylhistidine, B-Alanine, Creatine, Creatinine, TMAO

Tobacco use and coffee intake: Cotinine, Trans-3-hydroxycotinine, Trigonelline

Volume (ul)
150
100
200
200
Analytical technique
GC- and LC-MS/MS
LC- and MALDI-MS
GC- and LC-MS/MS
GC- and LC-MS/MS
Turnaround time (weeks)
1
1
1
1

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