BEVITAL AS

Targeted Metabolomics Services

Creatine

cr
Updated 06/06/2023

What is creatine?

Creatine plays an essential role in energy storage and transmission. It is synthesized by arginine:glycine amidinotransferase, which forms guanidinoacetate, which in turn undergoes methylation, catalyzed by S-adenosyl-L-methionine:N-guanidinoacetate methyltransferase, forming creatine. Creatine in plasma/serum is a biochemical marker of primary and secondary creatine defects. The reason for the inclusion of creatine into the analytical repertoire of BEVITAL is a marked decrease in plasma level (up to 40 %) in vitamin B6-deficient subjects (2).
Method: LC-MS/MS.

Indication(s)

Detection of primary and secondary creatine defects. Assessment of vitamin B6 status?

Specimen, collection and processing

Patient/subject: Creatine concentration is increased in subjects taking creatine supplements.
Matrix: EDTA plasma and serum.
Volume: Minimum volume is 50 µL, but 200 µL is optimal and allows reanalysis.
Preparation: The blood sample must be centrifuged and the plasma/serum fraction put on ice, and frozen.

Transportation

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

Reported values, interpretation

Reported values: Creatine in plasma/serum decreases with age, as described in a recent article. Median (2.5th -97.5th percentile) is 60 (16-97) µmol/L at the age of 0-12 years, 48 (14-92) at the age of 13-20 years and 31 (13-57) at the age > 20 years.

Literature

1. Midttun, O., Kvalheim, G., and Ueland, P.M. (2013). High-throughput, low-volume, multianalyte quantification of plasma metabolites related to one-carbon metabolism using HPLC-MS/MS. Anal Bioanal Chem 405, 2009-017.
2. da Silva, V.R., Rios-Avila, L., Lamers, Y., Ralat, M.A., Midttun, O., Quinlivan, E.P., Garrett, T.J., Coats, B., Shankar, M.N., et al. (2013). Metabolite profile analysis reveals functional effects of 28-day vitamin B-6 restriction on one-carbon metabolism and tryptophan catabolic pathways in healthy men and women. J Nutr 143, 1719-727.

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Biomarkers included

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
  • a-Hydroxyglutaric acid
  • B-Alanine
  • B-Aminoisobutyrate
  • B-Hydroxy B-methylbutyric acid
  • Phenylacetylglutamine

Acylcarnities

  • BB Butyrobetaine
  • C0 Carnitine
  • C2 Acetylcarnitine
  • C3 Propionylcarnitine
  • C3-DC Malonylcarnitine
  • C4 Butyrylcarnitine
  • C4-OH Hydroxybutyrylcarnitine
  • C4-DC Succinylcarnitine
  • iC5 Isovalerylcarnitine
  • C5-DC Glutarylcarnitine
  • C5:1 Tiglylcarnitine
  • C6 Hexanoylcarnitine
  • C8 Octanoylcarnitine
  • C10 Decanoylcarnitine
  • C12 Dodecanoylcarnitine
  • C14 Tetradecanoylcarnitine
  • C14-OH Hydroxytetradecanoylcarnitine
  • C16 Hexadecanoylcarnitine
  • C16-OH Hydroxyhexadecanoylcarnitine
  • C18 Octadecanoylcarnitine
  • C18-OH Hydroxyoctadecanoylcarnitine
  • C18:1 Octadecenoylcarnitine
  • C18:2 Octadecadienylcarnitine

TCA metabolites

  • a-Ketoglutarate
  • Citrate
  • Fumarate
  • Isocitrate
  • Lactate
  • Malate
  • Pyruvate

Ketone bodies

  • 3-Hydroxybutyrate
  • Acetoacetate

AGEs

Biomarkers included

SCFAs

  • Acetate
  • Butyrate
  • Formate
  • Isobutyrate
  • Isovalerate
  • Propionate
  • Valerate
  • α-Methylbutyrate

Proteins

  • C-Reactive protein
  • Calprotectin
  • Serum Amyloid A

Others

  • Kynurenine/tryptophan ratio
  • Neopterin
  • PAr index (PLP, PL, PA)
Biomarkers included

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
Biomarkers included

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

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