BEVITAL AS

Highlights

The analytical repertoire of BEVITAL is composed of methods based on cutting edge analytical technology. Most assays are developed by scientists and technicians with more than 20 years experience in gass-liquid chromatography and/or mass spectrometry. One dedicated scientist is responsible for each platform, its upgrade, performance and ruggedness.

Loss of analytical precision with non-matching internal standards

BEVITAL employs a strategy of using a dedicated (matching) internal standard for most analytes (only a few exceptions apply). Recently, we quantitated the consequences of substituting matching with non-matching internal standards on analytical precision. The use of non-matching internal standards, as used by some laboratories, may result in lower precision leading to wider confidence intervals in statistical analyses, so that biological important associations may escape detection.

Extensive upgrade of platforms

Metabolites have been added to platforms A (TCA metabolites and intermediates, short-chain fatty acids (SCFAs)), platform B (beta-alanine), platform C (short-chain carnitines), platform D (imidazole propionate and microbiota-derived indoles) and platform H (long-chain carnitines).

A novel functional marker of vitamin B6 status

By combining five metabolites in the kynurenine pathway into a simple index, HKr, a sensitive and specific indicator of intracellular vitamin B6 status is obtained. The index also underscores the merit of evaluating alterations in kynurenine metabolism when investigating vitamin B6 and health.

Stability curves

Data on the stability during storage and freezing/thawing of most biomarkers or metabolites included in the repertoire of BEVITAL by April 2019 is now available.

Inflammation markers, cystatin C and its proteoforms in 20 µL of sample

A new method (platform G) for the combined quantification of C-reactive protein (CRP), serum amyloid A (SAA), and calprotectin (S100A8/9) and the kidney function marker, cystatin C (CysC), and a number of proteoforms (11 for SAA, 4 for S100A8/9 and 4 for CysC) has been developed at BEVITAL. The method is characterized by low sample consumption, high capacity, and high precision, and has been designed for the assessment of biomarker status in precious samples from large biobanks.

Saving biobank material by combining platforms

A procedure involving combined sample workup for platforms B and H enabling quantification of 6 lipid-soluble and 26 water soluble biomarkers in 50 µL serum/plasma has been established. The method utilizes liquid-liquid extraction of the lipid soluble vitamins and further processing of the aqueous phase through the steps established for platform B.

Two review articles on vitamin B6 biomarkers

A review on vitamin B6 biomarkers has been published in Annual Review of Nutrition. It deals with both direct vitamin B6 biomarkers that measure B6 vitamers in plasma, serum and urine and functional biomarkers reflecting enzymatic or metabolic functions of vitamin B6, including novel markers like the PAr index and the HK:XA ratio. Another review on inflammation, vitamin B6 and related pathways has recently been published in Molecular Aspects of Medicine. Both articles are co-authored by scientists at BEVITAL.

Recovery of degraded biomarkers

The combined measurements of the degradation product and parent compound may correct for moderate biomarker decomposition. Such recovery assays have been validated and published for the conversion pyridoxal 5′-phosphate (PLP) to pyridoxal (PL), flavin mononucleotide (FMN) to riboflavin, for the oxidation of methionine to methionine sulfoxide and for the oxidation of 5-methyltetrahydrofolate to 4-alfa-hydroxy-5-methyltetrahydrofolate (hmTHF). In samples where folate has been extensively degraded beyond hmTHF, folate can be measured as p-aminobenzoylglutamate (pABG) equivalents by an assay involving oxidation and mild acid hydrolysis.

Vitamin and biomarker status across countries and continents

Biomarkers that are related to vitamin status, nutrition, inflammation and lifestyle have been measured in subjects from 20 cohorts recruited from the United States, Nordic countries, Asia, and Australia, participating in the Lung Cancer Cohort Consortium. The biochemical analyses have been carried out in a centralized laboratory, i.e. BEVITAL.

BEVITAL is partner in numerous projects

These include two EU projects, “Metabolomic profiles throughout the continuum of colorectal carcinogenesis” (MetaboCCC) and ”Biomarkers related to folate-dependent one-carbon metabolism in CRC recurrence and survival” (FOCUS), and one large multicenter study on lung cancer, organized within the frame of the lung cancer consortium (LC3), funded by US NCI. The latter study includes 11000 cases and controls recruited from 20 centers, in Europe, US, Asia and Australia.

April 25, 2024
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Cardiometabolic
Inflammation
Microbiome
Nutrition
Categories

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



Kynurenines, ratio-derived metabolites, proteins





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 (n)
65
18
20
41
View

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 acid 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: Acetoacetate, 3-Hydroxybutyrate

AGEs: Carboxyethyllysine, Carboxymethyllysine

View

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

Neopterin

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

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

View

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

View

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 (μl)
200
150
250
300
Analytical techniques
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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