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Table 1 Published biomarker classification schemes

From: A scheme for a flexible classification of dietary and health biomarkers

Criterion

Classification

Definition

Examples

References

   

Sample type

Biomarker

 

Temporal relationship with dietary intake

Short-term biomarkers

Biomarkers that respond to dietary intake within hours

Breath

Hydrogen (lactose intolerance)

[4]

   

Plasma

13C–glucose (lactose intolerance)

 
   

Serum

Vitamin C (postprandial spikes)

 
   

Serum

Triglycerides (postprandial spikes)

 
 

Medium-term biomarkers

Biomarkers that respond to dietary intake over weeks or months

Red blood cell

Essential fatty acid (average of the previous 120 days of intake of essential fatty acids)

Folate (average of the previous 120 days of intake of folate)

 
 

Long-term biomarkers

Biomarkers that respond to dietary intake over several months or years

Hair Toenail

Trace element (long-term intake of a trace element, e.g. Se)

 

Relevant functional outcomes

Markers of exposure to a food compound

Markers that are related to the exposure to the food compound being studied, such as a serum, fecal, breath, urine or tissue marker

Red blood cell

Blood

Folate (exposure to folate in food)

Tryptophan (exposure to tryptophan in food)

[5]

 

Markers of target function/biological response

Markers that are related to the target function or biological response such as changes in body fluids, levels of a metabolite, protein or enzyme or changes in a given function

Plasma

Physical

Reduction of homocysteine (response to dietary folate)

Blood pressure (response to dietary caffeine)

 
 

Markers of intermediate endpoint

Markers that are related to an appropriate intermediate endpoint of an improved state of health and well-being or reduction of risk of disease, or both, such as the measurement of biological processes that relate directly to the endpoint

Physical

Bone

Extent of narrowing of the carotid artery (cardiovascular disease)

Mineral density (risk of bone fracture)

 

Association with intake

Recovery biomarkers

Biomarkers based on recovery of certain food compounds directly related to intake and not subject to substantial inter-individual differences

Urine

Urine

Urine

Doubly labeled water (metabolic rate and total energy expenditure)

Nitrogen (protein intake)

Potassium and sodium

[6, 8]

 

Predictive biomarkers

Biomarkers that are sensitive, time dependent and show a dose-response relationship with intake levels but their overall recovery is lower than recovery biomarkers

Urine

24-h sucrose and fructose (sugar intake)

 
 

Concentration biomarkers

Biomarkers whose concentrations do correlate with intakes of corresponding foods or nutrients but the strength of the correlation is often lower (< 0.6) than that expected for recovery biomarkers (> 0.8)

Serum

Blood

Vitamins (vitamin intake)

Lipids (lipid intake)

 
 

Replacement biomarkers

Biomarkers that are closely related to concentration biomarkers and refer specifically to compounds for which information in food composition databases is unsatisfactory or unavailable

Urine

Serum Urine

Aflatoxin

Isoflavonoids and lignans (phytoestrogen intake)

Phytoestrogens (phytoestrogen intake)

 

Biological endpoint

Biomarker of exposure

Accurately reflecting intake/exposure

Any biological specimen

Plasma vitamin C

[3]

 

Biomarker of susceptibility

Accurately reflecting (an aspect of) susceptibility

Any biological specimen

Low plasma vitamin C (risk of scurvy); high serum cholesterol or blood pressure (susceptibility to myocardial infarction); low bone mineral density (susceptibility to fractures)

 
 

Biomarkers of effect and efficacy

An established biomarker of efficacy is an indicator of an improvement of a physiologic function or a decrease in risk factors for a disease (it follows that effect biomarkers would also include the corresponding null or negative outcomes)

Any biological specimen

Changes in: serum cholesterol; blood pressure; bone formation, resorption or density; prostate specific antigen

 

Purpose of the study

Biomarkers of dietary exposure

Biomarkers that are aimed at assessing dietary intake of different foods, nutrients, non-nutritive compounds or dietary patterns (recovery biomarkers, concentration biomarkers, recovery biomarkers and predictive biomarkers)

Urine

Nitrogen (protein intake)

[7]

 

Biomarkers of nutritional status

Biomarkers that reflect not only intake but also metabolism of the nutrient(s) and possibly effects from disease processes

Plasma

Homocysteine (folate deficiency, one-carbon metabolic processes)

 
 

Biomarkers of health/disease

Biomarkers related to different intermediate phenotypes of a disease or even to the severity of the disease

Plasma

Plasma

Total cholesterol (cardiovascular diseases)

Triglycerides (cardiovascular diseases)

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