et al. 2014 ), respiratory function (Schunemann et al. 2001 ), and intima-media
thickness (Riccioni et al. 2009 ).
Of interest, the biospecimen source may vary across studies. When multiple
biological sources of concentration biomarkers are associated with a health outcome
(as compared to only one biospecimen sample source), the confidence that a true
relationship exists is enhanced. As an example, a study of cognition and aging
showed that serum lutein, zeaxanthin, andβ-carotene were associated with higher
cognition, relationships that were also demonstrated for brain lutein andβ-carotene
in postmortem brain biopsy samples (Johnson et al. 2013 ).
For many concentration biomarkers, an extensive list of potential confounders
has been identified including both modifiable measures such as BMI, smoking
status, education, and alcohol use as well as non-modifiable measures such as
gender, age, season and/or residential location at time of biosampling (Woodside
et al. 2013 ). Table9.4summarizes various confounders that have been associated
with an influence on the relationship between biomarkers and health outcomes in
human studies.
Table 9.4 Possible confounders on the relationship between biomarkers and health outcomes
Factors Sources of variability Example biomarker
Demographic
characteristics- Gender
- Age
- Income/socioeconomic
status - Race/ethnicity
Serum fatty acids, urinary nitrogen
Carotenoids
Carotenoids
Vitamin DLifestyle •Body mass
index/adiposity- Smoking status
- Alcohol use
- Exercise
- Colonic microbiota
- Inflammation/stress
- Diet
Fat soluble nutrients and bioactives
Antioxidant nutrients
Folate, compounds undergoing hepatic
clearance
Urinary nitrogen, sodium, potassium
Short-chain fatty acids
Fatty acids
Absolute exposure potential for all nutrients,
bioactives
Genetics •Food palatability genes- Metabolism-associated
genes - Epigenetic variation
Supertaster and cruciferous vegetables
Caffeine, vitamin D, iron, folate
Folate, methyl donor nutrientsBiological sampling •Fasting versus
non-fasting- Sample source
- Length of storage
- Diurnal variation
- Seasonal variation
Most nutrients and bioactives
Most nutritional biomarkers
Fatty acids
Melatonin
Carotenoids, vitamin DAnalytical methods •Precision, accuracy- Detection limits
- Instrumentation/method
All nutritional biomarkers184 T.E. Crane and C.A. Thomson