Exposure to Nutrients

Why are nutrients relevant to human health?

Human nutrition has traditionally focused on the concept of nutrients, i.e., those natural products, compounds, and elements considered “essential” for life. All of the nutrients recognized as essential today have been known for at least several decades and are generally consumed in quantities sufficient to prevent the occurrence of deficiency diseases. Biomarkers for most of the key nutrients have been identified. More recently, human nutrition has focused on the prevention of chronic diseases and over-nutrition (very high intakes of energy and nutrients), which can have detrimental effects.

Foods contain compounds that may not be “essential” for life, but have beneficial effects. These compounds may have cumulative, interactive, or synergistic effects. Nutritional exposures and lack thereof have been associated with the risk of cardiovascular disease, cancer, and other chronic diseases.

Some chemical elements such as chromium, cobalt, copper, zinc, selenium, and manganese are considered essential nutrients at trace and ultratrace levels (see Trace Elements for more information on analyzing biospecimens for these elements).

What types of questions can be answered?

Nutritional biomarkers can be used to provide an internal estimate of intake of a particular type of food or compliance with a specific dietary protocol. Food frequency questionnaires are often prone to random and systematic error. Specific blood- and urine-based nutritional biomarkers can be used to confirm consumption of specific food groups as well as determine the internal dose of food-based nutrients/compounds. For example, plasma alkylresorcinols are a biomarker of whole grain wheat and rye intake, and urinary methylhistidines are biomarkers of meat consumption. Carotenoids and tocopherols are indicative of fruit and vegetable consumption. Phytoestrogens (e.g., genistein, isoflavone) are widely used as biomarkers of exposure to plant-derived estrogenic chemicals.

In addition, a number of compounds present in food are thought to have beneficial or harmful effects in the prevention or causation of human disease. Studies can be designed to explore associations between the internal dose of a particular food-based compound or vitamin with a particular disease outcome or health status. For example, urinary levels of dietary phenols have been linked to the prevention of cardiovascular disease, diabetes, cancer, and neurodegenerative diseases. Alternatively, elevated levels of fatty acids, some of which are essential, have been associated with chronic diseases including type 2 diabetes, cardiovascular disease, and certain cancers.

How can nutrient levels be assessed?

  • Analytes: A number of nutrients and nutrient classes can be analyzed, including alkylresorcinols, ascorbic acid, carotenoids/tocopherols, dietary phenols, fatty acids, folate, lycopenes, methylhistidines, phytoestrogens, retinol, and vitamin D derivatives. DNA adducts of aromatic amines found in charbroiled foods can also be measured.
  • Methods: Depending on the specific analyte, nutrient, and food compounds, various methods are used. For example, dietary phenols and phytoestrogens are measured in urine using a sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. Plasma levels of fatty acids are determined by gas chromatography mass spectrometry (GC-MS). Levels of serum retinol or plasma alkylresorcinols or methylhistidines are measured by LC-MS/MS assays. Plasma or serum levels of carotenoids, tocopherols, and lycopenes are determined by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Other nutrient biomarkers can be measured in plasma or serum through enzyme-linked immunosorbent assay (ELISA), colorimetric, and other methods.
  • Types of biospecimens: Depending on the specific analyte, nutrient and food compounds, biomarkers could be measured in either urine, plasma, or serum.
  • Types of environmental samples: HHEAR does not provide analysis of nutrients in environmental samples.

How does HHEAR ensure the quality of its analyses?

Most assays are well validated with respect to accuracy and precision, and use standards and embedded controls and blanks. Method validation studies include determining the accuracy, precision, method limit of detection, and limit of quantification of all assays, and, where appropriate, testing positive samples. For many assays, matrix-specific certified reference materials are available that ensure measurement traceability to International System of Units (SI) units. Internal matrix-specific quality control materials for both the low and high ends of the calibration ranges are included in all assays. For the multiplex assay, quality control procedures include bead counts, standard curves, coefficient of variation, control serum, and AssayChex beads.

What sample quality and quantity are necessary?

Sample quantity and quality are highly dependent on the biomarker to be measured. Generally, the following amounts of various biological matrices are required: up to 1 mL of plasma/serum or 0.5 mL of urine.

References

Campbell DR, Gross MD, Martini MC, Grandits GA, Slavin JL, Potter JD. Plasma carotenoids as biomarkers of vegetable and fruit intake. Cancer Epidemiology Biomarkers & Prevention. 1994;3:493-500.

Flint AJ, Hu FB, Glynn RJ, et al. Whole grains and incident hypertension in men. Am J Clin Nutr. 2009;90(3):493-498.

Martini MC, Campbell DR, Gross MD, Grandits GA, Potter JD, Slavin JL. Plasma carotenoids as biomarkers of vegetable intake: the University of Minnesota Cancer Prevention Research Unit Feeding Studies. Cancer Epidemiol Biomarkers Prev. 1995;4(5):491-496.

Myint T, Fraser GE, Lindsted KD, Knutsen SF, Hubbard RW, Bennett HW. Urinary 1-methylhistidine is a marker of meat consumption in Black and in White California Seventh-day Adventists. Am J Epidemiol. 2000;152(8):752-755.

Nettleton JA, Polak JF, Tracy R, Burke GL, Jacobs DR. Dietary patterns and incident cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis. Am J Clin Nutr. 2009;90(3):647-654.

Steffen BT, Guan W, Stein JH, et al. Plasma n-3 and n-6 Fatty Acids Are Differentially Related to Carotid Plaque and Its Progression: The Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol. 2018;38(3):653-659.