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How Could Nutrient levels in serum/plasma/urine be misleading?

Nutrient biomarkers are essential for determining the nutritional status of individuals. Many types of nutrient biomarkers are commonly used including serum/plasma/urine biomarkers and various functional biomarkers. Serum/plasma/urine nutrient levels have been widely used in population-based nutritional surveys, such as the U.S. National Health and Nutrition Examination Survey (NHANES) survey.


Circulating serum/plasma/urine nutrient levels are generalling influenced by short-term factors such as recent dietary intake, nutrient supplementations, or stress, and may not reflect long-term nutrient status or the overall body's nutrient reserve. Additionally, some nutrients have a wide range of normal values, making it difficult to interpret results without considering other factors. Another limitation of these nutrient biomarkers is that they may not capture subclinical deficiencies or excesses of certain nutrients.


For example, serum/plasma vitamin D levels may not accurately reflect an individual's vitamin D status if they have a low level of vitamin D-binding protein or other factors that affect vitamin D metabolism. However, the large number of participants in the populational survey outweighs the limitations of serum/plasma/urine nutrient biomarkers. Contrarily, when it comes to individualized nutrient assessments, relying on these nutrient levels could be misleading.


Functional biomarkers reflect the body's ability to utilize and process nutrients over a longer period. For instance, homocysteine and methylmalonic acid are the functional biomarkers that reflect an individual's vitamin B status more accurately than serum/plasma/urine B vitamin levels. As an amino acid that involving in methylation cycles, homocysteine levels are influenced by the availability of B vitamins such as folate, vitamin B12, and vitamin B6. Vitamin B12 insufficiency also elevates methylmalonic acid levels. Elevated homocysteine or methylmalonic acid levels have been associated with a higher risk of cardiovascular disease and other health conditions. Therefore, measuring homocysteine and methylmalonic acid levels can provide better insight into an individual's B vitamin status than their serum/plasma levels.


Iron status assessment is also another crucial aspect of nutritional evaluations. However, serum iron levels alone may not provide a complete picture of an individual's iron status, as they are influenced by the hepcidin hormone during inflammation, therefore the low serum iron level may not necessarily reflect low dietary intake. Combined biomarkers such as inflammatory markers, ferritin, and total iron-binding capacity (TIBC) should be included when assessing iron status to ensure an accurate interpretation of an individual's iron status.


In conclusion, all biomarker information is valuable in assessing nutrient status. While serum/plasma/urine nutrient levels are commonly used in many clinical settings, it is crucial to understand the limitations of these biomarkers and carefully handle the information within the clinical context and consider their relevant functional markers. By doing so, practitioners can develop personalized interventions that optimize overall health and wellness.


Ahluwalia N, et.al., Update on NHANES Dietary Data: Focus on Collection, Release, Analytical Considerations, and Uses to Inform Public Policy. Adv Nutr. 2016 Jan 15;7(1):121-34. doi: 10.3945/an.115.009258.


Fraser, W.D., et al. Vitamin D Measurement, the Debates Continue, New Analytes Have Emerged, Developments Have Variable Outcomes. Calcif Tissue Int 106, 3–13 (2020). https://doi.org/10.1007/s00223-019-00620-2


Bjørke Monsen AL, Ueland PM. Homocysteine and methylmalonic acid in diagnosis and risk assessment from infancy to adolescence. Am J Clin Nutr. 2003 Jul;78(1):7-21. doi: 10.1093/ajcn/78.1.7.


National Institutes of Health. Iron Fact Sheet for Health Professionals. Updated September 13, 2021. Available at: https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/. Accessed March 25, 2023.




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