While self-reported dietary content is often missing the point, this review shows how blood, urine, and skin biomarkers can enhance studies of fruit and vegetable intake, while also clarifying why no single marker is ready to work alone.
A descriptive review of candidate biomarkers of total fruit and vegetable intake. Image credit: Marilyn Barbone / Shutterstock
Narrative review article published in Nutritional Bulletin provides a detailed overview of the characteristics of currently available candidate biomarkers for estimating dietary intake of fruits and vegetables. Identifying effective biomarkers is particularly important to more objectively assess intake and strengthen research on the health benefits of consuming fruits and vegetables.
background
High intake of fruits and vegetables is consistently associated with a lower risk of several chronic diseases, including cardiovascular disease, asthma, diabetes, obesity, and certain cancers. These well-documented associations have greatly encouraged the inclusion of these food groups in national dietary guidelines.
However, dietary intake assessment methods used in most nutrition studies, such as food frequency questionnaires (FFQs), 24-hour dietary recalls, and food records, are susceptible to recall bias and other measurement errors, which can reduce the accuracy of dietary intake estimates and, therefore, the risk estimates obtained from these studies.
Several dietary biomarkers have been identified to improve the accuracy of the assessment. This represents a more objective and complementary approach to estimating dietary intake of fruits and vegetables and could potentially improve the validity of future epidemiological studies investigating the health benefits of these food groups.
Recent advances in metabolomics have facilitated the rapid identification of dietary biomarkers. However, validation has lagged behind discovery, in part due to the historical lack of standardized validation processes.
To promote the dissemination of biomarker-based methods in dietary intake assessment, this review provided a detailed analysis of the current evidence supporting the effectiveness, utility, strengths, and weaknesses of various candidate biomarkers for fruit and vegetable intake.
Validation criteria for fruit and vegetable intake biomarkers
Given the historical lack of a standardized validation process, researchers developed a set of eight criteria for systematically validating biomarkers of food intake using a consensus-based procedure. These include validity, dose-response, time-response, robustness, reliability, stability, analytical performance, and interlaboratory reproducibility.
Potential candidate biomarkers are evaluated against these criteria to determine their degree of validation. Several biomarkers have been identified in various body fluids such as blood, urine, and skin. Potential biomarkers include urinary potassium, flavonoids, hippuric acid, serum and red blood cell folate, serum vitamin C, and blood and skin carotenoids.
urinary potassium
Given that potassium is abundant in fruits and vegetables and potassium homeostasis in the body is maintained primarily through renal excretion, urinary potassium concentration is considered a potential biomarker of fruit and vegetable intake. Urinary potassium concentrations correlate better with dietary potassium intake than serum or plasma potassium concentrations.
However, studies investigating urinary potassium as a potential biomarker have shown that urinary potassium may be significantly correlated with vegetable intake in a dose-dependent manner, but not consistently with fruit intake or total fruit and vegetable intake.
Several factors can modulate renal potassium excretion, including the use of certain drugs, the presence of certain diseases, and endogenous levels of certain hormones. These factors may reduce the ability of urinary potassium to serve as a biomarker of fruit and vegetable intake.
Potassium in urine is stable over time, but collecting a 24-hour urine sample is time-consuming and may not be feasible for many people. All these factors collectively reduce the potential for urinary potassium to be a valid biomarker of total fruit and vegetable intake.
urinary flavonoids
Flavonoids are bioactive polyphenolic compounds found abundantly in fruits and vegetables. Concentrations of flavonoids and their metabolites in 24-hour urine samples are considered promising short-term biomarker candidates for assessing recent fruit and vegetable intake.
Several studies have reported that the sum of certain urinary flavonoid metabolites may serve as a promising biomarker of total fruit and vegetable intake. However, these flavonoid metabolites are not limited to fruits and vegetables, and the concentration of flavonoid metabolites in urine samples can vary depending on dietary intake, such as tea, chocolate, coffee, spices, and wine. This limitation highlights the need to identify and standardize specific flavonoids in fruits and vegetables.
Urinary concentrations of hippuric acid, one of the major metabolic end products of flavonoids, also hold promise as a potential biomarker in fruits and vegetables. Although some studies have shown a significant dose-dependent association between 24-hour urinary hippuric acid concentrations and self-reported fruit and vegetable intake, most research on this candidate biomarker has been conducted in children and adolescents.
Folic acid in serum and red blood cells
Fruits and vegetables are rich sources of dietary folate, and serum and red blood cell concentrations of this B vitamin are considered potential biomarkers of dietary intake. Existing evidence indicates that serum folate serves as an indicator of changes in dietary folate intake over the past few days and that red blood cell folate serves as a long-term indicator of dietary folate intake over the past 3–4 months. However, serum folate has been found to better reflect dietary fruit and vegetable intake than red blood cell folate.
Despite evidence of a dose-dependent relationship between serum folate and fruit and vegetable intake, one major limitation is that folate is not exclusively found in fruits and vegetables, and its concentrations can vary in response to other foods, especially supplements and fortified foods.
Another limitation is that several factors other than dietary folate intake can significantly influence serum and red blood cell folate concentrations, such as gender, age, energy intake, smoking, alcohol intake, and race/ethnicity.
vitamin c serum
Fruits and vegetables are the main dietary sources of vitamin C, and their serum concentrations can strongly reflect dietary intake of these food groups. One potential limitation of this candidate biomarker is that blood saturation occurs when healthy individuals consume 200 to 400 milligrams of vitamin C from their diet.
Decreased responsiveness above these intakes may reduce the sensitivity of serum vitamin C as a biomarker for detecting changes in fruit and vegetable intake, especially when dietary intakes of vitamin C from supplements or fortified or fortified foods are very high.
Overall, existing evidence suggests that serum vitamin C may serve as a useful biomarker of fruit and vegetable intake in populations where supplementation and consumption of vitamin C-fortified or fortified foods is limited and average intakes are below blood saturation levels.
blood carotenoids
Carotenoids are found in many common fruits and vegetables and cannot be synthesized by the human body. These factors make blood carotenoids promising marker candidates. The total amount of carotenoids in the blood increases significantly in response to short- and long-term intake of fruits and vegetables.
The Institute of Medicine’s Panel on Dietary Antioxidants and Related Compounds currently considers blood levels of carotenoids to be the biomarker of choice for fruit and vegetable intake, as there is a large body of evidence demonstrating their superiority over other candidate biomarkers tested. However, because blood sampling is invasive and some fruits and vegetables contain little carotenoids, interlaboratory reproducibility requires further study.
Skin carotenoids also have the potential to be alternative biomarkers for blood carotenoids, offering several advantages, including reduced time, cost, and invasiveness. However, skin carotenoids require additional validation through controlled clinical trials in different populations.
take home message
Current research has identified several biomarkers that are useful for estimating short-term or habitual intake of fruits and vegetables. Serum vitamin C, serum folate, urinary hippuric acid, urinary potassium, and urinary flavonoids are considered suitable for tracking short-term changes and compliance with dietary interventions, whereas blood and skin carotenoids and red blood cell folate are suitable for assessing habitual intake. However, further research is required to address several potential limitations, including factors influencing the concentrations of these biomarkers, standardization of appropriate analytical methods, and the effectiveness of these biomarkers in diverse populations. Combining biomarker panels may improve group-level estimates of fruit and vegetable intake, but still requires further validation and may not yet be precise enough for individual-level assessment.
