Biomarkers of Phytonutrients in Epidemiological Studies

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This entry is adapted from the peer-reviewed paper 10.3390/nu15040970

Phytonutrients are non-essential nutrients present in natural plants that are beneficial to human health. The phytonutrients contained in each plant are different. Among them, important phytonutrients include polyphenols, carotenoids, anthocyanins, chlorogenic acid and curcumin, which can regulate the physiological functions of the human body. Consuming phytonutrients through the diet may improve health and prevent chronic degenerative conditions including cancer, cardiovascular, and neurological illnesses. Biomarkers are a type of useful tools for determining the bioavailability of phytonutrients in humans, and their concentration in plasma, serum, or urine is the major indicator of a phytonutrient’s status. There are also emerging biomarkers from recent work in this field, such as stool polyphenols, breastmilk carotenoids, or macular pigment density for lutein and zeaxanthin. Research evidence based on biomarkers and epidemiological studies can effectively guide nutritional supplementation.

polyphenols cardiovascular cholesterol

1. Biomarker of Polyphenol and Its Application

Dietary polyphenols are a varied family of 500 distinct compounds with a wide range of structural variations. Numerous scientific studies have shown that dietary polyphenols help protect against chronic illnesses including cancer, diabetes, and cardiovascular disease ^[1]. A mean daily consumption of 850 mg of total polyphenols was reported ^[2]. Recent advances in analytical technologies and metabolomics have enabled massive collections of polyphenols in the blood or urine to be assessed as indicators of polyphenol metabolite exposure. Establishing a connection between biomarkers of dietary components and epidemiological research will aid in the provision of polyphenol supplements to persons who require them.

Cardiovascular diseases are the primary reason for mortality globally, and numerous studies have shown the preventive advantages of polyphenols on the cardiovascular system ^[3]. The cardiovascular protective effects of polyphenols can be linked to a variety of pathways, including anti-inflammatory activities, antioxidant capacity, platelet aggregation inhibition, and antithrombotic properties ^[4]. In a longitudinal research, 573 subjects were divided into three groups and their total polyphenol excretion (TPE) levels were examined. To help with solid phase extraction, Folin-Ciocalteu was employed to assess TPE in urine samples. Utilizing multiple linear regression models, the relationships between clinical cardiovascular risk variables and TPE were examined. During a 5-year follow-up, there were notable negative associations between changes in TPE and plasma triglyceride levels, glucose levels, and diastolic blood pressure. According to the results, increasing the consumption of polyphenols—measured as TPE in urine—might have a protective effect against several cardiovascular risk factors ^[5].

An expanding amount of epidemiological evidence suggests that individuals who consume a diet high in fruits and vegetables have a reduced probability of contracting chronic diseases as well as a lower overall mortality ^[4]^[6]. To explore the relation between total urinary polyphenols (TUP) and total dietary polyphenols (TDP) with cognitive decline in elderly population. Rabassa et al. recruited 652 elderly individuals without dementia and performed a 3-year follow-up test to explore the association between polyphenol intake and cognitive ability, using both the Mini Mental State Examination (MMSE) and the Trail-Making Test (TMT) to evaluate cognition. Higher TUP levels were linked with a decreased possibility of significant cognitive decline on the MMSE and TMT in logistic regression models adjusted for baseline cognitive scores and potential covariates. In a 3-year trial, high levels of polyphenols, a dietary biomarker of polyphenol consumption, were linked to a reduced risk of significant cognitive decline in elderly populations, suggesting a protective effect against cognitive impairment ^[7]. Another research investigated the connection between TUP and TDP and overall mortality in older people over 12-year period, in which 274 individuals died throughout the follow-up. TUP excretion, after adjusting for age and sex, appeared to be higher in individuals who lived than those people who passed away at enrolment. As a biomarker of the aged people death prediction, the elder people with higher TUP excretion rates likely live longer than those with lower ones ^[8].

Furthermore, the concentration of polyphenols in the plasma may be linked to specific malignancies. Murphy et al. utilized high pressure liquid chromatography combined with tandem mass spectrometry to evaluate the plasma concentrations of 35 polyphenols in 809 colon cancer patients and 809 matched controls. Equol and homovanillic acid were linked to colon cancer risk in false discovery rate-adjusted and continuous log-transformed multivariate models. Equol concentrations were revealed to be inversely connected to colon cancer risk when comparing the extreme quintiles, but homovanillic acid concentrations were discovered to be favorably related to colon cancer occurrence. Higher homovanillic acid concentrations were linked to a higher risk of colon cancer whereas higher equol concentrations were linked to a lower risk, suggesting that some polyphenols may play a role in colon carcinogenesis ^[9].

2. Biomarker of Carotenoid and Its Application

Carotenoids are fat-soluble chemicals of natural plants that humans cannot directly synthesize. Numerous studies have been focused on the biological beneficial effects of carotenoids against chronic diseases ^[10]. A vast variety of carotenoids may be absorbed by humans, and many of them can be identified in serum and tissues. Circulating carotenoid concentrations serve as trustworthy indicators of carotenoid consumption from food and can be utilized to support nutritional evaluation methods. Moreover, compared with self-reported data, plasma carotenoid concentrations have been used as a more accurate biomarker for assessing fruit and vegetable (FV) consumption, as nearly 90% of carotenoid daily intake is provided by FV ^[11].

It is possible to utilize the concentration of circulating carotenoids as a reliable biomarker of carotenoid intake from diet and to complement nutritional assessment strategies. Allore et al. investigated the association of fasting plasma carotenoid concentrations with physical and metabolic characteristics after intervention. The results showed that higher body weight and waist circumference were associated with lower plasma total carotenoid concentrations, whereas higher plasma LDL and HDL cholesterol concentrations were associated with higher plasma total carotenoid concentrations. Despite having much lower dietary carotenoid intake than men, women exhibited significantly higher plasma total carotenoid concentrations. By correcting circulating carotenoid concentrations for plasma HDL-cholesterol, gender inequalities in plasma carotenoid concentrations were eliminated. When employing plasma carotenoids as indicators of dietary intake in male and female, certain physical traits and plasma lipids should be considered since they correlate with circulating carotenoid concentrations ^[12].

A cross-sectional study in Singapore recruited 103 middle-aged and older people to investigate the use of skin carotenoid status (SCS) and plasma carotenoids to assess FV and carotenoid consumption in the elderly. Dietary carotenoids and FV and plasma carotenoid concentrations and SCS were detected using 3-day food recordings, HPLC, and a bio-photonic scanner utilizing Roman spectroscopy, respectively. After adjusting for statistically defined sociodemographic covariates, total dietary carotenoids were positively correlated with plasma carotenoids and SCS. This indicates that these nutritional parameters may influence carotenoid cycle and skin deposition ^[13]. Moreover, the correlation between serum carotenoids and their intake may be weakened by hyperglycemia in type 1 diabetes with increased oxidative stress, and thus depleted serum carotenoids. In order to investigate the association between the concentrations of serum carotenoid and type 1 diabetes. Namrata et al. analyzed data from a nutritional intervention study including youngsters with type 1 diabetes. Regression analysis of the serum carotenoid measurement can be useful to estimate the conditions of glycemic control, oxidative stress, FV and carotenoid intake since these conditions were correlated with the serum carotenoid concentration. People intaking more fruit, vegetables or other carotenoid containing food likely have higher concentration of serum carotenoid, and higher hyperglycemia was associated with lower serum carotenoids. The findings of this investigation validate serum carotenoids as indicators of FV as well as carotenoid consumption in young people with type 1 diabetes ^[14].

References

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Kan, J.; Wu, F.; Wang, F.; Zheng, J.; Cheng, J.; Li, Y.; Yang, Y.; Du, J. Phytonutrients: Sources, bioavailability, interaction with gut microbiota, and their impacts on human health. Front. Nutr. 2022, 9, 960309.
Bacanli, M.; Dilsiz, S.A.; Basaran, N.; Basaran, A.A. Effects of phytochemicals against diabetes. Adv. Food Nutr. Res. 2019, 89, 209–238.
Guo, X.; Tresserra-Rimbau, A.; Estruch, R.; Martinez-Gonzalez, M.A.; Medina-Remon, A.; Castaner, O.; Corella, D.; Salas-Salvadó, J.; Lamuela-Raventós, R.M. Effects of Polyphenol, Measured by a Biomarker of Total Polyphenols in Urine, on Cardiovascular Risk Factors After a Long-Term Follow-Up in the PREDIMED Study. Oxidative Med. Cell. Longev. 2016, 2016, 2572606.
Bulotta, S.; Capriglione, F.; Celano, M.; Pecce, V.; Russo, D.; Maggisano, V. Phytochemicals in thyroid cancer: Analysis of the preclinical studies. Endocrine 2021, 73, 8–15.
Rabassa, M.; Cherubini, A.; Zamora-Ros, R.; Urpi-Sarda, M.; Bandinelli, S.; Ferrucci, L.; Andres-Lacueva, C. Low Levels of a Urinary Biomarker of Dietary Polyphenol Are Associated with Substantial Cognitive Decline over a 3-Year Period in Older Adults: The Invecchiare in Chianti Study. J. Am. Geriatr. Soc. 2015, 63, 938–946.
Zamora-Ros, R.; Rabassa, M.; Cherubini, A.; Urpi-Sarda, M.S.; Ferrucci, L.; Andres-Lacueva, C. High concentrations of a urinary biomarker of polyphenol intake are associated with decreased mortality in older adults. J. Nutr. 2013, 143, 1445–1450.
Murphy, N.; Achaintre, D.; Zamora-Ros, R.; Jenab, M.; Boutron-Ruault, M.C.; Carbonnel, F.; Savoye, I.; Kaaks, R.; Kühn, T.; Boeing, H.; et al. A prospective evaluation of plasma polyphenol levels and colon cancer risk. Int. J. Cancer 2018, 143, 1620–1631.
Kan, J.; Wang, M.; Liu, Y.; Liu, H.; Chen, L.; Zhang, X.; Huang, C.; Liu, B.Y.; Gu, Z.; Du, J. A novel botanical formula improves eye fatigue and dry eye: A randomized, double-blind, placebo-controlled study. Am. J. Clin. Nutr. 2020, 112, 334–342.
Prentice, R.L.; Pettinger, M.; Neuhouser, M.L.; Tinker, L.F.; Huang, Y.; Zheng, C.; Manson, J.E.; Mossavar-Rahmani, Y.; Anderson, G.L.; Lampe, J.W. Application of blood concentration biomarkers in nutritional epidemiology: Example of carotenoid and tocopherol intake in relation to chronic disease risk. Am. J. Clin. Nutr. 2019, 1, 1189–1196.
Allore, T.; Lemieux, S.; Vohl, M.C.; Couture, P.; Lamarche, B.; Couillard, C. Correlates of the difference in plasma carotenoid concentrations between men and women. Br. J. Nutr. 2019, 121, 172–181.
Toh, D.W.K.; Loh, W.W.; Sutanto, C.N.; Yao, Y.; Kim, J.E. Skin carotenoid status and plasma carotenoids: Biomarkers of dietary carotenoids, fruits and vegetables for middle-aged and older Singaporean adults. Br. J. Nutr. 2021, 126, 1398–1407.
Sanjeevi, N.; Lipsky, L.M.; Nansel, T.R. Hyperglycemia and Carotenoid Intake Are Associated with Serum Carotenoids in Youth with Type 1 Diabetes. J. Acad. Nutr. Diet. 2019, 119, 1340–1348.

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1. Biomarker of Polyphenol and Its Application

2. Biomarker of Carotenoid and Its Application

References