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Nutritional Biomarkers in Health and Disease

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (31 July 2019) | Viewed by 41905

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Guest Editor
Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

Special Issue Information

Dear Colleagues,

Biomarkers of dietary intake have contributed extensively to our understanding of how diet affects chronic diseases. Their utility relies on their ability to either complement research using dietary assessment by questionnaires and/or evaluate dietary components that are difficult to assess by questionnaire, although their use as a replacement for dietary assessment by questionnaire needs to be carefully examined. The recent widespread use of these objective measures to assess diet–disease relationships should take into account their limitations. 

Prof. Hannia Campos
Guest Editor

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Keywords

Nutrient biomarkers
Dietary assessment
Fatty acids
Antioxidants
Vitamins
Clinical outcomes
Chronic disease

Published Papers (9 papers)

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Research

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17 pages, 916 KiB  
Article
Assessing Validity of Self-Reported Dietary Intake within a Mediterranean Diet Cluster Randomized Controlled Trial among US Firefighters
by Mercedes Sotos-Prieto, Costas Christophi, Alicen Black, Jeremy D Furtado, Yiqing Song, Prokopios Magiatis, Aikaterini Papakonstantinou, Eleni Melliou, Steven Moffatt and Stefanos N. Kales
Nutrients 2019, 11(9), 2250; https://doi.org/10.3390/nu11092250 - 19 Sep 2019
Cited by 12 | Viewed by 5593
Abstract
Collecting dietary intake data is associated with challenges due to the subjective nature of self–administered instruments. Biomarkers may objectively estimate the consumption of specific dietary items or help assess compliance in dietary intervention studies. Our aim was to use a panel of plasma [...] Read more.
Collecting dietary intake data is associated with challenges due to the subjective nature of self–administered instruments. Biomarkers may objectively estimate the consumption of specific dietary items or help assess compliance in dietary intervention studies. Our aim was to use a panel of plasma and urine biomarkers to assess the validity of self-reported dietary intake using a modified Mediterranean Diet Scale (mMDS) among firefighters participating in Feeding America’s Bravest (FAB), an MD cluster-randomized controlled trial. In our nested biomarker pilot study, participants were randomly selected from both the MD intervention group (n = 24) and the control group (n = 24) after 12-months of dietary intervention. At baseline data collection for the pilot study (t = 12-months of FAB), participants in the control group crossed-over to receive the MD intervention (active intervention) for 6-months. Participants in the intervention group continued in a self-sustained continuation phase (SSP) of the intervention. Food frequency questionnaires (FFQ), 13-item-mMDS questionnaires, 40 plasma fatty acids, inflammatory biomarkers and urinary hydroxytyrosol and tyrosol were analyzed at both time points. Spearman’s correlation, t-tests and linear regression coefficients were calculated using SAS software. Overall, the mMDS derived from the FFQ was highly correlated with the specific 13-domain-mMDS (r = 0.74). The concordance between the two questionnaires for low and high adherence to MD was high for all the participants in the parent trial (κ = 0.76). After 6 months of intervention in the pilot study, plasma saturated fatty acid decreased in both groups (active intervention: −1.3 ± 1.7; p = 0.002; SSP: −1.12 ± 1.90; p = 0.014) and oleic acid improved in the SSP (p = 0.013). Intake of olive oil was positively associated with plasma omega-3 (p = 0.004) and negatively with TNF-α (p < 0.001) at baseline. Choosing olive oil as a type of fat was also associated with higher levels of plasma omega-3 (p = 0.019) at baseline and lower TNF-α (p = 0.023) at follow up. Intake of red and processed meats were associated with lower serum omega-3 (p = 0.04) and fish consumption was associated with lower IL-6 at baseline (p = 0.022). The overall mMDS was associated with an increase in plasma omega-3 (p = 0.021). Good correlation was found between nutrient intake from the FFQ and the corresponding plasma biomarkers (omega-3, EPA and DHA). In this MD randomized controlled trial, some key plasma biomarkers were significantly associated with key MD diet components and the overall mMDS supporting the validity of the mMDS questionnaire as well as compliance with the intervention. Full article
(This article belongs to the Special Issue Nutritional Biomarkers in Health and Disease)
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14 pages, 572 KiB  
Article
Does the Metabolically Healthy Obese Phenotype Protect Adults with Class III Obesity from Biochemical Alterations Related to Bone Metabolism?
by Ligiane Marques Loureiro, Suzane Lessa, Rodrigo Mendes, Sílvia Pereira, Carlos José Saboya and Andrea Ramalho
Nutrients 2019, 11(9), 2125; https://doi.org/10.3390/nu11092125 - 06 Sep 2019
Cited by 10 | Viewed by 2805
Abstract
Obesity negatively affects the relationship between markers and micronutrients of bone metabolism. Testing the hypothesis that the metabolically healthy obese phenotype might be protected by those alterations was the aim of this study. A cross-sectional study was carried out in adults with class [...] Read more.
Obesity negatively affects the relationship between markers and micronutrients of bone metabolism. Testing the hypothesis that the metabolically healthy obese phenotype might be protected by those alterations was the aim of this study. A cross-sectional study was carried out in adults with class III obesity classified in Metabolically Healthy Obese (MHO) and Metabolically Unhealthy Obese (MUHO), according to the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP ATP III) criteria. Anthropometric, biochemical, and clinical variables were analyzed for sample characterization. To evaluate bone metabolism, markers (alkaline phosphatase and parathyroid hormone—PTH) and related nutrients (vitamin D, vitamin B12, calcium, phosphorus, magnesium, potassium and zinc) were analyzed. A total of 223 adults with class III obesity aged 41.20 ± 10.15 years were included. The MHO phenotype was identified in 32.73% of the sample. After logistic regression, it was observed that inadequacies of calcium (OR: 4.11; 95% CI: 2.33–6.66), phosphorus (OR: 3.03; 95% CI: 1.98–5.79), vitamin D (OR: 5.01; 95% CI: 2.92–6.71) and PTH (OR: 5.45; 95% CI: 4.49–6.74) were significantly higher in the MUHO group compared to the MHO Group. This study showed that the MHO phenotype does not protect adults from alterations in markers and micronutrients of bone metabolism. However, the MUHO phenotype presents a higher risk for alterations related to bone metabolism, which can favor the emergence of metabolic bone diseases. Full article
(This article belongs to the Special Issue Nutritional Biomarkers in Health and Disease)
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17 pages, 794 KiB  
Article
Comparison of the Utility of Total Plasma Fatty Acids Versus those in Cholesteryl Ester, Phospholipid, and Triglyceride as Biomarkers of Fatty Acid Intake
by Jeremy D. Furtado, Jorind Beqari and Hannia Campos
Nutrients 2019, 11(9), 2081; https://doi.org/10.3390/nu11092081 - 03 Sep 2019
Cited by 32 | Viewed by 4117
Abstract
Total plasma fatty acids or those in cholesteryl ester and phospholipids are often used to reflect fatty acid intake in epidemiological studies, but their relative performance as biomarkers of intake has not been clearly evaluated within a single population. The assessment of fatty [...] Read more.
Total plasma fatty acids or those in cholesteryl ester and phospholipids are often used to reflect fatty acid intake in epidemiological studies, but their relative performance as biomarkers of intake has not been clearly evaluated within a single population. The assessment of fatty acids in plasma fractions is more labor intensive. Thus, their use as biomarkers of dietary intake needs to be justified. Dietary intake was assessed in 200 population-based controls from a case-control study of diet and heart disease in Costa Rica by a validated food frequency questionnaire (FFQ). Fatty acids in fasting whole plasma and plasma fractions (cholesteryl ester, phospholipid, and triglyceride + free fatty acid) were measured in the 200 controls by the same laboratory using gas chromatography with flame ionization detection (GC-FID). We compared the plasma and plasma fractions data with the FFQ and adipose fatty acid profile using partial Spearman correlations to assess utility as biomarkers of intake and exposure. We found that whole plasma was equally or more strongly correlated with the FFQ and adipose fatty acid profile than either cholesteryl ester or phospholipid in most of the established markers of dietary intake, including dairy (15:0 and 17:0) and seafood (eicosapentaenoic acid and docosahexaenoic acid). Of the three plasma fractions, only fatty acids in the plasma triglyceride + free fatty acid fraction had stronger correlations with dietary intake than whole plasma. In our study population, fatty acids measured in fasting whole plasma perform as good as or better than those measured in plasma fractions as biomarkers for dietary fatty acid intake. Thus, the fractionation of plasma to evaluate long-term fatty acid intake may not be warranted. Full article
(This article belongs to the Special Issue Nutritional Biomarkers in Health and Disease)
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10 pages, 396 KiB  
Article
Association of Low Serum l-Carnitine Levels with Peripheral Arterial Stiffness in Patients Who Undergo Kidney Transplantation
by Yu-Hsien Lai, Ming-Che Lee, Guan-Jin Ho, Chin-Hung Liu and Bang-Gee Hsu
Nutrients 2019, 11(9), 2000; https://doi.org/10.3390/nu11092000 - 24 Aug 2019
Cited by 10 | Viewed by 2813
Abstract
l-carnitine is an important co-factor in fatty-acid metabolism, and its deficiency is associated with insulin resistance, which is independently associated with arterial stiffness. This study evaluated the relationship between serum l-carnitine level and peripheral arterial stiffness (PAS) in kidney transplantation (KT). [...] Read more.
l-carnitine is an important co-factor in fatty-acid metabolism, and its deficiency is associated with insulin resistance, which is independently associated with arterial stiffness. This study evaluated the relationship between serum l-carnitine level and peripheral arterial stiffness (PAS) in kidney transplantation (KT). Fasting blood samples were collected from 65 patients who underwent KT. We measured the brachial–ankle pulse wave velocity, and 36 patients (55.4%) had PAS. Patients with PAS had a significantly higher percentage of diabetes (p = 0.001), hypertension (p = 0.033), and metabolic syndrome (p = 0.044); higher waist circumference (p = 0.010), systolic blood pressure (p = 0.002), serum triglyceride level (p = 0.040), insulin level (p = 0.002), and homeostasis model assessment of insulin resistance (p = 0.002); lower high-density lipoprotein cholesterol (p = 0.036) and serum l-carnitine levels (p < 0.001); older age (p = 0.041); and a longer KT duration (p = 0.025) than those without PAS. Statistical analysis revealed an independent association between PAS in KT and KT duration (95% confidence interval (CI): 1.003–1.054, p = 0.029) and serum l-carnitine levels (95% CI: 0.842–0.998, p = 0.044). The area under the receiver operating characteristic curve indicated that the diagnostic power of l-carnitine to predict PAS was 0.789 (95% CI: 0.670–0.881, p < 0.001). Serum-free l-carnitine level is negatively associated with PAS in patients who undergo KT. Full article
(This article belongs to the Special Issue Nutritional Biomarkers in Health and Disease)
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13 pages, 592 KiB  
Article
Association between Postpartum Nutritional Status and Postpartum Depression Symptoms
by Yu-Hung Lin, Chiao-Ming Chen, Hui-Min Su, Shu-Ci Mu, Mei-Ling Chang, Pei-Yin Chu and Sing-Chung Li
Nutrients 2019, 11(6), 1204; https://doi.org/10.3390/nu11061204 - 28 May 2019
Cited by 16 | Viewed by 7520
Abstract
Taiwanese women may practice traditional confinement after childbirth, and no study has investigated the nutritional status and the effects of postpartum depression on such women. The aim of this study was to investigate the association between nutritional status and postpartum depression at 6–8 [...] Read more.
Taiwanese women may practice traditional confinement after childbirth, and no study has investigated the nutritional status and the effects of postpartum depression on such women. The aim of this study was to investigate the association between nutritional status and postpartum depression at 6–8 weeks postpartum. A cross-sectional study was conducted on postpartum women who returned to the obstetrics and gynecology clinic for routine examination from January 2016 to September 2017. A total of 344 women received assessments based on the Edinburgh Postnatal Depression Scale (EPDS). An EPDS score of ≥10 indicated the presence of postpartum depressive symptoms (PPDS). A total of 97 women without such symptoms and 23 with PPDS completed nutritional parameter analyses and questionnaires. The results showed that the prevalence of postpartum depression (PPD) was 8.4%. The proportion was 70% for those who practiced confinement at home, significantly higher than for those in the non-PPDS group (45%). The overall psychological stress score was significantly higher and the postpartum care satisfaction score was significantly lower in those with PPDS compared to those without. In terms of nutritional biomarkers, the plasma riboflavin levels in the PPDS group were significantly lower than those in their symptomless counterparts (13.9%). The vitamin D insufficiency and deficiency rates in the non-PPD and PPDS groups were 35%, 41%, 48%, 26%, respectively. However, compared with those in the non-PPDS group, those with PPDS had significantly higher ratios of Σn-6/Σn-3, C20:3n-6/C18:3n-6, and C20:4n-6/(C20:5n-3 + C22:6n-3) (by 8.2%, 79.7%, and 8.8%, respectively), whereas they had lower ratios of C22:6n-3/C22:5n-6 (by 15.5%). Higher plasma riboflavin and erythrocyte C16:1n-9, C24:1n-9, C18:3n-6, and C20:5n-3 levels and lower Σn-6 fatty acid and C22:5n-6 levels decreased the risk of PPD after type of confinement, overall mental stress scores, and postpartum care satisfaction scores were adjusted for the logistic regression analysis. In conclusion, the plasma riboflavin level and erythrocyte fatty acid composition are potentially major contributors to PPD development. Full article
(This article belongs to the Special Issue Nutritional Biomarkers in Health and Disease)
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11 pages, 659 KiB  
Article
Comparisons of Estimated Intakes and Plasma Concentrations of Selected Fatty Acids in Pregnancy
by Marie T. B. Madsen, Anne A. Bjerregaard, Jeremy D. Furtado, Thorhallur I. Halldorsson, Marin Ström, Charlotta Granström, Edward Giovannucci and Sjurdur F. Olsen
Nutrients 2019, 11(3), 568; https://doi.org/10.3390/nu11030568 - 06 Mar 2019
Cited by 10 | Viewed by 3147
Abstract
The growing interest in potential health effects of long-chain polyunsaturated fatty acids (PUFAs) makes it important to evaluate the method used to assess the fatty acid intake in nutrition research studies. We aimed to validate the questionnaire-based dietary intake of selected PUFAs: eicosapentaenoic [...] Read more.
The growing interest in potential health effects of long-chain polyunsaturated fatty acids (PUFAs) makes it important to evaluate the method used to assess the fatty acid intake in nutrition research studies. We aimed to validate the questionnaire-based dietary intake of selected PUFAs: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), α-linolenic acid (ALA), linoleic acid (LA), and arachidonic acid (AA) within the Danish National Birth Cohort (DNBC), by comparing 345 women’s reported intake with concentration of plasma biomarkers. The applied questionnaire- and biomarker data reflect dietary intake from around the same time point in mid-pregnancy and relationships were investigated by use of Pearson and Spearman correlation and linear regression statistics. We demonstrated moderate but consistent adjusted correlations between dietary intake estimates and the corresponding plasma biomarker concentrations (differences in plasma concentration per 100 mg/day greater intake of 0.05 (95% CI: 0.02; 0.08)) and 0.05 (95% CI: 0.01; 0.08) percentage of total plasma fatty acids for EPA and DHA, respectively). The associations strengthened when restricting the analyses to women with ALA intake below the median intake. We found a weak correlation between the dietary intake of ALA and its plasma biomarker with a difference in plasma concentration of 0.07 (95% CI: 0.03; 0.10) percent of total plasma fatty acids per 1 g/day greater intake, while the dietary intake of LA and AA did not correlate with their corresponding biomarkers. Full article
(This article belongs to the Special Issue Nutritional Biomarkers in Health and Disease)
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11 pages, 1222 KiB  
Article
Omega-3 Fatty Acid Supplementation, Pro-Resolving Mediators, and Clinical Outcomes in Maternal-Infant Pairs
by Tara M. Nordgren, Ann Anderson Berry, Matthew Van Ormer, Samuel Zoucha, Elizabeth Elliott, Rebecca Johnson, Elizabeth McGinn, Caleb Cave, Katherine Rilett, Kara Weishaar, Sai Sujana Maddipati, Harriet Appeah and Corrine Hanson
Nutrients 2019, 11(1), 98; https://doi.org/10.3390/nu11010098 - 05 Jan 2019
Cited by 19 | Viewed by 4916
Abstract
Omega (n)-3 fatty acids are vital to neonatal maturation, and recent investigations reveal n-3 fatty acids serve as substrates for the biosynthesis of specialized pro-resolving lipid mediators (SPM) that have anti-inflammatory and immune-stimulating effects. The role SPM play in the protection against negative [...] Read more.
Omega (n)-3 fatty acids are vital to neonatal maturation, and recent investigations reveal n-3 fatty acids serve as substrates for the biosynthesis of specialized pro-resolving lipid mediators (SPM) that have anti-inflammatory and immune-stimulating effects. The role SPM play in the protection against negative maternal-fetal health outcomes is unclear, and there are no current biomarkers of n-3 fatty acid sufficiency. We sought to ascertain the relationships between n-3 fatty acid intake, SPM levels, and maternal-fetal health outcomes. We obtained n-3 fatty acid intake information from 136 mothers admitted for delivery using a food frequency questionnaire and measured docosahexaenoic acid (DHA)-derived SPMs resolvin D1 (RvD1) and RvD2 in maternal and cord plasma. We found significantly elevated SPM in maternal versus cord plasma, and increased SPM levels were associated with at-risk outcomes. We also identified that increased DHA intake was associated with elevated maternal plasma RvD1 (p = 0.03; R2 = 0.18) and RvD2 (p = 0.04; R2 = 0.20) in the setting of neonatal intensive care unit (NICU) admission. These findings indicate that increased n-3 fatty acid intake may provide increased substrate for the production of SPM during high-risk pregnancy/delivery conditions, and that increased maternal plasma SPM could serve as a biomarker for negative neonatal outcomes. Full article
(This article belongs to the Special Issue Nutritional Biomarkers in Health and Disease)
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15 pages, 503 KiB  
Article
Serum Trace Elements and Their Associations with Breast Cancer Subgroups in Korean Breast Cancer Patients
by Rihwa Choi, Min-Ji Kim, Insuk Sohn, Serim Kim, Isaac Kim, Jai Min Ryu, Hee Jun Choi, Jae-Myung Kim, Se Kyung Lee, Jonghan Yu, Seok Won Kim, Seok Jin Nam, Jeong Eon Lee and Soo-Youn Lee
Nutrients 2019, 11(1), 37; https://doi.org/10.3390/nu11010037 - 24 Dec 2018
Cited by 42 | Viewed by 4436
Abstract
The relationships between serum levels of trace elements and breast cancer remain relatively unknown. In this study, we investigate serum levels of seven trace elements in Korean breast cancer patients compared to controls without breast cancer. Serum trace element levels were determined using [...] Read more.
The relationships between serum levels of trace elements and breast cancer remain relatively unknown. In this study, we investigate serum levels of seven trace elements in Korean breast cancer patients compared to controls without breast cancer. Serum trace element levels were determined using inductively coupled plasma mass spectrometry in Korean breast cancer patients before initiation of breast cancer treatment. Korean females without breast cancer served as a control group. Trace element levels were measured in the discovery cohort (n = 287) and were validated in an independent cohort (n = 142). We further investigated possible associations between trace element levels and the presence of lymph node metastasis, distant metastasis, or triple-negative breast cancer among breast cancer patients in subgroup analyses. Serum manganese and molybdenum levels were significantly higher (p < 0.05) in breast cancer patients than in controls. Serum copper levels were significantly higher in breast cancer patients with distant metastasis, while selenium levels were significantly lower. Other trace elements were neither significantly different between breast cancer patients and controls nor between subgroups of breast cancer patients. Our study provides insights about the potential roles and impacts of trace elements through an assessment of the associations between trace elements and breast cancer. Full article
(This article belongs to the Special Issue Nutritional Biomarkers in Health and Disease)
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Review

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18 pages, 4941 KiB  
Review
Plasma Transthyretin as A Biomarker of Sarcopenia in Elderly Subjects
by Yves Ingenbleek
Nutrients 2019, 11(4), 895; https://doi.org/10.3390/nu11040895 - 21 Apr 2019
Cited by 26 | Viewed by 6038
Abstract
Skeletal muscle (SM) mass, the chief component of the structural compartment belonging to lean body mass (LBM), undergoes sarcopenia with increasing age. Decreased SM in elderly persons is a naturally occurring process that may be accelerated by acute or chronic nutritional deficiencies and/or [...] Read more.
Skeletal muscle (SM) mass, the chief component of the structural compartment belonging to lean body mass (LBM), undergoes sarcopenia with increasing age. Decreased SM in elderly persons is a naturally occurring process that may be accelerated by acute or chronic nutritional deficiencies and/or inflammatory disorders, declining processes associated with harmful complications. A recently published position paper by European experts has provided an overall survey on the definition and diagnosis of sarcopenia in elderly persons. The present review describes the additional contributory role played by the noninvasive transthyretin (TTR) micromethod. The body mass index (BMI) formula is currently used in clinical studies as a criterion of good health to detect, prevent, and follow up on the downward trend of muscle mass. The recent upsurge of sarcopenic obesity with its multiple subclasses has led to a confused stratification of SM and fat stores, prompting workers to eliminate BMI from screening programs. As a result, investigators are now focusing on indices of protein status that participate in SM growth, maturation, and catabolism that might serve to identify sarcopenia trajectories. Plasma TTR is clearly superior to all other hepatic biomarkers, showing the same evolutionary patterns as those displayed in health and disease by both visceral and structural LBM compartments. As a result, this TTR parameter maintains positive correlations with muscle mass downsizing in elderly persons. The liver synthesis of TTR is downregulated in protein-depleted states and suppressed in cytokine-induced inflammatory disorders. TTR integrates the centrally-mediated regulatory mechanisms governing the balance between protein accretion and protein breakdown, emerging as the ultimate indicator of LBM resources. This review proposes the adoption of a gray zone defined by cut-off values ranging from 200 mg/L to 100 mg/L between which TTR plasma values may fluctuate and predict either the best or the worst outcome. The best outcome occurs when appropriate dietary, medicinal and surgical decisions are undertaken, resuming TTR synthesis which manifests rising trends towards pre-stress levels. The worst occurs when all therapeutic means fail to succeed, leading inevitably to complete exhaustion of LBM and SM metabolic resources with an ensuing fatal outcome. Some patients may remain unresponsive in the middle of the gray area, combining steady clinical states with persistent stagnant TTR values. Using the serial measurement of plasma TTR values, these last patients should be treated with the most aggressive and appropriate therapeutic strategies to ensure the best outcome. Full article
(This article belongs to the Special Issue Nutritional Biomarkers in Health and Disease)
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