Postprandial Micronutrient Variability and Bioavailability: An Interventional Meal Study in Young vs. Old Participants.

This study explores age- and time-dependent variations in postprandial micronutrient absorption after a micronutrient-rich intervention meal within the Biomiel (bioavailability of micronutrients in elderly) study. Comprising 43 healthy participants, the study compares young (n = 21; mean age 26.90 years) and old (n = 22; mean age 66.77 years) men and women, analyzing baseline concentrations and six-hour postprandial dynamics of iron (Fe), copper (Cu), zinc (Zn), selenium (Se), iodine (I), free zinc (fZn), vitamin C, retinol, lycopene, ß-carotene, α-tocopherol, and γ-tocopherol, along with 25(OH) vitamin D (quantified only at baseline). Methodologically, quantifications in serum or plasma were performed at baseline and also at 90, 180, 270, and 360 min postprandially. Results reveal higher baseline serum Zn and plasma lycopene concentrations in the young group, whereas Cu, Se, Cu/Zn ratio, 25(OH) vitamin D, α-tocopherol, and γ-tocopherol were higher in old participants. Postprandial variability of Zn, vitamin C, and lycopene showed a strong time-dependency. Age-related differences in postprandial metabolism were observed for Se, Cu, and I. Nevertheless, most of the variance was explained by individuality. Despite some limitations, this study provides insights into postprandial micronutrient metabolism (in serum/plasma), emphasizing the need for further research for a comprehensive understanding of this complex field. Our discoveries offer valuable insights for designing targeted interventions to address and mitigate micronutrient deficiencies in older adults, fostering optimal health and well-being across the lifespan.

Associations of circulating GDF15 with combined cognitive frailty and depression in older adults of the MARK-AGE study.

Growth differentiation factor-15 (GDF15) might be involved in the development of cognitive frailty and depression. Therefore, we evaluated cross-sectional associations of plasma GDF15 with combined cognitive-frailty-and-depression in older (i.e. ≥ 55 years) and younger adults of the MARK-AGE study. In the present work, samples and data of MARK-AGE ("European study to establish bioMARKers of human AGEing") participants (N = 2736) were analyzed. Cognitive frailty was determined by the global cognitive functioning score (GCF) and depression by the Self-Rating Depression Scale (SDS score). Adults were classified into three groups: (I) neither-cognitive-frailty-nor-depression, (II) either-cognitive-frailty-or-depression or (III) both-cognitive-frailty-and-depression. Cross-sectional associations were determined by unadjusted and by age, BMI, sex, comorbidities and hsCRP-adjusted linear and logistic regression analyses. Cognitive frailty, depression, age and GDF15 were significantly related within the whole study sample. High GDF15 levels were significantly associated with both-cognitive-frailty-and-depression (adjusted ß = 0.177 [0.044 - 0.310], p = 0.009), and with low GCF scores and high SDS scores. High GDF15 concentrations and quartiles were significantly associated with higher odds to have both-cognitive-frailty-and-depression (adjusted odds ratio = 2.353 [1.267 - 4.372], p = 0.007; and adjusted odds ratio = 1.414 [1.025 - 1.951], p = 0.035, respectively) independent of age, BMI, sex, comorbidities and hsCRP. These associations remained significant when evaluating older adults. We conclude that plasma GDF15 concentrations are significantly associated with combined cognitive-frailty-and-depression status and, with cognitive frailty and depressive symptoms separately in old as well as young community-dwelling adults.

Evaluation of Modern Approaches for the Assessment of Dietary Carotenoids as Markers for Fruit and Vegetable Consumption.

The assessment of dietary carotenoids via blood measurements has been widely used as a marker for fruit and vegetable consumption. In the present study, modern, non-invasive approaches to assess dietary carotenoids, such as skin measurements and an app-based short dietary record (ASDR), were compared with conventional methods such as plasma status and handwritten 3-day dietary records. In an 8-week observational study, 21 healthy participants aged 50-65 years recorded their daily consumption of carotenoid-rich fruits and vegetables via a specially developed ASDR. Anthropometry, blood samplings and assessment of skin carotenoids via Raman and reflection spectroscopy were performed at baseline, after four weeks and at the end of the study. App-based intake data showed good correlations with plasma α-carotene (r = 0.74, p < 0.0001), ß-carotene (r = 0.71, p < 0.0001), and total plasma carotenoids (r = 0.65, p < 0.0001); weak correlations with plasma lutein/zeaxanthin and ß-cryptoxanthin (both r = 0.34, p < 0.05); and no correlation with plasma lycopene. Skin measurements via reflection and Raman spectroscopy correlated well with total plasma carotenoids (r = 0.81 and 0.72, respectively; both p < 0.0001), α-carotene (r = 0.75-0.62, p < 0.0001), and ß-carotene (r = 0.79-0.71, p < 0.0001); moderately with plasma lutein/zeaxanthin (both r = 0.51, p < 0.0001); weakly with plasma ß-cryptoxanthin (r = 0.40-0.31, p < 0.05); and showed no correlation with plasma lycopene. Skin measurements could provide a more convenient and noninvasive approach of estimating a person's fruit and vegetable consumption compared to traditional methods, especially in studies that do not intend blood sampling. ASDR records might function as a suitable, convenient tool for dietary assessment in nutritional intervention studies.

Patterns of Dietary Blood Markers Are Related to Frailty Status in the FRAILOMIC Validation Phase.

The influence of nutritional factors on frailty syndrome is still poorly understood. Thus, we aimed to confirm cross-sectional associations of diet-related blood biomarker patterns with frailty and pre-frailty statuses in 1271 older adults from four European cohorts. Principal component analysis (PCA) was performed based on plasma levels of α-carotene, ß-carotene, lycopene, lutein + zeaxanthin, ß-cryptoxanthin, α-tocopherol, γ-tocopherol and retinol. Cross-sectional associations between biomarker patterns and frailty status, according to Fried's frailty criteria, were assessed by using general linear models and multinomial logistic regression models as appropriate with adjustments for the main potential confounders. Robust subjects had higher concentrations of total carotenoids, ß-carotene and ß-cryptoxanthin than frail and pre-frail subjects and had higher lutein + zeaxanthin concentrations than frail subjects. No associations between 25-Hydroxyvitamin D3 and frailty status were observed. Two distinct biomarker patterns were identified in the PCA results. The principal component 1 (PC1) pattern was characterized by overall higher plasma levels of carotenoids, tocopherols and retinol, and the PC2 pattern was characterized by higher loadings for tocopherols, retinol and lycopene together and lower loadings for other carotenoids. Analyses revealed inverse associations between PC1 and prevalent frailty. Compared to participants in the lowest quartile of PC1, those in the highest quartile were less likely to be frail (odds ratio: 0.45, 95% CI: 0.25-0.80, p = 0.006). In addition, those in the highest quartile of PC2 showed higher odds for prevalent frailty (2.48, 1.28-4.80, p = 0.007) than those in the lowest quartile. Our findings strengthen the results from the first phase of the FRAILOMIC project, indicating carotenoids are suitable components for future biomarker-based frailty indices.

Effects of Exercise and Omega-3-Supplemented, High-Protein Diet on Inflammatory Markers in Serum, on Gene Expression Levels in PBMC, and after Ex Vivo Whole-Blood LPS Stimulation in Old Adults.

Inflammaging is related to cell senescence and reflects an erratic immune system, which promotes age-associated diseases. Exercise and nutrition, particularly omega-3 fatty acids, are able to affect inflammation. Therefore, we examined the effects of an 8-week exercise and dietary intervention on the inflammatory response in community-dwelling old adults. All participants received weekly vibration and home-based resistance exercise. Furthermore, participants were randomized to either a control, high-protein (1.2-1.5 g/kg), or high-protein, omega-3-enriched (2.2 g/day) diet. Before and after treatment, inflammatory markers in fasting serum and after whole-blood ex vivo lipopolysaccharide (LPS) stimulation were assessed. Gene expression levels of inflammatory markers were quantified in peripheral blood mononuclear cells (PBMC). Sixty-one participants (age: 70.6 ± 4.7 years; 47% men) completed the study. According to generalized linear mixed models, a high-protein, omega-3-enriched diet decreased circulating anti-inflammatory interleukin (IL-) 10 and IL-1 receptor antagonist (IL-1RA). Sex-stratified analyses showed also significantly reduced pro-inflammatory markers in men with a high-protein, omega-3-enriched diet. Gene expression of IL-1RA was significantly reduced after both protein-enriched diets compared with controls. In comparison to a high-protein diet, exercise alone showed lower LPS-induced release of c-c motif chemokine ligand-2 (CCL-2), which tended to be more pronounced in men compared with women. Eight weeks of a high-protein, omega-3-enriched diet combined with exercise decreased circulating anti-inflammatory markers, and pro-inflammatory markers in men. A high-protein diet attenuated anti-inflammatory markers on gene expression level in PBMC. Exercise alone resulted in a lower pro-inflammatory response to LPS-exposure in whole-blood cultures.

Frailty is characterized by biomarker patterns reflecting inflammation or muscle catabolism in multi-morbid patients.

BACKGROUND: Frailty development is partly dependent on multiple factors like low levels of nutrients and high levels of oxidative stress (OS) and inflammation potentially leading to a muscle-catabolic state. Measures of specific biomarker patterns including nutrients, OS and inflammatory biomarkers as well as muscle related biomarkers like 3-methylhistidine (3MH) may improve evaluation of mechanisms and the complex networks leading to frailty. METHODS: In 220 multi-morbid patients (≥ 60 years), classified as non-frail (n = 104) and frail (n = 116) according to Fried's frailty criteria, we measured serum concentrations of fat-soluble micronutrients, amino acids (AA), OS, interleukins (IL) 6 and 10, 3MH (biomarker for muscle protein turnover) and serum spectra of fatty acids (FA). We evaluated biomarker patterns by principal component analysis (PCA) and their cross-sectional associations with frailty by multivariate logistic regression analysis. RESULTS: Two biomarker patterns [principal components (PC)] were identified by PCA. PC1 was characterized by high positive factor loadings (FL) of carotenoids, anti-inflammatory FA and vitamin D3 together with high negative FL of pro-inflammatory FA, IL6 and IL6/IL10, reflecting an inflammation-related pattern. PC2 was characterized by high positive FL of AA together with high negative FL of 3MH-based biomarkers, reflecting a muscle-related pattern. Frail patients had significantly lower factor scores than non-frail patients for both PC1 [median: -0.27 (interquartile range: 1.15) vs. 0.27 (1.23); P = 0.001] and PC2 [median: -0.15 (interquartile range: 1.13) vs. 0.21 (1.38); P = 0.002]. Patients with higher PC1 or PC2 factor scores were less likely to be frail [odds ratio (OR): 0.62, 95% CI: 0.46-0.83, P = 0.001 for PC1; OR: 0.64, 95% CI: 0.48-0.86, P = 0.003 for PC2] compared with patients with lower PC1 or PC2 factor scores. This indicates that increasing levels of anti-inflammatory biomarkers and increasing levels of muscle-anabolic biomarkers are associated with a reduced likelihood (38% and 36%, respectively) for frailty. Significant associations remained after adjusting the regression models for potential confounders. CONCLUSIONS: We conclude that two specific patterns reflecting either inflammation-related or muscle-related biomarkers are both significantly associated with frailty among multi-morbid patients and that these specific biomarker patterns are more informative than single biomarker analyses considering frailty identification.

The Effect of Dextrose or Protein Ingestion on Circulating Growth Differentiation Factor 15 and Appetite in Older Compared to Younger Women.

Growth differentiation factor 15 (GDF15) is a stress signal that can be induced by protein restriction and is associated with reduced food intake. Anorexia of aging, insufficient protein intake as well as high GDF15 concentrations often occur in older age, but it is unknown whether GDF15 concentrations change acutely after meal ingestion and affect appetite in older individuals. After an overnight fast, appetite was assessed in older (n = 20; 73.7 ± 6.30 years) and younger (n = 20; 25.7 ± 4.39 years) women with visual analogue scales, and concentrations of circulating GDF15 and glucagon-like peptide-1 (GLP-1) were quantified before and at 1, 2 and 4 h after ingestion of either dextrose (182 kcal) or a mixed protein-rich meal (450 kcal). In response to dextrose ingestion, appetite increased in both older and younger women, whereas GDF15 concentrations increased only in the older group. In older women, appetite response was negatively correlated with the GDF15 response (rho = -0.802, p = 0.005). Following high-protein ingestion, appetite increased in younger women, but remained low in the old, while GDF15 concentrations did not change significantly in either age group. GLP-1 concentrations did not differ between age groups or test meals. In summary, acute GDF15 response differed between older and younger women. Associations of postprandial appetite and GDF15 following dextrose ingestion in older women suggest a reduced appetite response when the GDF15 response is high, thus supporting the proposed anorectic effects of high GDF15 concentrations.

Effects of an Omega-3 Supplemented, High-Protein Diet in Combination with Vibration and Resistance Exercise on Muscle Power and Inflammation in Old Adults: A Pilot Randomized Controlled Trial.

BACKGROUND: Inflammaging is considered to drive loss of muscle function. Omega-3 fatty acids exhibit anti-inflammatory properties. Therefore, we examined the effects of eight weeks of vibration and home-based resistance exercise combined with a whey-enriched, omega-3-supplemented diet on muscle power, inflammation and muscle biomarkers in community-dwelling old adults. METHODS: Participants were randomized to either exercise (3x/week, n = 20), exercise + high-protein diet (1.2-1.5 g/kg, n = 20), or exercise + high-protein and omega-3-enriched diet (2.2 g/day, n = 21). Muscle power (watt/m2) and chair rise test (CRT) time (s) were assessed via CRT measured with mechanography. Furthermore, leg strength (kg/m2) and fasting concentrations of inflammatory (interleukin (IL-) 6, IL-10, high-mobility group box-1 (HMGB-1)) and muscle biomarkers (insulin-like growth factor (IGF-) 1, IGF-binding protein-3, myostatin) were assessed. RESULTS: Sixty-one participants (70.6 ± 4.7 years; 47% men) completed the study. According to generalized linear mixed models, a high-protein diet improved leg strength and CRT time. Only IGF-1 increased with additional omega-3. Sex-specific analyses revealed that muscle power, IL-6, IL-6/IL-10 ratio, and HMGB-1 improved significantly in the male high-protein, omega-3-enriched group only. CONCLUSION: Vibration and home-based resistance exercise combined with a high-protein, omega-3-enriched diet increased muscle power and reduced inflammation in old men, but not in old women. While muscle biomarkers remained unchanged, a high-protein diet combined with exercise improved leg strength and CRT time.

Pre-Operative Assessment of Micronutrients, Amino Acids, Phospholipids and Oxidative Stress in Bariatric Surgery Candidates.

Obesity has been linked to lower concentrations of fat-soluble micronutrients and higher concentrations of oxidative stress markers as well as an altered metabolism of branched chain amino acids and phospholipids. In the context of morbid obesity, the aim of this study was to investigate whether and to which extent plasma status of micronutrients, amino acids, phospholipids and oxidative stress differs between morbidly obese (n = 23) and non-obese patients (n = 13). In addition to plasma, malondialdehyde, retinol, cholesterol and triglycerides were assessed in visceral and subcutaneous adipose tissue in both groups. Plasma γ-tocopherol was significantly lower (p < 0.011) in the obese group while other fat-soluble micronutrients showed no statistically significant differences between both groups. Branched-chain amino acids (all p < 0.008) and lysine (p < 0.006) were significantly higher in morbidly obese patients compared to the control group. Malondialdehyde concentrations in both visceral (p < 0.016) and subcutaneous (p < 0.002) adipose tissue were significantly higher in the morbidly obese group while plasma markers of oxidative stress showed no significant differences between both groups. Significantly lower plasma concentrations of phosphatidylcholine, phosphatidylethanolamine, lyso-phosphatidylethanolamine (all p < 0.05) and their corresponding ether-linked analogs were observed, which were all reduced in obese participants compared to the control group. Pre-operative assessment of micronutrients in patients undergoing bariatric surgery is recommended for early identification of patients who might be at higher risk to develop a severe micronutrient deficiency post-surgery. Assessment of plasma BCAAs and phospholipids in obese patients might help to differentiate between metabolic healthy patients and those with metabolic disorders.

Fasting Concentrations and Postprandial Response of 1,2-Dicarbonyl Compounds 3-Deoxyglucosone, Glyoxal, and Methylglyoxal Are Not Increased in Healthy Older Adults.

Dicarbonyl stress describes the increased formation of 1,2-dicarbonyl compounds and is associated with age-related pathologies. The role of dicarbonyl stress in healthy aging is poorly understood. In a preliminary study, we analyzed 1,2-dicarbonyl compounds, namely 3-deoxyglucosone (3-DG), glyoxal (GO), and methylglyoxal (MGO) in plasma of older (25 months, n = 11) and younger (5 months, n = 14) male C57BL/6J (B6) mice via ultra performance liquid chromatography tandem mass spectrometry. Postprandial 3-DG was higher in younger compared to older mice, whereas no differences were found for GO and MGO. Subsequently, in the main study, we analyzed fasting serum of older women (OW, 72.4 ± 6.14 years, n = 19) and younger women (YW, 27.0 ± 4.42 years, n = 19) as well as older men (OM, 74.3 ± 5.20 years, n = 15) and younger men (YM, 27.0 ± 3.34, n = 15). Serum glucose, insulin, 1,2-dicarbonyl concentrations, and markers of oxidative stress were quantified. In a subgroup of this cohort, an oral dextrose challenge was performed, and postprandial response of 1,2-dicarbonyl compounds, glucose, and insulin were measured. In women, there were no age differences regarding fasting 1,2-dicarbonyl concentrations nor the response after the oral dextrose challenge. In men, fasting MGO was significantly higher in OM compared to YM (median: 231 vs 158 nM, p = .006), whereas no age differences in fasting 3-DG and GO concentrations were found. Glucose (310 ± 71.8 vs 70.8 ± 11.9 min·mmol/L) and insulin (7 149 ± 1 249 vs 2 827 ± 493 min·µIU/mL) response were higher in OM compared to YM, which did not translate into a higher 1,2-dicarbonyl response in older individuals. Overall, aging does not necessarily result in dicarbonyl stress, indicating that strategies to cope with 1,2-dicarbonyl formation can remain intact.

Altered Adiponectin Response in Older Women Following Dextrose and High-Fat Dietary Challenges.

SCOPE: Despite its beneficial properties, higher adiponectin concentrations are paradoxically associated with mortality in advanced age. Several mechanisms are being discussed. However, little is known about postprandial regulation of adiponectin in older adults. We assessed age-specific differences of the adiponectin response to different test meals considering potential determinants. METHODS AND RESULTS: Older (n = 20) and younger (n = 22) women are randomized to a dextrose (DEX) or high-fat (HF) dietary challenge. Postprandial adiponectin and fibroblast growth factor 21 (FGF21) concentrations are measured before and 60, 120, 240 min after ingestion. We assessed postprandial changes and group differences using linear mixed models controlled for possible determinants. In younger women, postprandial adiponectin remains stable after both test meals. In contrast, adiponectin increases following DEX and decreases after HF in older women, irrespective of control variables. Postprandial adiponectin is positively associated with malondialdehyde and inversely associated with interleukin-6 following DEX and also negatively associated with metabolic parameters after both test meals. In older women, elevated postprandial FGF21 concentrations are associated with a higher adiponectin response (ß = 30.7, 95% CI 10.6-50.8, p = 0.007). CONCLUSIONS: Adiponectin response is associated with type of dietary challenge, age, and FGF21 response. Age-group differences are partly attributable to metabolic parameters and oxidative stress.

Postprandial dynamics and response of fibroblast growth factor 21 in older adults.

BACKGROUND & AIMS: Fibroblast growth factor 21 (FGF21) plays a pivotal role in glucose and lipid metabolism and has been proposed as a longevity hormone. However, elevated plasma FGF21 concentrations are paradoxically associated with mortality in higher age and little is known about the postprandial regulation of FGF21 in older adults. In this parallel group study, we investigated postprandial FGF21 dynamics and response in older (65-85 years) compared to younger (18-35 years) adults following test meals with varying macronutrient composition. METHODS: Participants (n = 60 older; n = 60 younger) were randomized to one of four test meals: dextrose, high carbohydrate (HC), high fat (HF) or high protein (HP). Blood was drawn before and 15, 30, 60, 120, 240 min after meal ingestion. Postprandial dynamics were evaluated using repeated measures ANCOVA. FGF21 response was assessed by incremental area under the curve. RESULTS: Fasting FGF21 concentrations were significantly higher in older adults. FGF21 dynamics were affected by test meal (p < 0.001) and age (p = 0.013), when adjusted for BMI and fasting FGF21. Postprandial FGF21 concentrations steadily declined over 240 min in both age groups after HF and HP, but not after dextrose or HC ingestion. At 240 min, FGF21 concentrations were significantly higher in older than in younger adults following dextrose (133 pg/mL, 95%CI: 103, 172 versus 91.2 pg/mL, 95%CI: 70.4, 118; p = 0.044), HC (109 pg/mL, 95%CI: 85.1, 141 versus 70.3 pg/mL, 95%CI: 55.2, 89.6; p = 0.014) and HP ingestion (45.4 pg/mL, 95%CI: 34.4, 59.9 versus 27.9 pg/mL 95%CI: 20.9, 37.1; p = 0.018). FGF21 dynamics and response to HF were similar for both age groups. CONCLUSIONS: The age-specific differences in postprandial FGF21 dynamics and response in healthy adults, potentially explain higher FGF21 concentrations in older age. Furthermore, there appears to be a significant impact of acute and recent protein intake on FGF21 secretion.

Quantifying technical confounders in microbiome studies.

AIMS: Recent technical developments have allowed the study of the human microbiome to accelerate at an unprecedented pace. Methodological differences may have considerable impact on the results obtained. Thus, we investigated how different storage, isolation, and DNA extraction methods can influence the characterization of the intestinal microbiome, compared to the impact of true biological signals such as intraindividual variability, nutrition, health, and demographics. METHODS AND RESULTS: An observative cohort study in 27 healthy subjects was performed. Participants were instructed to collect stool samples twice spaced by a week, using six different methods (naive and Zymo DNA/RNA Shield on dry ice, OMNIgene GUT, RNALater, 95% ethanol, Zymo DNA/RNA Shield at room temperature). DNA extraction from all samples was performed comparatively using QIAamp Power Fecal and ZymoBIOMICS DNA Kits. 16S rRNA sequencing of the gut microbiota as well as qPCRs were performed on the isolated DNA. Metrics included alpha diversity as well as multivariate and univariate comparisons of samples, controlling for covariate patterns computationally. Interindividual differences explained 7.4% of overall microbiome variability, whereas the choice of DNA extraction method explained a further 5.7%. At phylum level, the tested kits differed in their recovery of Gram-positive bacteria, which is reflected in a significantly skewed enterotype distribution. CONCLUSION: DNA extraction methods had the highest impact on observed microbiome variability, and were comparable to interindividual differences, thus may spuriously mimic the microbiome signatures of various health and nutrition factors. Conversely, collection methods had a relatively small influence on microbiome composition. The present study provides necessary insight into the technical variables which can lead to divergent results from seemingly similar study designs. We anticipate that these results will contribute to future efforts towards standardization of microbiome quantification procedures in clinical research.

Medication Intake Is Associated with Lower Plasma Carotenoids and Higher Fat-Soluble Vitamins in the Cross-Sectional MARK-AGE Study in Older Individuals.

The regular use of medication may interfere with micronutrient metabolism on several levels, such as absorption, turnover rate, and tissue distribution, and this might be amplified during aging. This study evaluates the impact of self-reported medication intake on plasma micronutrients in the MARK-AGE Project, a cross-sectional observational study in 2217 subjects (age- and sex-stratified) aged 35-75 years from six European countries that were grouped according to age. Polypharmacy as possible determinant of micronutrient concentrations was assessed using multiple linear regression models adjusted for age-group, dietary fruit, vegetables, and juice intake, and other confounders. Younger participants reported taking fewer drugs than older participants. Inverse associations between medication intake and lutein (-3.31% difference per increase in medication group), ß-carotene (-11.44%), α-carotene (-8.50%) and positive associations with retinol (+2.26%), α-tocopherol/cholesterol (+2.89%) and γ-tocopherol/cholesterol (+1.36%) occurred in multiple adjusted regression models. Combined usage of a higher number of medical drugs was associated with poorer status of carotenoids on the one hand and higher plasma concentrations of retinol, α- and γ-tocopherol on the other hand. Our results raise concerns regarding the safety of drug combinations via the significant and surprisingly multifaceted disturbance of the concentrations of relevant micronutrients.

Plasma carotenoids, tocopherols and retinol - Association with age in the Berlin Aging Study II.

Regular consumption of fruits and vegetables, which is related to high plasma levels of lipid-soluble micronutrients such as carotenoids and tocopherols, is linked to lower incidences of various age-related diseases. Differences in lipid-soluble micronutrient blood concentrations seem to be associated with age. Our retrospective analysis included men and women aged 22-37 and 60-85 years from the Berlin Aging Study II. Participants with simultaneously available plasma samples and dietary data were included (n = 1973). Differences between young and old groups were found for plasma lycopene, α-carotene, α-tocopherol, ß-cryptoxanthin (only in women), and γ-tocopherol (only in men). ß-Carotene, retinol and lutein/zeaxanthin did not differ between young and old participants regardless of the sex. We found significant associations for lycopene, α-carotene (both inverse), α-tocopherol, γ-tocopherol, and ß-carotene (all positive) with age. Adjusting for BMI, smoking status, season, cholesterol and dietary intake confirmed these associations, except for ß-carotene. These micronutrients are important antioxidants and associated with lower incidence of age-related diseases, therefore it is important to understand the underlying mechanisms in order to implement dietary strategies for the prevention of age-related diseases. To explain the lower lycopene and α-carotene concentration in older subjects, bioavailability studies in older participants are necessary.

Associations of fat-soluble micronutrients and redox biomarkers with frailty status in the FRAILOMIC initiative.

BACKGROUND: A poor fat-soluble micronutrient (FMN) and a high oxidative stress status are associated with frailty. Our aim was to determine the cross-sectional association of FMNs and oxidative stress biomarkers [protein carbonyls (PrCarb) and 3-nitrotyrosine] with the frailty status in participants older than 65 years. METHODS: Plasma levels of vitamins A (retinol), D3 , E (α-tocopherol and γ-tocopherol) and carotenoids (α-carotene and ß-carotene, lycopene, lutein/zeaxanthin, and ß-cryptoxanthin), PrCarb, and 3-nitrotyrosine were measured in 1450 individuals of the FRAILOMIC initiative. Participants were classified into robust, pre-frail, and frail using Fried's frailty criteria. Associations between biomarkers and frailty status were assessed by general linear and logistic regression models, both adjusted for cohort, season of blood sampling, gender, age, height, weight, and smoking. RESULTS: Robust participants had significantly higher vitamin D3 and lutein/zeaxanthin concentrations than pre-frail and frail subjects; had significantly higher γ-tocopherol, α-carotene, ß-carotene, lycopene, and ß-cryptoxanthin concentrations than frail subjects, and had significantly lower PrCarb concentrations than frail participants in multivariate linear models. Frail subjects were more likely to be in the lowest than in the highest tertile for vitamin D3 (adjusted odds ratio: 2.15; 95% confidence interval: 1.42-3.26), α-tocopherol (2.12; 1.39-3.24), α-carotene (1.69; 1.00-2.88), ß-carotene (1.84; 1.13-2.99), lycopene (1.94; 1.24-3.05), lutein/zeaxanthin (3.60; 2.34-5.53), and ß-cryptoxanthin (3.02; 1.95-4.69) and were more likely to be in the highest than in the lowest tertile for PrCarb (2.86; 1.82-4.49) than robust subjects in multivariate regression models. CONCLUSIONS: Our study indicates that both low FMN and high PrCarb concentrations are associated with pre-frailty and frailty.

Associations of Plasma 3-Methylhistidine with Frailty Status in French Cohorts of the FRAILOMIC Initiative.

Frailty and sarcopenia are characterized by a loss of muscle mass and functionality and are diagnosed mainly by functional tests and imaging parameters. However, more muscle specific biomarkers are needed to improve frailty diagnosis. Plasma 3-methylhistidine (3-MH), as well as the 3-MH-to-creatinine (3-MH/Crea) and 3-MH-to-estimated glomerular filtration rate (3-MH/eGFR) ratios might support the diagnosis of frailty. Therefore, we investigated the cross-sectional associations between plasma 3-MH, 3-MH/Crea and 3-MH/eGFR with the frailty status of community-dwelling individuals (>65 years). 360 participants from two French cohorts of the FRAILOMIC initiative were classified into robust, pre-frail and frail according to Fried's frailty criteria. General linear models as well as bivariate and multiple linear and logistic regression models, which were adjusted for several confounders, were applied to determine associations between biomarkers and frailty status. The present study consisted of 37.8% robust, 43.1% pre-frail and 19.2% frail participants. Frail participants had significantly higher plasma 3-MH, 3-MH/Crea and 3-MH/eGFR ratios than robust individuals, and these biomarkers were positively associated with frailty status. Additionally, the likelihood to be frail was significantly higher for every increase in 3-MH (1.31-fold) and 3-MH/GFR (1.35-fold) quintile after adjusting for confounders. We conclude that 3-MH, 3-MH/Crea and 3-MH/eGFR in plasma might be potential biomarkers to identify frail individuals or those at higher risk to be frail, and we assume that there might be biomarker thresholds to identify these individuals. However, further, especially longitudinal studies are needed.

Gender- and age-dependencies of oxidative stress, as detected based on the steady state concentrations of different biomarkers in the MARK-AGE study.

Recently, Weber et al. published a thorough investigation of the age-dependency of oxidative stress (OS) determined by the steady state concentrations of different compounds - oxidation products and antioxidants - that are in common use as biomarkers of OS in 2207 healthy individuals of the cross-sectional MARK-AGE Project. The correlations among biomarkers were significant but weak. These findings may indicate different manifestations of OS and must further be evaluated. Here, we report a refined analysis of OS based on the above-mentioned original data. We show that malondialdehyde (MDA) appears to be sensitive to both gender and age. It is significantly lower and shows a greater age-dependence in women than in men. The age-dependency of MDA in women arises in a stepwise fashion. The age-dependent slope of the steady state concentration is maximal at the age between 50 and 55 years, indicating that it may be attributed to the change of metabolism in the post-menopause. Interestingly, total glutathione (GSH) decreased with age simultaneously with the increase in MDA. Different biomarkers yield different gender- and age-dependencies. Unlike the concentration of MDA, the concentrations of the other two oxidation products, i.e. protein carbonyls and 3-nitrotyrosine were similar in men and women and appeared to be independent of age in the healthy study population. The analyzed antioxidants exhibited different gender- and age-dependencies. In conclusion, it appears that all the biomarkers assessed here reflect different types of OS and that MDA and GSH reflect the same type of OS.

Methionine restriction prevents onset of type 2 diabetes in NZO mice.

Dietary methionine restriction (MR) is well known to reduce body weight by increasing energy expenditure (EE) and insulin sensitivity. An elevated concentration of circulating fibroblast growth factor 21 (FGF21) has been implicated as a potential underlying mechanism. The aims of our study were to test whether dietary MR in the context of a high-fat regimen protects against type 2 diabetes in mice and to investigate whether vegan and vegetarian diets, which have naturally low methionine levels, modulate circulating FGF21 in humans. New Zealand obese (NZO) mice, a model for polygenic obesity and type 2 diabetes, were placed on isocaloric high-fat diets (protein, 16 kcal%; carbohydrate, 52 kcal%; fat, 32 kcal%) that provided methionine at control (Con; 0.86% methionine) or low levels (0.17%) for 9 wk. Markers of glucose homeostasis and insulin sensitivity were analyzed. Among humans, low methionine intake and circulating FGF21 levels were investigated by comparing a vegan and a vegetarian diet to an omnivore diet and evaluating the effect of a short-term vegetarian diet on FGF21 induction. In comparison with the Con group, MR led to elevated plasma FGF21 levels and prevented the onset of hyperglycemia in NZO mice. MR-fed mice exhibited increased insulin sensitivity, higher plasma adiponectin levels, increased EE, and up-regulated expression of thermogenic genes in subcutaneous white adipose tissue. Food intake and fat mass did not change. Plasma FGF21 levels were markedly higher in vegan humans compared with omnivores, and circulating FGF21 levels increased significantly in omnivores after 4 d on a vegetarian diet. These data suggest that MR induces FGF21 and protects NZO mice from high-fat diet-induced glucose intolerance and type 2 diabetes. The normoglycemic phenotype in vegans and vegetarians may be caused by induced FGF21. MR akin to vegan and vegetarian diets in humans may offer metabolic benefits via increased circulating levels of FGF21 and merits further investigation.-Castaño-Martinez, T., Schumacher, F., Schumacher, S., Kochlik, B., Weber, D., Grune, T., Biemann, R., McCann, A., Abraham, K., Weikert, C., Kleuser, B., Schürmann, A., Laeger, T. Methionine restriction prevents onset of type 2 diabetes in NZO mice.

The Influence of Dietary Habits and Meat Consumption on Plasma 3-Methylhistidine-A Potential Marker for Muscle Protein Turnover.

SCOPE: 3-Methylhistidine (3-MH) as a potential biomarker for muscle protein turnover is influenced by meat intake but data on the impact of meat on plasma 3-MH are scarce. We determined the association of plasma 3-MH, 1-methylhistidine (1-MH), and creatinine with dietary habits and assessed the impact of a single white meat intervention during a meat-free period. METHODS AND RESULTS: Plasma 3-MH, 1-MH, and creatinine concentrations of healthy young omnivores (n = 19) and vegetarians (n = 16) were analyzed together with data on anthropometry, body composition, grip strength, and nutrition. After baseline measurements omnivores adhered to a meat-free diet for 6 days and received a defined administration of chicken breast on day four. At baseline, omnivores had higher plasma 3-MH and 1-MH concentrations than vegetarians. White meat administration led to a slight increase in plasma 3-MH in omnivores. The elevated 3-MH concentrations significantly declined within 24 h after white meat intake. CONCLUSION: 1-MH concentrations in plasma seem to be suitable to display (white) meat consumption and its influence on 3-MH plasma concentration. 3-MH in plasma may be used as a biomarker for muscle protein turnover if subjects have not consumed meat in the previous 24 h.