Vitamin D deficiency contributes to overtraining syndrome in excessive trained C57BL/6 mice.

Overtraining syndrome is a condition resulting from excessive training load associated with inadequate recovery and poor sleep quality, leading to performance decrements and fatigue. Here we hypothesized that vitamin D (VitD) deficiency is a lead factor in the development of the overtraining syndrome. To test this hypothesis, two groups of 60-week-old C57BL/6 mice followed a 16-week excessive eccentric-based overtraining by excessive downhill running with or without dietary VitD depletion (EX and EX-D- groups). Two control groups were trained by uphill running at the same load with or without VitD depletion (CX and CX-D- groups). Handgrip strength decreased throughout the protocol for all groups but the decrease was sharper in EX-D- group (VitD × training, p = 0.0427). At the end of the protocol, the mass of Triceps brachii muscle, which is heavily stressed by eccentric contractions, was reduced in eccentric-trained groups (training effect, p = 0.0107). This atrophy was associated with a lower concentration of the anabolic myokine IL-15 (training effect, p = 0.0314) and a tendency to a higher expression of the atrogene cathepsin-L (training effect, p = 0.0628). VitD depletion led to a 50% decrease of the fractional protein synthesis rate in this muscle (VitD effect, p = 0.0004) as well as decreased FGF21 (VitD effect, p = 0.0351) and increased osteocrin (VitD effect, p = 0.038) concentrations that would lead to metabolic defects. Moreover, the proportion of anti-inflammatory Th2 lymphocytes was significantly decreased by the combination of eccentric training with VitD depletion (vitD × training, p = 0.0249) suggesting a systemic inflammation. Finally, exploratory behavior time of mice was decreased by VitD depletion (VitD effect, p = 0.0146) suggesting a cognitive dysfunction. Our results suggest that VitD deficiency exacerbates the effects of overtraining.

Formulation, process conditions, and biological evaluation of dairy mixed gels containing fava bean and milk proteins: Effect on protein retention in growing young rats.

Food formulation and process conditions can indirectly influence AA digestibility and bioavailability. Here we investigated the effects of formulation and process conditions used in the manufacture of novel blended dairy gels (called "mixed gels" here) containing fava bean (Vicia faba) globular proteins on both protein composition and metabolism when given to young rats. Three mixed dairy gels containing casein micelles and fava bean proteins were produced either by chemical acidification (A) with glucono-δ-lactone (GDL) or by lactic acid fermentation. Fermented gels containing casein and fava bean proteins were produced without (F) or with (FW) whey proteins. The AA composition of mixed gels was evaluated. The electrophoretic patterns of mixed protein gels analyzed by densitometry evidenced heat denaturation and aggregation via disulfide bonds of fava bean 11S legumin that could aggregate upon heating of the mixtures before gelation. Moreover, fermented gels showed no particular protein proteolysis compared with gel obtained by GDL-induced acidification. Kinetics of acidification were also evaluated. The pH decreased rapidly during gelation of GDL-induced acid gel compared with fermented gel. Freeze-dried F, A, and FW mixed gels were then fed to 30 young (1 mo old) male Wistar rats for 21 d (n = 10/diet). Fermented mixed gels significantly increased protein efficiency ratio (+58%) and lean mass (+26%), particularly muscle mass (+9%), and muscle protein content (+15%) compared with GDL-induced acid gel. Furthermore, F and FW formulas led to significantly higher apparent digestibility and true digestibility (+7%) than A formula. Blending fava bean, casein, and whey proteins in the fermented gel FW resulted in 10% higher leucine content and significantly higher protein retention in young rats (+7% and +28%) than the F and A mixed gels, respectively. Based on protein gain in young rats, the fermented fava bean, casein, and whey mixed proteins gel was the most promising candidate for further development of mixed protein gels with enhanced nutritional benefits.

Low socio-economic status is a newly identified independent risk factor for poor vitamin D status in severely obese adults.

BACKGROUND: Hypovitaminosis D is very prevalent, especially in the obese population. However, the degree of severity and the parameters involved in vitamin D deficiency in this population are still unclear. The present study aimed to identify, from among the factors known to influence vitamin D status in a healthy population, those impacting the same parameter in obese population. METHODS: Serum 25-OH-D concentration was measured in 564 patients with class III obesity [i.e. severe and morbid obesity; mean (SD) body mass index (BMI) 42.04 (6.92) kg m-2 ] and their demographic, clinical, biological, anthropometric, dietary and socio-economic data were collected. RESULTS: We observed that 96% of the obese patients had serum 25-OH-D lower than 30 ng mL-1 . Severe vitamin D deficiency (serum 25-OH-D concentration <10 ng mL-1 ) affected 35% of this population. We found an inverse relationship between 25-OH-D levels and BMI (P = 0.012), fat mass (P = 0.041), metabolic syndrome (P < 0.0001), fasting blood glucose (P = 0.023), homeostasis model assessment for insulin resistance (P = 0.008), waist circumference (P = 0.001), and fasting blood triglycerides (P = 0.002) and C-reactive protein (P = 0.005). Low socio-economic status independently increased the risk of severe vitamin D deficiency [odds ratio (OR) = 1.98; 95% confidence interval (CI) 1.25-3.13], especially in the autumn-winter season (OR = 2.94; 95% CI 1.98-4.36), morbid obesity (OR = 3.19; 95% CI 1.49-6.82), metabolic syndrome (OR = 1.6; 95% CI 1.06-2.42) and inflammation (OR = 1.03; 95% CI 1.01-1.06). CONCLUSIONS: Vitamin D deficiency is extremely common among obese patients, and the prevalence of severe deficiency is high. The association of adiposity, high body mass index, metabolic syndrome and inflammation with vitamin D status is marked, whereas low socio-economic status appears to be a major risk factor for severe vitamin D deficiency, suggesting that vitamin D deficiency may at least in part be responsible for the greater health vulnerability of populations with low socio-economic status.

Arginine behaviour after arginine or citrulline administration in older subjects.

Arginine (ARG) and its precursor citrulline (CIT) are popular dietary supplements, especially for the elderly. However, age-related reductions in lean body mass and alterations in organ functions could change their bioavailability. Pharmacokinetics and tolerance to amino acid (AA) loads are poorly documented in elderly subjects. The objective here was to characterise the plasma kinetics of CIT and ARG in a single-dosing study design. Eight fasting elderly men underwent two separate isomolar oral loading tests (10 g of CIT or 9·94 g of ARG). Blood was withdrawn over an 8-h period to measure plasma AA concentrations. Only CIT, ornithine and ARG plasma concentrations were changed. Volume of distribution was not dependent on AA administered. Conversely, parameters related to ARG kinetics were strongly dependent on AA administered: after ARG load, elimination was higher (ARG>CIT; P=0·041) and admission period+time at peak concentration was lower (ARG

[Impact of HPV status on nutritional status during radio chemotherapy for oropharyngeal cancer]. / Impact du statut HPV sur l'évolution nutritionnelle au cours de la chimioradiothérapie des patients atteints d'un cancer de l'oropharynx.

PURPOSE: Patients with oropharyngeal cancer are at high nutritional risk before and during treatment. Little is known about the influence of human papillomavirus (HPV) infection on nutritional status and its evolution during treatment. MATERIALS AND METHODS: A single-center retrospective study was conducted between August 2017 and December 2020 including 48 patients (14 HPV-induced: HPV+ and 34 non-HPV-induced: HPV-) with oropharyngeal squamous cell carcinoma treated by radiotherapy±chemotherapy (RT/CT). Nutritional risk at the time of tumor assessment (TA) was assessed by weight loss, swallowing ability, and the presence of digestive disorders in 4 stages of increasing severity. Nutritional status was assessed by weight and nutrition risk index (NRI) at the time of TA, before the start and at 3 months from the end of RT±CT. During RT±CT, the NRI and the systemic inflammatory response index (SIRI=neutrophils * monocytes/lymphocytes) were assessed weekly. RESULTS: HPV+patients were at lower nutritional risk at TA (50% grade ≥2 vs 85%, P=0.02), lost more weight (6% of their body weight vs 3%, P=0.05), and increased their SIRI by 7.5 points more than HPV- patients (P=0.04) during RT/CT. CONCLUSION: HPV+ oropharyngeal cancer patients are at high nutritional risk even in the absence of undernutrition at the outset of management.

Blood biomarkers of mild traumatic brain injury: State of art.

BACKGROUND: Mild traumatic brain injury (mTBI) is one of the most common causes of emergency department visits around the world. Up to 90% of injuries are classified as mTBI. Cranial computed tomography (CCT) is a standard diagnosis tool to identify intracranial complications in adults with mTBI. Alternatively, children can be admitted for inpatient observation with CCT scans performed only on those with clinical deterioration. The use of blood biomarkers is a supplementary tool for identifying patients at risk of intracerebral lesions who may need imaging. METHOD: We realised a bibliographic state of art providing a contemporary clinical and laboratory framework for blood biomarker testing in mTBI management. RESULTS: The S100B protein is the only biomarker that can be used today in the clinical routine for management of mTBI with appropriate evidence-based medicine. Due to its excellent negative predictive value, S100B protein is an alternative choice to CCT scanning for mTBI management with considered, consensual and pragmatic use. In this state of art, we propose points to help clinicians and clinical pathologists use serum S100B protein in the clinical routine. A state of art on the different biomarkers (GFAP, UCH-L1, NF [H or L], tau, H-FABP, SNTF, NSE, miRNAs, MBP) is also conducted. Some of these other biomarkers, used alone (GFAP, UCH-L1) or in combination (GFAP+H-FABP±S100B±IL10) can improve the specificity of S100B. CONCLUSION: Using a bibliographic state of art, we highlighted the added values of the blood biomarkers for the clinical management of mTBI.

Nutritional factors in sport-related concussion.

BACKGROUND: Sports concussion is a major problem that affects thousands of people every year. Concussion-related neurometabolic changes are thought to underlie neurophysiological alterations and post-concussion symptoms, such as headaches and sensitivity to light and noise, disabilities of concentration and tiredness. The injury triggers a complex neurometabolic cascade involving multiple mechanisms. There are pharmaceutical treatments that target one mechanism, but specific nutrients have been found to impact several pathways, thus offering a broader approach. This has prompted intensive research into the use of nutrient supplements as a concussion prevention and treatment strategy. METHOD: We realised a bibliographic state of art providing a contemporary clinical and preclinical studies dealing with nutritional factors in sport-related concussion. RESULTS: Numerous supplements, including n-3 polyunsaturated fatty acids, sulfur amino acids, antioxidants and minerals, have shown promising results as aids to concussion recovery or prevention in animal studies, most of which use a fluid percussion technique to cause brain injury, and in a few human studies of severe or moderate traumatic brain injury. Current ongoing human trials can hopefully provide us with more information, in particular, on new options, i.e. probiotics, lactate or amino acids, for the use of nutritional supplements for concussed athletes. CONCLUSION: Nutritional supplementation has emerged as a potential strategy to prevent and/or reduce the deleterious effects of sports-related concussion and subconcussive impacts.

The Relationship between Frailty, Obesity and Social Deprivation in Non-Institutionalized Elderly People.

BACKGROUND: With the increasing prevalence of obesity and the risk of increased dependency among the elderly, it becomes important to characterize the link between obesity and frailty. The relationship between obesity and social deprivation would be bidirectional, with each influencing the other. OBJECTIVES: Main objective was to study the relationship between frailty as defined by Fried and obesity (Body Mass Index (BMI) and abdominal obesity). Secondary objective was to assess the relationship between frailty and social deprivation. MATERIALS AND METHODS: This was a cross-sectional study, with data collected between January 2014 and December 2015 using a senior periodic health prevention examination form used in the 4 sites of the health examination center, in Rhone, among non-institutionalized seniors (≥ 65 years). Frailty was defined according to Fried's criteria. Obesity was defined by a BMI ≥ 30 kg / m2 and a waist circumference > 88 cm for women and >102 cm for men. We studied the association between obesity according to BMI ≥ 30kg / m2 on the one hand and abdominal obesity on the other hand with frailty according to Fried. The analyzes were adjusted for gender, age, education level, not being in a relationship and social deprivation quantified by the assessment score of deprivation and health inequalities (EPICES score). RESULTS: 1593 senior health prevention examination forms were studied. According to BMI, senior women were almost twice as likely to be frail when obese (RR = 1.92, 95% CI [1.06 - 3.45], p = 0.018). The results were similar for abdominal obesity in women aged 65-74 years (RR = 2.12, 95% CI [1.03-4.35], p = 0.029). There was no relationship in men for both types of obesity. Seniors who were socially deprived were 2.7 times more likely to be frail than non-deprived seniors (adjusted RR = 2.76, 95% CI [1.808 - 4.203], p <0.001). CONCLUSIONS: Obesity (BMI ≥ 30kg / m2 and high waist circumference) was associated with increased frailty among older, non-institutionalized women who came for a periodic health prevention examination. Screening and prevention of obesity in the elderly appears to be a major public health issue, and remains a priority target for action.

Emotions generated by food in elderly French people.

Eating behaviour depends partly on food preference, which may be determined by different types of emotions. Among the emotions generated by food, disgust and pleasure are common and can lead to increased and reduced food consumption. We tested the hypothesis that (1) elderly men and women felt different emotions towards food, and (2) low energy intake is related to negative emotions towards food. In February 2004, a convenience sample of elderly participants was recruited locally by telephone. Food intake of 52 elderly people, aged 63-80 years, was monitored throughout each day for one week and made it possible to assign the elderly people to two groups (low and high energy intake from food consumption data). One month later, each of them assessed their likes or dislikes towards 30 food pictures (vegetables, cheeses, fruits, starchy foods, sweets, meat, fish, offal and eggs) using 19 emotional words (eight words with a positive valence: 'to like', 'thrilled', 'satisfaction', 'surprise', 'serene', 'amused', 'pride', 'interest', and 11 other words with a negative valence: 'disgust', 'indifference', 'guilt', 'uneasiness', 'nostalgia', 'impatience', 'doubt', 'frustration', 'embarrassment', 'disappointment' and 'lassitude'. The emotional intensities experienced with the different pictures were analysed by ANOVA for each group (men and women, small and big eaters). There were differences in likes and dislikes between men and women. Both guilty and liking scores towards food were generally higher in women than in men. Small eaters felt more doubt, unease, disappointment and indifference towards food than big eaters. In conclusion, the report of low food intake was related to more negative emotions towards foods that might be associated with the willingness to restrict food intake or to undernutrition.

90Y TOF-PET based EUD reunifies patient survival prediction in resin and glass microspheres radioembolization of HCC tumours.

Clinical studies reported a twofold ratio between the efficacies per Gy of resin versus glass spheres. Our aim is to investigate whether this difference could result from the different degrees of heterogeneity in sphere distribution between the two medical devices. The 90Y TOF-PET based equivalent uniform doses (EUD) was used for this purpose. 58 consecutive HCC radioembolizations were retrospectively analyzed. Absorbed doses D and Jones-Hoban EUD in lesions were computed. Radioembolization efficacy was assessed using Kaplan-Meier survival curves. In order to match together the glass and resin spheres survival curves using a 40 Gy-threshold, an efficacy factor of 0.73 and 0.36 has to be applied on their absorbed dose, respectively. Using EUD, a nice matching between glass and resin survival curves was obtained with a better separation of the responding and not responding survival curves. The results clearly support the fact that the activity heterogeneity observed in 90Y TOF-PET post radioembolization does not only result from statistical noise, but also reflects the actual heterogeneity of the spheres distribution. Use of EUD reunifies the efficacy of the two medical devices.

Effect of Vitamin D Treatment on Glucose Homeostasis and Metabolism in Lebanese Older Adults: A Randomized Controlled Trial.

BACKGROUND: A low serum 25-hydroxyvitamin D [(25(OH) D)] concentration was shown to correlate with higher fasting blood glucose (FBG) and insulin levels. Since age affect insulin sensitivity and the metabolism, we aimed in this randomized controlled trial to investigate the effect of vitamin D supplementation on glucose homeostasis and index of insulin resistance in elderly subjects living in Beirut, Lebanon. METHODS: Participants (n= 115) deficient in vitamin D were randomly divided into two groups, a group receiving 30,000 IU cholecalciferol/week for a period of 6 months, and a placebo group. The index of insulin resistance HOMA (homeostasis model assessment) was the primary outcome. Glucose homeostasis and metabolic markers were also measured at start of treatment and at 6 months. RESULTS: Vitamin D supplementation led to significant improvements in blood levels of [25(OH) D] (P< 0.0001), and a significant decreased of HOMA, PTH and FBG concentrations (P< 0.0001) in the intervention group compared to placebo. No significant changes were observed in HbA1c levels for both groups. Total cholesterol and LDL cholesterol concentrations have also decreased significantly in the intervention group (P< 0.0001). CONCLUSION: Short-term supplementation with cholecalciferol improved vitamin D status, and markers of insulin resistance in healthy elder population. This trial was registered at ClinicalTrials.gov; Identifier number#:NCT03478475.

Association of hypovitaminosis D with triceps brachii muscle fatigability among older women: Findings from the EPIDOS cohort.

BACKGROUND: Vitamin D affects physical performance in older adults. Its effects on muscles, notably on muscle strength, remain unclear. The objective of this cross-sectional study was to determine whether hypovitaminosis D is associated with triceps brachii muscle fatigability in community-dwelling older women. METHODS: A randomized subset of 744 women aged ≥75years from the EPIDOS cohort was categorized into two groups according to triceps brachii muscle fatigability, defined as loss of strength >5% between two consecutive maximal isometric voluntary contractions. Hypovitaminosis D was defined using consensual threshold values (i.e., serum 25-hydroxyvitamin D concentration [25OHD] ≤10 ng/mL, ≤20 ng/mL, and ≤30 ng/mL). Age, body mass index, comorbidities, use psychoactive drugs, physical activity, first triceps strength measure, hyperparathyroidism, serum concentrations of calcium, albumin and creatinine, season and study centers were used as potential confounders. RESULTS: The prevalence of hypovitaminosis D ≤ 30 ng/mL was greater among women with muscle fatigability compared with the others (P = .009). There was no between-group difference using the other definitions of hypovitaminosis D. The serum 25OHD concentration was inversely associated with the between-test change in triceps strength (adjusted ß = -0.09 N, P = .04). Hypovitaminosis D ≤ 30 ng/mL was positively associated with triceps fatigability (adjusted OR = 3.15, P = .02). CONCLUSIONS: Vitamin D concentration was inversely associated with the ability to maintain strength over time in this cohort of community-dwelling older women. This is a relevant new orientation of research toward understanding the involvement of vitamin D in muscle function.

Vitamin D and the Mechanisms, Circumstances and Consequences of Falls in Older Adults: A Case-Control Study.

OBJECTIVES: To determine i) whether cases of elderly fallers had lower serum 25-hydroxyvitamin D (25OHD) concentration than controls without history of falls; and ii) whether serum 25OHD concentration was associated with specific mechanisms, circumstances and consequences of falls. DESIGN: Case-control study with a 1:2 ratio. SETTING: Geriatric ward of the University Hospital of Angers, France, between February 2012 and March 2014. PARTICIPANTS: 216 inpatients (72 cases and 144 age- and gender-matched controls). MEASUREMENT: Falls were defined as involuntary events causing the person to the ground or other lower level. The main mechanisms, circumstances and consequences of falls were identified using standardized questionnaires. Vitamin D deficiency was defined as serum 25OHD concentration ≤25nmol/L. Age, gender, body mass index, polypharmacy, use antihypertensive drugs, use psychoactive drugs, disability, cognitive performance, serum concentrations of parathyroid hormone, creatinine and albumin, and season of evaluation were used as potential confounders. RESULTS: 216 participants (72 cases and 144 controls) were included in the study. There was no between-group difference in the prevalence of vitamin D deficiency (P=0.176). After adjusting for confounding factors, vitamin D deficiency was positively associated with falls (OR=4.03, P=0.014). Finally, the fallers with vitamin D deficiency exhibited more often orthostatic hypotension (68.8% against 33.3%, P=0.039) and a history of recurrent falls (85% against 50%, P=0.002) than those without vitamin D deficiency. CONCLUSION: This case-control study reported that vitamin D deficiency was associated with falls in older inpatients. There was a greater prevalence of orthostatic hypotension and of the reccurrence of falls among fallers with vitamin D deficiency, suggesting that vitamin D may influence the conditions predisposing to falls rather than the fall by itself.

In vivo evidences that insulin regulates human polymorphonuclear neutrophil functions.

Polymorphonuclear neutrophils (PMN) are able to destroy invasive mircoorganisms by a wide variety of functions. Whereas insulin does not stimulate hexose transport in PMN, previous reports have clearly shown that this hormone regulates glucose metabolism inside this cell, raising the question of insulin action on PMN functions in humans. It is interesting that in vitro studies established a strong relationship between specific binding of insulin to its PMN membrane receptor and the activation of the main PMN functions. Therefore, investigation in healthy subjects under strict euglycemia and physiological insulinemia was performed to understand the in vivo-specific action of insulin on PMN functions without hyperglycemia interferences. We determined numerous PMN functions before and after hyperinsulinemia (0.5 mU/kg/min) and euglycemia (0.9 g/l) clamp for 4 h in eight adult healthy volunteers (24+/-6 years). The total number of PMN and the number of PMN expressing CD11b, CD15, CD62L, and CD89 were significantly increased over baseline (P<0.001), whereas the density of these receptors was down-regulated (P<0.01) by insulin. PMN chemotaxis (+117%, P<0.05), phagocytosis (+29%, P<0.001), and bactericidal (+17-25%, P<0.001) capacities were increased during the insulin clamp (P<0.05). Therefore, insulin treatment may modulate PMN functions not only by attainment of a better metabolic control, as suggested by in vivo studies in diabetic patients, but also through a direct effect of insulin.

Involvement of glutamine, arginine, and polyamines in the action of ornithine alpha-ketoglutarate on macrophage functions in stressed rats.

The ability of ornithine alpha-ketoglutarate (OKG) to enhance macrophage cytotoxicity in stress situations has been described, but the mechanisms involved remain unclear. It is known that OKG administration generates glutamine (GLN), arginine (ARG), and polyamines. This study will (1) evaluate the effect of OKG on tumor necrosis factor alpha (TNF-alpha) secretion and nitric oxide (NO*) production in macrophages from glucocorticoid (DEX)-treated rats, and determine whether these effects can be reproduced by GLN or ARG supplementations, and (2) use in vivo metabolic inhibitors methionine sulfoximine (inhibitor of GLN synthetase), S-methylthiourea (inhibitor of inducible nitric oxide synthase), and difluoromethylornithine (inhibitor of ornithine decarboxylase) to assess the roles of GLN, ARG, and polyamines in OKG action. Controls received a mixture of nonessential amino acids (NEAA). GLN, ARG, and OKG all restored TNF-alpha secretion by macrophages of glucocorticoid-treated rats. The same results were obtained with GLN and ARG supplementation. However, the use of inhibitors clearly showed that OKG does not modulate TNF-alpha secretion by GLN, ARG, or polyamine pathways. We also observed that OKG enhanced NO* release by stimulated macrophages (DEX-OKG, 1.77 +/- 0.64 vs. DEX-NEAA, 0.29 +/- 0.29 nmol/ 10(6) cells, P < 0.05). Using inhibitors, it appears that this action of OKG is probably mediated via polyamine synthesis and GLN. However, an oral administration of an equimolar amount of GLN failed to reproduce the OKG-mediated effect, possibly because OKG generates more GLN in the systemic circulation than GLN itself when these substances are given orally. Our results underline the complexity of the mechanism of action of OKG, which can differ according to the functions of even a single cell type.

Fortification of Yogurts with Vitamin D and Calcium Enhances the Inhibition of Serum Parathyroid Hormone and Bone Resorption Markers: A Double Blind Randomized Controlled Trial in Women over 60 Living in a Community Dwelling Home.

OBJECTIVE: To evaluate whether fortification of yogurts with vitamin D and calcium exerts an additional lowering effect on serum parathyroid hormone (PTH) and bone resorption markers (BRM) as compared to iso-caloric and iso-protein dairy products in aged white women at risk of fragility fractures. DESIGN: A randomized double-blind controlled trial. SETTING: A community dwelling home. PARTICIPANTS: Forty-eight women over 60 years (mean age 73.4). INTERVENTION: Consumption during 84 days of two 125 g servings of either vitamin D and calcium-fortified yogurts (FY) at supplemental levels of 10 µg vitamin D3/d and 520 mg/d of calcium (total=800 mg/d), or non fortified control yogurts (CY) providing 280 mg/d of calcium. MEASUREMENTS: Serum changes from baseline (D0) to D28, D56 and D84 in 25OHD, PTH and in two BRM: Tartrate-resistant-acid-phosphatase-isoform-5b (TRAP5b) and carboxy-terminal-cross-linked-telopeptide of type-I-collagen (CTX). RESULTS: The 10 years risk of major and hip fractures were 13.1 and 5.0%, and 12.9 and 4.2 %, in FY and CY groups, respectively. From D0 to D84, serum 25OHD increased (mean±SE) from 34.3±2.4 to 56.3±2.4 nmol/L in FY (n=24) and from 35.0±2.5 to 41.3±3.0 nmol/L in CY (n=24), (P=0.00001). The corresponding changes in PTH were from 64.1±5.1 to 47.4±3.8 ng/L in FY and from 63.5±4.6 to 60.7±4.2 ng/L in CY (P=0.0011). After D84, TRAP5b was reduced significantly (P=0.0228) and CTX fell though not significantly (P=0.0773) in FY compared to CY. CONCLUSION: This trial in aged white women living in a community dwelling home at risk for osteoporotic fractures confirms that fortification of dairy products with vitamin D3 and calcium should provide a greater prevention of secondary hyperparathyroidism and accelerated bone resorption as compared to non-fortified equivalent foods.

Aging: a barrier to renutrition? Nutritional and immunologic evidence in rats.

BACKGROUND: Previous reports suggest that correcting the malnourished state is more difficult in elderly people than in younger ones and that protein requirements may be higher in elderly than in younger adults. OBJECTIVE: The aim of this study was to establish whether malnourished old rats respond to protein-supplemented nutritional repletion as do young adult rats. DESIGN: Adult (3 mo old) and old (22 mo old) rats were submitted to dietary restriction programs that induced similar metabolic and nutritional alterations. Malnourished adult and old rats were then killed (R groups) or refed for 1 wk with a high-protein diet (HPD; 23% protein) or a very-high-protein diet (VHPD; 27% protein). Control groups at both ages were fed ad libitum throughout the experiment. Effects of food repletion were evaluated in terms of protein metabolism, intestinal histomorphometry, and nonspecific immune status. RESULTS: In adult rats, HPD sufficed to increase body weight and restore basal values of liver weight and protein content (P: < 0.01 compared with the R adult group), nitrogen balance (P: < 0.01 compared with the R adult group), and hydrogen peroxide production by polymorphonuclear neutrophils and monocytes (P: < 0.01 compared with the R group); VHPD had no supplementary effect except on nitrogen balance. In old rats, HPD was less effective and greater benefit was observed with VHPD in terms of body weight gain (10%; P: < 0.01 compared with the old group fed HPD), albuminemia, muscle weight and protein content, plasma arginine concentration, and hydrogen peroxide production by stimulated polymorphonuclear neutrophils and monocytes compared with the old R group (P: < 0.01). CONCLUSION: Aging is a significant variable affecting the response to nutritional support.

Specific and nonspecific immune responses to fasting and refeeding differ in healthy young adult and elderly persons.

BACKGROUND: Undernutrition is a main cause of immunodeficiency. Many confounding factors limit the interpretation of immune function in hospitalized elderly patients. OBJECTIVE: We compared the effects of short-term fasting and refeeding on lymphocyte subset distribution and neutrophil function in healthy subjects. DESIGN: Seven young adult (x +/- SE age: 24 +/- 2 y) and 8 elderly (71 +/- 3 y) subjects were fed standardized diets (1.6 x predicted resting energy expenditure; 16% protein) for 7 d. They then fasted for 36 h and were refed for 4 h (42 kJ/kg). Lymphocyte subsets were quantified by using fluorochrome-conjugated monoclonal antibodies. Neutrophil chemotactic migration was evaluated by using a 2-compartment chamber. Neutrophil reactive oxygen species production was measured by using a luminol-amplified chemiluminescence assay and oxidation of 2'7'-dichlorofluorescein diacetate. RESULTS: Baseline total and cytotoxic T lymphocyte subpopulations were lower in elderly than in adult subjects (P < 0.01). Nutritional state had a significant effect (P < 0.05) on total, helper, and cytotoxic T and B lymphocyte counts in all subjects, and the response of lymphocyte subpopulations to nutritional fluctuations was significantly affected by age. The chemotactic index was lowered by fasting in both groups (P < 0.05 compared with basal values). After refeeding, neutrophil migration was restored in adult but not elderly subjects. The superoxide anion production rate increased with fasting and reverted to prefasting values with refeeding in both groups (P < 0.05). Fasting induced a significant decrease in hydrogen peroxide production in stimulated neutrophils that was reversed by refeeding in adult but not elderly subjects. CONCLUSION: The lack of response of lymphocyte subpopulation counts and neutrophil function to nutritional changes may help to explain the proneness of elderly persons to infection.