Gonzalo Palacios

A review of the cut-off points for the diagnosis of vitamin B12 deficiency in the general population

Abstract Vitamin B12 deficit is one of the most common vitamin deficiencies. However, there is no consensus on the cut-off points for vitamin B12 and its co-markers, such as folate, holotranscobalamin, methylmalonic acid and homocysteine. In order to establish the state of the art about cut-off points used to determine vitamin B12 deficiency in the last decades, the database MEDLINE was used for searching studies published in adults between December 1992 and May 2014 (69 articles), using search terms like ‘vitamin B12’, ‘cobalamin’, ‘cut-off’, ‘deficiency’ alone or in combinations. Broad ranges of cut-off points for vitamin B12 and its biomarkers were identified: vitamin B12 ranged between 100 pmol/L and 350 pmol/L, holotranscobalamin 20–50 pmol/L, methylmalonic acid 0.210–0.470 μmol/L, homocysteine 10–21.6 μmol/L, serum folate 3.7–15.9 nmol/L and red blood cell 124–397 nmol/L. For the majority of studies, the potential influence of age, analytical methods, gender and fortified food consumption was not taken in account when choosing cut-off values. This could explain the discrepancies between studies on vitamin B12 and folate deficiency prevalences. We conclude that there is inconsistency in the literature regarding vitamin B12 cut-offs. It would be necessary to establish different reference cut-offs according to age, considering the analytical methods used.

Reference values for leptin, cortisol, insulin and glucose, among European adolescents and their association with adiposity: The HELENA Study

BACKGROUND AND OBJECTIVE Adequate concentrations of leptin, cortisol, and insulin are important for a suitable metabolism and development during adolescence. These hormones jointly with glucose play a major role in fat metabolism and development of childhood obesity. Our main objective was to quantify biomarkers as leptin, cortisol, insulin and glucose status in European adolescents to contribute to establish reference ranges. METHODS A representative sample of 927 adolescents (45% males, 14.9±1.2 years for the overall population) from ten European cities of the HELENA study was used to obtain fasting blood samples for these biomarkers. The percentile distributions were computed by sex and age and percentiles were associated with BMI classification. RESULTS Serum leptin concentration in adolescents varied significantly according to BMI, sex and age (all p < 0.001). Cortisol presented a tendency to increase with age, both for females and males, while insulin and glucose were stable with age. Leptin and insulin were highest in obese adolescents (p < 0.001), whilst cortisol and glucose did not vary with BMI. Percentiles 5, 25, 50, 75 and 95, for hormones values were, respectively: 1.27, 4.06, 11.54, 26.70 and 65.33 ng/ml for leptin; 5.00, 8.11, 11.14, 15.00 and 24.51 μg/dl for cortisol and 3.65, 6.15, 8.52, 11.90 and 20.53 μlU/ml for insulin. CONCLUSIONS In adolescents, leptin, cortisol, insulin and glucose concentrations are differently affected by age, sex and BMI. Establishment of reference ranges (percentiles) of these biomarkers would be of great interest when pediatricians have to assess the trend of an adolescent to develop obesity years after.

Algorithm for the early diagnosis of vitamin B12 deficiency in elderly people

BACKGROUND The elderly population is particularly at risk for developing vitamin B12-deficiency. Serum cobalamin does not necessarily reflect a normal B12 status. The determination of methylmalonic acid is not available in all laboratories. Issues of sensitivity for holotranscobalamin and the low specificity of total homocysteine limit their utility. The aim of the present study is to establish a diagnostic algorithm by using a combination of these markers in place of a single measurement. METHODS We compared the diagnostic efficiency of these markers for detection of vitamin B12 deficiency in a population (n = 218) of institutionalized elderly (median age 80 years). Biochemical, haematological and morphological data were used to categorize people with or without vitamin B12 deficiency. RESULTS In receiver operating curves characteristics for detection on vitamin B12 deficiency using single measurements, serum folate has the greatest area under the curve (0.87) and homocysteine the lowest (0.67). The best specificity was observed for erythrocyte folate and methylmalonic acid (100% for both) but their sensitivity was very low (17% and 53%, respectively). The highest sensitivity was observed for homocysteine (81%) and serum folate (74%). When we combined these markers, starting with serum and erythrocyte folate, followed by holotranscobalamin and ending by methylmalonic acid measurements, the overall sensitivity and specificity of the algorithm were 100% and 90%, respectively. CONCLUSION The proposed algorithm, which combines erythrocyte folate, serum folate, holotranscobalamin and methylmalonic acid, but eliminate B12 and tHcy measurements, is a useful alternative for vitamin B12 deficiency screening in an elderly institutionalized cohort.

Dietary and lifestyle quality indices with/without physical activity and markers of insulin resistance in European adolescents: the HELENA study

Emerging data indicate that higher levels of insulin resistance (IR) are common among children and adolescents and are related to cardiometabolic risk; therefore, IR requires consideration early in life. In addition, there is a lack of conclusive evidence regarding the role of dietary nutrients on IR. The Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study (HELENA-CSS) was conducted in European adolescents aged 12·5–17·5 years. A total of 637 participants with valid homeostasis model assessment (HOMA) index data and who completed at least a 2 d 24 h dietary recall were included in the study (60% of the total HELENA-CSS sample). There were two dietary indices calculated, with the only difference between them being the inclusion or not of physical activity (PA). Markers of IR such as HOMA and the quantitative insulin sensitivity check index (QUICKI) were calculated. Pubertal status, BMI and cardiorespiratory fitness (CRF) were measured as potential confounders. The dietary index including PA was inversely associated with HOMA and directly with the QUICKI in females, but not in males, after adjusting for pubertal status, centre, BMI and CRF. In conclusion, the present study indicates that considering PA as part of the dietary index is of relevance as the resulted index is inversely related to IR independently of potential confounders including CRF. Overall, these findings suggest that intervention studies aimed at preventing IR in young people should focus on increasing the quality of the diet and also on including an optimal PA level in healthy adolescents.

Biomarkers of physical activity and exercise

Traditionally, biomarkers have been of interest in sports in order to measure performance, progress in training and for identifying overtraining. During the last years, growing interest is set on biomarkers aiming at evaluating health-related aspects which can be modulated by regular physical activity and sport. The value or concentration of a biomarker depends on many factors, as the training status of the subject, the degree of fatigue and the type, intensity and duration of exercise, apart from age and sex. Most of the biomarkers are measured in blood, urine and saliva. One of the main limitations for biochemical biomarkers is that reference values for blood concentration of biomarkers specifically adapted to physically active people and athletes are lacking. Concentrations can differ widely from normal reference ranges. Therefore, it is important to adapt reference values as much as possible and to control each subject regularly, in order to establish his/her own reference scale. Other useful biomarkers are body composition (specifically muscle mass, fat mass, weight), physical fitness (cardiovascular capacity, strength, agility, flexibility), heart rate and blood pressure. Depending on the aim, one or several biomarkers should be measured. It may differ if it is for research purpose, for the follow up of training or to prevent risks. For this review, we will get deeper into the biomarkers used to identify the degree of physical fitness, chronic stress, overtraining, cardiovascular risk, oxidative stress and inflammation.

What do we know about homocysteine and exercise? A review from the literature

Abstract High total homocysteine (tHcy) concentrations contribute to an increased risk of cardiovascular diseases and neurodegenerative disorders. Several investigations have focused on the effect of exercise on tHcy concentrations, but results remain controversial. The differences among the methodologies in the investigations make difficult the interpretation of results. This review differentiates the effects of exercise on tHcy and establishes the relation with the implicated biomarkers on tHcy metabolism related to exercise. The electronic database MEDLINE (http://www.ncbi.nlm.nih.gov) was used for searching studies published between years 2002 and 2015. ‘Homocysteine’, ‘Training ’, ‘Exercise’, ‘Physical Activity’ as well as combinations out of these terms were entered in the database. Articles were grouped in: 1) Acute effect of exercise on tHcy, 2) chronic exercise and tHcy, 3) relationship of physical activity (PA) level and cardiorespiratory fitness with tHcy, and 4) biomarkers related to tHcy and exercise. From a total of 30 articles, most of the studies analyzing the acute effect of exercise showed an increase on tHcy concentrations. Studies analyzing the chronic effect on tHcy concentrations showed contradictory results and no consensus exists probably due to the differences in the methodology, exercise interventions and participants characteristics. Low cardiorespiratory fitness seems to be associated with high tHcy; in contrast, the relation of PA levels and tHcy needs further research. Regarding biomarkers related to tHcy and exercise, some studies showed an increase of folate, vitamin B12, and creatine after acute exercise that could to be due to requirement of protein turnover and an increased metabolic demand of vitamin-B.

Associations between macronutrient intake and serum lipid profile depend on body fat in European adolescents: The Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study

The present study aimed to investigate the relationships between macronutrient intake and serum lipid profile in adolescents from eight European cities participating in the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) cross-sectional study (2006-7), and to assess the role of body fat-related variables in these associations. Weight, height, waist circumference, skinfold thicknesses, total cholesterol, HDL-cholesterol (HDL-C), LDL-cholesterol, TAG, apoB and apoA1 were measured in 454 adolescents (44% boys) aged 12.5-17.5 years. Macronutrient intake (g/4180 kJ per d (1000 kcal per d)) was assessed using two non-consecutive 24 h dietary recalls. Associations were evaluated by multi-level analysis and adjusted for sex, age, maternal education, centre, sum of four skinfolds, moderate-to-vigorous physical activity, sedentary behaviours and diet quality index for adolescents. Carbohydrate intake was inversely associated with HDL-C (β = - 0.189, P< 0.001). An inverse association was found between fat intake and TAG (β = - 0.319, P< 0.001). Associations between macronutrient intake and serum lipids varied according to adiposity levels, i.e. an inverse association between carbohydrate intake and HDL-C was only observed in those adolescents with a higher waist:height ratio. As serum lipids and excess body fat are the major markers of CVD, these findings should be considered when developing strategies to prevent the risk of CVD among adolescents.

Western and Mediterranean Dietary Patterns and Physical Activity and Fitness among Spanish Older Adults

Objectives: To assess prevailing food patterns, and its association with physical activity and fitness among Spanish older adults. Methods: Cross-sectional study in Spain, collecting data from a sample (n = 380; 54% female) aged 55–80 years (men) and 60–80 years (women) with no previously documented cardiovascular disease. Body weight, body fat and waist circumference were assessed. Physical activity performed was measured using the Minnesota Leisure-time Physical Activity Questionnaire (LTPA). Physical fitness was assessed using a validated physical fitness test battery. Food consumption was assessed by a validated semi-quantitative food-frequency questionnaire. Factor analysis identified two major dietary food patterns: “Western” (WDP) and “Mediterranean” (MDP) dietary patterns. Results: Participants in MDP’s fourth quartile were classified in the second (men) and third (men and women) tertile of LTPA. After adjusting for age, body fat, waist-to-height ratio, and METs, in both sexes, a negative significant association was found between 30-s Chair stand and 6-min walking test, a positive significant association was found between 30-m Gait speed and 8-foot Time Up-and-Go (except in men) tests with WDP. The 30-m Gait speed test was negatively associated with MDP in men. Conclusions: MDP is associated with more time spent on LTPA, and this association was independent of body composition and a fast gait speed in men. WDP is associated with slower gait speed and lower body strength, agility and aerobic endurance. MDP has protective effect on healthy physical fitness, and WDP may be a contributor to frailty.

Polymedication in institutionalized elderly and its effect on vitamin B12, folate, and homocysteine levels

AIM To determine drug consumption in institutionalized elderly living in the Region of Madrid (Spain) and to assess the relationship between drug intake and biochemical parameters for vitamin B12 (Cobalamin and Holotranscobalamin), serum folate (SF) and homocysteine (Hcy). METHODS 167 subjects (32% men), mean age 83 ± 7 years, were classified according to biochemical parameter levels (in or out of reference range) and drugs were classified according to ATC system. The relationship between drug intake and biochemical levels was studied by means of the Fisher exact test. RESULTS The daily mean drug intake was 5. Psicoleptic and antiacid drugs were the most consumed (both 53%). Cobalamin (median 158.2 pg/mL; 10.7% of individuals), SF (5.3 ng/mL; 52.1%) and holotranscobalamin (11.76 pmoL/L; 7.8%) deficiencies were observed. Hyperhomocysteinaemia (19.4 μmoL/L) was present in 65% of population. Antiaenemic drug intake normalized cobalamin, urologic drug and corticosteroids SF and psicoanaleptics holotranscobalamin levels. Drugs against pulmonar obstruction increased Hcy concentration (all p < 0.05). CONCLUSION There is a high prevalence of SF deficiency and hyperhomocysteinaemia in the studied population. The elevated number of drugs taken simultaneously by each subject makes it difficult to analyze which drugs are responsible for those alterations.

Impact of physical activity and sedentary lifestyle on hydration status and liquid intake in Spanish older adults

Introduction: Data on hydration status in older adults are scarce and there are very few studies focused on the impact of physical activity on drinking behaviour. Objective: To determine the impact of physical activity and sedentary lifestyle on fluid intake in Spanish older adults. Method: 430 non-institutionalized Spanish older adults (58% females), aged 55-80 years were divided into four groups: ILS (inactive and low sedentary), HIS (inactive and high sedentary), ALS (active and low sedentary) and AHS (active and high sedentary). Experimental data were collected by questionnaires, physical fitness tests, and osmolality was measured in serum. Data was analyzed using one-way ANOVA. Results: Serum osmolality values were within references values in all subjects, independently of the physical activity and sedentary level. Liquid intake increased in parallel with physical activity. There were significant differences between ILS/ALS (p=0.002) and IHS/ALS (p=0.001), and no differences were found between AHS/IHS (p=0.066). Conclusions: Spanish elderly seem to be well hydrated independently of the physical activity and sedentary level. Physical activity has a higher impact on fluid intake than sendentary lifestyle. Supported by Instituto Salud Carlos III (PI11/01791 & CB12/03/30038). ImFINE and NUCOX are members of the EXERNET research network.