Adherence to the Healthy Nordic Food Index and the incidence of acute myocardial infarction and mortality among patients with stable angina pectoris.

BACKGROUND: The Healthy Nordic Food Index (HNFI) has been associated with beneficial effects on markers of cardiovascular disease (CVD). Whether such effects are present among patients with established coronary heart disease is unknown. In the present study, we investigated the association between adherence to the HNFI and the risk of acute myocardial infarction (AMI) (fatal or nonfatal) and death among patients with stable angina pectoris. METHODS: In the Western Norway B-vitamin Intervention Trial, participants completed a 169-item semi-quantitative food frequency questionnaire. The HNFI was calculated from six food groups (fish, cabbage, apples/pears, root vegetables, whole grain bread and oatmeal), scoring 0-6. Three adherence groups were defined: 0-1 points (low), 2-3 points (medium) or 4-6 points (high). Cox regression analyses investigated associations between adherence to the HNFI and outcomes. RESULTS: Among 2019 men (79.7%) and women with mean age of 61.7 years, 307 patients experienced an AMI event during a median (25th and 75th percentiles) follow-up of 7.5 (6.3 and 8.7) years. Median follow-up for total mortality was 10.5 (9.3 and 11.7) years; 171 patients died from CVD and 380 from any cause. No association between HNFI and the risk of AMI was detected. However, the HNFI was associated with a reduced risk of all-cause death, both by linear estimates [hazard ratio (95% confidence interval = 0.91 (0.84-0.98)] and by comparison of the highest with the lowest adherence group [hazard ratio (95% confidence interval = 0.70 (0.52-0.95)]. CONCLUSIONS: The results of the present study suggest that a Healthy Nordic diet may reduce mortality in patients with established CVD.

Vitamin D supplementation and its influence on muscle strength and mobility in community-dwelling older persons: a systematic review and meta-analysis.

BACKGROUND: It has been suggested that vitamin D status or supplementation is important for maintaining or improving muscle strength and mobility in older adults. The study results, however, do not provide consistent results. We therefore aimed to summarise the available evidence systematically, including only studies conducted in community-dwelling older persons. METHODS: A systematic search of the literature was performed in April of 2016. The systematic review includes studies that used vitamin D with or without calcium supplementation as the exposure variable and various measurements of muscle strength and mobility. The meta-analysis was limited to studies using hand grip strength (HGS) and timed-up-and-go test as the outcome variables. RESULTS: A total of 15 studies out of 2408 articles from the literature search were included in the systematic review, providing 2866 participants above the age of 65 years. In the majority of studies, no improvement in muscle strength and mobility was observed after administration of vitamin D with or without calcium supplements. In the meta-analysis, we observed a nonsignificant change in HGS [+0.2 kg (95% confidence interval = -0.25 to 0.7 kg; seven studies)] and a small, significant increase in the timed-up-and-go test [0.3 s (95% confidence interval = 0.1 to 0.5 s; five studies)] after vitamin D supplementation. The meta-analyses showed a high degree of heterogeneity between the studies. CONCLUSIONS: In conclusion, we observed no improvement in muscle strength after the administration of vitamin D with or without calcium supplements. We did find a small but significant deterioration of mobility. However, this is based on a limited number of studies and participants.

Vitamin D is not linked to folate status and mRNA expression of intestinal proton-coupled folate transporter.

PURPOSE: In vitro studies discovered intestinal proton-coupled folate transporter (PCFT) as a vitamin D hormone-responsive gene. In vivo effects of vitamin D on PCFT and folate status are currently not available. METHODS: Three experiments were conducted. At first, vitamin D receptor knockout (VDR(-/-)) mice and corresponding wild-type (WT) mice were compared for their plasma and hepatic folate concentration and PCFT mRNA expression in intestinal mucosa. In a second experiment with rats, we analyzed the folate status of offspring in response to a maternal vitamin D-adequate (1,000 IU/kg) or vitamin D-deficient (0 IU/kg) diet that was fed for 11 weeks. Finally, the plasma folate concentration of healthy individuals was studied at baseline (in winter) and in response to an oral treatment for 8 weeks with 2,000 IU vitamin D3 per day or a placebo, respectively. RESULTS: Here, we show that folate status and intestinal PCFT mRNA abundance did not differ between the VDR(-/-) and the WT mice. No effect of vitamin D on folate status was also found in rat dams and their offspring, and plasma folate levels of individuals did not change in response to vitamin D. CONCLUSIONS: Current data from studies with model animals and humans provide no indication for a vitamin D effect on intestinal uptake and status of folate.

Vitamin D: do we get enough? A discussion between vitamin D experts in order to make a step towards the harmonisation of dietary reference intakes for vitamin D across Europe.

UNLABELLED: On September 29, 2011, acknowledged experts in the field of vitamin D, mainly European, were brought together in order to discuss the recent scientific advances in relation to vitamin D: the current requirements and associations with various health outcomes. In this article, the discussions resulting from the meeting are summarized. INTRODUCTION: Several groups at risk for developing vitamin D insufficiency have been identified. Accordingly, reviews indicate that a significant percentage of the population worldwide have serum 25-hydroxyvitamin D levels below 50 nmol/l. In addition to the role of vitamin D in bone health, recent studies suggest that it may play a pivotal role in other systems, e.g., the cardiovascular system, pancreas, muscle, immune system and brain. Most evidence, however, is obtained from observational studies and yet inconclusive. METHODS: To exchange and broaden knowledge on the requirements for vitamin D and its effect on various health outcomes, a workshop entitled "Vitamin D Expert Meeting: Do we get enough?", was organized. RESULTS: Despite low vitamin D levels worldwide, consensus on the definition of deficiency is not yet reached. In order to define cut-off points for vitamin D whilst taking into account extraskeletal health effects, randomized controlled trials in these fields are warranted. The experts do emphasize that there is evidence to suggest an important role for vitamin D in the maintenance of optimal bone health at all ages and that vitamin D supplementation, in most studies co-administered with calcium, reduces fracture risk in the senior population. CONCLUSION: To reach a serum 25-hydroxyvitamin D level of 50 nmol/l older adults aged ≥65 years are therefore recommended to meet a mean daily vitamin D intake of 20 µg (800 IU), which is best achieved with a supplement.

Validation of the German Diabetes Risk Score within a population-based representative cohort.

AIM: To validate the German Diabetes Risk Score within the population-based cohort of the Cardiovascular Disease - Living and Ageing in Halle (CARLA) study. METHODS: The sample included 582 women and 719 men, aged 45-83 years, who did not have diabetes at baseline. The individual risk of every participant was calculated using the German Diabetes Risk Score, which was modified for 4 years of follow-up. Predicted probabilities and observed outcomes were compared using Hosmer-Lemeshow goodness-of-fit tests and receiver-operator characteristic analyses. Changes in prediction power were investigated by expanding the German Diabetes Risk Score to include metabolic variables and by subgroup analyses. RESULTS: We found 58 cases of incident diabetes. The median 4-year probability of developing diabetes based on the German Diabetes Risk Score was 6.5%. The observed and predicted probabilities of developing diabetes were similar, although estimation was imprecise owing to the small number of cases, and the Hosmer-Lemeshow test returned a poor correlation (chi-squared = 55.3; P = 5.8*10⁻¹²). The area under the receiver-operator characteristic curve (AUC) was 0.70 (95% CI 0.64-0.77), and after excluding participants ≥66 years old, the AUC increased to 0.77 (95% CI 0.70-0.84). Consideration of glycaemic diagnostic variables, in addition to self-reported diabetes, reduced the AUC to 0.65 (95% CI 0.58-0.71). A new model that included the German Diabetes Risk Score and blood glucose concentration (AUC 0.81; 95% CI 0.76-0.86) or HbA(1c) concentration (AUC 0.84; 95% CI 0.80-0.91) was found to peform better. CONCLUSIONS: Application of the German Diabetes Risk Score in the CARLA cohort did not reproduce the findings in the European Prospective Investigation into Cancer and Nutrition (EPIC) Potsdam study, which may be explained by cohort differences and model overfit in the latter; however, a high score does provide an indication of increased risk of diabetes.

Increased cardiac troponin T and C-reactive protein levels in end-stage renal disease are associated with obstructive sleep apnea.

BACKGROUND: Increased cardiac troponin T (cTnT) and C-reactive protein (CRP) levels predict mortality in patients with end-stage renal disease (ESRD) on maintenance hemodialysis. Obstructive sleep apnea (OSA) is associated with severe cardiac stress and systemic inflammation. We hypothesized that in patients with ESRD elevated levels of cTnT and CRP are consequences of unrecognized OSA. METHODS: After diagnostic polysomnography, serum levels of cTnT and CRP were assessed in two groups of patients. The first group with normal renal function which served as a control group, was recruited from routine patient referrals to the sleep laboratory at the University Hospital Magdeburg. The second group consisted of patients with ESRD on thrice-weekly maintenance hemodialysis treatment (hemodialysis group). RESULTS: After screening, 15 patients in each group were eligible for inclusion. OSA (apnea hypopnea index (AHI) > or = 10) was associated with significantly elevated serum CRP levels of 5.1 +/- 4.9 mg/l in the control group and 11.6 +/- 10.2 mg/l in the hemodialysis group, compared with patients in the respective groups without OSA. In the control group, cTnT levels were below the lower detection limit, independent of OSA severity. Patients with ESRD but without OSA had low cTnT levels, similar to those of patients in the control group (0.014 +/- 0.01 ìg/l), whereas patients with ESRD and OSA had significantly elevated serum cTnT levels (0.38 +/- 0.3 microg/l, p < 0.05). CONCLUSIONS: OSA is associated with higher CRP levels in patients with normal or impaired renal function, but cTnT is elevated in OSA patients with impaired renal function only. In this pilot study, both parameters suggest an important role of sleep related breathing disorders on cardiac stress and chronic inflammation.

Vitamins are associated with survival in patients with end-stage renal disease: a 4-year prospective study.

BACKGROUND: Patients with end-stage renal disease are at high risk from premature death due mainly to cardiovascular disease and infections. Established risk factors do not sufficiently explain this increased mortality. We, therefore, investigated total mortality prospectively in a single-centre study in patients on hemodialysis and assessed the prognostic value of baseline disease status, laboratory variables including emerging risk factors, and the influence of vitamin treatment. METHODS: Patients (n = 102) were followed-up for 4 years or until death (n = 49). Survival was calculated by the Kaplan-Meier method. Cox-proportional hazards model was used to determine independent predictors of total mortality. RESULTS: The known risk factors age, baseline clinical atherosclerotic disease, low albumin and increased cardiac troponin T were significantly associated with mortality. Patients who received multivitamins during follow-up had a significantly lower mortality risk than those not receiving this treatment (hazard ratio 0.29, 95% confidence interval 0.15-0.56). These associations remained significant after adjustment for age, cardiovascular disease, albumin and cardiac troponin T at baseline. CONCLUSIONS: The present study suggests that multivitamin supplementation in patients with end-stage renal disease is closely associated with reduced mortality due to all causes. These observations have to be validated in randomized clinical intervention trials.

Association between Weight Change and Mortality in Community Living Older People Followed for Up to 14 Years. The Hordaland Health Study (HUSK).

OBJECTIVES: To study the importance of weight change with regard to mortality in older people. DESIGN: Prospective cohort study. PARTICIPANTS: The cohort includes participants in the Hordaland Health Study, Norway, 1997-99 (N=2935, age 71-74 years) who had previously participated in a survey in 1992-93. MEASUREMENTS: Participants with weight measured at both surveys were followed for mortality through 2012. Cox proportional hazards models were used to calculate risk of death according to changes in weight. Hazard ratios (HR) with 95% confidence intervals (CIs) for people with stable weight (± <5% weight change) were compared to people who lost (≥5%) or gained (≥5%) weight. Cox regression with penalized spline was used to evaluate the association between weight change (in kg) and mortality. Analyses were adjusted for age, sex, physical activity, smoking, diabetes, hypertension, and previous myocardial infarction or stroke. Participants with cancer were excluded. RESULTS: Compared to those with stable weight, participants who lost ≥5% weight had an increased mortality risk (HR 1.59 [95% CI: 1.35-1.89]) while the group with weight gain ≥5% did not (HR 1.07 [95% CI 0.90-1.28]). Penalized spline identified those who lost more than about three kg or gained more than about 12 kg as having increased risk of death. CONCLUSION: Even a minor weight loss of ≥5% or >3 kg were significantly associated with increased risk of mortality. Thus, weight should be routinely measured in older adults.

Cosinor modelling of seasonal variation in 25-hydroxyvitamin D concentrations in cardiovascular patients in Norway.

BACKGROUND/OBJECTIVES: Seasonal variation may reduce the validity of 25-hydroxyvitamin D (25OHD) as a biomarker of vitamin D status. Here we aimed to identify potential determinants of seasonal variation in 25OHD concentrations and to evaluate cosinor modelling as a method to adjust single 25OHD measurements for seasonal variation. SUBJECTS/METHODS: In Caucasian cardiovascular patients (1999-2004), we measured 25OHD by liquid chromatography tandem mass spectrometry in 4116 baseline and 528 follow-up samples. To baseline values, we fitted a cosinor model for monthly concentrations of 25OHD. Using the model, we estimated each patient's adjusted annual 25OHD value. Further, we studied how covariates affected the annual mean 25OHD concentration and seasonal variation of the study cohort. To evaluate the model, we predicted follow-up measurements with and without covariates and compared accuracy with carrying forward baseline values and linear regression adjusting for season, common approaches in research and clinical practice, respectively. RESULTS: The annual mean (59.6 nmol/l) was associated with participants' age, gender, smoking status, body mass, physical activity level, diabetes diagnosis, vitamin D supplement use and study site (adjusted models, P<0.05). Seasonal 25OHD variation was 15.8 nmol/l, and older age (>62 years) was associated with less variation (adjusted model, P=0.025). Prediction of follow-up measurements was more accurate with the cosinor model compared with the other approaches (P<0.05). Adding covariates to cosinor models did not improve prediction (P>0.05). CONCLUSIONS: We find cosinor models suitable and flexible for analysing and adjusting for seasonal variation in 25OHD concentrations, which is influenced by age.

Cardiac troponin T predicts mortality in patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease have a high risk of premature death, mainly as the result of cardiovascular disease (CVD), which is not sufficiently explained by the conventional risk factors. We therefore prospectively investigated total mortality and cardiovascular events in 102 patients on hemodialysis and assessed the prognostic value of baseline disease status and laboratory variables including total homocysteine and cardiac troponin T. METHODS AND RESULTS: Patients were followed for 2 years or until their first event of CVD (for outcome variable cardiovascular events, n=33) or death (for outcome variable total mortality, n=28). Survival was computed by the Kaplan-Meier method. Cox proportional hazards model was used to determine independent predictors of CVD events or total mortality. Cardiac troponin T emerged as the most powerful predictor of mortality, resulting in an almost 7-fold risk increase at concentrations >0.10 ng/mL (hazard ratio 6.85, 95% CI 3. 04 to 15.45). Total homocysteine level greater than median was also associated with mortality (hazard ratio 2.44, 95% CI 1.10 to 5.40). These hazard ratios did not change substantially after adjustment for other risk factors. Significant predictors for CVD events were baseline diabetes, cerebrovascular disease, serum glucose, and triglycerides. After adjustment, only glucose and triglycerides remained significantly related to CVD events (hazard ratio with 95% CI 1.33 [1.12 to 1.57] and 1.14 [1.04 to 1.26], respectively, for a 1-mmol/L increase in concentration). CONCLUSIONS: We conclude that total homocysteine and particularly cardiac troponin T are important predictors of mortality in patients with end-stage renal disease, whereas other laboratory variables and baseline disease status have less prognostic value.

Prevalences of hyperhomocysteinemia, unfavorable cholesterol profile and hypertension in European populations.

BACKGROUND: Hyperhomocysteinemia (HHCY) is a risk factor for cardiovascular diseases (CVD). HHCY may interact with hypertension (HTEN) and an unfavorable cholesterol profile (UNFAVCHOL) to alter the risk of CVD. OBJECTIVES: To estimate the prevalences of HHCY (1) isolated and (2) in combination with UNFAVCHOL and/or HTEN in different age categories. To provide information that may improve the screening and treatment of subjects at risk of CVD. DESIGN: Cross-sectional data on 12,541 men and 12,948 women aged 20 + y were used from nine European studies. RESULTS: The prevalence of isolated HHCY was 8.5% in subjects aged 20-40 y, 4.7% in subjects aged 40-60 y and 5.9% in subjects aged over 60 y. When combining all age groups, 5.3% had isolated HHCY and an additional 5.6% had HHCY in combination with HTEN and/or UNFAVCHOL. The combinations of risk factors increased with age and, except for HHCY&UNFAVCHOL, were more prevalent than predicted by chance. Of the young subjects (20-40 y), 24% suffered from one or more of the investigated CVD risk factors. This figure was 75.1% in the old subjects (60+ years). CONCLUSIONS: A substantial number of subjects in selected European populations have HHCY (10.9%). In half of these cases, subjects suffer also from other CVD risk factors like UNFAVCHOL and HTEN. Older people in particular tend to have more than one risk factor. Healthcare professionals should be aware of this when screening and treating older people not only for the conventional CVD risk factors like UNFAVCHOL and HTEN but also HHCY, as this can easily be reduced through increased intake of folic acid via supplement or foods fortified with folic acid.

LDL size distribution in relation to insulin sensitivity and lipoprotein pattern in young and healthy subjects.

OBJECTIVE: Smaller LDL particles are associated with an increased risk for coronary artery disease and have been found predominantly in subjects with the insulin resistance syndrome. Although insulin resistance has been suggested to be a basic defect, little is known about the relation between this predisposing factor (and associated metabolic disturbances) and LDL size distribution in young and metabolically healthy subjects. In the present study, we investigated the relation between insulin sensitivity, lipoprotein distribution, and LDL patterns in young adults to increase the understanding of the development of metabolic risk factors in an early phase of the life span. RESEARCH DESIGN AND METHODS: Young, clinically healthy subjects (n = 50; age 21.1-30.6 years) were enrolled in the study. Glucose metabolism was characterized by peripheral insulin sensitivity assessed by a hyperinsulinemic-euglycemic clamp and by levels of fasting insulin, C-peptide, and glucose. Lipoproteins were measured, and LDL fractions were additionally characterized by the diameter of the major LDL peak, estimated by 2-16% polyacrylamide gradient gel electrophoresis. Cholesterol ester transfer was estimated with a fluorescent spectroscopic method that measures the transfer of fluorescent cholesteryl linoleate between exogenous donor and acceptor particles. In this assay system, cholesterylester transfer protein (CETP) activity was only influenced by the plasma CETP concentration therefore reflecting more likely the CETP mass. RESULTS: In the entire study group, 47 subjects had LDL phenotype A (LDL diameter > 25.75 nm) and 3 subjects had an intermediate phenotype (25.50-25.75 nm). An interrelation between LDL size and LDL triglyceride (LDL-TG) per apolipoprotein (apo) B (Spearman's rank correlation analysis; r = -0.78; P < 0.001) or LDL cholesterol ester (CE) per apoB (r = 0.58, P < 0.001) was found, and 39% of the plasma samples studied were characterized by a monodispersed LDL pattern. Furthermore, LDL diameters correlated negatively with total TGs (men: r = -0.52, P < 0.001; women: r = -0.61, P < 0.001) and positively with insulin sensitivity (total population: r = 0.54, P < 0.001). In addition, LDL size was inversely related to the [VLDL + LDL cholesterol (CH)]/HDL-CH ratio and positively to the HDL-CE/TG ratio, which were both related vice versa to CETP activity levels. A direct relation between CETP activity levels and LDL size or composition was not observed. In a linear regression analysis including parameters of lipoprotein metabolism (TG, HDL cholesterol, CETP activity level), glucose metabolism (insulin sensitivity, fasting insulin), and sex, only TGs predicted significantly for 62% of LDL size variability. If the total study population was evaluated according to quintiles of insulin sensitivity, increasing TGs (analysis of variance, Scheffé test; P < 0.05) and CETP activity levels (P < 0.05) were combined with decreasing LDL particle diameters (P < 0.05) and with a preponderance of a monodispersed LDL pattern (60%) in the most insulin-resistant group. CONCLUSIONS: Among parameters of the lipoprotein and glucose metabolism, total TG is the single most important factor affecting LDL size variability, even in young adults. If the study population is evaluated according to insulin sensitivity, lipoprotein pattern is altered in a more atherogenic manner in the most insulin-resistant subjects. In this group, increasing TG and CETP activity levels are associated with decreasing LDL particle diameters and preponderance of a monodispersed LDL pattern. Although increasing CETP levels are combined with this particular lipoprotein profile, a direct relation to LDL size and composition is not found.

The association between nut consumption and the risk of total and ischemic stroke in a German cohort study.

BACKGROUND/OBJECTIVES: Nuts have beneficial effects on coronary heart disease and many cardiovascular risk factors. However, their effect on stroke is less established, and no studies on the topic are available in Northern and Central European populations. Therefore, we aimed at investigating the association between nut consumption and the risk of stroke in a German population. SUBJECTS/METHODS: We used data from a prospective cohort of 26,285 participants of the European Prospective Investigation into the Cancer and Nutrition Potsdam Study. During a median follow-up time of 8.3 years (interquartile range: 7.5-9.2), 288 incident cases of stroke occurred. Nut consumption (standard portion size of 50 g) was assessed at baseline with a semiquantitative food-frequency questionnaire. RESULTS: The median nut intake was 0.82 g per day, interquartile range: 0.41-4.11. In the multivariable model, an increased risk of stroke was observed among participants who never consumed nuts (hazard ratio (HR): 1.56, 95% confidence interval: 1.17-2.08), compared with those consuming <½ portion/week. However, there was no evidence of a dose-response relationship between nut consumption and stroke. Compared with those who consumed <½ portion/week, the multivariable HR for total stroke was 1.06 (0.75-1.52) among those who consumed ½ to 1 portion/week and 1.37 (0.92-2.05) for those who consumed >1 portion/week. Similar nonsignificant associations were observed in stratified analysis for gender, or for fatal and nonfatal stroke. CONCLUSIONS: We could not observe an association between nut consumption and the risk of developing stroke (fatal/nonfatal) in a population with low habitual nut consumption.

Vitamin supplementation can markedly reduce the homocysteine elevation induced by fenofibrate.

Elevated homocysteine concentrations are a risk factor for atherosclerotic disease. Recently it was reported that lipid lowering with fibrates increases homocysteine by up to 40%. Since elevated homocysteine concentrations can readily be lowered by vitamin supplementation, a randomized, double-blind crossover study was performed to investigate the effect of fenofibrate plus folic acid, vitamin B6 and B12 versus fenofibrate plus placebo in hyperlipidemic men. The crossover study comprised a run-in period of 6 weeks, a first treatment phase of 6 weeks, a washout phase of 8 weeks and a second treatment phase of 6 weeks. Vitamins were given at doses of 650 microg folic acid, 50 microg vitamin B12 and 5 mg vitamin B6 per day for a period of 6 weeks. After fenofibrate plus placebo the increase in homocysteine concentration was 44+/-47%. After fenofibrate plus vitamins it was 13+/-25%, being significantly lower than without vitamins. The increase in homocysteine in response to fenofibrate may counteract the cardioprotective effect of lipid lowering. The addition of vitamins involved in homocysteine metabolism can prevent most of the homocysteine increase seen after fenofibrate plus placebo. Addition of these vitamins to fenofibrate may therefore be warranted for routine use.

Factors explaining the difference of total homocysteine between men and women in the European Investigation Into Cancer and Nutrition Potsdam study.

Interestingly, plasma total homocysteine (tHcy) concentration is consistently higher in men than in women. This observation deserves further investigations because elevated tHcy concentrations have been shown to be independently associated with coronary, peripheral, and cerebral vascular diseases. It was the aim of the present study to define major determinants of plasma tHcy in a healthy middle-aged German population under particular consideration of the gender factor. The study population was obtained from an ongoing recruitment procedure for a cohort study and comprised 336 men and women, aged 40 to 65 years. Exclusion criteria were elevated creatinine levels in blood, history of skin or atherosclerotic diseases, current use of vitamins or other supplements, and heavy smoking. Plasma tHcy, folate, vitamin B12, vitamin B6, creatinine, testosterone and estradiol, protein, and hematocrit were measured. Fat-free mass was assessed by skinfold thickness. The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR), a key enzyme of folate and homocysteine metabolism, was determined by polymerase chain reaction (PCR) with restriction enzyme analysis. In this population, plasma tHcy ranged from 5 to 46 micromol/L. The frequency of the T allele of the MTHFR was 0.29, which is lower than in other populations. A total of 54.2% of this population was homozygote for the wild-type, 39.6% heterozygote, and 6.2% homozygote for the mutation. tHcy correlated negatively with folate and cobalamin concentration in blood and positively with creatinine. No correlation was seen with vitamin B6. From the gender-related variables, tHyc correlated significantly with fat-free mass and testosterone and inversely with estradiol. The difference between gender with regard to tHcy was mainly explained by differences in fat-free mass, but also by estradiol concentrations. The following contributions to the variation of tHcy were seen in a multivariate regression model: plasma cobalamin (11%), creatinine (11%), plasma folate (8%), fat-free mass (5%), estradiol (2%), MTHFR polymorphisms (2%), and plasma protein (1%). We concluded that tHcy in the general population has a variety of determinants ranging from nutrition, internal metabolic parameters to gender-related variables.

Supplementation with vitamin B12 decreases homocysteine and methylmalonic acid but also serum folate in patients with end-stage renal disease.

Hyperhomocysteinemia is frequently found in patients with end-stage renal disease (ESRD). Plasma total homocysteine (tHcy) concentrations may be reduced by supplementation with folic acid or combinations of folic acid, vitamin B12, and vitamin B6. Supplementation studies with vitamin B12 alone in patients with ESRD have not yet been published. In this study, we investigated the effects of intravenous injection of cyanocobalamin (1 mg/wk for 4 weeks) in ESRD patients (N = 14) with low serum cobalamin concentrations (<180 pmol/L). All patients had elevated levels of plasma tHcy, methylmalonic acid (MMA), and cystathionine before supplementation. After supplementation, plasma tHcy and MMA decreased 35% and 48%, respectively; however, cystathionine levels were unchanged. The extent of the plasma tHcy reduction tended to be influenced by the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR). Serum cobalamin increased significantly upon supplementation, whereas serum folate levels were substantially reduced by 47%. In contrast, red blood cell (RBC) folate was unchanged. This study shows that vitamin B12 supplementation effectively decreases both MMA and plasma tHcy in ESRD patients with low B12 levels. Furthermore, it illustrates the close interrelation between vitamin B12 and folate metabolism.

Response of hyperhomocysteinemia to folic acid supplementation in patients with end-stage renal disease.

BACKGROUND: Elevated concentrations of homocysteine are associated with an increased risk for cardiovascular disease. Reasons for elevated homocysteine concentrations are folate or vitamin B12 deficiency, renal disease or genetic abnormalities. A high prevalence of hyperhomocysteinemia is found in patients with end-stage renal disease (ESRD). Since these patients are also at increased risk for vitamin deficiency, a supplementation study comparing two doses of folic acid was performed in patients with ESRD treated with maintenance hemodialysis or with peritoneal dialysis. PATIENTS AND METHODS: Patients undergoing hemodialysis (n = 70) or peritoneal dialysis (n = 12) were supplemented with 2.5 mg or 5 mg folic acid (three times per week after each dialysis treatment) for four weeks in a parallel study design. In 20 hemodialysis patients, the effect of folic acid withdrawal was observed after four weeks. RESULTS: Both supplementation schemes reduced homocysteine to a similar extent (35%) but did not normalize homocysteine concentrations in the majority of patients. Dialysis also had a strong homocysteine lowering effect. After supplementation, 74% of the hemodialysis patients had post-dialysis homocysteine concentrations within the reference range (<16 micromol/l). Homocysteine concentrations remained decreased in 20 patients four weeks after withdrawal of folic acid supplementation. CONCLUSIONS: It is concluded that supplementation with 2.5 or 5 mg folic acid has a similar effect on homocysteine concentrations to supplementation regimens using 15 mg folic acid supplements. In contrast to the effect of folic acid supplementation in subjects with normal renal function, folic acid supplementation does not normalize homocysteine concentrations in ESRD patients.

Folic acid and Vitamin B6 supplementation and plasma homocysteine concentrations in healthy young women.

Elevated plasma homocysteine levels are a risk factor for atherosclerotic disease. Elevated fasting plasma homocysteine concentrations can be reduced by vitamin supplementation with folic acid, vitamin B6 and vitamin B12, but the effect of nutritive amounts of single vitamins on homocysteine plasma levels within the normal range is not known. This study was performed to investigate the effect of folic acid supplementation (400 micrograms/d) on fasting plasma homocysteine levels in healthy young women, in comparison to vitamin B6 (2 mg/d) or a combination of both vitamins. Healthy young women with normal homocysteine levels were supplemented for four weeks either with folic acid, vitamin B6 or the combination. The combination of folic acid and vitamin B6 reduced plasma homocysteine by 17%. Supplementation with folic acid reduced plasma homocysteine levels by 11.5%. The effect of folic acid and vitamin B6 was not significantly different from the effect of folic acid alone. Vitamin B6 had no effect on plasma homocysteine concentrations. Results show that homocysteine levels within the normal range are lowered by low-dose vitamin supplementation including folic acid.

The beauty of the face: an orthodontic perspective.

In esthetic dentistry, the practitioner needs to consider more than just tooth shade and contour. All too often, attention is directed toward reconstructing the dentition for function and esthetic appearance without regard for an existing malocclusion and facial imbalance. When an individual accepts esthetic dental reconstruction, it can be assumed that he or she is attempting to improve a self-image. Dentofacial balance must be considered to truly enhance a patient's potential to achieve the optimal dentofacial esthetic appearance and enhance self-image. Optimal care in the area of esthetics, therefore, requires that esthetic dentistry be considered a multidisciplined service encouraging cooperation among the patient's family dentist, orthodontist, oral and maxillofacial surgeon, prosthodontist, plastic surgeon, periodontist, and possibly others.