Search

Competing Interests: The authors made the following disclosures: D.R.P. is a consultant for Biogen Inc. and clinical trials’ principal/subinvestigator for Corbus Pharmaceuticals, Elorac, Inc., Eli Lilly and Company, Emerald Health Pharmaceuticals, Kadmon, Inc., Pfizer, Inc., and Soligenix, Inc. The other authors have no conflicts of interest to disclose.

Competing Interests: The authors made the following disclosures: D.R.P. is a consultant for Biogen, Inc. and Pfizer, Inc., and a clinical trials investigator for Pfizer, Inc., EMD Serono, Priovant, Emerald Health, Kadmon, and Argenx. B.S. is a consultant for Argenx and has served as a clinical trials investigator for Argenx, AstraZeneca, and Elorac. The other authors have no conflicts of interest to disclose.

Background: When the first known US case of COVID-19 (Coronavirus Disease 2019) was reported in early 2020, little was known about the impact of this novel virus on the cystic fibrosis community. As the majority of individuals with CF have chronic lung disease, this population was initially considered to be at high risk for severe disease as infection with a multitude of viruses has proven to cause pulmonary exacerbation. SARS-CoV-2 virus has proven challenging to study given the multiple disease manifestations, range of severity, and wave-like phenomenon that varies geographically. People with CF who become infected with COVID-19 can be asymptomatic or have symptoms ranging from mild cough and congestion to full respiratory failure, similar to the manifestations seen in non-CF individuals. By studying the seroprevalence, clinical course, and antibody durability due to COVID-19 and vaccinations, we will be better equipped to provide appropriate and informed care to people with CF., Methods: Between July 2020 and April 2021 we enrolled 123 people with CF (pwCF) who receive care at the MN CF Center. We monitored their serology every 6 months for SARS-CoV-2 immunoglobulins (nucleocapsid and spike IgG) for evidence of natural and induced immunity. Medication use, pulmonary function, exacerbation history, and hospitalizations were extracted via electronic medical record (EMR)., Results: 84% (101/120) of enrolled participants were vaccinated against SARS-CoV-2 during the study. Eighty three percent of the cohort showed evidence of either natural or induced "immunity." The average duration of antibody from induced immunity in participants was 6.1 months and from natural immunity was 7.4 months with an overall average duration of antibody of 6.8 months. Earliest antibody detected was 12 days after a single dose of the BNT162b2 vaccine and antibody was detectable across a span of 13 months. Eleven percent of vaccinated individuals did not have measurable IgG. 36% of non-responders (NRs) were solid organ transplant patients on chronic immunosuppressive therapy. Only 3 people within this cohort were hospitalized due to COVID pneumonia and all three survived., Conclusion: To our knowledge, this is the first report on the seroprevalence and longevity of SARS-CoV-2 IgG to 1 year in adults with CF after the widespread availability of SARS-CoV-2 vaccinations. These data show that pwCF respond to the COVID vaccination and produce long-lasting antibodies similar to the general population., Competing Interests: Authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript., (© 2024 The Authors. Published by Elsevier Ltd.)

Introduction: Despite widespread recognition of the health and social risks posed by parental incarceration (PI) and homelessness, these challenges are rarely considered in unison. We sought to (a) assess the experiences of homelessness among youth with and without a history of PI and (b) compare the health and healthcare utilization among youth with a combined history of PI and homelessness., Method: Examining data from eighth-, ninth-, and 11th-grade public school participants in the 2019 Minnesota Student Survey ( N = 110,904), we calculated univariate and multivariate analyses to characterize the health status and care utilization of youth who have experienced PI, past-year homelessness, or both., Results: We observed higher prevalence of homelessness among youth with a history of PI compared to those without. The group with dual PI-homelessness experience had a higher proportion of youth that were younger, male, and non-White; and living in poverty or urban areas compared to youth with PI history only. Even after accounting for demographic factors, the dual PI-homelessness group evidenced higher expected odds for several physical health conditions (e.g., asthma, diabetes), and differences in care utilization indicators relative to individual PI and homelessness groups., Discussion: Findings suggest that PI may be overrepresented among recently homeless youth and that youth with such dual experience possess distinct, and often elevated, health service needs. Health, education, housing, and other systems may need intersectoral strategies to better identify and support this at-risk subset of youth through clinical and policy approaches. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Pantothenic acid, also referred to as vitamin B 5 , is a water-soluble vitamin that has essential functions in the body as a component of coenzyme A (CoA) and acyl carrier protein (ACP). It is widely distributed in animal and plant-source foods. Nutritional deficiency of pantothenic acid is rare and toxicity negligible. Information on pantothenic acid intakes in the Nordic countries is limited and biomarker data from Nordic and Baltic populations is missing. Due to a lack of data, no dietary reference values (DRVs) were given for pantothenic acid in the Nordic Nutrition Recommendations (NNR) since 2012. The aim of this scoping review was to examine recent evidence relevant for updating the DRVs for NNR2023. Scientific literature since 2012 on associations of pantothenic acid with health-related issues in Nordic and Baltic countries was searched. No health concerns related to pantothenic acid were identified., Competing Interests: The authors have not received any funding or benefits from industry or elsewhere to conduct this study., (© 2023 Riitta Freese et al.)

Niacin is the precursor to pyridine nucleotides NAD (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine dinucleotide phosphate). Niacin (vitamin B 3 ) is the common term for nicotinic acid, nicotinamide and derivatives that exhibit the biological activity of nicotinamide. Furthermore, the indispensable amino acid tryptophan is the substrate for de novo synthesis of NAD. Thus, the requirements and intake of niacin are expressed as niacin equivalents (NE). The focus of interest for niacin over the last decade has primarily been on pharmacological doses of nicotinic acid as a lipid-lowering agent and other NAD precursors as potential enhancers of cellular NAD + concentrations. None of these studies, however, makes a useful contribution to understanding dietary requirements in healthy populations. The requirement for niacin is estimated based on the relationship between intake and biochemical indices of niacin status, primarily urinary excretion of nicotinamide metabolites., Competing Interests: The authors have not received any funding or benefits from industry or elsewhere to conduct this study., (© 2023 Riitta Freese and Vegard Lysne.)

Objectives: To evaluate uptake of lung cancer screening in an urban Native American clinic using 2 culturally targeted promotion strategies., Methods: Patients eligible for lung cancer screening from July 2019 to July 2021 were randomized to receive either a single culturally-targeted mailer from the clinic regarding possible eligibility for screening, or the same mailer plus a follow-up text message and additional mailing., Results: Overall, there were low rates of shared decision-making visit scheduling (8.5%) with no difference between promotion strategy groups (9.4% in control group vs 7.7% in culturally-targeted outreach group). Only about 50% of the lung cancer screening CT exams ordered were completed and returned to the clinic., Conclusions: While there was no difference between arms in this intervention, 8.5% of the sample did complete a shared decision-making visit after these low-cost interventions. The gap between the number of screening CTs ordered and number who completed the CT represents an area where further interventions should focus., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

There is a need for wastewater based epidemiological (WBE) methods that integrate multiple, variously sized surveillance sites across geographic areas. We developed a novel indexing method, Melvin's Index, that provides a normalized and standardized metric of wastewater pathogen load for qPCR assays that is resilient to surveillance site variation. To demonstrate the utility of Melvin's Index, we used qRT-PCR to measure SARS-CoV-2 genomic RNA levels in influent wastewater from 19 municipal wastewater treatment facilities (WWTF's) of varying sizes and served populations across the state of Minnesota during the Summer of 2020. SARS-CoV-2 RNA was detected at each WWTF during the 20-week sampling period at a mean concentration of 8.5 × 10 4 genome copies/L (range 3.2 × 10 2 -1.2 × 10 9 genome copies/L). Lag analysis of trends in Melvin's Index values and clinical COVID-19 cases showed that increases in indexed wastewater SARS-CoV-2 levels precede new clinical cases by 15-17 days at the statewide level and by up to 25 days at the regional/county level. Melvin's Index is a reliable WBE method and can be applied to both WWTFs that serve a wide range of population sizes and to large regions that are served by multiple WWTFs., (© 2021. The Author(s).)

Vegan diets are gaining popularity, also in families with young children. However, the effects of strict plant-based diets on metabolism and micronutrient status of children are unknown. We recruited 40 Finnish children with a median age 3.5 years-vegans, vegetarians, or omnivores from same daycare centers-for a cross-sectional study. They enjoyed nutritionist-planned vegan or omnivore meals in daycare, and the full diets were analyzed with questionnaires and food records. Detailed analysis of serum metabolomics and biomarkers indicated vitamin A insufficiency and border-line sufficient vitamin D in all vegan participants. Their serum total, HDL and LDL cholesterol, essential amino acid, and docosahexaenoic n-3 fatty acid (DHA) levels were markedly low and primary bile acid biosynthesis, and phospholipid balance was distinct from omnivores. Possible combination of low vitamin A and DHA status raise concern for their visual health. Our evidence indicates that (i) vitamin A and D status of vegan children requires special attention; (ii) dietary recommendations for children cannot be extrapolated from adult vegan studies; and (iii) longitudinal studies on infant-onset vegan diets are warranted., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

Early exposure to negative environmental impact shapes individual behavior and potentially contributes to any mental disease. We reported previously that accumulated environmental risk markedly decreases age at schizophrenia onset. Follow-up of matched extreme group individuals (≤1 vs. ≥3 risks) unexpectedly revealed that high-risk subjects had >5 times greater probability of forensic hospitalization. In line with longstanding sociological theories, we hypothesized that risk accumulation before adulthood induces violent aggression and criminal conduct, independent of mental illness. We determined in 6 independent cohorts (4 schizophrenia and 2 general population samples) pre-adult risk exposure, comprising urbanicity, migration, physical and sexual abuse as primary, and cannabis or alcohol as secondary hits. All single hits by themselves were marginally associated with higher violent aggression. Most strikingly, however, their accumulation strongly predicted violent aggression (odds ratio 10.5). An epigenome-wide association scan to detect differential methylation of blood-derived DNA of selected extreme group individuals yielded overall negative results. Conversely, determination in peripheral blood mononuclear cells of histone-deacetylase1 mRNA as 'umbrella mediator' of epigenetic processes revealed an increase in the high-risk group, suggesting lasting epigenetic alterations. Together, we provide sound evidence of a disease-independent unfortunate relationship between well-defined pre-adult environmental hits and violent aggression, calling for more efficient prevention.

Objective: Burnout tends to be high in Intensive Care Unit (ICU) settings. Stressors include serious patient illness, round-the-clock acute events, and end of life (non-beneficial) care. We report on an ICU with very low burnout scores. We sought to understand factors that might be responsible for these favorable outcomes., Design: We compared ICU scores on burnout and its predictors with scores in non ICU providers, merging scores in four ICUs (burn, medical, surgical and pediatrics). Analyses included descriptive statistics, as well as general estimating equations to assess odds of burnout in ICU vs non ICU clinicians., Setting: Annual wellness survey performed in October 2017 at Hennepin Healthcare System (HHS), an integrated system of care that includes an urban safety net hospital in Minneapolis, Minnesota., Participants: Six hundred seventy-nine providers (physicians and advanced practice providers)., Interventions: None., Measurements and Main Results: Annual surveys are performed using the validated Mini-Z 10 item wellness instrument. The Mini-Z assesses stress, satisfaction, and burnout, as well as known predictors including work control, chaos, teamwork, values alignment, and electronic medical record-related stress. Response rate in ICUs was 70% (64% elsewhere). Ten percent of ICU clinicians reported burnout, vs 37% of other providers (p = 0.015). ICUs were characterized as having lower chaos, less stress, and very high teamwork and values alignment between clinicians and leaders. Odds of burnout were four times lower in ICU clinicians (Odds Ratio 0.24, 95% CI 0.06, 0.96, p = 0.043). Of all HHS providers, those with values not aligned with leaders had 3.28 times the odds of burnout (CIs 1.92, 5.59, p < 0.001)., Conclusions: Low burnout can be present in a busy, safety net ICU. Explicitly aligning values between clinicians and leaders may hold promise as a remediable worklife factor for producing these favorable results., Competing Interests: Conflicts of interest: None

Objective: The objective of the present study was to explore whether dietary patterns (DP) are associated with nutritional status indicators among adolescent Mozambican girls. Design/Setting/Subjects In this population-based cross-sectional study we used the FFQ data of 547 girls aged 14-19 years from Central Mozambique to derive dietary patterns by means of principal component analysis. We used two-level linear regression models to examine the associations between the DP and anthropometric and biochemical indicators of nutritional status., Results: We identified three DP: 'Urban bread and fats', 'Rural meat and vegetables' and 'Rural cassava and coconut'. The 'Urban bread and fats' DP was positively associated with BMI-for-age Z-score (BMIZ), mid-upper arm circumference (MUAC), triceps skinfold (P for all<0·001) and blood Hb (P=0·025). A negative association was observed between the 'Urban bread and fats' DP and serum folate (P<0·001). The 'Rural meat and vegetables' DP and the 'Rural cassava and coconut' DP were associated negatively with BMIZ, MUAC and triceps skinfold (P for all<0·05), but the 'Rural meat and vegetables' DP was associated positively with serum ferritin (P=0·007)., Conclusions: Urban and rural DP were associated with nutritional status indicators. In a low-resource setting, urban diets may promote body fat storage and blood Hb concentrations but compromise serum folate concentration. It is important to continue valuing the traditional, rural foods that are high in folate.

Aim: To compare the effects of regular vs low-FODMAP rye bread on irritable bowel syndrome (IBS) symptoms and to study gastrointestinal conditions with SmartPill ® ., Methods: Our aim was to evaluate if rye bread low in FODMAPs would cause reduced hydrogen excretion, lower intraluminal pressure, higher colonic pH, different transit times, and fewer IBS symptoms than regular rye bread. The study was a randomized, double-blind, controlled cross-over meal study. Female IBS patients ( n = 7) ate study breads at three consecutive meals during one day. The diet was similar for both study periods except for the FODMAP content of the bread consumed during the study day. Intraluminal pH, transit time, and pressure were measured by SmartPill, an indigestible motility capsule., Results: Hydrogen excretion (a marker of colonic fermentation) expressed as area under the curve (AUC) (0-630 min) was [median (range)] 6300 (1785-10800) ppm∙min for low-FODMAP rye bread and 10 635 (4215-13080) ppm∙min for regular bread ( P = 0.028). Mean scores of gastrointestinal symptoms showed no statistically significant differences but suggested less flatulence after low-FODMAP bread consumption ( P = 0.063). Intraluminal pressure correlated significantly with total symptom score after regular rye bread (ρ = 0.786, P = 0.036) and nearly significantly after low-FODMAP bread consumption (ρ = 0.75, P = 0.052). We found no differences in pH, pressure, or transit times between the breads. Gastric residence of SmartPill was slower than expected. SmartPill left the stomach in less than 5 h only during one measurement (out of 14 measurements in total) and therefore did not follow on par with the rye bread bolus., Conclusion: Low-FODMAP rye bread reduced colonic fermentation vs regular rye bread. No difference was found in median values of intraluminal conditions of the gastrointestinal tract., Competing Interests: Conflict-of-interest statement: Laatikainen R has written a Finnish book on irritable bowel syndrome and diet; He is also founder and owner of Booston Ltd, which provides IBS-related dietetic services to IBS patients, healthcare professionals, and various organizations; Pirkola L, Hongisto SM, and Loponen J are employees of Fazer Bakeries; At the time of the research, Pirkola L was working at the University of Helsinki; Others have no personal interests to declare; Fazer Bakeries funded the study and provided the breads.

We build on the social heuristics hypothesis, the literature on the glucose model of self-control, and recent challenges on these hypotheses to investigate whether individuals exhibit a change in degree of trust and reciprocation after consumption of a meal. We induce short-term manipulation of hunger followed by the trust game and a decision on whether to leave personal belongings in an unlocked and unsupervised room. Our results are inconclusive. While, we report hungry individuals trusting and reciprocating more than those who have just consumed a meal in a high trust society, we fail to reject the null with small number of observations ( N = 101) and experimental sessions ( N = 8). In addition, we find no evidence of short-term hunger having an impact on charitable giving or decisions in public good game.

Diet is a major modifiable lifestyle factor that may affect the components of the metabolic syndrome. We aimed to investigate the association between relative proportions of macronutrients and the components of the metabolic syndrome in a population of individuals with type 1 diabetes. In all, 791 individuals without nephropathy, with plausible energy intake and known metabolic syndrome status, taking part in the Finnish Diabetic Nephropathy Study were included in the analyses. Dietary data were collected with a diet record. The association between the relative macronutrient intake and the outcome variables were analysed using multivariable nutrient density substitution models. The relative proportions of dietary macronutrients or fatty acids were not associated with the presence of the metabolic syndrome. In men, however, favouring carbohydrates over fats was associated with lower odds of the waist component, whereas favouring either carbohydrates or fats over proteins was associated with lower odds of the blood pressure component of the metabolic syndrome. In women, substituting carbohydrates for fats was associated with lower HDL-cholesterol concentration. Substituting carbohydrates or fats for alcohol or protein was, in men, associated with lower systolic blood pressure. To conclude, the relative distribution of macronutrients may have some relevance for the metabolic syndrome.

Aims: We studied the association between fear of hypoglycaemia (FoH) and various diabetes self-management practices., Methods: Data from 798 individuals with type 1 diabetes participating in the FinnDiane Study were included. Self-reported questionnaires were used to assess FoH and self-management practices (e.g. dietary intake, insulin administration, physical activity). For glycaemic control, we used both the latest HbA 1c measurements and the serial HbA 1c measurements from the medical files. Factor analysis was used to reveal underlying constructs within the food frequency section of the diet questionnaire., Results: In all, 44% and 63% of men and women reported FoH, respectively. In men, FoH was associated with higher mean serial HbA 1c levels, higher number of reported self-monitoring of blood glucose (SMBG), higher carbohydrate intake, and lower scores in the "high-fat" factor. In women, FoH was associated with a higher number of reported SMBGs and higher energy intake. No difference was observed in physical activity and insulin administration., Conclusions: FoH has various implications for the self-management of diabetes. More studies are however needed to assess on one hand the association between FoH and diabetes self-management, and on the other hand, FoH and its long term consequences, such as the emergence of diabetic complications and mortality.

Fruit and vegetable consumption produces changes in several biomarkers in blood. The present study aimed to examine the dose-response curve between fruit and vegetable consumption and carotenoid (α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin), folate and vitamin C concentrations. Furthermore, a prediction model of fruit and vegetable intake based on these biomarkers and subject characteristics (i.e. age, sex, BMI and smoking status) was established. Data from twelve diet-controlled intervention studies were obtained to develop a prediction model for fruit and vegetable intake (including and excluding fruit and vegetable juices). The study population in the present individual participant data meta-analysis consisted of 526 men and women. Carotenoid, folate and vitamin C concentrations showed a positive relationship with fruit and vegetable intake. Measures of performance for the prediction model were calculated using cross-validation. For the prediction model of fruit, vegetable and juice intake, the root mean squared error (RMSE) was 258.0 g, the correlation between observed and predicted intake was 0.78 and the mean difference between observed and predicted intake was - 1.7 g (limits of agreement: - 466.3, 462.8 g). For the prediction of fruit and vegetable intake (excluding juices), the RMSE was 201.1 g, the correlation was 0.65 and the mean bias was 2.4 g (limits of agreement: -368.2, 373.0 g). The prediction models which include the biomarkers and subject characteristics may be used to estimate average intake at the group level and to investigate the ranking of individuals with regard to their intake of fruit and vegetables when validating questionnaires that measure intake.

Many African diets are low in fat but are currently changing because of nutrition transition. We studied fat and fatty acid (FA) intake and the essential fatty acid (EFA) status of adolescent girls (aged 14-19 years, n 262) in Zambezia Province, central Mozambique. A cross-sectional study was carried out in a city as well as in the towns and rural villages of a coastal and an inland district. Dietary intake and FA sources were studied in a 24 h dietary recall. FA compositions of cholesteryl esters and phospholipids of non-fasting serum samples were analysed by GLC. Fat intake was low (13-18 % of energy) in all areas. Coconut and palm oil were the main sources of fat, and soyabean oil and maize were the main sources of PUFA. Compared to Food and Agriculture Organization/WHO 2010 recommendations, intake of linoleic acid (LA, 18 : 2n-6) was inadequate in the coastal district, and intakes of n-3 PUFA were inadequate in all areas. FA compositions of serum lipids differed between areas. The proportions of LA tended to be highest in the city and lowest in the rural areas. The phospholipid mead (20 : 3n-9):arachidonic acid (20 : 4n-6) ratio did not indicate EFA insufficiency. LA proportions in phospholipids were low, but those of long-chain n-6 and n-3 PUFA were high in comparison with Western adolescents. To conclude, fat sources, FA intake and EFA status differed between adolescent girls living in different types of communities. Fat intake was low, but EFA insufficiency was not indicated.

Background: There is very little published work on dietary intake and nutritional status of Mozambicans. We conducted a population-based cross-sectional study on the diet and nutritional status of adolescent girls in different types of communities in Zambézia Province, Central Mozambique, in two distinct seasons., Objective: The purpose of this paper is to present the design, methods, and study population characteristics of the Estudo do Estado Nutricional e da Dieta em Raparigas Adolescentes na Zambézia (the ZANE Study)., Methods: Data was collected in January-February 2010 ("hunger season") and in May-June 2010 ("harvest season"). A total of 551 girls in the age group 14-19 years old were recruited from one urban area and two districts (district towns and rural villages). The study protocol included a background interview, a 24-hour dietary recall interview, a food frequency questionnaire, anthropometric measurements, bioimpedance, hemoglobin measurement, and venous blood, urine, buccal cell, and fecal sampling., Results: Adolescent motherhood was common in all study regions. Stunting prevalence for the total study population as a weighted percentage was 17.8% (95/549; 95% CI 14.3-22.0) with no regional differences. Overweight was found mainly in the urban area where the prevalence was 12.6% (20/159; 95% CI 7.5-17.6), thinness was rare. There were regional differences in the prevalence of malaria parasitemia and intestinal helminth infestation, but not human immunodeficiency virus., Conclusions: The fully analyzed data from the ZANE Study will yield results useful for setting priorities in nutrition policy and further research on the diet and nutritional status in Mozambique and other countries with similar nutritional problems., Trial Registration: ClinicalTrials.gov: NCT01944891; http://www.clinicaltrials.gov/ct2/show/NCT01944891 (Archived by WebCite at http://www.webcitation.org/6L9OUrsq8).

This review focuses on parental decision making regarding the care and treatment of children with cancer. Articles were abstracted from the following sources: Ovid Databases (Cochrane Database of Systematic Reviews, Database of Abstracts of Review of Effects, Medline, and Social Work Abstracts) and EBSCOhost (Academic Search Premier and Academic Search Complete) using smart text. The criteria for the search were publications between 2005 and 2012 and publication in peer-review journals. The descriptors used were parents of children with cancer, decision making, decisions about childhood cancer, and parents. The search yielded 59 references, but after duplicates, as well as dated and irrelevant articles were removed, 17 articles were identified that focused specifically on the decisions parents make regarding the care and treatment of children with cancer. Coders agreed that the child's quality of life/well-being, parental hope/expectations, support/supportive care, communication, and information were important themes in considering the decisions parents made regarding the care and treatment of children with cancer. These themes provide insight into the needs of parents in making decisions about the care and treatment of children with cancer.

Aims: Oral L-arginine supplementation has been used in several studies to improve endothelium-dependent, nitric oxide (NO)-mediated vasodilation. L-Arginine treatment is hampered by extensive presystemic elimination due to intestinal arginase activity. In contrast, L-citrulline is readily absorbed and at least in part converted to L-arginine. The aim of our study was to assess this metabolic conversion and its subsequent pharmacodynamic effects., Methods: In a double-blind, randomized, placebo-controlled cross-over study, 20 healthy volunteers received six different dosing regimes of placebo, citrulline, and arginine. Pharmacokinetic parameters (C(max), T(max), C(min), AUC) were calculated after 1 week of oral supplementation. The ratio of plasma L-arginine over asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase (arginine/ADMA ratio), urinary cyclic guanosine monophosphate (cGMP) and nitrate excretion rates, and flow-mediated vasodilation (FMD) was measured to assess pharmacodynamic effects., Results: L-Citrulline dose-dependently increased AUC and C(max) of plasma L-arginine concentration more effectively than L-arginine (P < 0.01). The highest dose of citrulline (3 g bid) increased the C(min) of plasma L-arginine and improved the L-arginine/ADMA ratio from 186 +/- 8 (baseline) to 278 +/- 14 [P < 0.01, 95% confidence interval (CI) 66, 121]. Moreover, urinary nitrate and cGMP were increased from 92 +/- 10 to 125 +/- 15 micromol mmol(-1) creatinine (P = 0.01, 95% CI 8, 58) and from 38 +/- 3.3 to 50 +/- 6.7 nmol mmol(-1) creatinine (P = 0.04, 95% CI 0.4, 24), respectively. No treatment improved FMD over baseline. However, pooled analysis of all FMD data revealed a correlation between the increase of arginine/ADMA ratio and improvement of FMD., Conclusion: Our data show for the first time that oral L-citrulline supplementation raises plasma L-arginine concentration and augments NO-dependent signalling in a dose-dependent manner.