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Concept: Homocysteine

169

Considering that hyperhomocysteinemia is an independent risk factor for cardiovascular disease, the purpose of this study was to determine the kinetics of serum homocysteine (tHcy) and the vitamins involved in its metabolism (folates, B(12), and B(6)) in response to acute exercise at different intensities. Eight sedentary males (18-27 yr) took part in the study. Subjects were required to complete two isocaloric (400 kcal) acute exercise trials on separate occasions at 40% (low intensity, LI) and 80% VO(2peak) (high intensity, HI). Blood samples were drawn at different points before (pre4 and pre0 h), during (exer10, exer20, exer30, exer45, and exer60 min), and after exercise (post0, post3, and post19 h). Dietary, genetic, and lifestyle factors were controlled. Maximum tHcy occurred during exercise, both at LI (8.6 (8.0-10.1) µmol/L, 9.3% increase from pre0) and HI (9.4 (8.2-10.6) µmol/L, 25.7% increase from pre0), coinciding with an accumulated energy expenditure independent of the exercise intensity. From this point onwards tHcy declined until the cessation of exercise and continued descending. At post19, tHcy was not different from pre-exercise values. No values of hyperhomocysteinemia were observed at any sampling point and intensity. In conclusion, acute exercise in sedentary individuals, even at HI, shows no negative effect on tHcy when at least 400 kcal are spent during exercise and the nutritional status for folate, B(12), and B(6) is adequate, since no hyperhomocysteinemia has been observed and basal concentrations were recovered in less than 24 h. This could be relevant for further informing healthy exercise recommendations.

Concepts: Nutrition, Obesity, Cardiovascular disease, Vitamin, Folic acid, Negative feedback, Homocysteine, Homocystinuria

167

BACKGROUND: Strenuous physical activity can alter the status of folic acid, a vitamin directly associated with homocysteine (Hcy); alterations in this nutrient are a risk factor for cardiovascular disease. Handball players are a population at risk for nutrient deficiency because of poor dietary habits. OBJECTIVE: The aims of this study were to evaluate nutritional status for macronutrients and folic acid in members of a high-performance handball team, and determine the effect of a nutritional intervention with folic acid supplementation and education. DESIGN: A total of 14 high-performance handball players were monitored by recording training time, training intensity (according to three levels of residual heart rate (RHR): <60%, 60%--80% and >80%), and subjective perceived exertion (RPE) during a 4-month training period. Nutritional, laboratory and physical activity variables were recorded at baseline (Week 0), after 2 months of dietary supplementation with 200 mug folic acid (50% of the recommended daily allowance) (Week 8) and after 2 months without supplementation (Week 16). We compared training load and analyzed changes in plasma concentrations of Hcy before and after the intervention. RESULTS: Bivariate analysis showed a significant negative correlation (P < 0.01) between Hcy and folic acid concentrations (r = -0.84) at Week 8, reflecting a significant change in Hcy concentration (P < 0.05) as a result of hyperhomocysteinemia following the accumulation of high training loads. At Week 16 we observed a significant negative correlation (P < 0.01) between Hcy concentration and training time with an RHR <60%, indicating that aerobic exercise avoided abrupt changes in Hcy and may thus reduce the risk of cardiovascular accidents in high-performance athletes. CONCLUSION: Integral monitoring and education are needed for practitioners of handball sports to record their folic acid status, a factor that directly affects Hcy metabolism. Folic acid supplementation may protect athletes against alterations that can lead to cardiovascular events related to exertion during competition.

Concepts: Protein, Nutrition, Cardiovascular disease, Physical exercise, Vitamin, Essential nutrient, Folic acid, Homocysteine

29

Migraine is a highly disabling disease affecting a significant proportion of the Australian population. The methylenetetrahydrofolate reductase (MTHFR) C677T variant has been associated with increased levels of homocysteine and risk of migraine with aura (MA). Folic acid (FA), vitamin B6 , and B12 supplementation has been previously shown to reduce increased levels of homocysteine and decrease migraine symptoms. However, the influence of dietary folate intake on migraine has been unclear. The aim of the current study was to analyze the association of dietary folate intake in the form of dietary folate equivalent, FA, and total food folate (TFF) on migraine frequency, severity, and disability.

Concepts: Vitamin, Migraine, Anemia, Folic acid, Folate deficiency, Vitamin B12, B vitamins, Homocysteine

28

ABSTRACT Postural control impairments and dizziness, which are major health problems with high secondary morbidity and mortality, increase with aging. Elevated homocysteine (Hcy) level is an age-related metabolic disorder, known to be involved in cardiovascular, neurological, and multisensory dysfunctions. Elevated Hcy level might be involved in sensory balance control systems impairment and dizziness occurrence. Dizziness, fitness Instrumental Activity of Daily Living scale (fitness IADL), systolic arterial pressure with ankle-brachial blood pressure index and homocysteinemia were studied in 61 noninstitutionized elderly women. Clinical balance tests (timed “Up and Go”, 10-m walking and one-leg balance) and posturography (including sensory conflicting situations [SCS] and cognitive conflicting situations [CCS]) were performed. Clinical balance control was lower in dizzy women who presented particularly poor stability in SCS. Dizziness was related to low fitness IADL scores (odds ratio [OR] 0.452, 95% CI 0.216-0.946) and to elevated Hcy (OR 8.084, 95% CI 1.992-32.810). Elevated Hcy was correlated with balance disorders both in SCS and CCS. Dizziness is associated with a reduced ability in balance control management. Hcy is related both to dizziness and low postural performance. This relation between elevated Hcy levels and balance impairments, resulting in dizziness, may be explained by its angiotoxicity and neurotoxicity.

Concepts: Blood, Myocardial infarction, Cardiovascular disease, Blood pressure, Artery, Orthostatic hypotension, Homocysteine, Methionine

28

OBJECTIVE: To evaluate homocysteine levels in patients with Takayasu arteritis (TA) and in controls, and to analyze associations between homocysteine levels and paraoxonase 1 (PON1) activity, cysteine levels, methotrexate use, disease activity, extent of arterial involvement, and ischemic events in patients with TA. METHODS: A cross-sectional study was performed with 29 patients with TA and 30 controls who underwent clinical evaluation and blood sample collection in the fasting state. RESULTS: Among patients with TA, active disease was observed in 9 (31.0%) and previous arterial ischemic events in 10 (34.5%). Therapy with methotrexate was prescribed to 9 (31.0%) patients and it was associated with folic acid in 8 cases. Median homocysteine level was higher in patients with TA [10.9 μmol/l, interquartile range (IQR) 9.6-14.8] than in controls (6.9 μmol/l, IQR 5.1-11.9; p < 0.001). No difference was found regarding mean homocysteine levels between those using methotrexate and those under other therapies (12.8 ± 5.3 μmol/l vs 12.1 ± 3.2 μmol/l, respectively; p = 0.662). TA patients with active disease presented lower homocysteine levels (10.4 ± 2.1 μmol/l) compared to TA patients in remission (13.1 ± 4.2 μmol/l) (p = 0.034). A significant correlation was found between cysteine and homocysteine levels in patients with TA (ρ = 0.676, p < 0.0001), while there was no correlation between homocysteine and PON1 activity (ρ = 0.214, p = 0.265). Median homocysteine levels were higher in patients with ischemic events (13.2 μmol/l, IQR 10.9-17.5) compared to patients with no ischemic events (9.8 μmol/l, IQR 8.7-14.7; p = 0.027) and were associated with arterial ischemia in patients with TA (OR 1.31, 95% CI 1.01-1.71, p = 0.041). CONCLUSION: Patients with TA presented higher homocysteine levels than controls and homocysteine was associated with an increased risk of arterial ischemic events in TA.

Concepts: Median, Interquartile range, Folic acid, Methotrexate, Homocysteine, PON1, Paraoxonase, Takayasu's arteritis

27

OBJECTIVE: The aim of this study was to determine the effects of quercetin on homocysteine (Hcy) metabolism and hepatic antioxidant status in high methionine (Met)-fed rats. METHODS: Rats were fed for 6 wk the following diets: control, 1.0% Met, 1.0% Met and 0.1% quercetin, 1.0% Met and 0.5% quercetin, 1.0% Met and 2.5% quercetin-supplemented diets. Serum Hcy, Met, cysteine, serine, taurine, glutathione (GSH), quercetin and its metabolites, and activities of alanine transaminase (ALT) and aspartate transaminase (AST) were assayed. Hepatic malondialdehyde, GSH and carbonyls, and activity of superoxide dismutase and ferric-reducing antioxidant power also were measured. RESULTS: Serum Hcy was increased significantly after Met treatment and decreased after quercetin supplementation. Meanwhile, serum taurine was increased and serine decreased. However, the content of GSH in serum and liver was decreased in the quercetin-supplemented groups and activities of serum ALT and AST were enhanced in the 1.0% Met and 2.5% quercetin-supplemented groups. CONCLUSIONS: Quercetin is effective in decreasing serum Hcy level in high Met-fed rats and one of possible mechanisms is associated with increased transsulfuration of Hcy. Quercetin can acts as a prooxidant at high intake levels.

Concepts: Amino acid, Antioxidant, Liver function tests, Aspartate transaminase, Alanine transaminase, Cysteine, Homocysteine, Methionine

24

Homocystinuria (HCU) due to deficiency of cystathionine beta-synthetase is associated with increased plasma levels of homocysteine and methionine and is characterized by developmental delay, intellectual impairment, ocular defects, thromboembolism and skeletal abnormalities. HCU has been associated with increased risk for osteoporosis in some studies, but the natural history of HCU-related bone disease is poorly understood. The objective of this study was to characterize bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DXA) in a multi-center, retrospective cohort of children and adults with HCU. We identified 19 subjects (9 males) aged 3.5 to 49.2years who had DXA scans performed as a part of routine clinical care from 2002-2010. The mean lumbar spine (LS) BMD Z-score at the time of first DXA scan in this cohort was -1.2 (±SD of 1.3); 38% of participants had low BMD for age (as defined by a Z-score≤-2). Homocysteine and methionine were positively associated with LS BMD Z-score in multiple linear regression models. Our findings suggest that low BMD is common in both children and adults with HCU and that routine assessment of bone health in this patient population is warranted. Future studies are needed to clarify the relationship between HCU and BMD.

Concepts: Osteoporosis, Regression analysis, Linear regression, Bone, Skeletal system, Dual energy X-ray absorptiometry, Cysteine, Homocysteine

22

Cyprodinil belongs to the chemical class of anilinopyrimidines fungicides. In this study, baseline sensitivity of Sclerotinia sclerotiorum (Lib.) de Bary to cyprodinil was determined using 100 strains collected from the fields in Jiangsu Province of China. The EC50(50% effective concentration) values ranged from 0.0636-0.8163 μg/ml with a mean value of 0.1869 (±0.1118) ug/ml for mycelial growth. Nine cyprodinil-resistant mutants (Range of resistance factor: 20.22-271.59) were obtained from sensitive strains exposed on PDA medium amended with cyprodinil and the resistance was stable after their ten transfers on PDA without the fungicide or stored at 4 °C for two months. There was positive cross-resistance between cyprodinil and pyrimethanil but not to fludioxonil, dimetachlone, procymidone, carbendazim and boscalid in S. sclerotiorum. Compared with the parental strains, all of the nine cyprodinil-resistant mutants decreased in sclerotial production. The dry weight of mycelia, pathogenicity and cell membrane permeability of most resistant mutants decreased. The mycelial growth, oxalic acid content, and the response to various stress for resistant mutants were almost the same as the sensitive parental strains. Sequencing alignment results showed that there was no alteration of amino acid in cystathionine γ-synthase (MetB) and cystathionine β-lyase (MetC) between cyprodinil-resistant mutants and their sensitive parental strains, which indicated that MetB or MetC was not the molecular target of cyprodinil in S. sclerotiorum. The addition of amino acids L-methionine, L-cystine or L-cysteine decreased the inhibition of cyprodinil against mycelial growth of S. sclerotiorum, which indicated that cyprodinil could not only inhibited methionine biosynthesis but also suppressed cystine and cysteine biosynthesis. These results will contribute to evaluating the resistance risk of cyprodinil for management of the plant diseases of Sclerotinia stem rot caused by S. sclerotiorum and further increase our understanding about the mode of action of cyprodinil.

Concepts: Protein, Amino acid, Acid, Essential amino acid, Cysteine, Homocysteine, Cystine, Methionine

19

Early identification of cardiovascular diseases allows us to prevent the progression of these diseases. The Bale/Doneen Method, a prevention and treatment program for heart attacks and ischemic strokes, has been adopted nationally in primary care and specialty clinics.

Concepts: Myocardial infarction, Atherosclerosis, Blood vessel, Cardiovascular disease, Stroke, Low-density lipoprotein, Cardiovascular diseases, Homocysteine

6

Results from observational and genetic epidemiological studies suggest that lower serum homocysteine levels are associated with lower incidence of cardiovascular disease (CVD). Numerous randomized controlled trials have investigated the efficacy of lowering homocysteine with folic acid supplementation for CVD risk, but conflicting results have been reported.

Concepts: Epidemiology, Disease, Cardiovascular disease, Randomized controlled trial, Non-infectious disease, Folic acid, Asymmetric dimethylarginine, Homocysteine