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homocysteine

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Description

Homocysteine: A thiol-containing amino acid formed by a demethylation of METHIONINE. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

homocysteine : A sulfur-containing amino acid consisting of a glycine core with a 2-mercaptoethyl side-chain. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

L-homocysteine : A homocysteine that has L configuration. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID91552
CHEMBL ID469662
CHEBI ID17588
SCHEMBL ID35837
MeSH IDM0010514

Synonyms (51)

Synonym
(2s)-2-amino-4-sulfanylbutanoic acid
CHEBI:17588 ,
HCY ,
2-amino-4-mercapto-butyric acid
HCS ,
l-homocysteine
homocysteine
6027-13-0
l-2-amino-4-mercaptobutyric acid
C00155
DB04422
H-2800
bdbm50242405
CHEMBL469662 ,
(s)-2-amino-4-mercaptobutanoic acid
A832662
AKOS006272166
butanoic acid, 2-amino-4-mercapto- (van)
butanoic acid, 2-amino-4-mercapto-, (s)-
0lvt1qz0ba ,
nsc 43117
homocysteine (van)
einecs 227-891-0
nsc 118376
butyric acid, 2-amino-4-mercapto-, l-
2-amino-4-mercaptobutyric acid (van)
unii-0lvt1qz0ba
EPITOPE ID:143650
gtpl5198
(s)-homocysteine
homocysteine [mi]
FFFHZYDWPBMWHY-VKHMYHEASA-N
SCHEMBL35837
h-hcys-oh
(s)-2-amino-4-mercaptobutyric acid
DTXSID3041039
l-homocysteine, >=98.0% (nt)
2-amino-4-mercapto-butanoic acid
2-amino-4-mercapto-butanoate
l-2-amino-4-mercapto-butyric acid
2-amino-4-mercapto-dl-butyric acid
dl-2-amino-4-mercapto-butyric acid
2-amino-4-mercapto-dl-butyrate
(s)-2-amino-4-mercapto-butanoate
(s)-2-amino-4-mercapto-butanoic acid
CS-W011063
Q26992833
FS-6405
I11579
HY-W010347
(s)-2-amino-4-mercaptobutanoicacid

Research Excerpts

Toxicity

Homocysteine is a sulfur amino acid found in blood in micromolar concentrations. It can have toxic effects through a handful of general possible mechanisms. Treatment of the toxic hepatitis with heptral increased the level of cy tochrome P450, cytochrome b5 and glutation activity of glutationetranspherase glutathione.

ExcerptReferenceRelevance
" The toxic potencies of glutamate, quisqualate, and homocysteate were inversely proportional to the concentration of cystine in the medium, suggesting that they competitively inhibit cystine uptake."( Immature cortical neurons are uniquely sensitive to glutamate toxicity by inhibition of cystine uptake.
Coyle, JT; Murphy, TH; Schnaar, RL, 1990
)
0.28
" Criteria based on neurological indices, mortality, and weight loss indicated that the cys-gly complex of CH3Hg was significantly less toxic than CH3Hg or the other complexes."( Toxicity, distribution, and elimination of thiol complexes of methylmercury after intracerebral injection.
Balthrop, JE; Braddon-Galloway, S; Fair, PH; Wade, JL, 1986
)
0.27
" A serious chronic side effect of the drug is its hepatotoxicity, which may culminate in hepatic cirrhosis and death."( Methotrexate hepatotoxicity.
Barak, AJ; Beckenhauer, HC; Tuma, DJ, 1984
)
0.27
"The oxidative processes in Saccharomyces cerevisiae were shown to be more susceptible to the toxic effect of cysteine as compared to the glycolytic processes."( [Toxic effect of cysteine on cells of Saccharomyces cerevisiae growing on media of various compositions].
Blumberg, IaE; Damberg, BE,
)
0.13
" Toxicity assessments in the mouse yielded a LD50 of 297 mg/kg and in the rat 389 mg/kg."( Toxicity, biodistribution and radioprotective capacity of L-homocysteine thiolactone in CNS tissues and tumors in rodents: comparison with prior results with phosphorothioates.
Ali-Osman, F; Chin, L; Dwyer-Hansen, L; Grunbaum, Z; Krohn, KA; Livesey, J; Nelson, N; Rasey, JS; Spence, AM; Stein, D, 1995
)
0.29
"5 rat embryos L-homocysteine was not toxic at 1- and 2-mM concentrations."( Prevention of neural tube defects by and toxicity of L-homocysteine in cultured postimplantation rat embryos.
Blom, HJ; Copius Peereboom-Stegeman, JH; Deabreu, RA; Eskes, TK; Noordhoek, J; Trijbels, FJ; Vanaerts, LA, 1994
)
0.29
" A combination of high resolution proton nuclear magnetic resonance (1H NMR) spectroscopy of urine, renal histopathology and more routinely used clinical chemistry methods has been used to explore the acute toxic and biochemical effects of S-(1,2-dichlorovinyl)-L-cysteine (DCVC), S-(1,2-dichlorovinyl)-L-homocysteine (DCVHC) and 1,1,2-trichloro-3,3,3-trifluoro-1-propene (TCTFP) up to 48 h following their administration to male Fischer 344 (F344) rats."( Studies on the comparative toxicity of S-(1,2-dichlorovinyl)-L-cysteine, S-(1,2-dichlorovinyl)-L-homocysteine and 1,1,2-trichloro-3,3,3-trifluoro-1-propene in the Fischer 344 rat.
Anthony, ML; Beddell, CR; Lindon, JC; Nicholson, JK, 1994
)
0.29
" The toxic effects of the amino acid alone and the amino acid plus Cu2+ could be prevented by catalase and decreased by desferal, when either was present in the culture medium."( Lipid peroxidation and homocysteine induced toxicity.
Jones, BG; Rose, FA; Tudball, N, 1994
)
0.29
") is equally toxic to both wild-type and adenosine-kinase-deficient BHK cells at concentrations up to 100 microM; at higher concentrations, wild-type cells are more sensitive, as are cells over-expressing adenosine kinase."( The bis(adenosin-N6-yl) alkanes, a family of potential dinucleoside polyphosphate analogue precursors. Mechanism of growth inhibition and suppression of adenosine toxicity in lymphoid cells.
Chen, H; McLennan, AG, 1993
)
0.29
" Activation of the coagulation system and adverse effects of homocysteine on the endothelium and vessel wall are believed to underlie disease pathogenesis."( Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor.
Arnelle, DR; Choi, YB; D'Emilia, DM; Kim, WK; Kumar, S; Lipton, SA; Rayudu, PV; Stamler, JS, 1997
)
0.3
" These data indicate that NO ameliorates the potential, adverse properties of HC via S-nitrosylation in the pathogenesis of hyperhomocysteinemia."( S-nitrosation ameliorates homocysteine-induced neurotoxicity and calcium responses in primary culture of rat cortical neurons.
Kim, WK, 1999
)
0.3
" L-HCA induced a concentration-dependent neurotoxic effect, estimated by cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction, in primary neurons, but was significantly more toxic for hippocampal (EC(50)=197 microM) compared with cortical neurons (EC(50)=1016 microM) whereas D-HCA demonstrated only moderate (<20%) toxicity."( Inhibition of L-homocysteic acid and buthionine sulphoximine-mediated neurotoxicity in rat embryonic neuronal cultures with alpha-lipoic acid enantiomers.
Cuisinier, C; Jones, C; Lestage, P; Lockhart, B; Peyroulan, D; Villain, N, 2000
)
0.31
" Besides adverse effects on the endothelium and vessel wall, Hcy exert a toxic action on neuronal cells trough the stimulation of N-methyl-D-aspartate (NMDA) receptors."( [Hyperhomocysteinemia: atherothrombosis and neurotoxicity].
Fridman, O, 1999
)
0.3
" These findings underscore that moderate accumulation of excitotoxins at concentrations that alone do not appear to initiate adverse events may enhance the effects of other factors known to cause neurodegeneration such as Abeta."( Homocysteine potentiates beta-amyloid neurotoxicity: role of oxidative stress.
Ashline, D; Collins, SC; Dhitavat, S; Ho, PI; Ortiz, D; Rogers, E; Shea, TB, 2001
)
0.31
" Although severe folate deficiency may have adverse effects on NK-mediated cytotoxicity, moderate folate deficiency, a degree of depletion associated with an increased risk of several cancers, appears not to affect NK-mediated cytotoxicity in rats."( Severe folate deficiency impairs natural killer cell-mediated cytotoxicity in rats.
Hayek, M; Kim, YI; Mason, JB; Meydani, SN, 2002
)
0.31
" As administration of methionine causes endothelial dysfunction in laboratory examinations, we explored whether loading with this compound leads to clinically relevant adverse effects, especially in vasculature."( Methionine-loading test: evaluation of adverse effects and safety in an epidemiological study.
Andel, M; Janosíková, B; Kozich, V; Krupková-Meixnerová, L; Veselá, K; Vitová, A, 2002
)
0.31
"Our study suggests that although standard loading with L-methionine frequently causes transitory complications impairing perception and vigilance, the test does not have serious adverse effects on vasculature and may be considered a safe procedure."( Methionine-loading test: evaluation of adverse effects and safety in an epidemiological study.
Andel, M; Janosíková, B; Kozich, V; Krupková-Meixnerová, L; Veselá, K; Vitová, A, 2002
)
0.31
" Substrate-bound Abeta peptides were found to be toxic to the cells and to increase the rate of cell death."( Toxicity of substrate-bound amyloid peptides on vascular smooth muscle cells is enhanced by homocysteine.
Barrow, CJ; Beyreuther, K; Masters, CL; Mok, SS; Small, DH; Turner, BJ, 2002
)
0.31
" Homocysteine, a sulfur amino acid found in blood in micromolar concentrations, can have toxic effects through a handful of general possible mechanisms."( Possible mechanisms of homocysteine toxicity.
Acanfora, F; Cesare, CM; De Santo, NG; Ingrosso, D; Lombardi, C; Perna, AF; Romano, MM; Satta, E; Violetti, E, 2003
)
0.32
" In contrast, SAH and CA were toxic at concentrations of >100 microM after 48h."( Dopaminergic neurotoxicity of homocysteine and its derivatives in primary mesencephalic cultures.
Heider, I; Lehmensiek, V; Lenk, T; Müller, T; Storch, A, 2004
)
0.32
"A cross sectional study on 93 methotrexate treated patients with rheumatoid arthritis, comprising a clinical interview and physical examination to determine disease activity and methotrexate related adverse reactions."( Methotrexate related adverse effects in patients with rheumatoid arthritis are associated with the A1298C polymorphism of the MTHFR gene.
Aamar, S; Abou Atta, I; Ben-Yehuda, A; Berkun, Y; Friedman, G; Grenader, T; Levartovsky, D; Mevorach, D; Orbach, H; Rubinow, A, 2004
)
0.32
"1298CC polymorphism was more common in methotrexate treated rheumatoid patients than expected in the population, and was associated with a reduction in methotrexate related adverse effects."( Methotrexate related adverse effects in patients with rheumatoid arthritis are associated with the A1298C polymorphism of the MTHFR gene.
Aamar, S; Abou Atta, I; Ben-Yehuda, A; Berkun, Y; Friedman, G; Grenader, T; Levartovsky, D; Mevorach, D; Orbach, H; Rubinow, A, 2004
)
0.32
" Moreover, the transfectants were more susceptible to the toxic effects of Hcy-S-Hg-S-Hcy than wild-type cells."( Homocysteine, system b0,+ and the renal epithelial transport and toxicity of inorganic mercury.
Bridges, CC; Zalups, RK, 2004
)
0.32
" The addition of homocysteinic acid in a nontoxic concentration of 100 microM potentiated the toxic effect of NMDA and led to massive cell death."( Homocysteinic acid causes oxidative stress in lymphocytes by potentiating toxic effect of NMDA.
Boldyrev, AA, 2005
)
0.33
" Results of litter evaluation on GD18 showed that combined supplementation of FA and VB(12) ameliorated many of the adverse effects of ethanol."( The maternal combined supplementation of folic acid and Vitamin B(12) suppresses ethanol-induced developmental toxicity in mouse fetuses.
Li, Y; Long, Z; Shen, X; Tang, Y; Wang, J; Xu, Y; Zheng, X, 2006
)
0.33
"Cadmium is a toxic metal and no effective antidote exists at present."( Modulation of cadmium chloride toxicity by sulphur amino acids in hepatoma cells.
Fotakis, G; Timbrell, JA, 2006
)
0.33
" Grade 2/3 treatment-related adverse events were diarrhoea (34%), fatigue (27%), stomatitis (15%) and hand-foot syndrome (22%)."( A phase II study of fixed-dose capecitabine and assessment of predictors of toxicity in patients with advanced/metastatic colorectal cancer.
Beale, P; Clarke, SJ; Horvath, L; Ong, S; Rivory, L; Sharma, R, 2006
)
0.33
" The frequency of adverse events was slightly lower in the morning treatment group compared with the evening treatment group (27."( Efficacy and safety of fluvastatin-extended release in hypercholesterolemic patients: morning administration is equivalent to evening administration.
Abletshauser, C; Freisinger, F; März, W; Scharnagl, H; Stojakovic, T; Vogel, M, 2006
)
0.33
"Although many animal studies have reported that dietary excess of methionine causes toxic changes including growth suppression and hemolytic anemia, the biochemical mechanism and biomarkers for methionine toxicity have not been well elucidated."( Screening of toxicity biomarkers for methionine excess in rats.
Amao, M; Kawamata, Y; Kimura, T; Kodama, R; Sakai, R; Toue, S, 2006
)
0.33
" Nutritional and metabolic studies have employed amounts of methionine, including the d and dl isomers, both below and above the requirement and have not reported adverse effects in adults and children."( Toxicity of methionine in humans.
Garlick, PJ, 2006
)
0.33
" Taken together our data reveal that homocysteine is toxic to cerebellar Purkinje neurons in vitro, inhibiting both their survival and the outgrowth of neurites."( Neurotoxic effects of homocysteine on cerebellar Purkinje neurons in vitro.
Doherty, GH; Oldreive, CE, 2007
)
0.34
" Treatment of the toxic hepatitis with heptral increased the level of cytochrome P450, cytochrome b5, glutation activity of glutationetranspherase glutathione and reduced content of homocysteine."( [Efficacy and safety of heptral, vitamin B6 and folic acid during toxic hepatitis induced by CCL4].
Antelava, NA; Gogoluari, LI; Gogoluari, MI; Okudzhava, MV; Pirtskhalaĭshvili, NN, 2007
)
0.34
"Hot flushes, breast pain, vaginal atrophy, metabolic parameters, and adverse events."( Evaluation of bazedoxifene/conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile.
Constantine, G; Dorin, MH; Gass, MLS; Lobo, RA; Pickar, JH; Pinkerton, JV; Ronkin, S, 2009
)
0.35
" The incidences of breast pain and adverse events were similar between BZA/CE and placebo."( Evaluation of bazedoxifene/conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile.
Constantine, G; Dorin, MH; Gass, MLS; Lobo, RA; Pickar, JH; Pinkerton, JV; Ronkin, S, 2009
)
0.35
"45 mg) is an effective and safe treatment for menopausal symptoms."( Evaluation of bazedoxifene/conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile.
Constantine, G; Dorin, MH; Gass, MLS; Lobo, RA; Pickar, JH; Pinkerton, JV; Ronkin, S, 2009
)
0.35
" Toxic effects of homocysteine and the product of its spontaneous oxidation, homocysteic acid, are based on their ability to activate NMDA receptors, increasing intracellular levels of ionized calcium and reactive oxygen species."( Molecular mechanisms of homocysteine toxicity.
Boldyrev, AA, 2009
)
0.35
" This study has shown that it is possible to modulate homocysteine toxicity by preventing its conversion to a more toxic HTL by S-nitrosation."( Modulation of homocysteine toxicity by S-nitrosothiol formation: a mechanistic approach.
Morakinyo, MK; Simoyi, RH; Strongin, RM, 2010
)
0.36
" The use of folic acid supplements might reduce the adverse effects of smoking."( Folic acid supplements modify the adverse effects of maternal smoking on fetal growth and neonatal complications.
Bakker, R; Hofman, A; Jaddoe, VW; Steegers, EA; Timmermans, S, 2011
)
0.37
" STS was the most potent neurotoxin at killing NSC-34D cells with a toxic concentration at which 50% of maximal cell death is achieved (TC(50)=0."( Neurotoxic injury pathways in differentiated mouse motor neuron-neuroblastoma hybrid (NSC-34D) cells in vitro--limited effect of riluzole on thapsigargin, but not staurosporine, hydrogen peroxide and homocysteine neurotoxicity.
Armstrong, EJ; Brooks, BR; Hemendinger, RA; Radio, N, 2012
)
0.38
" Hcy-thiolactone has been implicated in these diseases because it has the ability to modify protein lysine residues and generate toxic N-Hcy-proteins with auto-immunogenic, pro-thrombotic, and amyloidogenic properties."( Metabolism and neurotoxicity of homocysteine thiolactone in mice: protective role of bleomycin hydrolase.
Borowczyk, K; Jakubowski, H; Tisończyk, J, 2012
)
0.38
" The aim of the present study was to determine the role of reactive oxygen species (ROS) in the in vitro toxic effects of HC on insulin secretion and function of BRIN-BD11 insulin-secreting cells."( Enhancement of homocysteine toxicity to insulin-secreting BRIN-BD11 cells in combination with alloxan.
Elsner, M; Flatt, PR; Gurgul-Convey, E; Lenzen, S; McClenaghan, NH; Scullion, SM, 2012
)
0.38
" Demographic characteristics were obtained and number of patients with MTX-related adverse affects, were recorded in the patient group."( Thymidylate synthase genetic polymorphism and plasma total homocysteine level in a group of Turkish patients with rheumatoid arthritis: relationship with disease activity and methotrexate toxicity.
Borman, P; Karabulut, H; Taşbaş, Ö; Tukun, A; Yorgancıoğlu, R,
)
0.13
" Thirty-six of the 64 patients showed adverse effects to MTX treatment."( Thymidylate synthase genetic polymorphism and plasma total homocysteine level in a group of Turkish patients with rheumatoid arthritis: relationship with disease activity and methotrexate toxicity.
Borman, P; Karabulut, H; Taşbaş, Ö; Tukun, A; Yorgancıoğlu, R,
)
0.13
" No differences were noted in adverse effects between the two treatment groups."( Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down's syndrome (TESDAD): a double-blind, randomised, placebo-controlled, phase 2 trial.
Benejam, B; Blanco-Hinojo, L; Bléhaut, H; Catuara-Solarz, S; Cuenca-Royo, A; de la Torre, R; de Sola, S; Del Hoyo, L; Delabar, JM; Dierssen, M; Dueñas-Espín, I; Espadaler, JM; Farré, M; Fitó, M; Hernandez, G; Janel, N; Langohr, K; Principe, A; Pujol, J; Rodriguez, J; Sanchez-Benavides, G; Videla, S; Xicota, L, 2016
)
0.43
" However, their single actions cannot explain the extent of brain damage observed in this disorder, and the characterization of co-adjuvant involved in the early toxic processes evoked in AD is essential."( Synergistic Toxicity of the Neurometabolites Quinolinic Acid and Homocysteine in Cortical Neurons and Astrocytes: Implications in Alzheimer's Disease.
Biasibetti-Brendler, H; Ferreira, F; Netto, CA; Pierozan, P; Schmitz, F; Wyse, ATS, 2018
)
0.48
" The highest toxic doses of hcy and sft were found to be 250 μM and 5 mM, respectively, but the maximum toxic effect was observed for hcy + sft (p < 0."( The sulfite molecule enhances homocysteine toxicity in SH-SY5Y cells.
Dodurga, Y; Gundogdu, G; Kucukatay, V, 2019
)
0.51
" Adverse events will be monitored throughout the trial."( Efficacy and safety of Xinnaoning capsule in treating chronic stable angina (qi stagnation and blood stasis syndrome): Study protocol for a multicenter, randomized, double-blind, placebo-controlled trial.
Chen, Y; Jia, ST; Lan, X; Li, J; Liu, Y; Wu, LQ; Xu, FQ; Zhang, P; Zhang, Y; Zhao, JN, 2019
)
0.51

Pharmacokinetics

Betaine has been used for more than 30 years in pyridoxine non-responsive cystathionine beta-synthase (pnrCBS) and cobalamin C (cblC) deficiencies. Little is known about the optimal therapeutic dosage and its pharmacokinetic in these patients.

ExcerptReferenceRelevance
" Absorption and pharmacokinetic parameters were determined in dog after oral and intravenous administration."( Pharmacokinetics and metabolism of S-adenosyl-L-homocysteine, in rats and dog.
Chabannes, B; Gharib, A; Pacheco, H; Sarda, N,
)
0.13
"The purpose of this study was to investigate the utility of plasma pharmacokinetic and pharmacodynamic measures including plasma deoxynucleosides, homocysteine and methylmalonic acid concentrations in understanding the time course and extent of the inhibition of thymidylate synthase (TS) by pemetrexed in the context of a phase I/II combination study with vinorelbine."( Pemetrexed pharmacokinetics and pharmacodynamics in a phase I/II study of doublet chemotherapy with vinorelbine: implications for further optimisation of pemetrexed schedules.
Clarke, SJ; Li, KM; Rivory, LP, 2007
)
0.34
"To evaluate the safety and describe the pharmacokinetic profile of OSI-7904L, a novel liposomal thymidylate synthase inhibitor, in combination with cisplatin (CDDP) in adults with advanced solid tumors."( Phase I, pharmacokinetic and biological correlative study of OSI-7904L, a novel liposomal thymidylate synthase inhibitor, and cisplatin in patients with solid tumors.
Berlin, JD; Chick, J; Drolet, DW; Horan, J; Papadopoulos, KP; Quaratino-Baker, C; Ricart, AD; Rothenberg, ML; Rowinsky, EK; Syed, S; Tolcher, AW; Vermeulen, W, 2008
)
0.35
" Pharmacokinetic samples, baseline plasma homocysteine, and genotype polymorphisms were evaluated."( Phase I, pharmacokinetic and biological correlative study of OSI-7904L, a novel liposomal thymidylate synthase inhibitor, and cisplatin in patients with solid tumors.
Berlin, JD; Chick, J; Drolet, DW; Horan, J; Papadopoulos, KP; Quaratino-Baker, C; Ricart, AD; Rothenberg, ML; Rowinsky, EK; Syed, S; Tolcher, AW; Vermeulen, W, 2008
)
0.35
" No major pharmacokinetic interactions between CDDP and OSI-7904L were observed."( Phase I, pharmacokinetic and biological correlative study of OSI-7904L, a novel liposomal thymidylate synthase inhibitor, and cisplatin in patients with solid tumors.
Berlin, JD; Chick, J; Drolet, DW; Horan, J; Papadopoulos, KP; Quaratino-Baker, C; Ricart, AD; Rothenberg, ML; Rowinsky, EK; Syed, S; Tolcher, AW; Vermeulen, W, 2008
)
0.35
" Pharmacokinetic interaction between the agents was not apparent."( Phase I, pharmacokinetic and biological correlative study of OSI-7904L, a novel liposomal thymidylate synthase inhibitor, and cisplatin in patients with solid tumors.
Berlin, JD; Chick, J; Drolet, DW; Horan, J; Papadopoulos, KP; Quaratino-Baker, C; Ricart, AD; Rothenberg, ML; Rowinsky, EK; Syed, S; Tolcher, AW; Vermeulen, W, 2008
)
0.35
" However, NAC clearance was reduced by 90% in ESRD, leading to a 7-fold larger AUC and 13-fold longer half-life compared with healthy control subjects."( Multiple-dose pharmacokinetics and pharmacodynamics of N-acetylcysteine in patients with end-stage renal disease.
Himmelfarb, J; McMenamin, ME; Nolin, TD; Ouseph, R; Ward, RA, 2010
)
0.36
" Betaine has been used for more than 30 years in pyridoxine non-responsive cystathionine beta-synthase (pnrCBS) and cobalamin C (cblC) deficiencies to lower the hyperhomocysteinemia, although little is known about the optimal therapeutic dosage and its pharmacokinetic in these patients."( Efficacy and pharmacokinetics of betaine in CBS and cblC deficiencies: a cross-over randomized controlled trial.
Alberti, C; Benoist, JF; de Baulny, HO; Feillet, F; Garcia-Segarra, N; Guilmin-Crépon, S; Haignere, J; Imbard, A; Kaguelidou, F; Kuster, A; Magréault, S; Perronneau, I; Schiff, M; Schlemmer, D; Toumazi, A, 2022
)
0.72

Compound-Compound Interactions

Conjugated equine estrogen alone or combined with medroxyprogesterone acetate lowered homocysteine levels in postmenopausal women. Dengzhan Shengmai capsule combined with butylphthalide soft capsule on oxidative stress indexes and serum homo.

ExcerptReferenceRelevance
"To investigate the effects of oral 17beta-estradiol administration continuously combined with dydrogesterone on fasting serum total homocysteine levels in postmenopausal women."( Postmenopausal oral 17beta-estradiol continuously combined with dydrogesterone reduces fasting serum homocysteine levels.
Jakobs, C; Kenemans, P; Mijatovic, V; Netelenbos, C; Peters-Muller, ER; Popp-Snijders, C; van der Mooren, MJ, 1998
)
0.3
"Oral micronized 17beta-estradiol (2 mg/d) continuously combined with one of four dosages of dydrogesterone (2."( Postmenopausal oral 17beta-estradiol continuously combined with dydrogesterone reduces fasting serum homocysteine levels.
Jakobs, C; Kenemans, P; Mijatovic, V; Netelenbos, C; Peters-Muller, ER; Popp-Snijders, C; van der Mooren, MJ, 1998
)
0.3
"Number of patients with gastric body atrophy identified with the combination of MMA and Hcy, and pepsinogen A combined with pepsinogen C or gastrin."( Advantages of serum pepsinogen A combined with gastrin or pepsinogen C as first-line analytes in the evaluation of suspected cobalamin deficiency: a study in patients previously not subjected to gastrointestinal surgery.
Kilander, AF; Lindgren, A; Lindstedt, G, 1998
)
0.3
" Serum pepsinogen A combined with pepsinogen C identified 100%, and combined with gastrin 88%, of the patients with gastric body atrophy and elevated metabolite tests, and 67 and 75%, respectively, of those who had not yet developed elevated metabolite tests."( Advantages of serum pepsinogen A combined with gastrin or pepsinogen C as first-line analytes in the evaluation of suspected cobalamin deficiency: a study in patients previously not subjected to gastrointestinal surgery.
Kilander, AF; Lindgren, A; Lindstedt, G, 1998
)
0.3
"Pepsinogen A, combined with pepsinogen C or gastrin, should be the first option in evaluating patients with suspected cobalamin deficiency who have not previously undergone gastrointestinal surgery."( Advantages of serum pepsinogen A combined with gastrin or pepsinogen C as first-line analytes in the evaluation of suspected cobalamin deficiency: a study in patients previously not subjected to gastrointestinal surgery.
Kilander, AF; Lindgren, A; Lindstedt, G, 1998
)
0.3
" Although the sample size is small, these findings suggest that daily administration of 400 microg/day folic acid combined with vitamin B12 and vitamin B6 may be equivalent to higher doses in reducing homocysteine levels in patients with CAD."( Reduction of homocysteine levels in coronary artery disease by low-dose folic acid combined with vitamins B6 and B12.
Abou-Ghazala, T; Alsous, F; Arheart, K; Gupta, A; Jacobsen, DW; Kruger, WD; Lobo, A; Moustapha, A; Nahlawi, M; Naso, A; Robinson, K; van Lente, F, 1999
)
0.3
" We enrolled 196 postmenopausal women, who were randomly allocated to receive on a continuous basis either 1mg of 17 beta-estradiol orally (n = 63) or 50 microg transdermally (n = 68) per day, both combined with a daily intake of 100 mg progesterone, or placebo (n = 65) over a period of 6 months."( Effects of oral and transdermal 17 beta-estradiol combined with progesterone on homocysteine metabolism in postmenopausal women: a randomised placebo-controlled trial.
Abalain, JH; Lacut, K; Moineau, MP; Mottier, D; Oger, E, 2004
)
0.32
"Conjugated equine estrogen alone or combined with medroxyprogesterone acetate lowered homocysteine levels in postmenopausal women."( Effect of oral conjugated equine estrogen combined with medroxyprogesterone acetate on plasma homocysteine levels in postmenopausal women.
Hsu, SC; Lee, JN; Liu, CM; Long, CY; Tsai, EM; Yang, CH, 2005
)
0.33
"To investigate the efficacy of enalapril combined with folic acid in lowering both blood pressure and plasma total homocysteine (Hcy) in essential hypertensive patients."( [Efficacy of enalapril combined with folic acid in lowering blood pressure and plasma homocysteine level].
Fu, J; Mao, GY; Qin, XH; Tang, GF; Tang, HQ, 2009
)
0.35
"As compared to enalapril alone, enalapril combined with folic acid showed a better efficacy in reducing both blood pressure and plasma Hcy level in hypertensive subjects."( [Efficacy of enalapril combined with folic acid in lowering blood pressure and plasma homocysteine level].
Fu, J; Mao, GY; Qin, XH; Tang, GF; Tang, HQ, 2009
)
0.35
" In the treatment group, fenofibrate alone and in combination with telmisartan was administered 2 weeks prior to renal ischemia."( Role of fenofibrate alone and in combination with telmisartan on renal ischemia/reperfusion injury.
Bhalodia, Y; Jivani, N; Sheth, N; Vaghasiya, J, 2010
)
0.36
" HC in combination with Alx resulted in a more pronounced decline in insulin secretion, including that induced by 20  mM alanine, by 43% (P<0."( Enhancement of homocysteine toxicity to insulin-secreting BRIN-BD11 cells in combination with alloxan.
Elsner, M; Flatt, PR; Gurgul-Convey, E; Lenzen, S; McClenaghan, NH; Scullion, SM, 2012
)
0.38
" We sought to determine whether Hcy or its genetic determinants influence blood clot properties alone or in combination with fibrinogen."( Homocysteine influences blood clot properties alone and in combination with total fibrinogen but not with fibrinogen γ' in Africans.
de Lange, Z; Nienaber-Rousseau, C; Pieters, M, 2015
)
0.42
"To investigate the effects of folic acid combined with vitamin B12 on deep vein thrombosis (DVT) in patients with homocysteine cerebral infarction."( Effects of folic acid combined with vitamin B12 on DVT in patients with homocysteine cerebral infarction.
Chang, YW; Li, ZF; Liu, SY; Shu, XJ; Wang, WH, 2017
)
0.46
"This experiment was aimed to investigate the effect of Dengzhan Shengmai capsule combined with butylphthalide soft capsule on oxidative stress indexes and serum homocysteine (Hcy) and C-reactive protein (CRP) levels in patients with vascular dementia (VD)."( Effects of Dengzhan Shengmai Capsule combined with butylphthalide soft capsule on oxidative stress indexes and serum Hcy and CRP levels in patients with vascular dementia.
Ma, Y; Sun, W, 2020
)
0.56
" However, studies on the association between HHcy combined with MS and stroke risk in hypertensive patients were absent."( Association Between Hyperhomocysteinemia Combined with Metabolic Syndrome and Higher Prevalence of Stroke in Chinese Adults Who Have Elevated Blood Pressure.
Bao, H; Cheng, X; Hu, F; Huang, X; Li, J; Wang, T; Yu, S; Zhou, W, 2022
)
0.72
"This study aimed to explore the clinical study of clopidogrel combined with Huoxue Tongluo prescription in improving transient ischemic attack (TIA) and the effect on MMP-9, Hcy, and CRP."( Clinical Study of Clopidogrel Combined with Huoxue Tongluo Prescription in Improving Transient Ischemic Attack and the Effect on MMP-9, Hcy, and CRP.
Chen, Z; Li, Y; Ma, L; Ma, Y; Meng, X, 2022
)
0.72
"Clopidogrel combined with Huoxue Tongluo prescription can significantly improve the therapeutic effect and reduce the levels of MMP-9, Hcy, and CRP in patients with TIA."( Clinical Study of Clopidogrel Combined with Huoxue Tongluo Prescription in Improving Transient Ischemic Attack and the Effect on MMP-9, Hcy, and CRP.
Chen, Z; Li, Y; Ma, L; Ma, Y; Meng, X, 2022
)
0.72
" Existing evidence shows that acupuncture has advantages in the treatment of AD, but whether the efficacy of acupuncture belongs to the placebo effect remains controversial, and there is no strict placebo-controlled clinical study to evaluate the efficacy and safety of acupuncture combined with Western medicine in the treatment of AD."( Clinical efficacy of acupuncture combined with Western medicine in the treatment of mild to moderate Alzheimer disease: A protocol of a randomized controlled trial.
Guo, R; He, J; Quan, L; Zhou, K, 2022
)
0.72
"This is a prospective randomized, a single-blind, sham-acupuncture controlled trial to study the clinical efficacy of acupuncture combined with Western medicine in the treatment of mild to moderate AD."( Clinical efficacy of acupuncture combined with Western medicine in the treatment of mild to moderate Alzheimer disease: A protocol of a randomized controlled trial.
Guo, R; He, J; Quan, L; Zhou, K, 2022
)
0.72
"This study will evaluate the efficacy of acupuncture combined with Western medicine in improving cognitive function and activities of daily living in AD patients."( Clinical efficacy of acupuncture combined with Western medicine in the treatment of mild to moderate Alzheimer disease: A protocol of a randomized controlled trial.
Guo, R; He, J; Quan, L; Zhou, K, 2022
)
0.72
"To analyze the predictive value of homocysteine (Hcy) combined with the Framingham risk score for cardio- and cerebrovascular disease in elderly patients with type 2 diabetes mellitus (T2DM) to provide a reference for clinical treatment."( Value of Hcy combined with Framingham score for predicting macrovascular disease in elderly patients with type 2 diabetes.
Liu, LP; Wang, L; Wang, ZH, 2023
)
0.91
" The subjects in the control group received only levodopa and benserazide hydrochloride treatment, while the observation group was treated with Resagiline in combination with the clinical control group."( Effects of rasagiline combined with levodopa and benserazide hydrochloride on motor function and homocysteine and IGF-1 levels in elderly patients with Parkinson's disease.
Gao, F; Gao, L; Miao, J; Yang, Y, 2023
)
0.91
"In patients with Parkinson's disease who are in the middle and late stages of the disease, the administration of Resagiline combined with levodopa and benserazide hydrochloride can significantly lower the body's serum Hcy level, significantly raise IGF-1 levels, and significantly improve motor function in patients with Parkinson's disease."( Effects of rasagiline combined with levodopa and benserazide hydrochloride on motor function and homocysteine and IGF-1 levels in elderly patients with Parkinson's disease.
Gao, F; Gao, L; Miao, J; Yang, Y, 2023
)
0.91
" The specific set of biomarkers and their combination with other risk markers may be a promising strategy for assessing CAS in the elderly, especially in global aging."( Homocysteine Combined with Apolipoprotein B as Serum Biomarkers for Predicting Carotid Atherosclerosis in the Oldest-Old.
Chen, M; Cheng, F; Li, Y; Liu, Z; Ning, C; Zhang, B; Zhao, Y; Zhou, Y, 2023
)
0.91

Bioavailability

Elevated levels of homocysteine also decreases the bioavailability of nitric oxide and modulates the levels of other metabolites including S-adenosyl methionine. The potential mechanisms by which elevated plasma homocy Steine leads to reduction in nitricoxide bioavailability include the disruptive uncoupling of nitrous oxide synthase activity and quenching of nitrics by oxidative stress.

ExcerptReferenceRelevance
" These results indicate that the compounds have sufficient potency and intracellular bioavailability to aid future studies focused on neuropeptide function and the contributions of neuropeptides to various disease processes."( Inhibition of peptidylglycine alpha-amidating monooxygenase by N-substituted homocysteine analogs.
Erion, MD; Jeng, AY; Tan, J; Wong, M, 1994
)
0.29
"These data indicate that hyperhomocyst(e)inemia is associated with impaired endothelium-dependent vasodilation in humans and suggest that the bioavailability of nitric oxide is decreased in hyperhomocyst(e)inemic humans."( Hyperhomocyst(e)inemia is associated with impaired endothelium-dependent vasodilation in humans.
Creager, MA; Gerhard, M; Omland, T; Tawakol, A; Wu, JT, 1997
)
0.3
"001 by one-way analysis of variance) independent of endothelial nitric-oxide synthase activity or protein levels and nos3 transcription, suggesting that Hcy affects the bioavailability of NO, not its production."( Homocyst(e)ine decreases bioavailable nitric oxide by a mechanism involving glutathione peroxidase.
Fabian, AJ; Freedman, JE; Johnson, JL; Keaney, JF; Loscalzo, J; Upchurch, GR; Welch, GN, 1997
)
0.3
" Data on bioavailability and distribution volume were obtained from two patients and two healthy controls by performing both intravenous and peroral Hcy loading."( Kinetic basis of hyperhomocysteinemia in patients with chronic renal failure.
Guttormsen, AB; Refsum, H; Svarstad, E; Ueland, PM, 1997
)
0.3
" To test these hypotheses, we determined the bioavailability of folate in serum and in ascitic/cystic fluids of ovarian carcinoma patients (n = 36)."( Homocysteine accumulation in human ovarian carcinoma ascitic/cystic fluids possibly caused by metabolic alteration of the methionine cycle in ovarian carcinoma cells.
Boiocchi, M; Corona, G; Donada, C; Fabris, M; Toffoli, G; Viel, A; Zarrelli, A, 1997
)
0.3
" However, research to establish the lowest effective dose of dietary folate/supplemental folic acid to optimise homocysteine levels and research on the bioavailability of folate is required."( Folate intake in Europe: recommended, actual and desired intake.
Brouwer, IA; de Bree, A; Steegers-Theunissen, RP; van Dusseldorp, M; van het Hof, KH, 1997
)
0.3
" pylori-induced gastritis, and the bioavailability of folates."( Coronary artery disease associated with Helicobacter pylori infection is at least partially due to inadequate folate status.
Markle, HV, 1997
)
0.3
"We studied the effects of 5-MTHF on NO bioavailability in vivo in 10 patients with FH and 10 matched control subjects by venous occlusion plethysmography, using serotonin and nitroprusside as endothelium-dependent and -independent vasodilators."( 5-methyltetrahydrofolate, the active form of folic acid, restores endothelial function in familial hypercholesterolemia.
Kastelein, JJ; Koomans, HA; Rabelink, TJ; van Dam, T; Verhaar, MC; Wever, RM, 1998
)
0.3
" Other possible mechanisms for homocysteine-mediated atherogenesis include: the altered methylation of DNA and altered regulatory proteins associated with cell membrane, decreased bioavailability of nitric oxide, increased elastolysis and collagen accumulation, overstimulation of N-methyl-D-aspartate receptors and excessive adhesion of monocytes and neutrophils to endothelium."( Pathogenesis of vascular disease in hyperhomocysteinaemia.
Domagała, TB; Libura, M; Szczeklik, A; Undas, A, 1998
)
0.3
" From the amount of additional folate (350 microgram/d) and folic acid (250 microgram/d) consumed, the relative bioavailability of dietary folate compared to folic acid was calculated to be 60-98%, depending on the endpoint used."( Dietary folate from vegetables and citrus fruit decreases plasma homocysteine concentrations in humans in a dietary controlled trial.
Brouwer, IA; Duran, M; Eskes, TK; Hautvast, JG; Meyboom, S; Steegers-Theunissen, RP; Thomas, CM; van Dusseldorp, M; van het Hof, KH; West, CE, 1999
)
0.3
" In-vitro studies have demonstrated that homocysteine decreases the production or bioavailability of vasodilator autacoids, such as prostacyclin and NO."( Homocysteine decreases endothelin-1 production by cultured human endothelial cells.
Atger, V; Benoit, MO; Borderie, D; Demuth, K; Lotersztajn, S; Moatti, N; Sauvaget, D, 1999
)
0.3
" Little is known about the bioavailability of constituents from vegetables and fruits and the effect of these constituents on markers for disease risk."( Fruits and vegetables increase plasma carotenoids and vitamins and decrease homocysteine in humans.
Broekmans, WM; Klöpping-Ketelaars, IA; Kok, FJ; Schuurman, CR; van den Berg, H; van Poppel, G; Verhagen, H, 2000
)
0.31
" Mechanisms responsible for endothelial dysfunction in hyperhomocyst(e)inemia may involve impaired bioavailability of endothelium-dependent nitric oxide."( Plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is elevated in monkeys with hyperhomocyst(e)inemia or hypercholesterolemia.
Bode-Böger, SM; Böger, RH; Heistad, DD; Lentz, SR; Sydow, K, 2000
)
0.31
" Mechanisms responsible for endothelial dysfunction in hyperhomocyst(e)inaemia are poorly understood, but may involve impaired bioavailability of endothelium-derived nitric oxide (NO)."( Elevation of asymmetrical dimethylarginine may mediate endothelial dysfunction during experimental hyperhomocyst(e)inaemia in humans.
Bode-Böger, SM; Böger, RH; Haynes, WG; Knapp, HR; Lentz, SR, 2001
)
0.31
"Endothelial dysfunction reflects reduced nitric oxide (NO) bioavailability due to either reduced production, inactivation of NO, or reduced smooth muscle responsiveness."( Evidence against oxidative stress as mechanism of endothelial dysfunction in methionine loading model.
Cockcroft, JR; Frenneaux, MP; Harrold, F; Jackson, SK; James, PP; Morris-Thurgood, J; Nightingale, AK; Tong, R, 2001
)
0.31
" Homocysteine levels are regulated by folate bioavailability and also by the methyl donor S-adenosylmethionine (SAM) and its metabolite S-adenosylhomocysteine (SAH)."( Endothelial dysfunction and elevation of S-adenosylhomocysteine in cystathionine beta-synthase-deficient mice.
Arning, E; Bottiglieri, T; Dayal, S; Faraci, FM; Heistad, DD; Lentz, SR; Maeda, N; Malinow, MR; Sigmund, CD, 2001
)
0.31
"Previous studies have demonstrated a relationship between hyperhomocysteinemia and endothelial dysfunction, reduced bioavailability of nitric oxide, elastinolysis and, vascular muscle cell proliferation."( Induction of oxidative stress by homocyst(e)ine impairs endothelial function.
Aru, GM; Mujumdar, VS; Tyagi, SC, 2001
)
0.31
" The recommendations should provide a margin of safety to allow for decreased intake, increased requirements, individual variability and bioavailability of natural food folates."( Importance of folate in human nutrition.
Krishnaswamy, K; Madhavan Nair, K, 2001
)
0.31
"In healthy humans, continuous treatment with nitroglycerin (GTN) causes nitric oxide synthase dysfunction, probably through the reduced bioavailability of tetrahydrobiopterin."( Folic acid prevents nitroglycerin-induced nitric oxide synthase dysfunction and nitrate tolerance: a human in vivo study.
Ahmed, S; Al-Hesayen, A; Burstein, JM; Gori, T; Kelly, S; Miner, SE; Parker, JD, 2001
)
0.31
" We hypothesize that the reduced bioavailability of tetrahydrobiopterin is involved in the pathogenesis of both phenomena."( Folic acid prevents nitroglycerin-induced nitric oxide synthase dysfunction and nitrate tolerance: a human in vivo study.
Ahmed, S; Al-Hesayen, A; Burstein, JM; Gori, T; Kelly, S; Miner, SE; Parker, JD, 2001
)
0.31
" The supply of folate depends primarily on the quantity and bioavailability of ingested folate and the rate of loss by urinary and fecal routes and through catabolism."( Prevention of pathologies associated with oxidative stress and dietary intake deficiencies: folate deficiency and requirements.
Gaté, L; Machover, D; Tapiero, H; Tew, KD, 2001
)
0.31
" Endothelial dysfunction due to reduced nitric oxide bioavailability is an early feature of vascular pathology."( Folate, homocysteine, endothelial function and cardiovascular disease. What is the link?
Ashfield-Watt, PA; Doshi, SN; McDowell, IF; Moat, SJ, 2001
)
0.31
"Folate depletion/repletion rat models are popular protocols for assessing the bioavailability of folate."( Plasma, liver and kidney folate and plasma homocysteine concentrations are poor response variables at very low dietary folate intakes, in a folate depletion/repletion rat model.
O'Leary, K; Sheehy, PJ, 2002
)
0.31
" The beneficial effect appears to be independent of its homocysteine-lowering capacity and is possibly related to an improved bioavailability of nitric oxide."( Is folate a promising agent in the prevention and treatment of cardiovascular disease in patients with renal failure?
De Vriese, AS; Lameire, NH; Schrijvers, BF; Verbeke, F, 2002
)
0.31
"These data show that the bioavailability of nitric oxide is reduced in aortae from diabetic rabbits due to excess production of superoxide, an effect augmented by homocysteine."( Homocysteine enhances impairment of endothelium-dependent relaxation and guanosine cyclic monophosphate formation in aortae from diabetic rabbits.
Angelini, GD; Jeremy, JY; Mikhailidis, DP; Shukla, N; Thompson, CS, 2002
)
0.31
" However, studies on bioavailability of endogenous folates, in particular of cereal sources, are scarce."( Functionality of endogenous folates from rye and orange juice using human in vivo model.
Bärlund, S; Kariluoto, S; Kärkkäinen, M; Lamberg-Allardt, C; Piironen, V; Salovaara, H; Vahteristo, L, 2002
)
0.31
" Folates from different rye products and orange juice showed good bioavailability that was similar to folic acid from fortified white bread."( Functionality of endogenous folates from rye and orange juice using human in vivo model.
Bärlund, S; Kariluoto, S; Kärkkäinen, M; Lamberg-Allardt, C; Piironen, V; Salovaara, H; Vahteristo, L, 2002
)
0.31
" This decision needs knowledge about the bioavailability of folic acid from fortified foods."( Study of wheat breakfast rolls fortified with folic acid. The effect on folate status in women during a 3-month intervention.
Bruce, A; Jägerstad, M; Johansson, M; Witthöft, CM, 2002
)
0.31
" This suggests a reduced NO bioavailability to produce vasodilation and an enhanced sensitivity to NO inhibition."( Hyperhomocysteinemia induces renal hemodynamic dysfunction: is nitric oxide involved?
Cuniberti, LA; Dominguez, GN; Fischer, PA; Martinez, V; Masnatta, LD; Ramirez, AJ; Werba, JP, 2003
)
0.32
" Studies have demonstrated that Hcy decreases bioavailability of endothelial nitric oxide (eNO), generates nitrotyrosine, and activates latent matrix metalloproteinase (MMP), instigating EE dysfunction."( Role of nitric oxide in matrix remodeling in diabetes and heart failure.
Hayden, MR; Tyagi, SC, 2003
)
0.32
" Other effects of homocysteine include: impaired generation and decreased bioavailability of endothelium-derived relaxing factor/nitric oxide; interference with many transcription factors and signal transduction; oxidation of low-density lipoproteins; lowering of endothelium-dependent vasodilatation."( [Hyperhomocysteinemia: an independent risk factor or a simple marker of vascular disease?. 1. Basic data].
Favier, A; Galan, P; Guilland, JC; Hercberg, S; Potier de Courcy, G, 2003
)
0.32
" Hyperhomocysteinemia impairs endothelial function, in part due to a diminished bioavailability of BH4 with resultant uncoupling of nitric oxide synthase."( Tetrahydrobiopterin attenuates homocysteine induced endothelial dysfunction.
Badiwala, MV; Dhillon, B; Li, SH; Maitland, A; Rao, V; Verma, S, 2003
)
0.32
" Hyperhomocysteinemia limits the bioavailability of nitric oxide, increases oxidative stress, stimulates the proliferation of vascular smooth muscle cells, and alters the elastic properties of the vascular wall."( Implications of oxidative stress and homocysteine in the pathophysiology of essential hypertension.
Araya, J; Orellana, M; Passalacqua, W; Rivera, G; Rodrigo, R, 2003
)
0.32
" Endothelial dysfunction refers mainly to reduced bioavailability of nitric oxide (NO), which is involved in homocysteinemediated vascular damage."( Interactions of homocysteine, nitric oxide, folate and radicals in the progressively damaged endothelium.
Stanger, O; Weger, M, 2003
)
0.32
" Oxidative stress and decreased nitric oxide (NO) bioavailability were reported in HHcy-induced vascular injury; however, the exact relationship is not understood."( Homocysteine altered ROS generation and NO accumulation in endothelial cells.
Hsieh, CC; Lau, YT; Tsen, CM; Yen, CH, 2003
)
0.32
" In addition, we investigated the bioavailability of calcium added to mineral water by measuring urinary calcium excretion and serum alkaline phosphatase activity."( Mineral water fortified with folic acid, vitamins B6, B12, D and calcium improves folate status and decreases plasma homocysteine concentration in men and women.
Karvonen, HM; Niskanen, LK; Sarkkinen, ES; Tapola, NS, 2004
)
0.32
" It has been suggested that oxidative stress may predispose to a decrease in NO bioavailability and induce the flux of Hcy through the liver transsulfuration pathway."( Opposite effect of methionine-supplemented diet, a model of hyperhomocysteinemia, on plasma and liver antioxidant status in normotensive and spontaneously hypertensive rats.
Berthelot, A; Courderot-Masuyer, C; Jacqueson, A; Nicod, L; Richert, L; Robin, S, 2004
)
0.32
"The bioavailability of dietary folate has been estimated to be approximately 50% of that of synthetic folic acid."( Bioavailability of heptaglutamyl relative to monoglutamyl folic acid in healthy adults.
Katan, MB; Kok, FJ; Melse-Boonstra, A; Verhoef, P; West, CE, 2004
)
0.32
"Our goal was to quantify the bioavailability and bioefficacy of low doses of polyglutamyl folic acid relative to that of monoglutamyl folic acid."( Bioavailability of heptaglutamyl relative to monoglutamyl folic acid in healthy adults.
Katan, MB; Kok, FJ; Melse-Boonstra, A; Verhoef, P; West, CE, 2004
)
0.32
" The relative bioavailability of polyglutamyl folic acid was 64% (52%, 75%) on the basis of serum folate and was 68% (51%, 84%) on the basis of erythrocyte folate concentrations."( Bioavailability of heptaglutamyl relative to monoglutamyl folic acid in healthy adults.
Katan, MB; Kok, FJ; Melse-Boonstra, A; Verhoef, P; West, CE, 2004
)
0.32
"The natural folate derivative, 5-methyltetrahydrofolate ([6S]-5-MTHF), could be an option for supplementation and fortification but its bioavailability remains unclear."( The short-term bioavailabilities of [6S]-5-methyltetrahydrofolate and folic acid are equivalent in men.
Connolly, E; Krämer, K; McKillop, DJ; McNulty, H; McPartlin, JM; Molloy, A; Pentieva, K; Reichert, R; Scott, JM; Strain, JJ; Ward, M, 2004
)
0.32
"Our aim was to study the bioavailability of polyglutamyl folic acid relative to that of monoglutamyl folic acid across GCPII 1561 genotypes."( Bioavailability of polyglutamyl folic acid relative to that of monoglutamyl folic acid in subjects with different genotypes of the glutamate carboxypeptidase II gene.
Blom, HJ; Lievers, KJ; Melse-Boonstra, A; Verhoef, P, 2004
)
0.32
" The bioavailability of heptaglutamyl folic acid relative to that of monoglutamyl folic acid was calculated by using the changes in serum folate concentration in the treatment groups, after correction for changes in the placebo group and for the administered dose."( Bioavailability of polyglutamyl folic acid relative to that of monoglutamyl folic acid in subjects with different genotypes of the glutamate carboxypeptidase II gene.
Blom, HJ; Lievers, KJ; Melse-Boonstra, A; Verhoef, P, 2004
)
0.32
" The bioavailability of heptaglutamyl folic acid relative to that of monoglutamyl folic acid was not significantly different between subjects with the CC (64%; 52%, 76%) and CT genotypes (70%; 49%, 91%)."( Bioavailability of polyglutamyl folic acid relative to that of monoglutamyl folic acid in subjects with different genotypes of the glutamate carboxypeptidase II gene.
Blom, HJ; Lievers, KJ; Melse-Boonstra, A; Verhoef, P, 2004
)
0.32
"The 1561T allele of the GCPII gene does not impair the bioavailability of polyglutamyl folic acid."( Bioavailability of polyglutamyl folic acid relative to that of monoglutamyl folic acid in subjects with different genotypes of the glutamate carboxypeptidase II gene.
Blom, HJ; Lievers, KJ; Melse-Boonstra, A; Verhoef, P, 2004
)
0.32
" Oxidative stress and reduced NO bioavailability have been proposed as a mechanism for the adverse effects of chronically elevated plasma homocysteine levels."( Acute hyperhomocysteinemia decreases NO bioavailability in healthy adults.
Asmis, R; Haefeli, WE; Linder, L; Litynsky, P; Nyfeler, J; Romerio, SC; Wenk, M, 2004
)
0.32
"The concept of dietary folate equivalents (DFEs) in the United States recognizes the differences in bioavailability between natural food folates and the synthetic vitamin, folic acid."( Determining bioavailability of food folates in a controlled intervention study.
Armstrong, NC; Bradbury, I; Dunn, AA; Hannon-Fletcher, MP; Kerr, MA; McNulty, H; Molloy, AM; Pentieva, K; Scott, JM; Strain, JJ; Ward, M, 2004
)
0.32
"We compared the bioavailability of food folates with that of folic acid under controlled conditions."( Determining bioavailability of food folates in a controlled intervention study.
Armstrong, NC; Bradbury, I; Dunn, AA; Hannon-Fletcher, MP; Kerr, MA; McNulty, H; Molloy, AM; Pentieva, K; Scott, JM; Strain, JJ; Ward, M, 2004
)
0.32
" Overall estimations of folate bioavailability relative to that of folic acid were found to be between 30% (spinach) and 59% (yeast)."( Determining bioavailability of food folates in a controlled intervention study.
Armstrong, NC; Bradbury, I; Dunn, AA; Hannon-Fletcher, MP; Kerr, MA; McNulty, H; Molloy, AM; Pentieva, K; Scott, JM; Strain, JJ; Ward, M, 2004
)
0.32
"Relative bioavailability estimates were consistent with the estimates from the metabolic study that were used as a basis to derive the US DFE value."( Determining bioavailability of food folates in a controlled intervention study.
Armstrong, NC; Bradbury, I; Dunn, AA; Hannon-Fletcher, MP; Kerr, MA; McNulty, H; Molloy, AM; Pentieva, K; Scott, JM; Strain, JJ; Ward, M, 2004
)
0.32
"The objective was to evaluate whether cow milk enhances the bioavailability of food folate in humans."( Effect of cow milk on food folate bioavailability in young women.
Dirienzo, DB; Fishell, VK; Johnston, KE; Kris-Etherton, PM; Maddox, DH; Picciano, MF; Ruch, AL; Tamura, T; West, SG; Zhao, G, 2004
)
0.32
"The inclusion of cow milk in the diet enhanced the bioavailability of food folate as assessed by the changes in erythrocyte folate and plasma tHcy concentrations but not in plasma folate concentrations."( Effect of cow milk on food folate bioavailability in young women.
Dirienzo, DB; Fishell, VK; Johnston, KE; Kris-Etherton, PM; Maddox, DH; Picciano, MF; Ruch, AL; Tamura, T; West, SG; Zhao, G, 2004
)
0.32
" It is released by the endothelium, and reduced NO bioavailability is responsible for impaired endothelium-dependent vasorelaxation in hyperhomocyst(e)inemia and other metabolic disorders associated with vascular disease."( Asymmetric dimethyl-L-arginine (ADMA): a possible link between homocyst(e)ine and endothelial dysfunction.
Stanger, O; Stühlinger, MC, 2005
)
0.33
"The aim of this study was to investigate whether milk fortified with folic acid enhances the folate status of humans and whether the presence of folate-binding proteins (FBP) in pasteurised milk affects the bioavailability of folic acid from fortified milk."( Bioavailability of folic acid from fortified pasteurised and UHT-treated milk in humans.
Castenmiller, JJ; de Jong, RJ; Siebelink, E; van den Berg, H; van Vliet, T; Verwei, M; West, CE, 2005
)
0.33
" The bioavailability of folic acid from pasteurised milk relative to that of folic acid from UHT milk was 74-94% (NS), depending on the parameter used."( Bioavailability of folic acid from fortified pasteurised and UHT-treated milk in humans.
Castenmiller, JJ; de Jong, RJ; Siebelink, E; van den Berg, H; van Vliet, T; Verwei, M; West, CE, 2005
)
0.33
" No significant effect of endogenous FBP was found on the bioavailability of folic acid from milk."( Bioavailability of folic acid from fortified pasteurised and UHT-treated milk in humans.
Castenmiller, JJ; de Jong, RJ; Siebelink, E; van den Berg, H; van Vliet, T; Verwei, M; West, CE, 2005
)
0.33
" Impaired flow-mediated dilatation (FMD) is a measure of endothelial dysfunction resulting from reduced bioavailability of nitric oxide (NO)."( Homocysteine and endothelial function in human studies.
McDowell, IF; Moat, SJ, 2005
)
0.33
" The aim of this study was to examine the molecular mechanism by which Hcy triggers oxidative stress and reduces bioavailability of nitric oxide (NO) in cardiac microvascular endothelial cells (MVEC)."( Mechanisms of homocysteine-induced oxidative stress.
Moshal, KS; Ovechkin, AV; Sedoris, KC; Steed, M; Tyagi, N; Tyagi, SC, 2005
)
0.33
" A key vascular phenotype observed in hyperhomocysteinemic animals is endothelial dysfunction, manifested by decreased bioavailability of endothelium-derived nitric oxide."( Mechanisms of homocysteine-induced atherothrombosis.
Lentz, SR, 2005
)
0.33
" In order to make sure about the adequacy of doses and bioavailability of drug, testes parameters were also considered."( Chronic administration of nandrolone decanoate does not increase the plasma homocysteine level of male rats.
Golbahar, J; Mirkhani, H; Shokri, S, 2005
)
0.33
" Chronic ethanol consumption could affect the bioavailability of amino acids such as methionine."( Hepatic S-adenosylmethionine after maternal alcohol exposure on offspring rats.
Artillo, R; Carreras, O; Murillo, ML; Murillo-Fuentes, ML; Ubeda, N; Varela-Moreiras, G, 2005
)
0.33
" Elevated levels of homocysteine also decreases the bioavailability of nitric oxide and modulates the levels of other metabolites including S-adenosyl methionine and S-adenosyl homocysteine which may result in cardiovascular or neurological disorders."( Mining literature for a comprehensive pathway analysis: a case study for retrieval of homocysteine related genes for genetic and epigenetic studies.
Brahmachari, V; Mahajan, A; Sengupta, S; Senthilkumar, RD; Sharma, A; Sharma, P; Sundaramoorthy, E, 2006
)
0.33
" Like many other cardiovascular risk factors, hyperhomocysteinemia produces endothelial dysfunction due to impaired bioavailability of endothelium-derived nitric oxide (NO)."( ADMA and hyperhomocysteinemia.
Dayal, S; Lentz, SR, 2005
)
0.33
" It has been demonstrated, however, that copper augments the inhibitory effect of homocysteine on nitric oxide (NO)-mediated relaxation of the rat aorta through increased superoxide formation, which reacts with NO thereby reducing the bioavailability of NO."( Penicillamine administration reverses the inhibitory effect of hyperhomocysteinaemia on endothelium-dependent relaxation and superoxide formation in the aorta of the rabbit.
Angelini, GD; Jeremy, JY; Jones, RA; Koupparis, A; Persad, R; Shukla, N, 2006
)
0.33
" Relative oral bioavailability (RBV) values, with the L-isomer of Met and Cys set at 100% (isosulfurous basis), are near 100% for D-Met for animals but only about 30% for humans."( Comparative species utilization and toxicity of sulfur amino acids.
Baker, DH, 2006
)
0.33
" Such events decrease NO bioavailability and thus condition the development of various diseases like arteriosclerosis, hypertension, diabetes, heart and renal failure."( [The main determinants of endothelial dysfunction].
Garaliene, V, 2006
)
0.33
" Thus, acute HHcy increases arterial permeability by generating O2- to an extent whereby nitric oxide bioavailability is reduced."( Hyperhomocysteinemia increases arterial permeability and stiffness in mice.
Athanassious, CN; Lentz, SR; Mullick, AE; Rutledge, JC; Symons, JD; Zaid, UB, 2006
)
0.33
" Decreased nitric oxide (NO) bioavailability and increased vascular superoxide production in vascular disease states are due in part to endothelial NO synthase (eNOS) uncoupling related to deficiency of the eNOS cofactor tetrahydrobiopterin (BH4), but whether this mechanism is important in human atherosclerosis and represents a rational therapeutic target remains unclear."( 5-methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels: effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling.
Antoniades, C; Cai, S; Channon, KM; de Bono, J; Lee, J; Leeson, P; Neubauer, S; Pillai, R; Ratnatunga, C; Refsum, H; Shirodaria, C; Warrick, N, 2006
)
0.33
" Flavonols at two dosages in oatmeal porridge were rapidly absorbed, and a relatively small amount of sea buckthorn oil added to the porridge seemed to have increased the bioavailability of sea buckthorn flavonols consumed at the higher dose."( Absorption of flavonols derived from sea buckthorn (Hippophaë rhamnoides L.) and their effect on emerging risk factors for cardiovascular disease in humans.
Ahotupa, M; Kallio, H; Suomela, JP; Vasankari, T; Yang, B, 2006
)
0.33
" Because of the rather low bioavailability of most polyphenolic compounds, how much of an effect dietary polyphenols would have on DNA methylation in humans is not clear."( Dietary polyphenols may affect DNA methylation.
Chen, D; Fang, M; Yang, CS, 2007
)
0.34
"HHcy directly modulates substrate use by the heart independent of changes in hemodynamics or ventricular function by reducing NO bioavailability through the generation of superoxide."( Hyperhomocysteinemia alters cardiac substrate metabolism by impairing nitric oxide bioavailability through oxidative stress.
Hintze, TH; Kinugawa, S; Koller, A; Ojaimi, C; Recchia, FA; Suematsu, N; Wang, Z; Xu, X, 2007
)
0.34
" We provide a new hypothesis whereby reduced conversion of arginine to citrulline is related to increased ornithine levels, but decreased bioavailability of nitric oxide, resulting in impaired blood vessel relaxation and hypertension."( Hypertension in spontaneously hypertensive rats occurs despite low plasma levels of homocysteine.
Fu, M; Haugen, E; Kondziella, D; Zetterberg, H, 2008
)
0.35
" The ADMA-mediated regulation of nitric oxide (NO) production is determined by the quantitative bioavailability of intracellular and extracellular ADMA."( Asymmetric dimethylarginine (ADMA) in vascular, renal and hepatic disease and the regulatory role of L-arginine on its metabolism.
Sim, AS; Wang, J; Wang, XL; Wilcken, DE, 2007
)
0.34
"In the absence of dietary modification, supplementation with the fruit and vegetable juice concentrate capsules proved to be a highly bioavailable source of phytonutrients."( Four week supplementation with mixed fruit and vegetable juice concentrates increased protective serum antioxidants and folate and decreased plasma homocysteine in Japanese subjects.
Kawashima, A; Koike, H; Komatsu, Y; Madarame, T; Wise, JA, 2007
)
0.34
" The molecular mechanisms responsible for decreased bioavailability of endothelium-derived nitric oxide (NO) by Hcy involve an increase of vascular oxidant stress and inhibition of important antioxidant capacity."( Homocysteine and glutathione peroxidase-1.
Handy, DE; Loscalzo, J; Lubos, E, 2007
)
0.34
" Nitric oxide (NO) bioavailability was detected by a NO probe."( Cystathionine-beta-synthase gene transfer and 3-deazaadenosine ameliorate inflammatory response in endothelial cells.
Kumar, M; Moshal, KS; Rodriguez, WE; Sen, U; Tyagi, N; Tyagi, SC, 2007
)
0.34
" Elevated levels of homocysteine also decrease the bioavailability of nitric oxide and modulate the levels of other metabolites including S-adenosyl methionine and S-adenosyl homocysteine which may result in cardiovascular diseases."( Immunoregulatory effects of homocysteine on cardiovascular diseases.
Dai, J; Wang, X, 2007
)
0.34
" Natural food folates have a limited ability to enhance folate status as a result of their poor stability under typical cooking conditions and incomplete bioavailability when compared with the synthetic vitamin, folic acid (as found in supplements and fortified foods)."( Intake and status of folate and related B-vitamins: considerations and challenges in achieving optimal status.
McNulty, H; Scott, JM, 2008
)
0.35
"A crossover single-dose bioavailability study (n = 3) using gamma-tocopherol as exposure marker and a crossover unblinded dietary intervention study (5 weeks) in subjects at risk (n = 25)."( Consumption of restructured meat products with added walnuts has a cholesterol-lowering effect in subjects at high cardiovascular risk: a randomised, crossover, placebo-controlled study.
Blanco-Navarro, I; Blázquez-García, S; Granado-Lorencio, F; Herrero-Barbudo, C; Olmedilla-Alonso, B; Pérez-Sacristán, B, 2008
)
0.35
" CZ ameliorated decrease bioavailability of NO in the diabetic animal."( Ciglitazone, a PPARgamma agonist, ameliorates diabetic nephropathy in part through homocysteine clearance.
Kumar, M; Kundu, S; Rodriguez, WE; Sen, U; Tyagi, N; Tyagi, SC, 2008
)
0.35
" Low vitamin B-12 intake may lead to decreased bioavailability and functional deficiency of cobalamin."( Vitamin B-12 and homocysteine status among vegetarians: a global perspective.
Elmadfa, I; Singer, I, 2009
)
0.35
" We sought to distinguish the effects of plasma versus vascular tissue 5-MTHF and homocysteine on vascular redox and endothelial nitric oxide bioavailability in human vessels."( MTHFR 677 C>T Polymorphism reveals functional importance for 5-methyltetrahydrofolate, not homocysteine, in regulation of vascular redox state and endothelial function in human atherosclerosis.
Antoniades, C; Baarholm, OA; Channon, KM; Cunnington, C; Leeson, P; Pillai, R; Ratnatunga, C; Refsum, H; Shirodaria, C; Stefanadis, C; Tousoulis, D; Van-Assche, T, 2009
)
0.35
" Nitric oxide bioavailability was evaluated by organ bath studies on saphenous vein rings."( MTHFR 677 C>T Polymorphism reveals functional importance for 5-methyltetrahydrofolate, not homocysteine, in regulation of vascular redox state and endothelial function in human atherosclerosis.
Antoniades, C; Baarholm, OA; Channon, KM; Cunnington, C; Leeson, P; Pillai, R; Ratnatunga, C; Refsum, H; Shirodaria, C; Stefanadis, C; Tousoulis, D; Van-Assche, T, 2009
)
0.35
" Vascular 5-MTHF, rather than plasma or vascular homocysteine, is a key regulator of endothelial nitric oxide synthase coupling and nitric oxide bioavailability in human vessels, suggesting that plasma homocysteine is an indirect marker of 5-MTHF rather than a primary regulator of endothelial function."( MTHFR 677 C>T Polymorphism reveals functional importance for 5-methyltetrahydrofolate, not homocysteine, in regulation of vascular redox state and endothelial function in human atherosclerosis.
Antoniades, C; Baarholm, OA; Channon, KM; Cunnington, C; Leeson, P; Pillai, R; Ratnatunga, C; Refsum, H; Shirodaria, C; Stefanadis, C; Tousoulis, D; Van-Assche, T, 2009
)
0.35
" The bioavailability of polyglutamyl folate may be impaired in the subjects, even when their total folate intake was sufficient."( Relationship between genetic polymorphism, serum folate and homocysteine in Alzheimer's disease.
Hiraoka, M; Kagawa, Y; Kageyama, M, 2008
)
0.35
"In conclusion, uric acid decreased NO bioavailability and enhanced superoxide generation in A23187-stimulated bovine aortic endothelial cells."( The effect of uric acid on homocysteine-induced endothelial dysfunction in bovine aortic endothelial cells.
Kubala, L; Lojek, A; Papezikova, I; Pekarova, M, 2009
)
0.35
"Oat-bran helps to improve constipation management and B12 bioavailability in elderly, with multiple chronic diseases who live in nursing homes."( The status of vitamins B6, B12, folate, and of homocysteine in geriatric home residents receiving laxatives or dietary fiber.
Dietrich, A; Elmadfa, I; Gisinger, C; Sturtzel, B; Wagner, KH, 2010
)
0.36
" This effect is probably mediated by a reduction of nitric oxide bioavailability in endothelium."( Acute hyperhomocysteinemia impairs endothelium function in subjects with type 2 diabetes mellitus.
Doupis, J; Eleftheriadou, I; Gonis, A; Katsilambros, N; Kokkinos, A; Pavlatos, S; Perrea, D; Tentolouris, N, 2010
)
0.36
"The addition of folic acid to the US food supply, along with the critical role of folate in certain health outcomes, has intensified worldwide interest in the bioavailability of folate."( Folate bioavailability: implications for establishing dietary recommendations and optimizing status.
Caudill, MA, 2010
)
0.36
" GNMT expression in vivo improves folate retention and bioavailability in the liver."( GNMT expression increases hepatic folate contents and folate-dependent methionine synthase-mediated homocysteine remethylation.
Chen, YM; Chiang, EP; Lin, YJ; Liu, SP; Wang, YC,
)
0.13
" In this study, we examined the effect of AMPK phosphorylation on Hcy-induced NO bioavailability impairment and NADPH oxidase 4 (Nox4) derived reactive oxygen species (ROS) accumulation in EPCs."( AMP-activated protein kinase inhibits homocysteine-induced dysfunction and apoptosis in endothelial progenitor cells.
Chen, Z; Jia, F; Lu, G; Wu, C, 2011
)
0.37
" Levodopa bioavailability was higher on day 2 due to the COMT inhibition."( Inhibition of catechol-O-methyltransferase modifies acute homocysteine rise during repeated levodopa application in patients with Parkinson's disease.
Muhlack, S; Müller, T; Woitalla, D, 2011
)
0.37
"Homocysteine is a cardiovascular risk factor, its metabolism is influenced by certain B vitamins and it is associated with endothelial dysfunction probably due to impaired bioavailability of NO caused by homocysteine-induced accumulation of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase."( Homocysteine and asymmetric dimethylarginine in relation to B vitamins in elderly people.
Elmadfa, I; Fabian, E; Kickinger, A; Wagner, KH, 2011
)
0.37
"The significant correlation between homocysteine and ADMA observed in this study may be an important mechanism decreasing NO bioavailability and so causing endothelial dysfunction."( Homocysteine and asymmetric dimethylarginine in relation to B vitamins in elderly people.
Elmadfa, I; Fabian, E; Kickinger, A; Wagner, KH, 2011
)
0.37
" Folates interact with the endothelial enzyme NO synthase (eNOS) and, exert effects on the cofactor bioavailability of NO and thus, on peroxynitrite formation."( Enzymatic and non-enzymatic antioxidative effects of folic acid and its reduced derivates.
Stanger, O; Wonisch, W, 2012
)
0.38
" Using a murine model of mild HHcy (cbs(+/-) mouse), we show that 3-NT is significantly elevated in cerebral microvessels with concomitant reductions in serum NO bioavailability as compared with wild-type littermate controls (cbs(+/+))."( Nitrative stress in cerebral endothelium is mediated by mGluR5 in hyperhomocysteinemia.
Banks, WA; Beard, RS; Bearden, SE; Chen, CH; Ercal, N; Erickson, MA; Mayo, JN; Price, TO, 2012
)
0.38
" While Hcy has been shown to promote endothelial dysfunction by decreasing the bioavailability of nitric oxide and increasing oxidative stress in the vasculature, the effects of Hcy on cardiomyocytes remain less understood."( Homocysteine induces cardiomyocyte dysfunction and apoptosis through p38 MAPK-mediated increase in oxidant stress.
Cui, L; Handy, DE; Jiang, B; Joseph, J; Liao, R; Loscalzo, J; Pimental, D; Wang, X, 2012
)
0.38
" Decreased bioavailability of nitric oxide (NO) may result in abnormal reactions between the vessel wall and platelets and is thus involved in the initiation and progression of atherosclerosis."( Influence of oral contraceptive pills on homocysteine and nitric oxide levels: as risk factors for cardiovascular disease.
Aghdashi, EM; Fallah, S; Nouroozi, V; Samadikuchaksaraei, A; Seifi, M, 2012
)
0.38
"In hyperhomocysteinemia (HHcy), an independent risk factor for cardiovascular diseases, endothelial dysfunction due to reduced bioavailability of nitric oxide is a consistent finding."( Asymmetric dimethylarginine in adults with cystathionine β-synthase deficiency.
Blom, HJ; Castro, R; Jakobs, C; Janssen, MC; Kluijtmans, LA; Rivera, I; Rocha, MS; Smulders, Y; Tavares de Almeida, I; Teerlink, T, 2012
)
0.38
"Orally LD-treated patients with Parkinson disease had a lower LD dose compared with the ones on an LD infusion, but LD, 3-OMD, and homocysteine bioavailability was not different."( Methyl group-donating vitamins elevate 3-O-methyldopa in patients with Parkinson disease.
Jugel, C; Klostermann, F; Muhlack, S; Müller, T,
)
0.13
"Entacapone increases the bioavailability of levodopa and simultaneously alleviates partially its resulting hyperhomocysteinemia."( [Effects of entacapone on plasma homocysteine in Parkinson's disease patients on levodopa].
Li, Q; Liu, W; Sun, YN; Wang, Y; Yang, JF; Zhang, BS; Zhang, W; Zhao, P, 2013
)
0.39
" The bioavailability of the many antioxidant ingredients a vitamin and trace element composition was investigated, to reveal the neuroprotective (preventive) potential of the composition."( Neuroprotective impact of a vitamin trace element composition - a randomized, double blind, placebo controlled clinical trial with healthy volunteers.
Endler, T; Mosgoeller, W; Muss, C, 2015
)
0.42
" We confirmed the bioavailability of ingredients, and determined metabolic parameters associated with the integrity of the blood brain barrier, mitochondrial deficiency (Q 10), neurodegeneration (homocystein), and antioxidative capacity (e."( Neuroprotective impact of a vitamin trace element composition - a randomized, double blind, placebo controlled clinical trial with healthy volunteers.
Endler, T; Mosgoeller, W; Muss, C, 2015
)
0.42
" The potential mechanisms by which elevated plasma homocysteine level leads to reduction in nitric oxide bioavailability include the disruptive uncoupling of nitric oxide synthase activity and quenching of nitric oxide by oxidative stress, the enzymatic inhibition by asymmetric dimethylarginine, endoplasmic reticulum stress with eventual endothelial cell apoptosis, and chronic inflammation/prothrombotic conditions."( Homocysteine-Induced Endothelial Dysfunction.
Kan, MY; Lai, WK, 2015
)
0.42
" GNMT expression in vivo improves folate retention and bioavailability in the liver."( Regulation of Folate-Mediated One-Carbon Metabolism by Glycine N-Methyltransferase (GNMT) and Methylenetetrahydrofolate Reductase (MTHFR).
Chiang, EP; Ko, HA; Lin, YJ; Tang, FY; Wang, YC; Wu, MT, 2015
)
0.42
" This interaction may modulate their bioavailability and effectiveness."( N- and S-homocysteinylation reduce the binding of human serum albumin to catechins.
Arru, D; Carru, C; Cossu, A; Giordo, R; Mangoni, AA; Pintus, G; Posadino, AM; Scanu, B; Sotgia, S; Zinellu, A, 2017
)
0.46
" It demonstrates importance of reducing bioavailability of nitric oxide, which is an antioxidant in physiological concentrations, in the development of oxidative stress in lung mitochondria during hyperhomocysteinemia."( [Metabolic changes in pulmonary mitochondria of rats with experimental hyperhomocysteinemia].
Belskikh, ES; Bulatetskiy, SV; Medvedev, DV; Ryabkov, AN; Uryasev, OM; Zvyagina, VI, 2017
)
0.46
"Homeostasis around vascular endothelium is a function of the equilibrium between the bioavailability of nitric oxide (NO) and oxidizing reactive oxygen species (ROS)."( Endothelial dysfunction, endothelial nitric oxide bioavailability, tetrahydrobiopterin, and 5-methyltetrahydrofolate in cardiovascular disease. Where are we with therapy?
Ng, GA; Ng, LL; Yuyun, MF, 2018
)
0.48
"To investigate the ingredients' bioavailability of the complex vitamin-mineral-trace element composition LaVita® we recruited healthy volunteers for six months and observed the changes of pregnancy relevant parameters by means of laboratory measures."( Potential of the multivitamin-mineral-trace element composition LaVita® before, during and after pregnancy.
Doerfler, D; Endler, TA; Mosgoeller, W; Muss, C, 2019
)
0.51
"Owing to the widespread use of vitamin supplements to prevent and compensate for deficiencies, the equivalence of natural versus synthetic vitamins with respect to their bioavailability and metabolic influence is discussed controversially."( [Bioavailability of natural versus synthetic B vitamins and their effects on metabolic processes].
Cvirn, G; Fuchs, N; Lamont, E; Lindschinger, B; Lindschinger, M; Markolin, G; Schimetta, W; Schmid, I; Tatzber, F; Wonisch, W, 2020
)
0.56
" However, its bioavailability is low."( Nanoemulsification of Rice Bran Wax Policosanol Enhances Its Cardio-protective Effects via Modulation of Hepatic Peroxisome Proliferator-activated Receptor gamma in Hyperlipidemic Rats.
Imam, MU; Ishaka, A; Ismail, M, 2020
)
0.56
"Nar could increase the ROS elimination and decrease eNOS uncoupling, subsequently upregulate the NO bioavailability and endothelial function by activating AMPKα/Sirt1 signaling pathway."( Naringenin ameliorates homocysteine induced endothelial damage via the AMPKα/Sirt1 pathway.
Cao, Z; Chen, Y; Hu, J; Li, C; Li, H; Li, W; Liu, G; Liu, L; Liu, R; Liu, Y; Liu, Z; Lu, C; Song, Y, 2021
)
0.62
" Levodopa bioavailability and its maximum concentration were higher with opicapone."( Effects of One-Day Application of Levodopa/Carbidopa/Entacapone versus Levodopa/Carbidopa/Opicapone in Parkinson's Disease Patients.
Müller, T; Schlegel, E; Thiede, HM; Zingler, S, 2022
)
0.72

Dosage Studied

Dietary folic acid reduced homocysteine levels by 25% (95% confidence interval [CI]: 23 to 28%) with similar effects in a daily dosage range of 0.5%. There was no dose-response relationship between homocy Steine concentration and severity of preeclampsia.

ExcerptRelevanceReference
" The total dosage was between 30 and 50g Pod."( [Radio-chemotherapy of cervix carcinoma. I. Clinical part].
Paeschke, KD, 1976
)
0.26
" In the majority of neurons two phases in the dose-response relationship could be distinguished."( Membrane currents induced by L-homocysteic acid in mouse cultured hippocampal neurons.
Vlachová, V; Vyklický, L, 1992
)
0.28
" L-Aspartate (L-Asp) produced a similar dose-response relationship."( Electrogenic uptake contributes a major component of the depolarizing action of L-glutamate in rat hippocampal slices.
Blake, JF; Brown, MW; Collingridge, GL; Frenguelli, BG, 1991
)
0.28
" In the fibroblasts, MTX with thymidine + hypoxanthine rescue induced a marked increase in Hcy export, and the dose-response paralleled the cytotoxicity curves obtained for MTX without rescue."( Interaction between methotrexate, "rescue" agents and cell proliferation as modulators of homocysteine export from cells in culture.
Christensen, B; Djurhuus, R; Refsum, H; Ueland, PM, 1991
)
0.28
" From reviews of metabolite values in blood samples either fasting (11 articles) or after a methionine load (8 articles), and of measures of enzyme activity (12 articles), it is apparent that (1) The heterozygous phenotype cannot be identified consistently by any single measure (there is overlap with normal values); and (2) the exaggerated gene dosage effect (negative allelic complementation) present in most heterozygotes does not assist their classification."( Detection of heterozygotes for recessive alleles. Homocyst(e)inemia: paradigm of pitfalls in phenotypes.
McGill, JJ; Mettler, G; Rosenblatt, DS; Scriver, CR, 1990
)
0.28
" Arteriosclerosis seems to be increased in heterozygotes as well (cystathionine beta-synthase gene dosage 50%) but rare in Down syndrome (cystathionine beta-synthase gene dosage 150%)."( Homocysteine, factor VII and antithrombin III in subjects with different gene dosage for cystathionine beta-synthase.
Brattström, L; Hultberg, B; Israelsson, B; Tengborn, L, 1989
)
0.28
" GDEE in a dosage of 4 mmol/kg almost completely blocked homocysteine-induced seizures in mice; smaller dosages had no effect or only slight inhibitory effects."( Selective inhibition of homocysteine-induced seizures by glutamic acid diethyl ester and other glutamate esters.
Freed, WJ,
)
0.13
" These reductions were prevented by pretreatment with homocysteine at a dosage which had been shown to inhibit protein carboxyl and other methylation reactions in brain."( Homocysteine prevents apomorphine-induced decreases in dopamine metabolites.
Salama, AI; Saller, CF, 1985
)
0.27
"Ara-C at very low dosage has been reported to decrease the host toxicity of ara-AMP or ara-A in combination with 2'-deoxycoformycin, a potent adenosine deaminase inhibitor, while increasing the toxicity to intracerebral L1210 leukemia."( Biochemical and biophysical approaches to improving the anticancer effectiveness of Ara-adenine.
Eyring, H; Miles, DL; Miles, DW, 1982
)
0.26
"Chronic dosing of rats with isoniazid (INH) leads to an increase in the incidence of short "spontaneous" sprouts on motor end plates in the rat sternocostalis muscle."( The effects of chronic isoniazid intoxication on motor end plate sprouting in rat sternocostalis muscle and on responses to partial denervation and local botulinum toxin.
Cavanagh, JB; Kemplay, S, 1984
)
0.27
" The animals were dosed for 7 days with MMC 1 mg/kg/d and some were then kept without treatment for a further."( Fluctuation of trace elements during methylmercury toxication and chelation therapy.
Bapu, C; Purohit, RC; Sood, PP, 1994
)
0.29
" The corresponding dose-response curve revealed a half-maximum of current activation at 350 microM."( Glial cells in the mouse hippocampus express AMPA receptors with an intermediate Ca2+ permeability.
Seifert, G; Steinhäuser, C, 1995
)
0.29
" These in vitro studies support our hypothesis that enhanced metabolism of ara-C in DS cells may be a contributing factor to the superior survival rate of DS children with AML and is possibly based on a gene dosage effect of genes localized to chromosome 21 including cystathionine-beta-synthase."( Enhanced metabolism of 1-beta-D-arabinofuranosylcytosine in Down syndrome cells: a contributing factor to the superior event free survival of Down syndrome children with acute myeloid leukemia.
Buck, SA; Gurney, JG; Matherly, LH; Ravindranath, Y; Stout, ML; Taub, JW, 1996
)
0.29
" A graded dose-response relationship between plasma homocysteine concentration over its full range and cardiovascular risk strongly supports causality."( Vitamins as homocysteine-lowering agents.
Brattström, L, 1996
)
0.29
" We conducted a placebo-controlled eight-week trial of the effect on plasma homocysteine of adding supraphysiologic dose folic acid (15 mg/day), B-6 (100 mg/day), and B-12 (1 mg/day) to the usual daily dosing of 1 mg folic acid, 10 mg B-6, and 12 micrograms B-12, in 27 hyperhomocysteinemic dialysis patients."( High dose-B-vitamin treatment of hyperhomocysteinemia in dialysis patients.
Bendich, A; Bostom, AG; Hume, AL; Lapane, KL; Nadeau, MR; Rosenberg, IH; Selhub, J; Shemin, D; Yoburn, D, 1996
)
0.29
" There was a marked positive dose-response relation between coffee consumption and plasma tHcy, which was stronger than the relation between coffee and total serum cholesterol."( Coffee consumption and plasma total homocysteine: The Hordaland Homocysteine Study.
Kvåle, G; Nordrehaug, JE; Nygård, O; Refsum, H; Stensvold, I; Ueland, PM; Vollset, SE, 1997
)
0.3
" We identified clear dose-response relationships for both plasma folate and homocysteine with increased quintile of breakfast cereal and of fruit and vegetable use."( Dietary intake pattern relates to plasma folate and homocysteine concentrations in the Framingham Heart Study.
Rosenberg, IH; Selhub, J; Tucker, KL; Wilson, PW, 1996
)
0.29
" A dose-response effect with no toxicity was obtained when the ETH dose was increased 10 fold."( Methionine deprivation and methionine analogs inhibit cell proliferation and growth of human xenografted gliomas.
Bourgeois, Y; Bras Gonçalves, RA; Demerseman, P; Dutrillaux, B; Lopez, R; Miccoli, L; Poirson-Bichat, F; Poisson, M; Poupon, MF, 1997
)
0.3
" A dose-response effect was noted between total homocysteine level and risk."( Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project.
Andria, G; Bellet, H; Boers, GH; Brattström, LE; Daly, LE; de Valk, HW; Garcon, D; Graham, IM; Higgins, I; Israelsson, B; McMaster, D; Meleady, R; Palma-Reis, RJ; Parrot-Rouland, FM; Refsum, HM; Robinson, K; Rubba, P; Sales Lúis, AC; Sheahan, RG; Tan, KS; Ueland, PM; Uiterwaal, CS; Verhoef, P; Wautrecht, JC; Witteman, J, 1997
)
0.3
" The dosage of these two substances help to differenciate between both carencies, but it is not determinant of any of them and is an expensive method."( [Megaloblastic anemia: rapid and economical study].
Cicchetti, G; Marín, GH; Tentoni, J, 1997
)
0.3
" Finally, no dose-response relationship between cumulative exposure to metformin (dose x duration of treatment) and the serum total homocysteine level could be demonstrated."( Does metformin increase the serum total homocysteine level in non-insulin-dependent diabetes mellitus?
Bouter, LM; Heine, RJ; Hoogeveen, EK; Jakobs, C; Kostense, PJ; Stehouwer, CD, 1997
)
0.3
" There was a continuous dose-response relationship, with risk increasing by 41% (95% CI, 20%-65%) for each 5-micromol/L increase in the serum homocysteine level."( Homocysteine and ischemic heart disease: results of a prospective study with implications regarding prevention.
Law, MR; McPartlin, J; Scott, JM; Wald, NJ; Watt, HC; Weir, DG, 1998
)
0.3
" No influence of dydrogesterone dosage was found."( Postmenopausal oral 17beta-estradiol continuously combined with dydrogesterone reduces fasting serum homocysteine levels.
Jakobs, C; Kenemans, P; Mijatovic, V; Netelenbos, C; Peters-Muller, ER; Popp-Snijders, C; van der Mooren, MJ, 1998
)
0.3
" We conclude that a supraphysiological dose of folic acid is superior to standard multivitamin dosing for the reduction of fasting tHcy levels in chronic RTRs."( Enhanced reduction of fasting total homocysteine levels with supraphysiological versus standard multivitamin dose folic acid supplementation in renal transplant recipients.
Beaulieu, AJ; Bostom, AG; Gohh, RY; Hakas, D; Han, H; Jacques, PF; Selhub, J, 1999
)
0.3
" A significant dose-response relationship between serum folate concentrations and risk of recurrent early pregnancy loss suggested a protective effect by high serum folate concentrations."( Homocysteine and folate levels as risk factors for recurrent early pregnancy loss.
Blom, HJ; den Heijer, M; Eskes, TK; Nelen, WL; Steegers, EA; Thomas, CM, 2000
)
0.31
" Thank to the development of methods allowing the routine dosage of all these parameters, general practitioners can now easily establish the oxidative stress status of their patients and, as fonction of getting patterns, detect populations at risk of developing cardiovascular diseases."( [Determination of plasma concentrations of antioxidants, antibodies against oxidized LDL, and homocysteine in a population sample from Liège].
Chantillon, AM; Chapelle, JP; Cheramy-Bien, JP; Christiaens, G; Defraigne, JO; Gielen, J; Limet, R; Paulissen, G; Pincemail, J; Siquet, J,
)
0.13
" We also performed the dosage of plasma levels of B6 and B12 vitamins and of red cells folates."( [Influence of smoking on homocysteinemia at baseline and after methionine load].
Azinheira, J; Correia, JM; Luís, AS; Pina, JE; Reis, HP; Reis, RP, 2000
)
0.31
"To evaluate plasma homocysteine (Hcy) concentrations in children receiving sodium valproate (VPA) and carbamazepine (CBZ), monotherapy, in comparison with healthy control subjects and to determine the possible relationship between Hcy levels and dosage and plasma concentrations of the antiepileptic drugs."( Hyperhomocysteinemia in children treated with sodium valproate and carbamazepine.
Chiarelli, F; Giuva, T; Morgese, G; Pascarella, R; Trotta, D; Verrotti, A, 2000
)
0.31
" Measurement of the rate of ROS production in the presence of varying concentrations of cysteine together with 20 microM ferrous iron revealed a dose-response relationship."( Configuration of thiols dictates their ability to promote iron-induced reactive oxygen species generation.
Bondy, SC; Campbell, A; Yang, EY, 2000
)
0.31
" Homocysteine reduction is known to be maximal at a folic acid dosage of 1 mg/d, but the effect of lower doses (relevant to food fortification) is unclear."( Randomized trial of folic acid supplementation and serum homocysteine levels.
Bishop, L; Hennessy, E; Law, M; McPartlin, J; Scott, J; Wald, DS; Wald, NJ; Weir, D, 2001
)
0.31
" Food folate intake had an inverse dose-response relation with tHcy that was limited to nonusers of supplements."( Association of folate intake and serum homocysteine in elderly persons according to vitamin supplementation and alcohol use.
Allen, RH; Baumgartner, RN; Garry, PJ; Koehler, KM; Rimm, EB; Stabler, SP, 2001
)
0.31
" We evaluated prospectively the effect of increasing the folic acid dosage from 1 to 6 mg per dialysis on plasma total homocysteine levels of haemodialysis patients with and without a history of occlusive vascular artery disease (OVD)."( Difference in the homocysteine-lowering effect of folic acid in haemodialysis patients with and without occlusive vascular disease.
Bersier, LF; Boulat, O; Descombes, E; Fellay, G, 2001
)
0.31
" The results showed that HCY did cause damage to embryonic development and the damages of HCY on embryos were characterized in a significant dose-response pattern."( [Effects of homocysteine on post-implantation rat embryo cultured in vitro].
Chen, X; Li, Y; Zhao, R, 2001
)
0.31
" Different shapes of the dose-response relationship were seen for the 3 vascular disease categories."( Plasma total cysteine as a risk factor for vascular disease: The European Concerted Action Project.
El-Khairy, L; Graham, IM; Refsum, H; Ueland, PM; Vollset, SE, 2001
)
0.31
" A curvilinear relationship exists between these cofactors and tHcy levels, with the dose-response relationship shifted to the right in the weight loss group."( Elevated homocysteine levels with weight loss after Lap-Band surgery: higher folate and vitamin B12 levels required to maintain homocysteine level.
Dixon, JB; Dixon, ME; O'Brien, PE, 2001
)
0.31
" There is an altered dose-response relationship with higher serum B(12) and folate levels required to maintain recommended tHcy levels."( Elevated homocysteine levels with weight loss after Lap-Band surgery: higher folate and vitamin B12 levels required to maintain homocysteine level.
Dixon, JB; Dixon, ME; O'Brien, PE, 2001
)
0.31
"05) with three vitamin dosages weekly, but not with one dosage weekly."( Homocyst(e)ine metabolism in hemodialysis patients treated with vitamins B6, B12 and folate.
Graefe, U; Henning, BF; Riezler, R; Tepel, M; Zidek, W, 2001
)
0.31
" The four groups of ten subjects received either placebo bid, chromium polynicotinate (Cr) 200 microg bid, grape seed extract (GSE) 100 mg bid, or a combination of Cr and GSE at the same dosage bid."( Effects of niacin-bound chromium and grape seed proanthocyanidin extract on the lipid profile of hypercholesterolemic subjects: a pilot study.
Bagchi, D; Bui, M; Echard, B; Myers, A; Preuss, HG; Talpur, N; Tutuncuoglu, SO; Wallerstedt, D, 2000
)
0.31
" Acute hyperhomocysteinaemia had no significant effect on incremental microvascular vasodilator dose-response curves to Ach and SNP, or circulating levels of vWF."( Acute hyperhomocysteinaemia affects pulse pressure but not microvascular vasodilator function.
Bonham, JR; Davis, KR; Donnelly, R; Moat, S; Pearson, H, 2001
)
0.31
"0 micromol of HCY/per embryo could disturb their heart development and differentiation of blood vessels at fetal ages of two and four days, in a dose-response pattern, with 24."( [Effects of homocysteine on cardiovascular development in early chicken embryo].
Chen, X; Li, S; Li, Y; Li, Z; Qi, P, 1999
)
0.3
"This trial sought to examine the effects of high dosage of folic acid and vitamin C supplementation on red blood cell folate (RCF), serum folate (SF) and homocysteine (Hcy) levels in subjects who smoke more than 15 cigarettes per day."( Effect of folic acid and vitamin C supplementation on folate status and homocysteine level: a randomised controlled trial in Italian smoker-blood donors.
Cafolla, A; Costante, A; De Luca, AM; Dragoni, F; Funaro, D; Girelli, G; Scott, CS; Tosti, ME, 2002
)
0.31
" The results of preformulation studies enabled detection of drug-excipients interactions and selection of compatible excipient system to the given drug composition to formulate dosage form of required stability, processability and effectiveness."( [Formulation of tablets decreasing plasma homocysteine levels].
Budavári, Z, 2001
)
0.31
" The relationship between Cbl supplement dosage and the biochemical parameters was dose dependent."( Is low-dose oral cobalamin enough to normalize cobalamin function in older people?
Day, A; Evans, L; Freedman, M; Garcia, A; Paris-Pombo, A, 2002
)
0.31
"To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of betaine in the treatment of classical homocystinuria due to cystathionine beta-synthase (CbetaS) deficiency with a view to optimizing the dosage regimen."( An indirect response model of homocysteine suppression by betaine: optimising the dosage regimen of betaine in homocystinuria.
Bonham, JR; Chakrapani, A; Johnson, TN; Matthews, A; Moat, SJ; Rostami-Hodjegan, A; Tucker, GT; Wraith, JE, 2002
)
0.31
" PK-PD simulation indicated minimal benefit from exceeding a twice-daily dosing schedule and a 150 mg kg(-1) day(-1) dosage for betaine."( An indirect response model of homocysteine suppression by betaine: optimising the dosage regimen of betaine in homocystinuria.
Bonham, JR; Chakrapani, A; Johnson, TN; Matthews, A; Moat, SJ; Rostami-Hodjegan, A; Tucker, GT; Wraith, JE, 2002
)
0.31
"PK-PD modelling allows recommendations for optimal dosage of betaine in the treatment of homocystinuria, that have the potential for improved patient compliance and both therapeutic and pharmacoeconomic benefit."( An indirect response model of homocysteine suppression by betaine: optimising the dosage regimen of betaine in homocystinuria.
Bonham, JR; Chakrapani, A; Johnson, TN; Matthews, A; Moat, SJ; Rostami-Hodjegan, A; Tucker, GT; Wraith, JE, 2002
)
0.31
"The dose-response effects of whole almonds, taken as snacks, were compared with low-saturated fat (<5% energy) whole-wheat muffins (control) in the therapeutic diets of hyperlipidemic subjects."( Dose response of almonds on coronary heart disease risk factors: blood lipids, oxidized low-density lipoproteins, lipoprotein(a), homocysteine, and pulmonary nitric oxide: a randomized, controlled, crossover trial.
Connelly, PW; Faulkner, D; Haight, JS; Jenkins, DJ; Kendall, CW; Lapsley, KG; Marchie, A; Parker, TL; Qian, W; Spiller, GA; Vidgen, E, 2002
)
0.31
"Serum MMA, tHcy, and other metabolites at baseline and after each 6-week dosing interval."( Response of elevated methylmalonic acid to three dose levels of oral cobalamin in older adults.
Allen, RH; Beresford, SA; Brodkin, KI; Rajan, S; Stabler, SP; Wallace, JI, 2002
)
0.31
" From the dose-response curve, the adequate daily dose of folic acid was estimated to be 392 micro g, which decreased plasma homocysteine concentrations 22%."( Folic acid and reduction of plasma homocysteine concentrations in older adults: a dose-response study.
Brouwer, IA; Clarke, R; Katan, MB; Melse-Boonstra, A; van Oort, FV; Verhoef, P; West, CE, 2003
)
0.32
" There were positive and significant dose-response relationships between measures of cigarette smoking (cigarettes per day, pack-years, and serum cotinine levels) and elevated levels of novel risk factors."( Relationship between cigarette smoking and novel risk factors for cardiovascular disease in the United States.
Bazzano, LA; He, J; Muntner, P; Vupputuri, S; Whelton, PK, 2003
)
0.32
" In addition, a significant dose-response relation between plasma folate concentrations and risk for schizophrenia suggested a protective effect by high plasma folate concentrations."( Homocysteine metabolism and B-vitamins in schizophrenic patients: low plasma folate as a possible independent risk factor for schizophrenia.
Blom, H; Ellenbroek, B; Eskes, T; Muntjewerff, JW; Steegers, E; van der Put, N; Zitman, F, 2003
)
0.32
" Starting at a plasma homocysteine concentration of approximately 10 micromol/l, the risk increase follows a linear dose-response relationship with no specific threshold level."( DACH-LIGA homocystein (german, austrian and swiss homocysteine society): consensus paper on the rational clinical use of homocysteine, folic acid and B-vitamins in cardiovascular and thrombotic diseases: guidelines and recommendations.
Dierkes, J; Fowler, B; Geisel, J; Herrmann, W; Pietrzik, K; Stanger, O; Weger, M, 2003
)
0.32
"3 microM, respectively; whereas the dose-response curve of D,L-homocysteine revealed an IC50 of 401 microM."( Implications for hyperhomocysteinemia: not homocysteine but its oxidized forms strongly inhibit neuronal network activity.
Fleischer, W; Görtz, P; Hoinkes, A; Otto, F; Schwahn, B; Siebler, M; Wendel, U, 2004
)
0.32
" There was no difference in Hcy reduction following the administration of either high or low dosage of vitamins B6 and B12 utilized in the present study."( Comparative study of response to treatment with supraphysiologic doses of B-vitamins in hyperhomocysteinemic hemodialysis patients.
Abassi, Z; Brenner, B; Green, J; Khankin, E; Lanir, N; Nakhoul, F; Plawner, M; Ramadan, R, 2004
)
0.32
" DDAH activity had a decreasing dose-response relationship with increasing L-homocysteine concentrations."( Homocysteine increases the production of asymmetric dimethylarginine in cultured neurons.
Selley, ML, 2004
)
0.32
" Hence, a reduction in CsA dosage in kidney transplant recipients (KTR) may improve long-term outcomes."( Analysis of the cardiovascular risk profile in stable kidney transplant recipients after 50% cyclosporine reduction.
Cardarelli, F; Cosimi, AB; Delmonico, FL; Farrell, ML; Pascual, M; Saidman, SL; Shih, V; Tolkoff-Rubin, N; Winkelmayer, WC; Wong, W, 2004
)
0.32
" Starting at a plasma homocysteine concentration of approximately 10 micromol/l, the risk increase follows a linear dose-response relationship with no specific threshold level."( Clinical use and rational management of homocysteine, folic acid, and B vitamins in cardiovascular and thrombotic diseases.
Dierkes, J; Fowler, B; Geisel, J; Herrmann, W; Pietrzik, K; Stanger, O; Weger, M, 2004
)
0.32
" A daily dosage of 75 to 150 mg is sufficient to reduce the rate of future cardiac events."( [Risk management of coronary artery disease--pharmacological therapy].
Hofmann, T, 2004
)
0.32
" Dose-response relationships, a criterion for causality, were examined linking exposures to likelihood of case status."( Case-control study of multiple chemical sensitivity, comparing haematology, biochemistry, vitamins and serum volatile organic compound measures.
Baines, CJ; Cole, DE; Jazmaji, V; Loescher, B; Marshall, L; McKeown-Eyssen, GE; Riley, N, 2004
)
0.32
"Although there are controversies on dosing and timing, the use of acetylcysteine together with hydration should be considered to protect patients from radiographic contrast media-induced nephropathy."( N-Acetylcysteine in nephrology; contrast nephropathy and beyond.
Tepel, M; Zidek, W, 2004
)
0.32
" A dose of 6 g betaine/d has been used in the treatment of homocystinuria, but data on the dose-response are scarce."( The effect of low doses of betaine on plasma homocysteine in healthy volunteers.
Alfthan, G; Aro, A; Nissinen, K; Saarela, J; Tapani, K, 2004
)
0.32
"Subjects received oral SAMe for 4 weeks; the dosage was titrated over 5 days to 1600 mg/day."( Bioavailability and lack of toxicity of S-adenosyl-L-methionine (SAMe) in humans.
Cohen, BM; Damico, KE; Gören, JL; Sarmiento, IA; Stoll, AL, 2004
)
0.32
" Notably, adjusted (for age and sex) dose-response curves for the postmethionine increase in homocysteine or fasting homocysteine versus betaine showed that the inverse associations were most pronounced at low serum folate, an observation that was confirmed by analyses of interaction."( Betaine and folate status as cooperative determinants of plasma homocysteine in humans.
Blom, HJ; den Heijer, M; Holm, PI; Keijzer, MB; Midttun, Ø; Ueland, PM; Vollset, SE, 2005
)
0.33
" There was no dose-response relationship between homocysteine concentration and severity of preeclampsia."( Mapping the theories of preeclampsia: the role of homocysteine.
Carroli, G; Khan, KS; Kilby, MD; Latthe, PM; Mignini, LE; Villar, J, 2005
)
0.33
" However, because of a lack of consistency in data, dose-response relationship, and biologic plausibility, the observed association cannot be considered causal from the current literature."( Mapping the theories of preeclampsia: the role of homocysteine.
Carroli, G; Khan, KS; Kilby, MD; Latthe, PM; Mignini, LE; Villar, J, 2005
)
0.33
" Serum vitamin B12 was related to BMD in dose-response fashion up to about 200 pmol/L, and subjects with serum Hcy > or = 20 micromol/L had significantly lower BMD than subjects with serum Hcy < 10 micromol/L."( Relation between homocysteine and B-vitamin status indicators and bone mineral density in older Americans.
Jacques, PF; Morris, MS; Selhub, J, 2005
)
0.33
" If blood pressure was above normal on the 15th day of follow-up, the metoprolol dosage was doubled."( Beta blocker effects on plasma homocysteine levels in patients with hypertension.
Atar, I; Atar, IA; Aydinalp, A; Bozbaş, H; Demircan, S; Korkmaz, ME; Müderrisoğlu, H; Ozin, B; Yildirir, A, 2005
)
0.33
" Regardless of the dosage of progestin used, there was no impact on homocysteine metabolism after 3 years of therapy."( Effect of oral conjugated equine estrogen combined with medroxyprogesterone acetate on plasma homocysteine levels in postmenopausal women.
Hsu, SC; Lee, JN; Liu, CM; Long, CY; Tsai, EM; Yang, CH, 2005
)
0.33
"In this Aboriginal community with remarkably high rates of cigarette smoking among its youth, an independent dose-response relation was found between current smoking exposure and both traditional (systolic blood pressure) and nontraditional (homocysteine level) cardiovascular risk factors."( Cigarette smoking and cardiovascular risk factors among Aboriginal Canadian youths.
Connelly, PW; Hanley, AJ; Harris, SB; Retnakaran, R; Zinman, B, 2005
)
0.33
" Experiments with adenosine demonstrated that the selected dose of SPT elicited marked rightward shifts in the dose-response curves for both the inotropic and vascular actions."( Acute dilatory and negative inotropic effects of homocysteine are inhibited by an adenosine blocker.
Boerma, M; Hauer-Jensen, M; Joseph, J; Kennedy, RH; Melchert, RB; Owings, R, 2006
)
0.33
" Even though Cys and its oxidized product (cystine) are equally efficacious at levels at or below their dietary requirements for maximal growth, Cys is far more toxic than cystine when administered orally in the pharmacologic dosing range."( Comparative species utilization and toxicity of sulfur amino acids.
Baker, DH, 2006
)
0.33
" Delivered dosage of dialysis (Kt/V) was calculated by Daugirdas formula."( [Characteristics of hyperhomocysteinemia in dialysis patients].
Kes, P; Lovcić, V; Reiner, Z, 2006
)
0.33
"5% of patients, inadequate dosage of dialysis is the consequence of insufficient function of the A-V fistula and lack of patient cooperation."( [Characteristics of hyperhomocysteinemia in dialysis patients].
Kes, P; Lovcić, V; Reiner, Z, 2006
)
0.33
" Some reports support our observation that the dosage of folic acid required for tHcy decrease is 15-30 mg, and that the dosage higher than 60 mg does not significantly decrease tHcy concentration."( [The treatment of hyperhomocysteinemia in patients on dialysis: folic acid or the high-flow polysulphonic membrane?].
Kes, P; Kusec, V; Lovcić, V; Zeljko, R, 2006
)
0.33
" Dose-response analyses indicated a positive association between plasma tHcy and risk of fracture in both sexes and a negative association between plasma folate and risk of fracture among women only."( Plasma homocysteine, folate, and vitamin B 12 and the risk of hip fracture: the hordaland homocysteine study.
Gjesdal, CG; Meyer, HE; Refsum, H; Tell, GS; Ueland, PM; Vollset, SE, 2007
)
0.34
" These data should be confirmed to evaluate the importance of homocysteine dosage in the diagnosis of NASH."( [Steatosis, chronic hepatitis virus C infection and homocysteine].
Pofelski, J; Roblin, X; Zarski, JP, 2007
)
0.34
" The current study was undertaken to obtain information on the dose-response pattern of different metabolic criteria related to the homeostasis of vitamin B(12) and homocysteine in gestating sows receiving various concentrations of dietary vitamin B(12) (cyanocobalamin)."( Effects of concentrations of cyanocobalamin in the gestation diet on some criteria of vitamin B12 metabolism in first-parity sows.
Giguère, A; Girard, CL; Guay, F; Laforest, JP; Matte, JJ; Simard, F, 2007
)
0.34
" Post hoc analysis, which should be interpreted with caution, seemed to indicate a dose-response effect: the change in FMD was -0."( Folic acid improves vascular reactivity in humans: a meta-analysis of randomized controlled trials.
de Bree, A; Draijer, R; van Mierlo, LA, 2007
)
0.34
"Potential reasons for this non-significant result may be found in a dose-response relationship, advancement of disease progression in our sample population, or potentially the lack of a significant relationship between fish oil and tHcy."( Omega-3 fatty acid supplementation and total homocysteine levels in end-stage renal disease patients.
Beavers, DP; Beavers, KM; Bowden, RG; Gentile, M; Wilson, RL, 2008
)
0.35
" An unusual dose-response pattern was observed in that at 6 mg/day CP-778,875 only increased HDL cholesterol by 3% and decreased HDL(2) cholesterol by 24%."( Efficacy and safety of a potent and selective peroxisome proliferator activated receptor alpha agonist in subjects with dyslipidemia and type 2 diabetes mellitus.
Contant, CF; Francone, OL; Gao, X; Lewin, AJ; Nguyen, TT; Terra, SG, 2008
)
0.35
"There are no large randomized trials of the effect of folic acid dosing regimens on blood folate and homocysteine concentrations."( Folate status and homocysteine response to folic acid doses and withdrawal among young Chinese women in a large-scale randomized double-blind trial.
Bailey, LB; Berry, RJ; Erickson, JD; Gindler, J; Hao, L; Hu, DJ; Li, S; Li, Z; Yang, QH; Zhang, BL; Zhang, L; Zhu, JH, 2008
)
0.35
"Changes in folate and homocysteine concentrations were unaffected by different dosing schedules."( Folate status and homocysteine response to folic acid doses and withdrawal among young Chinese women in a large-scale randomized double-blind trial.
Bailey, LB; Berry, RJ; Erickson, JD; Gindler, J; Hao, L; Hu, DJ; Li, S; Li, Z; Yang, QH; Zhang, BL; Zhang, L; Zhu, JH, 2008
)
0.35
"Using data from 7038 Hordaland Homocysteine Study participants, we fitted regression models and dose-response curves of tCys and tHcy with BMI."( Homocysteine, cysteine, and body composition in the Hordaland Homocysteine Study: does cysteine link amino acid and lipid metabolism?
Elshorbagy, AK; Gjesdal, CG; Nurk, E; Nygård, O; Refsum, H; Tell, GS; Tverdal, A; Ueland, PM; Vollset, SE, 2008
)
0.35
" Cumulative lifetime L-dopa dosage and fasting MMA levels were associated with PN severity."( Neuropathy as a potential complication of levodopa use in Parkinson's disease.
Brown, MS; Furtado, S; Suchowersky, O; Toth, C; Zochodne, D, 2008
)
0.35
" Correcting the insufficiency by dosing folate along with the SSRI results in a significantly better antidepressant response."( The methylation, neurotransmitter, and antioxidant connections between folate and depression.
Miller, AL, 2008
)
0.35
" There were no statistical differences in disease duration, anti-dsDNA, C3, C4, disease activity, and medication dosage between SLE patients stratified by fasting insulin levels."( Elevation of fasting insulin and its association with cardiovascular disease risk in women with systemic lupus erythematosus.
Huang, WN; Tso, TK, 2009
)
0.35
" Those subjects were randomized to receive either 5 mg/d of oral folic acid or an equivalent dosage of placebo."( Role of folic acid in atherosclerosis after kidney transplant: a double-blind, randomized, placebo-controlled clinical trial.
Einollahi, B; Farhangi, S; Farjad, R; Firouzan, A; Kalantar, A; Kardavani, B; Khatami, F; Nafar, M; Pour-Reza-Gholi, F, 2009
)
0.35
" The 1 mM dosage of homocysteine in staurosporine-differentiated RGC-5 cells also did not induce cell death above control levels, although 18 hr treatment of non-differentiated RGC-5 cells with 5 mM homocysteine decreased survival by 50%."( Sensitivity of staurosporine-induced differentiated RGC-5 cells to homocysteine.
Allen, JB; Bozard, BR; Dun, Y; Duplantier, J; Farooq, A; Ganapathy, PS; Ha, Y; Smith, SB, 2010
)
0.36
"Hc levels were significantly higher in patients taking levodopa and were not related to levodopa dosage or treatment duration."( [Homocysteine and cognitive impairment in Parkinson's disease].
Avilés, F; Cañizares, F; Carles-Díes, R; Fernández-Barreiro, A; Herrero, MT; Martín-Fernández, JJ; Morsi-Hassan, O; Parra, S; Villegas, I,
)
0.13
"2) g) were estimated in a 12-week dose-response experiment."( Response of European sea bass (Dicentrarchus labrax) to graded levels of methionine (total sulfur amino acids) in soya protein-based semi-purified diets.
Calligaris, M; Messina, M; Tibaldi, E; Tulli, F, 2010
)
0.36
"03), although no significant dose-response relationship was found."( Serum folate, vitamin B-12, and homocysteine and their association with depressive symptoms among U.S. adults.
Beydoun, HA; Beydoun, MA; Shroff, MR; Zonderman, AB, 2010
)
0.36
" A randomized, double-blind, placebo-controlled, dose-response trial with a parallel-group design was conducted."( Effects of folic acid supplementation on serum folate and plasma homocysteine concentrations in older adults: a dose-response trial.
Anderson, CA; Appel, LJ; Charleston, J; Jee, SH; Narrett, M, 2010
)
0.36
" The dosage of homocysteine was measured by high performance liquid chromatography."( The association between homocysteine level and metabolic syndrome in patients of prior myocardial infarction.
Agoşton-Coldea, L; Dobie, L; Lupu, S; Mărginean, A; Mocan, T, 2010
)
0.36
"2%) were treated by first generation antipsychotics with a mean daily dosage of 401."( [Hyperhomocysteinemia and schizophrenia: case control study].
Bouslama, A; Douki, W; Gaha, L; Mabrouk, H; Mechri, A; Najjar, MF; Omezzine, A; Younes, MK, 2011
)
0.37
" Concerning therapeutic features, plasma Hcys did not differ with type of antipsychotic and was not related to daily dosage of antipsychotics."( [Hyperhomocysteinemia and schizophrenia: case control study].
Bouslama, A; Douki, W; Gaha, L; Mabrouk, H; Mechri, A; Najjar, MF; Omezzine, A; Younes, MK, 2011
)
0.37
" Our findings are consistent with a relatively sharp threshold effect between severely elevated plasma homocysteine and thrombotic risk in HCU and indicate that the HO mouse model can serve as a useful tool for both testing novel treatment strategies and examining the optimal timing and dosing of betaine treatment with a view toward optimizing clinical outcome."( Long-term betaine therapy in a murine model of cystathionine beta-synthase deficient homocystinuria: decreased efficacy over time reveals a significant threshold effect between elevated homocysteine and thrombotic risk.
Allen, RH; Greiner, LS; Jiang, H; Maclean, KN; Stabler, SP, 2012
)
0.38
"Coenzyme Q10 supplementation at a dosage of 150 mg appears to decrease the inflammatory marker IL-6 in patients with CAD."( Effects of coenzyme Q10 supplementation on inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, and homocysteine) in patients with coronary artery disease.
Chen, SJ; Huang, YC; Lee, BJ; Lin, PT, 2012
)
0.38
" The aim of our study is to appreciate the clinical usefulness of the dosage serum homocysteine and malondialdehyde, as an oxidative stress marker, in the pregnancies complicated with risk of abortion or preterm birth."( The influence of homocysteine and oxidative stress on pregnancy outcome.
Antal, L; Bodog, A; Bodog, F; Micle, O; Muresan, M, 2012
)
0.38
" The increase in the dosage of this gene results in an altered profile of metabolites involved in the folate pathway, including reduced homocysteine (Hcy), methionine, S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM)."( Genetic polymorphisms modulate the folate metabolism of Brazilian individuals with Down syndrome.
Biselli, JM; Carvalho, VM; Eberlin, MN; Fonseca, MF; Goloni-Bertollo, EM; Haddad, R; Pavarino, EC; Vannucchi, H; Zampieri, BL, 2012
)
0.38
"After adjusting for potential confounders, the rates of bone loss at the proximal femur sites were significantly accelerated in a dose-response fashion across increasing tHcy concentrations in premenopausal women and men, but not in postmenopausal women."( High serum total homocysteine levels accelerate hip bone loss in healthy premenopausal women and men.
Ahn, SH; Bae, SJ; Choe, JW; Kim, BJ; Kim, EH; Kim, GS; Kim, HK; Kim, SY; Kim, TH; Koh, JM; Lee, SH; Lim, KH; Pyun, KH, 2013
)
0.39
"We determined LD, 3-OMD, and homocysteine plasma concentrations in relation to daily LD dosage administered orally or as duodenal infusion with and without vitamins."( Methyl group-donating vitamins elevate 3-O-methyldopa in patients with Parkinson disease.
Jugel, C; Klostermann, F; Muhlack, S; Müller, T,
)
0.13
" The same 3-OMD and homocysteine accumulation despite the applied higher LD dosage during the infusion indicates a limited methylation capacity."( Methyl group-donating vitamins elevate 3-O-methyldopa in patients with Parkinson disease.
Jugel, C; Klostermann, F; Muhlack, S; Müller, T,
)
0.13
" There is also a positive dose-response relationship between tHcy and abdominal aortic diameter."( Plasma total homocysteine is associated with abdominal aortic aneurysm and aortic diameter in older men.
Flicker, L; Golledge, J; Hankey, GJ; McCaul, KA; Norman, PE; van Bockxmeer, FM; Wong, YY; Yeap, BB, 2013
)
0.39
"The objective of this study was to examine the dose-response relationship between As and global methylation of peripheral blood mononuclear cell (PBMC) DNA in apparently healthy Bangladeshi adults chronically exposed to a wide range of As concentrations in drinking water."( A dose-response study of arsenic exposure and global methylation of peripheral blood mononuclear cell DNA in Bangladeshi adults.
Alam, S; Gamble, MV; Graziano, JH; Hall, MN; Harper, KN; Ilievski, V; Levy, D; Liu, X; Mey, JL; Niedzwiecki, MM; Oka, J; Parvez, F; Siddique, AB; Slavkovich, V; van Geen, A,
)
0.13
"We conducted a dose-response meta-analysis in healthy adults to quantify the typical response of recognized folate biomarkers to a change in folic acid intake."( Biomarker responses to folic acid intervention in healthy adults: a meta-analysis of randomized controlled trials.
Collings, R; Duffy, ME; Dullemeijer, C; Hoey, L; Hooper, L; Hughes, CF; McNulty, H; Rankin, A; Souverein, OW; Strain, JJ, 2014
)
0.4
"Folate biomarkers (serum/plasma and red blood cell folate) increased in response to folic acid in a dose-response manner only up to an intake of 400 μg/d."( Biomarker responses to folic acid intervention in healthy adults: a meta-analysis of randomized controlled trials.
Collings, R; Duffy, ME; Dullemeijer, C; Hoey, L; Hooper, L; Hughes, CF; McNulty, H; Rankin, A; Souverein, OW; Strain, JJ, 2014
)
0.4
"Studies administering >400 μg folic acid/d show no dose-response relation and thus will not yield meaningful results for consideration when generating dietary folate recommendations."( Biomarker responses to folic acid intervention in healthy adults: a meta-analysis of randomized controlled trials.
Collings, R; Duffy, ME; Dullemeijer, C; Hoey, L; Hooper, L; Hughes, CF; McNulty, H; Rankin, A; Souverein, OW; Strain, JJ, 2014
)
0.4
" MSH provoked a dose-response reversal of the redox state of aged plasma, and the thiol action was confirmed by in vivo experiments."( The control of hyperhomocysteinemia through thiol exchange mechanisms by mesna.
Bartalini, S; Coppo, L; Di Giuseppe, D; Di Simplicio, P; Frosali, S; Margaritis, A; Priora, R; Summa, D; Ulivelli, M, 2014
)
0.4
" The significant increase in odds ratios for CKD in progressive homocysteine levels reveals a dose-response effect."( Serum homocysteine level is positively associated with chronic kidney disease in a Taiwan Chinese population.
Chao, MC; Davidson, LE; Hsu, HS; Hu, SL; Li, CI; Li, TC; Lin, CC; Lin, CH; Lin, WY; Liu, CS, 2014
)
0.4
" A dose-response relation exists between folate intake or plasma level and disease risk within the normal range."( Critical evaluation of lowering the recommended dietary intake of folate.
Koletzko, B; Obeid, R; Pietrzik, K, 2014
)
0.4
"Guanidinoacetic acid (GAA) is an intermediate in the biosynthesis of creatine (Cr), yet its use in human nutrition is limited due to a lack of a clear understanding of its' dose-response effect."( Dose-response effects of oral guanidinoacetic acid on serum creatine, homocysteine and B vitamins levels.
Drid, P; Hoffman, JR; Ostojic, SM; Stojanovic, M, 2014
)
0.4
"5 μmol/L on average at post-administration, yet no dose-response differences were found between trials."( Dose-response effects of oral guanidinoacetic acid on serum creatine, homocysteine and B vitamins levels.
Drid, P; Hoffman, JR; Ostojic, SM; Stojanovic, M, 2014
)
0.4
" The dose-response relationship between Hcy concentration and risk of poor outcome was statistically significant (p-value for trend  = 0."( High homocysteine and blood pressure related to poor outcome of acute ischemia stroke in Chinese population.
Liu, C; Lv, L; Sun, W; Tong, W; Xu, T; Zhao, L; Zhong, C; Zhou, M, 2014
)
0.4
" In addition, the homocysteine blood concentration just before the first cycle dosage of pemetrexed was significantly elevated relative to the 2-3 cycle."( Phase II study of oral vitamin B12 supplementation as an alternative to intramuscular injection for patients with non-small cell lung cancer undergoing pemetrexed therapy.
Hosomi, Y; Nagamata, M; Nakahara, Y; Okamura, T; Okuma, Y; Shimokawa, T; Sunami, K; Takagi, Y; Takahashi, S; Watanabe, K; Yomota, M, 2016
)
0.43
"2% completed their planned dosage within a 9-week feasibility time frame."( Reduced folate and serum vitamin metabolites in patients with rectal carcinoma: an open-label feasibility study of pemetrexed with folic acid and vitamin B12 supplementation.
Björkqvist, HG; Carlsson, GU; Gustavsson, BG; Kurlberg, GK; Odin, EA; Stoffregen, CC; Tångefjord, MT, 2016
)
0.43
" Multivitamin supplements were taken at a dosage of one pill every day for 12 weeks through the oral route."( Effects of Multivitamin Supplements on Cognitive Function, Serum Homocysteine Level, and Depression of Korean Older Adults With Mild Cognitive Impairment in Care Facilities.
Kim, SY; Lee, HK; Sok, SR, 2016
)
0.43
"These results suggest that PA and MSA are associated with lower homocysteine and that there may be a dose-response relationship when combining both forms of exercise, which is an important finding as higher homocysteine is predictive of increased all-cause and CVD-specific mortality."( Single and combined associations of accelerometer-assessed physical activity and muscle-strengthening activities on plasma homocysteine in a national sample.
Buckner, SL; Loenneke, JP; Loprinzi, PD, 2017
)
0.46
" This study has provided evidence that a high dosage of folic acid supplements throughout pregnancy reduces Hcy concentrations at the time of delivery."( The Effect of High Dose Folic Acid throughout Pregnancy on Homocysteine (Hcy) Concentration and Pre-Eclampsia: A Randomized Clinical Trial.
Alizadeh, M; Bidadi, S; Ghojazadeh, M; Ghorbanihaghjo, A; Kazemi-Shishvan, M; Sayyah-Melli, M, 2016
)
0.43
"  Madopar dosage was maintained in both groups."( The effect of levodopa benserazide hydrochloride on homocysteinemia levels in patients with Parkinson's disease and treatment of hyperhomocysteinemia.
Cao, LD; Guo, G; Wu, QY; Xu, S, 2016
)
0.43
" Subgroup analysis indicated that the follow-up time, the dosage of folic acid and vitamin B12 and B6, the history of diseases had no confounding effect on the incidence of cardio-cerebrovascular disease events."( [Meta-analysis on effect of combined supplementation of folic acid, vitamin B12 and B6 on risk of cardio-cerebrovascular diseases in randomized control trials].
Dang, SN; Lan, X; Yan, H; Zhao, YL, 2016
)
0.43
" Low levodopa dosing and antioxidants in the rotigotine patch matrix prevented cysteinyl-glycine fall."( Levodopa, placebo and rotigotine change biomarker levels for oxidative stress.
Herrman, L; Kinkel, M; Muhlack, S; Müller, T, 2017
)
0.46
"Chronic ethanol/alcohol (AL) dosing causes an elevation in homocysteine (Hcy) levels, which leads to the condition known as Hyperhomocysteinemia (HHcy)."( Exercise Mitigates Alcohol Induced Endoplasmic Reticulum Stress Mediated Cognitive Impairment through ATF6-Herp Signaling.
Behera, J; George, AK; Kelly, KE; Mondal, NK; Richardson, KP; Tyagi, N, 2018
)
0.48
" An age-, sex-, and race-adjusted model showed dose-response relations between plasma homocysteine concentrations and AF incidence in both ARIC and MESA."( Homocysteine and Incident Atrial Fibrillation: The Atherosclerosis Risk in Communities Study and the Multi-Ethnic Study of Atherosclerosis.
Alonso, A; Folsom, AR; Heckbert, SR; Kubota, Y; Norby, FL, 2019
)
0.51
" These dose-response estimates may be used to derive folate intake reference values."( Systematic Review of Observational Studies with Dose-Response Meta-Analysis between Folate Intake and Status Biomarkers in Adults and the Elderly.
de Groot, LCPGM; Duffy, M; Dullemeijer, C; Geelen, A; Glibetić, M; Gurinović, M; Hoey, L; McNulty, H; Nikolić, M; Novaković, R; Renkema, JMS; Ristić-Medić, D; Souverein, OW; Van't Veer, P, 2018
)
0.48
" The doses and schedule of systemic and intrathecal methotrexate, given from post-natal age 3-7 weeks, were chosen to model the effects of repeated methotrexate dosing on the developing brains of young children with ALL."( Methotrexate causes persistent deficits in memory and executive function in a juvenile animal model.
Cole, PD; Gulinello, ME; Maxwell, RR; Spira, M; Wen, J; Wolf, AJ, 2018
)
0.48
"This study aimed to comprehensively assess the dose-response relationship between blood homocysteine levels and risk of all cause, Alzheimer and vascular dementia, as well as cognitive impairment without dementia (CIND)."( Hyperhomocysteinemia and risk of incident cognitive outcomes: An updated dose-response meta-analysis of prospective cohort studies.
Chen, S; Zhou, F, 2019
)
0.51
" The dose-response meta-analyses were conducted to assess potential linear and non-linear dose-response relations."( Hyperhomocysteinemia and risk of incident cognitive outcomes: An updated dose-response meta-analysis of prospective cohort studies.
Chen, S; Zhou, F, 2019
)
0.51
"This study has provided evidence that a high dosage of FA supplement from 3 months before pregnancy until the entire pregnancy reduces the recurrent pre-eclampsia."( The effect of folic acid throughout pregnancy among pregnant women at high risk of pre-eclampsia: A randomized clinical trial.
Huang, J; Kong, H; Su, Y; Wang, F; Xin, H; Zheng, L, 2020
)
0.56
"Prolonged hyperthyroidism and hypothyroidism were modeled in experimental rats by dosing the animals with L-thyroxine and thiamazole, respectively, for 21 days."( The impact of B vitamins on the functioning of methylation cycle in the liver and the kidneys of hyper- and hypothyroid rats.
Bulko, I; Dmytrenko, I; Korda, M; Nechyporuk, V; Pentiuk, L, 2020
)
0.56
"Prolonged hyperthyroidism and hypothyroidism were modeled in experimental rats by dosing the animals with Lthyroxine and thiamazole, respectively, for 21 days, and prolonged with HHCy administered with excessive exogenous HCy, for 21 days."( Implementation of programmed cell death in circulating neutrophils and its special characteristics in experimentally induced hyperhomocysteinemia in a setting of thyroid dysfunction.
Andriichuk, V; Korda, M; Kovalchuk, O; Nechyporuk, V; Pentiuk, L, 2020
)
0.56
" And, it was suggested that the dosage of metformin should be less than 1700 mg/days."( The effect of metformin on homocysteine levels in patients with polycystic ovary syndrome: A systematic review and meta-analysis.
Bai, Y; Fang, Z; Li, X; Pan, H; Wang, F; Yang, X; Zhang, C, 2021
)
0.62
" Kaplan-Meier curves showed a gene dosage effect of the T allele in MTHFR C677T polymorphism on the accelerated progression of spinal OA severity (P = 0."( Associations of Homocysteine Metabolism With the Risk of Spinal Osteoarthritis Progression in Postmenopausal Women.
Miyazaki, A; Nakamura, Y; Nakano, M; Shiraki, M; Suzuki, T; Takahashi, J; Urano, T; Watanabe, K, 2021
)
0.62
" Our study found a dose-response association between plasma homocysteine levels, especially a Hcy level >13."( Dose-response association between plasma homocysteine and white matter lesions in patients with hypertension: a case-control study.
Cai, X; Li, N; Liu, Y; Yuan, Y, 2022
)
0.72
" Betaine has been used for more than 30 years in pyridoxine non-responsive cystathionine beta-synthase (pnrCBS) and cobalamin C (cblC) deficiencies to lower the hyperhomocysteinemia, although little is known about the optimal therapeutic dosage and its pharmacokinetic in these patients."( Efficacy and pharmacokinetics of betaine in CBS and cblC deficiencies: a cross-over randomized controlled trial.
Alberti, C; Benoist, JF; de Baulny, HO; Feillet, F; Garcia-Segarra, N; Guilmin-Crépon, S; Haignere, J; Imbard, A; Kaguelidou, F; Kuster, A; Magréault, S; Perronneau, I; Schiff, M; Schlemmer, D; Toumazi, A, 2022
)
0.72
"Our analysis shows that there is no overt benefit to increasing betaine dosage higher than 100 mg/kg/day to lower tHcy concentrations in pnrCBS and cblC deficiencies."( Efficacy and pharmacokinetics of betaine in CBS and cblC deficiencies: a cross-over randomized controlled trial.
Alberti, C; Benoist, JF; de Baulny, HO; Feillet, F; Garcia-Segarra, N; Guilmin-Crépon, S; Haignere, J; Imbard, A; Kaguelidou, F; Kuster, A; Magréault, S; Perronneau, I; Schiff, M; Schlemmer, D; Toumazi, A, 2022
)
0.72
"At present, the relationship between serum homocysteine (Hcy), fibrinogen (FIB), lipoprotein-a (LPa), and PAD is uncertain, and there has been no meta-analysis to establish the dose-response relationship between their exposure levels and PAD."( Relationship between serum homocysteine, fibrinogen, lipoprotein-a level, and peripheral arterial disease: a dose-response meta-analysis.
Han, Y; Jiang, D; Wang, H; Wu, P; Zhang, H; Zhang, J; Zong, Y, 2022
)
0.72
" The robust error meta-regression method was used to assess the linear and non-linear dose-response relationship between exposure level and PAD risk."( Relationship between serum homocysteine, fibrinogen, lipoprotein-a level, and peripheral arterial disease: a dose-response meta-analysis.
Han, Y; Jiang, D; Wang, H; Wu, P; Zhang, H; Zhang, J; Zong, Y, 2022
)
0.72
" Le profil de la mutation du gène MTR A2756G et le dosage de l’homocystéine (Hcy) ont été évalués respectivement par réaction en chaîne par polymérase et par test immunologique enzymatique."( Assessment of MTR Rs1805087 SNP as Possible Modifier of Sickle Cell Disease Severity in a Nigerian Population.
Aiyelokun, OE; Akinsola, OJ; Davies, NO; Ogbenna, AA; Olowoselu, FO; Osunkalu, VO; Taiwo, IA, 2022
)
0.72
" Significant nonlinear dose-response relationships were observed for the associations of folate with anemia, vitamin B12 with vitamin B-complex deficiencies, anemia and cholelithiasis, and homocysteine with cerebrovascular disease."( Phenome-wide association study of genetically predicted B vitamins and homocysteine biomarkers with multiple health and disease outcomes: analysis of the UK Biobank.
Bennett, D; Campbell, H; Duthie, S; Eguiagaray, IM; Li, X; Little, J; MacFarlane, AJ; McNulty, H; Momoli, F; Montazeri, A; Munger, R; Rubini, M; Senekal, M; Theodoratou, E; Wang, L, 2023
)
0.91
" A dose-response curve with an inflection point at 22."( Association between homocysteine level and length of stay in patients with lower extremity atherosclerotic disease: a retrospective cohort study.
Li, X; Wang, X; Xu, L; Yang, Y; Yu, L; Zang, S, 2023
)
0.91
" Knowing the pleiotropic negative impact of Hcy on gametes, embryos and pregnancy in general, we strongly recommend a Hcy dosage in both members of couples seeking treatment for pregnancy."( The importance of preconception Hcy testing: identification of a folate trap syndrome in a woman attending an assisted reproduction program.
Clément, A; Clément, P; Menezo, YJR; Viot, G, 2023
)
0.91
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (2)

RoleDescription
fundamental metaboliteAny metabolite produced by all living cells.
mouse metaboliteAny mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (3)

ClassDescription
amino acid zwitterionThe zwitterionic form of an amino acid having a negatively charged carboxyl group and a positively charged amino group.
homocysteineA sulfur-containing amino acid consisting of a glycine core with a 2-mercaptoethyl side-chain.
serine family amino acidAn L-alpha-amino acid which is biosynthesised from 3-phosphoglycerate (i.e. serine, glycine, cysteine and homocysteine). A closed class.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathways (33)

PathwayProteinsCompounds
Folate metabolism ( Folate metabolism )2039
Glycine and Serine metabolism ( Glycine and Serine metabolism )3649
Methionine and Cysteine metabolism ( Methionine and Cysteine metabolism )2342
Oxidative stress and redox pathway019
Metabolic Epileptic Disorders2589
folate metabolism022
cysteine biosynthesis/homocysteine degradation08
methionine biosynthesis020
superpathway of lysine, threonine and methionine biosynthesis II032
superpathway of lysine, threonine and methionine biosynthesis I038
methionine and S-adenosylmethionine synthesis010
formylTHF biosynthesis II027
formylTHF biosynthesis I026
methionine biosynthesis II018
methionine biosynthesis I017
Folic acid network070
AtMetExpress overview0109
Folate-alcohol and cancer pathway012
One-carbon donor022
Trans-sulfuration and one-carbon metabolism020
Selenium micronutrient network095
Vitamin B12 metabolism050
Folate-alcohol and cancer pathway hypotheses012
Folate metabolism156
Trans-sulfuration pathway014
One-carbon metabolism013
EV release from cardiac cells and their functional effects02
Methionine de novo and salvage pathway148
Biochemical pathways: part I0466
Amino acid metabolism094
Ethanol effects on histone modifications017
SAM cycle111
SMM cycle15
Homocysteine biosynthesis07
Methionine biosynthesis II017

Protein Targets (1)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
N(G),N(G)-dimethylarginine dimethylaminohydrolase 1Homo sapiens (human)IC50 (µMol)640.00007.80008.25708.7140AID386453
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (11)

Processvia Protein(s)Taxonomy
citrulline metabolic processN(G),N(G)-dimethylarginine dimethylaminohydrolase 1Homo sapiens (human)
regulation of systemic arterial blood pressureN(G),N(G)-dimethylarginine dimethylaminohydrolase 1Homo sapiens (human)
arginine catabolic processN(G),N(G)-dimethylarginine dimethylaminohydrolase 1Homo sapiens (human)
nitric oxide mediated signal transductionN(G),N(G)-dimethylarginine dimethylaminohydrolase 1Homo sapiens (human)
negative regulation of cell population proliferationN(G),N(G)-dimethylarginine dimethylaminohydrolase 1Homo sapiens (human)
negative regulation of vascular permeabilityN(G),N(G)-dimethylarginine dimethylaminohydrolase 1Homo sapiens (human)
positive regulation of nitric oxide biosynthetic processN(G),N(G)-dimethylarginine dimethylaminohydrolase 1Homo sapiens (human)
positive regulation of angiogenesisN(G),N(G)-dimethylarginine dimethylaminohydrolase 1Homo sapiens (human)
nitric oxide metabolic processN(G),N(G)-dimethylarginine dimethylaminohydrolase 1Homo sapiens (human)
negative regulation of cellular response to hypoxiaN(G),N(G)-dimethylarginine dimethylaminohydrolase 1Homo sapiens (human)
arginine metabolic processN(G),N(G)-dimethylarginine dimethylaminohydrolase 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (4)

Processvia Protein(s)Taxonomy
catalytic activityN(G),N(G)-dimethylarginine dimethylaminohydrolase 1Homo sapiens (human)
dimethylargininase activityN(G),N(G)-dimethylarginine dimethylaminohydrolase 1Homo sapiens (human)
metal ion bindingN(G),N(G)-dimethylarginine dimethylaminohydrolase 1Homo sapiens (human)
amino acid bindingN(G),N(G)-dimethylarginine dimethylaminohydrolase 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (2)

Processvia Protein(s)Taxonomy
cytosolN(G),N(G)-dimethylarginine dimethylaminohydrolase 1Homo sapiens (human)
extracellular exosomeN(G),N(G)-dimethylarginine dimethylaminohydrolase 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (17)

Assay IDTitleYearJournalArticle
AID390212Antioxidant activity assessed as DPPH radical scavenging activity at 36 uM after 30 mins in presence of Cu2++2008Bioorganic & medicinal chemistry, Nov-15, Volume: 16, Issue:22
Double edge redox-implications for the interaction between endogenous thiols and copper ions: In vitro studies.
AID390225Antioxidant activity assessed as DPPH radical scavenging activity after 40 mins in absence of Cu2+2008Bioorganic & medicinal chemistry, Nov-15, Volume: 16, Issue:22
Double edge redox-implications for the interaction between endogenous thiols and copper ions: In vitro studies.
AID390210Antioxidant activity assessed as reducing capacity of Iodine solution at 0.25mM after 30 mins in presence of Cu2++2008Bioorganic & medicinal chemistry, Nov-15, Volume: 16, Issue:22
Double edge redox-implications for the interaction between endogenous thiols and copper ions: In vitro studies.
AID390218Induction of ascorbic acid oxidation preincubated for 60 mins in presence of Cu2++2008Bioorganic & medicinal chemistry, Nov-15, Volume: 16, Issue:22
Double edge redox-implications for the interaction between endogenous thiols and copper ions: In vitro studies.
AID390224Antioxidant activity assessed as ABTS radical scavenging activity after 30 mins in absence of Cu2+2008Bioorganic & medicinal chemistry, Nov-15, Volume: 16, Issue:22
Double edge redox-implications for the interaction between endogenous thiols and copper ions: In vitro studies.
AID386462Inhibition of human recombinant DDAH1 assessed as inactivation rate at 1 mM2007The Journal of biological chemistry, Nov-30, Volume: 282, Issue:48
Inhibition of human dimethylarginine dimethylaminohydrolase-1 by S-nitroso-L-homocysteine and hydrogen peroxide. Analysis, quantification, and implications for hyperhomocysteinemia.
AID390227Antioxidant activity assessed as DPPH radical scavenging activity at 36 uM after 3 mins in presence of Cu2++2008Bioorganic & medicinal chemistry, Nov-15, Volume: 16, Issue:22
Double edge redox-implications for the interaction between endogenous thiols and copper ions: In vitro studies.
AID390216Induction of ascorbic acid oxidation preincubated for 3 mins in presence of Cu2++2008Bioorganic & medicinal chemistry, Nov-15, Volume: 16, Issue:22
Double edge redox-implications for the interaction between endogenous thiols and copper ions: In vitro studies.
AID390219Induction of ascorbic acid oxidation preincubated for 300 mins in presence of Cu2++2008Bioorganic & medicinal chemistry, Nov-15, Volume: 16, Issue:22
Double edge redox-implications for the interaction between endogenous thiols and copper ions: In vitro studies.
AID390209Antioxidant activity assessed as reducing capacity of DTNB at 20 uM after 30 mins in presence of Cu2++2008Bioorganic & medicinal chemistry, Nov-15, Volume: 16, Issue:22
Double edge redox-implications for the interaction between endogenous thiols and copper ions: In vitro studies.
AID386452Inhibition of human recombinant DDAH1 after 20 mins2007The Journal of biological chemistry, Nov-30, Volume: 282, Issue:48
Inhibition of human dimethylarginine dimethylaminohydrolase-1 by S-nitroso-L-homocysteine and hydrogen peroxide. Analysis, quantification, and implications for hyperhomocysteinemia.
AID390220Effect on CU2+-mediated superoxide-dependent cytochrome c reduction at 10 to 30 uM2008Bioorganic & medicinal chemistry, Nov-15, Volume: 16, Issue:22
Double edge redox-implications for the interaction between endogenous thiols and copper ions: In vitro studies.
AID390217Induction of ascorbic acid oxidation preincubated for 30 mins in presence of Cu2++2008Bioorganic & medicinal chemistry, Nov-15, Volume: 16, Issue:22
Double edge redox-implications for the interaction between endogenous thiols and copper ions: In vitro studies.
AID390211Antioxidant activity assessed as ABTS radical scavenging activity at 4 uM after 30 mins in presence of Cu2++2008Bioorganic & medicinal chemistry, Nov-15, Volume: 16, Issue:22
Double edge redox-implications for the interaction between endogenous thiols and copper ions: In vitro studies.
AID390226Antioxidant activity assessed as ABTS radical scavenging activity at 4 uM after 3 mins in presence of Cu2+2008Bioorganic & medicinal chemistry, Nov-15, Volume: 16, Issue:22
Double edge redox-implications for the interaction between endogenous thiols and copper ions: In vitro studies.
AID386453Inhibition of human recombinant DDAH12007The Journal of biological chemistry, Nov-30, Volume: 282, Issue:48
Inhibition of human dimethylarginine dimethylaminohydrolase-1 by S-nitroso-L-homocysteine and hydrogen peroxide. Analysis, quantification, and implications for hyperhomocysteinemia.
AID390222Effect on CU2+-mediated superoxide-dependent lucigenin reduction by chemiluminescence assay at 10 to 30 uM2008Bioorganic & medicinal chemistry, Nov-15, Volume: 16, Issue:22
Double edge redox-implications for the interaction between endogenous thiols and copper ions: In vitro studies.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (15,108)

TimeframeStudies, This Drug (%)All Drugs %
pre-19901297 (8.58)18.7374
1990's1829 (12.11)18.2507
2000's6439 (42.62)29.6817
2010's4345 (28.76)24.3611
2020's1198 (7.93)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials1,348 (8.49%)5.53%
Reviews1,867 (11.76%)6.00%
Case Studies292 (1.84%)4.05%
Observational88 (0.55%)0.25%
Other12,276 (77.35%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]