Effect of cobalamin derivatives on in vitro enzymic DNA methylation: methylcobalamin can act as a methyl donor

Pfohl‐Leszkowicz, Annie; Keith, Gérard; Dirheimer, G.

doi:10.1021/bi00246a024

Cited by 46 publications

(21 citation statements)

References 19 publications

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“…48 The observation that methylcobalamin can serve as a methyl donor in vitro in the DNA methylase reaction provides one possible mechanism for a pharmacologic effect of Cbl therapy. 49 Analogously, pharmacologic doses of B 6 vitamers have been shown to alter enzymes of vitamin B 6 metabolism, B 6 -dependent apoenzymes, and unrelated enzyme proteins both in vitro and in vivo. [50][51][52][53][54][55] It is concluded that (1) short-term intraindividual variations in Cbl, MMA, and HCys values can affect the recognition of Cbl deficiency; (2) Cbl levels well within the reference range are common in patients with clinical disorders responsive to Cbl therapy; (3) metabolites are frequently normal in patients with hematologic or neurologic abnormalities responsive to pharmacologic doses of Cbl; and (4) the presence of elevated metabolite levels are not predictive of a clinical response to Cbl therapy.…”

Section: Discussionmentioning

confidence: 99%

Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing

Solomon

2005

Blood

136

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IntroductionWhile cobalamin (Cbl) deficiency classically causes macrocytic anemia, anemia can occur without macrocytosis, and both neurologic and cognitive dysfunction often develop in the absence of hematologic changes. 1-5 Symptoms consistent with Cbl deficiency, including paresthesias, unsteady gait, fatigue, and impaired memory, are commonly encountered in the ambulatory care setting, and early recognition of Cbl deficiency is important to prevent progressive, irreversible neurologic and cognitive impairment. 6,7 Although treatment with Cbl is often initiated after the finding of a low serum Cbl level, many patients with low Cbl levels are not Cbl deficient. 8,9 As a result, measurements of the Cbl-dependent metabolites, methylmalonic acid (MMA) and homocysteine (HCys), have recently been used to confirm the presence of Cbl deficiency. Retrospective studies of patients at academic medical centers with low serum Cbl levels and clinically overt Cbl deficiency found MMA and/or HCys levels more than 3 standard deviations (SD) above the normal mean in almost all patients. 8,10-12 Thus, algorithms for the diagnosis of Cbl deficiency were developed that suggest initial measurement of serum Cbl followed by determination of MMA and HCys when Cbl levels are intermediate or when suspicion of clinically significant Cbl deficiency is high. 8,[13][14][15][16][17][18][19][20] However, because little attention has been given to the study of patients with clinical findings consistent with Cbl deficiency but normal vitamin and metabolite levels, the negative predictive value of these tests is uncertain. Indeed, Cbl levels are normal in some patients with overt deficiency, 11 and currently available Cbl assay kits may not be reliable. 21,22 Moreover, because studies from academic centers usually employed special diagnostic or research laboratory facilities, their findings may not be representative of those obtainable in other ambulatory care settings.Thus, a retrospective review of patients evaluated for Cbl deficiency during a 10-year period at a staff model HMO utilizing a national commercial laboratory was performed. Initially, only patients with low serum Cbl levels or elevated metabolite levels received therapeutic trials of Cbl. However, in the seventh year of the study period, one patient with total absence of vibratory sensation in the iliac crest, knees, and ankles had complete recovery following 2 months of Cbl therapy despite normal Cbl, MMA, and HCys levels. Thereafter, therapy was offered to all patients with hematologic or neurologic abnormalities consistent with Cbl deficiency regardless of the results of screening studies. Patients, materials, and methods Laboratory methodsSerum Cbl was measured by the ADVIA Centaur chemiluminescence assay (Bayer Diagnostics, Tarrytown, NY). Normal Cbl values were 200 to 1100 pg/mL, but higher reference ranges have been suggested, 11,13,16,17,20,23,24 and the statement "patients with values less than 300 pg/mL may experience unexplained neuropsychiatric or hematologic abnormali...

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Section: Discussionmentioning

confidence: 99%

Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing

Solomon

2005

Blood

136

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“…Pyridoxine alone or in combination with thiamin and cyanocobalamin able to increase the synthesis 29 .…”

Section: Resultsmentioning

confidence: 99%

Antinociceptive and Anti-inflammatory Effects of Diclofenac Sodium Along with B Vitamins on Acute Pulpitis

Kabir

Jahan²,

Sultana³

et al. 2016

J Bangladesh Soc Physiol

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Background: In acute pulpitis intense pain and inflammatory changes are the main features of the patients. Diclofenac sodium is commonly used in the treatment of dental pain but has many side effects. To reduce the dose and duration of traditional analgesic drugs several members of B vitamins (B 1 , B 6 , B 12 ) can be used. Objective: To observe the combined effects of diclofenac sodium with B vitamins in acute pulpitis patients. Method: This prospective interventional study was carried out in the Department of Physiology, Sir Salimullah Medical College (SSMC), Dhaka between July 2014 and June 2015. Ethical permission was taken from the Institutional Ethics Committee (IEC) of SSMC. Sixty diagnosed acute pulpitis patients of both sexes, aged 18-40 years were included by purposive sampling from the Out Patient Department of Dental unit of SSMC. They were divided into 2 groups (30 patients in each group), as diclofenac treated group received only diclofenac sodium (DS) for 5 days and combined treated group received combination of DS with B vitamins (BV) for same duration (DS&BV). Both the groups were studied two times i.e before taking Diclofenac Sodium on day 1 (DS d 1), after taking Diclofenac Sodium on day 5 (DS d 5) and before taking both DS with B vitamins on day 1 (DS & BV d 1), after taking both DS with B Vitamins on day 5 (DS & BV d 5). The intensity of pain was scored by Visual Analog Scale (VAS) by using a Verbal Descriptive Scale (VDS) as a guide. Again, serum CRP level was measured by latex method. The statistical analysis was done by paired sample't' test. Results: In this study, VAS score (p<0.001, p<0.01 respectively) and serum CRP (p<0.001) level were significantly reduced in acute pulpitis patients after 5 days treatment of diclofenac sodium with B vitamins supplementation in comparison to their pre supplemented state and to the patients treated with only diclofenac sodium. Conclusion: The present study revealed that, the combination of diclofenac sodium along with B vitamins reduce pain and inflammation more efficiently than the treatment with diclofenac alone.

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“…DNA methylation is altered in the spinal cord in ALS patients [28]. High concentrations of methylcobalamin act as a competitive antagonist of S-adenosyl-L-methionine, a major methyl-donor, thus inhibiting DNA methylation in vitro, whereas low concentrations enhance DNA methylation [29]. It is possible that ultra-high doses of methylcobalamin have an impact on the epigenetic abnormality of ALS [30].…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effect of ultra-high dose methylcobalamin in wobbler mouse model of amyotrophic lateral sclerosis

Ikeda

Iwasaki

Kaji

2015

Journal of the Neurological Sciences

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Effect of cobalamin derivatives on in vitro enzymic DNA methylation: methylcobalamin can act as a methyl donor

Cited by 46 publications

References 19 publications

Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing

Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing

Antinociceptive and Anti-inflammatory Effects of Diclofenac Sodium Along with B Vitamins on Acute Pulpitis

Neuroprotective effect of ultra-high dose methylcobalamin in wobbler mouse model of amyotrophic lateral sclerosis

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