Randomized trial of two different doses of pyridoxine in the prevention of capecitabine-associated palmar-plantar erythrodysesthesia

Aim: The aim of the present study was to compare the efficacy of 200 mg versus 400 mg daily of pyridoxine in preventing or delaying the onset of palmar‐plantar erythrodysesthesia (PPE) in capecitabine‐treated patients. Methods: Patients with histologically confirmed breast cancer or colorectal cancer receiving single agent capecitabine started at 2000 to 2500 mg/m² daily from day 1 to 14 every 3 weeks were randomly assigned to receive 200 mg or 400 mg daily of pyridoxine for PPE prophylaxis. The primary endpoint was the reduction of incidence of grade 2 or greater PPE. Secondary endpoints were reduction of severe PPE and prolongation of time to development of grade 2 or greater PPE. Results: There were 56 patients in this study. The baseline characteristics were generally similar in both groups. The high dose arm had less PPE than the low dose arm (11 of 28 or 39% vs 20 of 28 or 71%, relative risk = 0.26 [0.08, 0.79], P = 0.031). Grade III PPE developed in 3 of 28 (10.7%) versus none in patients receiving 200 mg versus 400 mg pyridoxine, respectively (relative risk 2.12 [1.594, 2.819], P = 0.24). High dose pyridoxine had a longer time to development of grade 2 or greater PPE compared to the low dose arm, 87 days versus 62 days. The 400 mg pyridoxine group had, however, a worsened tumor response and tended to have greater tumor treatment failure and shorter time to treatment failure. Conclusion: With the limitation of sample size in this study, there was a trend to improve PPE incidence and time to event with a higher dose of pyridoxine. Further validation of these results in a larger population is warranted.     

Dietary intake of B-vitamins in mothers born a child with a congenital heart defect

Background Periconceptional use of multivitamins reduces the risk of a child with a congenital heart defect (CHD). Data on the impact of maternal diet, however, are lacking. Aim of the study We investigated the association between the maternal dietary intake of B-vitamins and having a child with a CHD. Methods A case-control study was performed in 192 mothers of a child with a CHD and 216 mothers of a healthy child. Mothers filled out food frequency questionnaires covering the current dietary intake, and general questionnaires at 17 months after the index-pregnancy. Maternal blood samples were taken to determine B-vitamin and plasma total homocysteine (tHcy) concentrations as nutritional biomarkers. Pregnant and lactating mothers and those with another diet compared with the preconceptional period were excluded for analysis. Case-mothers and controls were compared using the Mann-Whitney U test and logistic regression. Results The dietary intake of macronutrients and B-vitamins was comparable between both groups, but all mothers had a substantially lower median folate intake (cases 161 μg, controls 175 μg) than the Dutch recommended dietary allowance of 300 μg. Within the case-group, the intake of proteins and vitamin B₆ and the concentrations of serum vitamin B₁₂ and folate were significantly lower in hyperhomocysteinemics (tHcy ≥ 14.5 μmol/l) than in normohomocysteinemics. The maternal educational level was positively associated with B-vitamin intake, except for vitamin B₁₂ in controls. Low educated case-mothers showed a significantly lower median vitamin B₁₂ intake than controls (2.8 μg and 3.8 μg, P = 0.01). The CHD risk doubled if vitamin B₁₂ intake in these mothers reduced by 50% (OR 2.0; 95% CI: 1.1–3.5). Conclusions A diet low in vitamin B₁₂ is associated with an increased risk of a child with a CHD, especially in low educated women. A disbalance in the maternal intake of proteins and low folate intake may play a role as well, but needs further investigation. As hyperhomocysteinemia is a strong risk factor for adult cardiovascular disease, these data may imply that the hyperhomocysteinemic mothers and their children should be targeted for nutritional interventions.     

Amplitude-integrated encephalography in pyridoxine-dependent seizures and pyridoxine-responsive seizures

Pyridoxine-dependent seizures are rare in newborn infants, although recent data suggest that the prevalence probably is underestimated. In all newborn infants with recurrent epileptic seizures the general recommendation is to administer pyridoxine and simultaneously record an electroencephalogram (EEG). Conclusion: One infant with pyridoxine-responsive seizures and another with pyridoxine-dependent seizures had different electroclinical responses on amplitude-integrated EEG monitoring (aEEG) when pyridoxine was administered.     

Pyridoxine hydrochloride treatment of carpal tunnel syndrome: a review

It has been hypothesized that idiopathic carpal tunnel syndrome (CTS) is a manifestation of vitamin B6 deficiency. Some claim that B6 supplementation can alleviate symptoms. Others argue that pain relief occurs because of vitamin B6's anti-nociceptive properties or because B6 supplementation addresses an unrecognized peripheral neuropathy. Few studies on CTS and B6 employed electrodiagnostic techniques in diagnosis, and few showed a correlation between symptoms and improved electrodiagnostic parameters with supplementation. Other studies failed to measure or estimate B6 levels. Nevertheless, it appears reasonable to recommend vitamin B6 supplementation to people with CTS. Some patients will improve symptomatically with low risks of toxicity in recommended doses.     

Psychiatric manifestations of homocystinuria due to cystathionine β-synthase deficiency: Prevalence,natural history,and relationship to neurologic impairment and vitamin B6-responsiveness

Homocystinuria commonly affects the central nervous system (CNS), primarily as mental retardation, seizures, and stroke. Case reports have long suggested a predisposition to schizophrenia, but no careful study of predisposition to psychiatric illness has been performed. Accordingly, we evaluated 63 persons with homocystinuria due to cystathionine β-synthase deficiency for psychiatric disturbance, intelligence, evidence of other CNS problems, and responsiveness to vitamin B₆. The overall rate of clinically significant psychiatric disorders was 51%, predominated by four diagnostic categories: episodic depression (10%), chronic disorders of behavior (17%), chronic obsessive-compulsive disorder (5%), and personality disorders (19%). The average IQ was 80 ± 27 (1 SD); and an IQ of ≤ 79 was two-thirds more commom among vitamin B₆-nonresponsive patients compared to vitamin B₆-responsive patients. Aggressive behavior and other disorders of conduct were particularly common among patients with mental retardation and among vitamin B₆-nonresponsive patients.     

A double‐blind,randomized trial of pyridoxine versus placebo for the prevention of pegylated liposomal doxorubicin‐related hand‐foot syndrome in gynecologic oncology patients

BACKGROUND:

The objective of this study was to compare the incidence of hand‐foot syndrome (HFS) in patients who received pyridoxine versus placebo during pegylated liposomal doxorubicin (PLD) chemotherapy for recurrent ovarian, breast, or endometrial cancer.

METHODS:

Patients received PLD 40 mg/m² for a maximum of 6 cycles. Patients were assigned randomly to receive pyridoxine 100 mg twice daily (Group A) or placebo (Group B) and received standard HFS education. Patients completed the Functional Assessment of Cancer Therapy quality‐of‐life (QOL) questionnaire. The incidence of HFS as measured by common toxicity criteria was compared between groups. Analyses were conducted according to an intent‐to‐treat basis. Chi‐square tests or Fisher exact tests were used.

RESULTS:

Thirty‐four patients were enrolled (18 in Group A and 16 in Group B), and 5 patients were unevaluable for HFS assessment. Overall, 15 of 29 patients (52%) had HFS (all grades), and 10 of 29 patients (35%) had grade 2/3 events. Eight of 15 patients in Group A (53%) and 7 of 14 patients in Group B (50%) had HFS (P = .857). For grade 2/3 events, there was no difference between groups: Six of 15 events (40%) occurred in Group A, and 4 of 14 events (29%) occurred in Group B (P = .70). There was no difference in QOL scores between patients who had grade 2/3 HFS and patients who had grade 0/1 HFS. QOL analysis revealed that all patients had elevated social well being.

CONCLUSIONS:

Pyridoxine as administered in the current study did not prevent HFS in patients who received PLD. It is possible that QOL is not compromised in patients with HFS because they may have increased social well being while coping with their disease. Cancer 2010. © 2010 American Cancer Society.     

高效液相色谱法同时测定维生素B_6中两种生物活性成分

目的建立同时测定血浆中两种不同形式维生素B6（吡哆醇Pyridoxine,PN和吡哆醛Pyridoxal,PL）的高效液相色谱法。方法采用Luna C18色谱柱（150 mm×4.6 mm,5μm）,外标法,荧光检测器（波长为λE326 nm,λM400 nm）,流动相：甲醇-磷酸缓冲液（12∶88）,pH3.2,流速：1.2 ml/min进行分析。结果在2.5~160μg/ml浓度范围内,血中PN、PL测定的平均回收率分别为（86.0±4.74）%和（96.1±3.52）%,RSD分别为4.25%和3.85%。血中PN、PL的最低检出浓度分别是2.37、1.28μg/ml。结论该法灵敏、快速、准确、重复性好。