Failure of vitamin B6 to reverse the L-dopa effect in patients on a dopa decarboxylase inhibitor

Abstract

SUMMARY Seven patients with Parkinsonism previously on L-dopa were placed on a regimen of L-dopa and alpha methyl dopa hydrazine (a dopa decarboxylase inhibitor). Two of these patients had previously shown marked clinical deterioration of the L-dopa improvement when given pyridoxine. None of the seven patients receiving alpha methyl dopa hydrazine demonstrated any change in their condition when given pyridoxine. The failure of vitamin B6 to reverse the clinical effect of L-dopa in patients receiving both L-dopa and a peripheral dopa decarboxylase inhibitor suggests that reversal of the L-dopa effect induced by vitamin B6 is due to increasing the activity of the enzyme dopa decarboxylase outside the central nervous system.In patients with Parkinsonism receiving L-dopa (L-3, 4-dihydroxyphenylalanine), vitamin B6 has recently been shown to cause a loss or reversal of the L-dopa effect (Duvoisin, Yahr, and Cote, 1969; Yahr, Duvoisin, Schear, Barrett, and Hoehn, 1970 Sourkes, 1966). There is at the present time no explanation as to why a cofactor (B6), which is necessary for conversion of dopa to dopamine, when given in excessive amounts actually inhibits the clinical effects of L-dopa. At least two different possible mechanisms could explain this. Pyridoxine in excessive amounts could increase the activity of dopa decarboxylase in the periphery. This would increase the metabolism of L-dopa, lower L-dopa blood levels, and decrease the penetration and metabolism of L-dopa within the central nervous system. It is also possible that pyridoxine could act through a mechanism not involving dopa decarboxylase.We have evaluated the effects of pyridoxine on patients receiving both L-dopa and a dopa decarboxylase inhibitor, (alpha methyl dopa hydrazine). These observations help to explain the paradoxical effects of large amounts of pyridoxine in patients receiving L-dopa. METHODS AND RESULTSSeven patients with Parkinsonism who had been on L-dopa for at least one year were included in this study. These patients ranged in age from 43 to 67 with an average age of 57 years. The patients had had Parkinsonism for an average of seven years with a range of from four to 11 years. The patients had been evaluated according to the criteria of Hoehn

<i>L</i>-Dopa, B₆, and <i>α</i>-Methyldopa Hydrazine

“…Lechat et al [13] first demonstrated in animals that previous administration of a peri pheral dopa decarboxylase inhibitor would block the ability of pyridoxine to antagonize the antiparkinson properties of L-dopa. Our studies [11], as well as those of Yahr et al [21] and Papavasiliou et al [17], have clear ly shown this to be the case also in parkinsonian patients simultaneously treated with L-dopa and a dopa decarboxylase inhibitor. None of the pa tients showed loss of L-dopa effect when given pyridoxine.…”

“…Paradoxically, they showed vi tamin B0 to cause a loss or reversal of the L-dopa effect [5,22]. Others have shown that vitamin B0 failed to reverse the clinical effect of L-dopa in patients receiving both L-dopa and a peripheral dopa decarboxylase in hibitor [11,17]. This suggests that B0-induced reversal of the L-dopa ef fect is due to accelerated decarboxylation of L-dopa to dopamine in extra cerebral tissues.…”

Pyridoxal 5′‐phosphate deficiency causes a loss of aromatic l‐amino acid decarboxylase in patients and human neuroblastoma cells, implications for aromatic l‐amino acid decarboxylase and vitamin B6 deficiency states

“…Pyridoxine treatment has been demonstrated to reverse the clinical effect of l ‐dopa; however, when l ‐dopa was given in combination with a peripheral AADC inhibitor, such as carbidopa or benserazide, pyridoxine did not have this effect (Duvoisin et al. 1969; Klawans et al. 1971).…”

Potential Influences of Complementary Therapy on Motor and Non-Motor Complications in Parkinsonʼs Disease

“…carbidopa, benserazide) with levodopa may minimize this interaction. [66] In a prospective, population-based, cohort study of 5289 people, higher dietary intake of vitamin B 6 was associated with a significantly lower risk of incident PD among smokers only; however, no reduction in risk was observed for dietary folate or vitamin B 12 . [44] The authors postulated that the limitation of the effect to smokers might have been due to a combined benefit of vitamin B 6 and smoking, which has been independently associated with a lower risk of PD (see section 2.5).…”