B6 Depletion by Carbidopa

The effects of carbidopa on vitamin B6 in the human body (Part 1 of 4)

Chemical reactions in the body fall into one of two groups:

1. Reversible
2. Irreversible

Reverse Chemical Reactions

Estimates are that 99% of all chemical reactions in the body are reversible. With reversible chemical reactions, an equilibrium between the substrate and the product of metabolism occurs (see Figure 1).¹

Irreversible Chemical Reactions

Irreversible chemical reactions go in only one direction¹, from the substrate to a product of metabolism. Irreversible chemical reactions in the body tend to be bad, very bad. Irreversible reactions are definitive and quickly remove things from the body. Carbidopa binds irreversibly to vitamin B6 and vitamin B6-dependent enzymes. Every molecule of carbidopa that binds to a molecule of vitamin B6 permanently removes the B6 molecule or B6-dependent enzyme molecule from the system. Before 2000 prescription L-dopa without carbidopa was available. Plain prescription L-dopa without carbidopa, manufactured by three companies, was simultaneously stopped in 1999. Since 1999 the only prescription form of L-dopa contains carbidopa.

Carbidopa and benserazide (as found in Madopar, which is not available in the United States) bind irreversibly to vitamin B6 and vitamin B6 enzymes. Irreversible binding of carbidopa with vitamin B6 immediately deactivates and removes B6 from the system. The molecular weight of carbidopa and B6 are similar. Therefore, giving one milligram of carbidopa can remove one milligram of B6 from the system. The US recommended daily allowance of B6 is about 2 milligrams per day.² Therefore, the patient taking 200 mg of carbidopa per day can deactivate and remove 100 times the US recommended daily allowance of vitamin B6 from the system each day. Depending on the starting B6 health of the patient, the magnitude of B6 depletion over time can vary.^3,4,5,6,7,8

Figure 1

This website discusses and documents the effects of vitamin B6 depletion by carbidopa. In a recent paper, the following laboratory study documented the impact of carbidopa on vitamin B6 in humans, Figure 2. In patients taking carbidopa for more than three years:

• 79.2% of patients had a significant vitamin B6 deficiency
• 37.5% had vitamin B6 levels so low that they were undetectable by the lab

¹ Reversible vs. Irreversible Reactions – Chemistry LibreTexts last accessed December 10, 2021
² Vitamin B6 – Health Professional Fact Sheet (nih.gov) last accessed December 10, 2021
³ Ng LK, Chase TN, Colburn RW, Kopin IJ. Release of (3 H)dopamine by L-5-hydroxytryptophan. Brain Res. 1972;45(2):499–502.
⁴ Bertoldi M. Mammalian Dopa decarboxylase: structure, catalytic activity and inhibition. Arch Biochem Biophys. 2014;546:1–7.
⁵ Wu F, Christen P, Gehring H. A novel approach to inhibit intracellular vitamin B6-dependent enzymes: proof of principle with human and plasmodium ornithine decarboxylase and human histidine decarboxylase. FASEB J. 2011;25(7):2109–2122.
⁶ Cellini B, Montioli R, Oppici E, Voltattorni CB. Biochemical and computational approaches to improve the clinical treatment of dopa decarboxylase-related diseases: an overview. Open Biochem J. 2012;6:131–138.
⁷ Bartlett MG. Biochemistry of the water soluble vitamins: a lecture for first year pharmacy students. Am J Pharm Educ. 2003; 67(2):Article 64.
⁸ Palfreyman MG, Danzin C, Bey P, et al. Alpha-difluoromethyl DOPA, a new enzyme-activated irreversible inhibitor of aromatic L-amino acid decarboxylase. J Neurochem. 1978;31(4):927–932.