In 2014, Mary Hinz, MD, et al, published a paper that hypothesized that carbidopa depleted the body of vitamin B6 and that this decrease in B6 levels led to progressive neurodegeneration in patients with Parkinson’s disease. Two recent papers provide additional evidence that seems to support that assertion.
Issues with Carbidopa and Vitamin B6
L-DOPA is often used in the treatment of Parkinson’s disease. L-DOPA is converted in the body into dopamine; in order for this to occur, it has to be modified (decarboxylated) via an enzyme (called DOPA decarboxylase) which requires pyridoxal-5-phosphate, which is the active form of vitamin B6.
In order to avoid the adverse effects of L-DOPA stimulation of dopamine receptors in the body, which includes nausea, vomiting, dizziness and hypotension, L-DOPA is given with drugs called decarboxylase inhibitors, such as carbidopa and benserazide. These decarboxylase inhibitors block the decarboxylation of L-DOPA to dopamine in the body without altering this process in the brain. If these drugs accomplished this without additional effects, we’d have ourselves a winner; unfortunately, that isn’t the case.
Carbidopa binds to pyridoxal-5-phosphate (vitamin B6). Because this bond is irreversible, chronic treatment with carbidopa produces a long-term systemic vitamin B6 depletion. This depletion can be especially pronounced in those people treated with high doses of L-DOPA/carbidopa (i.e., more than 300-600 mg L-DOPA/day).
Vitamin B6 plays many important roles in neurotransmitter and amino acid metabolism and it is known that vitamin B6 deficiency can lead to depression, confusion and peripheral polyneuropathy – all conditions associated with neurotransmitter imbalance. Once more, vitamin B6 plays many other important functions in human metabolism, including folate metabolism, methylation, protein synthesis, carbohydrate and fat metabolism, mitochondrial function, blood formation and maintaining antioxidant status. That is to say, it is very important to maintain overall health.
Issues and risks associated with vitamin B6 deficiency in Parkinson’s patients were described as early as the 1970s; however, the measurement of vitamin B6 is still not routinely conducted, so there was no way to determine the extent of the damage.
Carbidopa Causes Vitamin B6 Depletion
That all changed with a recent paper, published in October 2020, which documents the degree of vitamin B6 depletion caused by carbidopa. This research showed that in patients taking carbidopa over a three year period, 79.2% had vitamin B6 deficiency (verified by laboratory testing) and in 37.5% of these patients, there was NO vitamin B6 detected on laboratory analyses. This study shows that taking carbidopa depletes vitamin B6 in most people over time.
We know that vitamin B6 plays a role in many vital metabolic processes. A second paper, published by a group of Chinese researchers showed that vitamin B6 deficiency was associated with increased overall mortality. If we couple this knowledge with the fact that between 1960 and 1975, when L-DOPA was given without carbidopa, that the rate of death in those diagnosed with Parkinson’s disease was decreasing, but that since the FDA approved carbidopa in 1975, that the Parkinson’s death rate has increased by over 600%, we may have found the culprit.
The good news is that we can eliminate the need for carbidopa by correcting the underlying neurotransmitter imbalances that cause L-DOPA induced nausea, vomiting, dizziness and hypotension via properly balanced amino acid therapy. This can be done at the same time dopamine levels are being raised and optimized using L-DOPA derived from plants (like Mucuna pruriens) along with laboratory testing to guide recommendations.
- Wilson MP, Plecko B, Mills PB, et al. Disorders affecting vitamin B6 metabolism. J Inherit Metab Dis 2019;42(4):629–646.
- Pazirandeh S, Burns DL. Overview of water-soluble vitamins. Waltham (MA): UpToDate; 2019. [updated 2019 Jul 1; 2019 Jun 6]. Available at:http://www.uptodate.com/. Accessed July 10, 2019.
- Paiardini A, Contestabile R, Buckle AM, et al. PLP-dependent enzymes. Biomed Res Int 2014;856076:1–2.
- Friedman SA. Levodopa and pyridoxine-deficient states. JAMA 1970; 214(8):1563.
- Müller T, van Laar T, Cornblath DR, et al. Peripheral neuropathy in Parkinson’s disease: levodopa exposure and implications for duodenal delivery. Parkinsonism Relat Disord 2013;19(5):501–507.
- Urban PP, Wellach I, Faiss S, et al. Subacute axonal neuropathy in Parkinson’s disease with cobalamin and vitamin B6 deficiency under duodopa therapy. Mov Disord 2010;25(11):1748–1752.