People with Parkinson’s disease (PD) often hear about how protein can interfere with carbidopa/levodopa, but fewer realize that it is also important to pay attention to Vitamin B6 and B12. Carbidopa/levodopa can interfere with Vitamin B6 and Vitamin B12 processing, causing deficiencies in these vitamins. Low levels of Vitamin B6 and B12 can cause or worsen many neurologic symptoms such as numbness and tingling of hands and feet), depression, fatigue and walking problems. In rare cases, Vitamin B6 deficiency can lead to seizures.
As a result, the Food and Drug Administration (FDA) is now requiring carbidopa/levodopa manufacturers to change the labeling of all levodopa products to include a warning that they can cause Vitamin B6 deficiency.
Carbidopa/levodopa remains the most effective treatment for PD but its metabolism uses up B6 and B12 in ways that can impact overall health. Understanding these vitamin relationships can help people with PD and their care partners know when testing or supplementation may support general neurologic health and wellbeing.
Today we will explore why carbidopa/levodopa may cause Vitamin B6, as well as Vitamin B12 deficiency, what the potential consequences are, and what can be done to correct the problem.
How does Levodopa affect Vitamin B6 and B12?
Carbidopa/levodopa and Vitamin B6 Interaction
Levodopa is converted into dopamine once it reaches the brain, where it replaces the dopamine lost in PD. However, without combining levodopa with carbidopa, much of the levodopa would be converted into dopamine in the bloodstream before reaching the brain. This would be a problem because only levodopa crosses the blood-brain barrier; dopamine does not. Therefore, for the oral levodopa to be effective, it needs to remain as levodopa until it enters the brain.
Without carbidopa, so much levodopa would need to be ingested to allow for a small amount to make it into the brain, that the side effects of the levodopa, specifically nausea, would not be tolerated by most people. The development of the combination medication carbidopa/levodopa was transformative for the field of Parkinson’s disease, and this medication remains the most effective treatment today.
But how does carbidopa block the conversion of levodopa into dopamine? It inactivates Vitamin B6 which is a cofactor for the enzyme that converts levodopa into dopamine. Therefore, with carbidopa around, the enzyme that converts levodopa into dopamine does not work as well and less levodopa is converted into dopamine in the bloodstream and more makes it into the brain.
For most individuals, despite the fact that carbidopa binds to Vitamin B6, vitamin levels remain normal because it is replenished readily in a balanced diet. However, it is possible for carbidopa to contribute to Vitamin B6 deficiency, particularly in people on high doses of oral levodopa (>1000 mg/day).
The Role of Vitamin B6 in Your Body
Vitamin B6 supports many vital functions within the body, including neurotransmitter production (dopamine, serotonin, GABA), red blood cell formation, immune function, and nerve health. Symptoms of Vitamin B6 deficiency include fatigue, anemia, depression, confusion/cognitive issues, and peripheral neuropathy such as numbness, tingling, or balance problems. In severe cases, it can even lead to seizures. A recent review by the FDA of 14 cases of seizures in people with PD taking levodopa prompted the change in levodopa labelling. Of the 14 cases reviewed, all were taking doses over 1000 mg per day Vitamin B6 deficiency occurred more rapidly from onset of treatment in those taking over 1500 mg per day. Vitamin B6 levels can be checked with a blood test and if found to be low, can be corrected with oral supplementation.
Carbidopa/levodopa and Vitamin B12
As discussed above, without carbidopa, levodopa would be converted into dopamine in the bloodstream via a Vitamin B6-dependent enzyme. There is a second pathway that breaks down levodopa, via the enzyme catechol-O-methyltransferase (COMT). This enzyme requires vitamin B12, B6, and folate as cofactors. This pathway also converts methionine to homocysteine. Therefore, chronic levodopa use can accelerate the consumption of these B vitamins and can contribute to elevated homocysteine levels.
Vitamin B12 plays a key role in nerve function, red blood cell production, and DNA synthesis. Vitamin B12 deficiency in general is very common as people age due to reduced stomach acid and impaired vitamin absorption. Risk factors for deficiency include long-term antacid medications use, metformin therapy, GI disorders, surgery, and vegetarian/vegan diets. And PD patients are even more likely to have Vitamin B12 deficiency than the general older population because of the utilization of this vitamin in levodopa metabolism.
Vitamin B12 deficiency symptoms include fatigue, peripheral neuropathy, anemia, depression, and cognitive issues. It is also associated with elevated homocysteine which may be directly harmful as well. Vitamin B12 levels can be checked with a blood test and repleted with supplementation.
Should People with PD Take Vitamin Supplements?
If diet alone is not able to correct vitamin levels, supplements can also be an option. It is important to first test the levels and consult your doctor before taking supplements with PD. If levels are low, supplementation is usually safe, and effective. Vitamin B12 may be given orally, sublingually, or by injection, depending on absorption. Vitamin B6 is typically supplemented at modest doses to avoid toxicity. Taking high-dose supplements can be dangerous and is discouraged, especially for Vitamin B6.
Tips & Takeaways
- Vitamin B6 helps convert levodopa to dopamine, and carbidopa blocks this conversion outside the brain, so more medication reaches its target.
- Vitamin B6 deficiency can occur in people taking carbidopa/levodopa, especially those on high-dose oral therapy (above 1000 mg a day.)
- Vitamin B12 deficiency is common in older adults and may be even more frequent in PD.
- Both deficiencies can cause peripheral neuropathy, leading to numbness, tingling, pain, and balance problems that worsen mobility.
- In rare cases, Vitamin B6 deficiency can cause seizures.
- The FDA now requires manufacturers of levodopa products to add a warning that levodopa can lead to Vitamin B6 deficiency.
- Levodopa metabolism raises homocysteine, which may contribute independently to nerve injury.
- Simple blood tests can measure vitamin levels, and supplementation is usually safe and effective when needed.
- Avoid high-dose vitamin supplements without medical guidance, especially Vitamin B6, which can cause nerve damage in excess.
This blog was written by Clark Jones, PhD, and was reviewed, edited, and approved by Dr. Rebecca Gilbert.