Homocysteine and Parkinson’s disease: should you be tested?
Long-term levodopa can quietly use up key B vitamins. Nutritional therapist Melody Mackeown on why that matters for your nerves and balance, and what to ask for.
If you live with Parkinson’s disease and take levodopa, your B vitamin status is worth knowing about. The research on homocysteine and Parkinson’s disease points to a clear link between levodopa and B vitamins: the way the body breaks down this medication draws on Vitamin B12, folate, and Vitamin B6, and over years of treatment some people can start to run low. This article explains why it happens, what to look out for, and which tests are worth discussing.
In this article, we'll explore:
Why levodopa affects B vitamins
Levodopa remains a very effective medication for Parkinson’s disease, and for many people, it is taken for years, often at gradually increasing doses. What is less widely known is that the way the body processes levodopa places extra demand on several B vitamins.
One of the primary routes for breaking down levodopa is methylation, carried out by an enzyme called COMT (catechol-O-methyltransferase). Each time levodopa is methylated, the body produces homocysteine as a by-product. In simple terms, more levodopa can mean more homocysteine.
To keep homocysteine in check, the body relies on three nutrients:
Folate and vitamin B12, which recycle homocysteine back into methionine
Vitamin B6, which converts homocysteine into other useful compounds, such as cysteine
Over years of treatment, this extra workload may draw down vitamin B12 and folate in some people, allowing homocysteine to build up.
The Vitamin B6 connection
Vitamin B6 deserves its own attention. Levodopa is almost always combined with a second drug that stops it being converted to dopamine before it reaches the brain. In the UK, this is usually carbidopa (in co-careldopa, such as Sinemet) or benserazide (in co-beneldopa, such as Madopar).
Both drugs work by binding to pyridoxal 5’-phosphate, the active form of vitamin B6. This is how they do their job, but it also means they can lower vitamin B6 levels, particularly at higher doses or with intestinal gel formulations. Case reports have linked severe vitamin B6 deficiency in people taking these medicines to neuropathy, anaemia, and, rarely, seizures.
Why this matters: nerves, balance, and more
Raised homocysteine and low vitamin B12 or vitamin B6 have all been associated with peripheral neuropathy, which is damage to the nerves in the hands and feet. Signs can include:
Numbness, tingling or pins and needles
Burning or shooting pain in the feet or hands
Reduced sensation, which can affect balance and increase the risk of falls
Because balance problems, pain, and altered sensation are also common in Parkinson’s disease, neuropathy can easily be put down to the condition itself. However, a low B vitamin level is one cause that is worth ruling out because it can be checked.
Raised homocysteine has also been studied in relation to cognition, mood, and cardiovascular health more generally, which is another reason it is worth monitoring.
Who may be at greater risk?
Levodopa is not the only factor. The risk of low B vitamin status tends to rise when several of the following overlap:
Age: vitamin B12 absorption naturally declines over time, partly because stomach acid production falls
Other medications: acid-suppressing medicines (such as proton pump inhibitors) and metformin for type 2 diabetes can reduce vitamin B12 absorption
Digestive health: low stomach acid, H. pylori infection and other gut conditions can affect absorption
Diet and appetite: plant-based diets, reduced appetite or unintended weight loss can all lower intake
Medication dose: higher levodopa doses or intestinal gel therapy
When several of these sit alongside long-term levodopa, monitoring becomes even more worthwhile.
Which blood tests are worth asking about?
Standard blood tests do not always tell the full story, so it helps to know which markers can add useful information:
Vitamin B12: A result within the normal range can sometimes hide a functional deficiency at the tissue level
Methylmalonic acid (MMA) or active B12 (holotranscobalamin): these can help reveal a deficiency that a standard B12 test misses
Folate: ideally checked alongside B12, as the two work together
Vitamin B6: not always included in routine testing, so it may need to be specifically requested
Homocysteine: useful to track, but in people taking levodopa, it rises partly because of the medication itself, so it needs careful interpretation rather than being read in isolation
Baseline testing before symptoms develop is especially valuable because it gives you and your healthcare team something to compare with over time.
If your GP or neurologist does not feel testing is needed, private testing is also available, including through a nutritional therapist, and any results can be shared with your GP.
What can help?
If you are on long-term levodopa, regular review of your B vitamin status is a sensible principle, rather than waiting for symptoms to appear. Correcting a genuine deficiency early is usually more straightforward than addressing problems once they are established.
A few broader principles are worth keeping in mind:
Food choices need balancing: many foods that provide Vitamin B12 and Vitamin B6 are also rich in protein, which can compete with levodopa for absorption. This is one reason a personalised approach works better than general advice.
One change at a time: if supplementation is recommended, introducing it as a single, deliberate change makes it easier to see whether it is helping.
Let results guide dosing: more is not better. Very high intakes of vitamin B6 can themselves cause nerve problems, and the form and timing of vitamin B6 matter in relation to levodopa medication.
Retest: follow-up blood tests show whether an approach is working and whether anything needs adjusting.
What this looks like for you will depend on your diet, medication history, digestive health, and any symptoms already present.
What does the research say about homocysteine and Parkinson’s disease?
The link between levodopa and raised homocysteine is well described and is one of the more consistently reproduced findings in Parkinson’s disease nutrition research. Studies have also linked levodopa exposure to higher methylmalonic acid and lower vitamin B12 in people who develop neuropathy, and with lower active vitamin B6 compared with people not yet taking levodopa.
What is less certain is whether correcting these levels prevents or reverses neuropathy. Despite this, the testing is simple, deficiencies are treatable, and the potential consequences of missing them are significant. That makes a strong practical case for monitoring.
Key takeaways
Long-term levodopa places extra demand on vitamin B12, folate, and vitamin B6, and over time, this can leave some people running low and allow homocysteine to rise. Low B vitamin levels have been linked with peripheral neuropathy, which is easy to mistake for Parkinson’s disease itself. The research is still unclear on how much correcting these levels makes a difference to neuropathy, but the tests are simple, and knowing your baseline gives you and your healthcare team something to compare with over time. If you take levodopa, it is worth asking your GP or neurologist about checking your B vitamin status, and if you notice new numbness, tingling, or changes in your balance, mention it rather than assuming it is part of the condition.
Work with Melody
Melody Mackeown is a Nutritional Therapist specialising in Parkinson’s disease and digestive health. She holds a BSc in Psychology, an MSc in Personalised Nutrition, and a Dip ION from the Institute for Optimum Nutrition, London. She is registered with BANT and CNHC, and supports individuals living with symptoms of Parkinsonism, an existing diagnosis, or those concerned about their risk.
Melody works through the lens of personalised nutrition, drawing on functional testing where appropriate to build a tailored plan around each individual’s unique biochemistry, symptoms and goals.
"If you'd like to find out more about working with me, visit my profile."
References
Kim JH, Jin S, Eo H, Oh MS, Lim Y. Two faces of catechol-O-methyltransferase inhibitor on one-carbon metabolism in Parkinson’s disease: a meta-analysis. Nutrients. 2023;15(4):901. doi:10.3390/nu15040901
Quan Y, Xu J, Xu Q, Guo Z, Ou R, Shang H, Wei Q. Association between the risk and severity of Parkinson’s disease and plasma homocysteine, vitamin B12 and folate levels: a systematic review and meta-analysis. Front Aging Neurosci. 2023;15:1254824. doi:10.3389/fnagi.2023.1254824
Periñán MT, Macías-García D, Jesús S, et al. Homocysteine levels, genetic background, and cognitive impairment in Parkinson’s disease. J Neurol. 2023;270(1):477–485. doi:10.1007/s00415-022-11361-y
Oral levodopa therapy, vitamin B6 and peripheral neuropathy: a cross-sectional observational study. Mov Disord Clin Pract. 2024. doi:10.1002/mdc3.14243
Wise A, Lemus HN, Fields M, Swan M, Bressman S. Refractory seizures secondary to vitamin B6 deficiency in Parkinson disease: the role of carbidopa-levodopa. Case Rep Neurol. 2022.
Disclaimer
This article is for informational purposes only and does not replace medical advice. Do not change medication, start supplements, or make substantial dietary changes without discussing them with the appropriate healthcare professional.
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