May 25, 2020
Parkinson’s Disease: Hyperhomocysteinemia & The Levodopa Connection

Parkinson’s Disease: Hyperhomocysteinemia & The Levodopa Connection

A number of studies have now confirmed that treatment with the medication Levodopa leads to an increase in homocysteine levels in Parkinson’s Disease patients.

Scientific research has found that Homocysteine (Hcy) exerts multiple neurotoxic mechanisms that have been linked to the pathogenesis of neurodegenerative disorders, cardiovascular disease and many other serious health problems.

Levodopa is one of the main medications that is used to treat Parkinson’s disease symptoms. Levodopa is a chemical building-block that the body converts into dopamine. It replaces the dopamine that is lost in Parkinson’s.

It has been suggested that breakdown of L-dopa by catechol-O-methyltransferase results in increased homocysteine formation.

The studies seem to suggest that elevated homocysteine levels in Parkinson’s disease patients may have a number of serious consequences such as an increased risk of osteoporosis, dementia, cognitive impairment, cardiovascular disease, stroke and of course the potential for increased Parkinson’s disease progression.

Let’s take a look at some of the current scientific research below on levodopa, Parkinson’s disease and hyperhomocysteinemia.

Levodopa treatment leads to an increase in Homocysteine(Hcy) levels

Levodopa Increases Homocysteine StudiesChronic treatment with levodopa (LD), considered the standard treatment for PD, leads to an increase in homocysteine concentration in serum and cerebro-spinal fluid. [1]

Several studies observed elevated plasma Hcy levels in Parkinson’s Disease (PD) patients treated with L-dopa, compared to healthy controls and to patients with other neurodegenerative disorders. [2]

A study from 2010 published in the Calcified Tissue International Journal concluded that the findings indicate that hyperhomocysteinemia due to levodopa intake may be one additional risk factor for osteoporosis and fracture in PD patients. [5]

Another study from 2010 performed a medline search to identify all published studies on Homocysteine, cognitive dysfunction and dementia during the course of PD from 1966 to 31/03/2010.

The study concluded that the available data seems to indicate a potential role of L-dopa related hyperhomocysteinemia on cognitive impairment and dementia during the course of PD. [6]

A study from 2003 published in the archives of neurology found that levodopa-related hyperhomocysteinemia is associated with increased risk for coronary artery disease(CAD).

Levodopa therapy, rather than Parkinson’s Disease(PD) is a cause of hyperhomocysteinemia in patients with PD. [8]

Vitamin B6, B12 & Folic Acid – Methylation & Gene Mutations(MTHFR)

MTHFR Gene Mutation, Vitamin B12 & Parkinsons DiseaseElevated homocysteine levels are influenced by a number of genetic, dietary and environmental factors.

There are many nutrients which are essential for healthy methylation function, some of these include Vitamin B6, Vitamin B12 and Folic Acid.

A lack of dietary intake of any of the above nutrients will impact methylation function and consequently homocysteine levels.

One study from 2003 concluded that B-vitamin requirements necessary to maintain normal plasma homocysteine concentrations are higher in L-dopa-treated patients than in those not on L-dopa therapy. B-Vitamin supplements may be warranted for PD patients on L-dopa therapy. [9]

Leafy greens are an excellent dietary source of folate and individuals with gene mutations such as MTHFR should consume at least 1 cup daily in order to obtain enough folate.

Sardines are an excellent source of Vitamin B12 and contain many other beneficial nutrients for individuals with Parkinson’s Disease such as longchain anti-inflammatory Omega-3 fatty acids(EPA/DHA), immunomodulatory Vitamin D, selenium, Co-Enzyme Q10 and many others.

Polymorphism’s and gene mutations such as MTHFR(Methylenetetrahydrofolate reductase) are extremely common in the general population and can significantly impact methylation function and as a consequence affect homocysteine metabolism, leading to a rise in homocysteine levels.

It is also worth noting that the current scientific literature also suggests that blood tests such as serum Vitamin B12 are not an accurate indicator of true Vitamin B12 status.

In order to get a true picture of Vitamin B12 status, tests such as methylmalonic acid, homocysteine and holotranscobalamin(active b12 test) should also be checked.


[1] [Homocysteine and its role in pathogenesis of Parkinson’s disease and other neurodegenerative disorders].

[2] Elevated homocysteine levels in Parkinson’s Disease: is there anything besides L-dopa treatment?

[3] Genetic and environmental factors for hyperhomocysteinaemia and its clinical implications in Parkinson’s disease.

[4] Hyperhomocysteinemia in levodopa-treated patients with Parkinson’s disease dementia.

[5] Hyperhomocysteinemia due to levodopa treatment as a risk factor for osteoporosis in patients with Parkinson’s disease.

[6] Hyperhomocysteinemia in L-dopa treated patients with Parkinson’s disease: potential implications in cognitive dysfunction and dementia?

[7] Homocysteine and levodopa: should Parkinson disease patients receive preventative therapy?

[8] Elevated plasma homocysteine levels in patients treated with levodopa: association with vascular disease.

[9] Effect of L-dopa on plasma homocysteine in PD patients: relationship to B-vitamin status.
The information in this article has not been evaluated by the FDA and should not be used to diagnose, cure or treat any disease, implied or otherwise.

One thought on “Parkinson’s Disease: Hyperhomocysteinemia & The Levodopa Connection

  1. My husband is 80 years and has been suffering from PD for the past 15 years. Lately he started hallucinating and I didn’t know how to handle the situation. He cannot sleep and tried to find and catch the imaginary people who he thinks are real. he was taken Entacapone with Levodopa, Carbidopa, and Pramipexole and started physical therapy to strengthen muscles. nothing was really working to help his condition.I took him off the Siferol (with the doctor’s knowledge) and started him on parkinson’s herbal formula i ordered from Health Herbal Clinic, his symptoms totally declined over a 5 weeks use of the Parkinsons disease natural herbal formula.i read reviews from other previous patients who used the herbal formula, my husband is now active, he can now go about daily exercise!! his symptoms so much reduced that now I hardly notice them.Visit there website www. healthherbalclinicc. weebly. com or email Info@ healthherbalclinic. net

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