Can Berberine Supplements Improve Parkinson Patients?

Berberine is found in numerous plants of the Berberis genus of evergreen shrubs that are more commonly called barberry. The most common member of the genus is Berberis vulgaris but there are numerous popularly cultivated members such as Berberis thunbergii, Berberis candidula, and Berberis canadensis (American barberry). In addition to being found in plants of the Berberis family, berberine is present in plants of the Coptis genus (such as Coptis chinensis: Chinese goldthread), Oregon grape (Mahonia aquifolium), goldenseal (Hydrastis canadensis), and yellowroot (Xanthorhiza simplicissma). Numerous parts of the Berberis plant have been used for a variety of medicinal purposes including the roots, the bark, and the fruit.

Berberine has been used in China for decades as a treatment for diarrhea. More recently the use of berberine as an herbal therapy for hyperlipidemia and type 2 diabetes has been documented showing that oral berberine can result in lower levels of both blood lipids and blood glucose.

A recent paper published in the Nature journal, Signal Transduction and Targeted Therapy, suggests that oral berberine may have benefits in the treatment of Parkinson disease due to its ability to improve the levels of dopamine in the brain:

Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson’s disease by regulating gut microbiota

Parkinson disease is characterized by loss of neurons in a region of the brain called the substantia nigra that produce and release the neurotransmitter, dopamine. For this reason these neurons are referred to as dopaminergic neurons. Parkinson disease is a progressively debilitating disorder that encompasses both movement and non-movement dysfunction. Movement issues include tremor, bradykinesia, rigidity, and shuffling/stooped gait while the non-movement symptoms, include dysautonomia, neuropsychiatric problems, sensory (especially altered sense of smell) problems, and sleep difficulties.

The pathway for the synthesis of the catecholamines, which includes dopamine, norepinephrine, and epinephrine, from the amino acid tyrosine is detailed in my website in the Amino Acid Derivatives: Neurotransmitters, Nitric Oxide, and More page. The rate-limiting step in this pathway is catalyzed by the enzyme, tyrosine hydroxylase (TH).

Tyrosine hydroxylase requires the cofactor, tetrahydrobiopterin (BH₄), for its activity. In the course of converting tyrosine to levodopa (L-DOPA) the BH₄ is oxidized to dihydrobiopterin (BH₂). The BH₄ is normally regenerated from BH₂ through the action of the enzyme commonly called dihydropteridine reductase (quinoid dihydropteridine reductase: QDPR). When ingested berberine is converted to dihydroberberine by bacterial nitroreductase and this compound can contribute to the regeneration of BH₄ thereby increasing the potential for enhanced activity of TH.

Results from this publication show that oral administration of berberine, to mice, can influence the production of L-DOPA in the intestines by gut bacteria. The intestinal L-DOPA then enters the blood where it can be taken up by the brain and converted, via the action of DOPA decarboxylase, to dopamine. Why this process is beneficial to Parkinson patients stems from the fact that the main intervention in the progression of Parkinson disease is the administration of L-DOPA.

That intestinal bacteria contribute to L-DOPA production was demonstrated in this study through the use of antibiotic treatment. Mice treated with antibiotics had, on average 73% less intestinal bacteria than untreated mice. In addition, the increase in the level of DOPA and dopamine in the blood and brain of mice fed berberine was abolished by concurrent treatment with antibiotics.

The increases in brain dopamine in berberine treated mice was verified to originate in the gut by the administration of tracer labeled tyrosine. Blood, liver homogenates, brain homogenates, and gut bacteria were incubated with the tracer labeled tyrosine in vitro, followed by detection of labeled dopamine in each of the four systems. Results showed that labeled dopamine was detected in the brain homogenate and gut bacteria, but not in the blood nor liver homogenates. This indicates that the brain and intestinal bacteria are the main sites of

dopamine biosynthesis in vivo. The brain does not have dihydroberberine thus, it appears that the increased brain dopamine following berberine ingestion was from DOPA produced by gut bacteria.

To further demonstrate that intestinal bacteria utilize dihydroberberine to enhance DOPA production resulting in increased levels of dopamine in the brain the investigators utilized inhibitors of TH (bleomycin A5) and DOPA decarboxylase (benserazide). Administration of either inhibitor did not alter the levels of gut bacteria but did inhibit the production of DOPA and dopamine by the bacteria and resulted in reduced levels of dopamine in the brain.

Production of DOPA and dopamine by gut bacteria has been shown to occur in 4 genera were

Enterococcus, Escherichia-Shigella, Pseudomonas, and Lactobacillus. When partial germ free mice had two strains of bacteria, Enterococcus faecalis and Enterococcus faecium, transplanted to their guts there was evidence of both increased levels of DOPA and dopamine in the brain and evidence of improved brain function.

TAKE HOME: It is very likely that oral administration of berberine by patients with Parkinson disease may hold promise in aiding the reduction of the motor and non-motor symptoms of the disease. However, caution should be taken given the potential for alter prescription drug metabolism and function in the context of berberine ingestion due to the fact that berberine has been shown to be an inhibitor (weakly) of several cytochrome P450 (CYP) enzymes, specifically the CYP2D6 and CYP3A4 enzymes.