Parkinson’s Disease and Dopamine Deficiency in Asheville, NC
Parkinson’s disease (PD) is a neurodegenerative disorder that affects predominately dopamine-producing (“dopaminergic”) neurons in the part of the brain called the substantia nigra. This area of the brain is unique because it produces dopamine, which in the brain functions as a neurotransmitter—a chemical released by neurons to send signals to other nerve cells. The brain includes several distinct dopamine pathways, one of which plays a major role in reward-motivated behavior. Most types of rewards increase the level of dopamine in the brain. Other brain dopamine pathways are involved in motor control and in controlling the release of various hormones. Outside the central nervous system, dopamine functions primarily as a local chemical messenger. In blood vessels, it inhibits norepinephrine release and acts as a vasodilator. In the kidneys, it increases sodium excretion and urine output. In the pancreas, it reduces insulin production, which greatly impacts hunger and growth. In the digestive system, it reduces gastrointestinal motility and protects intestinal mucosa. In the immune system, it reduces the activity of lymphocytes.
As wide ranging as the effects of dopamine are in general function, in PD the loss of dopamine seems to lead to the symptoms that define PD. Symptoms generally develop slowly over years, although the age of onset and progression of symptoms is different from one person to another due to the diversity of the disease and the diversity of those afflicted. People with PD may experience:
- Tremor, mainly at rest and described as pill rolling tremor in hands. Other forms of tremor are possible
- Slowness of movements (bradykinesia)
- Limb rigidity
- Gait and balance problems
The cause of PD remains incompletely understood. Exposure to certain pesticides and history of traumatic brain injury (TBI) may increase risk while higher intake of vitamin D, caffeine, and tobacco may be associated with lower incidence. This by no means endorses tobacco use. For most people with PD, genes and environment may both contribute. While many Parkinson’s patients report one or more family members with the disease, it is not always clear that one or several genes are the cause. Similarly, while some patients suspect that exposure to one or another chemical or environmental toxin caused their PD, this hasn’t been demonstrated. Scientists currently believe that in the majority of cases, genetic and environmental factors interact to cause PD. If a continuum existed, with exclusively genetic causes at one end and exclusively environmental causes at the other, different PD patients would likely fall at many different places along that continuum.
Although there is no cure, management options vary and include medical, nutritional, and surgical. PD itself is not fatal, but disease complications can be serious. The Centers for Disease Control and Prevention (CDC) rated complications from PD as the 14th leading cause of death in the United States in 2015. Although estimates vary, about 50,000 people are diagnosed with PD in the U.S. each year and about half a million people have the disease. PD affects one in 100 people over age 60. While the average age at onset is 60, people have been diagnosed as young as 18. Because the rate of PD increases in older adults, the disease burden will increase as our lifespans lengthen unless prevention and treatment options improve. There is no scientifically validated preventive course to reduce the risk of its onset. The single biggest risk factor for Parkinson’s disease is advancing age. Men have a somewhat higher risk than women.
To maintain quality of life and control symptoms, people with PD need dopaminergic support because they lack dopamine in the central nervous system (CNS), mainly due to impairment of neurons in the substantia nigra. All FDA approved treatments for PD treat symptoms without slowing or halting the disease progression. Symptom control with levodopa has been effective since the 1960s, as it crosses the blood brain barrier into the CNS and is converted into dopamine by the enzyme aromatic L-amino acid decarboxylase located in serotonergic neurons. This reaction requires vitamin B6 be present or dopamine cannot be synthesized. Dosing levodopa optimally to control symptoms is difficult due to adverse effect.
To manage nausea, believed to occur when levodopa in the blood stream is converted into dopamine, carbidopa was added to standard PD treatments. Carbidopa prevents levodopa breakdown in the blood stream, but it also depletes body stores of vitamin B6. Supplementation with B6 inhibits carbidopa, which creates a difficult position. B6 is an important in the body, being required for optimal function in at least 300 (discovered) human biochemical pathways, including helping the body make the neurotransmitters serotonin and norepinephrine, which influence mood, and the hormone melatonin, which helps regulate the body clock. Depression and sleep disturbances are common side effects with conventional PD therapy. In fact, since carbidopa was added to standard of care protocols for PD in 1975, the PD death rate has increased by over 300% (see graph).Carbidopa-levodopa drug combinations remains standard of care for PD. Treatment with levodopa, critical for symptom management and the only known path to increase CNS dopamine levels is also toxic to serotonin producing neurons, which could further explain side effects of levodopa treatment.
I believe management of levodopa side effects doesn’t require carbidopa. By supporting B6 levels and further supporting the relative nutritional deficiencies that are the hallmarks of PD, it need not be a progressive disease. I believe a PD diagnosis can be managed, and that we can preserve quality of life and allow normal aging.
Parkinson’s disease death rates in the United States between 1976 and 2011, all ages, age-adjusted, male and female.