There are, literally, hundreds of thousands of potential toxins in the air, the soil, in your home, at your work, and in your food and water. Whether any given toxin causes PD has not yet been clinically proven. Effects of toxins, and the possibility of their causing PD-like symptoms, depends on chemical structure, concentration in the environment, duration of exposure (usually measured in months or years), the toxin’s ability to penetrate your skin, nose, lungs or gut and reach your brain, its ability to attach itself to the pigmented neurons in your substantia nigra, and its ability to damage your DNA or the proteins in your cells.
The toxin may act directly or through free radicals (an unstable atom or group of atoms that are highly reactive and capable of biological damage). Each cell in your body has a limited ability to repair the damaged DNA, to “soak-up” the free radicals. The molecules that “soak-up” the free radicals are called antioxidants. Antioxidants work by offering easy electron targets for the free radicals, thus “trapping” the electron and making it stable. Each cell has only a limited quantity of antioxidants.
While it has not been proven that free radicals cause PD, or that increasing your intake of antioxidants prevents PD, a diet that includes antioxidant-rich foods, such as blueberries, cranberries, apples, and blackberries, will certainly increase your body’s ability to fight off free radicals. While antioxidants are needed to soak-up or inactivate free radicals, not all free radicals are bad. Determining which free radicals are good and under which conditions is a challenge; one being met by a better understanding of the cell and its naturally occurring antioxidants. One such naturally occurring antioxidant is the pigmented melanin granules in the substantia nigra, the granules that give the nigra, the “black substance,” its name. Some of the toxins that have been linked to PD or PD-like symptoms include:
- Chlorine—including chlorine used in bleaches, detergents, and swimming pools; methylene chloride used in pharmaceuticals, chemical processing, and aerosols; perchloroethylene and tricholoroethylene used in adhesives and cleaning; and polyvinyl chloride used in plastics.
- Manganese—including exposure from mining or welding.
- Mercury—used (in the past) in dental amalgams, fluorescent lamps, thermometers, and in the preservative Thimerosol in vaccines.
- MPTP —a chemical used in making animal models of PD. ? Rotenone —a pesticide used in making animal models of PD.
Even though mercury has been linked to PD-like symptoms, the amount of mercury given off from dental amalgams is small—not enough to make you sick. The methyl mercury found in fish and other sea animals (clams, oysters, snails), is also not enough to make you sick. It is possible that the cumulative effect of mercury in one’s system could cause neurological symptoms; however, there is no proof that mercury in humans or animals causes PD.
Likewise, increased iron in the brain has been linked to PD. Interestingly, while the normal brain contains 50 mg of iron; the Parkinson brain contains five times as much iron: 250 mg. Iron helps several enzymes involved in DNA and protein synthesis and repair. Although there is no proof at this time that the increased iron in the substantia nigra is a cause of PD, many investigators are trying to develop drugs, chelators, which detoxify and remove metal ions from the brain.
The goal of iron chelation in the brain is to prevent any iron-mediated injury to the neurons. The MAO-B inhibitor, rasagiline is, in part, an iron chelator and some believe this may be partly responsible for their usefulness. Finally, some people wonder if manganese fumes from welding can cause PD. Manganese poisoning can result from exposure to manganese dust and vapors, such as occurs in certain miners and welders, and from the ingestion of food that is contaminated with man-ganese.
Manganese, when inhaled or ingested, is excreted through the kidney and feces, as well as through saliva, perspiration, and the lungs. Once manganese is absorbed, its distribution depends upon its transformation, its binding to the body’s proteins, and its entry into the brain. Welding, the process of joining metals together using a filler and an electric arc, produces fumes and gases that contain a number of elements, including manganese. Welding may cause upper respiratory symptoms, pulmonary edema (water on the lung), pulmonary fibrosis (scarring of the lung) and lung cancer. Welding has also been associated with bladder and throat cancers.
Neurologic complications include confusion and delusions from the fumes (called “fume fever”). Parkinson symptoms have been described in both miners and welders. Although manganese miners are known to develop PD symptoms from inhalation of manganese dust or ingestion of food contaminated with manganese, it’s unclear whether this also happens in welders. At Washington University in St. Louis, a study compared the features of PD in 15 career welders to control groups with PD. Researchers found that welders had a younger age at onset (46 years) of PD compared with controls (63 years). There was no difference in frequency of tremor, slowness of movement, rigidity, postural instability, family history, clinical depression, or dementia. All treated welders responded to levodopa.
Motor fluctuations and dyskinesias occurred at a similar frequency in welders and the control group. PET scans with 6-flurodopa obtained in several welders showed findings typical of PD. This suggests, but does not prove, that welding causes a PD-like disorder. There is a strong disagreement as to whether welding causes PD. Most experts believe welding does not cause PD. As post-mortem studies have not been done on welders, it is not known if the pathology of PD in welders is similar to or different from true PD.
Agent Orange is the name of herbicide developed for the military, primarily for use as a defoliant to destroy enemy cover during the Vietnam War (1964–1972), and is thought by some to cause PD. Agent Orange is a 50-50 mix of two chemicals, including tetrachlorodiben-zodioxin (TCDD), which were mixed with kerosene or diesel fuel and dispersed by aircraft. An estimated 19 million gallons of Agent Orange were used in Vietnam during the war. Part of the concern about Agent Orange was about its contamination with dioxin. Dioxins are found in nature and are related to toxins that may cause cancer. In laboratory tests on animals, dioxin causes several diseases but not, to date, PD.
The other concern about Agent Orange regards TCDD and how it affects the brain. Veterans who served in the military during the Vietnam War are now at an age range when PD occurs and many claim their PD is related to Agent Orange. However, it is not known if there’s a higher prevalence of PD among veterans who were exposed to Agent Orange versus age-matched controls. Likewise, it is not known if there’s a higher prevalence of PD among Vietnamese who were exposed to Agent Orange versus age-matched controls. Furthermore, individual veterans had different levels of exposure depending on their military tasks.
The likelihood is that, barring new developments, the role of Agent Orange in causing PD will stay unresolved. Some people wonder if drugs, either prescription or non-prescription, can cause PD. What the medical community has found is that PD symptoms, not true PD, can be caused by drugs, and these symptoms are reversible upon stopping the drug. In contrast, true PD is an irreversible disease. Occasionally a person with unrecognized PD is “unmasked” by taking drugs; the person’s PD would have appeared eventually, but it appeared sooner because of the drug. Drugs known to cause PD symptoms include haldol, mellaril, prolixin, stellazine, and thorazine. Called major tranquillizers (also known as neuroleptics), these were the first drugs successfully used to treat the symptoms of psychosis and schizophrenia.
Other drugs causing PD symptoms include orap, risperidal, trilafon, and zyprexa. These are newer drugs, and they have been used to successfully treat the symptoms of bi-polar disorder, obsessive-compulsive disorder, psychosis, and schizophrenia. As a rule, they are less likely to cause PD symptoms than haldol, prolixin, stellazine, and thorazine. Not all medications that cause PD symptoms treat psychiatric problems; compazine and reglan, drugs used to treat nausea, vomiting, and acid reflux, may also cause such symptoms. These drugs all have in common an ability to fully or partly block dopamine receptors in the brain.
In effect, they cause PD symptoms by making the receptors unavailable to the brain’s own dopamine. Drugs known to cause PD symptoms also include reserpine (a drug once used to lower blood pressure) and tetrabenazine (used to control dyskinesia, a condition described later). These two drugs deplete the brain of dopamine. This depletion is temporary and levels return to normal after the drugs are stopped.
The prevalence of PD symptoms in people taking these prescription drugs varies from 15–60% and depends on the drug, the dose, time on the drug, the person’s age (older people are more susceptible), and the person’s sensitivity; some people are more likely to develop PD symptoms than others. Usually, PD symptoms appear weeks or months after the drug is started (rarely sooner) and disappear weeks or months after the drug is stopped. The symptoms of drug-caused PD are almost indistinguishable from true PD; however there are two differences:
1. Drug-induced PD symptoms appear on both sides of the body at the same time. The symptoms of true PD appear first on one side of the body, and later on the other side.
2. The “pill-rolling,” resting tremor of PD is less common in drug-caused PD symptoms. An action tremor, one that appears when the hands are moving and one faster than the pill-rolling tremor, is characteristic of drug-caused PD symptoms.
It’s not known whether drug-caused PD symptoms are a “predictor” of the later development of PD. Drug-caused PD symptoms may be associated with dyskinesia—dance-like involuntary movements. Dyskinesia may involve the face, tongue, head and neck, trunk, arms and legs. The movements are called tardive (meaning delayed) dyskinesia because they appear after the drug is started, or sometimes after the drug is stopped. Although drug-caused PD symptoms and tardive dyskinesia are likely mediated by different mechanisms, the two may coexist in the same person. This combination presents a challenge because the treatment of one may aggravate the other.
In another category are drugs that cause permanent PD symptoms. Illegal drugs such as amphetamines, cocaine, and methamphetamine all deplete dopamine from stores in the brain and could, with chronic use, result in PD symptoms. The most notorious example of a drug that caused PD, and later became a means of creating an animal model of PD, is the drug abbreviated MPTP, a narcotic-like drug, the actions of which were described by Dr. J. William Langston.
The Case of the Frozen Addict, Langston describes how a young heroin addict, George Carillo, unknow-ingly injected himself with heroin that had been contaminated with MPTP. Over several days George became increasingly paralyzed and even lost the ability to talk. Medical personal at a county hospital ER were unable to find a cause or cure and after many inconclusive tests, he was sent to a special hospital unit.
In the hospital, George was diagnosed by Dr. Langston as having PD. Later, it was determined that George and several other addicts had developed PD as a result of injecting themselves with heroin contaminated with MPTP. MPTP was later shown by Dr. Langston (now at the California Parkinson Institute) and Dr. Stanley Burns (now at the Barrow Neurological Institute) to act as a “guided missile,” specifically destroying nerve cells in the substantia nigra, the same nerve cells destroyed by the process that causes PD.
The difference between MPTP-related PD and true PD is that, in true PD, the dying cells contain a round structure called a Lewy body , but this is absent in MPTP-caused PD. The Lewy body tells us something about what causes PD, but as yet researchers have not figured out exactly what it is. MPTP has served as an excellent means of causing PD in animals, which has provided researchers with insights into how PD may start and progress. It has also helped in the development of new drugs for PD.