These findings are based on data from over 700 long-time residents
of California's Central Valley, one of America's primary crop-growing regions. Using a system based on geographical information in combina-tion with land-use maps and pesticide-use reporting data, the researchers estimated the overall exposures to
two commonly used agricultural pesticides-maneb and paraquat-from 1974 to 1999.
They found that exposure to either one or both of these pesticides was strongly related to PD. People exposed to a combination of both pesticides, particularly at a young age, had the highest risk of all-around four times greater than those with no such pesticide exposure (Am J Epidemiol, 2009; 169: 919-26).
The results are shocking, but this is not the first time that pesticides have been linked to Parkinson's. In fact, although PD is a disease of ageing, there is now a convincing body of evidence suggesting that pesticide exposure could be a major cause.
More worrying, it's not just agricultural pesticides that have been implicated. Several studies show that the pesticides we use in our homes and gardens may also dramatically increase our chances of developing the disease.
Perhaps some of the most compelling evidence so far comes from a family study conducted by researchers at the Duke University Medical Center and University of Miami Miller School of Medicine. Most studies examining the relationship between pesticide expos-ure and PD have been conducted in populations of unrelated individuals, but this multicentre study looked at the association in individuals of the same family-a design that makes it less likely that unconsidered factors could be influencing the results.
Using telephone interviews, the researchers quizzed 310 PD sufferers regarding their use of pesticides, and compared their answers with those
of 296 relatives and other related controls without the disease. They found that individuals with PD were significantly more likely to report using pesticides-either at home or at work-than their unaffected relatives.
Overall, the risk increased by 60 per cent, but varied depending on the frequency of pesticide use and the duration of exposure. Those with the highest exposures had the highest risk, but even those in the lowest exposure category were significantly more likely to have PD. Interestingly, the use of protective gear during pesticide application had no effect on the results (BMC Neurol, 2008; 8: 6).
Another US study has reported similar findings. Researchers from the University of Texas Health Science Center looked at pesticide exposure in an East Texas population and found that any type of exposure was strongly related to PD. However, the team also specifically looked at pesticide use in the home. They found that those who used rotenone or other pesticides in their gardens increased their chances of developing PD by more than 10 times (J Agromedicine, 2008; 13: 37-48).
Their findings are supported by previous evidence linking household pesticides to PD. Lorene Nelson and colleagues at Stanford University in California reported nearly a decade ago that using insecticides and herbicides in your home or garden
can double your risk of developing
the condition (Lancet, 2000; 355: 1701; http://news.bbc.co.uk/2/hi/ health/738020.stm). Their study involved more than 1000 people and was the first to show that it's not just those who work with pesticides who have increased risks of developing PD.
These human studies are only a small sample from the wealth of data connecting pesticides to this neurodegenerative disorder. Indeed, a 2006 review conducted by UK scientists identified a total of 40 studies focusing on the pesticides- Parkinson's link. These studies came from all over the world and consistently showed pesticides to be an important risk factor for PD (Environ Health Perspect, 2006; 114: 156-64).
Besides the evidence in humans, there's also a substantial amount of animal and laboratory data suggesting that pesticides have the potential to cause PD.
Mirroring the results of the latest UCLA study, both maneb and paraquat have been found to cause PD-like toxic effects in mice (Eur J Neurosci, 2003; 18: 589-600). As observed in humans, it appears that exposure to these two pesticides together has a greater neurotoxic effect than either pesticide alone (Environ Health Perspect, 2006; 114: 156-64).
Also, the timing of exposures appears to be important. One study noted no immediate changes in mice exposed to either maneb or paraquat as pups. However, when re-exposed to the pesticides as adults, they developed permanent and progressive brain-cell loss similar to that seen in PD. The researchers suggested that developmental exposure to neurotoxi-cants such as pesticides could be involved in the triggering of neuro-degenerative disorders, and may even be altering the normal ageing process (Neurotoxicology, 2002; 23: 621-33).
Other pesticides, including rotenone-a naturally derived pesticide commonly used in home gardening-have also demonstrated neurotoxic actions that could potentially play a role in the development of PD. Several plausible biological mechanisms have been suggested although, primarily, it appears that pesticides can cause selective degeneration of the dopa-minergic neurons of the substantia nigra (deeply pigmented gray matter) in the midbrain, a hallmark feature of Parkinson's (Environ Health Perspect, 2006; 114: 156-64; Nippon Yakurigaku Zasshi, 2002; 119: 15-20; Nature Neuroscience, 2000; 3: 1301-6).
Although such laboratory data may not necessary apply to humans, combined with the numerous studies linking human pesticide exposure to PD, it suggests that avoiding these toxic chemicals may play a major role in the prevention of PD-and possibly other neurodegenerative disorders as well.
Other chemical culprits
But the story doesn't end there. In addition to pesticides, a number of other environmental contaminants also appear to be involved in the development of Parkinson's.
Polychlorinated biphenyls (PCBs), for instance, are man-made organic compounds that were formerly-and widely-used in the construction of electrical and hydraulic equipment. They have been linked to PD in two occupational studies from the US showing that female workers exposed to PCBs were around two to three times more likely to die with PD compared with the rest of the general population (Environ Health, 2006; 5: 13; Epidemiology, 2006; 17: 8-13).
What's more, as with pesticides, there is considerable animal and laboratory evidence to back this up. It appears that even low levels of PCB exposure-as seen in the general population-has the potential to disrupt normal dopamine functioning in the brain, which could eventually lead to PD (Toxicol Sci, 2006; 92: 490-9).
Besides PCBs, heavy metals such as lead and manganese have also been associated likely to have PD as individuals with the lowest exposures (Environ Health Perspect, 2006; 114: 1872-6). In another study, workers with long-term exposure to manga-nese displayed several signs of brain degeneration as determined by a series of neurofunctional tests (Environ Res, 1994; 64: 151-80).
Other metals, such as aluminium, mercury, copper and iron, have also been linked to PD (Neuroepidemiology, 1999; 18: 303-8). It's possible that, as with pesticides, heavy metals can have permanent neurotoxic effects that may well be contributing to the development of PD.
Genes vs environment
Taken altogether, these data indicate the importance of the environment in neurological disorders such as PD. Experts now estimate that genes alone are responsible for less than 10 per cent of PD cases-and even then, environmental factors may be involved (Environ Health Perspect, 2009; 117: 117-21).
The most likely scenario in the vast majority of Parkinson's cases is that environmental factors interact with a person's genetic makeup to bring about PD. More research is needed to ascertain precisely how this happens, but it is likely that exposure to certain environmental toxicants such as pesticides-and particularly at a young age-play an important predisposing role.
Ultimately, this suggests that Parkinson's is not simply a disease of growing old. As is the case with more and more conditions, it is likely that PD and other dementias could be largely prevented by cleaning up our surroundings and living as non-toxic-ally as we can.
For more information on Parkinson's disease and the role of environment, see WDDTY vol 14 no 5.
Avoid pesticides. Use pest-prevention methods or non-toxic alternatives rather than poisonous pesticides. An all-purpose insect spray, for example, can be made up by mixing together one garlic bulb, one onion, 1 tbsp of cayenne pepper and 4 cups of water. Pour the mixture through a coffee filter, then add 1 tbsp of liquid soap and apply with a spray bottle. (For more tips, see WDDTY vol 19 no 2, pages 20-21.)
- Limit consumption of high-fat meat and fish, which are major sources of heavy metals and PCBs.
- Exercise. A large-scale US study reported that high levels of moderate-to-vigorous physical activity-such as jogging, cycling or aerobics-were associated with a lower risk of PD (Mov Disord, 2008; 23: 69-74).
- Maintain a healthy weight. Evidence suggests that people with a higher body mass index (BMI) are at an increased risk of PD (Neurology, 2006; 67: 1955-9).
- Drink tea. Human and animal evidence indicates that tea-drinking can reduce the risk of a number of neurological disorders, including PD, Alzheimer's and other dementias (CNS Neurosci Ther, 2008; 14: 352-65).
- Limit dairy intake. High intakes of dairy nearly doubled the risk of PD, particularly in men (Ann Neurol, 2002; 52: 793-801). Another study reported similar results, and found a slightly increased risk in women, too (Am J Epidemiol, 2007; 165: 998-1006).
- Take supplements. Several individual nutrients appear to be protective against PD, including vitamins E and B6, and coenzyme Q10 (Lancet Neurol, 2005; 4: 362-5; Neurology, 2006; 67: 315-8; Nervenarzt, 2007; 78: 1378-82). It is recommended that all high-risk groups take a multiple antioxidant supplement-but make sure it doesn't include iron, copper or manganese (see www.jacn.org/cgi/content/full/18/5/413 for details on dosages).
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