July 13 2010 NHS (UK)
Parkinson's disease is caused by a lack of dopamine in the brain
“Low vitamin D levels may increase a person's risk of developing Parkinson's disease,” BBC News has reported. Its website said that people with the lowest levels of vitamin D had a three-fold higher risk of developing Parkinson’s disease.
The news is based on research that followed over 3,000 Finnish people aged 50 to 79 years over a period of 29 years. Scientists took a measurement of the participants’ blood vitamin D levels and looked at how the subsequent risk of developing Parkinson’s disease over the period related to their blood vitamin D levels.
This high-quality, preliminary study showed an increased risk of developing Parkinson’s disease in those patients with the lowest vitamin D levels compared to the highest. However, Finland is a northern latitude country and so all the participants had relatively low levels of vitamin D, which the body produces using sunlight. Further research is needed to follow up whether this association is found in larger cohorts of people from different latitudes, who may have higher vitamin D levels than in this study.
The study was carried out by researchers from the national Institute for Health and Welfare in Finland and was funded by the US National Institutes of Health. The study was published in the peer-reviewed medical journal Archives of Neurology.
This study was covered accurately by BBC News, which pointed out that it is still uncertain if there is a level of vitamin D that is optimal for brain health or a point where vitamin D becomes toxic for humans.
This was a cohort study that looked at whether vitamin D levels in the blood earlier in life are associated with developing Parkinson’s disease later in life.
The researchers suggest that patients with Parkinson’s disease have been found to have lower vitamin D in cross-sectional studies. Problematically, cross-sectional studies, which only look at participants at one point in time, can only tell us about the vitamin D levels found in patients had already developed the disease.
To explore the possible relationship, the researchers wanted to see whether the vitamin D levels predicted Parkinson’s disease several decades later. This research looked at incidence in a population who had been followed for 29 years on average, and who were from northern latitudes (Finland) where exposure to the sun is limited and therefore the vitamin D they derived from the sun was usually low.
The researchers used data from the Mini-Finland Health Survey, which was carried out from 1978 to 1980 across 40 areas of Finland. They used data from 3,173 individuals who were free from Parkinson’s disease and psychotic disorders and who were aged between 50 and 79 years at the time of the survey.
The questionnaire contained data on socioeconomic background, medical history and lifestyle as well as baseline examination measurements of height, weight, blood pressure, cholesterol and vitamin D levels in the blood.
Cases of Parkinson’s disease were diagnosed and verified by two separate clinicians; a standard practice in the Finnish health system. Finnish patients with Parkinson’s disease can receive free medication after applying with a certificate issued by their treating neurologist. These certificates contain the symptom history and clinical findings in the patients. A neurologist from a social insurance institution then has to agree with the diagnosis described on the certificate for medication costs to be reimbursed.
Patients were followed up for an average of 29 years from their baseline examination until their diagnosis of Parkinson’s disease or death from other causes. During this period 50 members of the cohort developed Parkinson’s disease.
The researchers used an established statistical technique called the ‘Cox proportional hazards model’ to estimate the strength of association (relative risk) between vitamin D levels and the risk of developing Parkinson’s disease.
The researchers found that vitamin D concentration was lower among people with Parkinson’s disease but it was also associated with age, sex, marital status, leisure time, physical activity, smoking, alcohol consumption, BMI, diabetes, high blood pressure, blood cholesterol levels and the season in which the measurement was taken.
After adjusting for these confounding factors the researchers found that individuals with higher vitamin D levels had a lower risk of Parkinson’s disease compared to individuals with low vitamin D. The relative risk of developing Parkinson’s disease was 67% lower for the quarter of patients with the highest vitamin D levels, compared to the quarter of patients with the lowest vitamin D.
The researchers suggest that an optimal blood vitamin D concentration is 75-80 nmol/l. People in:
- the lowest quartile had vitamin D concentrations of 8 to 28 nmol/l (men), 7 to 25 nmol/l (women).
- the highest quartile had vitamin D concentrations in the range 57 to 159 nmol/l (men), 50 to 151 nmol/l (women).
The researchers say that a low serum vitamin D level predicts an elevated risk of Parkinson’s disease incidence. They say that although the study population as a whole had low vitamin D levels, a dose-response relationship was found; in other words, the lower the vitamin D level the higher the chance of Parkinson’s disease.
The study did not look at mechanisms underlying the association but the researchers suggest that vitamin D could act as an antioxidant, regulate neuron activity or act through detoxification mechanisms. They also say that an enzyme that makes the active form of vitamin D is found in high concentrations in the substantia nigra, the region of the brain that is affected most by Parkinson’s disease.
An editorial accompanying this research article says that some epidemiological studies have shown a latitudinal north-south gradient for Parkinson’s disease, similar to that seen for multiple sclerosis. However, it cautions that the evidence does not seen to be as strong for Parkinson’s as it is for multiple sclerosis (MS) because other studies have not confirmed the potential link.
The authors say the research study “provides the first promising human data to suggest that inadequate vitamin D status is associated with the risk of developing Parkinson’s disease”. They add that further work is needed in both basic and clinical arenas to understand the exact role, mechanisms, and optimum concentration of vitamin D in Parkinson’s disease.
This was a well-conducted study that looked prospectively at the role of vitamin D in the risk of developing Parkinson’s disease, although there are some limitations to the study that the researchers highlight:
- There were a small number of cases of Parkinson’s disease within this cohort. The researchers suggest this may have affected the accuracy of their estimates of risk.
- The study only took a single measurement of vitamin D, which may not reflect typical variations in concentrations across the seasons and across the lifetime of each individual.
- The blood samples had been stored for a relatively long time so the possibility that the vitamin D levels changed with storage cannot be excluded.
- The study did not address whether there is a critical time in life that suboptimal vitamin D levels affect the risk of Parkinson’s disease.
- The study did not include information on dietary intake of vitamin D from vitamin D rich foods such as oily fish. Such foods may contain other nutrients that may be beneficial against Parkinson’s disease.
- The risk factors for Parkinson’s disease are not well known and therefore not all possible influencing factors may have been taken into account in the analysis.
This relatively small, preliminary study was of good quality but the researchers say that larger follow-up cohort studies are needed. Clinical trials focusing on the effect of vitamin D supplements on the incidence of Parkinson’s disease also merit follow up, they say.
It is worth noting that as this study was conducted in people who all had low levels of vitamin D. It is not known, from this study, if there is a level of vitamin D above which there is no further reduction in the risk of Parkinson’s disease. This is important as excessive amounts of vitamin D taken as supplementation in people with normal levels can cause toxicity.
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Arch Neurol. 2010 Jul;67(7):808-11.
Knekt P, Kilkkinen A, Rissanen H, Marniemi J, Sääksjärvi K, Heliövaara M.
National Institute for Health and Welfare, Helsinki, Finland. paul.knekt at thl.fi
OBJECTIVE: To investigate whether serum vitamin D level predicts the risk of Parkinson disease. DESIGN: Cohort study.
SETTING: The study was based on the Mini-Finland Health Survey, which was conducted from 1978 to 1980, with Parkinson disease occurrence follow-up through the end of 2007. During the 29-year follow-up period, 50 incident Parkinson disease cases occurred. Serum 25-hydroxyvitamin D level was determined from frozen samples stored at baseline. Estimates of the relationship between serum vitamin D concentration and Parkinson disease incidence were calculated using the Cox model.
PARTICIPANTS: Three thousand one hundred seventy-three men and women, aged 50 to 79 years and free of Parkinson disease at baseline. Main Outcome Measure Parkinson disease incidence.
RESULTS: Individuals with higher serum vitamin D concentrations showed a reduced risk of Parkinson disease. The relative risk between the highest and lowest quartiles was 0.33 (95% confidence interval, 0.14-0.80) after adjustment for sex, age, marital status, education, alcohol consumption, leisure-time physical activity, smoking, body mass index, and month of blood draw.
CONCLUSIONS: The results are consistent with the suggestion that high vitamin D status provides protection against Parkinson disease. It cannot, however, be excluded that the finding is due to residual confounding and further studies are thus needed. PMID: 20625085
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