Acta Neurol Scand 2015: 132: 242–250 DOI: 10.1111/ane.12390
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA
Vitamin D deficiency in Parkinson’s disease patients with orthostatic hypotension Jang W, Park J, Kim JS, Youn J, Oh E, Kwon KY, Jo KD, Lee MK, Kim H-T. Vitamin D deficiency in Parkinson’s disease patients with orthostatic hypotension. Acta Neurol Scand 2015: 132: 242–250. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objectives – The purpose of our study was to investigate the associations between serum vitamin D3 levels and orthostatic hypotension (OH) in patients with Parkinson’s disease (PD). Materials and methods – Fifty-five patients with PD were enrolled in this study. Blood pressure (BP) measurements were gathered while the patients were in the supine position and while standing up. Then, the patients were divided into two groups: PD patients with and without OH. We compared the levels of serum 25-hydroxyvitamin D3 and 1, 25dihydroxyvitamin D3 (calcitriol) between the two groups. Results – Serum 25-hydroxyvitamin D and calcitriol levels were significantly decreased in patients with OH compared with those without OH. The systolic and diastolic BPs and symptom severities significantly negatively correlated with the serum 25-hydroxyvitamin D and calcitriol levels. Conclusions – Although the underlying mechanism for this association is not fully understood, our results suggest that low vitamin D status is associated with OH in patients with PD.
W. Jang1,*, J. Park2,*, J. S. Kim3, J. Youn4, E. Oh5, K. Y. Kwon6, K. D. Jo1, M. K. Lee1, H.-T. Kim7 1 Department of Neurology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea; 2Department of Neurology, Haeundae Paik Hospital, Inje University, Busan, Korea; 3Department of Neurology, Soonchunhyang University College of Medicine, Seoul, Korea; 4Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 5Department of Neurology, Chungnam National University Hospital, College of Medicine, Daejeon, Korea; 6Department of Family Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 7Department of Neurology, Hanyang University College of Medicine, Seoul, Korea Key words: Parkinson’s disease; orthostatic hypotension; 25-hydroxyvitamin D; calcitriol
K. D. Jo, Department of Neurology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Bangdong-ri, Sacheon-myeon, Gangneung-si, Gangwondo 210-711, Korea Tel.: +82 33 610 3196 Fax: +82 33 610 3196 e-mail: [email protected] W. Jang, Department of Neurology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Bangdong-ri, Sacheon-myeon, Gangneung-si, Gangwondo 210-711, Korea Tel.: +82 33 610 3197 Fax: +82 33 610 3197 e-mail: [email protected] *These two authors contributed equally to this work. W. Jang, J. Park2, J. S. Kim, J. Youn, E. Oh are the part of KOJYP study group Accepted for publication 4 February 2015
Introduction
Beyond classical motor functions, non-motor symptoms (NMSs) are now regarded as important components of Parkinson’s disease (PD) because they are commonly found and substantially affect the quality of life of patients with PD (1). Among these symptoms, autonomic dysfunction has been reported in the various stages of PD, and orthostatic hypotension (OH) is one of the most common and disabling symptoms. Although OH is an important and challenging 242
problem affecting the patients with PD, there is insufficient evidence for specific PD-related OH treatment. Vitamin D plays an important role as a hormone with autocrine and paracrine functions that affect bone and mineral metabolism. Recently, several studies have revealed the additional role of vitamin D in neuroprotection, although the exact mechanism by which vitamin D protects neuronal cells against cytotoxic damage has not been fully investigated (2–4). Considering that the pathophysiology of OH in PD is thought to be associated with the
Vitamin D and OH in PD patients impairment of sympathetic neurons because of the neurodegenerative process, the neuroprotective properties of vitamin D may be associated with OH in PD. Furthermore, low vitamin D levels have recently been proposed to play an important role in PD pathogenesis and progression, and vitamin D receptor polymorphisms may also play a role in the development of PD, as shown in certain genetic studies (5–7). In particular, Suzuki et al. suggest that the FokI/CC genotype of the vitamin D receptor gene is associated with a mild form of PD, and it has been reported that the FokI C allele is significantly higher in patients with PD than in controls in a Hungarian population (6, 7). However, Petersen et al. reported no association between PD and vitamin D receptor polymorphism or 25-hydroxyvitamin D levels in the Faroe Islands population, which has double the prevalence of PD (8). Therefore, the role of vitamin D in PD remains controversial. There is also evidence that vitamin D may influence systolic and diastolic blood pressure (BP) and may affect vasomotor and cardiac function in response to orthostasis (9). Therefore, neurocirculatory control of vitamin D itself also may play a role in the pathophysiology of OH in patients with PD (10). In this study, we investigated the association between serum vitamin D levels and the presence of OH in patients with PD as well as the correlation between vitamin D levels and disease severity. Materials and methods Patients
This study was designed as a cross-sectional, monocentre, observational study of 55 patients with PD. All patients with PD participated in the Neurology Clinic of Gangneung Asan Hospital from February to September 2013. The patients were diagnosed according to the criteria issued by the United Kingdom Parkinson’s Disease Society Brain Bank (11). The exclusion criteria were as follows: (i) cognitive impairment (MMSE-K
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA
Vitamin D deficiency in Parkinson’s disease patients with orthostatic hypotension Jang W, Park J, Kim JS, Youn J, Oh E, Kwon KY, Jo KD, Lee MK, Kim H-T. Vitamin D deficiency in Parkinson’s disease patients with orthostatic hypotension. Acta Neurol Scand 2015: 132: 242–250. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objectives – The purpose of our study was to investigate the associations between serum vitamin D3 levels and orthostatic hypotension (OH) in patients with Parkinson’s disease (PD). Materials and methods – Fifty-five patients with PD were enrolled in this study. Blood pressure (BP) measurements were gathered while the patients were in the supine position and while standing up. Then, the patients were divided into two groups: PD patients with and without OH. We compared the levels of serum 25-hydroxyvitamin D3 and 1, 25dihydroxyvitamin D3 (calcitriol) between the two groups. Results – Serum 25-hydroxyvitamin D and calcitriol levels were significantly decreased in patients with OH compared with those without OH. The systolic and diastolic BPs and symptom severities significantly negatively correlated with the serum 25-hydroxyvitamin D and calcitriol levels. Conclusions – Although the underlying mechanism for this association is not fully understood, our results suggest that low vitamin D status is associated with OH in patients with PD.
W. Jang1,*, J. Park2,*, J. S. Kim3, J. Youn4, E. Oh5, K. Y. Kwon6, K. D. Jo1, M. K. Lee1, H.-T. Kim7 1 Department of Neurology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea; 2Department of Neurology, Haeundae Paik Hospital, Inje University, Busan, Korea; 3Department of Neurology, Soonchunhyang University College of Medicine, Seoul, Korea; 4Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 5Department of Neurology, Chungnam National University Hospital, College of Medicine, Daejeon, Korea; 6Department of Family Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 7Department of Neurology, Hanyang University College of Medicine, Seoul, Korea Key words: Parkinson’s disease; orthostatic hypotension; 25-hydroxyvitamin D; calcitriol
K. D. Jo, Department of Neurology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Bangdong-ri, Sacheon-myeon, Gangneung-si, Gangwondo 210-711, Korea Tel.: +82 33 610 3196 Fax: +82 33 610 3196 e-mail: [email protected] W. Jang, Department of Neurology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Bangdong-ri, Sacheon-myeon, Gangneung-si, Gangwondo 210-711, Korea Tel.: +82 33 610 3197 Fax: +82 33 610 3197 e-mail: [email protected] *These two authors contributed equally to this work. W. Jang, J. Park2, J. S. Kim, J. Youn, E. Oh are the part of KOJYP study group Accepted for publication 4 February 2015
Introduction
Beyond classical motor functions, non-motor symptoms (NMSs) are now regarded as important components of Parkinson’s disease (PD) because they are commonly found and substantially affect the quality of life of patients with PD (1). Among these symptoms, autonomic dysfunction has been reported in the various stages of PD, and orthostatic hypotension (OH) is one of the most common and disabling symptoms. Although OH is an important and challenging 242
problem affecting the patients with PD, there is insufficient evidence for specific PD-related OH treatment. Vitamin D plays an important role as a hormone with autocrine and paracrine functions that affect bone and mineral metabolism. Recently, several studies have revealed the additional role of vitamin D in neuroprotection, although the exact mechanism by which vitamin D protects neuronal cells against cytotoxic damage has not been fully investigated (2–4). Considering that the pathophysiology of OH in PD is thought to be associated with the
Vitamin D and OH in PD patients impairment of sympathetic neurons because of the neurodegenerative process, the neuroprotective properties of vitamin D may be associated with OH in PD. Furthermore, low vitamin D levels have recently been proposed to play an important role in PD pathogenesis and progression, and vitamin D receptor polymorphisms may also play a role in the development of PD, as shown in certain genetic studies (5–7). In particular, Suzuki et al. suggest that the FokI/CC genotype of the vitamin D receptor gene is associated with a mild form of PD, and it has been reported that the FokI C allele is significantly higher in patients with PD than in controls in a Hungarian population (6, 7). However, Petersen et al. reported no association between PD and vitamin D receptor polymorphism or 25-hydroxyvitamin D levels in the Faroe Islands population, which has double the prevalence of PD (8). Therefore, the role of vitamin D in PD remains controversial. There is also evidence that vitamin D may influence systolic and diastolic blood pressure (BP) and may affect vasomotor and cardiac function in response to orthostasis (9). Therefore, neurocirculatory control of vitamin D itself also may play a role in the pathophysiology of OH in patients with PD (10). In this study, we investigated the association between serum vitamin D levels and the presence of OH in patients with PD as well as the correlation between vitamin D levels and disease severity. Materials and methods Patients
This study was designed as a cross-sectional, monocentre, observational study of 55 patients with PD. All patients with PD participated in the Neurology Clinic of Gangneung Asan Hospital from February to September 2013. The patients were diagnosed according to the criteria issued by the United Kingdom Parkinson’s Disease Society Brain Bank (11). The exclusion criteria were as follows: (i) cognitive impairment (MMSE-K
