No Vitamin D Deficiency in Patients With Parkinson’s Disease

doi:10.21203/rs.3.rs-1128183/v1

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No Vitamin D Deficiency in Patients With Parkinson’s Disease

https://doi.org/10.21203/rs.3.rs-1128183/v1

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Previous trials describe a decrease of vitamin D levels in patients with Parkinson’s disease and relationships to clinical disease severity. This case control study found not significant but higher 25-OH-vitamin D plasma levels in patients with Parkinson’s disease patients compared with age and sex matched controls and no associations to clinical parameters, such as rating scores of disease severity or assessments of cognitive function. A certain variability of vitamin D concentration was observed in both cohorts. These outcomes put into perspective the emerging discussion on the importance of vitamin D in patients with Parkinson’s disease. Our results warrant further confirmatory research with a strict matching design of patients and controls, which has not been done in previous investigations. We stress that this case control study does not allow any comment on the putative beneficial effects of vitamin D supplementation, i.e. on bone mass or bone mineral density in patients with Parkinson’s disease.

Cellular & Molecular Neuroscience

Neurology

Vitamin D

blood

case control study

Many studies investigated associations between Parkinson's disease (PD) and vitamin D status (Lv et al., 2014). The conclusion remains elusive. There are reports that PD patients have lower vitamin D levels than healthy controls (Luo et al., 2018). Moreover vitamin D levels negatively correlate with PD risk and severity (Liu & Zhang, 2014; Barichella et al., 2020). Possible reasons are reduced mobility in combination with sunlight deprivation, gastrointestinal dysfunction with inadequate vitamin D intake (Wang et al., 2015; Wang et al., 2016). Vitamin D is an essential support for the gastrointestinal absorption of calcium, magnesium, phophate and zinc (Kheiri et al., 2018; Shoemaker & Mowry, 2018). Therefore the common onset of reduced bone mineral density in PD is discussed as consequence of vitamin D insufficiency (van den Bof et al., 2013a; van den Bof et al., 2013b). Vitamin D supplementation has even been suggested for prevention and delay of progression of PD (Evatt, 2010; Liu et al., 2013; Evatt, 2014). Higher vitamin D concentrations predispose for better cognitive function in PD patients (Santangelo et al., 2021). However one study only showed the presence of only slight and not significant lower vitamin D levels (Petersen et al., 2014). One believes that this outcome may be explained with the harsh climate, frequent cloud cover, high latitude and the low vitamin content in the common diet of the Faroe Islands, where this trial was undertaken (Lv et al., 2014). Only few foods contain vitamin D, which is biological inactive similar to the one from skin synthesis. Activation of vitamin D takes place by enzymatic hydroxylation in the liver and kidney with generation of 1,25-dihydroxycholecalciferol or 1,25-dihydroxyvitamin D₃, (1,25-(OH)₂D₃) (Muller et al., 2019). In view of the emerging aforementioned discussions on the role of vitamin D in PD, we performed a further case control study and determined vitamin D concentrations in PD patients and matched controls.

Subjects

60 treated PD patients (sex: 19 female, 41 male; age 72,28 ± 2.98 years) (Table 1) and 60 age and sex matched controls (sex: 19 female, 41 male; age 72,58 ± 3.33) participated.

Table 1
Scored clinical characteristics of PD patients
	mean	SD	minimum	maximum
UPDRS I-IV	40,95	20,44	6	104
UPDRS I	3,08	2,99	0	12
UPDRS II	14,4	8,27	2	42
UPDRS III	19,4	11,57	2	56
UPDRS IV	4,07	4,03	0	19
MOCA	20,68	5,58	8	30

all data are given as mean ± standard deviation (SD); MOCA, Montreal Cognitive Assessment; UPDRS I, Unified Parkinson’s Disease Rating Scale mental behaviour; UPDRS II, Unified Parkinson’s Disease Rating Scale activities of daily living; UPDRS III, Unified Parkinson’s Disease Rating Scale motor examination; UPDRS IV, Unified Parkinson’s Disease Rating Scale motor complications; UPDRS I-IV, total UPDRS score.

Design

25-OH-vitamin D levels were determined. Intake of vitamin D, respectively vitamin K containing formulations was an exclusion criterion (Ferguson et al., 2019). Blood was taken during an out-patient visit. Scoring of PD symptoms with the Unified Parkinson’s Disease rating scale (Fahn et al., 1987) and performance of the Montreal Cognitive Assessment (MoCA) was executed before blood sampling (Nasreddine et al., 2005).

Methods

Blood samples were drawn in EDTA containing tubes. Vitamin D assessment was performed with LC-MS (company: Chromsystems®), which combines reversed-phase high performance liquid chromatography (HPLC [company: Shimadzu ®] with mass spectrometry [AB-Sciex API5000®].

Statistics

The Mann Whitney U-test for independent samples was used for comparisons. Spearman rank correlation was employed for the correlation analysis. Data showed no normal distribution. A seasonal adjustment as time dependent variable of vitamin D was not performed (Brola et al., 2016).

Ethics

The study protocol and the patient informed consent form were reviewed and approved by the independent ethics committee of the Medical Faculty in the University of Wuerzburg, Germany (sign: 30/17 on 4-19-2017). Participants gave written informed consent after information on the study protocol.

Data availability

The data sets generated or analysed during the current study are available from the corresponding author on reasonable request.

There was no significant difference of 25-OH-vitamin D between PD patients (17,59 ± 9,28 [µg/l; mean ± SD]) and controls (15,69 ± 8,43) (Figure 1). No significant associations between vitamin D levels and clinical parameters were found (Table 2). There was no impact of sex and age (results not shown).

Table 2
Correlation analysis between 25-(OH)-vitamin D blood concentrations and clinical parameters
variable 1	variable 2	R	p
25-(OH)-vitamin D	UPDRS	-0,056	ns
25-(OH)-vitamin D	UPDRS I	-0,054	ns
25-(OH)-vitamin D	UPDRS II	-0,08	ns
25-(OH)-vitamin D	UPDRS III	-0,012	ns
25-(OH)-vitamin D	UPDRS IV	0,087	ns
25-(OH)-vitamin D	MOCA	-0,027	ns

R, correlation coefficient; p, p-value

We did not find significant higher 25-OH-vitamin D blood concentrations in treated PD patients in comparison with matched controls. No correlation to rating scores for PD and neuropsychological assessments of cognitive function appeared. Our outcomes put into perspective the emerging discussion on the importance of vitamin D in PD to a certain extent. We show that a certain variability of vitamin D concentration was observed in both cohorts. Our results warrant further confirmatory research with a strict matching design of patient and controls. We stress that the design of this case control study does not allow any comment on the putative beneficial effects of vitamin D supplementation, i.e. on bone mass or bone mineral density in PD patients (Liu et al., 2013; Lv et al., 2014; Ozturk et al., 2016; Ozturk et al., 2020). It is known that vitamin D elevation shifts blood flow parameters in a manner, that tissue microcirculation is improved (Muller et al., 2019). As consequence, oxygen transport and –perfusion of tissue may increase and improve mitochondrial function and defence of oxidative stress (Glueck et al., 2016). Both, mitochondrial impairment and reduction of free radical scavenging capacity, play an essential role in the pathophysiology of chronic neurodegenerative disorders (Siotto et al., 2019). Various trials demonstrated beneficial effects on body function following vitamin D supplementation in disease entities, such as cognitive dysfunction (Wise, 2015).

There are several limitations. We only assessed once and there were not taken off PD medication. Therefore the correlation analysis cannot provide profound value on the assessments of functional deficits in relation to vitamin D measurement in our PD cohort.

In conclusion, vitamin D levels did not significantly vary between PD patients and matched controls and did not show any relationship to disease severity in contrast to other clinical investigations.

ETHICAL STATEMENT:

o Ethics approval and consent to participate: 19 04 2017

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the University of Wuerzburg

o Consent for publication: 19 04 2017: The authors affirm that human research participants provided informed consent for publication

o Availability of data and materials: The data sets generated or analysed during the current study are available from the corresponding author on reasonable request.

o Competing interests: none, The authors have no relevant financial or non-financial interests to disclose.

o Funding: none

o Authors' contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Thomas Mülle, Georg Karp, Wilfried Kuhn. The first draft of the manuscript was written by Thomas Müller and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

W Kuhn: A, B, E, ; G Karp: A, B, E; T Müller: A – E (Definition of author roles: A: execution, B: design, C: analysis, D: writing, E: editing

o Acknowledgements: We thank the participating patients.

o Authors' information (optional):

Barichella M, Cereda E, Iorio L, Pinelli G, Ferri V, Cassani E, Bolliri C, Caronni S, Pusani C, Schiaffino MG, Giana A, Quacci E, Esposito C, Monti GF, Colombo A, Sorbo FD, Cilia R, Sacilotto G, Riboldazzi G, Zecchinelli AL, Pezzoli G (2020) Clinical correlates of serum 25-hydroxyvitamin D in Parkinson's disease. Nutr Neurosci : 1-9
Brola W, Sobolewski P, Szczuchniak W, Goral A, Fudala M, Przybylski W, Opara J (2016) Association of seasonal serum 25-hydroxyvitamin D levels with disability and relapses in relapsing-remitting multiple sclerosis. Eur J Clin Nutr 70: 995-999
Evatt ML (2010) Beyond vitamin status: is there a role for vitamin d in Parkinson disease? Arch Neurol 67: 795-797
Evatt ML (2014) Parkinson disease: Low vitamin D and Parkinson disease--a causal conundrum. Nat Rev Neurol 10: 8-9
Fahn S, Elton R., Members of the UPDRS Development Committee (1987) Unified Parkinson's Disease Rating Scale. 153-163 New York, Macmillan.
Ferguson CC, Knol LL, Halli-Tierney A, Ellis AC (2019) Dietary Supplement Use is High among Individuals with Parkinson Disease. South Med J 112: 621-625
Glueck CJ, Jetty V, Rothschild M, Duhon G, Shah P, Prince M, Lee K, Goldenberg M, Kumar A, Goldenberg N, Wang P (2016) Associations between Serum 25-hydroxyvitamin D and Lipids, Lipoprotein Cholesterols, and Homocysteine. N Am J Med Sci 8: 284-290
Kheiri B, Abdalla A, Osman M, Ahmed S, Hassan M, Bachuwa G (2018) Vitamin D deficiency and risk of cardiovascular diseases: a narrative review. Clin Hypertens 24: 9
Liu Y, Li YW, Tang YL, Liu X, Jiang JH, Li QG, Yuan JY (2013) Vitamin D: preventive and therapeutic potential in Parkinson's disease. Curr Drug Metab 14: 989-993
Liu Y, Zhang BS (2014) Serum 25-hydroxyvitamin D predicts severity in Parkinson's disease patients. Neurol Sci 35: 67-71
Luo X, Ou R, Dutta R, Tian Y, Xiong H, Shang H (2018) Association Between Serum Vitamin D Levels and Parkinson's Disease: A Systematic Review and Meta-Analysis. Front Neurol 9: 909
Lv Z, Qi H, Wang L, Fan X, Han F, Wang H, Bi S (2014) Vitamin D status and Parkinson's disease: a systematic review and meta-analysis. Neurol Sci 35: 1723-1730
Muller T, Lohse L, Blodau A, Frommholz K (2019) Vitamin D rise enhances blood perfusion in patients with multiple sclerosis. J Neural Transm (Vienna ) 126: 1631-1636
Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H (2005) The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53: 695-699
Ozturk EA, Gundogdu I, Tonuk B, Kocer BG, Tombak Y, Comoglu S, Cakci A (2016) Bone mass and vitamin D levels in Parkinson's disease: is there any difference between genders? J Phys Ther Sci 28: 2204-2209
Ozturk EA, Gundogdu I, Tonuk B, Umay E, Kocer BG, Cakci A (2020) Bone mineral density and serum vitamin D status in Parkinson's disease: Are the stage and clinical features of the disease important? Neurol India 68: 394-400
Petersen MS, Bech S, Christiansen DH, Schmedes AV, Halling J (2014) The role of vitamin D levels and vitamin D receptor polymorphism on Parkinson's disease in the Faroe Islands. Neurosci Lett 561: 74-79
Santangelo G, Raimo S, Erro R, Picillo M, Amboni M, Pellecchia MT, Pivonello C, Barone P, Vitale C (2021) Vitamin D as a possible biomarker of mild cognitive impairment in parkinsonians. Aging Ment Health 25: 1998-2002
Shoemaker TJ, Mowry EM (2018) A review of vitamin D supplementation as disease-modifying therapy. Mult Scler 24: 6-11
Siotto M, Filippi MM, Simonelli I, Landi D, Ghazaryan A, Vollaro S, Ventriglia M, Pasqualetti P, Rongioletti MCA, Squitti R, Vernieri F (2019) Oxidative Stress Related to Iron Metabolism in Relapsing Remitting Multiple Sclerosis Patients With Low Disability. Front Neurosci 13: 86
van den Bos F, Speelman AD, Samson M, Munneke M, Bloem BR, Verhaar HJ (2013a) Parkinson's disease and osteoporosis. Age Ageing 42: 156-162
van den Bos F, Speelman AD, van NM, van der Schouw YT, Backx FJ, Bloem BR, Munneke M, Verhaar HJ (2013b) Bone mineral density and vitamin D status in Parkinson's disease patients. J Neurol 260: 754-760
Wang J, Yang D, Yu Y, Shao G, Wang Q (2016) Vitamin D and Sunlight Exposure in Newly-Diagnosed Parkinson's Disease. Nutrients 8: 142
Wang L, Evatt ML, Maldonado LG, Perry WR, Ritchie JC, Beecham GW, Martin ER, Haines JL, Pericak-Vance MA, Vance JM, Scott WK (2015) Vitamin D from different sources is inversely associated with Parkinson disease. Mov Disord 30: 560-566
Wise J (2015) Low vitamin D is linked to faster cognitive decline in older adults. BMJ 351: h4916

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No Vitamin D Deficiency in Patients With Parkinson’s Disease

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