Research Article| Volume 345, ISSUE 1-2, P184-188, October 15, 2014

Download started.


Vitamin D deficiency in patients with primary immune-mediated peripheral neuropathies


      • All patients with autoimmune peripheral neuropathies (PNP) had vitamin D deficiency.
      • Vitamin D levels were lower in patients with PNP than in healthy controls.
      • Motor neuron disease patients had comparable vitamin D status to healthy controls.
      • We suggest monitoring of vitamin D status in PNP patients.



      T cells are important in the immunopathology of immune-mediated peripheral neuropathies (PNP) and activated vitamin D regulates the immune response through increasing the amount of regulatory T cells. An association between vitamin D deficiency and polyneuropathy has been stipulated; hence we assessed whether patients with primary immune-mediated PNP have low vitamin D [25(OH)D] levels.


      Plasma levels of 25(OH)D were analyzed in 26 patients with primary immune-mediated PNP, 50 healthy matched blood donors and 24 patients with motor neuron disease (MND). INCAT score was assessed in patients with Guillain–Barré syndrome and chronic inflammatory demyelinating polyneuropathy. ALSFRS-R score was applied to MND patients and the modified Rankin (mRankin) scale compared disability among patient groups.


      Mean 25(OH)D value in PNP patients was 40 ± 16 nmol/l, compared to 69 ± 21 nmol/l in healthy blood donors (p < 0.001). MND patients had a higher mean 25(OH)D than PNP patients (59 ± 26 nmol/L; p = 0.006) and comparable levels to healthy blood donors (p = 0.15). Mean 25(OH)D value was not higher in PNP patients with pre-existing vitamin D3 supplementation of 800 IU/day (N = 6; 35 ± 18 nmol/L) than in unsupplemented PNP patients (42 ± 16 nmol). INCAT score ranged from 0 to 10 (mean 3.5) and ALSFRS-R ranged from 11 to 44 (mean 31). mRankin score was more severe in MND patients (mean 3.5) compared to PNP patients (mean 2.1).


      All patients with primary immune-mediated PNP were diagnosed with vitamin D deficiency and they had significantly lower 25(OH)D values than healthy control persons and MND patients. We suggest monitoring of vitamin D status in patients with autoimmune PNP, since immune cells are responsive to the ameliorative effects of vitamin D.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of the Neurological Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Van den Bergh P.Y.
        • Hadden R.D.
        • Bouche P.
        • Cornblath D.R.
        • Hahn A.
        • Illa I.
        • et al.
        European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society — first revision.
        Eur J Neurol. 2010; 17: 356-363
        • Merkies I.S.
        • Faber C.G.
        Fatigue in immune-mediated neuropathies.
        Neuromuscul Disord. 2012; 22: S203-S207
        • Nyati K.K.
        • Prasad K.N.
        • Rizwan A.
        • Verma A.
        • Paliwal V.K.
        TH1 and TH2 response to Campylobacter jejuni antigen in Guillain–Barre syndrome.
        Arch Neurol. 2011; 68: 445-452
        • Prietl B.
        • Pilz S.
        • Wolf M.
        • Tomaschitz A.
        • Obermayer-Pietsch B.
        • Graninger W.
        • et al.
        Vitamin D supplementation and regulatory T cells in apparently healthy subjects: vitamin D treatment for autoimmune diseases?.
        Isr Med Assoc J. 2010; 12: 136-139
        • Hewison M.
        Vitamin D and immune function: an overview.
        Proc Nutr Soc. 2012; 71: 50-61
        • Munger K.L.
        • Levin L.I.
        • Hollis B.W.
        • Howard N.S.
        • Ascherio A.
        Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis.
        JAMA. 2006; 296: 2832-2838
        • Carlander B.
        • Puech-Cathala A.M.
        • Jaussent I.
        • Scholz S.
        • Bayard S.
        • Cochen V.
        • et al.
        Low vitamin D in narcolepsy with cataplexy.
        PLoS One. 2011; 6: e20433
        • Azali P.
        • Barbasso Helmers S.
        • Kockum I.
        • Olsson T.
        • Alfredsson L.
        • Charles P.J.
        • et al.
        Low serum levels of vitamin D in idiopathic inflammatory myopathies.
        Ann Rheum Dis. 2013; 72: 512-516
        • Askmark H.
        • Haggard L.
        • Nygren I.
        • Punga A.R.
        Vitamin D deficiency in patients with myasthenia gravis and improvement of fatigue after supplementation of vitamin D3: a pilot study.
        Eur J Neurol. 2012; 19: 1554-1560
        • Soderstrom L.H.
        • Johnson S.P.
        • Diaz V.A.
        • Mainous 3rd., A.G.
        Association between vitamin D and diabetic neuropathy in a nationally representative sample: results from 2001–2004 NHANES.
        Diabet Med. 2012; 29: 50-55
        • Agmon-Levin N.
        • Kivity S.
        • Tzioufas A.G.
        • Lopez Hoyos M.
        • Rozman B.
        • Efes I.
        • et al.
        Low levels of vitamin-D are associated with neuropathy and lymphoma among patients with Sjogren's syndrome.
        J Autoimmun. 2012; 39: 234-239
        • Hughes R.
        • Bensa S.
        • Willison H.
        • Van den Bergh P.
        • Comi G.
        • Illa I.
        • et al.
        Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy.
        Ann Neurol. 2001; 50: 195-201
        • Merkies I.S.
        • Schmitz P.I.
        • van der Meche F.G.
        • Samijn J.P.
        • van Doorn P.A.
        Clinimetric evaluation of a new overall disability scale in immune mediated polyneuropathies.
        J Neurol Neurosurg Psychiatry. 2002; 72: 596-601
        • Cedarbaum J.M.
        • Stambler N.
        • Malta E.
        • Fuller C.
        • Hilt D.
        • Thurmond B.
        • et al.
        The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III).
        J Neurol Sci. 1999; 169: 13-21
        • Banks J.L.
        • Marotta C.A.
        Outcomes validity and reliability of the modified Rankin scale: implications for stroke clinical trials: a literature review and synthesis.
        Stroke. 2007; 38: 1091-1096
        • Cutolo M.
        • Otsa K.
        • Uprus M.
        • Paolino S.
        • Seriolo B.
        Vitamin D in rheumatoid arthritis.
        Autoimmun Rev. 2007; 7: 59-64
        • Lucas R.M.
        • Ponsonby A.L.
        • Dear K.
        • Valery P.C.
        • Pender M.P.
        • Taylor B.V.
        • et al.
        Sun exposure and vitamin D are independent risk factors for CNS demyelination.
        Neurology. 2011; 76: 540-548
        • Ritterhouse L.L.
        • Crowe S.R.
        • Niewold T.B.
        • Kamen D.L.
        • Macwana S.R.
        • Roberts V.C.
        • et al.
        Vitamin D deficiency is associated with an increased autoimmune response in healthy individuals and in patients with systemic lupus erythematosus.
        Ann Rheum Dis. 2011; 70: 1569-1574
        • Holick M.F.
        Resurrection of vitamin D deficiency and rickets.
        J Clin Invest. 2006; 116: 2062-2072
        • Lagishetty V.
        • Liu N.Q.
        • Hewison M.
        Vitamin D metabolism and innate immunity.
        Mol Cell Endocrinol. 2011; 347: 97-105
        • Theodoratou E.
        • Tzoulaki I.
        • Zgaga L.
        • Ioannidis J.P.
        Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials.
        BMJ. 2014; 348: g2035
        • Skversky A.L.
        • Kumar J.
        • Abramowitz M.K.
        • Kaskel F.J.
        • Melamed M.L.
        Association of glucocorticoid use and low 25-hydroxyvitamin D levels: results from the National Health and Nutrition Examination Survey (NHANES): 2001–2006.
        J Clin Endocrinol Metab. 2011; 96: 3838-3845
        • Holick M.F.
        Vitamin D deficiency.
        N Engl J Med. 2007; 357: 266-281
        • Tang J.
        • Zhou R.
        • Luger D.
        • Zhu W.
        • Silver P.B.
        • Grajewski R.S.
        • et al.
        Calcitriol suppresses antiretinal autoimmunity through inhibitory effects on the Th17 effector response.
        J Immunol. 2009; 182: 4624-4632
        • Daniel C.
        • Sartory N.A.
        • Zahn N.
        • Radeke H.H.
        • Stein J.M.
        Immune modulatory treatment of trinitrobenzene sulfonic acid colitis with calcitriol is associated with a change of a T helper (Th) 1/Th17 to a Th2 and regulatory T cell profile.
        J Pharmacol Exp Ther. 2008; 324: 23-33
        • Bischoff-Ferrari H.A.
        • Kiel D.P.
        • Dawson-Hughes B.
        • Orav J.E.
        • Li R.
        • Spiegelman D.
        • et al.
        Dietary calcium and serum 25-hydroxyvitamin D status in relation to BMD among U.S. adults.
        J Bone Miner Res. 2009; 24: 935-942
        • Heaney R.P.
        • Dowell M.S.
        • Hale C.A.
        • Bendich A.
        Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D.
        J Am Coll Nutr. 2003; 22: 142-146
        • Steingrimsdottir L.
        • Gunnarsson O.
        • Indridason O.S.
        • Franzson L.
        • Sigurdsson G.
        Relationship between serum parathyroid hormone levels, vitamin D sufficiency, and calcium intake.
        JAMA. 2005; 294: 2336-2341
        • Turner M.R.
        • Hardiman O.
        • Benatar M.
        • Brooks B.R.
        • Chio A.
        • de Carvalho M.
        • et al.
        Controversies and priorities in amyotrophic lateral sclerosis.
        Lancet Neurol. 2013; 12: 310-322
        • Sato Y.
        • Honda Y.
        • Asoh T.
        • Kikuyama M.
        • Oizumi K.
        Hypovitaminosis D and decreased bone mineral density in amyotrophic lateral sclerosis.
        Eur Neurol. 1997; 37: 225-229
        • Karam C.
        • Barrett M.J.
        • Imperato T.
        • MacGowan D.J.
        • Scelsa S.
        Vitamin D deficiency and its supplementation in patients with amyotrophic lateral sclerosis.
        J Clin Neurosci. 2013; 20: 1550-1553
        • Holick M.F.
        • Matsuoka L.Y.
        • Wortsman J.
        Age, vitamin D, and solar ultraviolet.
        Lancet. 1989; 2: 1104-1105
        • Long K.
        • Nguyen L.T.
        Roles of vitamin D in amyotrophic lateral sclerosis: possible genetic and cellular signaling mechanisms.
        Mol Brain. 2013; 6: 16
        • Loken-Amsrud K.I.
        • Holmoy T.
        • Bakke S.J.
        • Beiske A.G.
        • Bjerve K.S.
        • Bjornara B.T.
        • et al.
        Vitamin D and disease activity in multiple sclerosis before and during interferon-beta treatment.
        Neurology. 2012; 79: 267-273