Highlights
- •The effect of vitamin D supplements on depressive symptoms and immunological biomarkers was explored in an RRMS population.
- •48 weeks of high-dose vitamin D3 supplementation did not reduce depression scores compared to placebo.
- •Vitamin D3 supplements did not skew cytokine balances towards a more anti-inflammatory profile compared to placebo.
- •Additional studies need to further elucidate whether vitamin D supplements ameliorate manifest depression in MS.
Abstract
Depressive symptoms are common in multiple sclerosis (MS), and both depression and
MS have been associated with a poor vitamin D status. As cytokine-mediated inflammatory
processes play a role in the pathogenesis of both disorders, we hypothesized that
vitamin D3 supplementation reduces depressive symptoms in MS via its immunomodulatory properties.
In this randomized pilot study relapsing remitting (RR) MS patients received either
vitamin D3 supplementation (n = 20; 14.000 IU/day) or placebo (n = 20) during 48 weeks. Pre- and post-supplementation depression scores, measured using the Hospital
Anxiety Depression Scale (HADS) depression subscale (HADS-D), showed a significant
decrease within the vitamin D3 group (median HADS-D 4.0 to 3.0, p = 0.02), a trend towards a decrease within the placebo group (median HADS-D 3.0 to 2.0,
p = 0.06), but no significantly different reductions between groups (p = 0.78). Furthermore, no reductions in pro- and anti-inflammatory cytokine balances,
secreted by stimulated leukocytes and CD8+ T cells, were found in the vitamin D3 compared to the placebo arm. Therefore, we found no evidence for a reduction of depressive
symptoms or related biomarkers upon vitamin D3 supplementation in RRMS patients in this exploratory study. Whether vitamin D3 supplementation is of benefit in manifest depression in MS needs to be assessed by
additional studies.
Abbreviations:
25(OH)D (15-hydroxyvitamin D), FSS (fatigue severity scale), HADS (hospital anxiety and depression scale), IFNγ (interferon-gamma), IL (interleukin), PBMC (peripheral blood mononuclear cells), RRMS (relapsing remitting multiple sclerosis), TNFα (tumor necrosis factor alpha)Keywords
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 accessOne-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:
Subscribe to Journal of the Neurological SciencesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Fatigue in multiple sclerosis: mechanisms, evaluation, and treatment.Sleep. 2010; 33: 1061-1067
- Depression in multiple sclerosis: a review.J. Neurol. Neurosurg. Psychiatry. 2005; 76: 469-475
- Cross-national epidemiology of major depression and bipolar disorder.JAMA. 1996; 276: 293-299
- Current and remitted depression and anxiety disorders as risk factors for medication nonadherence.J. Clin. Psychiatry. 2015; 76: e1114-e1121
- History and evolution of the monoamine hypothesis of depression.J. Clin. Psychiatry. 2000; 61: 4-6
- Cytokine-serotonin interaction through IDO: a neurodegeneration hypothesis of depression.Med. Hypotheses. 2003; 61: 519-525
- Hippocampal volume reduction in major depression.Am. J. Psychiatry. 2000; 157: 115-118
- The dexamethasone suppression test for melancholia.Br. J. Psychiatry. 1982; 140: 292-304
- The macrophage theory of depression.Med. Hypotheses. 1991; 35: 298-306
- Inflamed moods: a review of the interactions between inflammation and mood disorders.Prog. Neuro-Psychopharmacol. Biol. Psychiatry. 2014; 53: 23-34
- Review: cytokines and the pathogenesis of multiple sclerosis.J. Neurosci. Res. 1996; 45: 322-333
- CSF cytokines/chemokines as biomarkers in neuroinflammatory CNS disorders: a systematic review.Cytokine. 2016; 77: 227-237
- Anti-inflammatory effects of antidepressants through suppression of the interferon-gamma/interleukin-10 production ratio.J. Clin. Psychopharmacol. 2001; 21: 199-206
- Endocrine and immune substrates of depressive symptoms and fatigue in multiple sclerosis patients with comorbid major depression.J. Neurol. Neurosurg. Psychiatry. 2011; 82: 814-818
- A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers.JAMA Psychiatry. 2013; 70: 31-41
- The psychoneuroimmuno-pathophysiology of cytokine-induced depression in humans.Int. J. Neuropsychopharmacol. 2002; 5: 375-388
- Low serum IL-10 concentrations and loss of regulatory association between IL-6 and IL-10 in adults with major depression.J. Psychiatr. Res. 2009; 43: 962-969
- A meta-analysis of cytokines in major depression.Biol. Psychiatry. 2010; 67: 446-457
- Vitamin D as an immune modulator in multiple sclerosis, a review.J. Neuroimmunol. 2008; 194: 7-17
- Vitamin D status does not affect disability progression of patients with multiple sclerosis over three year follow-up.PLoS One. 2016; 11: e0156122
- The association between low vitamin D and depressive disorders.Mol. Psychiatry. 2014; 19: 444-451
- Vitamin D status in patients with MS is negatively correlated with depression, but not with fatigue.Acta Neurol. Scand. 2011; 124: 171-175
- Effects of vitamin D on the peripheral adaptive immune system: a review.Autoimmun. Rev. 2011; 10: 733-743
- Higher levels of reported sun exposure, and not vitamin D status, are associated with less depressive symptoms and fatigue in multiple sclerosis.Acta Neurol. Scand. 2014; 129: 123-131
- Vitamin D supplementation to reduce depression in adults: meta-analysis of randomized controlled trials.Nutrition. 2015; 31: 421-429
- Immune regulatory effects of high dose vitamin D3 supplementation in a randomized controlled trial in relapsing remitting multiple sclerosis patients receiving IFN-b; the SOLARIUM study.J. Neuroimmunol. 2016; 300: 47-56
- Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”.Ann. Neurol. 2005; 58: 840-846
- Validation of the hospital anxiety and depression scale for use with multiple sclerosis patients.Mult. Scler. 2009; 15: 1518-1524
- The hospital anxiety and depression scale.Acta Psychiatr. Scand. 1983; 67: 361-370
- Measuring fatigue in patients with multiple sclerosis: reproducibility, responsiveness and concurrent validity of three Dutch self-report questionnaires.Disabil. Rehabil. 2010; 32: 1870-1876
- The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus.Arch. Neurol. 1989; 46: 1121-1123
- Serum 25-hydroxyvitamin D concentrations and depressive symptoms among young adult men and women.Nutrients. 2014; 6: 4720-4730
- Low vitamin D status is associated with more depressive symptoms in Dutch older adults.Eur. J. Nutr. 2015;
- Vitamin D in schizophrenia, major depression and alcoholism.J. Neural Transm. 2000; 107: 839-842
- Association between depressive symptoms and 25-hydroxyvitamin D in middle-aged and elderly Chinese.J. Affect. Disord. 2009; 118: 240-243
- Vitamin D and depression: a systematic review and meta-analysis comparing studies with and without biological flaws.Nutrients. 2014; 6: 1501-1518
- Vitamin D supplementation for depressive symptoms: a systematic review and meta-analysis of randomized controlled trials.Psychosom. Med. 2014; 76: 190-196
- Mood and coping in clinically isolated syndrome and multiple sclerosis.Acta Neurol. Scand. 2014; 129: 374-381
- Randomized trial of a brief depression prevention program: an elusive search for a psychosocial placebo control condition.Behav. Res. Ther. 2007; 45: 863-876
Article info
Publication history
Published online: April 19, 2017
Accepted:
April 4,
2017
Received in revised form:
March 10,
2017
Received:
February 2,
2017
Identification
Copyright
© 2017 Elsevier B.V. All rights reserved.
