JOM Volume 26, Number 3, 2011 Review Article 127

Effectiveness of Vitamin D in the

Treatment of Mood Disorders:
A Literature Review

Baljit K. Khamba ND, MPH;1 Monique Aucoin, BMSc, ND (cand.);5 Dina Tsirgielis, BSc;1
Alex Copeland, BSc;1 Monica Vermani, PsyD;1,3 Catherine Cameron, MD;1 Isaac
Szpindel, MD;1 Bob Laidlaw, BSc;1 Irvin Epstein, MD;1,2 Martin Katzman, MD1,2,3,4
1
START Clinic for Mood and Anxiety Disorders, 2 Department of Psychiatry, University of Toronto,
3
Department of Psychology, Lakehead University, 4 Northern Ontario School of Medicine, 5 The Canadian Col-
lege of Naturopathic Medicine

Abstract Depression is a mood disorder that has a significant negative impact on the lives of many
individuals. Since vitamin D deficiency is prevalent in the North American population, recent sci-
entific research is investigating the connection between insufficient vitamin D and the pathogenesis
of mood disorders, as well as the nutrient’s potential as a therapeutic agent. Several epidemiological
studies have shown a relationship between low levels of vitamin D and the presence of depression. A
small number of intervention trials have found a potential trend toward the reduction of depressive
symptoms from vitamin D supplementation; however, many of the studies had limitations which
restrict the conclusions that can be drawn. Further research in the field is warranted.

Background: Vitamin D The main function of vitamin D is the

Vitamin D is a steroid hormone that plays maintenance of blood calcium and phos-
several important physiologic roles. Some of phorous concentrations to facilitate cellular,
these actions, including an impact on mood neuromuscular and ossification functions
health, have been recently hypothesized and are through enhancing absorption of these in-
the subject of investigation. Vitamin D can be gested nutrients in the small intestine and by
obtained from dietary sources such as fish liver mobilizing bone stores.1 The consequence of
oils, fatty fish, egg yolks and fortified milk and severe deficiency is a condition called rickets
it can be synthesized in the skin in response to which is characterized by severe bone de-
sun light exposure.1 While most vitamin defi- formation. While fortification of milk has
ciencies are rare in the developed world, vita- served to decrease the incidence of rickets,1
min D is the only one that remains prevalent.2,3 many studies have found large percentages
People living at northern latitudes receive less of the population to have deficient or in-
sun exposure during the winter. Additionally, sufficient levels of serum vitamin D.5-7 In-
cultural trends of increasingly sedentary life- adequate levels have been associated with
styles, more indoor activities, and increasing chronic diseases including osteoporosis, can-
awareness about the risk of excess sun exposure, cer, diabetes, neurodegenerative, autoimmune
contribute to vitamin D deficiency.4 and infectious diseases.1 In older adults, de-

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 128 Journal of Orthomolecular Medicine Vol 26, No 3, 2011

ficiency has been associated with decreased pating in their routine activities. Commonly,
physical function, increased risk of fractures, they may withdraw from family and friends.
frailty and mortality.5 In addition to correct- Patients may also have thoughts of death or
ing deficiency and treating osteomalacia and suicide.19 Patients with dysthymia also suffer
rickets,1 evidence supports the use of vitamin from chronically low mood lasting at least
D supplementation in hyperparathyroidism, two years although their symptoms are not
hypothyroidism,2 psoriasis,8 osteoporosis,9 as severe as in MDD.9
muscle weakness/pain,10 fall prevention,11 A recent study identified 8.2 percent of
immunomodulation,12 multiple sclerosis,13 Canadians and Americans meet the criteria
and prevention of cancer1 and heart dis- for MDD. Conventional treatment for de-
ease.14 The Canadian guidelines for recom- pression uses a combination of anti-depres-
mended dietary intakes of vitamin D are 600 sant pharmacotherapy targeted at modulat-
international units (IU) for individuals aged ing neurotransmitters and psychotherapy.19
1 to 70 and 800 IU for those 71 or older, There is also significant research to support
although higher doses are used in the treat- the use of exercise as an effective inter-
ment of some conditions.15 vention.20 Complementary and alternative
Newer research on vitamin D has iden- medical interventions for depression include
tified possible mechanisms through which it omega-3 essential fatty acids, tryptophan, S-
could affect mood. Vitamin D is able to pass adenosylmethionine, folic acid, vitamin B12
through the blood-brain barrier and its recep- and zinc.21
tors are found widely throughout the brain Seasonal Affective Disorder (SAD),
including the cortex, cerebellum and limbic another type of depression, is characterized
system.16 It has been shown to stimulate se- by the development of recurrent depres-
rotonin, down-regulate glucocorticoid recep- sion during the fall or winter. While many
tor genes which are up-regulated in depressed of the emotional and cognitive symptoms
states and provide a neuroprotective effect.17 are similar to those of depression, vegetative
Low vitamin D leads to elevation of parathy- symptoms such as increased sleep, appetite,
roid hormone which is associated with de- carbohydrate cravings and weight gain are
pression. The depression tends to resolve after more common in SAD patients compared
treatment of the hyperparathyroidism.18 to a decrease in sleep, appetite and weight in
depression patients. Studies have estimated
Mood disorders the prevalence to be 1-9% based on differ-
Depression and other mood disorders ent populations and methodologies.22 It has
are a major health concern globally. These been hypothesized that changes in serotonin
disorders have significant impact on quality contributes to SAD pathogenesis.23 While
of life, morbidity and mortality and it has SAD is most often treated with photother-
been estimated that by 2020, depression will apy, pharmacotherapy and cognitive behav-
rank second in global health burden to heart ioural therapy have also shown benefit.24
disease based on disability-adjusted years.16 Insufficiency and/or deficiency of vita-
Depression is characterized by persis- min D may play a role in the pathogenesis of
tently low mood and feelings of sadness and mood disorders. Supplementation could be
hopelessness. In Major Depressive Disorder an effective antidepressant therapy.25
(MDD), this low mood lasts longer than two
weeks and is accompanied by other symp- Methods
toms that include decreased interest or plea- The Medline (PubMed) database was
sure in activities, changes to weight and sleep, searched for articles published prior to
fatigue and impaired concentration and feel- February 2011 that matched any combina-
ings of worthlessness or guilt. People expe- tion of the following keywords: vitamin D,
riencing depression may feel overwhelmed vitamin D deficiency, 25-hydroxyvitamin
and exhausted, and, as a result, stop partici- D, depression, generalized anxiety disorder,

Khamba.indd 128 8/23/11 1:46:35 PM

 Effectiveness of Vitamin D in the Treatment of Mood Disorders: A Literature Review 129

Figure 1. Observational Studies

Reference Type of Sample Topic Results Conclusion

Study Size
Berk M, Jacka FN, Cross- 53 Chart review 58% of patients had High rates of Vita-
Williams LJ, et al: sectional audit of patients insufficient 25OHD min D insufficiency
Is this D vitamin to in psychiatric facil- levels and 11% had in psychiatric
worry about? Vitamin ity where serum moderate defi- inpatients
D insufficiency in an 25-hydroxyvitamin ciency (68% and 12%
inpatient sample. D (25OHD) levels respectively when
Aust NZ J Psychiatr, were routinely tested in the winter)
2008;42:874-878. tested compared to 30%
and 7.2% of healthy
controls
Armstrong DJ, Meen- Cross- 75 Relationship be- No relationship be- Higher rates of
agh GK, Bickle I et al: sectional tween current lev- tween 25OHD status anxiety and depres-
Vitamin D deficiency is els of 25OHD and and Fibromyalgia sion in fibromyalgia
associated with anxiety anxiety, depres- Impact Questionnaire patients were asso-
and depression in fibro- sion, fibromyalgia- score; Mean Hospital ciated with deficient
myalgia. Clin Rheumatol, related disability Anxiety and Depres- serum 25OHD levels
2007;26:551-554. sion Score among de-
ficiency patients was
31, among insufficient
patients was 22.5 and
among patients with
normal levels was 23.5
(p<0.05)
Wilkins CH, Sheline YI, Cross- 80 Study of patients After adjustment was Vitamin D
Roe CM et al: Vitamin sectional with mild Al- made for age, sex, race deficiency was
D deficiency is associ- zheimer’s disease and season, significant associated with
ated with low mood and and non-demented increase in presence of lower mood and
worse cognitive perfor- controls looking active mood disorders poorer cognitive
mance in older adults. for associations seen among patients performance
Am J Geriatr Psychiatr, between current with deficient and
2006; 14:1032-1040. 25OHD levels and insufficient 25OHD
cognitive, mood compared to controls
and physical health with adequate levels
(p=0.022 for deficient
and p=2.54 for insuf-
ficient)
Nanri A, Mizoue T, Cross- 527 Relationship be- No significant Author concluded
Matsushita Y et al: Asso- sectional tween low 25OHD difference in level that vitamin D was
ciation between serum and depressive of depressive symp- not protective in
25-hydroxyvitamin D symptoms. Serum toms between the the pathogenesis of
and depressive symp- 25OHD and Center two offices. Among depression
toms by survey season. for Epidemiological participants in office
Eur J Clin Nutr, 2009; 63: Studies Depres- B, prevalence of de-
1444-1447. sion Scale (CES-D) pressive symptoms
score assessed in decreased with
participants from increasing 25OHD;
office A in July and however, the results
participants from did not reach statis-
office B in November tical significance

Khamba.indd 129 8/23/11 1:46:35 PM

 130 Journal of Orthomolecular Medicine Vol 26, No 3, 2011

Figure 1. Observational Studies, cont’d

Reference Type of Sample Topic Results Conclusion
Study Size

Hoogendijk WJ, Lips P, Cross- 1,282 Association between Vitamin D levels were There was an
Dik MG, et al: Depres- sectional depression and 14% lower in patients association
sion Is associated with serum 25OHD and with minor depression between lower
decreased 25-hy- parathyroid hor- or major depressive levels of vitamin
droxyvitamin D and mone (PTH) levels in disorder (p<0.001). D/higher levels of
increased parathyroid older adults Depression severity PTH and higher
hormone levels in older (CES-D score) was sig- incidence and
adults. Arch Gen Psy- nificantly associated severity of clinical
chiatr, 2008; 65: 508-512. with the decreasing depression
25OHD and increas-
ing PTH according to
quartile of blood levels
(both: p<0.001)
Lee DM, Tajar A, O’Neill Cross- 3,151 Association be- Serum 25OHD was Lower levels of
TW: Lower vitamin D sectional tween depressive significantly lower in 25OHD were asso-
levels are associated symptoms, serum men with Beck De- ciated with higher
with depression among 25OHD and PTH pression Inventory-II BDI-II scores
community-dwelling Eu- (BDI-II) scores ≥ 14
ropean men. J Psychop- (depressed men)
harmacol, 2010 [Epub
ahead of print].
Reed SD, Laya MB, Mel- Cross- 71 Association between All women had insuf- No association exists
ville J et al: Prevalence sectional low 25OHD and ficient vitamin D levels: between the sever-
of Vitamin D Insufficien- fatigue, musculoskel- 12.3% severe, 40.9% ity of vitamin D defi-
cy and Clinical Associa- etal complaints and moderate and 44.9% ciency and the pres-
tions among Veiled East depressive symptoms mildly deficient. When ence of depression;
African Women in Wash- in veiled women comparing the mean however, because
ington State. J Womens vitamin D levels of pa all participants were
Health (Larchmt), 2007; tients with or without deficient, study
16: 206-213. mild/moderate depres- could not compare
sion symptoms, pain, depression levels
fatigue and muscle to those of controls
weakness no differ- with adequate
ence was found 25OHD
Stewart R, Hirani V: Cross- 2,070 Relationship Patients with <10 There was an as-
Relationship Between sectional between low serum ng/mL 25OHD had sociation between
Vitamin D Levels and 25OHD and depres- significantly higher low vitamin D
Depressive Symptoms in sion in the elderly frequency of depres- levels and depres-
Older Residents From a sion than control sive symptoms/
National Survey Popula- clinically signifi cant
tion. Psychosom Med, depression in elderly
2010; 72(7): 608-12. patients

anxiety disorder, comorbidity, diagnosis and Discussion

treatment, hypovitaminosis. Articles were There were 14 studies that fit the criteria
screened and those that reported on the re- parameters; see Figures 1 and 2 (10 cross-
lationship between vitamin D insufficiency/ sectional, one cohort, one quasi-experiment,
deficiency and psychiatric disorders or re- four RCTs). Of the 10 cross-sectional stud-
lated psychiatric conditions were included ies, eight reported a significant correlation
in Figures 1 and 2, (p.129-133). between low levels of 25OHD and the

Khamba.indd 130 8/23/11 1:46:36 PM

 Effectiveness of Vitamin D in the Treatment of Mood Disorders: A Literature Review 131

Figure 1. Observational Studies, cont’d

Reference Type of Sample Topic Results Conclusion

Study Size
Milaneschi Y, Shardell Cohort 639 Cohort study assess- Patients with Lower levels of
M, Corsi AM, et al: ing for the develop- 25OHD levels in the serum vitamin D
Serum 25-hydroxyvita- ment of depression 3 lower two tertiles at in elderly patients
min D and depressive and 6 years after as- baseline had larger increased the risk
symptoms in older sessment of 25OHD increases in CES-D of developing
women and men. J deficiency scale than those in depression in the
Clin Endocrinol Metab, the higher tertile. future
2010;95:3225–3233. Lower 25OHD levels
associated with
higher probability of
developing depres-
sion during follow-
up period
Schneider B, Weber B, Cross- 120 Role of vitamin D sta- 25OHD and 1,25-di- Vitamin D status
Frensch A, et al: Vitamin sectional tus in schizophrenia, hydroxyvitamin D3 among psychiatric
D in schizophrenia, major alcoholism and major were significantly patients had no
depression and alcohol- depressive disorder lower in psychiatric relationship to the
ism. J Neural Transm, patients than in pathogenesis of
2000; 107:839-842. healthy controls depression, which
when considering was likely the re-
the group as a whole sult of confound-
(p<0.02). Patients ing factors, such
with schizophrenia as malnutrition or
and depression inadequate sun
had lower levels of exposure
1,25-dihydroxyvita-
min D3 than patients
with alcoholism or
healthy controls
Jorde R, Sneve M, Figen- Cross- 441 Relationship between When comparing There was a rela-
schau Y, et al: Effects of sectional baseline serum participants with tionship between
vitamin D supplementa- & Ran- 25OHD levels and 25OHD <40 nmol/L lower serum
tion on symptoms of de- domized baseline Beck Depres- to remaining partici- 25OHD and in-
pression in overweight Cotrolled sion Inventory (BDI) pants, the deficient creased depression
and obese subjects: Trial (RCT) scores, including participants had a in overweight and
randomized double subscales 1-13 (men- significantly higher obese individuals
blind trial. J Intern Med, tal symptoms) and mean BDI score (6.0
2008;264:599-609. 14-21(somatic-vege- vs 4.5) and BDI 1-13
tative symptoms) subscale score (2.0 vs
1), (p <0.01)

presence of mood disorders. Several of but did not reach statistical significance. The
these studies involved a large number of other cross-sectional study compared the se-
subjects, included control subjects and verity of vitamin D deficiency with depres-
used well validated evaluation tools like sion, but did not use non-deficient controls
the BDI-II. Of the two remaining cross- as a point of comparison. While these studies
sectional studies, one showed an inverse suggest a relationship between 25OHD and
relationship between 25OHD and mood, mood, they do not necessarily give credence

Khamba.indd 131 8/23/11 1:46:36 PM

 132 Journal of Orthomolecular Medicine Vol 26, No 3, 2011

Figure 2. Intervention Studies

Reference Type of Inter- Subjects Assessment of Result Conclusion

Study vention Intervention

Jorde R, Sneve M, RCT Weekly 441 patients BDI at baseline Both vitamin D Supplemen-
Figenschau Y, et al: dose of with BMI of and after one supplementation tation with
Effects of vitamin 40,000 IU, 28-47, age year of supple- groups had significant vitamin D
D supplementa- 20,000 IU 21-70 mentation. reductions in mean for one year
tion on symptoms or 0 IU of BDI and subscale might have a
of depression in vitamin scores after one positive effect
overweight and D3 plus year. In the placebo on depression
obese subjects: 500 mg of group, a significant in overweight
randomized calcium per reduction in BDI 14-21 and obese
double blind trial. day for one subscale was seen. individuals
J Intern Med, 2008; year When comparing 1998; 135:
264: 599-609. BDI change over 12 319-323.
months in vitamin D
vs placebo groups,
significant improve-
ment seen in BDI 1-13
score (p<0.05) but
not using intention to
treat analysis
(p= 0.051)

Lansdowne AT, RCT 800 IU, 44 healthy The positive and Significant improve- Vitamin D
Provost SC: Vita- 400IU or participants negative affect ment in positive supplementa-
min D3 enhances 0 IU of age 18-43 score affect score in both tion in healthy
mood in healthy vitamin D3 vitamin D groups controls during
subjects during plus 8000 (p<0.001). The winter im-
winter. Psychop- – 10 000 IU outcomes from the proves positive
harmacol, 1998; vitamin A different vitamin affect and may
135: 319-323 for 5 days D3 doses did not decrease nega-
during the differ significantly. tive affect
winter Improvements seen
in the negative affect
score did not reach
statistical significance
Shipowick CD, Quasi- 5000 IU 6 patients BDI-II completed Mean BDI-II score Supplementa-
Moore CB, Corbett experi- vitamin D3 with vitamin at baseline and decreased from tion of Vitamin
C, et al: Vitamin mental per day for D deficiency after 8 weeks of 31 to 21 D in deficient
D and depressive pre-test, 8 weeks (<40 ng/mL), supplementation (p = 0.020) population
symptoms in post-test during the age 23-55 during the
women during design winter; no winter may
the winter: A control or decrease
pilot study. Appl blinding depressive
Nur Res, 2009; 22: symptoms
221-225

to the hypothesis that vitamin D deficiency and as a result may have lower sun exposure.
plays a role in the pathogenesis of mood dis- Additionally, depressed individuals often
orders or its potential as a therapeutic agent. experience a decrease in appetite and eat
It is well known that depressed individuals poorly, which may result in broad-spectrum
are more likely to be less physically active26 nutrient deficiencies, including vitamin D3.

Khamba.indd 132 8/23/11 1:46:37 PM

 Effectiveness of Vitamin D in the Treatment of Mood Disorders: A Literature Review 133

Figure 2. Intervention Studies, cont’d

Reference Type of Inter- Subjects Assessment of Result Conclusion
Study vention Intervention

Sanders KM, Stuart RCT Annual dose 2,317 com- 12-item Short 12-item Short The mental
Al, Williamson of 500,000 munity Form Health Form Health Sur- well-being
EJ, et al: Annual IU of dwelling Survey (SF-12) vey: no difference of older
high-dose vitamin Vitamin D3 Australian assessing physical in physical (41.4 women in
D3 and mental well- or placebo women, and mental com- vs. 41.2, p= 0.66) Australia did
being: a randomized in autumn/ at least 70 ponents of health; or mental (52.5 not appear to
controlled trial. Br J winter years of WHO Well-being vs. 52.6, p= 0.75) benefit from
Psychiatry, 2011; 198: age selected Index was done scores between annual high
357-364. for a trial in subset of 150 treatment and dose vitamin
on fractures patients placebo groups. D supplemen-
WHO Well- tation
being Index in
patient subset:
no differences
in questionnaire
scores or use of
medication be-
tween treatment
and placebo
groups and no
trend between
serum 25OHD
and scores

Vieth R, Kimball S, Hu RCT 95 mcg/ 112 patients Completed brief In the 4000 IU Vitamin D
A, Walfish PG: Ran- week (600 with vitamin questionnaire group, the cor- supplementa-
domized comparison IU/ day) or D deficiency based on screen- relation between tion improves
of the effects of the 700 mcg/ ing for depression; wellbeing score wellbeing;
vitamin D3 adequate week (4000 6 questions on and months of 4000 IU is
intake versus 100 IU/day) of mood, energy, being on vitamin safe for 1-year
mcg (4,000 IU) per vitamin D3 sleep, pleasure, D was statisti- and produces
day on biochemical for one year concentration, cally significant a greater
responses and the and weight (p=0.002). Al- therapeutic
wellbeing of patients. change though improve- response than
Nutr J, 2004; 3: 8. ments were 600 IU
observed for the
600 IU group, they
were not statisti-
cally significant.
Neither group had
changes in serum
calcium

One cohort study addressed the issue sion symptoms were only assessed on two
of causality.5 This study observed serum occasions, depressive episodes that occurred
25OHD levels at baseline in 639 non-de- at other times over the six year period were
pressed elderly patients and monitored for not factored in the statistical analysis. De-
the development of depression after three spite this, participants with lower baseline
and six years. One limitation of this study 25OHD levels reported greater increases in
was the timing of follow-up. Because depres- scores on the CES-D suggesting that ad-

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 134 Journal of Orthomolecular Medicine Vol 26, No 3, 2011

equate vitamin D may be protective. Of the six intervention trials, five

Among the RCTs, results varied. The showed a trend towards reduced depression
largest study was conducted on elderly with vitamin D3 supplementation. While
women in Australia as part of a study on hip methodological challenges existed in all of
fractures and falls. While this study failed to the studies, the results suggest that the vita-
show a benefit in well-being there were sev- min might be beneficial.
eral weaknesses in the study.27 Because the
study took place in a country known for its Conclusion
high sun exposure, a very small percent of the The results suggest an association be-
participants were deficient at baseline. Sur- tween vitamin D insufficiency and deficiency
prisingly, the treatment group experienced and the presence of mood disorders. Vitamin
a 15% increased risk of falls and a 26% in- D3 supplementation might also be helpful
creased risk of fractures. It is well established in the treatment of mood disorders. More
that these events have significant adverse ef- RCTs are warranted to determine the level
fects on elderly individuals’ wellbeing, which of insufficiency and deficiency that places an
may have negated any psychological benefits individual at risk for mood disorders, and to
from vitamin D supplementation. While determine the optimal dosage of vitamin D3
the population of patients receiving the in- yielding sufficient antidepressant effects in
tervention was large, the subgroup in which healthy and at-risk populations.
well-being was assessed was relatively small.
Additionally, a large annual dose of vitamin References
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