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Vitamin D and the Effect on Mental Health

Original Editor - Kapil Narale

Top Contributors - Kapil Narale, Lucinda hampton and Tolulope Adeniji  

Introduction

Vitamin D contains antioxidant properties. Vitamin D has immunomodulatory, neuroprotective, and neurotrophic properties and can affect the parts of the brain involved in the pathophysiology of depression and anxiety. Vit D is important for mood disorders preventions or treatments[1]. Vitamin D deficiency can be associated with an increased risk of mental health impairments. [2]

Vitamin D

Vitamin D has many beneficial physiological functions, including the balance of calcium [3] and phosphate [4], and the metabolism of bone, muscle, and energy. [3] It helps with cell growth and neuromuscular and immune function. It also is involved in immunomodulation, neuroplasticity, and oxidative stress. [4] Extreme minimal levels of Vitamin D may lead to poor physical performance. [5] It can have a negative effect on the muscles of the lower limb responsible for postural control, and with exercise and grip strength, and affect immunity. [6] Low Vitamin D levels can also play a role in non-skeletal, age-associated diseases, including cancer, heart disease, metabolic syndrome, Type 2 diabetes mellitus, stroke, and neurodegenerative and neuropsychiatric diseases. [4]

Normal values of 25(OH)D (vitamin D) vary between 50–160 nmol/L. Values between 25–50 nmol/L are defined as vitamin D insufficiency. Vitamin D deficiency is defined as <25 nmol/L. These levels are seen to be lower in individuals with darker skin. [7][8]

The majority of Vitamin D is produced when the ultraviolet B rays [9] [4] (260-320nm wavelength [4]) from the sun have an interaction with the skin. In fact, 90% of Vitamin D comes from this interaction. It is evident that Vitamin D has an effect on muscle physiology, since Vitamin D receptors are present in muscle cells. It is seen that vitamin D supplements help improves neuromuscular performance, as well as improving muscular strength and postural control. [9]

Vitamin D can also be obtained from the diet, but in minor quantities. Vitamin D2 can be obtained from plants, fungi, or yeast, while Vitamin D3 can be found in plants, and some meat sources, and especially cold-water fish. [4]

In areas with a minimal exposure to the sun, there may be an association of low levels of Vitamin D with with an increased risk of depression, which can lead to suicidal thoughts. It is seen that there is an even higher risk of suicide where there is an even lower concentration of Vitamin D. When concentrations of Vitamin D are increased due to supplementation, cognitive function and mood are improved. Vitamin D also affects the function of the Central Nervous System. As noted below, Vitamin D is involved in the processes of over 1000 genes within the brain. [6]

Suboptimal levels of Vitamin D are common in Denmark. It is noted that the prevalence of vitamin D deficiency in blood donors is 18%, and vitamin D insufficiency is 47%. [10] Vitamin D deficiency is seen to be prevalent during the Winter time, due to increased covering of the skin [9], and from working indoors. Working indoors was seen as a risk factor for mood difficulties in civil servants, as observed in a Danish cross-sectional study. [9]

Vitamin D supplementation is encouraged to achieve the necessary levels of Vitamin D in the body. Recommended levels of intake are different for different people based on various factors, but an intake of 5000 IU/day is considered a safe upper limit of intake. However for a long term supplementation, 2000 IU/day would be the safe recommended limit. Doses > 5000IU can lead to life-threatening hypercalcemia, which can have toxic effects such as nausea, vomiting, weakness, polyurea, nephrocalcinosis, or even renal failure. [4]

Calcitrol and Vitamin D

One of the key functions of calcitriol is its involvement in the synthesis and degradation of neurotransmitters. It also plays an important role in regulating various neurotrophic factors, and is an antioxidative defense mechanism for the brain. [2]

Calcitrol binds to a specific ligand, the Vitamin D receptor (VDR), which affects the gene expression of various target genes. VDR is located within the Central Nervous System (CNS), and the necessary enzymes and receptors spread throughout the human brain. The Vitamin D endocrine system acts within the CNS. [2]

Calcitrol activates the gene expression of tyrosine hydroxylase, which increases the use of dopamine, adrenaline, and noradrenaline. It may advance the activation of cholinergic function, accelerating the activity of choline acetyltransferase and reducing the activity of acetylcholine esterase. [2]

Calcitriol helps enhance nerve growth factor (NGF) and glial derived neurotrophic factor (GDNF). It also helps increase the activity of neurotrophin-3 (NT-3), and decrease neurotrophin-4 (NT-4). NGF is important for the prenatal development of the brain, and it may prevent degradation of the cholinergic system in Alzheimer’s Disease. It can be noted that NGF, NT-3, and GDNF can be factors for depression and schizophrenia. GDNF can act as a treatment with Parkinson's Disease, and dependence disorders. [2]

Vitamin D defends the brain against oxidative damage. It increases the gene expression of the enzyme aiding in the function of the most important antioxidant in the brain, glutathione, and helps increases the levels of this antioxidant. [2]

It is seen that alterations in the Vitamin D supply in the brain, can interfere with brain functions directed to psychiatric and neuropsychiatric behaviours. There can be disorders developed on a seasonal basis. The lack of vitamin D exposure can lead to a delay in early brain development, and even brain degeneration in the elderly. [2]

It is noted that Vitamin D helps cause a more positive and happier mood in healthy adults, in the Winter months. [2]

Vitamin D and the Effect on Anxiety

According to Davis et al, Anxiety is defined as: [11]

"a negative, vague, and unpleasant emotional state derived from the anticipation of a potential hazard and generates hypervigilance and alertness, even in the absence of immediate danger."

Anxiety can be a normal symptom of day-to-day living, but when seen in unreasonable amounts, it can be considered pathological. There are many different types of anxiety with differing clinical characteristics, but the somatic, cognitive, behavioural characteristics all affect the normal functioning of an individual.

Not all anxiety medications or anti-depressive drugs are effective for all types of individuals or to address all types of anxiety, as there can be adverse effects and reduce adherence to treatment methods. [12] However, it is seen that Vitamin D, which has antioxidant and anti-inflammatory properties, can be used to help relieve anxiety. [4] It is noted that anxiety symptoms can be associated with low levels of Vitamin D, [13][14] [15][16] however it can be shown that an association doesn't have to be present. [17][18][19]

Some studies found that there was an association between Vitamin D supplementation and the reduction of anxiety, while other studies did not observe such an association[20]. Research needs to be conducted to observe this association between general anxiety and the use of Vitamin D supplementation, since such studies do not exist. [4]

Vitamin D and Major Depressive Disorder (MDD)

Major Depressive Disorder (MDD) is a neuropsychiatric condition, which can be highlighted by low mood, decreased self-esteem, loss of interest or satisfaction in daily pleasurable activities (anhedonia), and fatigue. This is seen to occur at double the prevalence in females, and it is seen to leave an impairment to a person's daily functioning. [21]

Depressive symptoms may be a result from a dysfunction in neurotrophic support and neurogenesis, neuroinflammation, disturbance of bioenergetic signaling, oxidative stress, and excitotoxicity. These can all occur from long-term stress, which can be a result from the facilitation of the peripheral macrophages and central microglia, dysfunction of the hypothalamus–pituitary–adrenal (HPA) axis and hypercortisolemia, and a consequent impairment of synaptic plasticity, dendritic spine growth, and synaptic communication. [4]

Since Vitamin D has a positive effect on neuroimmunomodulation and neuroplasticity, and may reduce oxidative stress, it has been used to prevent and/or treat major depressive disorder. Vitamin D may have a positive effect on metabolic and/or inflammatory conditions. Further research is needed to determine whether Vitamin D is effective against depressive symptoms, which may be associated with systemic inflammatory conditions. [4]

Developmental Vitamin D Deficiency and Adult Schizophrenia

Vitamin D deficiency, due to poor nutrition, during pregnancy or early childhood has been suggested as a possible risk factor for developing mental illnesses such as schizophrenia later in life. Consequently, individuals born during the Winter months have a greater risk of developing schizophrenia. [2]

It may also occur in individuals who grew up in areas where exposure to the sun is limited. [2]

Vitamin D Deficiency and Autism Spectrum Disorders

Some studies suggest a potential link between Vitamin D deficiency in early childhood and an increased risk of developing autism spectrum disorder, though more research is needed. The prevalence of autism increased in the US when individuals were advised on avoiding exposure to the sun. There may be more children with autism born in areas where there is more rain than sun. This was mainly noted in Washington State, Oregon, and California. [2]

Seasonal Affective Disorders

See the Seasonal Affective Disorders page for a thorough explanation on this topic.

Possible Negative Effects

Increased exposure to sunlight raises the risk of skin cancer, particularly malignant melanoma. However, avoiding sunlight altogether can increase the risk of vitamin D deficiency and associated health issues. With the change of minimising exposure to sunlight, there was a noted increased prevalence of major depressive disorder in the US and Europe, especially among children and adolescents. There can also be an increased prevalence of autism spectrum disorder. [2]

Applicability to Clinicians

Clinicians of medical professions are prone to mental illnesses due to the demands of the type of work they perform. About 20% of doctors experience mental illnesses during their careers. Male and female doctors both have a higher risk of suicide compared to the general public. [22] Surgeons who are middle aged are most likely to seek help from their GPs/family doctors with symptoms of depression, anxiety, and burnout. [23][24]

Due to the mental and physical demand of the type of work that clinicians perform, it is essential that they take advantage of supplements to increase the stores of vitamins and minerals in the body. It is interesting to note that the mental demands such as focus, attention, technical skill, and levels of stress, of Doctors or Surgeons can be comparable to that of Olympic Athletes. [25]

Clinicians are prone to experiencing Vitamin D deficiency due to working indoors with very minimal exposure to natural light. Clinicians, like surgeons, who need precise fine motor control, would need to maintain optimal Vitamin D levels, not experiencing a deficiency, thus can benefit from a supplement. [9]

Video Resources

Here are some videos explaining the effect of Vitamin D on mental health:

[26]
[27]


References

  1. ↑ Akpınar Ş, Karadağ MG. Is vitamin D important in anxiety or depression? What is the truth?. Current nutrition reports. 2022 Dec;11(4):675-81.Available:https://pmc.ncbi.nlm.nih.gov/articles/PMC9468237/ (accessed 19.10.2024)
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 Humble M.B. Vitamin D, light and mental health. Journal of Photochemistry and Photobiology B: Biology. 2010:101;142-149.
  3. ↑ 3.0 3.1 Gaffney-Stomberg E, Lutz L.J, Rood J.C, Cable J.S, Pasiakos S.M, Young A.Y, McClung J.P. Calcium and vitamin D supplementation maintains parathyroid hormone and improves bone density during initial military training: a randomized, double-blind, placebo controlled trial. Bone. 2014:68:46–56.
  4. ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 Casseb G.A.S, Kaster M.P, Rodrigues A.L.S. Potential Role of Vitamin D for the Management of Depression and Anxiety. CNS Drugs. 2019:33:619–637.
  5. ↑ He C.S, Aw Yong X.H, Walsh N.P, Gleeson M. Is there an optimal vitamin D status for immunity in athletes and military personnel? Exercise Immunology Reviews. 2016:22:42–64.
  6. ↑ 6.0 6.1 Umhau J.C, George D.T, Heaney R.P, et al. Low vitamin D status andsuicide: a case-control study of active duty military service members. PLoS One 2013:8:1-7.
  7. ↑ Fitzpatrick T.B. The validity and practicality of sun-reactive skin types I through VI. Archives of Dermatology. 1988:124(6):869–871.
  8. ↑ Godar D.E, Pope S.J, Grant W.B, Holick M.F. Solar UV doses of adult Americans and vitamin D(3) production. Dermatoendocrinology. 2011:3(4):243–250.
  9. ↑ 9.0 9.1 9.2 9.3 9.4 Parrya D.A, Oeppenb R.S, Aminc M, Brennand M.A. Can dietary supplements improve a clinician’s well-being and health? British Journal of Oral and Maxillofacial Surgery. 2018:56:85–89.
  10. ↑ Mosekilde L, Nielsen L.R, Larsen E.R, Moosgaard B, Heickendorff L. Vitamin D deficiency. Definition and prevalence in Denmark. UgeskrLaeger. 2005:167(1):29–33.
  11. ↑ Davis M, Walker D.L, Miles L, Grillon C. Phasic vs sustained fear in rats and humans: role of the extended amygdala in fear vs anxiety. Neuropsychopharmacology. 2010:35(1):105–135.
  12. ↑ Farach F.J, Pruitt L.D, Jun J.J, Jerud A.B, Zoellner L.A, Roy-Byrne P.P. Pharmacological treatment of anxiety disorders: current treatments and future directions. Journal of Anxiety Disorders. 2012:26(8):833–843.
  13. ↑ Pu D, Luo J, Wang Y, Ju B, Lv X, Fan P, He L. Prevalence of depression and anxiety in rheumatoid arthritis patients and their associations with serum vitamin D level. Clinical Rheumatology. 2018:37(1):179–184.
  14. ↑ Karonova T.L, Andreeva A.T, Beljaeva O.D, Bazhenova E.A, Globa PJ, Vasil’eva E.J, Grineva E.N. Anxiety/depressive disorders and vitamin D status. Zhurnal nevrologii i psikhiatrii imeni SS Korsakova. 2015:115(10 pt 2):55–58.
  15. ↑ Bicikova M, Duskova M, Vitku J, Kalvachova B, Ripova D, Mohr P, Starka L. Vitamin D in anxiety and affective disorders. Physiological Research. 2015:64(2):101–103.
  16. ↑ Han B, Zhu F.X, Yu H.F, Liu S, Zhou J.L. Low serum levels of vitamin D are associated with anxiety in children and adolescents with dialysis. Scientific Reports. 2018:8(1):5956.
  17. ↑ Bossola M, Ciciarelli C, Di Stasio E, Conte GL, Vulpio C, Luciani G, Tazza L. Correlates of symptoms of depression and anxiety in chronic hemodialysis patients. General Hospitaluty Psychiatry. 2010:32(2):125–131.
  18. ↑ Can M.S, Baykan H, Baykan O, Erensoy N, Karlidere T. Vitamin D levels and vitamin D receptor gene polymorphism in major depression. Psychiatry Danub. 2017:29(2):179–185.
  19. ↑ Huang J.Y, Arnold D, Qiu C.F, Miller R.S, Williams M.A, Enquobahrie DA. Association of serum vitamin D with symptoms of depression and anxiety in early pregnancy. Journal of Women’s Health. 2014:23(7):588–595.
  20. ↑ Akpınar, Ş., & Karadağ, M. G. (2022). Is vitamin D important in anxiety or depression? What is the truth?. Current nutrition reports, 11(4), 675-681.
  21. ↑ Otte C, Gold S.M, Penninx B.W, Pariante C.M, Etkin A, Fava M, Mohr D.C, Schatzberg A.F. Major depressive disorder. Natural Reviews of Disorders Primers. 2016:2:160-165.
  22. ↑ Gerada C, Jones R. Surgeons and mental illness: a hid-den problem? BMJ Careers 2014. Available from URL: http://careers.bmj.com/careers/advice/view-article.html?id=20017282 (last accessed 20 November 2017).
  23. ↑ Balch C.M, Freischlag J.A, Shanafelt T.D. Stress and burnout among surgeons: understanding and managing the syndrome and avoiding the adverse consequences. Archives of Surgery. 2009:144:371–376.
  24. ↑ Sharma A, Sharp D.M, Walker L.G, Monson J.R.T. Stress and burnout in colorectal and vascular surgical consultants working in the UK National Health Service. Psychooncology 2008:17:570–576.
  25. ↑ Colbert S.D, Scott J, Dale T, Brennan P.A. Performing to a world class standard under pressure - can we learn lessons from the Olympians? British Journal of Oral Maxillofacial Surgery. 2012:50:291–297.
  26. ↑ Nootropedia. Vitamin D - Improve Cognitive Performance and Mood (but Don't Take Too Much). Available from: https://www.youtube.com/watch?v=AwTN9rVJ5Aw&t=2s&ab_channel=Nootropedia (accessed 6 July 2024).
  27. ↑ The Anxious Resistance. Boost Your Mental Health with Vitamin D: The Ultimate Guide. Available from: https://www.youtube.com/watch?v=V7EnVUe1EaU&t=104s&ab_channel=TheAnxiousResistance (accessed 6 July 2024).
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