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A review of the research shows the effectiveness of vitamin D and other nutrients on depression and suicide

by Max Langen

FOR IMMEDIATE RELEASE
Orthomolecular Medicine News Service, April 4, 2023

OMNS (April 4, 2023) Globally, approximately 800,000 people die from suicide every year, [1,2] which seems shocking. This is more than the entire population of Seattle, Washington. In the age groups 15 to 29 and 15 to 44, suicide is the second and third leading cause of death. [2] According to experts, the number of attempted suicides is even 10 to 30 times higher (in some subgroups, it may even be up to 200 times higher). [2] In other words, there may be 8 to more than 24 million attempted suicides per year.

Besides the huge emotional pain the victims go through, almost all of these 800,000 people have relatives and friends who will often suffer from severe emotional trauma, shock, grief, pain, anger, guilt etc. after their loved one committed suicide. Thus, the amount of pain associated with and resulting from suicide and suicide attempts is immeasurably high. It is a worldwide emergency.

While suicide has many different causes and risk factors, many recent studies have suggested that low sunshine exposure and vitamin D deficiency may be a major factor in suicide. A recent meta-analysis of 20 studies showed a significant association between latitude and suicide. A higher latitude was associated with a higher prevalence of suicide. [1] In other words, more exposure to sunshine seems to be protective by reducing the risk of suicide.

Many additional studies have shown that vitamin D deficiency is associated with a higher risk of suicidal ideation, suicide attempts and completed suicide. [3-8] People who attempted suicide had significantly lower vitamin D levels than healthy controls. [6-8] A genetic predisposition to lower vitamin D levels was also associated with a higher risk of suicide attempts, which suggests that vitamin D may have a preventative potential against suicide attempts. [9] People with a genetic predisposition to lower vitamin D levels might require higher amounts of vitamin D to stay healthy.

A recent study of more than 1 million US veterans investigated whether there is an association between prescribed supplementation of vitamin D and suicide attempts or intentional self harm. The authors conducted a propensity score matching in order to reduce the risk of confounding and to make the vitamin D-treated groups and the control groups as comparable as possible. The results showed that vitamin D supplementation cut the risk of a suicide attempt or intentional self harm almost in half. [10]

Subgroup analyses also showed that those who had the lowest vitamin D levels pre supplementation had the strongest risk reduction with regard to suicide attempts or self harm. The stronger the deficiency, the greater the benefit from taking it. For example, in the group of veterans who had 0 to 19 ng/ml pre supplementation, the risk reduction due to supplementation of D3 was 64%. Among those who had a level of 20 to 39 ng/ml pre supplementation, each additional percentage point increase in average daily dosage of D3 was associated with a 9.6% reduction. Also, black veterans achieved an even higher reduction in risk due to supplementation of vitamin D than white veterans. This was likely due in part to the fact that dark skinned individuals get less vitamin D from sunlight so they tend to have a higher prevalence of deficiency, and thus benefit more from it. [10]

Our brain requires sufficient sunshine and vitamin D to function properly. With a deficiency of vitamin D and other nutrients, synthesis of neurotransmitters no longer functions correctly, inflammatory processes increase, [7] the brain no longer has the energy to adequately deal with the challenges in life, and thus depression may arise.

An insufficiency of vitamin D (< 30 ng/ml) affects 75% of the global adult population. [11,12] Since those who attempt suicide are more likely to have a deficiency of vitamin D, this suggests that a correction of this global vitamin D insufficiency might have the potential to help prevent hundreds of thousands of suicides and millions of suicide attempts per year.

This suggestion is further supported by five recent studies:

  • A meta-analysis of 25 placebo-controlled RCTs with more than 7000 participants indicated that supplementation of vitamin D reduces negative emotions. [13]
  • A meta-analysis of 3 RCTs with more than 150 diabetic patients showed that vitamin D improved depressive symptoms significantly more than a placebo. [14]
  • A meta-analysis of 29 studies with more than 4500 participants showed that supplementation of vitamin D reduced the incidence of depression. A daily dose of >2800 IU was effective for the prevention and treatment of depression, especially among participants with low baseline levels. [15]
  • A meta-analysis of 18 placebo-controlled RCTs confirmed that supplementation of vitamin D reduces symptoms of depression. Further, patients with more severe depression responded even better than those with less severe symptoms. [15]
  • And finally, an umbrella meta-analysis showed that people with low vitamin D levels have a higher risk of developing depression than those with a sufficient level. Supplementation of (especially higher doses of) vitamin D reduced depression scores more than a placebo. [16]

Worldwide, more than 250 million people suffer from depression. The prevalence of depression among adults is estimated to be 5%. And this is the main cause of suicide. [2]

Unfortunately, while vitamin D deficiency is common among depressed patients and is likely one of the main causes of this severely disabling condition, many only receive antidepressants or psychotherapy. Without a doubt, antidepressants or psychotherapy may be helpful. However, such approaches do not correct nutrient deficiencies, which is why many patients do not respond to these therapies and don´t get well. These individuals will often be described as “treatment resistant”, which is a misleading statement that often causes them even more desperation. The reason they do not get well may be that the treatment they received is incorrect or incomplete. When severe nutrient deficiencies exist, the brain metabolism will not function correctly. Biochemical healing is only possible if all required nutrients are provided in adequate doses.

A double-blind placebo-controlled study showed that combined treatment with the antidepressant fluoxetine + vitamin D was significantly more effective in the treatment of depressive disorders than fluoxetine alone. [18] And interestingly, in a double-blind study with the omega-3 fatty acid EPA, the combination of fluoxetine + EPA was also significantly more effective for patients with major depressive disorder than fluoxetine monotherapy. [19]

“Dr. Carl C. Pfeiffer said that there is a nutritional alternative to nearly every drug, and Dr. Abram Hoffer cautioned that patients that use drugs only do not get well. I firmly agree.” — Andrew Saul, PhD.

When taking vitamin D, co-factors should not be forgotten. Without them, vitamin D can not be activated correctly and won’t work as intended. Also, if the cofactors are not considered, the risk of side effects is increased. Nutrients work together in the body, and the body requires all of them to support its metabolism (synergy). Therefore, in order to protect physical and mental health and make sure that all biochemical or metabolic processes (including in the brain) can be carried out as intended by nature, all nutrients need to be provided in adequate and coordinated doses.

Magnesium and vitamin K2 are among the most important cofactors. Half of all adults in the USA do not consume adequate magnesium, which explains why a deficiency of this mineral is extremely common, affecting many or most of the people in America and Europe. In fact, depending on the population, the rate of magnesium deficiency or insufficiency may range between 30 to 90%. [12,20] Something similar is true for vitamin K2. Up to 97% of older adults suffer from a deficiency or insufficiency of vitamin K2 [21] which is another huge public health challenge.

Interestingly, a deficiency of magnesium is another important cause of depression and treatment with magnesium has shown in RCTs to be effective. In recent studies, it significantly reduced symptoms of depression. [22,23] Thus the widespread undersupply of the cofactor magnesium is likely another major factor in suicidality. And even vitamin K2 is likely effective for depression. In a new RCT, supplementation of K2 significantly alleviated depression in women with polycystic ovary syndrome (PCOS). [24]

The protocol comprising vitamins D and K2, magnesium, and omega-3 fatty acids is helpful as a basis for excellent physical and mental health. If everyone got adequate amounts of these nutrients, we would likely see fewer cases of suicides and depression. Nutritional therapy / Orthomolecular medicine saves lives. The doses required are based on individual need. A qualified orthomolecular therapist who can provide medical advice may help finding the appropriate doses and can also help finding out whether individual contraindications exist. If the vitamin D blood level is known, this free vitamin D calculator can be used to help guide dosing: https://www.grassrootshealth.net/project/dcalculator

Long term supplementation of vitamin D (5000-10,000 IU/d) is safe for most adults. [25] This dose will bring the level of a typical adult up to 40-60 ng/ml, which will empower the body’s immune system to prevent viral infections and autoimmune disease, reduce the risk of cancer, and lower the risk of depression during the winter months. Also, the metabolism of vitamin D requires magnesium, so it is often helpful to take both together. [11,12] Magnesium (300-500 mg/d in citrate, malate, gluconate, or chloride form) and vitamin K2 (100 mcg/d for each 5000 – 10,000 IU/d D3) should be taken with vitamin D. It is best to find the appropriate dose for the individual, which can be based on lab testing. [11,12] Magnesium should be taken several hours apart from thyroid medications and some antibiotics.

And of course, several other nutrients also relevant for the prevention and treatment of depression. For example, niacin can be helpful for enhancing mental health. [26,27] Omega-3 fatty acids (walnuts, flaxseed meal/oil, and 300-600 mg/d of DHA & EPA) are helpful for health including brain function. [28-30] Eating disorders are a major risk factor in suicide. [31]

For people who are dealing with suicidal ideation, note that therapists who are working in this field often describe the experience that most of those who attempted suicide but survived are happy that they did! No matter how dark or hopeless things may look in a given moment, each situation can change and improve. There is always hope and everyone can find a new perspective or something worth living for. And please do not stay alone with these thoughts and feelings. You can talk (anonymously) to people or therapists who would really like to listen, to help you solve the challenges in life and find new perspectives. You can always find a good empathic person. Stay strong; the sun will come back to you.

In the United States, if someone you know is considering suicide, help is available by calling 988, available in English or Spanish every day 24 hours per day, or visit: https://988lifeline.org/help-someone-else. And here is a 4 minute Mayo Clinic Teen Suicide Prevention public service video: https://www.mayoclinic.org/vid-20141366

(Max Langen has found that his own health problems were greatly alleviated by orthomolecular medicine. He is currently working on a book about it, and has plans to qualify as a therapist.)

Are You Getting Enough Vitamin D?

The only way to know is to test your levels! Testing versus blind supplementation is essential to know for sure if what you are taking is the right amount for you. Once you test your vitamin D (and other levels) to know where you are NOW, you can account for any upcoming changes in lifestyle over the coming months and adjust your intake to reach (or maintain) your targets.

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References:

1. An S, Lim S, Kim HW, et al. (2023) Global prevalence of suicide by latitude: A systematic review and meta-analysis. Asian J Psychiatr. 81:103454. https://pubmed.ncbi.nlm.nih.gov/36634498

2. Bachmann S (2018) Epidemiology of Suicide and the Psychiatric Perspective. Int J Environ Res Public Health 15:1425. https://pubmed.ncbi.nlm.nih.gov/29986446

3. Umhau JC, George DT, Heaney RP, et al. (2013) Low vitamin D status and suicide: a case-control study of active duty military service members. PLoS One. 8:e51543. https://pubmed.ncbi.nlm.nih.gov/23308099

4. Calderón Espinoza I, Chavarria-Avila E, Pizano-Martinez O, et al. (2022) Suicide Risk in Rheumatoid Arthritis Patients is Associated With Suboptimal Vitamin D Levels. J Clin Rheumatol. 28:137-142. https://pubmed.ncbi.nlm.nih.gov/35293886

5. Kim SY, Jeon SW, Lim WJ, et al. (2020) Vitamin D deficiency and suicidal ideation: A cross-sectional study of 157,211 healthy adults. J Psychosom Res. 134:110125. https://pubmed.ncbi.nlm.nih.gov/32388454

6. Gokalp G (2020) The association between low vitamin D levels and suicide attempts in adolescents. Ann Clin Psychiatry 32:106-113. https://pubmed.ncbi.nlm.nih.gov/32384132

7. Grudet C, Malm J, Westrin A, Brundin L (2014) Suicidal patients are deficient in vitamin D, associated with a pro-inflammatory status in the blood. Psychoneuroendocrinology 50:210-9. https://pubmed.ncbi.nlm.nih.gov/25240206

8. Atik D, Cander B, Dogan S, et al. (2020). Relationship between suicidal patients and vitamin D: A prospective case-control study. J Surg and Med. 4:766-770. https://dergipark.org.tr/en/pub/josam/issue/56766/727963

9. Wei YX, Liu BP, Qiu HM, et al. (2021) Effects of vitamin D-related gene polymorphisms on attempted suicide. Psychiatr Genet. 31:230-238. https://pubmed.ncbi.nlm.nih.gov/34412081

10. Lavigne JE, Gibbons JB. (2023) The association between vitamin D serum levels, supplementation, and suicide attempts and intentional self-harm. PLoS One. 18:e0279166. https://pubmed.ncbi.nlm.nih.gov/36724169

11. Reddy P, Edwards LR (2019) Magnesium Supplementation in Vitamin D Deficiency. American Journal of Therapeutics 26:e124-e132. https://pubmed.ncbi.nlm.nih.gov/28471760

12. Dean C (2017) The Magnesium Miracle. Ballantine Books. ISBN-13: 978-0399594441

13. Cheng YC, Huang YC, Huang WL. (2020) The effect of vitamin D supplement on negative emotions: A systematic review and meta-analysis. Depress Anxiety. 37:549-564. https://pubmed.ncbi.nlm.nih.gov/32365423

14. Putranto R, Harimurti K, Setiati S, et al. (2022) The Effect of Vitamin D Supplementation on Symptoms of Depression in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Acta Med Indones. 54:574-584. https://pubmed.ncbi.nlm.nih.gov/36624711

15. Xie F, Huang T, Lou D, et al. (2022) Effect of vitamin D supplementation on the incidence and prognosis of depression: An updated meta-analysis based on randomized controlled trials. Front Public Health. 10:903547. https://pubmed.ncbi.nlm.nih.gov/35979473

16. Srifuengfung M, Srifuengfung S, Pummangura C, et al. (2023) Efficacy and acceptability of vitamin D supplements for depressed patients: A systematic review and meta-analysis of randomized controlled trials. Nutrition 108:111968. https://pubmed.ncbi.nlm.nih.gov/36716601

17. Musazadeh V, Keramati M, Ghalichi F, et al. (2023) Vitamin D protects against depression: Evidence from an umbrella meta-analysis on interventional and observational meta-analyses. Pharmacol Res. 187:106605. https://pubmed.ncbi.nlm.nih.gov/36509315

18. Khoraminya N, Tehrani-Doost M, Jazayeri S, et al. (2013) Therapeutic effects of vitamin D as adjunctive therapy to fluoxetine in patients with major depressive disorder. Aust N Z J Psychiatry 47:271-275. https://pubmed.ncbi.nlm.nih.gov/23093054

19. Jazayeri S, Tehrani-Doost M, Keshavarz SA, et al. (2008) Comparison of therapeutic effects of omega-3 fatty acid eicosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder. Aust N Z J Psychiatry 42:192-198. https://pubmed.ncbi.nlm.nih.gov/18247193

20. DiNicolantonio JJ, O’Keefe JH. (2021) Magnesium and Vitamin D Deficiency as a Potential Cause of Immune Dysfunction, Cytokine Storm and Disseminated Intravascular Coagulation in covid-19 patients. Mo Med. 118:68-73. https://pubmed.ncbi.nlm.nih.gov/33551489

21. Pizzorno L, Pizzorno J. (2022) Vitamin D (Like Every Nutrient) is a Team Player. Integr Med (Encinitas). 21:8-14. https://pubmed.ncbi.nlm.nih.gov/36644600

22. Afsharfar M, Shahraki M, Shakiba M, et al. (2021) The effects of magnesium supplementation on serum level of brain derived neurotrophic factor (BDNF) and depression status in patients with depression. Clin Nutr ESPEN. 42:381-386. https://pubmed.ncbi.nlm.nih.gov/33745609

23. Tarleton EK, Littenberg B, MacLean CD, et al. (2017) Role of magnesium supplementation in the treatment of depression: A randomized clinical trial. PLoS One 12:e0180067. https://pubmed.ncbi.nlm.nih.gov/28654669

24. Tarkesh F, Namavar Jahromi B, Hejazi N, Hoseini G. (2022) Effect of vitamin K2 administration on depression status in patients with polycystic ovary syndrome: a randomized clinical trial. BMC Womens Health 22:315. https://pubmed.ncbi.nlm.nih.gov/35883082

25. Grant WB (2021)Top Vitamin D Papers in 2021: Benefits ignored at a time they are most needed. Orthomolecular Medicine News Service http://orthomolecular.org/resources/omns/v18n02.shtml

26. OMNS (2005) Mental Health Treatment That Works. Orthomolecular Medicine News Service. http://orthomolecular.org/resources/omns/v01n11.shtml

27. Saul AW, Hoffer A, Foster HD (2023) Niacin: the Real Story, 2nd Ed. Basic Health Pub. ISBN-13:‎ 978-1684429028

28. Healy-Stoffel M, Levant B (2018) N-3 (Omega-3) Fatty Acids: Effects on Brain Dopamine Systems and Potential Role in the Etiology and Treatment of Neuropsychiatric Disorders. CNS Neurol Disord Drug Targets. 17:216-232. https://pubmed.ncbi.nlm.nih.gov/29651972

29. Patrick RP, Ames BN (2015) Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior. FASEB J. 29:2207-2222. https://pubmed.ncbi.nlm.nih.gov/25713056

30. Mehdi S, Manohar K, Shariff A, et al. (2023) Omega-3 Fatty Acids Supplementation in the Treatment of Depression: An Observational Study. J Pers Med. 13:224. https://pubmed.ncbi.nlm.nih.gov/36836458

31. Greenblatt JM (2011) Nutritional Risk Factors for Suicide. Psychology Today. https://www.psychologytoday.com/us/blog/the-breakthrough-depression-solution/201109/nutritional-risk-factors-suicide

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