Vitamin D Has More Benefits Than Previously Thought
Vitamin D has long been known as an important vitamin for bone health, preventing conditions such as osteoporosis and rickets. More recently, research suggests that vitamin D may also protect against conditions such as cancer, heart failure, diabetes, respiratory tract infections, and autoimmune disease.
Many Americans have low vitamin D or a vitamin D deficiency. The human body produces vitamin D in large amounts when the skin is exposed to ultraviolet B rays in sunlight. Vitamin D can also be absorbed from vitamin D–fortified foods such as dairy products, some orange juice, and cereals. Some foods such as fatty fish, beef liver, and egg yolks naturally contain some vitamin D, but it is difficult to get enough vitamin D just from consuming these foods.
Low mood or seasonal affective disorder (SAD), in which people feel depressed during winter periods of limited exposure to sunshine, have been linked to low vitamin D.
Other symptoms of low vitamin D vary but can include pain in the joints, bones, or muscles; fatigue; and breathing problems.
Editor’s Note: A few small studies have suggested that 1,500 IU per day of vitamin D supplements can help depressed mood, even in those with normal vitamin D levels. Several studies have indicated that children or adolescents with psychiatric disorders are especially likely to be vitamin D–deficient. Another study found that higher amounts of vitamin D (4,000 IU) could improve cognition in healthy volunteers more than lower doses could. Vitamin D also improved cognition in people with multiple sclerosis and in those with the autoimmune disease Hashimoto’s thyroiditis.
Vitamin D Deficiency in Newborns Linked to Higher Risk of Schizophrenia in Adulthood
A 2018 study by Darryl W. Eyles in the journal Scientific Reports found that newborns with vitamin D deficiency were more likely to develop schizophrenia later in life. The study made use of several Danish data depositories and had a large sample size of 2,602 participants. In this case control study, registries of patients treated for schizophrenia were matched up to preserved dried blood samples collected at their births, and these were compared to other dried blood samples from people without schizophrenia who shared the same sex and birthdate.
The researchers divided participants into quintiles based on vitamin D levels at birth. Compared to those who fell into the fourth quintile, those in the lowest quintile were 44% more likely to be diagnosed with schizophrenia in adulthood. The researchers also determined polygenic risk scores for each participant, that is, they calculated schizophrenia risk based on the presence of various genes. The two processes together explained 1.2% of the variance in schizophrenia diagnoses.
Risk factors for vitamin D deficiency include being born in the winter or spring, living in high-latitude locations, spending early life in an urban setting, and being darker-skinned (especially in high-latitude locations). These risk factors are all correlated with decreased skin absorption of UV rays from the sun, which is how the human body produces vitamin D. The vitamin D receptor is expressed in the brain in areas that are relevant to schizophrenia, such as areas with a lot of dopamine activity, and each of the above risk factors also applies to schizophrenia.
As expected, participants born in the winter and spring had lower vitamin D levels. Participants whose parents had immigrated to Denmark had lower vitamin D than those with parents native to Denmark.
Newborns’ vitamin D levels depend completely on their mothers’ vitamin D levels, so Eyles and colleagues suggest that ensuring pregnant women have adequate vitamin D levels could prevent some cases of schizophrenia.
Adolescents with Bipolar Disorder May Have Higher Levels of Vitamin D–Binding Protein
Vitamin D binding protein. Illustration: Emw [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)]
A 2018 article by Brawnie Petrov and colleagues in the journal Translational Psychiatry suggests that adolescents with bipolar disorder have higher levels of vitamin D–binding protein than adolescents without a mood disorder. The researchers wrote that vitamin D–binding protein “responds early to cellular damage by binding…structural proteins and activating inflammatory cells.”
This pilot study suggests that measuring levels of vitamin D–binding protein could be a useful marker of bipolar disorder. The study was small, with only 12 participants who had bipolar disorder, 11 who had unipolar depression, and 13 with no mood disorder. The researchers hope to follow up with larger studies in adolescents and adults using blood that has already been collected from people with bipolar disorder.
Vitamin D–binding protein is not measured by a standard blood test. The study authors used a technique where they “fished” for inflammatory factors that might be linked to mood disorders. The researchers began by looking for a link between other inflammatory markers in the blood and bipolar disorder, which have repeatedly been found in other studies, but they did not find any such association. There also did not seem to be a link between bipolar illness and vitamin D levels in the blood, only vitamin D–binding protein levels.
It can be especially difficult to distinguish early bipolar disorder from unipolar depression, and if the results of this small study are replicated, a blood test might eventually help to identify people with bipolar disorder earlier.
Vitamin D3 Improves Depression in Older Adults
Researcher Negin Masoudi Alavi and colleagues reported in the journal Clinical Nutrition in 2018 that compared to placebo, 50,000 IU of vitamin D3 taken weekly for eight weeks improved depression in depressed patients over the age of 60.
Although the literature about vitamin D3’s effects on depression are mixed, a 2014 meta-analysis by Simon Spedding in the journal Nutrients found that in studies of vitamin D-deficient depressed participants whose vitamin D levels were restored to normal levels by the end of the study, vitamin D significantly improved depression. (Spedding attributed earlier mixed results to studies that did not clearly correct a vitamin D deficiency.) A 2013 study by Nayereh Khoraminya and colleagues in the Australian and New Zealand Journal of Psychiatry suggested that a 1500 IU dose of vitamin D3 combined with the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine improved depression more than fluoxetine plus placebo in depressed patients who were not necessarily deficient in vitamin D. Another study by Jacqueline A. Pettersen in the journal Experimental Gerontology found that in healthy adults, 4,000 IU of vitamin D3 improved cognitive functioning (namely visual memory) more than 400 IU.
Editor’s Note: Given these promising studies, the safety of D3, and fact that psychiatric patients are often deficient in vitamin D3, taking vitamin D3 supplements to improve depression might be worth trying.
High-Dose Vitamin D May Improve Cognition More Than Low-Dose Vitamin D
Vitamin D deficiency has been associated with dementia and cognitive decline, but supplements may help. In a study of 82 healthy individuals with low vitamin D levels, high-dose vitamin D supplements (4000 IU/day) improved visual/nonverbal memory more than did low-dose vitamin D supplements (400 IU/day) over 18 weeks.
The 2017 study took place in Canada, where short winter days can make it more difficult to get sufficient levels of vitamin D from sunlight. The higher-dose supplements raised blood levels of vitamin D compared with the lower-dose supplements.
Those who received the higher doses performed better at tests of visual memory such as the Pattern Recognition Memory Task and the Paired Associates Learning Task, but their performance on tests of verbal memory was not significantly different from those in the lower-dose group. This suggests that higher vitamin D levels are particularly important to visual/nonverbal memory.
The study by Jacqueline A. Pettersen was published in the journal Experimental Gerontology.
Dutch Study Links Low Vitamin D to Bipolar Disorder
A 2016 study in the Netherlands found that people with bipolar disorder are more likely to have vitamin D deficiency than the general population. Vitamin D deficiency has been linked to other psychiatric disorders including schizophrenia and unipolar depression. Poor diet and lack of exposure to sunlight can put someone at risk for vitamin D deficiency.
The study, led by Remco Boerman and published in the Journal of Clinical Psychopharmacology, included 118 adults with bipolar disorder, 149 with schizophrenia, and 53 with schizoaffective disorder. More than 30% of these participants had deficient levels of vitamin D. Only 15% had optimum levels of the vitamin. More than 22% of the participants with bipolar disorder were deficient in vitamin D, while close to 35% of those with schizophrenia and schizoaffective disorder were deficient.
Study participants had vitamin D levels that were 25% lower than those of the white Dutch population, and vitamin D deficiency was 4.7 times more common in those with psychiatric disorders than the general Dutch population.
The authors suggested screening people with bipolar disorder, schizophrenia, and schizoaffective disorder for low levels of vitamin D.
Vitamin D Deficiency Linked to Depression, But Supplements Helped
A review article in the Journal of Affective Disorders in 2017 summarized findings linking vitamin D to depression. Researcher Gordon B. Parker and colleagues found an association between low vitamin D levels and depression. They also found that vitamin D supplements improved treatment in people with clinical depression and vitamin D deficiency.
Editor’s Note: Vitamin D supplements are an obvious recommendation for people who are deficient. What has not yet been resolved is whether vitamin D is helpful to people who are depressed but not vitamin D deficient.
In a 2013 study in the Australian and New Zealand Journal of Psychiatry, Nayereh Khoraminya and colleagues suggested that a 1500 IU dose of vitamin D3 combined with the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine was more effective than fluoxetine plus placebo in depressed patients who were not necessarily deficient in vitamin D.
Giving Infants Vitamin D Can Reduce Type 1 Diabetes
A 2001 cohort study in Finland showed that giving vitamin D supplements to infants may reduce their risk for type 1 diabetes. The data for the study, by Elina Hyppönen and colleagues in the journal The Lancet, came from 10,366 people born in 1966. Their mothers were part of a medical registry that collected information on vitamin D given to children during the first year of their lives.
Of the 10,366 people in Hyppönen’s study, 81 had been diagnosed with type 1 diabetes by the end of 1997. Those participants who were given vitamin D supplements during their first year of life were less likely to be diagnosed with type 1 diabetes than other participants. Those who regularly took the recommended dose at the time, 2000 IU daily, during their first year of life had significantly lower diabetes rates 33 years later.
Vitamin D Supplementation May Not Be Effective in Bipolar Depression, But Is Still Worth Doing
In some studies, vitamin D supplementation (1,500 IU/day) has been found to improve unipolar depression. Recently, researchers led by Wendy K. Marsh found that compared to placebo, 12 weeks of vitamin D3 supplementation (5,000 IU/day) did not produce greater improvement in depressive symptoms. The study, presented at the 2016 meeting of the Society of Biological Psychiatry, included 33 adult participants whose vitamin D levels remained deficient throughout the study.
Editor’s Note: Caution is urged in interpreting this small study, especially because the participants did not achieve healthy levels of vitamin D.
Low levels of vitamin D are common in children and adults with bipolar disorder. Future research may explore whether raising vitamin D levels to healthy levels has a beneficial effect on mood. There are many other benefits to vitamin D supplementation. It can improve cognition, regulate calcium and phosphorus absorption, and maintain healthy bones and teeth. It may also protect against diseases such as cancer, type 1 diabetes, multiple sclerosis, rheumatoid arthritis, and Crohn’s disease. Improved cardiovascular health is also a possible benefit of vitamin D supplementation.
Low Vitamin D Linked to Small Hippocampus & Schizophrenia
Low levels of vitamin D have been linked to schizophrenia in several studies. In one, infants with low vitamin D were more likely to develop schizophrenia in adulthood, but supplementation reduced this risk. A 2015 article by Venkataram Shivakumar and colleagues in the journal Psychiatry Research: Neuroimaging found that among patients with schizophrenia who were not currently taking (or in some cases, had never taken) antipsychotic medication, low levels of vitamin D were linked to smaller gray matter volume in the right hippocampus, an area involved in schizophrenia.
Vitamin D has neuroprotective effects and is important to normal brain development and function. Vitamin D is essential to the production of brain-derived neurotrophic factor (BDNF), a protein that is important for learning and memory, and vitamin D also reduces oxidative stress. BDNF deficiency and oxidative stress have both been linked to schizophrenia, and they both can cause abnormalities in the hippocampus.
