Vitamin D plays an overlooked role in brain health

- and deficiencies increase your risk of anxiety, depression, dementia, Alzheimer’s disease, autism, schizophrenia, and other neurological diseases

Psychological disorders represent society’s single largest disease burden, and an increasing number of people are affected by it. There can be a variety of causes, and lack of vitamin D appears to be an alarming risk factor. This is because vitamin D is involved in a host of different functions that are relevant for brain neurons, including signaling substances and the brain’s reward system that affects our mood. Vitamin D also helps protect the brain against toxins, atherosclerosis, and inflammation, according to a review article that is published in the science journal Cureus. But there are questions that need to be answered. How much vitamin D do we need? Can we get enough from sun exposure? Is there enough vitamin D in a regular vitamin pill? Why do children, seniors, pregnant women, overweight individuals, and dark-skinned people have an increased need for vitamin D? And which mineral is extremely important for the body’s ability to utilize vitamin D?

The brain is the main organ of our nervous system. It features around 125 billion neurons that are connected in a highly complicated network. A single neuron typically connects with approximately 10,000 other neurons. Through human evolution, specific parts of the brain have developed the ability to handle language skills, memory processes, sensory skills, higher thought processes, and intentional actions. The brain also harbors a reward system that affects our mood.
Around 60 percent of the brain’s dry weight consists of lipids such as cholesterol, omega-3, and omega-6. We also need vitamins and minerals that control a host of different enzyme processes and help produce neurotransmitters. Therefore, being vitamin D-deficient can have a catastrophic impact on brain health and our mental well-being. If such a deficiency is not corrected, the risk of psychological and neurological disorders increases. It also increases the risk that various types of treatment such as talk therapy and medication fail to treat the underlying cause.

Vitamin D’s journey from sunlight to the active form of the nutrient in the brain

When the sun sits high in the sky, its UVB rays help us synthesize vitamin D in our skin with help from a cholesterol precursor. First, we produce a prohormone called cholecalciferol. This form of vitamin D, which is also found in supplements, is not biologically active. Helped by enzymes, the liver then converts cholecalciferol into 25-hydroxy-vitamin D, the form of vitamin D that is measured in the blood. When the body needs vitamin D, the kidneys convert 25-hydroxy-vitamin D into 1,25-dihydroxy-vitamin D with help from other enzymes.
Recent studies have shown that circulating 25-hydroxy-vitamin D is able to cross the blood-brain-barrier and enter the neurons and glial cells, where it is converted into the active form (1,25-dihydroxy-vitamin D). The active form of vitamin D binds to the vitamin D receptor (VDR) of the target cell, which is located in the cell nucleus. Afterwards, the cell can carry out the required functions.
Science estimates that vitamin D regulates around 10 percent of our genes. Lack of vitamin D may therefore prevent neurons, glial cells, and other cells from being able to carry out their tasks, even if the cells are otherwise perfectly healthy.
Over the past decades, numerous studies have shown a relation between vitamin D and brain health. Vitamin D has the following functions in the brain and nervous system:

1. Regulates genes
2. Increases the density of neurons in the hippocampus, which is important for memory and orientation
3. Increases neurotrophin levels in hippocampus, which helps protect neurons
4. Regulates neurotransmitters such as dopamine, serotonin, and acetylcholine
5. Regulates nerve growth factor (NGF)
6. Regulates mechanisms that protects against oxidative stress caused by free radicals
7. Counteracts brain atrophy
8. Regulates the calcium metabolism of the nervous system
9. Regulates the immune system
10. Inhibits pro-inflammatory cytokines
11. Increases the brain’s excretion of harmful beta-amyloid protein
12. Supports the cerebral blood flow

Anxiety and aggressive behavior

Indefinable anxiety is a growing problem in all age groups. There can be many underlying causes, especially in a society that places great demands on the individual. If the nervous system lacks nutrients, we become even more vulnerable to life’s challenges.
A review article from 2015 revealed that people who suffer from anxiety or depression have low vitamin D levels in their blood. In school children, lack of vitamin D increases the risk of anxiety, aggressive behavior, and depression later in life, according to another study that is published in the science journal Nutrition in 2019.

Depression and winter depression

The feeling of joy and happiness as well as that of depression are rooted in the brain’s neural network. Vitamin D’s ability to regulate neurotransmitters like dopamine in the reward center of the brain is therefore of vital importance to our mental well-being. The same is the case with vitamin D’s role in regulating serotonin levels.
A large Irish study has revealed that vitamin D-deficient people older than 50 years are far more likely to become depressed. The study also showed that vitamin D deficiencies are far more common in this age group and that vitamin D supplementation can significantly improve your mood. Several other studies have also showed a link between depression and lack of vitamin D.
Many people at northern latitudes tend to feel depressed during the winter period. In many cases, the reason is that vitamin D levels dip in the dark and cold months, where the sun sits too low in the sky for us to be able to synthesize the nutrient. Besides, the liver only stores limited amounts of vitamin D. The lack of strong daylight during the winter season plays a role, as well.
Vitamin D also regulates the calcium metabolism in our nervous system, which plays a vital yet overlooked role. Ideally, nearly all of our calcium (99 percent) should be stored in our bones and teeth, while neurons, glial cells, and cells in our soft tissues should be virtually devoid of calcium.
If too many calcium ions enter the nerve cells, the cells go into a cramp, they become stressed, and that may trigger depression and other conditions. Therefore, vitamin D is so important for regulating the body’s calcium distribution, and magnesium also plays a key role in this process.
Vitamin D’s anti-inflammatory properties are also important, as brain inflammation is believed to be the cause of depression in thirty percent of cases.

Dementia and loss of cognitive functions

With age, our risk of developing neurodegenerative disorders such as dementia increases. Mild, cognitive impairment is when brain functions such as memory and lingual skills decrease without necessarily preventing the patient from managing a normal life. But there is also a risk that this condition leads to dementia, in which case the patient is no longer able to manage on his or her own.
A meta-analysis from 2017 showed that having low levels of vitamin D (below 25 nmol/L) increases the risk of dementia, especially in people older than 65 years of age. A study from 2016 (Annweiler C et al.) showed that lack of vitamin D is quite common among people 65 years and older with signs of dementia and loss of cognitive skills. An alarmingly high number of people around the world are affected by dementia, which is caused by other neurodegenerative disorders.

Alzheimer’s disease

Alzheimer’s disease is the underlying cause of dementia in more than 50% of the cases, and the risk goes up with age. This disease is characterized by the build-up of plaque from the beta-amyloid protein. Over time, these protein deposits destroy the brain cells, eventually causing them to perish. Alzheimer’s disease is a slowly progressing disorder, which typically leads to death in a matter of 7-10 years. It is therefore of vital importance to start preventing the disease as soon as possible.
The afore-mentioned study from 2016 (Annweiler C. et al.) showed that vitamin D is able to control the beta-amyloid build-up, the calcium metabolism in the nerve cells, and inflammation, all of which are key areas in Alzheimer’s disease.
Another thing that characterizes the disease is lack of the neurotransmitter acetylcholine, which brain cells use to communicate. Here, vitamin D helps control the formation of this neurotransmitter. Other risk factors in Alzheimer’s disease are smoking, too much alcohol, being overweight, and having type 2 diabetes and insulin resistance of the brain. In fact, that is why Alzheimer’s disease is also referred to as type 3 diabetes. In two percent of the cases, genetic flaws are to blame.

Parkinson’s disease

Parkinson’s disease, which causes trembling, is one of the most common disorders among old people, and it gradually gets worse. It causes accelerating loss of dopamine-containing brain cells. Dopamine is a neurotransmitter that is used to control our movements. There is no effective treatment for the disease, and existing therapies are only able to suppress symptoms without addressing the underlying causes. Vitamin D helps regulate levels of dopamine in the brain, which makes it a useful supplement for preventing the disease and also convenient as add-on therapy.

Autism

Autism is characterized by grave disturbances of behavior, communication, and social interaction. The increasing rate of autism is linked to the widespread problems with vitamin D deficiency, according to studies carried out by scientists Rhonda Patrick and Bruce Ames at the Children’s Hospital Oakland Research Institute (CHORI). Autism was once associated with low serotonin levels in the brain, but the more precise mechanisms involved were not revealed until recently. The scientists have found that vitamin D regulates a gene and an enzyme that are responsible for converting the amino acid tryptophan into serotonin. Serotonin is a brain neurotransmitter that influences our mood. Anti-depressive medication works by controlling serotonin levels, but the problem is that serotonin has many other functions in the brain and throughout the rest of the body. People with autism often have elevated serotonin levels in their intestines and low serotonin levels in the brain. The studies showed that vitamin D is able to suppress the intestinal serotonin synthesis, while increasing serotonin synthesis in the brain at the same time.
During pregnancy, vitamin D plays a particularly important role in the development of the unborn child’s brain. Vitamin D also plays a vital role in the synthesis of serotonin, and if levels of serotonin are too low, it may affect the function and structure of the brain.

Lack of vitamin D in neonates increases the risk of schizophrenia later in life

Schizophrenia is characterized by brain dysfunctions such as hallucinations, delusion, and thought disturbances. The disease typically begins in the teenage years or early adulthood. It may be caused by various genetic and environmental causes with subsequent damage to the glial cells. Scientists also look at vitamin D, which is highly important for the development of the unborn child’s brain. It turns out that vitamin D-deficient neonates are 44 percent more likely to develop schizophrenia later in life, compared with neonates without vitamin D deficiency. This was shown in a study carried out by scientists from Denmark and Australia. With this vital insight, we may be able to prevent many cases of schizophrenia. The researchers therefore advise pregnant women to get enough vitamin D, just like there is focus on folic acid in pregnancy.

Vitamin D and its importance for the child’s brain development during pregnancy

Vitamin D is now considered a neuroactive steroid hormone with particularly great importance for the nervous system. During pregnancy, the fetus is totally dependent on the mother’s vitamin D status, and the nutrient is transferred to the fetus through the placenta. Vitamin D is able to cross through the fetus’ blood-brain-barrier and support a number of different functions such as converting tryptophan into serotonin, which is important for the structure and function of the brain.
Vitamin D is also involved in the formation of the myelin sheaths, which protect the nerve cells in the same way as the plastic cover on electric wires and cables. The myelin sheaths also enable faster transmission of the nerve impulses.
According to scientist Rhonda Patrick, PhD, low levels of vitamin D during critical periods of a pregnancy may result in the development of weak myelin sheaths in the fetus, causing the child’s nerve cells to be more vulnerable, thereby increasing its risk of neurological disorders.
A study published in the British Journal of Nutrition shows that lack of vitamin D during pregnancy has a negative impact on the toddler’s social development and motor skills. It is therefore vital for pregnant women to get plenty of vitamin D.

Increased focus on vitamin D supplementation in pregnancy

Although health authorities recommend vitamin D supplements for pregnant women, it appears that many women forget to take the supplements or do not take them on a regular basis. It may be an advantage to measure the vitamin D status of the pregnant women, especially during the winter and spring, where they are most likely to be deficient.

Official recommendations, optimal needs, and supplementation

The sun during the summer period is our primary source of vitamin D. We only get small quantities of the nutrient from our diet. Also, vitamin D deficiency is caused by factors such as e.g. too much indoor activity, ageing processes, the use of sun factor cream, having dark skin, being overweight, and being pregnant.
Daily reference intake (RI) levels for vitamin D vary from country to country. In Denmark, the RI level for adults is 5 micrograms, while the Danish health authorities recommend a daily 10-microgram supplement for pregnant women, infants, people with dark skin, and people that do not get enough sunlight. A 20-microgram supplement is recommended for nursing home residents and people older than 70 years.
Many scientists believe that the actual need for vitamin D is much greater and recommend as much as 30-100 micrograms daily. Vitamin D is a lipid-soluble nutrient, so the best absorption and utilization is obtained with vitamin D in an oil formula in softgel capsules.

Important: We need magnesium to activate vitamin D

Cholecalciferol is the form of vitamin D that we synthesize from sunlight, and it is also the form that we get from supplements. This form of the nutrient is not biologically active until it is converted by the liver and activated by the kidneys with help from magnesium-containing enzymes. Therefore, being magnesium-deficient may lower the activation of vitamin D and the man processes, in which is it involve. So make sure to get plenty of magnesium from dietary sources of supplementation.

References

Alexander Muacevic and John R Adler: The Role of Vitamin D in Brain health: A Mini Literature Review. Cureus 2018

Sonia L. Robinson et al. Vitamin D Deficiency in Middle Childhood is related to Behavior Problems in Adolescence. The Journal of Nutrition, 2019

M Bicikova et al. Vitamin D in anxiety and affective disorders. Psysiol Res. 2015

Robert Briggs et al. Vitamin D Deficiency is Associated With an Increased Likelihood of Incident Depression in Community-Dwelling Older adults. J Am Med Dir Asso 2019

Rapaport MH et al. Inflammation as a predictive biomarker for response to omega-3 fatty acids in major depressive disorder: a proof-of-concept study. Molecular Psychiatry 2015

Evelina Lukaszyk et al. Cognitive Functioning of Geriatric Patients: Is Hypovitaminosis D the Next Marker of Cognitive Dysfunction and Dementia. Nutrients, August 2018.

Jacqueline Pettersen. Does high dose vitamin D supplementation enhance cognition? : A randomized trial in healthy adults. Experimental Gerontology. February 2017.

R.P. Patrick, B.N. Ames. Vitamin D hormones regulates serotonin synthesis. The FASEB Journal 2014

Science News. Causal link found between vitamin D, serotonin synthesis and autism in new study. Science Daily. 2014

Darryl W Eyles et al. The association between neonatal Vitamin D status and risk of schizophrenia. Scientific Reports. 2018

University of Queensland. Link between neonatal vitamin D deficiency and schizophrenia confirmed. ScienceDaily. 2018

Andrea L. Darling et al. Association between maternal vitamin status in pregnancy and neurodevelopmental outcomes in childhood: results from the Avon Longitudinal Study of Parents and Children. (ALSPAC) British Journal of Nutrition, 2017

Anne Marie Uwitonze, Mohammed S Razzaque. Role of magnesium in Vitamin D Activation and Function. The Journal of the American Osteopathic Association. 2018

Qi Dai et al. Magnesium status and supplementation influence vitamin D status and metabolism; results from a randomized trial. The American Journal of Clinical Nutrition 2018

www.neurodegenerationresearch.eu/da/om-jpnd/hvad-er-neurodegenerativ-sygdom/

ttps://videnskab.dk/krop-sundhed/dopamin-fremmer-hjernens-beloenningstilstand

http://www.videnscenterfordemens.dk/hjernen/nerveceller-og-deres-udloebere/

https://www.psykiatrifonden.dk/viden/fakta.aspx