Vitamin D and The Human Brain

Abstract

Vitamin D plays a role in many important biological functions; deficits lead to problems with cardiovascular health, bone mineral density, muscle mass and function, abdominal density, insulin resistance, Type 1 and 2 diabetes, kidney disease, liver disease, cognitive impairment, metabolic syndrome, immune disorders, cancer, and pregnancy complications. Participants with a vitamin D deficit and no major illnesses were given a placebo or 3000 IU daily of vitamin D for one year with monthly word recall tests. Participants receiving the vitamin showed a statistically significant improvement on the word recall tests. These results support the hypothesis that vitamin D improves memory.

The International Osteoporosis Foundation defines a concentration of 0-10 ng/ml 25-hydroxyvitamin D as a severe deficiency, 10-20 ng/ml as a deficiency, 20-30 ng/ml as an insufficiency, 30-80 ng/ml as optimal, and >100ng/ml as at risk for toxicity (Matyjaszek-Matuszek, Lenart-Lipinska, & Wozniakowska, 2015). Humans absorb 80-90% of their vitamin D from ultraviolet beta radiation from the sun. 7-dehydrocholesterol present in the body is converted to cholecalciferol with the aid of ultraviolet beta radiation. The additional 10-20% is derived from their diet in the form of ergocalciferol. Supplements are also an option. These products are further synthesized in the liver, then kidneys, producing the steroids 20-hydroxyvitamin D and 1,25-dihydroxyvitamin D (Darwish, Zeinoun, Ghusn, Khoury, Tamim, & Khoury, 2015; Matyjaszek-Matuszek et al., 2015).

Vitamin D has its own receptors, which makes it a hormone. Vitamin D receptors are found in neurons, glial cells, skeletal system, enterocytes, adipose tissue, renal tubular cells, immune cells, pancreatic cells, myocytes, cardiomyocytes, endothelium cells, and some cancer cells (Darwish et al., 2015; Matyjaszek-Matuszek et al., 2015). Vitamin D is a lipid soluble transcription factor thought to regulate about 3% of the human genome.

Vitamin D has long been known to play a vital part in calcium-phosphate homeostasis. Recent studies have shown a correlation between a wide variety of illnesses and vitamin D. Vitamin D concentration positively correlates with cardiovascular health, bone mineral density, muscle mass and function (Arabi, Awada, Ayoub, El-Hajj Fuleihan, 2006). Vitamin D concentration negatively correlates with mortality, abdominal density, hypertension, insulin resistance, Type 1 and 2 diabetes, age, kidney disease, liver disease, sunscreen use, cognitive impairment, smoking, obesity, and air pollution (Darwish et al., 2015; Matyjaszek-Matuszek et al., 2015). Low vitamin D has also been linked to metabolic syndrome, immune disorders, and pregnancy complications. Vitamin D is a growth inhibitor for prostate, colon, breast, lung, liver, ovarian, and pancreatic cancers (Matyjaszek-Matuszek et al., 2015). Rats with no functional vitamin D receptors have cardiovascular disease, myocardial hypertrophy, and endothelial dysfunction (Ni, Watts, Ng, 2014).

Vitamin D insufficiency is known to correlate with cognitive decline in the elderly. Elderly people with low vitamin D self-report more memory loss than elderly people with healthy levels of vitamin D (De Neree Tot Babberich, Gourdeau, Pointel, Lemarchant, Beauchet, & Annweiler, 2015). Darwish (2015) found a significant positive correlation between visuospatial memory and vitamin D concentration in people as young as 30. In northern latitudes, Vitamin D blood concentrations fluctuate with the seasons, higher in the summer and lower in the winter. Working memory and executive functioning are shown to decrease in the winter and increase in the summer (Pettersen, Fontes, & Duke, 2014). Diabetic rats have a poorer episodic memory and have less cholinergic transmission in their prefrontal cortices than health rats. A vitamin D supplement of 500IU/day for 10 weeks improves the episodic memory and cholinergic transmission of diabetic rats (Alrefaie & Alhayani, 2015).

We hypothesize that giving 3000 IU of Vitamin D daily to people deficient in Vitamin D for one year will improve their episodic memory as demonstrated in a word recall test. The participants will have a starting level of 10-20 ng/ml of serum 25-hydroxyvitamin D in their blood, which is classified as a vitamin D deficiency by the International Osteoporosis Foundation. Vitamin D blood tests and word recall tests will be administered on a monthly basis for one year. A correlation with vitamin D and memory has been demonstrated. This longitudinal experiment will give causal evidence showing that more vitamin D leads to an improvement in memory. Vitamin D is important to the functioning of the human brain and body. This study will expand our knowledge on the value of vitamin D supplements.

Methods

500 participants with a vitamin D deficiency (10-20 ng/ml serum 25-hydroxyvitamin D in their blood) were recruited through doctors’ offices and college campuses in Vermont with fliers asking for healthy volunteers between the ages of 20-40. They were paid $20 per visit to the research center. Each had English as a self-reported first language, completed high school, and a Body Mass Index (kg/m²) in the healthy range of 18.5 and 24.99 (Quetelet & Knox, 18; “WHO:: Global Database on Body Mass Index,” n.d.). They had not smoked, taken a vitamin D supplement, or any medication known to affect cognition in the last 3 months. Participants were between the ages of 20-40, with a mean age of 27. Women in any stage of menopause were excluded. Participants had no history of drug or alcohol abuse, traumatic brain injury, neurological, psychiatric, or cognitive disorders. Participants were screened for depression and anxiety disorders with the Hopkins Symptoms Checklist-25 (Parloff, Kelman, & Frank, 1954), scoring less than 1.75 on the depression and anxiety sections. Participants had intelligence quotients within one standard deviation from the average (85-115) (Terman, 1916). Participants had a healthy range of calcium and vitamin B12 in their blood.

Materials and Procedures

Participants were sorted randomly into 2 groups, a control group taking a placebo and a group taking 3000 IU of Vitamin D daily for one year. Vitamin D levels and episodic memory as demonstrated in a word recall test were tested on the first of each month. People with unsafe vitamin D levels were dropped from the study and recommended a course of action. Blood was stored as a serum at -20°C until 5 mL was tested with electrochemiluminecent immunoassay for serum 1,25-dihydroxyvitamin D levels.

Results

The expectation was that giving 3000 IU of Vitamin D daily to participants deficient in Vitamin D for one year would improve their memory in comparison to participants taking a placebo as demonstrated in a word recall test. Participants in the control group recalled 61% of words in the word recall test before starting the placebo, 68% of words 6 months after starting the placebo, and 63% of words 12 months after starting the placebo. Participants in the Vitamin D group recalled 59% of words before starting to take Vitamin D, 74% of words 6 months after starting to take Vitamin D, and 80% of words 12 months after starting to take Vitamin D (Figure 1).

Figure 1 Percentage of words recalled in a word recall test given at the beginning of the study, six months, and twelve months after the study began

Discussion

The hypothesis that giving 3000 IU of Vitamin D daily to people deficient in Vitamin D improves memory was supported. The percentage of words recalled increased from 59% to 80% in the group receiving vitamin D and fluctuated from 61% to 68% back down to 63% for the group taking the placebo. This is a statistically significant difference, which suggests vitamin D positively affects memory. This is the first study showing causal rather than correlational evidence that we are aware of after thoroughly searching relevant literature. Limitation of this study include size; 57 out of the initial 500 participants left the study for various reasons. The word recall test was repeated 13 times. The increase in percent recall may be partially due to increased familiarity with word recall tests. Vitamin D deficiency is a widespread problem, particularly in winter months in northern latitudes. Vitamin D receptors are found all over the body including the nervous system, skeletal system, skin, adipose tissue, immune cells, and some cancer cells. The extent of the effects of vitamin D is still unknown. Future studies should further explore what types of memory vitamin D effects, what the ideal dose is when considering latitude, lifestyle, absorbency, age, size, and blood levels of vitamin D.