Should you be ordering vitamin D levels in your patients? Vitamin D studies have proliferated recently. The recent finding that vitamin D receptors are found in the brain, along with the well known association between low sunlight exposure and seasonal affective disorder, has led doctors to wonder whether there is an association between vitamin D deficiency and depression.

What is Vitamin D?
Vitamin D is a fat-soluble vitamin that has two forms—vitamin D2 or ergocalciferol, and vitamin D3 or cholecalciferol. Vitamin D3 is produced in the skin upon exposure to ultraviolet B radiation from sunlight. Variations in age, skin pigmentation, latitude, time of day of exposure, and time of the year affect the actual amount of exposure. In general, for a fair-skinned person, adequate amounts of vitamin D can be generated by exposing the arms and legs to direct sunlight for five to 30 minutes twice a week (Parker G and Brotchie H, Acta Psychiatr Scand 2011;Apr 12, online ahead of print).

Vitamin D3 can also be obtained from animal dietary sources, such as deep sea fatty fish, egg yolks, liver, or fortified foods. Vitamin D2 can be found in plant dietary sources, such as shitake mushrooms, and is commercially produced for fortification by irradiation of yeast. Less than 10% of vitamin D is derived from dietary sources. Both vitamin D2 and D3 are converted to the prohormone 25-hydroxyvitamin D (25(OH)D) in the liver, and vitamin D status is determined by measurement of serum 25(OH)D levels.

Vitamin D Deficiency in Children
The reference range for normal vitamin D levels varies from lab to lab and continues to be a matter of debate. The Institute of Medicine (IOM) and the American Academy of Pediatrics have defined vitamin D deficiency as a serum level less than 11 ng/ml. (Bone disease is usually evident at these levels.) Vitamin D insufficiency has been defined by levels lower than 20 ng/ml. Levels between 21 ng/ml and 29 ng/ml may be defined as relative insufficiency. A 25(OH)D level greater than 30 ng/ml is usually considered optimal (some would argue greater than 40 ng/ml, but most experts consider the goal range to be 30 ng/ml to 60 ng/ ml).

Most pediatricians assume that children receive adequate amounts of vitamin D from sunlight and dietary sources such as milk. The universal feeling is that receiving adequate sun exposure is problematic only in extremes of latitude, in winter, for those who are of very dark complexion, and in people with extreme clothing coverage.

Interestingly, however, a recent study conducted in an area with excellent ambient sun exposure and conducive to year-round outdoor activity (the American Southwest) showed high levels of insufficiency (14% of healthy children had vitamin D levels of less than 20 ng/ml, 49% had levels lower than 30ng/ml, and only 15% had sufficient levels of greater than 40 ng/ml) (Szalay EA et al, J Pediatr Orthop 2011;31(4):469–473).

Pediatricians commonly recommend regular use of sunscreen to minimize damage caused by sun exposure. Sunscreen with a sun protection factor (SPF) of eight or greater effectively prevents vitamin D production by the skin. On top of that, the amount of time that children play outside continues to decrease. A 2006 survey in Minnesota found that 40% of children regularly watch television by age three months, and 90% watch regularly by age two (Jordan A, Dev Behav Pediatr 2004;25(3):196–206). Children between two and 17 years of age may spend more than six non-school hours per day with electronic media. These factors combined may result in today’s children having an elevated risk of vitamin D insufficiency compared to previous generations of children.

Testing for Serum 25(OH)D Levels and Using Vitamin D Supplementation
The lab test to measure vitamin D levels can range in cost from $25 to $250. Given recent data regarding high rates of vitamin D deficiency in children, coupled with the fact that obtaining adequate vitamin D from food is nearly impossible (to obtain 1,000 international units per day (IU/d) of vitamin D, a child would need to drink ten eight-ounce glasses of milk or eat two to three servings of salmon plus several glasses of milk daily), supplementation might be more cost-effective than mass testing of levels.

In 1997, The IOM established adequate intake levels for vitamin D at 200 IU/d for infants and children, a level assumed to maintain serum vitamin D levels if the child receives no vitamin D through sun exposure. This recommendation was doubled to 400 IU/d in 2008 as higher intake levels were shown to prevent rickets. In 2010, after reviewing more recent data, the IOM increased the recommended daily allowance to 600 IU for children and adults (and 800 IU/d for those over age 70) (Dietary Reference Intakes for Calcium and Vitamin D. Eds, Institute of Medicine of the National Academies, Food and Nutrition Board 2010. Chapter 5. Dietary reference intakes for adequacy: calcium and vitamin D. National Academies Press. 291–340).

In children without adequate sun exposure or to correct a deficiency, 800 to 1,000 IU/d may be required to maintain adequate levels. The dosage found in most children’s multivitamins is 400 IU/d, and this amount of intake likely has little effect on serum vitamin D levels. As a reference point, 400 IU/d raises the vitamin D level in a healthy adult by 3 ng/ml to 5 ng/ml, depending upon the baseline level. To increase the blood level from 20 ng/ml to 32 ng/ml in an adult, an additional 1,700 IU/d of vitamin D may be needed (Barger-Lux MJ et al, Osteoporos Int 1998;8(3):222–230). Therefore, the current recommended allowances may be set at unrealistically low levels if the goal is to prevent or to treat insufficiency or deficiency.

For vitamin D supplementation, you should use vitamin D3, as vitamin D2 has only one third the potency of D3. Vitamin D3 can be purchased by itself in small tablets, capsules, gummy forms or liquid. Vitamin D in any form, as a fat-soluble vitamin, does have potential for toxicity, although this is rarely seen with levels below 150 ng/ml. An extensive review of multiple studies found that vitamin D toxicity in adults was not evident in trials using less than 10,000 IU/d (Szalay EA et al, op.cit). Consequences of vitamin D toxicity include hypercalcemia (clinically presenting as nausea, vomiting, increased thirst, depression), kidney stones, and soft tissue and vascular calcifications.

Vitamin D and Depression
So what does all this have to do with psychiatry? One word: depression. A number of cross sectional clinical and epidemiologic studies have investigated whether there is a relationship between vitamin D levels and depressive symptomatology or illness in adults. Nine out of 13 such studies found that low levels of vitamin D were significantly associated with higher rates of depression diagnoses or depressive symptoms.

Because vitamin D deficiency may be related to living in areas with decreased sunlight or in higher latitudes, it has been theorized that vitamin D deficiency may play a role in the development of seasonal affective disorder. However, two studies were not able to show a difference in vitamin D levels when patients with seasonal affective disorder were compared to controls. Additionally, bright light therapy did not show any improvement in vitamin D levels. None of these studies included pediatric populations.

Only one controlled study of vitamin D supplementation in non-seasonal depression has been published. In that study, 441 overweight and obese patients were randomized to receive 20,000 or 40,000 IU of vitamin D3 or placebo weekly for one year. Although patients were not necessarily clinically depressed (rather, had depressive symptoms as measured by Beck Depression Inventory), at baseline, those with vitamin D levels lower than 16 ng/ml had greater depressive symptomalogy than those with higher levels. The two groups receiving vitamin D supplementation had significant improvement in their scores, whereas the placebo group did not (Jorde R et al, J Intern Med 2008;264(6):599–609).

Vitamin D supplementation has been studied in two controlled studies of seasonal affective disorder (SAD). In the first study (n=15), eight patients received a one-time 100,000 IU dose of vitamin D and seven received light therapy for one month. Vitamin D levels increased significantly in both groups: in 74% of those supplemented and in 36% of those who received light therapy. All patients in the vitamin D group showed improvement in all depression outcome measures compared to those treated with light therapy, none of whom showed significant changes in mood scores (Gloth FM et al, J Nutr Health Aging 1999;3(1):5–7). The second controlled study was conducted with women in England with SAD and who were greater than 70 years of age. In this six-month study, 912 patients received calcium with 800 IU/d of vitamin D and 1,205 received no supplementation. No significant differences were noted in mental health outcome measures in either group (Dumville JC et al, J Nutr Health Aging 2006;10(2):151–153).

Vitamin D Deficiency & Depression: Take Home Facts


 

• Vitamin D deficiency and insufficiency in children may be quite common.


• The IOM and the AAP have defined vitamin D deficiency as a serum level <11 ng/ml; insufficiency as levels of <20 ng/ml; and relative insufficiency as levels between 21 ng/ml and 29 ng/ml. A vitamin D serum level >30ng/ml is usually considered optimal.


• Historically, the recommended vitamin D intake levels have been too low and were recently increased.
  There is some evidence that vitamin D deficiency may contribute to depression; however, current studies cannot convincingly support this theory.


• Similarly, there is some evidence that supplementation may improve depressive symptoms; however, due to paucity of data (and absolute lack of data in children), conflicting results and limitations in study size and design, an evidence-based recommendation to supplement cannot be made.


• No studies investigated the role of vitamin D supplementation in addition to antidepressant treatment, so no conclusions can be made with regard to its role as an augmenting agent.


• Given the high rates of deficiency and insufficiency and the relative safety of 400 IU/day to 800 IU/day, a case could be made for supplementation in children who have tested with low serum vitamin D levels whose lifestyle and geography may predispose them to vitamin D insufficiency, if not for depression then for overall bone health.