Vitamin D and Mental Illness von John Jacob Cannell MD
Aus dem Amerikanischen - ein engagierter forschernder Arzt
ABSTRACT
We propose vitamin D plays a role in mental illness based on the following five reasons: Epidemiological evidence shows an association between reduced sun exposure and mental illness. Mental illness is associated with low 25-hydroxyvitamin D [25(OH)D] levels. Mental illness shows a significant comorbidity with illnesses thought to be associated with vitamin D deficiency. Theoretical models (in vitro or animal evidence) exist to explain how vitamin D deficiency may play a causative role in mental illness. Studies indicate vitamin D improves mental illness.
First, we review recent evidence concerning the hitherto unexpectedly high human requirements for vitamin D. Then, we briefly review the physiology, toxicology, and evidence for widespread vitamin D deficiency.
After that we review epidemiological evidence that mental illness has increased as humans have migrated out of the sun followed by additional epidemiological evidence that associates vitamin D deficiency with mental illness. Studies associating season of birth with mental illness are briefly reviewed. Two small reports studied the association of low 25(OH) D levels with mental illness and both were positive.
Depression has significant co-morbidity with illnesses associated with hypovitaminosis D such as osteoporosis, diabetes, heart disease, hypertension, multiple sclerosis, and rheumatoid arthritis. Schizophrenia is associated with cardiac disease , diabetes (before the introduction of the atypical antipsychotics) , osteoporosis , and hypertension —but not multiple sclerosis.
Vitamin D has a significant biochemistry in the brain. Nuclear receptors for vitamin D exist in the brain and vitamin D is involved in the biosynthesis of neurotrophic factors, synthesis of nitric oxide synthase, and increased glutathione levels—all suggesting an important role for vitamin D in brain function. Animal data indicates that tyrosine hydroxylase, the rate-limiting enzyme for all the brain's monoamines, is increased by vitamin D. Rats born to severely vitamin D deficient dams have profound brain abnormalities.
We found only three small studies in which vitamin D was given to improve mood, but two found a positive effect. The negative study used homeopathic doses (low doses) of vitamin D2 ergocalciferol.
Finally we briefly review toxicity and suggest treatment. Fear of vitamin D toxicity is unwarranted but rampant in the medical profession. Because vitamin D deficiencies are so widespread in the western world, psychiatrists should suspect the deficiency—especially in blacks, the aged, and those who avoid the sun. Serum 25(OH)D levels should be obtained when deficiency is suspected. Judicial exposure to sunlight, oral vitamin D, or both, aimed at restoring circulating levels of25(OH)D to between 50–80 ng/mL, is the treatment of choice for vitamin D deficiency in mentally ill patients. Cholecalciferol is the preferred oral preparation of vitamin D.HUMAN REQUIREMENTS FOR VITAMIN D
TOXICITY
Vieth attempted to dispel fears in the medical community about physiological doses of vitamin D in 1999 with his exhaustive and well-written review. His conclusions: fear of vitamin D toxicity is unwarranted, and such unwarranted fear is rampant in the medical profession. Even Ian Monroe, the chair of the relevant IOM committee, wrote to the Journal to compliment Vieth's work and to promise his findings will be considered at the time of a future Institute of Medicine review. That was more than 2 years ago.
Vieth indirectly asked the medical community to produce any evidence 10,000 units of vitamin D a day was toxic, saying, "Throughout my preparation of this review, I was amazed at the lack of evidence supporting statements about the toxicity of moderate doses of vitamin D." He added, "If there is published evidence of toxicity in adults from an intake of 250 µg(10,000 IU) per day, and that is verified by the25(OH)D concentration, I have yet to find it."
It is true that a few people may have problems with high calcium due to undiagnosed vitamin D hypersensitivity syndromes such as primary hyperparathyroidism, granulomatous disease (mainly sarcoidosis), or some cancers. This is not vitamin D toxicity and such syndromes often occur in patients with relative vitamin D deficiencies.
Cholecalciferol is certainly toxic in excess, and is used a rodent poison for this purpose. Animal data indicates signs of toxicity can occur with ingestion of 0.5 mg/kg(20,000 IU/kg), while the oral LD50 for cholecalciferol in dogs is about 88 mg/kg(3,520,000 IU/kg). This would be equivalent to a 50 kg adult taking 176,000,000 IU or 440,000 standard 400 IU cholecalciferol capsules. Vieth reports human toxicity begins to occur after chronic consumption of approximately 40,000 IU a day.
One could compare vitamin D toxicity to water intoxication. For example, 8 glasses of water a day is recommended consumption. However, regular consumption of 80 glasses a day (as seen in compulsive water intoxication) can be fatal. So you could say that water has a therapeutic index of 10 (80/8).
Most vitamin D experts now say that humans should get about 4,000 units of vitamin D a day (from all sources), but 40,000 units a day will hurt them (over several years). Therefore, vitamin D has a therapeutic index of 10 (40,000/4,000), the same as water. Although we are not saying it is as safe as water, we are saying vitamin D is safe when used in the doses nature uses it.
The single most important fact anyone needs to know about vitamin D is how much nature supplies if we behave naturally, e.g., go into the sun. Whites make about 20,000 units of vitamin D within 30 minutes of full body exposure to the sun (minimal erythemal dose). Vitamin D production in the skin occurs within minutes and is already maximized before your skin turns pink. Furthermore, if one stays in the sun long enough, the sun starts destroying excess vitamin D, a natural safeguard against toxicity.
Fear of the fatal form of skin cancer, malignant melanoma, keeps many people out of the sun. The problem with the theory is that the incidence of melanoma continues to increase dramatically although many people have been completely avoiding the sun for years. We are not saying sunburns are safe, they are not. We are saying that brief full body sun exposure (one-third minimal erythemal doses) may slightly increase your risk of non-melanoma skin cancer, but it is a much smarter thing to do than suffering from vitamin D deficiency.
Although there are documented cases of pharmacological overdoses from ergocalciferol, the only documented case of pharmacological (not industrial) toxicity from cholecalciferol we could find was intoxication from an over-the-counter supplement called Prolongevity. On closer inspection, however, it seemed more like an industrial accident but is interesting because it gives us some idea of the safety of cholecalciferol. The powder consumed contained up to 430 times the amount of cholecalciferol contained on the label (2,000 IU). The man had been taking between 156,000–2,604,000 IU of cholecalciferol (equivalent to between 390–6510 of the 400 IUcapsules) a day for 2 years. He recovered uneventfully after treatment with glucocorticoids and sunscreen.
VITAMIN D AS TREATMENT
It is too early to say that repletion of the vitamin D system will improve psychiatric symptoms, but there is limited evidence that it may. Once vitamin D deficiency is diagnosed in a psychiatric patient, or any patient, the physician needs to replete the vitamin D system with sunlight, an artificial source ofUVB, oral vitamin D3, or a combination of the three alternatives. Regardless of the method used, the physician should be sure 25(OH)Dlevels are maintained between 50–80 ng/mL.
In Caucasian patients who want to avoid taking medication, judiciously exposing of as much skin as possible to direct midday sunlight for a few minutes (time needed depends on skin type) 3 times a week during those months when UVB occurs at their latitude (The Holick method) will maintain vitamin D levels.
Black patients will need 5–10 times longer in the sun. After several months of sun exposure, a 25(OH)D level should be obtained again to ensure levels between 50–80 ng/mL. Artificial light sources are available which emit UVB and which have been shown to increase serum25(OH)D levels.
For those who want to avoid the sun or artificial light sources, cholecalciferol is the preferred form of vitamin D. It is the compound your skin makes naturally when exposed to UVB. It is more potent and is safer than the synthetic analog, ergocalciferol, in more common use. Cholecalciferol is 1.7 times more efficient at raising 25(OH)D levels than is ergocalciferol. If oral cholecalciferol is the only source of vitamin D (complete lack of UVB exposure), at least 5,000 IU per day will be needed to ensure serum 25(OH)D levels in the desirable range.
Unfortunately, when doctors don't prescribe ergocalciferol, they sometimes prescribe newer vitamin D analogs, costing thousands of times more than cholecalciferol. Vitamin D analogs are contraindicated in vitamin D deficiency because they may cause hypercalcemia and fail to address the real problem: low stores of25(OH)D. Cholecalciferol, or ergocalciferol, will replete the vitamin D system by filling up your gas tank with vitamin D. Giving newer, synthetic 1,25 vitamin D analogs for vitamin D deficiency is like shooting ether into your engine to keep your car running.
There is reason to hope that treating vitamin D deficiency will help improve the lives of psychiatric patients. It also seems clear that restoring physiological serum levels of25(OH)D will hurt very few, if any, patients.
John Jacob Cannell MD Executive Director 2003.09.07 updated 2010.01.08