Normal 24-hour urine calcium concentrations after long-term daily oral intake of vitamin D in doses ranging from 5000 to 50,000 international units in 14 adult hospitalized psychiatric patients.

Many controversies exist regarding vitamin D3 supplementation. These include not only diseases that are responsive to vitamin D supplementation, but also the long-term safety of prolonged daily oral vitamin D3 intake above 4000-10,000 International Units (IU). In particular, supplementation levels that do not result in adverse events, and the upper limits of safe serum 25-hydroxyvitamin D (25OHD) concentrations. Adverse reactions reported to occur with excessive vitamin D intake include hypercalcemia, renal failure, calcium crystal formation, undetectable parathyroid hormone concentrations, and hypercalciuria, all of which are reported to be reversible. To address the long-term safety of vitamin D supplementation, we previously reported data from patients in our hospital who have been voluntarily supplemented with vitamin D3 ranging from 5,000 to 10,000 IU/day since July 2011 as a standard of care for the prevention and treatment of vitamin D deficiency. Historically 90% of patients have agreed to daily supplementation, with most taking 10,000 IU/day. These data indicate no evidence for hypercalcemia, renal failure, calcium crystal formation, nephrolithiasis. or undetectable parathyroid hormone concentrations in patients taking 5000 or 10,000 IU/day for extended periods of time. As another measure for potential vitamin D toxicity, we retrospectively assessed 24-hour urine calcium excretion in 14 individuals on long-term daily oral vitamin D intake ranging from 5000 to 50,000 IU/day to further assess the safety of supplementation using these doses. This included patients taking either 5000 (4), 10,000 (9), or 50,000 (1) IU/day. Time on supplementation ranged from 10 to 102 months. A patient taking 400 IU/day and getting frequent sun exposure was also included. All fifteen 24-hour urine calcium measurements were normal. The current findings complement our experience with over 7000 patients in the past 13 years, indicating that prolonged daily oral intake of vitamin D3 ranging from 5000 to 10,000 IU/day is safe.

Daily oral dosing of vitamin D3 using 5000 TO 50,000 international units a day in long-term hospitalized patients: Insights from a seven year experience.

Vitamin D3 is a secosteroid hormone produced in the skin in amounts estimated up to 25,000 international units (IUs) a day by the action of UVB radiation on 7-dehydrocholesterol. Vitamin D deficiency is common due to both lack of adequate sun exposure to the skin, and because vitamin D is present in very few food sources. Deficiency is strongly linked to increased risk for a multitude of diseases, several of which have historically been shown to improve dramatically with either adequate UVB exposure to the skin, or to oral or topical supplementation with vitamin D. These diseases include asthma, psoriasis, rheumatoid arthritis, rickets and tuberculosis. All patients in our hospital have been routinely screened on admission for vitamin D deficiency since July 2011, and offered supplementation to either correct or prevent deficiency. During this time, we have admitted over 4700 patients, the vast majority of whom agreed to supplementation with either 5000 or 10,000 IUs/day. Due to disease concerns, a few agreed to larger amounts, ranging from 20,000 to 50,000 IUs/day. There have been no cases of vitamin D3 induced hypercalcemia or any adverse events attributable to vitamin D3 supplementation in any patient. Three patients with psoriasis showed marked clinical improvement in their skin using 20,000 to 50,000 IUs/day. Analysis of 777 recently tested patients (new and long-term) not on D3 revealed 28.7% with 25-hydroxyvitaminD3 (25OHD3) blood levels < 20 ng/ml, 64.1% < 30 ng/ml, a mean 25OHD3 level of 27.1 ng/ml, with a range from 4.9 to 74.8 ng/ml. Analysis of 418 inpatients on D3 long enough to develop 25OHD3 blood levels > 74.4 ng/ml showed a mean 25OHD3 level of 118.9 ng/ml, with a range from 74.4 to 384.8 ng/ml. The average serum calcium level in these 2 groups was 9.5 (no D3) vs 9.6 (D3), with ranges of 8.4 to 10.7 (no D3) vs 8.6 to 10.7 mg/dl (D3), after excluding patients with other causes of hypercalcemia. The average intact parathyroid hormone levels were 24.2 pg/ml (D3) vs. 30.2 pg/ml (no D3). In summary, long-term supplementation with vitamin D3 in doses ranging from 5000 to 50,000 IUs/day appears to be safe.

Vitamin D, cod liver oil, sunshine, and phototherapy: Safe, effective and forgotten tools for treating and curing tuberculosis infections - A comprehensive review.

Tuberculosis remains an epidemic throughout the world, with over 2 billion people, or more than one third of the world's population, infected with TB. In 2015, there were an estimated 10.4 million new cases of tuberculosis, and 1.8 million deaths, making TB one of the top ten causes of death worldwide. Approximately 95% of new TB cases occur in developing countries, where the costs of treatment force many patients and their families into poverty. The United Nations and the World Health Organization are working to end this global epidemic. Historically, cod liver oil in the 1840's, phototherapy in the 1890's, sunshine in the 1890's and 1930's, oral vitamin D in doses of 100,000-150,000 international units a day the 1940's, and injectable vitamin D in the 1940's were all shown to be able to safely treat tuberculosis. However, for reasons that are unclear, these treatments are no longer being used to treat tuberculosis. We will review several reports that documented the clinical efficacy of these seemingly disparate treatments in treating tuberculosis. Taken together, however, these reports show the consistent efficacy of vitamin D in treating tuberculosis infections, regardless of whether the vitamin D was produced in the skin from the effects of phototherapy or sunshine, taken orally as a pill or in cod-liver oil, or put into solution and injected directly into the body. We will discuss how vitamin D, through its action as a steroid hormone that regulates gene transcription in cells and tissues throughout the body, enables the body to eradicate TB by stimulating the formation of a natural antibiotic in white blood cells, the mechanism of which was discovered in 2006. We will speculate as to why vitamin D, cod liver oil, sunshine, and phototherapy are no longer being used to treat tuberculosis, in spite of their proven efficacy in safely treating this disease dating back to the early 1800's. In fact, in 1903 the Nobel Prize in Medicine or Physiology was awarded to a physician who was able to cure hundreds of cases of long-standing lupus vulgaris (cutaneous TB) with refracted light rays from an electric arc lamp. Vitamin D, cod liver oil, sunshine, and phototherapy have never been shown to lose their ability to safely eradicate tuberculosis infections, and deserve consideration to be re-examined as first-line treatments for tuberculosis. These treatments have the potential to help cost-effectively and safely end the global TB epidemic.

D2/D3 dopamine receptor binding with [F-18]fallypride in thalamus and cortex of patients with schizophrenia.

BACKGROUND: Abnormalities in the dopaminergic system are implicated in schizophrenia. [F-18]fallypride is a highly selective, high affinity PET ligand well suited for measuring D2/D3 receptor availability in the extrastriatal regions of the brain including thalamus, prefrontal, cingulate, and temporal cortex, brain regions implicated in schizophrenia with other imaging modalities. METHODS: Resting [F-18]fallypride PET studies were acquired together with anatomical MRI for accurate coregistration and image analysis on 15 drug naïve schizophrenics (10 men, 5 women, mean age 28.5 years) and 15 matched controls (9 men, 6 women, mean age 27.4 years). Dopamine D2/D3 receptor levels were measured as binding potential (BP). The fallypride BP images of each subject were spatially normalized and subsequently smoothed for group comparison. Measures of significance between the schizophrenic and control groups were determined using statistical parametric mapping (SPM). The medial dorsal nucleus and pulvinar were also traced on coregistered MRI for detailed assessment of BP in these regions. RESULTS: The thalamus of patients with schizophrenia had lower [F-18]fallypride BP than normal controls and this was the brain area with the greatest difference (range -8.5% to -27.2%). Left medial dorsal nucleus and left pulvinar showed the greatest decreases (-21.6% and -27.2% respectively). The patients with schizophrenia also demonstrated D2/D3 BP reduction in the amygdala region, cingulate gyrus, and the temporal cortices. CONCLUSIONS: These findings suggest that drug naïve patients with schizophrenia have significant reductions in extrastratial D2/D3 receptor availability. The reductions were most prominent in regions of the thalamus, replicating other studies both with high affinity D2/D3 ligands and consistent with FDG-PET studies, further supporting the hypothesis of thalamic abnormalities in this patient population.

Measuring dopamine neuromodulation in the thalamus: using [F-18]fallypride PET to study dopamine release during a spatial attention task.

We used the highly selective D2/D3 dopamine PET radioligand [F-18]fallypride to demonstrate that cognitive task induced dopamine release can be measured in the extrastriatal region of the thalamus, a region containing 10-fold fewer D2 dopamine receptors than the striatum. Human studies were acquired on 8 healthy volunteers using a single [F-18]fallypride injection PET imaging session. A spatial attention task, previously demonstrated to increase FDG uptake in the thalamus, was initiated following a period of radioligand uptake. Thalamic dopamine release was statistically tested by measuring time-dependent alterations in the kinetics (focusing on specific binding) of the [F-18]fallypride using the linearized extension of the simplified reference region model. Voxel-based analysis of the dynamic PET data sets revealed a high correlation (r = 0.86, P = 0.0067) between spatial attention task performance and thalamic dopamine release. Various aspects of the kinetic model were analyzed to address concerns such as blood flow artifacts and model bias, as well as issues with task timing and regional variations in D2/D3 receptor density. In addition to the thalamus, measurement of dopamine neuromodulation using [F-18]fallypride and a single injection PET protocol can be extended to other extrastriatal regions of the brain, such as the amygdala, hippocampus, and regions of the temporal cortex. However, issues of task timing and detection sensitivity will vary depending on regional D2/D3 dopamine receptor density. Measurements of extrastriatal dopamine neuromodulation hold great promise to further our understanding of extrastriatal dopamine involvement in normal cognition and neuropsychiatric pathology.

Thalamic and prefrontal FDG uptake in never medicated patients with schizophrenia.

OBJECTIVE: Because neuroleptic treatment may cause long-lasting changes in brain structure and function, a group of patients with schizophrenia who had never been medicated was recruited to examine regional glucose metabolic rates in the frontal-striato-thalamic circuit. METHOD: Twelve never medicated patients with schizophrenia (seven men, five women; mean age=29 years) and 13 normal volunteers (eight men and five women; mean age=28.5 years) underwent (18)F-fluorodeoxyglucose (FDG) positron emission tomography, and coregistered anatomical magnetic resonance imaging scans were also obtained. During FDG uptake, subjects performed a spatial attention task previously shown to activate the pulvinar region of the thalamus. RESULTS: Diminished regional glucose metabolism was found in the medial dorsal nucleus, posterior thalamus, and prefrontal cortex of patients with schizophrenia relative to normal volunteers, extending earlier results from studies of medicated and previously medicated patients. CONCLUSIONS: The finding of lower relative metabolic rates in the frontothalamic circuits of patients with schizophrenia is consistent with extended circuit deficits involving interactions of frontal executive areas with thalamic sensory and association processes.