High 1,25-Dihydroxyvitamin D and Low 25-Hydroxyvitamin D Concentrations in Plasma in Patients Receiving Antiepileptic Drugs

Abstract: Plasma 25-hydroxyvitamin D (25-OH D), 1,25-dihydroxy vitamin D (1,25-(OH)₂ D) and parathyroid hormone (PTH) concentrations were determined in 30 outpatients receiving various antiepileptic drugs (AED). None of the patients exhibited high plasma PTH levels. The plasma 1,25-(OH) ₂ D levels were normal or high, a'though in a third of the patients the 25-OH D levels were reduced. There was a corre'ation between the 25-OH D and serum calcium levels. These findings suggest that the low plasma concentrations of 25-OH D, not 1,25-(OH)₂ D, might play an important part in the occurrence of AED-induced disturbances of bone metabolism.     

中国北方地区老年人冬季维生素D缺乏与骨量丢失**☆

背景：中国北方地区老年人维生素D营养状态存在季节变化,冬春季维生素D缺乏严重。 目的：分析沈阳市老年人冬季维生素D缺乏对骨量丢失的影响。 方法：随机选择沈阳市60岁以上汉族健康老年人100名,于2000-03检测受试者血浆中25羟维生素D、甲状旁腺激素、钙和磷,清晨空腹2 h尿中脱氧吡啶、钙、磷、肌酐,2000-03/2005-03两次检测髋部骨密度。 结果与结论：基线时,血浆25羟维生素D浓度为(31.0±12.30) nmol/L,40%受试者低于25 nmol/L;血浆甲状旁腺激素水平为(29.4±11.5) ng/L,血浆25羟维生素D浓度低于25 nmol/L者甲状旁腺激素水平为(34.6±13.5) ng/L,血浆25羟维生素D浓度与甲状旁腺激素呈负相关(r=-0.479,P < 0.000 1)。5年后股骨颈骨丢失率为(3.05±4.07)%,大转子为(1.46±5.02)%,经体质量和身高变化率校正后,股骨颈骨丢失率与基线血浆25羟维生素D浓度呈负相关(r=-2.3,P=0.02),股骨颈骨丢失率基线血浆25羟维生素D浓度≤ 25 nmol/L者高于浓度>25 nmol/L者103%( F=7.206 2,P=0.008 5)。其他检测指标与骨丢失无显著相关性。说明老年人群冬季维生素D缺乏严重,维生素D缺乏促进骨量丢失,影响骨健康。     

Abnormal bone and calcium metabolism in immobilized Parkinson's disease patients.

To elucidate the influence of immobilization-induced hypercalcemia on bone metabolism in Parkinson's disease (PD), we measured serum biochemical indexes and bone mineral density (BMD) in the second metacarpals of 142 elderly PD patients and 99 age-matched healthy controls. Serum concentrations of 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25-[OH](2)D), ionized calcium, intact parathyroid hormone (PTH), and intact bone Gla protein (BGP) were measured. Urinary deoxypyridinoline (D-Pyr) was also measured. Increased serum calcium levels (mean, 1.27 mmol/L) were observed in PD patients, and the levels correlated negatively with the Unified Parkinson's Disease Rating Scale III (UPDRS III), indicating the presence of immobilization-induced bone resorption with resultant hypercalcemia. Decreased serum concentrations of 1,25-[OH](2)D (mean, 88.7 pmol/L) and 25-OHD (mean, 29.7 nmol/L) were noted. Serum PTH was decreased (mean, 25.2 ng/L). Serum BGP was decreased while urinary D-Pyr concentration elevated. A negative correlation was observed between 1,25-[OH](2)D levels and serum calcium or UPDRS III (P < 0.0001). In disabled PD patients, immobilization-induced hypercalcemia may inhibit secretion of PTH, which in turn suppresses 1,25-[OH](2)D production. 25-OHD insufficiency may also contribute to decreased 1,25-[OH](2)D. These abnormalities may be corrected by the suppression of bone resorption with bisphoshonate, and supplementations of calcium and vitamin D should be avoided in these patients.     

Metabolism of vitamin D2 and vitamin D3 in patients on anticonvulsant therapy

We examined the effect of short-term treatment with pharmacological doses of vitamin D2 or vitamin D3 on the serum concentration of 1,25(OH)2D metabolites in epileptic patients on chronic anticonvulsant drug therapy. Nine patients were studied before and after treatment with vitamin D2 4000 IU daily for 24 weeks and 10 before and after treatment with vitamin D3 in the same dose. Before treatment the serum concentrations of 1,25(OH)2D and 25(OH)D were significantly lower in epileptics than in normal subjects (P less than 0.01). Vitamin D2 treatment increased the serum concentration of 1,25(OH)2D2, but a corresponding decrease in 1,25(OH)2D3 resulted in an unchanged serum concentration of total 1,25(OH)2D. The serum concentration of 25(OH)D2 and 25(OH)D increased significantly, whereas there was a small decrease in 25(OH)D3. Vitamin D3 treatment did not change the serum concentration of 1,25(OH)2D3 whereas serum 25(OH)D3 increased significantly. The correlation between the serum ratio of 1,25(OH)2D2/1,25(OH)2D3 and 25(OH)D2/25(OH)D3 estimated on vitamin D2-treated epileptic patients and normal subjects was highly significant (P less than 0.01). The data indicate that the serum concentration of 1,25(OH)2D2 and 1,25(OH)2D3 are directly proportional to the amount of their precursors 25(OH)D2 and 25(OH)D3 and that the concentration of total 1,25(OH)2D is tightly regulated.     

1,25-dihydroxyvitamin D3 reverses experimental autoimmune encephalomyelitis by inhibiting chemokine synthesis and monocyte trafficking

Multiple sclerosis (MS) is a complex neurodegenerative disease whose pathogenesis involves genetic and environmental risk factors leading to an aberrant, neuroantigen-specific, CD4+ T cell-mediated autoimmune response. In support of the hypothesis that vitamin D3 may reduce MS risk and severity, we found that vitamin D3 and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) inhibited induction of experimental autoimmune encephalomyelitis (EAE), an MS model. To investigate how 1,25-(OH)2D3 could carry out anti-inflammatory functions, we administered 1,25-(OH)2D3 or a placebo to mice with EAE, and subsequently analyzed clinical disease, chemokines, inducible nitric oxide synthase (iNOS), and recruitment of dye-labeled monocytes. The 1,25-(OH)2D3 treatment significantly reduced clinical EAE severity within 3 days. Sharp declines in chemokines, inducible iNOS, and CD11b+ monocyte recruitment into the central nervous system (CNS) preceded this clinical disease abatement in the 1,25-(OH)2D3-treated animals. The 1,25-(OH)2D3 did not directly and rapidly inhibit chemokine synthesis in vivo or in vitro. Rather, the 1,25-(OH)2D3 rapidly stimulated activated CD4+ T cell apoptosis in the CNS and spleen. Collectively, these results support a model wherein inflammation stimulates a natural anti-inflammatory feedback loop. The activated inflammatory cells produce 1,25-(OH)2D3, and this hormone subsequently enhances the apoptotic death of inflammatory CD4+ T cells, removing the driving force for continued inflammation. In this way, the sunlight-derived hormone could reduce the risk of chronic CNS inflammation and autoimmune-mediated neurodegenerative disease.     

Antidepressants differentially related to 1,25-(OH)2 vitamin D3 and 25-(OH) vitamin D3 in late-life depression

A low plasma 25-OH vitamin D₃ level is a universal risk factor for a wide range of diseases and has also been implicated in late-life depression. It is currently unknown whether the biologically active form of vitamin D, that is, 1,25-(OH)₂ vitamin D₃, is also decreased in late-life depression, or whether vitamin D levels correlate with specific depression characteristics. We determined plasma 25-OH vitamin D₃, 1,25-(OH)₂ vitamin D₃ and parathormone levels in 355 depressed older persons and 124 non-depressed comparison subjects (age⩾60 years). Psychopathology was established with the Composite International Diagnostic Interview 2.1, together with potential confounders and depression characteristics (severity, symptom profile, age of onset, recurrence, chronicity and antidepressant drug use). Adjusted for confounders, depressed patients had significantly lower levels of 25-OH vitamin D₃₃ (Cohen''s d =0.28 (95% confidence interval: 0.07–0.49), P=0.033) as well as 1,25-(OH)₂ vitamin D₃ (Cohen''s d =0.48 (95% confidence interval: 0.27–0.70), P<0.001) than comparison subjects. Of all depression characteristics tested, only the use of tricyclic antidepressants (TCAs) was significantly correlated with lower 1,25-(OH)₂ vitamin D₃ levels (Cohen''s d =0.86 (95% confidence interval: 0.53–1.19), P<0.001), but not its often measured precursor 25-OH vitamin D₃. As vitamin D levels were significantly lower after adjustment for confounders, vitamin D might have an aetiological role in late-life depression. Differences between depressed and non-depressed subjects were largest for the biologically active form of vitamin D. The differential impact of TCAs on 25-OH vitamin D₃ and 1,25-(OH)₂ vitamin D₃ levels suggests modulation of 1-α-hydroxylase and/or 24-hydroxylase, which may in turn have clinical implications for biological ageing mechanisms in late-life depression.     

1,25-dihydroxyvitamin D3 treatment decreases macrophage accumulation in the CNS of mice with experimental autoimmune encephalomyelitis

Sunlight, which is required for vitamin D biosynthesis, may be protective in multiple sclerosis (MS), due to the immunoregulatory functions of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), the hormonally active vitamin D metabolite. This hypothesis provided the impetus for the experiments reported here investigating mechanisms whereby 1,25-(OH)2D3 may inhibit murine experimental autoimmune encephalomyelitis (EAE). Severe EAE was induced, 1,25-(OH)2D3 or mock treatment was administered, and clinical disease, histopathological disease, and encephalitogenic cells in the central nervous system (CNS) were analyzed within 24-72 h of the treatment. The mock-treated mice remained paralyzed (stage 3 EAE) while most hormone-treated animals regained the partial use of both hind limbs (stage 2 EAE) within 72 h of treatment. A histopathological examination showed the hormone-treated mice had a 50% decrease in white matter and meningeal inflammation at 72 h post treatment. A flow cytometric analysis of cell surface markers on spinal cord cells recovered 24 h post treatment showed the mock-treated mice with EAE had about 7.0 +/- 2.3 million Mac-1+ cells/cord, whereas the hormone-treated mice had about 2.1 +/- 2.6 million Mac-1+ cells/cord, which was not significantly different from the unmanipulated control mice. Otherwise, the flow cytometric analysis detected no significant differences between the groups with respect to CD4+ or CD8+ T cells or B cells or macrophages in draining lymph nodes or spinal cords. These results are discussed with regard to possible fates for the 5 million Mac-1+ cells that were rapidly lost from the inflamed CNS in the 1,25-(OH)2D3-treated mice, and the possible beneficial effect of hormone treatment in resolving acute MS.     

Low serum 24,25 dihydroxyvitamin D in Duchenne muscular dystrophy

Levels of serum 24,25(OH)2D3 (0.69 +/- 0.17 ng/ml) were lower in DMD patients than in age-matched controls (2.13 +/- 0.15 ng/ml). Circulating levels of 1,25(OH)2D3 and 25(OH)D3 were within the accepted normal range. Bearing in mind the proposed pathophysiologic role of calcium in DMD and the influence of vitamin D metabolites on muscle ATP and protein synthesis, as well as on sarcoplasmic reticulum calcium transport and muscle mitochondrial calcium content, the above findings of low or deficient 24,25(OH)2D3 levels in DMD could be meaningful from the etiologic and therapeutic points of view.     

Influence of solar irradiation on vitamin D levels in children on anticonvulsant drugs

Previous studies about the serum levels of vitamin D metabolites in epileptic patients have given conflicting results. We have investigated the influence of chronic anti-epileptic treatment on mineral metabolism in 17 ambulatory epileptic children who were studied for 2 seasons with high and low levels of solar radiation, respectively. No differences in serum calcium, phosphate or 1.25-dihydroxyvitamin D were observed between patients and control children. Patients also had normal levels of 25-hydroxyvitamin D [25(OH)D] in summer. However, serum 25(OH)D concentrations were lower in patients than in controls in winter months (12.6 +/- 1.4 versus 19.6 +/- 1.2 ng/ml, P less than 0.001). These findings point out the influence of the intensity of solar irradiation, and subsequently of vitamin D availability, on the effect of anticonvulsant drugs on vitamin D metabolism, and may help to explain the conflicting results of previous reports. Prophylactic vitamin D therapy should be considered when climatic conditions or patients' life styles do not allow an adequate exposure to sunlight.     

Influence of immobilization upon calcium metabolism in the week following hemiplegic stroke

Hip fractures on the paretic side are a serious post-stroke complication and may result from disuse hemiosteopenia, hypovitaminosis D, and an increasing risk of falls. To evaluate short-term immobilization effects, we assessed calcium metabolism in 89 patients 1 week after the hemiplegic stroke and in 36 controls. Patient activity was rated using the Barthel index (BI). Sera from stroke patients and control subjects were assayed for ionized calcium, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OHD), 1, 25-dihydroxyvitamin D (1,25-(OH)(2)D), bone Gla protein (BGP; a bone formation marker) and pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP; a bone resorption marker). Patients' serum concentrations of ionized calcium and ICTP were higher than in controls and correlated negatively with BI; their BGP concentrations were low, correlating positively with BI. Concentrations of serum 25-OHD, 1,25-(OH)(2)D, and PTH also were low; serum 25-OHD was at a deficient level (<10 ng/ml) in nine patients (10%), an insufficient level (10-20 ng/ml) in 56 (63%), and a sufficient level (>20 ng/ml) in only 24 (27%). PTH correlated negatively with calcium and 1,25-(OH)(2)D. Hypovitaminosis D is common in acute stroke patients. Immobilization from acute hemiplegia can increase bone resorption and serum calcium, and inhibit PTH secretion and 1,25-(OH)(2)D production to add to the effects of hypovitaminosis D.     

Genetic analysis of vitamin D related genes in Canadian multiple sclerosis patients. Canadian Collaborative Study Group

The objective of this study was to investigate genes involved in the metabolism and function of vitamin D as candidate genes for genetic susceptibility to MS. Restriction fragment length polymorphisms and highly polymorphic microsatellite markers within or very close to the 1,25(OH)2D3 receptor (VDR) [12q14], the vitamin D binding protein (DBP) [4q12], and the 25(OH)D2 1alpha-hydroxylase [12q13] loci were analyzed for linkage or association with MS. We found no evidence for linkage or association of these candidate genes with MS in the Canadian population.     

Vitamin D has a direct immunomodulatory effect on CD8+ T cells of patients with early multiple sclerosis and healthy control subjects

Little is known on a putative effect of vitamin D on CD8+ T cells. Yet, these cells are involved in the immmunopathogenesis of MS. We assessed the cytokine profile of EBV-specific CD8+ T cells of 10 early MS patients and 10 healthy control subjects with or without 1,25(OH)(2)D(3) and found that, with 1,25(OH)(2)D(3), these cells secreted less IFN-γ and TNF-α and more IL-5 and TGF-β. CD4+ T cell depletion or even culture with CD8+ T cells only did not abolish the immunomodulatory effect of 1,25(OH)(2)D(3) on CD8+ T cells, suggesting that 1,25(OH)(2)D(3) can act directly on CD8+ T cells.     

Vitamin D status in children with intractable epilepsy, and impact of the ketogenic diet

PURPOSE: The aim of this study was to describe vitamin D status in children with intractable epilepsy prescribed newer antiepileptic drugs (AEDs) before initiation of and during 15-month treatment with the ketogenic diet (KD). METHODS: Serum vitamin D (25-OHD and 1,25-OHD) and parathyroid hormone (PTH) were assessed in prepubertal children with intractable epilepsy before initiation of and during KD therapy. Three-day weighed dietary records including KD and vitamin and mineral supplementation were obtained at baseline and at 1 month. RESULTS: Forty-five children (aged 5.1 +/- 2.7 years) were enrolled. Before KD therapy, 4% had deficient and 51% had insufficient serum 25-OHD levels. Vitamin D intake was less than recommended in 47%. Adequate vitamin D intake, fewer AEDs, and generalized seizures were associated with higher serum 25-OHD levels (p < 0.01). After 3 months on the KD, 25-OHD levels increased (p < 0.001), and PTH declined (p < 0.001). Over the next 12-month period, 25-OHD levels steadily declined (p < 0.001), and PTH did not significantly change. CONCLUSIONS: Children with intractable epilepsy treated with newer AEDs had poor vitamin D status. Their status improved over the first 3 months of KD therapy with vitamin D supplementation and slowly declined thereafter.     

Effect of 1,25-dihydroxyvitamin D(3) on cultured mesencephalic dopaminergic neurons to the combined toxicity caused by L-buthionine sulfoximine and 1-methyl-4-phenylpyridine

A decrease in intracellular glutathione content may be related to the primary event in Parkinson's disease, so increasing the glutathione level may have a therapeutic benefit. The biologically active form of vitamin D, 1,25-dihydroxyvitamin D(3) [1, 25-(OH)(2)D(3)] has been recently reported to enhance the intracellular glutathione concentration in the central nervous system. Exposing rat cultured mesencephalic neurons for 24 hr to a mixture of L-buthionine sulfoximine (BSO) and 1-methyl-4-phenylpyridium ions (MPP(+)) resulted in a relatively selective damage to dopaminergic neurons. This damage has been accompanied by a reduction of intracellular glutathione levels. Low doses, i.e., 1-100 nM, of 1,25-(OH)(2)D(3) protect cultured dopaminergic neurons against this toxicity, although higher concentrations of this active form of vitamin D have been found to enhance the toxic effect. Generation of reactive oxygen species (ROS) by this toxicity has been attenuated in cultures being pretreated with low concentrations of 1,25-(OH)(2)D(3). Because the hormone increases the intracellular glutathione content in cultures, determining how this hormone suppresses ROS generation may involve the enhancement of the antioxidative system. These data suggest that low doses of 1,25-(OH)(2)D(3) are able to protect mesencephalic dopaminergic neurons against BSO/MPP(+)-induced toxicity that causes a depletion in glutathione content.     

Association between plasma concentrations of vitamin D metabolites and depressive symptoms throughout pregnancy in a prospective cohort of Brazilian women

Plasma concentrations of vitamin D metabolites can be inversely associated with depressive symptoms. However, few longitudinal studies have investigated this association, especially during pregnancy. The aim of this study was to investigate the association between concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxivitamin D [1,25(OH)₂D] with the occurrence of depressive symptoms throughout pregnancy. A prospective cohort of 179 women was followed at 5th-13th, 20th-26th and 30th-36th gestational weeks. At each trimester of pregnancy, the plasma concentrations of 25(OH)D and 1,25(OH)₂D were analyzed by liquid chromatography tandem mass spectroscopy. Vitamin D status was categorized according to the Endocrine Society Practice Guidelines and the Institute of Medicine. Depressive symptoms were measured at each trimester using the Edinburgh Postnatal Depressive Scale (cutoff ≥13). Statistical analyses included random intercept logistic regression models for longitudinal analyses. In the first trimester, the prevalence of 25(OH)D <75, <50 and <30 nmol/L were 69.3%, 14.0% and 1.7%, respectively. Prevalence of depressive symptoms were 20.1%, 14.7% and 7.8% for the first, second and third trimesters, respectively. The probability of occurrence of depressive symptoms decreased throughout pregnancy (p-value = 0.005). Women with higher concentrations of 25(OH)D in the first trimester presented a lower odds ratio (OR) for the development of depressive symptoms during pregnancy (OR = 0.98; 95%CI: 0.96 to 0.99, p-value = 0.047) in the adjusted model. In conclusion, there was a higher prevalence of vitamin D inadequacy and depressive symptoms during the first trimester. Higher 25(OH)D concentrations in the first trimester were associated with a decrease of 2% in the odds for presenting depressive symptoms throughout pregnancy.     

1,25-dihydroxyvitamin D3 regulates the expression of VDR and NGF gene in Schwann cells in vitro

The vitamin D receptor (VDR) is a nuclear receptor that mediates the effect of the active metabolite of vitamin D3, the 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). To investigate the potential role of this hormone in the peripheral nervous system, we have studied the VDR expression in Schwann cells. The VDR mRNA was detected by Northern blot analysis in rat primary cultures of Schwann cells, and its levels were strongly increased in the presence of 1,25-(OH)2D3. Using the mouse Schwann cell line, MSC80, we showed that concentrations as low as 10^-10 M of hormone stimulated the expression of the VDR gene and strongly increased the amounts of activated VDR, capable of binding to the specific vitamin D responsive element (VDRE). We also found that 1,25-(OH)2D3 stimulated the expression of the nerve growth factor gene in MSC80. These data suggest a role for the hormone in the peripheral nervous system, possibly as a mediator actived in trauma. J. Neurosci. Res. 53:742–746, 1998. © 1998 Wiley-Liss, Inc.     

Serum vitamin D metabolites in epileptic patients treated with 2 different anti-convulsants

The serum concentrations of the vitamin D metabolites 25-hydroxy-vitamin D (25OHD), 24,25-dihydroxyvitamin D (24,25(OH)₂D), and 1,25-dihydroxyvitamin D (1,25(OH)₂D) were measured in 18 epileptic patients and 10 controls. The patients were divided according to the anti-convulsant treatment they had been receiving for at least 1 year: 9 patients had received phenytoin and 9 patients carbamazepine, as the sole anti-convulsant therapy.
The serum 25OHD was decreased in the patients on phenytoin ( P < 0.01). whereas the other serum vitamin D metabolites were normal. Moreover, serum alkaline phosphatase was increased ( P < 0.001) and serum calcium was decreased ( P < 0.001) in this patient group.
In the patient group treated with carbamazepine (a negligible liver inductor), changes in serum 25OHD and serum alkaline phosphatase were less pronounced ( P < 0.05), but the same degree of hypocalcaemia ( P < 0.001) was present.
Our data suggest that liver induction in epileptic patients on anti-convulsant drugs cannot explain the pathophysiology behind anti-convulsant osteomalacia.     

Rag-1-dependent cells are necessary for 1,25-dihydroxyvitamin D(3) prevention of experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is a demyelinating disease involving genetic and environmental risk factors. Geographic, genetic, and biological evidence suggests that one environmental risk factor may be lack of vitamin D. Here, we investigated how 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) inhibits experimental autoimmune encephalomyelitis (EAE), an MS model. The experiments used adoptive transfer of TCR-transgenic (TCR1) cells specific for myelin basic protein (MBP) peptide into unprimed recipients. When unprimed TCR1 splenocytes were transferred, and the recipients were immunized with peptide, the mock-treated mice developed EAE, but the 1,25-(OH)(2)D(3)-treated recipients remained disease-free. Both groups had TCR1 T cells that proliferated in response to MBP Ac1-11 and produced IFN-gamma but not IL-4 in the lymph node. In the central nervous system (CNS), the mock-treated mice had activated TCR1 T cells that produced IFN-gamma but not IL-4, while the 1,25-(OH)(2)D(3)-treated mice had TCR1 T cells with a non-activated phenotype that did not produce IFN-gamma or IL-4. When activated TCR1 T cells producing IFN-gamma were transferred into unprimed mice, the mock-treated and the 1,25-(OH)(2)D(3)-treated recipients developed EAE. Likewise, the 1,25-(OH)(2)D(3) did not inhibit Th1 cell IFN-gamma production or promote Th2 cell genesis or IL-4 production in vitro. Finally, the 1,25-(OH)(2)D(3) inhibited EAE in MBP-specific TCR-transgenic mice that were Rag-1(+), but not in animals that were Rag-1-null. Together, these data refute the hypothesis that the hormone inhibits Th1 cell genesis or function directly or through an action on antigen-presenting cells, or promotes Th2 cell genesis or function. Instead, the evidence supports a model wherein the 1,25-(OH)(2)D(3) acts through a Rag-1-dependent cell to limit the occurrence of activated, autoreactive T cells in the CNS.     

Administration of 1,25-dihydroxyvitamin D3 results in the elevation of hippocampal seizure threshold levels in rats

Electrical stimulation of the dorsal hippocampal formation of the rat was employed to determine the effect of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), the hormonal form of vitamin D, on induced seizure thresholds. Stereotaxic injection of 100 micrograms or 50 micrograms 1,25-dihydroxyvitamin D3 in 2 microliter propylene glycol into the hippocampus resulted in a significant elevation in seizure threshold in all animals treated. 1,25-dihydroxyvitamin D3-induced increases were noted within 5-10 min and lasted at least 120-180 min after injection when the experiments were terminated. Intravenous injection of 1,25-(OH)2D3 also resulted in a significant elevation of seizure threshold; however, the increase was transient, lasting only 30 min. This effect was specific since 200 micrograms vitamin D3 or 200 micrograms 25-hydroxyvitamin D3 (25-(OH)D3), injected into the hippocampus, had no effect on seizure threshold levels. This investigation represents the first direct demonstration of a role for 1,25-(OH)2D3 in the regulation of seizure activity and suggests, along with the previously demonstrated presence of immunoreactive vitamin D-dependent calcium binding protein and receptors for 1,25-dihydroxyvitamin D3 in the brain, that the vitamin D endocrine system may play a significant role in the physiological mechanisms underlying convulsive disorders.     

Vitamin D from different sources is inversely associated with Parkinson disease

An inverse association between Parkinson disease (PD) and total vitamin D levels has been reported, but whether vitamin D from different sources, that is, 25(OH)D2 (from diet and supplements) and 25(OH)D3 (mainly from sunlight exposure), all contribute to the association is unknown. Plasma total 25(OH)D, 25(OH)D2, and 25(OH)D3 levels were measured by liquid chromatography–tandem mass spectrometry in PD patients (n = 478) and controls (n = 431). Total 25(OH)D was categorized by clinical insufficiency or deficiency; 25(OH)D2 and 25(OH)D3 were analyzed in quartiles. Vitamin D deficiency (total 25[OH]D < 20 ng/mL) and vitamin D insufficiency (total 25[OH]D < 30 ng/mL) are associated with PD risk (odds ratio [OR] = 2.6 [deficiency] and 2.1 [insufficiency]; P < 0.0001), adjusting for age, sex, and sampling season. Both 25(OH)D2 and 25(OH)D3 levels are inversely associated with PD (P_trend < 0.0001). The association between 25(OH)D2 and PD risk is largely confined to individuals with low 25(OH)D3 levels (P_trend = 0.0008 and 0.12 in individuals with 25[OH]D3 < 20 ng/mL and 25[OH]D3 ≥ 20 ng/mL, respectively). Our data confirm the association between vitamin D deficiency and PD, and for the first time demonstrate an inverse association of 25(OH)D2 with PD. Given that 25(OH)D2 concentration is independent of sunlight exposure, this new finding suggests that the inverse association between vitamin D levels and PD is not simply attributable to lack of sunlight exposure in PD patients with impaired mobility. The current study, however, cannot exclude the possibility that gastrointestinal dysfunction, a non‐motor PD symptom, contributes to the lower vitamin D2 levels in PD patients. © 2014 International Parkinson and Movement Disorder Society