The Effects of a Low Glutamate Dietary Intervention on Anxiety and PTSD in Veterans with Gulf War Illness (FS15-08-19)

Abstract Objectives Glutamate is an amino acid and also serves as the most ubiquitous neurotransmitter in the human body. Previous work has shown that dysregulated glutamatergic neurotransmission is implicated in the etiology of anxiety disorders. Objective: To examine the effect of a low glutamate dietary intervention on anxiety and Posttraumatic Stress Disorder (PTSD) in veterans with Gulf War Illness (GWI). Methods Forty veterans with GWI are being recruited for a randomized-controlled clinical trial testing the effects of a low glutamate diet on neurological symptoms. After consent, subjects complete baseline measures, then subjects are randomized to the low-glutamate diet or a wait-listed control group. For the active intervention phase, they follow a 1-month low glutamate diet and then are re-tested prior to entering a double-blind, placebo-controlled crossover challenge with monosodium glutamate (MSG) or placebo, to test for return of symptoms. Preliminary data are presented here for changes observed on the Generalized Anxiety Disorder 7-item (GAD-7) scale and the PTSD Checklist (PCL-C) after one month on the diet in subjects recruited to date. Pre-post diet scores were compared for anxiety and PTSD using a Wilcoxon Signed Rank test in SAS. Results Seventeen veterans (M = 15; F = 2) with GWI have been recruited to date (mean age = 50 ± 4 yrs). Preliminary analyses demonstrate that after one month on the diet, significant improvements were noted for anxiety (score reduced from a median (IQ range) of 9 (13) to 5 (10), p = 0.01) and for PTSD (median (IQ) score reduced from 58 (33) to 43 (28), p = 0.04). Conclusions This study suggests that consuming a low glutamate diet may improve anxiety and PTSD in veterans suffering from Gulf War Illness. More research is needed to further explore the role of dietary glutamate in anxiety disorders. Funding Sources U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Gulf War Illness Research Program under Award No. W81XWH-17-1-0457. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.

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The Low Glutamate Diet Significantly Improves Pain and Other Symptoms in Veterans with Gulf War Illness

Current Developments in Nutrition ◽

10.1093/cdn/nzaa057_027 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1211-1211

Author(s):

Kathleen Holton ◽

Anna Kirkland ◽

Elizabeth Brandley ◽

John VanMeter ◽

James Baraniuk

Keyword(s):

Chronic Pain ◽

Effect Size ◽

Dietary Intervention ◽

Monosodium Glutamate ◽

Gulf War ◽

Diet Group ◽

Control Group ◽

Diet Change ◽

Gulf War Illness ◽

Double Blind

Abstract Objectives The objective was to examine if a low glutamate diet can reduce symptoms in Gulf War Illness (GWI), a multi-symptom chronic pain condition. Methods Forty GW veterans were recruited from across the US. Baseline measures included assessment of symptoms, myalgic score, tender point count, and dolorimetry. Subjects were randomized to the low glutamate diet, or to a wait-listed control group, starting the diet one month later. Measures were evaluated post-diet, and then subjects were randomized to a double-blind placebo-controlled crossover challenge with monosodium glutamate (MSG)/placebo to assess whether symptoms return/worsen in each condition. Challenge data have not yet been un-blinded, and thus are not included in this abstract. Symptom scores were compared between those randomized to immediate dietary intervention versus wait-listed controls (independent t-tests). After everyone completed the 1-month diet, change scores were analyzed for the whole group (Wilcoxon Signed Rank tests). Improvement was defined as ‘much’ or ‘very much’ improved on the patient global impression of change (PGIC) score, and the effect size was calculated (Cohen's d). Results After 1-month, overall symptom number (mean (SD)) significantly differed between the diet group (11(6)) and the wait-listed controls (18(6)), P = 0.0007. The diet had a very large effect size, d = 1.17, with no adverse effects reported. When comparing pre-post scores after all subjects followed the 1-month diet, the number of symptoms went from a mean(SD) of 21(5) at baseline to 12(6) post-diet, P < 0.0001. The severity of remaining symptoms was also significantly reduced (all P < 0.0001). Seventy-two % of subjects met the PGIC criteria for improvement. Highly significant improvements in pain measures were also observed for myalgic score (P < 0.0001), number of tender points (P < 0.0001), and average dolorimetry (P < 0.001). Conclusions These striking results suggest that the low glutamate diet may be an effective treatment for chronic pain and symptoms associated with Gulf War Illness. Funding Sources Department of Defense (DoD), US Army Medical Research Acquisition Activity, Office of the Assistant Secretary of Defense for Health Affairs through the GWI Research Program. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the DoD.

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Gulf War Veterans with Psychiatric Symptoms (Anxiety, Depression, and PTSD) Significantly Improve on a Low Glutamate Diet

Current Developments in Nutrition ◽

10.1093/cdn/nzaa057_008 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1192-1192

Author(s):

Elizabeth Brandley ◽

Anna Kirkland ◽

Kathleen Holton

Keyword(s):

Dietary Intervention ◽

Psychiatric Symptoms ◽

Gulf War ◽

Control Group ◽

Gulf War Illness ◽

War Veterans ◽

Double Blind ◽

Double Blind Placebo ◽

Gulf War Veterans ◽

Anxiety Depression

Abstract Objectives The objective of this study was to assess the effects of a low glutamate dietary intervention on measures of anxiety, depression, and PTSD in veterans with Gulf War Illness (GWI). Methods Forty Gulf War veterans were recruited from across the U.S. for a clinical trial examining the effects of a low glutamate diet on symptoms of GWI. During baseline testing, subjects completed the GAD-7 anxiety measure, the PCL-C PTSD scale, and the Center for Epidemiologic Studies Depression Scale (CES-D), and then were randomized to immediate dietary intervention or a wait-listed control group. All participants received intensive dietary training before starting the diet. After one month on the diet, post-diet testing was completed, then subjects were randomized into a double-blind, placebo-controlled crossover challenge with MSG/placebo to test for a return of symptoms. The challenge data has not yet been un-blinded; therefore, it will not be discussed in this abstract. Pre-post diet change scores were analyzed using the Wilcoxon Signed Rank tests via SPSS®v26. Results Results demonstrate highly significant improvements in psychiatric symptoms associated with GWI after one-month on a low glutamate diet. Scores were reduced from a median (IQ range) of 9(13) to 4(8), P = 0.001 for anxiety; from 27(15) to 19(10), P < 0.001 for depression; and from 57(32) to 39(32), P < 0.001 for PTSD. Conclusions These results suggest that a low glutamate diet may improve depression, anxiety, and PTSD in veterans with GWI. Future analysis of the double-blind, placebo-controlled crossover challenge data will provide a better understanding of whether challenge with glutamate can significantly increase anxiety, depression and PTSD relative to placebo. Funding Sources The US Army Medical Research Acquisition Activity, 820 Chandler St, Fort Detrick MD 21,702–5014 is the awarding and administering acquisition office. This work is supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Gulf War Illness Research Program. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.

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A Low Glutamate Diet Improves Cognitive Functioning in Veterans with Gulf War Illness

Current Developments in Nutrition ◽

10.1093/cdn/nzaa057_033 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1217-1217

Author(s):

Anna Kirkland ◽

Elizabeth Brandley ◽

Kathleen Holton

Keyword(s):

Adult Adhd ◽

Dietary Intervention ◽

Gulf War ◽

Self Report ◽

Rank Test ◽

Gulf War Illness ◽

Double Blind ◽

Cognitive Domains ◽

Double Blind Placebo ◽

The Us

Abstract Objectives The objective of this research was to investigate a novel low glutamate dietary intervention for Gulf War Illness (GWI), a chronic multi-symptom disorder that includes cognitive dysfunction. Methods Forty GW veterans with GWI were recruited from across the US. As part of a larger clinical trial, participants completed computerized cognitive testing and the Adult ADHD Self-Report Scale (ASRS) using CNS Vital Signs® (CNSVS) software. Before diet initiation, subjects received intensive dietary counseling. Post-diet assessments were completed after 1 month on the diet, and then participants were randomized to a 2-week double-blind placebo-controlled crossover challenge with glutamate (MSG)/placebo administered over 3 days of each week. The CNSVS battery was administered again on the 3rd day of each challenge week. The challenge data have not yet been un-blinded, and therefore will not be included in this abstract. Pre-post testing (t-test or Wilcoxon Signed Rank test) was conducted for each domain in the CNSVS battery, including an overall marker of neurocognitive function (NCI) and the ASRS. Results Several cognitive domains were significantly improved after 1-month on the low glutamate diet, including NCI (P < 0.01), executive functioning (P = 0.01), cognitive flexibility (P < 0.05), motor speed (P < 0.01), processing speed (P < 0.05), and psychomotor speed (P = 0.001). However, reaction time was slower at post-diet testing (P = 0.01). ADHD symptoms were also significantly improved at post-diet (P < 0.0001). Conclusions Veterans with GWI showed major improvements in cognitive function after 1-month on a low glutamate diet, including improvement in overall neurocognitive status. Upcoming analysis of the double-blind placebo-controlled crossover challenge data will provide additional information on which cognitive domains are directly affected by challenge with glutamate relative to placebo. Funding Sources The US Army Medical Research Acquisition Activity, 820 Chandler St, Fort Detrick MD 21,702–5014 is the awarding and administering acquisition office. This work is supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Gulf War Illness Research Program. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.

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The Low Glutamate Diet Effectively Improves Pain and Other Symptoms of Gulf War Illness

Nutrients ◽

10.3390/nu12092593 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2593

Author(s):

Kathleen F. Holton ◽

Anna E. Kirkland ◽

Michael Baron ◽

Shalini S. Ramachandra ◽

Mackenzie T. Langan ◽

...

Keyword(s):

Symptom Score ◽

Effect Size ◽

Monosodium Glutamate ◽

Tender Point ◽

Gulf War ◽

Control Group ◽

Individual Response ◽

Gulf War Illness ◽

Diet Intervention ◽

Gastrointestinal Problems

Gulf War Illness (GWI) is a multisymptom disorder including widespread chronic pain, fatigue and gastrointestinal problems. The objective of this study was to examine the low glutamate diet as a treatment for GWI. Forty veterans with GWI were recruited from across the US. Outcomes included symptom score, myalgic score, tender point count, dolorimetry and the Chalder Fatigue Scale. Subjects were randomized to the low glutamate diet or a wait-listed control group, with symptom score being compared after one month. Subjects then went onto a double-blind, placebo-controlled crossover challenge with monosodium glutamate (MSG)/placebo to test for return of symptoms. Symptom score was compared between diet intervention and wait-listed controls with an independent t-test and effect size was calculated with Cohen’s d. Change scores were analyzed with Wilcoxon Signed Rank tests. Crossover challenge results were analyzed with General Linear Models and cluster analysis. The diet intervention group reported significantly less symptoms (p = 0.0009) than wait-listed controls, with a very large effect size, d = 1.16. Significant improvements in average dolorimetry (p = 0.0006), symptom score, tender point number, myalgic score and the Chalder Fatigue Scale (all p < 0.0001) were observed after the 1-month diet. Challenge with MSG/placebo resulted in significant variability in individual response. These results suggest that the low glutamate diet can effectively reduce overall symptoms, pain and fatigue in GWI, but differential results upon challenge suggest that other aspects of the diet, or underlying differences within the population, may be driving these changes. Future research is needed to identify potential nutrient effects, biomarkers, and underlying metabolic differences between responders and non-responders.

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Efficacy and safety of oral hydroxyurea in transfusion-dependent β-thalassaemia: a protocol for randomised double-blind controlled clinical trial

BMJ Open ◽

10.1136/bmjopen-2020-041958 ◽

2020 ◽

Vol 10 (10) ◽

pp. e041958

Author(s):

Nirmani Yasara ◽

Nethmi Wickramarathne ◽

Chamila Mettananda ◽

Aresha Manamperi ◽

Anuja Premawardhena ◽

...

Keyword(s):

Clinical Trial ◽

Sri Lanka ◽

Intervention Group ◽

Primary Outcome Measure ◽

Control Group ◽

Controlled Clinical Trial ◽

Efficacy And Safety ◽

Scientific Publications ◽

Double Blind ◽

Fetal Haemoglobin

IntroductionDespite being one of the first diseases to be genetically characterised, β-thalassaemia remains a disorder without a cure in a majority of patients. Most patients with β-thalassaemia receive only supportive treatment and therefore have a poor quality of life and shorter life spans. Hydroxyurea, which has shown to induce fetal haemoglobin synthesis in human erythroid cells, is currently recommended for the treatment of sickle cell disease. However, its clinical usefulness in transfusion-dependent β-thalassaemia is unclear. Here, we present a protocol for a randomised double-blind controlled clinical trial to evaluate the efficacy and safety of oral hydroxyurea in transfusion-dependent β-thalassaemia.Methods and analysisThis single-centre randomised double-blind placebo-controlled clinical trial is conducted at the Thalassaemia Centre of Colombo North Teaching Hospital, Ragama, Sri Lanka. Adult and adolescent patients with haematologically and genetically confirmed transfusion-dependent β-thalassaemia are enrolled and randomised into the intervention or control group. The intervention group receives oral hydroxyurea 10–20 mg/kg daily for 6 months, while the control group receives a placebo which is identical in size, shape and colour to hydroxyurea without its active ingredient. Transfused blood volume, pretransfusion haemoglobin level, fetal haemoglobin percentage and adverse effects of treatment are monitored during treatment and 6 months post-treatment. Cessation or reduction of blood transfusions during the treatment period will be the primary outcome measure. The statistical analysis will be based on intention to treat.Ethics and disseminationEthical approval has been obtained from the Ethics Committee of Faculty of Medicine, University of Kelaniya (P/116/05/2018) and the trial is approved by the National Medicinal Regulatory Authority of Sri Lanka. Results of the trial will be disseminated in scientific publications in reputed journals.Trial registration numberSLCTR/2018/024; Pre-results.

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Curcumin nanomicelle versus curcumin improves lipid profile, stress oxidative factors and inflammatory markers in patients undergoing coronary elective angioplasty; A Randomized Clinical Trial

10.21203/rs.2.18679/v1 ◽

2019 ◽

Author(s):

Bijan Helli ◽

Hadis Gerami ◽

Maria Kavianpour ◽

Habib Heybar ◽

Seyed Kianoosh Hosseini ◽

...

Keyword(s):

Clinical Trial ◽

Lipid Profile ◽

Inflammatory Markers ◽

Interleukin 1 ◽

Stress Index ◽

Inflammatory Factors ◽

Control Group ◽

Controlled Clinical Trial ◽

Double Blind ◽

Stress Oxidative

Abstract Background: Curcumin exhibited antioxidant and anti-inflammatory effects. The aim of this study, assess and compare curcumin and nano- curcumin effects on lipid profile, oxidative stress index and inflammatory factors of heart patients.Methods: This Randomized, Double-Blind, Placebo-Controlled Clinical Trial conducted on 90 patients undergoing coronary elective angioplasty. Patients were randomly divided into 3 groups. The first group received a 500 mg capsule of curcumin daily. The second group received an 80 mg capsule of nano- curcumin daily. The placebo group also received capsules similar to curcumin for 8 weeks. Lipid profile, stress oxidative factors and inflammatory markers measured in baseline and end of the investigation.Results: At the end of study, statistically significant changes was seen in the total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) in the intervention groups to the control group (p<0.05). These changes in the nano-curcumin group were greater than the curcumin group. Curcumin and nano-curcumin supplementation also caused a statistically significant improvement in plasma levels of total antioxidant capacity (TAC), malondialdehyde (MDA), Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), high-sensitivity C-reactive protein (hs-CRP), Interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in comparison to the placebo (p<0.05).Conclusion: Complementary therapy of cardiovascular patients with curcumin and nano-curcumin supplements, could improve lipid profile, stress oxidative index and, inflammatory factors. The effects of curcumin on nano formula may be better for cardiac patients due to high bioavailability. However, further investigation is suggested in this regard.

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Efficacy and Safety of Ejiao (Asini Corii Colla) in Women With Blood Deficient Symptoms: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial

Frontiers in Pharmacology ◽

10.3389/fphar.2021.718154 ◽

2021 ◽

Vol 12 ◽

Author(s):

Li Zhang ◽

Zhongju Xu ◽

Tao Jiang ◽

Jialu Zhang ◽

Pinxian Huang ◽

...

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Blood Cell ◽

Control Group ◽

Placebo Control ◽

Controlled Clinical Trial ◽

Efficacy And Safety ◽

Double Blind ◽

Placebo Control Group ◽

Sf 36

Equus asinus L [Equidae; Asini Corii Colla] (donkey-hide gelatin, Ejiao), a well-known traditional Chinese medicine, has been widely used to nourish the blood, especially for women. The aim of this study was to assess the efficacy and safety of Ejiao in blood-deficient patients. A total of 210 participants were recruited and randomly allocated into the placebo control group and Ejiao-treated group (6 g/day). The primary outcomes on the efficacy of Ejiao included traditional Chinese medicine symptom scores, blood indicators, and SF-36. The secondary outcomes were changes in fireness and safety evaluation. Results showed that Ejiao treatment for 8 weeks had significantly improved dizziness symptoms. Among the tested 24 blood biochemical parameters, the hematocrit and red blood cell numbers decreased in the placebo control group, but decreased significantly less in the Ejiao treatment group. The white blood cell and neutrophil counts increased in the Ejiao group but were within the normal range. In addition, the quality of life improved as the scores in SF-36 domains were significantly higher in the Ejiao group. At the same time, there was no significant change in the fire–heat symptoms score or other safety parameters. Considering all these, our study showed that Ejiao has a promising effect in women suffering from blood deficiency without obvious adverse effects.

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Diagnosis of Gulf War Illness Using Laser-Induced Spectra Acquired from Blood Samples

Applied Spectroscopy ◽

10.1177/00037028211042049 ◽

2021 ◽

pp. 000370282110420

Author(s):

Rosalba Gaudiuso ◽

Sirui Chen ◽

Efi Kokkotou ◽

Lisa Conboy ◽

Eric Jacobson ◽

...

Keyword(s):

Blood Plasma ◽

Correct Diagnosis ◽

Difference Spectrum ◽

Gulf War ◽

Classification Model ◽

Control Group ◽

Plasma Samples ◽

Gulf War Illness ◽

Breakdown Spectroscopy ◽

The Difference

Gulf War illness (GWI) is a chronic illness with no known validated biomarkers that affects the lives of hundreds of thousands of people. As a result, there is an urgent need for the development of an untargeted and unbiased method to distinguish GWI patients from non-GWI patients. We report on the application of laser-induced breakdown spectroscopy (LIBS) to distinguish blood plasma samples from a group of subjects with GWI and from subjects with chronic low back pain as controls. We initially obtained LIBS data from blood plasma samples of four GWI patients and four non-GWI patients. We used an analytical method based on taking the difference between a mean LIBS spectrum obtained with those of GWI patients from the mean LIBS spectrum of those of the control group, to generate a “difference” spectrum for our classification model. This model was cross-validated using different numbers of differential LIBS emission peaks. A subset of 17 of the 82 atomic and ionic transitions that provided 70% of correct diagnosis was selected test in a blinded fashion using 10 additional samples and was found to yield 90% classification accuracy, 100% sensitivity, and 83.3% specificity. Of the 17 atomic and ionic transitions, eight could be assigned unambiguously to species of Na, K, and Fe.

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THE EFFECTS OF CURCUMIN ADMINISTRATION ON EXPRESSION PATTERNS OF VEGF AND COX-2 IN FERTILE ENDOMETRIUM: A RANDOMISED CLINICAL TRIAL

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2019.v11s6.33581 ◽

2019 ◽

pp. 149-152

Author(s):

RAJUDDIN RAJUDDIN ◽

BUDI WIWEKO ◽

LUTFI NUGROHO

Keyword(s):

Clinical Trial ◽

Biological Activities ◽

Expression Patterns ◽

Control Group ◽

Controlled Clinical Trial ◽

Vegf Expression ◽

Double Blind ◽

Endometrial Stromal Cells ◽

Cox 2 ◽

Fertile Women

Objective: Curcumin (diferuloylmethane) is a a compound isolated from turmeric with biological activities, including antifertility. Curcumin inhibits COX-2 expression in granulosa cells of ovarian follicles and disrupts vascular endothelial growth factor (VEGF) derived angiogenesis in the endometrium, reducing endometrial receptivity. The purpose of this study was to examine the effects of curcumin on COX-2 and VEGF expression in endometrium of fertile women. Methods: A prospective double-blind placebo-controlled clinical trial was conducted in a group of fertile women with regular menstrual cycles, aged between 20-30 y, married, and with children. Subjects were divided into a group receiving daily 800 mg encapsulated curcumin. Curcumin orally for ten days, starting on the third day of the first menstrual day, and a control group. Endometrial biopsy was performed using a microcuret and immunohistochemistry was used to assess VEGF and COX-2 expression. The results were analysed using an independent sample t-test. Results: In the curcumin-treated group, VEGF expression was significantly lower than the control group (p<0.05), and COX-2 expression was higher but not significantly so (p>0.05). Conclusion: The curcumin causes VEGF expression in endometrium is lower and negatively affects the growth of endometrial stromal cells.

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Vitamin D Treatment Attenuates Heart Apoptosis After Coronary Artery Bypass Surgery: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248420920495 ◽

2020 ◽

Vol 25 (4) ◽

pp. 338-345 ◽

Cited By ~ 1

Author(s):

Erfan Tasdighi ◽

Manouchehr Hekmat ◽

Mahmoud Beheshti ◽

Ramin Baghaei ◽

Seyed Mohsen Mirhosseini ◽

...

Keyword(s):

Vitamin D ◽

Coronary Artery ◽

Coronary Artery Bypass ◽

Artery Bypass ◽

Bypass Graft ◽

Control Group ◽

Controlled Clinical Trial ◽

Double Blind ◽

Inflammatory Status ◽

Significant Difference

Background: Vitamin D plays an important role in immune system and in the regulation of inflammatory cytokines. Coronary artery bypass graft (CABG) with cardiopulmonary bypass (CPB) is associated with an extensive inflammatory response. The aim of this study is to examine the effect of vitamin D treatment on the apoptosis and inflammatory changes developed after CABG. Methods: This trial was conducted on 70 patients undergoing CABG with CPB. Patients were randomly administered either in placebo or in the group of orally consuming 150 000 IU vitamin D daily for 3 consecutive days before surgery. The right atrium sample was taken to assess caspases 2, 3, and 7 activity using immunohistochemistry method. The serum level of interleukin-10 (IL-10) and insulin-like growth factor 1 (IGF-1) were compared at intervals. Results: The average number of positive cells for caspases 2 and 3 were less in vitamin D group ( P = .006 and P < .001, respectively). There was an increase in serum levels of IL-10 after 3 days from vitamin D treatment before surgery (vitamin D group = 4.4 ± 4.9 ng/mL and control group = 1 ± 0.5 ng/mL, P = .001). After operation, IL-10 increased in both groups, higher level in vitamin D group ( P < .001). The comparison of serum IGF-1 showed significant difference after 3 days ( P = .006) and remained higher in vitamin D group after CPB ( P < .001). Conclusions: These findings suggest the apoptosis rate after CPB can be reduced by vitamin D. Vitamin D treatment may improve the inflammatory status before and after surgery. Further studies are needed to confirm the antiapoptotic property of vitamin D and clinical implication.

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