The Pleiotropic Effect of Vitamin D
Hindawi, Volume 2013, Article ID 898125, 6 pages http://dx.doi.org/10.5402/2013/898125
Yu-Hsien Lai 1 and Te-Chao Fang 1,2,3
1 Division of Nephrology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital, No. 707, Section 3, Chung Yang Road, Hualien 97004, Taiwan
2 School of Medicine, Tzu Chi University, Hualien, Taiwan
3 Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
Correspondence should be addressed to Te-Chao Fang; fangtechao at yahoo.com.tw Received 17 June 2013; Accepted 5 August 2013 Academic Editors: T. Doi and C. G. Musso
The novel roles of vitamin D were discovered and valued in this century. In addition to the maintenance of calcium and phosphorus balance, vitamin D regulates the function of the kidneys, heart, and immune system. Moreover, its anti-inflammatory, antiapoptotic, and antifibrotic roles have gained considerable attention. Vitamin D is also important for the maintenance of homeostasis by regulation of hormone secretion, cell proliferation, and differentiation. This paper will review these pleiotropic functions of vitamin D.
1. Introduction
Since the beginning of the 20th century, scientists have been exploring the functions of vitamin D. The roles of this vitamin in endocrine system and metabolic bone diseases were already well studied by 1970. In this century, the discovery of vitamin D receptor has provided more insight on its additional functions [1]. Vitamin D receptors are present on many organs, such as the pancreas, large and small intestines, muscles, and nervous system [2]. Vitamin D was found to regulate the cell cycle and subsequently influence organ functions by binding to its receptor on the cells of the immune, nervous, and cardiovascular systems [3]. In the kidneys, vitamin D exerts protective effects by inhibiting renal fibrosis, inflammation, and progression of proteinuria.
Vitamin D deficiency is strongly associated with various cardiovascular and metabolic diseases such as hypertension, type 1 diabetes, myocardial infarction, and stroke. Moreover, vitamin D deficiency is related to several autoimmune diseases such as rheumatoid arthritis, systemic sclerosis, and systemic lupus erythematosus. Studies also have shown a negative correlation between serum vitamin D concentration and incidence of colorectal cancer and breast cancer [4]. These phenomena suggest that vitamin D plays protective roles in many diseases.As the importance of vitaminD for endocrine function has gained attention, the pursuit of paracrine and autocrine functions of vitamin D will continue in this century [5].
2. Metabolism of Vitamin D
Vitamin D is a fat-soluble vitamin produced by exposure of the skin to sufficient ultraviolet B radiation and absorption from the gastrointestinal tract. After vitamin D3 is synthesized, it is transported to the liver where 25-hydroxyvitamin D3 is formed via hydroxylation by 25-hydroxylase. 25-Hydroxyvitamin D3 is further converted into the physiologically active vitamin D3 (1,25-dihydroxyvitamin D3)inthe mitochondria of the proximal convoluted tubules. The active vitamin D3 and vitamin D-binding protein are then transported to different organs for further metabolism [6]. In patients with chronic kidney disease, the serum level of the active form of vitamin D3 is decreased because of elevated blood concentration of fibroblast growth factor-23 (FGF-23) and related inflammatory cytokines [7,8]. Because the level of circulating vitamin D3 decreases, the levels of 25-hydroxyv-itamin D entering other types of cells also reduce relatively [9].
The daily recommended vitamin D intake is 5-15 ug, but the amount of vitamin D from UV irradiation via skin or oral intake is inadequate to meet the demand for most people nowadays [5]. Because the incidence of vitamin D toxicity is rare in healthy adults, increased daily vitamin D intake is suggested [8, 10]. If the daily intake of vitamin D can reach 50 ffg, the concentration of serum vitamin D in the blood can increase from 25 nmol/L to 75 nmol/L [11]. Increasing vitamin D intake would be helpful in disease prevention and management [12].
3. Vitamin D Receptor
The gene for vitamin D receptor was discovered in 1988 and has been found to be present in the cells of many tissues, including parathyroid cells, pancreatic cells, macrophages, keratinocytes, special nerve cells, and renal tubular cells. Vitamin D receptor is widely expressed in almost all cells, and vitamin D regulates approximately 3% of the human genes via its endocrine effects [13]. The active form of vitamin D is released in smooth muscle, colon, and immune cells, besides renal cells, via local hydroxylation of 25-hydroxyvitamin D by 1a-hydroxylases [14,15].
4. Anti-Inflammatory Effect of Vitamin D
Oneofthe functionsofvitamin Distopromote the differentiation of monocytes into macrophages, dendritic cells, and lymphocytes. These cells represent the first line of defense of the nonspecific immune system and play an important role in infection control [10]. Many studies have found that the lack of vitamin D or vitamin D receptor causes altered innate and adaptive immune functions. Patients with diseases associated with vitamin D deficiency, such as rickets or chronic kidney disease, are known to have recurrent infections [16,17]. The effectofvitamin Donimmunesystemcan be attributed to the paracrine feedback mechanism, whereby it reduces inflammatory response, affects the differentiation of active CD4+ T cells, and enhances the inhibitory function of T cells. The active form of vitamin D also promotes the differentiation of monocytes into mature macrophages by induction of p21 [18]. C/EBP/? (CCAAT-enhancer-binding protein beta) is an important transcriptional factor which provides macrophages with antibacterial, antiviral, and antitumor activities and for the IL-12 synthesis [19]. Vitamin D induces C/EBP/? that contributes to the monocyte-macrophage lineage differentiation, increases the activity of macrophages, and promotes their cytotoxicity. Therefore, vitamin D enhances host defense against bacterial infections, as well as growth of tumor cells [20].
In 2007, Schauber et al. found that vitamin D can stimulate human skin cells to synthesize the antimicrobial peptide cathelicidin, which can enhance the innate immune function [21]. The active vitamin D-vitamin D receptor complex was found to influence Mycobacterium tuberculosis infection mainly by inhibiting the synthesis of IL-12 and y-interferon, as well as the Th1 immune responses [22]. A meta-analysis study showed that the serum 25-hydroxyvitamin D concentrations were significantly lower in patients with tuberculosis than in the control group [23]. Vitamin D deficiency has also been found to be associated with increased incidence of respiratory diseases, such as influenza; Mycobacterium tuberculosis infection; and chronic respiratory diseases, such as cystic fibrosis, interstitial lung disease, and chronic obstructive pulmonary disease.
The active vitamin D has also been found to have inhibitory effects on transplant rejection. Studies on heart transplantation have shown that active vitamin D may be more effective than cyclosporine in prolonging the survival of the transplanted organ and will not increase the rate of infection [24].In kidney transplantation, the active vitamin D also extends the viability of the transplanted kidney and reduces the progression of renal fibrosis [25]. The above antirejection effect occurs through the TGF-/?/Smad3 pathway [26].
5. Antiapoptotic and Antifibrotic Effects of Vitamin D
In normal tissues, vitamin D plays an important role in regulating the proliferation by promoting apoptosis. For example, in breast tissue, vitamin D regulates apoptosis according to the requirements of the body at different physiological stages such as pregnancy and breastfeeding [27]. In addition to the normal tissues, vitamin D has been reported to be important in the regulation of hyperplasia in cancerous and noncancerous tissues via initiation of apoptosis in glioma, melanoma, and breast cancer cells [28]. In breast cancer cells, vitamin D induced apoptosis via interaction between Bcl2 and Bax [29]. In colorectal cancer, the transcription factor Snail reduces the expression of the vitamin D receptor, thereby influencing the progression of colon cancer cells [30]. The amount of vitamin D receptor is an important factor in determining its potency in the regulation of tumor growth.
In the nervous system, the active vitamin D affects the conduction of the motor neurons and synthesis of neuro-trophic factors, thus preventing damages to the neurons [31].
Further, excess formation of keratin in psoriasis is due to the overexpression of TGF-a. Vitamin D helps in reducing the proliferation of keratinocytes, hence treating psoriasis by inhibiting the growth cycle of the TGF-a/EGFR (epidermal growth factor receptor) [32].
6. Vitamin D in Kidney Disease, Diabetes Mellitus, and Cardiovascular Disease
Active vitamin D has a negative feedback on the renin-angiotensin system, which plays a key role in regulating blood pressure, electrolyte levels, and volume status. When patients have low serum levels of active vitamin D, they may develop high blood pressure or diseases related to high plasma renin activity [33]. Studies on knockout mice lacking active vitamin D receptor expression revealed elevated levels of renin and angiotensin II in the blood, which in turn caused a significant increase in blood pressure, cardiac hypertrophy, and water retention [34].
Calcitriol, an analogue of the active vitamin D, exerted inhibitory effects on renal interstitial myofibroblasts and thereby inhibited the progression to renal interstitial fibrosis [35]. Several studies on nephropathy showed that active vitamin D protects the kidneys through its anti-inflammatory and antifibrotic effects [36,37]. Vitamin D deficiency has also been found to be associated with earlier-onset and highly severe diabetes mellitus, presumably because of abnormal insulin secretion and immune dysfunctions. The condition of such diabetes patients can be improved by calcitriol supplementation [38]. A UK population-based study found that patients with type 1 diabetes had lower serum 25-hydrox-yvitamin D concentrations than did healthy subjects of the same age. The study also found that the 3 main genes controlling the 25-hydroxyvitamin D metabolism are related to the incidence of type 1 diabetes [39]. Both in vitro and in vivo studies also showed that vitaminD could prevent the destruction of pancreatic beta-cells and reduce the incidence of autoimmune diabetes mellitus, possibly secondary to inhibition of proinflammatory cytokines, such as tumor necrosis factor (TNF-a) 5].
In the cardiac system, vitamin D maintains cardiovascular health by direct binding to vitamin D receptor on the myocardial cells, and thus regulating the hypertrophy of myocardial cells and the synthesis and release of atrial natri-uretic peptide [40, 41]. Vitamin D has been shown to inhibit angiogenesis and increase matrix G1A protein synthesis and thus inhibit the synthesis of inflammatory cytokines such as tumor necrosis factor and interleukin [42]. On the other hand, vitamin D inhibits the calcification of blood vessels by regulating the activities of interleukins [43]. In patients with end-stage renal disease, vitamin D supplementation has been found to improve left ventricular function and muscle weakness, but the mechanism underlying this function is not known yet [11]. Vitamin D deficiency has been found to be associated with a variety of cardiovascular and other diseases, such as hypertension, diabetes mellitus, myocardial infarction, stroke, congestive heart failure, peripheral vascular disease, and atherosclerosis [12]. Therefore, the serum level of vitamin D is considered to be an important independent predictor of cardiovascular diseases 5].
7. Vitamin D in the Immune System
The interaction of vitamin D with the immune system is one of its most well-known effects [44]. The active vitamin D regulates innate and adaptive immune system, because its receptors are widely present on many immune cells, such as macrophages, dendritic cells, T cells, and B cells [45]. Vitamin D is thought to be able to activate cathelicidins, antimicrobial peptides present within the lysosomes of macrophages, and polymorphonuclear leukocytes [46]. Cathelicidins play a key role in innate immune defense against bacterial infections [47]. Cathelicidins regulate the transcription of vitamin D receptor as its gene promoter contains the functional response to vitamin D [48]. The active vitamin D regulates this antimicrobial peptide function in many different types of cells, including macrophages, keratinocytes, lung epithelial cells, placental trophoblast cells, and myeloid cell lines [21, 49, 50]. Therefore, active vitamin D has been found to inhibit the initiation of many diseases, such as experimental autoimmune encephalomyelitis, thyroiditis, type 1 diabetes mellitus, inflammatory bowel disease, systemic lupus erythematosus, andLymearthritis 16, 51].
In vitro studies on systemic lupus erythematosus revealed that the abnormal immune response may be reversed by addition of vitamin D; therefore, vitamin D deficiency is considered to be associated with loss of immune tolerance [52]. Studies on rheumatoid arthritis found that the disease activity is negatively correlated with serum vitaminD concentration, and such a correlation is independent of the parathyroid function [53].
8. Vitamin D and Cancer
Several studies have shown that vitamin D plays a protective role in several types of cancer, such as prostate, breast, and colon cancer [10]. Vitamin D has also been found to inhibit proliferation of a variety of human leukemia cell lines and induce differentiation of normal and leukemic myeloid precursor, thereby increasing maturation and decreasing aggressiveness of potential leukemic cells. Therefore, vitamin D is helpful in the treatment of leukemia and other myelo-proliferative disorders [54].
The state of knowledge on the protective effects in cancer ofvitamin D is as follows.
- (1) Active vitamin D promotes the transcription of the cyclin-dependent kinase inhibitor p21 [18]. This is sufficient to suppress growth of cells of the monocyte-macrophage lineage and promote their differentiation.
- (2) Active vitamin D induces the synthesis of the cyclin-dependent kinase inhibitor p27 [55].
- (3) The proliferation of tumor cells is due to the overex-pression of the TGF-a/EGFR pathway. Active vitamin D could inhibit the TGF-a/EGFR growth pathway [32].
- (4) In human epithelial cell tumors, C/EBP/? is considered to be effective in the inhibition of the carcinogenic cell cycle protein D1 [56]. In contrast, the C/ EBP/? isoform LIP can enhance the activity of the carcinogenic cyclin D1 and induce cell growth. Therefore, the proliferative property of human tumors is inversely correlated to the intracellular C/EBP/?-to-LIP ratio [57]. The active vitamin D can induce the expression of C/EBP/? and prevent the proliferation of LIP epidermal growth factor receptor, thus reducing the occurrence of EGFR-driven related cancers [58].
- (5) Vitamin D plays a major role in cell metabolism as it regulates cell maturation, differentiation, and apop-tosis [10]. These features are related to the suppressed expression of antiapoptotic proteins such as Bcl2 in cancer cells and arrest of cell cycle in G0/G1, which reduces the rate of proliferation [59]. Vitamin D was also found to have anti-inflammatory effects that can delay and prevent the development of cancers [60].
Studies have found that the adequacy of the content of vitamin D in the body is an important factor in predicting several types of cancer prognosis and mortality [5].
Table 1: The pleiotropic effects of vitamin D and associated mechanisms and diseases.
| Pleiotropic effects | Mechanism | Associated diseases | |
| Anti-inflammation | (1) affects the differentiation of active CD4+ T-cells (2) enhances the inhibitory function of T-cells (3) promotes differentiation of monocyte into mature macrophages by inducing p21%%%(4) induces C/EBP/5 which contribute to the monocyte-macrophage lineage differentiation, increase the activity of macrophages, and promote their antibacterial and antiviral activities (5) inhibits the synthesis of IL-12, y-interferon, and Th1 immune responses (6) inhibits TGF-j3/Smad3 pathway on transplant rejection | (1) recurrent infections in rickets or CKD patients (2) increased incidence of respiratory diseases, such as influenza, mycobacterium tuberculosis, and chronic respiratory diseases, such as cystic fibrosis, interstitial lung disease, and chronic obstructive pulmonary disease | |
| Antiapoptosis and antfibrosis | (1) induce apoptosis via interaction between Bcl2 and Bax in breast cancer cells (2) affect the conduction of the motor neurons and synthesis of neurotrophic factors, thus preventing damage ofthe neurons (3) inhibit the growth cycle of the TGF-a/EGFR and reduce the proliferation of keratinocytes | (1) progression ofcancer cells (2) excess formation of keratin in psoriasis | |
| Cardiovascular diseases | (1) have negative feedback on renin-angiotensin system in regulating blood pressure, electrolyte and volume status (2) have direct binding to vitamin D receptor on the myocardial cells and regulate the hypertrophyof myocardial cells (3) have synthesis and release of atrial natriuretic peptide (4) inhibit angiogenesis and increase matrix G1A protein synthesis, thus inhibiting inflammatory cytokines such as tumor necrosis factor and interleukin (5) inhibit calcification of blood vessels by regulating interleukins | (1) hypertension, water retention (2) cardiac hypertrophy, myocardial infarction, stroke, congestive heart failure, peripheral vascular disease, and atherosclerosis | |
| Kidney diseases | (1) inhibit renal interstitial myofibroblasts, inhibiting the progression to renal interstitial fibrosis | (1) renal fibrosis | |
| Diabetes mellitus (DM) | (1) prevents the destruction of pancreatic beta-cells (2) reduces autoimmune diabetes mellitus, possibly secondary to inhibition of proinflammatory cytokines, such as tumor necrosis factor (TNF-a) | (1) earlier onset and more severe DM (2) type I DM | |
| Immune system | (1) activates cathelicidins, an antimicrobial peptide within the lysosomes of macrophages and polymorphonuclear leukocytes | (1) increases initiation of experimental autoimmune encephalomyelitis, thyroiditis, type 1 diabetes mellitus, inflammatory bowel disease, systemic lupus erythematosus, and Lyme arthritis (2) increases the disease activity of rheumatoid arthritis | |
| Cancers | (1) promote the transcription of cyclin-dependent kinase inhibitors, p21 (2) induce synthesis of the cyclin-dependent kinase inhibitors, p27 (3) inhibit the TGF-a/EGFR growth pathway (4) induce the expression of C/EBP/5 and prevent proliferation of LIP epidermal growth factor receptor, thus reducing EGFR-driven related cancers (5) suppress expression of anti-apoptotic proteins such as Bcl2 of cancer cells, arrest of cell cycle in G0/G1, thus slowing proliferation of cancer cells | (1) prostate, breast, and colon cancers (2) leukemia and other myeloproliferative disorders | |
9. Conclusions
In the past decades, the function of vitamin D has been more deeply understood. The discovery of the vitamin D receptor enabled further investigations on the association of acute and chronic diseases with vitamin D deficiency. The pleiotropic effects of vitamin D and associated mechanisms are summarized in Table 1. In addition, the paracrine and autocrine effects of vitaminD have a protective role in many diseases. Therefore, the application of vitamin D in disease treatment and prevention should be pursued.
References in PDF
See also Vitamin D Life
Proof that Vitamin D Works has the following summary
Vitamin D prevents or treats 94 health problems
ADHD, Alcoholic Liver Cirrhosis, ALS, Alzheimer's, Antibiotic Use in Seniors, Asthma, Autism, Autoimmune Diseases, Back pain, Blood Cell Cancer, Breast Cancer, Cardiovascular, Cholesterol, Chronic Hives, Chronic Kidney Disease, Cluster Headaches, Congestive Heart Failure (Infants), COPD, Crohn's Disease, C-Section and Pregnancy Risks, Cystic Fibrosis, Depression, Diabetes, Diabetic Neuropathy, Eczema, Falls, Fatigue, Fatty Liver (Child), Fibromyalgia, Gestational Diabetes, Gingivitis, Growing Pains, Hay Fever, Heart Attack, Hemodialysis, Hepatitis-C, Hip Fractures, Hypertension, Influenza, Irritable Bowel Syndrome, Ischemic Stroke, Knee Osteoarthritis, Leg Ulcers, Low Birth Weight, Lupus, Male Infertility, Menstrual Pain, Metabolic Syndrome, Middle Ear Infection (Infants), Mite Allergy, Multiple Sclerosis, Non-Alcoholic Fatty Liver Disease, Osteoarthritis, Parkinson's Disease, Perinatal Depression, Pneumonia (Ventilator-associated), Poor Sleep, PreDiabetes, Preeclampsia, Pre-term Birth, Prostate Cancer, Quality of Life, Raynaud's Pain, Respiratory Tract Infection, Restless Leg Syndrome, Rheumatoid Arthritis, Rickets, Sarcopenia, Sepsis, Short Neonates, Sickle Cell, Stronger Senior Muscles, Survive ICU, TB, Tonsillitis, Trauma Death, Traumatic Brain Injury, Tuberculosis, Ulcerative Colitis, Urinary Tract Infection, Vaginosis, Vertigo, Warts, Weight Loss
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| Health Problem | Treat Prevent | Reduction by Vit D | RCT = Randomized Controlled Trial * = link to additional RCT CT = Clinical Trial |
| Hypertension | T P | 149 to 142 mm Hg HT risk reduced 10X | RCT* *, 2400 IU. 100,000 IU* When Vitamin D > 40 ng |
| Cardiovascular after attack | T | 32 % fewer deaths | CT 1000 IU |
| Diabetes Type 1 | P | 85 % | 12,000 kids, 2000 IU |
| Diabetes Type 2 | T | 62 % | RCT* CRP reduction, 4000 IU Injection is far better - RCT * RCT 50,000 IU/2weeks + probiotics RCT 5,000 IU daily 6 months |
| Back Pain | T | 95 % reduced 50% | 5000/10000 IU 60,000 IU weekly |
| Influenza | P | 90 % | RCT *, 2000 IU |
| Falls | P | 50% | RCT, 100,000 IU monthly RCT with Meals on Wheels 2016 |
| Hip Fractures | P | 30 % | RCT * 800 IU |
| Rickets | P | 98 % | Turkey, 400 IU NOT RCT, given to all children |
| Raynaud's Syndrome | T | 40 % | RCT, visual scale, 20000 IU Avg |
| Menstrual pain | P | 76 % | RCT, 7000 IU Avg, 70% reduction 2018 PMS reduced by half |
| Pregnancy risks | P | 50 % | RCT, 4000 IU |
| C-section, unplanned | P | 50 % | RCT, 4000 IU, small study |
| Low birth weight | P | 60 % | RCT * 1000 IU of D2 |
| TB | P | 60 % | RCT, 800 IU |
| Breast Cancer | P | 60 % | RCT, 1100 IU (2007) |
| Rheumatoid Arthritis pain | T | 40 % | RCT, 500 IU, added to prescription |
| Cystic Fibrosis | T | 75 % 2nd study improved | RCT, pilot 4X fewer deaths 250,000 IU RCT, pilot 8,200 IU |
| Chronic Kidney | T | 90 to 70 PTH | RCT, 3500 IU, |
| Respiratory Tract Infection | P | 63 % | 3 RCT, 4000 IU 1 year 2nd 2000/800 IU 20,000 IU weekly |
| Lupus | T T | zero flares Pain reduced | Loading then 100,000 IU monthly, RCT too RCT 4,000 IU |
| Sickle Cell | T | Less pain | RCT, up to 100,000 IU/week |
| Leg ulcer healing | T | 4X faster | RCT, 50,0000 IU/week, small study |
| Traumatic Brain Injury | T | 2X | RCT, 20,0000 IU/day with progesterone |
| Parkinson's Disease | T | Stabilized | RCT, 1200 IU/day |
| Multiple Sclerosis | P T | 68% 95% were CURED | RCT, 7100 IU prevent pre-MS ==> MS 20,000 to 140,000 IU/day |
| Congestive Heart Failure | T | 90 % | RCT, 1000 IU infants (also: Adults, not RCT) |
| Middle Ear Infection | P | 30 % | RCT, 1000 IU infants |
| Gingivitis | T | 88 % | RCT, 2000 IU |
| Muscle in seniors | T | 17 % more muscle | RCT, 4000 IU |
| Antibiotic use when >70y | T | 47 % | RCT, 60,000 IU monthly |
| Infants taller | Benefit | 1 cm tall | RCT, 50,000 IU weekly, for 8 weeks while pregnant |
| Gestational Diabetes | T | Reduced 3X | RCT, 2 doses of 50,000 IU |
| After Heart Attack | T | +6% ejection fraction | RCT, 800,000 IU one time |
| Prostate Cancer | T | Fewer +cores | RCT, 4000 IU (2012) |
| Asthma | P T | Reduced symptoms | RCT, 60K IU/month; RCT 50K IU/week Need good D at 4 weeks into preg. |
| Depression | T | Reduced | RCT 300,000 IU injection RCT 1500 IU helped Prozac RCT 50,000 IU weekly, elderly |
| Low vitamin D while breastfed | P | All infants > 20 mg | RCT, 5,000 IU |
| Fibromyalgia | T | Half of many still has Fibro | RCT, 30-48 ng RCT 50K IU/week |
| Hives, Chronic | T | Reduced 40% | RCT, 4000 IU added |
| Cholesterol | T | Reduced 4 mg | RCT, 400 IU + Ca |
| Weight Loss | T | lost 5 more lbs | RCT, 2000 IU +diet +exercise |
| Gestational Diabetes | P | 40% | RCT * , 5,000 IU |
| Chronic Obstructive Pulmonary Disease | T | 17X improvement | CT, 50,000 IU weekly RCT 100,000 IU monthly |
| Asthma | T | 1/2 Asthma attacks | RCT >42 mg of vitamin D |
| Quality of Life (QoL) | T | Nursing Home QoL | CT, 4,000 IU in daily bread |
| Death of Critically Ill Patients | T | 20% increase in survivability | RCT 540 K IU loading than 90K monthly |
| Restless Leg Syndrome | T | Score 26 ==> 10 | CT, Vitamin D dose size not stated in abstract |
| Hepatitis-C | T | Aided normal drugs | RCT 2.000 IU |
| Crohn's disease | T | improved when > 30 ng 2nd study fewer relapses | RCT 2,000 IU 10,000 IU RCT |
| Pre-term birth | P | 2.5X decrease, also: fewer c-section & better Apgar | RCT 2,000 IU India |
| Cluster headaches | T | CH eliminated in 60% | 10,000 IU, Mg, Omega-3, etc |
| Autism | T | 80% improved | CT 300 IU/kg/day for 3 months |
| PreDiabetes | T | ~20% reduced | RCT 60,000 IU/month |
| Weight loss: Overweight and Obese | T | 12 lbs in 6 months | RCT 100,000 IU/month |
| Sarcopenia = muscle loss | T | 27% increase | RCT 1,000 IU |
| Growing Pains | T | 60% decrease | ~100,000 IU/month -NOT RCT 2nd study, similar results |
| Osteoarthritis pain | T | 60% decrease | 50,000 IU/weekly - NOT RCT |
| ALS | T | helped | 2,000 IU - NOT RCT, given to all |
| Vertigo | T | 3X reduction if raised > 10ng | 600,000 IU load, then maint. NOT RCT, given to all |
| Warts | T | 80% eliminated injection | NOT RCT 60,000 IU/injection |
| Metabolic Syndrome | P | reduced 44% when VitD increased by 30 ng | NOT RCT, given to all |
| Hay fever | P | reduced 48% | RCT 1,000 IU for 30 days |
| Preeclampsia | P | Recurrance cut in half 3 RCT 3.6 X less likely if > 30 ng | 50,000 IU every 2 weeks 4,000 IU daily |
| Blood cell cancer Multiple Myeloma | T | Survival 90% vs 50% | 10,000 IU/week NOT RCT, given to all |
| Irritable Bowel Syndrome | T | Reduced | 3,000 IU spray RCT |
| Urinary Tract Infection | P | 50% reduction | RCT 20,000 IU weekly |
| Mite Allergy | P | 5X reduction | RCT 2,000 IU preg, 800 IU child |
| Perinatal depression (depression near birth) | T | 50% reduction | RCT 2,000 IU for just a few weeks |
| Vaginosis | T | 10X reduction | RCT 2,000 IU |
| Eczema | T | Reduced | 2 RCT 1,600 IU |
| Non-Alcoholic Fatty Liver Disease | T | Reduced | RCT 20,000 IU weekly |
| Knee Osteoartiritis | T | Pain Reduced | RCT 60,000 IU monthly after loading dose |
| Tuberculosis | T | Faster Recovery | RCT single 450,000 IU dose |
| Stroke - Ischemic | T | Faster Recovery | RCT single 600,000 IU injection RCT single 300,000 IU injection |
| Sepsis | T | Reduce ICU and Hospital length of stay by 7 days each | RCT 400,000 IU |
| Trauma deaths | T | 50% fewer deaths | Vitamin D & Glutamine NOT RCT, given to all |
| Hemodialysis patients | T | helped | 50,000 IU weekly NOT RCT, given to all |
| Fatty liver - child | T | 2 X reduction | RCT Vitamin D & DHA |
| Fatigue | T | Reduced | 100,000 IU single dose NOT RCT, given to all |
| Sleep Disorders | T | Nicely treated | RCT 50.000 IU bi-weekly |
| Pneumonia (Ventilator-associated) | T | RCT Death rate cut in half | 300,000 IU injection |
| Infertile males | T | birth rate doubled | RCT 300,000 IU + maint |
| Waist size | T | Waist size reduced 3 cm | 100,000 IU loading + maint for 6 months for those with Metabolic Syndrome NOT RCT, given to all |
| Attention Deficient Hyperactivity Disorder | T | Reduced Reduced | RCT 3,000 IU for 12 weeks RCT 50,000 IU weekly |
| Alcoholic liver cirrhosis | T | improved survival | 1,000 IU of vitamin D NOT RCT |
| Diabetic nephropathy | T | Reduced HOMA-IR, FRS | RCT 50,000 IU weekly |
| Ulcerative Colitis | T | Reduced 60% | RCT 50,000 IU nano daily for a week |
| Obese weight loss | T | Lost 3X more pounds | $10 of Vitamin D added to calorie restriction & walking |
| Endometriosis | T | Nicely treated | RCT 50.000 IU bi-weekly |
| Diabetic Wounds | T | 4X more likely to heal | RCT 6,400 daily |
| Alzheimer's | T | Often reverse | Each person gets a different amount of Vit D, Omega-3, B12, Iron, etc |
| Autoimmune | P | Decrease 30% | RCT Vit D + Omega-3 |
| Smoking | T | reduce problems | RCT 50,000 bi-weekly |
| Tonsillitis | T | Virtually eliminated | RCT 50,000 weekly |
Chart of Vitamin D levels vs disease - Grassroots Health June 2013 has the following chart