Have to wait at least till 2020 for trial completion, and perhaps 2023 for trial publication
Download the PDF from VitaminDWiki.
Doctors advised to wait 5+ years and let million suffer and/or die
When there is uncertainty about whether supplementation is warranted, the usual medical principle is to err on the side of caution and to avoid excess. Thus, while awaiting the results of the large trials now in progress, physicians would be well advised to follow current USPSTF and IOM recommendations and avoid overscreening and overprescribing supplemental vitaminD.
Note - to avoid excess does not apply for Vitamin D.
Many trials have shown no safety risk for even 10,000 IU of vitamin D
1000 IU of vitamin D (per kg) can indeed be toxic – 1947
10,000 IU vitamin D daily is safe, toxicity start at 150 ng (for monotherapy)– Jan 2013
As much as 10000 IU vitamin D is safe – review April 2012
Proof that Vitamin D Works at VitaminDWiki has the following summary table
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
Reminder: Translate icon in the upper right selects a different language
Click on underlined items for details
| 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 |
Many stories on the web reporting on this publication - such as
- Debating Vitamin D: Leading Docs Still Wrangling On Best Dose For Patients
includes comments by the authors and rebuttal
Comment by Dr. William Grant on PubMed
In their viewpoint piece, Vitamin D and clinical practice at a crossroads, Manson and Bassuk state among other things that the Institute of Medicine (IOM) set the recommended dietary allowance for vitamin D at 600 IU/d for those living in the upper latitudes of North America aged to 70 years and 800 IU/d for those older in order to reach a 25-hydroxyvitamin D [25(OH)D] concentration of 20 ng/mL (50 nmol/L) [1]. However, it is not clear how the Dietary Reference Intakes for Calcium and Vitamin D committee arrived at that number. For example, on p. 3-20 of the vitamin D and calcium IOM report [2], Figure 3-4 from Cashman et al. [3] is given as Figure 3-4, although without the 95% confidence intervals as in the original paper. The results were based on a 22-week placebo, randomized controlled supplementation study involving men and women aged 20-40 years. Inspection of Figure 2 in Ref. 3 indicates that it would take 1155 IU/d vitamin D3 for 97.5% of the 20-40 year old population sampled to reach 50 nmol/L. In a subsequent paper based on a systematic review and meta-analysis of vitamin D intake and 25(OH)D concentrations, the same group determined that it would take 930 IU/d vitamin D3 for people living in northern Europe to reach 50 nmol/L [4]. Further complicating matters is the fact that not all of the contributions from diet are accounted for in most studies. It is becoming apparent that some food such as meat has vitamin D in the form of 25(OH)D. Thus, vegans in the UK have 25(OH)D concentrations 20 nmol/L lower than omnivores [5], so require higher vitamin D intake from non-dietary sources or solar UVB exposure.
Their comment that "while awaiting the results of the large trials now in progress, physicians would be well advised to follow current USPSTF and IOM recommendations and avoid overscreening and overprescribing supplemental vitamin D" is also not well grounded. The IOM restricted its assessment of the benefits of vitamin D to vitamin D randomized controlled trials [RCTs] with substantial benefits by 2010. [ comment by VitaminDWiki - IOM data cutoff mid 2008] A number of trials since then demonstrated health benefits, e.g., for biomarkers of inflammation, where it was found that RCTs with baseline 25(OH)D concentrations below 48 nmol/L had a 50% chance of findings benefits from vitamin D supplementation compared to 25% with baseline 25(OH)D concentrations above 50 nmol/L [6]. In addition, ecological, observational, clinical, and laboratory studies have found many health benefits of solar UVB exposure and/or vitamin D. Since the IOM report was published (29 November, 2010), 13,535 publications with vitamin D in the title or abstract have been published at PubMed.gov as of 23 February, 2015, compared with 27,775 published before that date. Many of these publications strengthen the case for vitamin D supplementation and UVB exposure.
In terms of confounding factors related to observational studies, one not mentioned in Ref. 1 is the possibility that solar UV exposure may have health benefits in addition to vitamin D production. As a result, 25(OH)D concentrations may be an index of UVB exposure. Beneficial effects of UV exposure in addition to vitamin D production have been reported for intestinal cancer [7], multiple sclerosis [8], and blood pressure [9].
As for concern about adverse effects of higher 25(OH)D concentrations based on observational studies, it should be noted that most such studies do not obtain any information from participants about vitamin D supplementation prior to having 25(OH)D concentrations measured. Thus, those with adverse health outcomes and high 25(OH)D concentrations may have started taking vitamin D supplements shortly before blood draw. For example, studies of frailty vs. 25(OH)D concentration found a U-shaded relation for elderly women [10] but a linear inverse relation for elderly men [11]. Elderly women in the U.S. are much more likely to be advised to take vitamin D supplements than men, and starting to take vitamin D late in life cannot erase the adverse effects of years of low 25(OH)D concentrations. In addition, meta-analyses of observational studies of health outcomes with respect to 25(OH)D concentrations do not show U-shaped relations for cardiovascular disease [12] or all-cause mortality rates [13.
As to their comment regarding how interest in vitamin D could jeopardize ongoing vitamin D RCTs, that should not be the case if trial participants are screened by measuring 25(OH)D concentration prior to acceptance and including only those with 25(OH)D concentrations below 50 nmol/L then dropping any who are subsequently prescribed supplements in excess of the IOM recommendations. Over 99% of the population is not enrolled in vitamin D RCTs and should not be held hostage to ongoing or planned trials since there appear to be many health benefits and very few risks of vitamin D supplementation below 4000 IU/d [[14] even by the IOM's admission [2].
References
- 1. Manson JE, Bassuk SS. Vitamin D research and clinical practice: at a crossroads. JAMA. 2015 Feb 19. doi: 10.1001/jama.2015.1353. [Epub ahead of print]
- 2. Ross AC, Taylor CL, Yaktine AL, Del Valle HB, eds. ; Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Dietary Reference Intakes for Calcium and Vitamin D. Institute of Medicine. ISBN: 0-309-16395-1, 482 pages, (2010) Available from National Academies Press at: http://www.nap.edu/catalog/13050.html
- 3. Cashman KD, Hill TR, Lucey AJ, et al. Estimation of the dietary requirement for vitamin D in healthy adults. Am J Clin Nutr. 2008;88(6):1535-42.
- 4. Cashman KD, Fitzgerald AP, Kiely M, Seamans KM. A systematic review and meta-regression analysis of the vitamin D intake-serum 25-hydroxyvitamin D relationship to inform European recommendations. Br J Nutr. 2011;106(11):1638-48.
- 5 Crowe FL, Steur M, Allen NE, et al. Plasma concentrations of 25-hydroxyvitamin D in meat eaters, fish eaters, vegetarians and vegans: results from the EPIC-Oxford study. Public Health Nutr. 2011;14(2):340-6.
- 6. Cannell JJ, Grant WB, Holick MF. Vitamin D and inflammation. Dermato-Endocrinology. 2014;6(1):e983401-1-10.
- 7. Rebel H, der Spek CD, Salvatori D, et al.UV exposure inhibits intestinal tumour growth and progression to malignancy in intestine-specific Apc mutant mice kept on low vitamin D diet. Int J Cancer. 2015;136(2):271-7.
- 8. Zivadinov R, Treu CN, Weinstock-Guttman B, et al. Interdependence and contributions of sun exposure and vitamin D to MRI measures in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2013;84(10):1075-81.
- 9. Opländer C, Volkmar CM, Paunel-Görgülü A, et al. Whole body UVA irradiation lowers systemic blood pressure by release of nitric oxide from intracutaneous photolabile nitric oxide derivates. Circ Res. 2009;105(10):1031-40.
- 10. Ensrud KE, Ewing SK, Fredman L, et al. Circulating 25-hydroxyvitamin D levels and frailty status in older women. J Clin Endocrinol Metab. 2010;95(12):5266-73.
- 11. Ensrud KE, Blackwell TL, Cauley JA, et al. Circulating 25-hydroxyvitamin D levels and frailty in older men: the osteoporotic fractures in men study. J Am Geriatr Soc. 2011;59(1):101-6.
- 12. Wang L, Song Y, Manson JE, et al. Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: A meta-analysis of prospective studies. Circ Cardiovasc Qual Outcomes. 2012;5(6):819-29.
- 13. Garland CF, Kim JJ, Mohr SB, et al. Meta-analysis of all-cause mortality according to serum 25-hydroxyvitamin D. Am J Pub Health. 2014;104(8):e43-50.
- 14. Vieth R. Implications for 25-hydroxyvitamin D testing of public health policies about the benefits and risks of vitamin D fortification and supplementation. Scand J Clin Lab Invest Suppl. 2012;243:144-53.
Disclosure I receive funding from Bio-Tech Pharmacal, Inc. (Fayetteville, AR), MediSun Technology (Highland Park, IL), and the Vitamin D Council (San Luis Obispo, CA).
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