Optimal Vitamin D Status: A Critical Analysis on the Basis of Evidence-Based Medicine
The Journal of Clinical Endocrinology & Metabolism August 1, 2013 vol. 98 no. 8 E1283-E1304
Roger Bouillon, roger.bouillon at med.kuleuven.be
Natasja M. Van Schoor,
Evelien Gielen,
Steven Boonen Deceased May 20, 2013
Chantal Mathieu,
Dirk Vanderschueren and
Paul Lips
- Clinical and Experimental Endocrinology (R.B., C.M., D.V.), KU Leuven, Departments of Endocrinology and Laboratory Medicine, UZ Leuven, 3000 Leuven, Belgium; Department of Internal Medicine, Endocrine Section, and
- Department of Epidemiology and Biostatistics (N.M.V.S., P.L.), EMGO Institute for Health and Care Research, VU University Medical Centre, 1007 MB Amsterdam, The Netherlands; and
- Gerontology and Geriatrics (E.G., S.B.), KU Leuven and Geriatric Medicine, UZ Leuven, 3000 Leuven, Belgium
Context: Public health authorities around the world recommend widely variable supplementation strategies for adults, whereas several professional organizations, including The Endocrine Society, recommend higher supplementation.
Methods: We analyzed published randomized controlled clinical trials to define the optimal intake or vitamin D status for bone and extraskeletal health.
Conclusions: The extraskeletal effects of vitamin D are plausible as based on preclinical data and observational studies. However, apart from the beneficial effects of 800 IU/d of vitamin D3 for reduction of falls in the elderly, causality remains yet unproven in randomized controlled trials (RCTs). The greatest risk for cancer, infections, cardiovascular and metabolic diseases is associated with 25-hydroxyvitamin D (25OHD) levels below 20 ng/mL. There is ample evidence from RCTs that calcium and bone homeostasis, estimated from serum 1,25-dihydroxyvitamin D and PTH, calcium absorption, or bone mass, can be normalized by 25OHD levels above 20 ng/mL. Moreover, vitamin D supplementation (800 IU/d) in combination with calcium can reduce fracture incidence by about 20%. Such a dose will bring serum levels of 25OHD above 20 ng/mL in nearly all postmenopausal women. Based on calculations of the metabolic clearance of 25OHD, a daily intake of 500–700 IU of vitamin D3 is sufficient to maintain serum 25OHD levels of 20 ng/mL.
Therefore, the recommendations for a daily intake of 1500–2000 IU/d or serum 25OHD levels of 30 ng or higher for all adults or elderly subjects, as suggested by The Endocrine Society Task Force, are premature.
Fortunately, ongoing RCTs will help to guide us to solve this important public health question.
Abreviations:
BMD = bone mineral density
BMI = body mass index
CI = confidence interval
CKD = chronic kidney disease
CL = confidence limit
COPD = chronic obstructive pulmonary disease
FGF23 = fibroblast growth factor 23
HR = hazard ratio
1,25(OH)2D = 1,25-dihydroxyvitamin D
25OHD = 25-hydroxyvitamin D
OR = odds ratio
RCT = randomized controlled trials
RR = relative risk
VDR = vitamin D receptor.
See also VitaminDWiki
- Vitamin D also TREATS
- Summary of Vitamin D trials - Grant Nov 2012
- Vitamin D Recommendations around the world - IU and ng which includes the following
- Proof that Vitamin D Works has the following data - the above study seems to ignore the data
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 | ||
- Overview Pregnancy and vitamin D which has the following summary
IU Cumulative Benefit Blood level Cofactors Calcium $*/month 200 Better bones for mom
with 600 mg of Calcium6 ng/ml increase Not needed No effect $0.10 400 Less Rickets (but not zero with 400 IU)
3X less adolescent Schizophrenia
Fewer child seizures20-30 ng/ml Not needed No effect $0.20 2000 2X More likely to get pregnant naturally/IVF
2X Fewer dental problems with pregnancy
8X less diabetes
4X fewer C-sections (>37 ng)
4X less preeclampsia (40 ng vs 10 ng)
5X less child asthma
2X fewer language problems age 542 ng/ml Desirable < 750 mg $1 4000 2X fewer pregnancy complications
2X fewer pre-term births49 ng/ml Should have
cofactors< 750 mg $3 6000 Probable: larger benefits for above items
Just enough D for breastfed infant
More maternal and infant weightShould have
cofactors< 750 mg $4