Does Vitamin D Sufficiency Equate to a Single Serum 25-Hydroxyvitamin D Level or Are Different Levels Required for Non-Skeletal Diseases?
Nutrients 2013, 5(12), 5127-5139; doi:10.3390/nu5125127 (doi registration under processing)
Simon Spedding 1,[email protected], Simon Vanlint 2 Howard Morris 1,3and Robert Scragg 4
1 Division of Health Sciences, University of South Australia, Adelaide, SA 5000, Australia
2 Discipline of General Practice, School of Population Health, University of Adelaide, Adelaide, SA 5005, Australia
3 SA Pathology, PO Box 14, Rundle Mall, Adelaide, SA 5000, Australia
4 School of Population Health, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
Received: 28 October 2013; in revised form: 27 November 2013 / Accepted: 28 November 2013 / Published: 16 December 2013
Objective: Clarify the concept of vitamin D sufficiency, the relationship between efficacy and vitamin D status and the role of Vitamin D supplementation in the management of non-skeletal diseases. We outline reasons for anticipating different serum vitamin D levels are required for different diseases.
Method: Review the literature for evidence of efficacy of supplementation and minimum effective 25-hydroxyvitamin D (25-OHD) levels in non-skeletal disease.
Results: Evidence of efficacy of vitamin supplementation is graded according to levels of evidence.
Minimum effective serum 25-OHD levels are lower for
- skeletal disease, e.g., rickets (25 nmol/L), osteoporosis and fractures (50 nmol/L), than for
- premature mortality (75 nmol/L) or non-skeletal diseases, e.g., depression (75 nmol/L), diabetes and cardiovascular disease (80 nmol/L),
- falls and respiratory infections (95 nmol/L) and
- cancer (100 nmol/L).
Conclusions: Evidence for the efficacy of vitamin D supplementation at serum 25-OHD levels ranging from 25 to 100 nmol/L has been obtained from trials with vitamin D interventions that change vitamin D status by increasing serum 25-OHD to a level consistent with sufficiency for that disease. This evidence supports the hypothesis that just as vitamin D metabolism is tissue dependent, so the serum levels of 25-OHD signifying deficiency or sufficiency are disease dependent.
Summary of study and some links to other Vitamin D Life pages
| Premature mortality | Level 1 (Systematic Review) | 75 nmol | 30 ng |
| Falls prevention | Level 1 (Systematic Review) | 95 nmol | 38 ng |
| Cancer prevention | Level 2 (RCT) | 100 nmol | 40 ng |
| Respiratory infection prevention | Level 2 (RCT) | 95 nmol | 38 ng |
| Diabetes prevention | Level 2 (RCT) | 80 nmol | 32 ng |
| Depression treatment | Level 2 (RCT) | 75 nmol | 30 ng |
| Musculoskeletal pain management | Level 2 (RCT) | ||
| Musculoskeletal strength | Level 3-1 (Pseudo RCT) | ||
| Dental disease | Level 3-2 (Study with Controls) | > 84nmol | > 37 ng |
| Cardiovascular disease | Level 3-2 (Study with Controls) | 80 nmol | 32 ng |
| Health service utilisation | Level 3-2 (Study with Controls) | ||
Australian National Health and Medical Research Council Evidence Hierarchy
- 1 Systematic review of Level II studies
- 2 Randomised controlled trial,
- 3-1 Pseudo-randomised controlled trial
- 3-2 Comparative study with concurrent controls:
non-randomised, experimental trial,cohort study, case-control study, or interrupted time series with a control group - 3-3A comparative study without concurrent controls:
historical control study, or two or more single arm study, Interrupted time series without a parallel control group - 4 Case series with either post-test or pre-test/post-test outcomes
PDF is attached at the bottom of this page
Comment by Vitamin D Life
There is a lot of evidence that the higher the vitamin D levels, the less occurrence of a particular disease as well of fewer of all diseases.
The study on this page just shows the detectable beginnings of disease prevention due to vitamin D
A nice summary of the prevention evidence is in the following chart
There are also many studies which prove that vitamin D TREATS diseases.
See also Vitamin D Life
- Is 50 ng of vitamin D too high, just right, or not enough
- Click on following chart for details of increasing vitamin D llevels to deal with different diseases
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
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 |