Tuesday, 16 December 2008

Vitamin D

A 77% reduction in new all-cause cancers in women over the age of 55.
From https://academic.oup.com/ajcn/article/85/6/1586/4633053

Vitamin D is known as the "Sunshine Vitamin" and it was once thought that a deficiency in it was rare and that it was only involved in calcium homoeostasis in bones and that a lack of it caused only Rickets. Recent research has shown that not only is Vitamin D involved in a whole host of bodily processes, but also that an insufficiency in it is very common, leading to an increased risk factor for a whole host of degenerative diseases, such as Coronary Heart Disease and Cancer.

What is Vitamin D?

There's a good overview on Vitamin D here.
See also University Lecture: The D-Lightful Vitamin D for Health by Michael F. Holick.

How common is Vitamin D deficiency?

According to Hyppönen and Power, in a large sample of the white British population born in 1958, 60.9% of subjects had serum 25(OH)D (the active metabolite of Vitamin D) of less than 75nmol/L in Summer & Autumn, and 87.1% had serum 25(OH)D of less than 75nmol/L in Winter & Spring. To convert units from nmol/L to ng/mL, divide by 2.5.

Here's my experience of Vitamin D3. For many years, I was struggling to cope with my job and I eventually took early retirement on the grounds of ill-health. In mid-2006 I was given a serum 25(OH)D test and the result was 73nmol/L. As the Reference Range for serum 25(OH)D is 50-200 nmol/L, I was technically not deficient in Vitamin D. Subsequent events suggested otherwise.

In January 2007, after reading the above study and a study by Vieth, Kimball, Hu and Walfish, I began to supplement with 2,000iu/day of Vitamin D3 and also used a UVB+IR lamp for 3 minutes each night. At first, nothing happened and I was pretty sceptical about getting any improvement. However, after about 8 weeks, I began to notice an awakening in my brain. This continued, and by March 2007, I was feeling quite perky. Friends commented on the fact that I had become very chatty and I was also waking early in the morning raring to go, totally unlike my former self. In May 2007, I had another serum 25(OH)D test and the result was 115nmol/L. Another interesting result was my serum triglycerides, something that's usually always higher than desirable. My TGs were 1.4mmol/L (RR less than 1.8mmol/L). This was the lowest result since tests began in 2002.

I began to get bored with standing around stark naked in front of a UV lamp for 3 minutes each night and I stopped doing this. Slowly, my brain began to go back to sleep. I couldn't understand why as I thought that 2,000iu/day of Vitamin D3 (5 x RDA) was more than enough.

In November 2007, I had another serum 25(OH)D test. When I saw my endocrinologist in December 2007, I was quite shocked to see that the result was now 70nmol/L. I immediately increased my Vitamin D3 intake to 5,000iu/day (12.5 x RDA) and within 2 weeks, my brain started to wake up again. In May 2008, serum 25(OH)D was 173nmol/L and in September 2008 it was 163nmol/L. I'm still taking 5,000iu/day.

See also The urgent need to recommend an intake of vitamin D that is effective.

What foods contain it?

For a list of the foods highest in Vitamin D, see here. Beware of foods that have been supplemented, as Vitamin D2 may have been used. This is less effective than Vitamin D3 according to Armas, Hollis and Heaney. Vegetarians and vegans may not want to eat foods containing Vitamin D3 as this is sourced from animals (e.g. the lanolin from a sheep's coat). Eating the Standard English Diet, it is difficult to obtain 5,000iu/day of Vitamin D. The cheapest way to get a lot of it is by going out in the sun in a swimsuit for 20 or so minutes in the middle of the day in Summer and Autumn, which costs absolutely nothing. As Vitamin D is fat-soluble, the body can build up stores to keep itself supplied during Winter and Spring.

Vitamin D deficiency, Insulin Resistance and The Metabolic Syndrome and Type 2 Diabetes

According to Hyppönen and Power, there is a strong association between decreasing 25(OH)D, increasing Body Mass Index (BMI) and increasing HbA1c (glycated haemoglobin).

According to Khaw, Wareham, Bingham, Luben, Welch and Day, increasing HbA1c is associated with increasing Relative Risk of mortality, summarised here.

According to Chiu, Chu, Go and Saad, there is a positive correlation of 25(OH)D concentration with insulin sensitivity and a negative effect of hypovitaminosis D on ß cell function. Subjects with hypovitaminosis D are at higher Relative Risk of Insulin Resistance and The Metabolic Syndrome.

In January 2003, I had Impaired Glucose Tolerance (fasting serum glucose = 6.0mmol/L and 2 hours post-75g glucose load serum glucose = 8.7mmol/L). A sandwich used to send me to sleep.

By September 2008, I had Normal Glucose Tolerance (fasting serum glucose = 5.0mmol/L and 2 hours post-75g glucose load serum glucose = 3.7mmol/L). I also no longer suffered from hyperinsulinaemic sleeps. Result!

Vitamin D deficiency and Cancer

According to Lappe, Travers-Gustafson, Davies, Recker and Heaney, subjects receiving 1400-1500mg/day supplemental calcium and 1100iu/day supplemental Vitamin D3 have a Relative Risk of getting any type of cancer of 0.402 which is equivalent to a 60% reduction in the risk of getting cancer compared to the non-supplementing group.

If the first 12 months results are discarded (to exclude any subjects who already had cancer when they started the study), the RR is 0.232 which is equivalent to a 77% reduction in the risk of getting cancer. I wonder what the result would have been had 5,000iu/day of Vitamin D3 been used.
See also Diaz, Paraskeva, Thomas, Binderup and Hague.

Vitamin D deficiency and Mental function

According to Vieth, Kimball, Hu and Walfish as mentioned above, supplementing with 4,000iu/day of Vitamin D3 produces a large reduction in the "Miserableness Factor" without affecting serum Calcium levels.

According to Wilkins, Sheline, Roe, Birge and Morris, Vitamin D deficiency is associated with low mood and worse cognitive performance in older adults.

According to Gloth, Alam and Hollis, Improvement in 25(OH) D is significantly associated with improvement in depression scale scores in a group of 15 subjects with SAD.

According to Cherniack, Troen, Florez, Roos and Levis, Hypovitaminosis D is prevalent among older adults, and several studies suggest an association between hypovitaminosis D and basic and executive cognitive functions, depression, bipolar disorder, and schizophrenia.

Vitamin D deficiency and High Blood Pressure

According to Forman, Giovannucci, Holmes, Bischoff-Ferrari, Tworoger, Willett and Curhan, plasma 25(OH)D levels are inversely associated with the risk of incident hypertension.

Vitamin D deficiency and the Immune System

According to Cannell, Vieth, Umhau, Holick, Grant, Madronich, Garland and Giovannucci, Vitamin D deficiency predisposes children to respiratory infections.

According to Ginanjar, Sumariyono, Setiati and Setiyohadi, The active form of vitamin D produces and maintains self immunologic tolerance.

Vitamin D Deficiency and Falls

According to Dharmarajan, Akula, Kuppachi and Norkus, in the pilot study of older adults with gait imbalance and falls, vitamin D deficiency was observed in 54% of patients tested and previously unrecognised.

Vitamin D Deficiency and Chronic Pain

According to Plotnikoff and Quigley, all patients with persistent, non-specific musculoskeletal pain are at high risk for the consequences of unrecognised and untreated severe hypovitaminosis D.
According to Al Faraj and Al Mutairi, Vitamin D deficiency is a major contributor to chronic low back pain in areas where vitamin D deficiency is endemic.
According to Gloth, Lindsay, Zelesnick and Greenough, there may be a pain syndrome associated with vitamin D depletion that appears as hyperaesthesia worsened by light, superficial pressure or even small increments of movement.

NEW! Vitamin D deficiency and Autism

Autism spectrum disorder and low vitamin D at birth: a sibling control study.

But doesn't the sun damage the skin and cause skin cancer?

Inappropriate sun exposure can certainly damage the skin.  

Chronic overexposure to the sun (e.g. farmers and other outdoor workers) causes wrinkly, leathery skin and skin cancers such as Basal Cell Carcinoma and Squamous Cell Carcinoma. These are benign skin cancers which are removable and rarely fatal.

Acute overexposure to the sun (e.g. people getting severe sunburn on foreign holidays) causes the much more serious Malignant Melanoma. This condition, if not caught early enough, has a very high risk of mortality.

However, sensible sun exposure has more benefits than hazards. See Does solar exposure, as indicated by the non-melanoma skin cancers, protect from solid cancers: vitamin D as a possible explanation. EDIT: See also Is Vitamin D Shooting Me in the Foot?

Is it possible to get too much Vitamin D?

It is possible to overdose with Vitamin D by supplementation. According to Vieth, published cases of vitamin D toxicity with hypercalcaemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intakes of greater than 40,000iu/day. See also Pharmacokinetics of vitamin D toxicity.

People suffering from Sarcoidosis, Primary Hyperparathyroidism, a history of Calcium Kidney Stones and Milk-Alkali Syndrome need to consult their GP before supplementing with Vitamin D. People prescribed Warfarin also need to be careful, as Warfarin is a Vitamin K recycling antagonist, which can result in calcification of tissues.

It isn't possible to overdose by sun exposure, as the metabolic processes down-regulate when ~10,000iu has been produced. To find out when the sun is strong enough to produce Vitamin D in your skin, see the Vitamin D Synthesis in Human Skin Calculator.

EDIT: Insufficient Vitamin A can result in Vitamin D toxicity. See Is Vitamin D Safe? Still Depends on Vitamins A and K! Testimonials and a Human Study.

EDIT: Vitamins A & D are synergistic, not antagonistic. See New Evidence of Synergy Between Vitamins A and D: Protection Against Autoimmune Diseases.

I've found a cheap source of 5,000iu Vitamin D3 gelcaps. See https://uk.iherb.com/pr/vitamin-d3-5-000-iu-360-softgels/18335 That's a 1 year supply for about £10 including postage. You can use discount code NIG935 to get 5% off your first order.

10,000iu Vitamin D3 gelcaps are also available. See https://uk.iherb.com/pr/Healthy-Origins-Vitamin-D3-10-000-IU-360-Softgels/21298

Addendum:- Some editorials, meta-studies and human Randomised Controlled Trials on Vitamin D and Vitamin D3 from 2005.
The Role of Vitamin D in Cancer Prevention
Estimates of optimal vitamin D status.
Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy.
Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials.
The re-emerging burden of rickets: a decade of experience from Sydney.
An excess of widespread pain among South Asians: are low levels of vitamin D implicated?
Vitamin D is associated with improved survival in early-stage non-small cell lung cancer patients.
Vitamin D and prevention of colorectal cancer.
Should older people in residential care receive vitamin D to prevent falls? Results of a randomized trial.
Effect of vitamin D replacement on musculoskeletal parameters in school children: a randomized controlled trial.
Effect of cholecalciferol plus calcium on falling in ambulatory older men and women: a 3-year randomized controlled trial.
Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial.
Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes.
Risk factors for vitamin D inadequacy among women with osteoporosis: an international epidemiological study.
A system for improving vitamin D nutrition in residential care.
Impact of dietary and lifestyle on vitamin D in healthy student girls aged 11-15 years.
How much vitamin D3 do the elderly need?
Lower levels of plasma 25-hydroxyvitamin D among young adults at diagnosis of autoimmune type 1 diabetes compared with control subjects: results from the nationwide Diabetes Incidence Study in Sweden (DISS).
A meta-analysis of second cancers after a diagnosis of nonmelanoma skin cancer: additional evidence that solar ultraviolet-B irradiance reduces the risk of internal cancers.
Risk assessment for vitamin D.
Supplementation with calcium + vitamin D enhances the beneficial effect of weight loss on plasma lipid and lipoprotein concentrations.
Serum 25(OH)D levels, dietary intake of vitamin D, and colorectal adenoma recurrence.
The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults.
Optimal vitamin D status for colorectal cancer prevention: a quantitative meta analysis.
A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study.
Potentially modifiable determinants of vitamin D status in an older population in the Netherlands: the Hoorn Study.
Fracture prevention with vitamin D supplementation: considering the inconsistent results.
A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer.
The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis.
A single dose of vitamin D enhances immunity to mycobacteria.
Does solar exposure, as indicated by the non-melanoma skin cancers, protect from solid cancers: vitamin D as a possible explanation.
Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women's Health Study.
Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial.
Bone mineral density and bone markers in patients with a recent low-energy fracture: effect of 1 y of treatment with calcium and vitamin D.
Vitamin D deficiency in multicultural primary care: a case series of 299 patients.
Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials.
Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents.
Vitamin D status and response to Vitamin D(3) in obese vs. non-obese African American children.
Vitamin D and skin physiology: a D-lightful story.
Additive benefit of higher testosterone levels and vitamin D plus calcium supplementation in regard to fall risk reduction among older men and women.
Rapid correction of low vitamin D status in nursing home residents.
Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals.
Prevalence of vitamin d insufficiency in patients with Parkinson disease and Alzheimer disease.
Exploration of association of 1,25-OH2D3 with augmentation index, a composite measure of arterial stiffness.
Vitamin D and prevention of colorectal adenoma: a meta-analysis.
The tolerability and biochemical effects of high-dose bolus vitamin D2 and D3 supplementation in patients with vitamin D insufficiency.
Administration of oral vitamin D induces cathelicidin production in atopic individuals.
Estimation of the dietary requirement for vitamin D in healthy adults.
Changes in 25-Hydroxyvitamin D3 to oral treatment with vitamin D3 in postmenopausal females with osteoporosis.
Vitamin D or hormone D deficiency in autoimmune rheumatic diseases, including undifferentiated connective tissue disease.
High-dose oral vitamin D3 supplementation in the elderly.
A double-blind, randomized, placebo-controlled trial of the short-term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men.
Vitamin D deficiency in older men.
Serum vitamin D and risk of pancreatic cancer in the prostate, lung, colorectal, and ovarian screening trial.
Vitamin D supplementation during Antarctic winter.
Vitamin D insufficiency and treatment with oral vitamin D3 in northern-dwelling patients with chronic kidney disease.
Long-term effects of giving nursing home residents bread fortified with 125 microg (5000 IU) vitamin D(3) per daily serving.
Effects of vitamin D and calcium supplementation on markers of apoptosis in normal colon mucosa: a randomized, double-blind, placebo-controlled clinical trial.
Estimation of the dietary requirement for vitamin D in free-living adults >=64 y of age.
Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers.
Plasma 25-hydroxyvitamin D concentration and metabolic syndrome among middle-aged and elderly Chinese individuals.
Meta-analysis: longitudinal studies of serum vitamin D and colorectal cancer risk.
Effect of vitamin D supplementation in the institutionalized elderly.
Calcitriol ointment 3 microg/g is safe and effective over 52 weeks for the treatment of mild to moderate plaque psoriasis.
Association between 25-hydroxyvitamin D levels and cognitive performance in middle-aged and older European men.
Low parathyroid hormone levels in bedridden geriatric patients with vitamin D deficiency.
Increased levels of 25 hydroxyvitamin D and 1,25-dihydroxyvitamin D after rosuvastatin treatment: a novel pleiotropic effect of statins?
Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects.
Vitamin D and depressive symptoms in women during the winter: a pilot study.
Treatment of vitamin D deficiency increases lower limb muscle strength in institutionalized older people independently of regular physical activity: a randomized double-blind controlled trial.
Vitamin D, parathyroid hormone and the metabolic syndrome in middle-aged and older European men.
Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient - a randomised, placebo-controlled trial.
Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials.
Meta-analysis of vitamin D, calcium and the prevention of breast cancer.
Effects of vitamin d and calcium on proliferation and differentiation in normal colon mucosa: a randomized clinical trial.
Combination of alfacalcidol with calcium can improve quadriceps muscle strength in elderly ambulatory Thai women who have hypovitaminosis D: a randomized controlled trial.
Vitamin D(3) induces expression of human cathelicidin antimicrobial peptide 18 in newborns.
Levels of vitamin D and cardiometabolic disorders: systematic review and meta-analysis.
No significant effect on bone mineral density by high doses of vitamin D3 given to overweight subjects for one year.
Effects of supplemental vitamin D and calcium on oxidative DNA damage marker in normal colorectal mucosa: a randomized clinical trial.
Vitamin D levels, lung function, and steroid response in adult asthma.
Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations:a nested case-control study.
Pandemic preparedness for swine flu influenza in the United States.
Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren.
Vitamin D supplementation suppresses age-induced bone turnover in older women who are vitamin D deficient.
Suppression of C-terminal telopeptide in hypovitaminosis D requires calcium as well as vitamin D.
A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis.
Milk fortified with the current adequate intake for vitamin D (5 microg) increases serum 25-hydroxyvitamin D compared to control milk but is not sufficient to prevent a seasonal decline in young women.
Vitamin D-vitamin K interaction: effect of vitamin D supplementation on serum percentage undercarboxylated osteocalcin, a sensitive measure of vitamin K status, in Danish girls.
Vitamin D status and impact of vitamin D3 and/or calcium supplementation in a randomized pilot study in the Southeastern United States.
Calcium/vitamin D supplementation and coronary artery calcification in the Women's Health Initiative.
Circulating 25-hydroxyvitamin D and risk of pancreatic cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.*
A 16-week randomized clinical trial of 2000 international units daily vitamin D3 supplementation in black youth: 25-hydroxyvitamin D, adiposity, and arterial stiffness.
The effect of narrowband UV-B treatment for psoriasis on vitamin D status during wintertime in Ireland.
Effects of vitamin D supplementation to children diagnosed with pneumonia in Kabul: a randomised controlled trial.
Dairy calcium intake, serum vitamin D, and successful weight loss.
Atorvastatin increases 25-hydroxy vitamin D concentrations in patients with polycystic ovary syndrome.
A randomized controlled trial of the effects of vitamin D on muscle strength and mobility in older women with vitamin D insufficiency.
Serum 25-hydroxyvitamin D concentration is associated with functional capacity in older adults with heart failure.
Effect of vitamin D supplementation on testosterone levels in men.
Vitamin D production depends on ultraviolet-B dose but not on dose rate: a randomized controlled trial.
Vitamin D(3) is more potent than vitamin D(2) in humans.
Nutrients and foods for the primary prevention of asthma and allergy: systematic review and meta-analysis.
High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial.
Circulating 25-hydroxyvitamin D levels and frailty in older men: the osteoporotic fractures in men study.
Association of low serum 25-hydroxyvitamin D levels and mortality in the critically ill.
Effects of vitamin D supplementation on 25-hydroxyvitamin D, high-density lipoprotein cholesterol, and other cardiovascular disease risk markers in subjects with elevated waist circumference.
Changes in balance, functional performance and fall risk following whole body vibration training and vitamin D supplementation in institutionalized elderly women. A 6 month randomized controlled trial.
Diet induced thermogenesis, fat oxidation and food intake following sequential meals: influence of calcium and vitamin D.
The response of elderly veterans to daily vitamin D3 supplementation of 2,000 IU: a pilot efficacy study.
Meta-analysis: Circulating vitamin D and ovarian cancer risk.
Relation of vitamin D level to maximal oxygen uptake in adults.
Vitamin D status in patients with stage IV colorectal cancer: findings from Intergroup trial N9741.
Circulating levels of vitamin D and colon and rectal cancer: the Physicians' Health Study and a meta-analysis of prospective studies.
Burning daylight: balancing vitamin D requirements with sensible sun exposure.
Relationships between vitamin D status and cardio-metabolic risk factors in young European adults.
Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis.
Vitamin D status and early age-related macular degeneration in postmenopausal women.
Vitamin D and clinical disease progression in HIV infection: results from the EuroSIDA study.
Annual high-dose vitamin D3 and mental well-being: randomised controlled trial.
Vitamin D status and outcomes in heart failure patients.
The impact of vitamin D status on periodontal surgery outcomes.
The role of paricalcitol on proteinuria.
Effects of weight loss on serum vitamin D in postmenopausal women.
Vitamin D status and mortality risk in CKD: a meta-analysis of prospective studies.
Vitamin D intake and risk of cardiovascular disease in US men and women.
Meta-analysis: Serum vitamin D and colorectal adenoma risk.
Calcium plus vitamin D supplementation and the risk of nonmelanoma and melanoma skin cancer: post hoc analyses of the women's health initiative randomized controlled trial.
Effects of vitamin D and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial.
Vitamin D supplementation for prevention of mortality in adults.
The effect of calcium plus vitamin D on risk for invasive cancer: results of the Women's Health Initiative (WHI) calcium plus vitamin D randomized clinical trial.
New clinical trials with vitamin D and analogs in renal disease.
The relation between vitamin D deficiency and fibromyalgia syndrome in women.
Interventions for latent autoimmune diabetes (LADA) in adults.
Calcium and vitamin D supplementation is associated with decreased abdominal visceral adipose tissue in overweight and obese adults.
Effect of vitamin D supplementation on muscle strength, gait and balance in older adults: a systematic review and meta-analysis.
Vitamin D3 and the risk of CVD in overweight and obese women: a randomised controlled trial.
Low 25-hydroxyvitamin D is associated with increased mortality in female nursing home residents.
Improvement of vitamin D status resulted in amelioration of biomarkers of systemic inflammation in the subjects with type 2 diabetes.
Vitamin D supplementation in infants with chronic congestive heart failure.
Vitamin D reduces musculoskeletal pain after infusion of zoledronic acid for postmenopausal osteoporosis.
Consumption of vitamin D-and calcium-fortified soft white cheese lowers the biochemical marker of bone resorption TRAP 5b in postmenopausal women at moderate risk of osteoporosis fracture.
Vitamin D improves viral response in hepatitis C genotype 2-3 naïve patients.
Vitamin D supplementation in the treatment of atopic dermatitis: a clinical trial study.
Effect of vitamin D repletion on urinary calcium excretion among kidney stone formers.
25-Hydroxyvitamin D levels and the risk of stroke: a prospective study and meta-analysis.
Improvement of vitamin D status via daily intake of fortified yogurt drink either with or without extra calcium ameliorates systemic inflammatory biomarkers, including adipokines, in the subjects with type 2 diabetes.
Treatment of vitamin D insufficiency in children and adolescents with inflammatory bowel disease: a randomized clinical trial comparing three regimens.
Therapeutic effects of calcium & vitamin D supplementation in women with PCOS.
Higher vitamin D dietary intake is associated with lower risk of alzheimer's disease: a 7-year follow-up.
Vitamin D3 supplementation at 4000 international units per day for one year results in a decrease of positive cores at repeat biopsy in subjects with low-risk prostate cancer under active surveillance.
Comparison of narrowband ultraviolet B exposure and oral vitamin D substitution on serum 25-hydroxyvitamin D concentration.
The relation between sunscreen layer thickness and vitamin D production after ultraviolet B exposure: a randomized clinical trial.
Circulating 25-hydroxyvitamin D concentration and the risk of type 2 diabetes: results from the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort and updated meta-analysis of prospective studies.
Vitamin D3 therapy corrects the tissue sensitivity to angiotensin ii akin to the action of a converting enzyme inhibitor in obese hypertensives: an interventional study.
The effect of combined calcium and cholecalciferol supplementation on bone mineral density in elderly women with moderate chronic kidney disease.
Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis.
Relative effectiveness of oral 25-hydroxyvitamin D3 and vitamin D3 in raising wintertime serum 25-hydroxyvitamin D in older adults.
Vitamin D supplementation and depression in the women's health initiative calcium and vitamin D trial.
Vitamin D with calcium reduces mortality: patient level pooled analysis of 70,528 patients from eight major vitamin D trials.
An open label, randomized controlled study of oral calcitriol for the treatment of proteinuria in patients with diabetic kidney disease.
Ergocalciferol from mushrooms or supplements consumed with a standard meal increases 25-hydroxyergocalciferol but decreases 25-hydroxycholecalciferol in the serum of healthy adults.
Narrowband ultraviolet B three times per week is more effective in treating vitamin D deficiency than 1600 IU oral vitamin D₃ per day: a randomized clinical trial.
Vitamin D intake is inversely related to risk of developing metabolic syndrome in African American and white men and women over 20 y: the Coronary Artery Risk Development in Young Adults study.
Vitamin D and gestational diabetes: a systematic review and meta-analysis.
Associations between 25-hydroxyvitamin D and weight gain in elderly women.
Effect of cholecalciferol as adjunctive therapy with insulin on protective immunologic profile and decline of residual β-cell function in new-onset type 1 diabetes mellitus.
A pooled analysis of vitamin D dose requirements for fracture prevention.
Determinants and effects of vitamin D supplementation on serum 25-hydroxy-vitamin D levels in patients with rheumatoid arthritis.
Vitamin D is a major determinant of bone mineral density at school age.
Effect of vitamin D and inhaled corticosteroid treatment on lung function in children.
Serum 25-hydroxyvitamin D3 and D2 and non-clinical psychotic experiences in childhood.
Vitamin D deficiency in postmenopausal, healthy women predicts increased cardiovascular events: a 16-year follow-up study.
Randomized trial of vitamin D supplementation and risk of acute respiratory infection in Mongolia.
25-hydroxyvitamin d levels and risk of ischemic heart disease, myocardial infarction, and early death: population-based study and meta-analyses of 18 and 17 studies.
Association of low serum 25-hydroxyvitamin D levels and acute kidney injury in the critically ill.
A 12-week double-blind randomized clinical trial of vitamin D₃ supplementation on body fat mass in healthy overweight and obese women.
Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies.
Relation of severe deficiency of vitamin D to cardiovascular mortality during acute coronary syndromes.
Vitamin D reduces left atrial volume in patients with left ventricular hypertrophy and chronic kidney disease.
Interventions for preventing falls in older people in care facilities and hospitals.
Vitamin D and risk of death from vascular and non-vascular causes in the Whitehall study and meta-analyses of 12,000 deaths.
Calcium plus vitamin D3 supplementation facilitated fat loss in overweight and obese college students with very-low calcium consumption: a randomized controlled trial.
Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes.
Effect of vitamin D supplementation on progression of knee pain and cartilage volume loss in patients with symptomatic osteoarthritis: a randomized controlled trial.
Lipoprotein lipase links vitamin D, insulin resistance, and type 2 diabetes: a cross-sectional epidemiological study.
The effect of different doses of vitamin D supplementation on insulin resistance during pregnancy.
Vitamin D and dental caries in controlled clinical trials: systematic review and meta-analysis.
Vitamin D deficiency and depression in adults: systematic review and meta-analysis.
Improving the vitamin D status of vitamin D deficient adults is associated with improved mitochondrial oxidative function in skeletal muscle.
Low 25-OH vitamin D is associated with benign prostatic hyperplasia.
Correcting vitamin D insufficiency improves insulin sensitivity in obese adolescents: a randomized controlled trial.
Vitamin D levels in Alzheimer's and Parkinson's diseases: a meta-analysis.
Supplemental vitamin D and physical performance in COPD: a pilot randomized trial.
Vitamin D and risk of future hypertension: meta-analysis of 283,537 participants.
Randomized clinical trial of vitamin D3 doses on prostatic vitamin D metabolite levels and ki67 labeling in prostate cancer patients.
Randomized, double-blind, placebo-controlled trial of vitamin D supplementation in Parkinson disease.
Anti-inflammatory effect of vitamin D on gingivitis: a dose-response randomised control trial.
Role of vitamin D in children with respiratory tract infection.
Effect of vitamin D supplementation and ultraviolet B exposure on serum 25-hydroxyvitamin D concentrations in healthy volunteers: a randomized, crossover clinical trial.
Vitamin D and multiple sclerosis: what is the clinical impact?
Is hypovitaminosis D associated with abdominal aortic aneurysm, and is there a dose-response relationship?
Plasma vitamin D levels, menopause, and risk of breast cancer: dose-response meta-analysis of prospective studies.
Impact of vitamin D on chronic kidney diseases in non-dialysis patients: a meta-analysis of randomized controlled trials.
Serum 25-hydroxyvitamin D levels and the risk of depression: a systematic review and meta-analysis.
The effect of vitamin D-related interventions on multiple sclerosis relapses: a meta-analysis.
Vitamin D status and physical function in nursing home residents: a 1-year observational study.
Maternal vitamin D status and risk of pre-eclampsia: a systematic review and meta-analysis.
Meta-analysis: vitamin D and non-alcoholic fatty liver disease.
Serum 25-hydroxyvitamin D and breast cancer risk: a meta-analysis of prospective studies.
Treatment with oral active vitamin D is associated with decreased risk of peritonitis and improved survival in patients on peritoneal dialysis.
Vitamin D supplementation affects serum high-sensitivity C-reactive protein, insulin resistance, and biomarkers of oxidative stress in pregnant women.
The role of vitamin D supplementation in the risk of developing pneumonia: three independent case-control studies.
Short-term vitamin D3 supplementation lowers plasma renin activity in patients with stable chronic heart failure: an open-label, blinded end point, randomized prospective trial (VitD-CHF trial).
Vitamin D and psychosis: mini meta-analysis.
Meta-analysis of memory and executive dysfunctions in relation to vitamin D.
Vitamin D intake and lung cancer risk in the Women's Health Initiative.
Association of low serum 25-hydroxyvitamin D levels and sepsis in the critically ill.
Vitamin D favorably alters the cancer promoting prostaglandin cascade.
Vitamin D intake and risk of type 1 diabetes: a meta-analysis of observational studies.
Effect of vitamin D supplementation on antibiotic use: a randomized controlled trial.
Effects of vitamin D supplementation on glucose metabolism, lipid concentrations, inflammation, and oxidative stress in gestational diabetes: a double-blind randomized controlled clinical trial.
Improvement in high-density lipoprotein cholesterol levels in argentine Indian school children after vitamin D supplementation.
Vitamin D supplementation for prevention of mortality in adults.
Beneficial role for supplemental vitamin D3 treatment in chronic urticaria: a randomized study.
Vitamin D3 supplementation during weight loss: a double-blind randomized controlled trial.
Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies.

*See https://www.slideshare.net/TedHutchinson/ow-to-optimize-vitamin-d-supplementation-to-prevent-cancer-based-on-cellular-adaptation-and-hydroxylase-enzymology for an explanation.

If you want to do a search, click PubMed.


Dr. Art Ayers said...

Great post! It is nice to have all of this info in one place. This also shows that the impact of vitamin D deficiency is also related to chronic inflammation, since the symptoms are the same. It is fascinating that vitamin D deficiency can result in back problems that are similar to those caused by the gluten triggered autoimmune coeliac.

Nigel Kinbrum said...

Thanks for the thumbs-up!

My mum calls the 5000iu caps her "happy pills". She used to be a major sun-worshipper, but completely stopped sunbathing when she turned 75-ish. She started showing signs of dementia when she was 77. She'll be 79 in a couple of weeks time.

In the last week, her mental faculties have noticeably improved, so I'm doubling the amount of smoked salmon that she eats from 150g/week to 300g/week to see if the increase from 100g/week to 150g/week a few weeks ago was the cause.

Thanks for your comments.

Unknown said...

Hi Nige,

Thanks for the info.

I'm 43 and over the past few months have noticed a reduction in my cognition (forgetting easy to remember facts, finding it hard to search for a word to complete a sentence). At first I just put it down to tiredness and age. I am also worried as my dad was diagnosed with pre-senile dementia in his mid-late 40's and died a few years later - in my dark hours I wonder if what I'm going through could be connected.

A couple of questions if I may:-
1)Is the doseage of 5000iu a day applicable to everyone or are there exceptions
2) Does the supplementaion need to be stopped or lowered during times of sunshine (although living in the UK I guess that would be rare :-).
3) Is this supplementation something to continue for the rest of my life?

Many Thanks

TedHutchinson said...

1)Is the doseage of 5000iu a day applicable to everyone or are there exceptions

Dr Davis of the Heartscanblog
finds that at Latitude 42 Wisconsin, where not only do they enjoy more hours sunshine daily, more sunny days annually but also have easier access to vitamin d fortified milk/cereals, that it takes 5000iu/daily for women and 6000iu/daily for men to maintain a blood level in the desirable range. (60-70 ng/ml 150~175nmol/l.)
Without a 25(OH)D test it is impossible to predict how your individual body responds to D3 supplementation.
You may sign up here http://www.grassrootshealth.org/daction/index.php for a 25(OH)D test every six months for £20ish for the next 5 yrs. Ideally you need to supplement at 5000iu/d for 3 months then test. Then correct intake by 100iu/d for each 1ng or 2.5nmol/l required adjustment. If I were a betting man I would predict that most UK readers will require around 2000iu/d more than Dr Davis suggests between October~March but will be fine with 5000iu/f 6000iu/m from March~September providing they get out in the sun whenever possible.

2) Does the supplementaion need to be stopped or lowered during times of sunshine (although living in the UK I guess that would be rare :-).

NO the production of D3 near the surface of the skin is selflimiting that means if your body doesn't need it then it stays near the surface and is processed on into supra sterols your system doesn't use. Remember also that Vit D3 is biologically inert. On it's own it's useless. It has to go through 2 further hydrolations to become an active substance Calcitriol and what is even more clever is that at the second hydrolation for each active molecule a matching neutralising molecule is also formed so there are checks and balances throughout the process. You have to work very hard to get Vitamin d toxicity.

3) Is this supplementation something to continue for the rest of my life?
YES. Either that or you can move to somewhere where you can sunbathe nude daily at midday with the possibility of getting sunburnt. Though a quarter of the time needed to get sunburnt is all that is required for Vitamin D synthesis.
Be warned though. By the time your skin burns there is absolutely NO VITAMIN D LEFT whatsoever near the surface of your skin to repair that damage. That is why sunburn leads to more cancer but regular nonburning sun exposure reduces incidence of 17 different cancers including the breast, colon prostate.

TedHutchinson said...

I meant to explain where to get your 5000iu Cholecalciferol Vit d3.

I use these https://secure.bio-tech-pharm.com/detail.aspx?product_id=18&cat_id=2&subcat_id=0
From Bio~tech. I take one with my cooked breakfast.

Dr Davis of the Heartscanblog prefers D3 dissolved in oil so he recommends these Carlson 2000iu
To average 5000iu take one on odd days of the week and 2 on even days. In fact there is little difference between weekly /daily supplementation so if you want to take 17/18 in one go once a week that's only going to be a problem for breast feeding or pregnant ladies in which case they should supplement daily. Everyone else it doesn't really matter.

If you hate ordering from the USA you may want to use
The vitamin Service.
I've not use them myself but I have been told they are fine. Again you would need to alternate 2/3 drops or take 5 drops every other day.

I haven't used these yet but Now foods 5000iu may make life easier for some

If you are totally useless at remembering to take daily supplements then these 50,000iu
would be useful. One every 10 days=5000iu/d.
Just recently I've upped my intake to 7000iu and so I use one of these each week.

In case anyone is wondering the problem with USA orders is the customs duty on entry for orders £18 or more. With the £ down against the $ is brought the danger level down. It wouldn't be so bad if it were just the tax but carriers and the Post Office charge £8 or more just to collect the £4 tax which seems unfair.

That's one reason I like IHERB if you use a discount code like WAB666 you earn a $5 discount and that reduces your order value so you may avoid the tax. You'll get your own $5 discount code then an if you pass it round to your mates/relatives etc you get further discounts off your next order so you can perpetuate the discount. I know it's just a trivial amount but using any legal dodge to avoid paying tax pleases me.

TedHutchinson said...

Vitamin D: Requirements for Optimal Health William B. Grant,
this slide presentation gives a good summary of the situation regarding Vitamin D as it was in 2004. In Vitamin D history that means even people like Grant, will have had to change their opinions given the latest research, but it summarises what Nige has already stated in his excellent blog on the topic.

Nigel Kinbrum said...

I've only just noticed this comment! Thanks to Ted for stepping in in my absence.

A couple of questions if I may:-
1)Is the doseage of 5000iu a day applicable to everyone? Yes.

2) Does the supplementaion need to be stopped or lowered during times of sunshine? (although living in the UK I guess that would be rare :-).You can if you get enough suitable sun exposure. As it only costs me 8p for 5,000iu, I take 5,000iu/day whether or not I get any sun exposure.

3) Is this supplementation something to continue for the rest of my life? If you don't get enough sun exposure for the rest of your life, then yes.

You can get 5,000iu caps from Bio-tech Pharmacal.

As the £ is weak against the $, 2 pots now costs ~£20 so you may get stung for £3 VAT + £8 Royal Mail handling. :-(

Nigel Kinbrum said...

I've slightly duplicated what Ted wrote.

There's a lecture on Vitamin D by Michael Holick at http://www.uvadvantage.org/portals/0/pres/

It's a good lecture, but there are 2 problems with it, so I won't put it in the Vitamin D Blog.

1) If you stop it, you have to re-start from the beginning.

2) It opens a large number of tabs, one for each slide.

Rosso said...

Just had a debate about 30 mins ago with the GP about D3. Shockingly told it was a waste of money and that I should just be outside more and not wear a Muslim headscarf? WTF?

Nigel Kinbrum said...

So 8p a day is a waste of money? I wonder how much money is spent on drugs prescribed to treat the symptoms of Vitamin D deficiency?

Your GP is ignorant. You could point him in the direction of my Blog. If he chooses to not read it, he is also apathetic and bone-idle!

Anonymous said...

It seems you where way ahead with your supplementation and Sunbed UVB exposure. See http://products.mercola.com/tanning-bed/?aid=CD353 for more info.
I tried to recreate this sunbed using Special Medical treatment lamps but they are only available upon recommendation if you have psoreasis are other severe skin conditions. I was wondering how you managed top make yours ?

Henry North London 2.0 said...

Finally Someone else who has recognised this...

I was derided by my medical colleagues as being completely mad when I suggested that Vitamin D was necessary

I have bookmarked this page and will be getting all those studies down

Thanks very much.

Will help amazingly in my next interview.... Cant wait to see the look on their faces...

Nigel Kinbrum said...

Hi Henry. Sorry it took so long to moderate your post but I had a lie-in this morning!

I see from your profile that you're a Doctor. How long have you been practising? I find it somewhat amusing when I talk to Health Professionals (my GP & Endocrinologist) and I find that I, a retired Electronic Engineer, know more about cell biochemistry & metabolism than they do! My cousin works in cancer research. I told her about methylglyoxal. She asked me how it worked. I told her that it inhibited glycolysis in cancer cells. She said "What's glycolysis?" I replied "Read my blog!"

It was Ted Hutchinson who got me interested in Vitamin D3 back in 2007. So, thank you Ted.

Cheers, Nige.

Anonymous said...

Synthetic vitamins are never a good choice.Nothing beats mother nature.Plain and simple!

Nigel Kinbrum said...

Hi anonymous.

I agree. That's why I only recommend & take cholecalciferol (D3) which is what's in food and also what's synthesised (see what I did there?) by the action of UVB on 7-dehydrocholesterol in our skin (also in sheep's lanolin, which is what commercial non-vegetarian D3 is extracted from).

Cheers, Nige.

Anonymous said...

Vitamin D from the sun and natural food sources is regulated by the body so that you cant overdose on It.The body doesnt require much natural Vitamin D for proper function.Synthetic vitamin D taken in pill or gelcap form is not regulated by the body.Most of it is urinated out and the body tries to store the rest in fat tissue.The body does not recognize it as a natural substance and tries to get rid of it.Thats why you have to take so much of it to even show up in the bloodstream.Not a good Idea! it will bioacumulate in the fat tissue and possibly give you problems in the future.Im gonna stick to real naturals.


Nigel Kinbrum said...

Hi Anonymous2

I guess you didn't see what I did in my comment immediately above yours. Sunshine doesn't contain Vitamin D. However, the UVB in sunshine that's strong enough synthesises Vitamin D in the skin. This then enters the blood. Therefore, your "natural" Vitamin D is just as synthetic as the stuff extracted from sheep's lanolin, where exactly the same process occurs. That's the form I use. The only difference is that oral Vitamin D is absorbed through the lining of the gut to get into the blood. Yes, oral Vitamin D can be overdosed unlike sun-derived Vitamin D. However, oral Vitamin D doesn't age the skin or raise the risk for simple skin cancers.

Your evidence that the body doesn't need much Vitamin D for proper function is what exactly? Why should I believe you instead of all of the peer-reviewed studies showing that 600iu/day isn't enough to alleviate a lot of common health problems?

All fat-soluble vitamins (also B12) are stored. The level in the body increases until equilibrium is reached where the rate of usage by the body equals the rate of intake.

Make your mind up. Is "synthetic" Vitamin D urinated out or is it accumulated?

Cheers, Nige.

Henry North London 2.0 said...

Been practising for 16 years. Now retired due to ill health. Been researching my own health (physician heal thyself) for last 3 years and have made a lot of enemies by promoting the Vitamin D3. First off wanted to lose weight, the eat low fat diet didnt seem to work, and I despaired, went low carb and that research by me on a personal level took me to the paleo diet and the Vitamin D

I recently got rid of a nasty cough with green sputum with hi dose Vitamin D3 One of my doctor friends who was also bashed by the GMC sent me some cholecalciferol concentrate 1g=50000iu Took about 400000 for three or four days and then about 200000 for a few days after that.

Gone Didnt need antibiotics,

Sorry about the length of time to respond. Its been a hard year.

Nigel Kinbrum said...

Hello again Henry (now V2.0)

I'm sorry to hear that you've been having a hard time and I hope that you manage to resolve your health problems. Vitamin D3 Stoss therapy is quite effective. My 25(OH)D level is near the top end of the RR so I don't need to take a Stoss dose to bump it up.

Cheers, Nige.

ROHIT said...

Hi ,

Thank you for the information. I think it’s probably overkill on my part, but who knows

for sure anyway. Good and Natural Vitamins thing for us. Thanks again and best wishes!

for more info visit : http://trapezepart.com/

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