The case for optimum Vitamin D

Scientific medical research shows that optimal levels of Vitamin D have the potential to:

  • Reduce the risk of many cancers
  • Lower the risk of dementia
  • Reduce asthma symptoms
  • Reduce the risk of bone fractures
  • … and even increase life span

Yet, according to the leading vitamin D researchers, the majority of us have well below optimum levels of vitamin D in the blood and a significant percentage fail to reach even the Recommended Daily Allowance which experts are now labelling as inadequate.

The NHS recognised in July 2016 the importance of vitamin D and recommends:

“Adults and children over the age of one should consider taking a daily supplement containing 10mcg of vitamin D, particularly during autumn and winter. Those with a higher risk of vitamin D deficiency are being advised to take a supplement all year round.”

However, a huge weight of evidence shows that just avoiding deficiency with ‘adequate’ levels of vitamin D is not enough – and that reaching optimum blood levels of vitamin D can confer major health benefits.

Unfortunately there is a confusion of what constitutes ‘adequate’ and ‘optimum’ levels. Indeed the UK is in the unhappy position of having an official Reference Nutrient Intake/Recommended Daily Amount that is half the latest recommendation from Public Health England and a third of the new US RDA levels!

This report aims to give you the evidence to make a considered decision on whether you need to supplement with vitamin D – you almost certainly do – and how much is both safe and optimum.

WHY WE ARE DEFICIENT IN VITAMIN D

“We estimate that vitamin D deficiency is the most common medical condition in the world.”

 Dr Michael F Holick, Professor of Medicine, Physiology and Biophysics, Boston University School of Medicine

As at mid-2016 there are over 35,000 published studies on the effects of vitamin D.

Specialists in the Vitamin D research field agree that you should supplement with vitamin D – especially in the winter. The form should be vitamin D3 – cholecalciferol – the natural form you make in response to sunlight, not the artificial form D2 which is less well utilised.

The reasons for supplementation are that:

  • Low dietary intakes and sun-avoidance make D depletion very common indeed, and the situation is even worse in older age groups, as the ability of the skin to make vitamin D declines with age – which is why the US RDA for the over 70s is higher.
  • It’s very difficult to reach the level of vitamin D from food sources alone, as very few foods contain vitamin D. Milk is fortified with some vitamin D, which is one reason why rickets is now almost unknown, but main food sources include oily fish like salmon, mackerel, sardines and to a lesser extent eggs.
  • For most people, sunlight is the main source of vitamin D, but in the northern hemisphere (UK, Europe, North America) in winter, very few occupations allow enough exposure to produce levels that are optimally health protective. Even in summer the risk of skin cancer through over-exposure causes many people to either cover up or to use high factor sunscreens.
  • Most people are below the optimum level in winter, and the risk of deficiency is increased further for people with darker skin (for whom more exposure is needed to make the same amount of vitamin D through sunlight), for people with whole body covering and for the housebound. Obese people have lower blood levels of vitamin D because more is stored in fat tissue and unavailable in circulating blood.

This table shows how big a gap there is between even the current UK average dietary intakes of vitamin D and the RDAs, let alone the vitamin D levels that experts in the field recommend.

The average intakes in USA are somewhat higher, but still well below their own RDAs. We’ll explain how we have calculated the optimum vitamin D supplementation level shortly.

Note: Vitamin D in food or in supplements is measured as either International Units (IU) or micrograms (mcg or μg). There are 40 IU in 1 mcg.  RDA stands for Recommended Daily Amount, also referred to as  RNI (Reference Nutrient Intake).

Men Women
Average UK daily vitamin D intake from food alone 148 IU 3.7 mcg 112 IU 2.8 mcg
UK/EU Reference Nutrient Intake (RNI) 200 IU 5 mcg
UK NHS recommendations July 2016 400 IU 10 mcg
USA Recommended Daily Amount up to 70 (Food and Nutrition Board) 600 IU 15 mcg
USA Recommended Daily Amount over 70 800 IU 20 mcg
Optimum Recommended Daily Supplement Level based on leading expert research outlined in this report WINTER  2,500 IU  62.5 mcg
 SUMMER 800 IU 20 mcg

The expert supplement recommendations recognise that vitamin D’s role in health goes far beyond maintaining healthy bones and preventing osteoporosis.

But how much is enough? And how much is too much? Vitamin D is fat soluble, which means it is mostly retained by the body rather than any excess being excreted as it the case of vitamin C, so it is possible to take too much.

Unfortunately it’s not easy to follow the research without understanding some definitions.

We will then give you the highlights of many thousands of studies.

SOME DEFINITIONS
Vitamin D in food or in supplements is measured in either International Units (IU) or micrograms (mcg or μg). There are 40 IU in 1 mcg.

The concentration of activated vitamin D (also known as calcidiol) in the blood is what really matters, however, and is the best indicator of your vitamin D status. This is measured in nanograms per millilitre (ng/ml) of blood.  [Or sometimes nanomoles per litre (nmol/l).]

The relationship between ng/ml of vitamin D-calcidiol in the blood and the IU of vitamin D consumed in foods and supplements is not a simple one. However, it has been calculated by the Vitamin D Council (a non-profit scientific advisory organisation in the USA) – see table.

There is a consensus amongst the experts we quote in this report that a vitamin D-calcidiol blood level below 20 ng/ml means you are deficient.

On average they recommend you need to get to a blood level of 35 ng/ml – and to get to that level (from an average starting point of 15 ng/ml) indicates a supplement level of 2,500 IU in winter and somewhat less in summer.

NOTE: In the interest of readability, we will refer to the activated vitamin D in the blood as vitamin D-calcidiol, as distinct from simply vitamin D for what is in food and supplements.

Blood levels of vitamin D-calcidiol related to supplementation levels

[assuming start level is 15 ng/ml]

Vitamin D Council

 

To achieve this blood level … Take this level of vitamin D3 supplement per day … Equivalent in mcg
20 ng/ml 500 IU 12.5 mcg
30 ng/ml 1,700 IU 42.5 mcg
40 ng/ml 3,200 IU 80.0 mcg
50 ng/ml 4,900 IU 122.5 mcg
 so to reach 35 ng/ml  suggests 2,500 IU  62.5 mcg

Blood tests

Having a blood test to measure the amount of vitamin D in your blood is the only certain way to know if you’re getting enough vitamin D or not. The blood test you need, which measures the 25(OH)D or calcidiol is called a 25(OH)D blood test.

You can get a blood test at your doctor’s or go to a clinic.  In-home testing kits are also available, which are easy to use and involve pricking your finger to take a small blood sample and sending this away to a laboratory.

More about the activation of vitamin D in the body

Vitamin D obtained from sun exposure, food, and supplements is initially biologically inert. It must undergo two chemical processes in the body for activation. The first occurs in the liver and converts vitamin D to 25-hydroxyvitamin D [25(OH)D], also known as calcidiol. That’s what the blood test measures

The second occurs primarily in the kidney and forms the physiologically active 1,25-dihydroxyvitamin D [1,25(OH)2D], also known as calcitriol.

HEALTH THREATS AND BENEFITS

“No other method to prevent cancer has been identified that has such a powerful impact.”

 Dr Cedric Garland, Department of Family and Preventive Medicine, University of California Los Angeles

Of the over 35,000 published studies on the effects of vitamin D, more than 850 references show vitamin D’s effectiveness against one threat alone – cancer.

For full references to the articles quoted, and others, please refer to the References section at the end, cited by chapter and subject.

HEALTH THREATS FROM VITAMIN D DEFICIENCY

Research shows that Vitamin D deficiency:

·         increases your risk of auto-immune disease, and hypertension and heart problems (Dr Michael Holick, Boston University School of Medicine)

·         is associated with more severe strokes (American Stroke Association) and poorer outcomes in patients who have had a stroke.

·         is associated with an increased risk for over a dozen different cancers, including breast and colon cancer.

·         is linked to an increase in risk of Type 1 diabetes in children whose mothers were vitamin D deficient.

·         is a predictor of hardening of the arteries in middle age for those who were low in vitamin D during childhood.

HEALTH BENEFITS FROM OPTIMUM VITAMIN D STATUS

On the positive side, people who have optimum levels of Vitamin D benefit from:

Improved DNA repair and positive gene expression

·         Research by Dr Michael Holick and reported in his book The Vitamin D Solution shows that supplementing with 2,000 IU of vitamin D per day for 4 months up-regulated dozens of different genes that control important metabolic processes. This included improved DNA repair, which has implications for slower ageing and reduced cancer risk.

Increased brain health and reduced risk of Alzheimer’s

There are vitamin D receptors in many areas of the brain, especially in the hippocampus and cortex, respectively critical for memory and higher order thinking. And neurons respond positively when activated by vitamin D.

·         A study at Exeter University found that severe vitamin D deficiency correlated with a 100% increase in Alzheimer’s risk [meaning that risk was doubled].

·         Another US study produced similar findings and in 2014 a study in the journal Neurology confirmed that “vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer’s disease”.

The mechanisms are not yet clear, but since vitamin D is a key nutrient for the immune system, some of the beneficial effects on the brain may come from its role in enhancing the immune system and in reducing inflammation – which is a known element in Alzheimer’s and dementia.

Reduced cancer risk

·         Dr Cedric Garland, of the University of California San Diego School of Medicine, calculates that raising the minimum year-round blood levels of vitamin D-calcidiol (to between 40 and 60 ng/ml) would prevent approximately 58,000 new cases of breast cancer and 49,000 new cases of colorectal cancer in the USA and Canada each year.

·         The Canadian Cancer Society recommends vitamin D supplementation following a study published in the American Journal of Clinical Nutrition showing that increasing vitamin D intake could potentially halve cancer risk.

·         Research by Joan Lappe and Robert Heaney found that when menopausal women were given enough vitamin D to raise blood levels of vitamin D-calcidiol to 40ng/ml they had a 77% lower risk of all cancers after 4 years of supplementation.

·         A report in Anticancer Research in 2011 found that a vitamin D-calcidiol level of 47ng/ml was associated with a 50% lower risk of breast cancer, although other studies have not found such a clear connection.

·         Perhaps the clearest evidence for the ability of vitamin D to lower the risk of cancer is in colon and rectal cancers. The huge-scale Nurses’ Health and Health Professionals studies found that those with an average blood level of vitamin D-calcidiol of 40ng/ml had a 34% lower risk than those with the lowest average of 18ng/ml.

·         Finally a report in Clinical Oncology noted that patients with colorectal cancer had a median vitamin D-calcidiol level of 17ng/ml and concluded that anything below 20ng/ml can be considered a serious deficiency state.

Vitamin D is a hormone as well as a vitamin and is a powerful agent for regulating normal cell growth, so its potential role in cancer prevention is logical. Indeed there are many population studies that show that higher levels of vitamin D in the blood are related to lower cancer levels.

Reduced asthma symptoms

Over 5.4 million people in the UK alone, including 1.5 million children, suffer asthma and there are 1,400 asthma-related deaths every year.

·         A report in the Journal of Allergy and Clinical Immunology shows that vitamin D can significantly improve symptoms in asthma sufferers.  Researchers from Kings College, London found that vitamin D3 works better than steroids at reducing levels of a chemical in the body (called IL-17A), which aggravates symptoms in asthma sufferers. It appears as though asthma sufferers may be able to at least reduce their steroid intakes.

·         Professor Adrian Martineau is the lead researcher at the Asthma UK Centre for Applied Research, Queen Mary University of London. Commenting on a double blind study, when one group added 1,000 to 2,000 IU of vitamin D to their normal medication while the second group took a placebo, he said: “We found that taking a vitamin D supplement in addition to standard asthma treatment significantly reduced the risk of severe asthma attacks without causing side effects.”  It is not yet clear whether the beneficial effects applied to all patients or just those with low starting levels of vitamin D.

Reduced hypertension (high blood pressure)

Since vitamin D is involved in the production of another hormone (renin) which in turn is involved in regulating blood pressure, it could be expected that optimum levels of vitamin D may help lower blood pressure.

·         Results from the American National Health and Nutrition Examination Survey (NHANES) do indeed show that people with the lowest blood levels of vitamin D-calcidiol (under 15ng/ml) have an increased risk of higher blood pressure.

·         This might be expected to translate into lower levels of heart disease. A 2008 study published in Circulation magazine showed that people with a vitamin D-calcidiol blood level of 15ng/ml had a 60% extra risk of heart disease.

Other studies have failed to find such a clear correlation, which is not surprising as heart disease has several causes – of which chronic sub-clinical inflammation in tissues is almost certainly the key.So dosing with a single vitamin is unlikely to be anywhere near as effective as supplementing with a range of anti-inflammatory nutrients combined with a Mediterranean style diet and activity levels.

Reduced health costs and increased life expectancy

·         Dr William Grant, of the non-profit organisation Sunlight, Nutrition and Health Research Center has been researching vitamin D for more than 25 years. He believes – as most researchers in the field do – that the current RDA recommendations are too low and that that high doses (3,000 to 4,000 IU a day) can reduce the economic burden of disease in Western developed countries by about 10 percent. Applied to the UK National Health Service, that would be an annual saving of £12 billion!In the European Journal of Clinical Nutrition, he estimated that doubling blood levels of vitamin D around the world would increase life expectancy by two years on average.

Reduced risk of Type 1 diabetes

·         A study conducted in Finland, where children in the 1960s received 2,000 IU of vitamin D a day during the first year of life and were followed for 31 years, showed that they reduced their risk of developing Type 1 diabetes by 88%.

Bone Health

·         Dr Robert Heaney of the Osteoporosis Research Center, Creighton University, Omaha, concluded that a blood level of 30ng/ml vitamin D-calcidiol (which is deemed acceptable by many doctors today) is actually at the bottom of the range needed for skeletal health. The International Osteoporosis Foundation concurs and states that people with limited sun exposure or absorption problems may need as much as 2,000 IU a day.

Depression, Mood and Seasonal Affective Disorder (SAD)

·         Research on Vitamin D and depression by the Vitamin D Council found a correlation between low levels of vitamin D and depression, but was unable to say whether low vitamin D status was a causal factor in depression or a result.

·         However, one double-blind randomised trial – the gold standard in research –published in the Journal of Internal Medicine in 2008 concluded that: “There appears to be a relation between serum levels of 25(OH)D and symptoms of depression. Supplementation with high doses of vitamin D seems to ameliorate these symptoms indicating a possible causal relationship.”

·         Vitamin D deficiency is certainly associated with Seasonal Affective Disorder (SAD), a form of depression that usually begins in the autumn and continues throughout the winter months.  SAD affects almost 10% of the population, more women than men and normally starts in early adulthood. Symptoms include feeling sad or anxious, fatigue, concentration problems, and irritability.A new study led by researchers from the University of Georgia does identify low vitamin D levels with greater risk of Seasonal Affective Disorder. Co-author Michael Kimlin points out that vitamin D plays a part in the production of both dopamine and serotonin, noting that past research has associated low levels of these neurotransmitters with depression.

“Therefore, it is logical that there may be a relationship between low levels of vitamin D and depressive symptoms.” 

Reduced infections

Vitamin D helps regulate the expression of genes that affect your immune system and its ability to fight bacterial and viral pathogens. So it’s an important supplement in the flu season.

·         Several studies, including a Yale study published in 2010, have found that supplement levels varying from 600 IU to 1,200 IU to 2,000 IU a day reduce the risk of colds and flu in the winter.

Faster recovery after muscular injury

·         A recent report in the journal Nutrients showed faster recovery of muscle strength after injury.

Reduced risk of falls in the elderly

Since skeletal muscle needs vitamin D, as well as calcium and magnesium, it’s logical that deficiency can weaken muscles.

·         Studies have indeed shown that supplementing with vitamin D can decrease the risk of falls by an average of 50%. The minimum blood level to aim for appears to be at least 30ng/ml vitamin D-calcidiol.

CONCLUSIONS

“I would challenge anyone to find a nutrient or any factor that has such consistent anti-cancer benefits as vitamin D. The data are really quite remarkable.”

 Dr Edward Giovannucci, Professor of Nutrition and Epidemiology, Harvard School of Public Health

To give a historical context, our hunter-gatherer ancestors spent a good deal of time outdoors and during the summer months made, in their skin, up to 20,000 IU of vitamin D a day.

So it is clear that our bodies adapted to far higher levels of vitamin D than most of us experience today. We have limited our sun exposure, and cultural or religious factors can make this limitation even more acute.

Ageing and obesity are also important, as they reduce the ability of the skin to make vitamin D by up to 75%; and a number of drugs (including anticonvulsants, the anti-inflammatory corticosteroids, and cholestyramine), are also linked to lower blood levels of vitamin D-calcidiol.

There is a wide variety of advice on what vitamin D supplement levels prevent deficiency or protect against disease – from a minimum of 400 IU to as much as 5,000 IU!

Here are some of the recommendations from health bodies and leading researchers:

The USA’s Endocrine Society, Vitamin D Council and Institute of Medicine

  • A blood level of up to 20 ng/ml vitamin D-calcidiol indicates you are deficient in vitamin D.

With vitamin D levels in this range you’re more likely to develop osteoporosis and your bones may be affected because your body isn’t absorbing enough calcium. You’re more likely to fracture or break bones and more likely to have a fall.

Consensus Statement from the UK’s Cancer Research UK, Diabetes UK, Multiple Sclerosis Society, National Heart Forum, National Osteoporosis Society, British Association of Dermatologists and Primary Care Dermatology Society

  • Those at risk of low sun exposure should take a 10 mcg / 400 IU supplement of vitamin D a day (7 mcg a day for children aged 6 months to 5 years). However, this implies a blood level of vitamin D-calcidiol of slightly below 20ng/ml.

Dr Walter Willett, Department of Nutrition, Harvard School of Public Health

After analysing 20 clinical trials on vitamin D and the effect on preventing fractures and falls, he concludes that blood levels of 30 to 44 ng/ml vitamin D-calcidiol provide optimal benefits, without increasing health risks.

  • “These levels can be best obtained with oral doses in the range of 1,800 to 4,000 IU vitamin D per day.”

Dr Cedric Garland, University of California San Diego School of Medicine

  • Optimum level of 40-60 ng/ml vitamin D-calcidiol, implying 3,000 to 6,000 IU of vitamin D supplements.

Dr William Grant, Sunlight, Nutrition and Health Research Center

  • Suggests 3,000 to 4,000 IU a day.

Dr Robert Heaney, for the Osteoporosis Research Center

After researching Vitamin D for decades, he concluded that a blood level of at least 30 ng/ml of vitamin D-calcidiol is needed.

  • Implies a supplement level of 1,700 IU of Vitamin D per day.

Dr Heaney has stated that the term “deficiency” for nutrients such as vitamin D doesn’t necessarily mean a clinical disease state, but an increased risk for certain diseases, such as osteoporosis, cancer, infections, diabetes, hypertension and cardiovascular disease. People who are seemingly healthy may really be “deficient.”

University of California Berkeley

They produced an excellent report on Vitamin D, which concludes that:  “Unless you’ve been tested and know that your (blood) vitamin D level is adequate—at least 20 ng/ml vitamin D-calcidiol, though we think 30 ng/ml is a better target—consider taking a supplement.”

  • They conclude that a supplement level of 1,000 IU may be enough for many people, although ‘your healthcare provider may advise a higher dose (usually 1,000 to 3,000 IU)’,

Although there are significant variations in the expert advice above, it is possible to summarise as follows:

Deficient level Optimal level WINTER supplement level to get to 35 ng/ml SUMMER supplement level to get to 35 ng/ml Higher levels recommended and safe
Less than 20 ng/ml 30 – 40
ng/ml
say 35 ng/ml
2,500 IU
(62.5 mcg)
800 IU
(20 mcg)
4,000 IU(100 mcg)

What is the safe level?

At the heart of medicine is the advice to ‘Do no harm’, and we are very mindful of this axiom. Too much vitamin D can cause an abnormally high blood calcium level, which could result in confusion, abnormal heart rhythm, nausea, constipation, and even kidney stones. A lot more is not necessarily better.

The European Food Safety Authority have recently published new guidance on the upper tolerable levels for vitamin D, which suggests that adults should not exceed 4,000 IU (100 mcg) per day as there is “no evidence for safety above this level”.

The UK NHS states: “Do not take more than 100 mcg (4,000 IU) of vitamin D a day, as it could be harmful. This applies to adults, including pregnant and breastfeeding women and the elderly, and children aged 11-17 years. Children aged 1-10 years should not have more than 50 mcg a day (2,000 IU)”.

The US National Institutes of Health agrees with an Upper Safe Limit of: “4,000 IU/day for children 9 years and older, and adults, including pregnant and lactating women.”

In the interest of balance, however, we should note that Doctors Heaney and Holick (see above) carried out a study in 2002 and in Michael Holick’s words showed …

“… that you can take up to 10,000 IU of vitamin D a day for almost a half a year and not worry about vitamin D intoxication”.

This echoes work from Professor Reinhold Vieth of the University of Toronto, a vitamin D pioneer. He researched all the old publications that claimed that excess vitamin D was toxic, only to discover no actual scientific papers showing toxicity!  He says …

“… 10,000 IU/day could not be toxic since we make that much and more from a full exposure to sun”.

RECOMMENDATIONS

 First a caveat –  vitamin D is not a magic bullet!

Before we reach our own conclusion on the optimum level, it’s important to note a serious point about health research. Human lifestyles are very varied – which makes research on isolated nutrients incredibly difficult to interpret.

Vitamin D on its own is not going to going to magically transform anyone’s health. And despite clear evidence that low vitamin D levels are linked to a wide range of life-threatening diseases, it’s quite probable that low vitamin D status is also a marker for a generally unhealthy lifestyle – lack of physical activity, overweight and poor diet.

OUR FINAL RECOMMENDATION

So finally – and bearing in mind the caveat above and some conflicting expert advice – what level of vitamin D should you aim for?

Our recommendation for vitamin D supplementation, allowing for normal dietary and sunshine sources, is as follows:

Recommended total daily D3
supplement level in WINTER
Recommended total daily D3 supplement level in SUMMER
Children over 10 and Young adults under  20 1,000 IU 25 mcg 400 IU 10 mcg
Adults with outdoor occupations 1,000 IU 25 mcg 800 IU 20 mcg
All other adults 2,500 IU 62.5 mcg 800 IU 20 mcg

 

IMPORTANT NOTE: Many people will already be taking an A-Z supplement. These will normally include vitamin D at a level of between 200 and 400 IU. Other supplements like NutriShield may contain up to 800 IU of vitamin D3.

Therefore an ADDITIONAL daily supplement of 2,000 IU of vitamin D3 is ideal and safe.

Children of over 10 years and young adults up to 20 could take a supplement of 1,000 IU a day or 2,000 IU every other day.

Cancer patients are at even greater risk of Vitamin D depletion as chemotherapeutic drugs may cause photosensitivity reactions and malabsorption of many nutrients. The literature supports a supplement level of at least 5,000 IU a day in this case, although ONLY under an oncologist’s guidance.

A NOTE ABOUT THE IMPORTANCE OF COMBINING NUTRIENTS

However persuasive the case for vitamin D supplementation is, there are many other nutrients with excellent substantiation for health support and disease prevention, including curcumin and Omega 3; so it’s the combination of foods and supplements that has the biggest impact on health.  It would be a mistake to rely on Vitamin D alone.

For this reason, Dr Paul Clayton designed the comprehensive health supplement called NutriShield, which contains not just vitamins and minerals, but Omega 3, curcumin, anti-inflammatory polyphenols (derived from fruits and vegetables), lycopene, lutein, vitamin K2 and more. It already contains 800 IU of vitamin D3.

As outlined above, an additional 2,000 IU a day in winter is safe and indicated by the research for all adults, and is even more important for older people and those with darker skins.

 

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REFERENCES BY SECTION AND SUBJECT

Deficiency and Measurement

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Food and Nutrition Board, Institute of Medicine (USA). Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academy Press, 2010.

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Looker AC, Pfeiffer CM, Lacher DA, Schleicher RL, Picciano MF, Yetley EA. Serum 25-hydroxyvitamin D status of the US population: 1988-1994 compared with 2000-2004. Am J Clin Nutr 2008;88:1519-27.

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National Institutes of Health (USA). https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/

National Institute of Standards and Technology (USA). NIST releases vitamin D standard reference material, 2009.

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Health Threats and Benefits
All-cause Mortality and Meta-Surveys

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Giovannucci E. Can vitamin D reduce total mortality? Arch Intern Med 2007;167:1709-10.

Grant WB. An estimate of the global reduction in mortality rates through doubling vitamin D levels. European Journal of Clinical Nutrition (2011) 65, 1016–1026

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Alzheimer’s and Dementia

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Arthritis

Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, Saag K. Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women’s Health Study. Arthritis Rheum 2004;50:72-7.

Asthma

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Blood Pressure

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Zhao G, Ford ES, Li C, Croft JB. Serum 25-hydroxyvitamin D levels and all-cause and cardiovascular disease mortality among US adults with hypertension: the NHANES linked mortality study. J Hypertens. 2012 Feb;30(2):284-9.

Cancer

Freedman DM, Looker AC, Chang S-C, Graubard BI. Prospective study of serum vitamin D and cancer mortality in the United States. J Natl Cancer Inst 2007;99:1594-602.

Garland C, University of California San Diego School of Medicine. Higher levels of vitamin D correspond to lower cancer risk. (online) Plos ONE, April 6 2016

Jenab M, Bueno-de-Mesquita HB, Ferrari P, van Duijnhoven FJB, Norat T, Pischon T, et al. Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations: a nested case-control study. BMJ 2010;340:b5500.

Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr June 2007 vol. 85 no. 6 1586-1591

Mohr SB, Gorham ED, Alcara JE, Kane CJ, Macera CA, Parson JK, Wingard DL, Garland df. Serum 25-Hydroxyvitamin D and Prevention of Breast Cancer: Pooled Analysis. Anticancer Research September 2011 vol. 31 no. 9 2939-2948.

National Cancer Institute (USA). https://www.cancer.gov/about-cancer/causes-prevention/risk/diet/vitamin-d-fact-sheet

Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL, O’Sullivan MJ, et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 2006;354:684-96.

Depression and Seasonal Affective Disorder

Jorde R, Sneve M, Figenschau Y, Svartberg J, Waterloo K. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial.  Jnl Int Med 2008; 264(6);599-609

Stewart AE, Roecklein KA, Tanner S, Kimlin MG. Possible contributions of skin pigmentation and vitamin D in a polyfactorial model of seasonal affective disorder. Med Hypotheses. 2014 Nov;83(5):517-25.

Diabetes

Chiu KC, Chu A, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr 2004;79:820-5.

Hyppönen E, Läärä E, Reunanen A, Järvelin M-R, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 2001; 358: 1500–03

Pittas AG, Dawson-Hughes B, Li T, Van Dam RM, Willett WC, Manson JE, et al. Vitamin D and calcium intake in relation to type 2 diabetes in women. Diabetes Care 2006;29:650-6.

Falls and Muscle injury

Barker T, Henriksen VT, Martins TB et al. Higher Serum 25-Hydroxyvitamin D Concentrations Associate with a Faster Recovery of Skeletal Muscle Strength after Muscular Injury. Nutrients 2013, 5(4), 1253-1275

Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, Orav JE, Stuck AE, Theiler R, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ 2009;339:b3692.

Ensrud KE, Ewing SK, Fredman L, Hochberg MC,Cauley JA, Hillier TA, et al. Circulating 25-hydroxyvitamin D levels and frailty status in older women. J ClinEndocrinolMetab 2010;95:5266-5273.

Heart Disease and Stroke

American Heart Assoc/American Stroke Assoc. www.stroke.ahajournals.org/content/47/Suppl_1/

Heaney RP. Long-latency deficiency disease: insights from calcium and vitamin D. Am J Clin Nutr 2003;78:912-9.

Judd S, Tangpricha V. Vitamin D Deficiency and Risk for Cardiovascular Disease. Circulation. 2008 Jan 29; 117(4): 503–511.

Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle P, Koerfer R. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 2006;83:754-9.

Stroke Association (USA). http://strokeconnection.strokeassociation.org/Summer-2015/Vitamin-D-May-Make-A-Difference

Infections

Sabetta, J. Vitamin D May Help Prevent Respiratory Tract Infections. (online) Plos ONE, June 16 2010.

Osteoporosis and other Bone Disease

American Academy of Dermatology. Position statement on vitamin D. November 1, 2008.

Buckley LM, Leib ES, Cartularo KS, Vacek PM, Cooper SM. Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1996;125:961-8.

Compston JE, Horton LW. Oral 25-hydroxyvitamin D3 in treatment of osteomalacia associated with ileal resection and cholestyramine therapy. Gastroenterology 1978;74:900-2.

de Sevaux RGL, Hoitsma AJ, Corstens FHM, Wetzels JFM. Treatment with vitamin D and calcium reduces bone loss after renal transplantation: a randomized study. J Am Soc Nephrol 2002;13:1608-14.

International Osteoporosis Foundation Report 2009

Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006;354:669-83.

LeBoff MS, Kohlmeier L, Hurwitz S, Franklin J, Wright J, Glowacki J. Occult vitamin D deficiency in postmenopausal US women with acute hip fracture. JAMA 1999;251:1505-11.

Lukert BP, Raisz LG. Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann Intern Med 1990;112:352-64.

National Institutes of Health (USA). Osteoporosis and Related Bone Diseases National Research Center. Osteoporosis overview. October 2010.

Parfitt AM. Osteomalacia and related disorders. In: Avioli LV, Krane SM, eds. Metabolic bone disease and clinically related disorders. 2nd ed. Philadelphia: WB Saunders, 1990:329-96.

Rickets

Goldring SR, Krane S, Avioli LV. Disorders of calcification: osteomalacia and rickets. In: DeGroot LJ et al., eds. Endocrinology. 3rd ed. Philadelphia: WB Saunders, 1995:1204-27.

Wagner CL, Greer FR; American Academy of Pediatrics Committee on Nutrition [Breastfeeding]. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics 2008;122:1142-1152.

Ward LM, Gaboury I, Ladhani M, Zlotkin S. Vitamin D-deficiency rickets among children in Canada. CMAJ 2007;177:161-166.

Wharton B, Bishop N. Rickets. Lancet 2003;362:1389-400.

Other Diseases

Gough H, Goggin T, Bissessar A, Baker M, Crowley M, Callaghan N. A comparative study of the relative influence of different anticonvulsant drugs, UV exposure and diet on vitamin D and calcium metabolism in outpatients with epilepsy. Q J Med 1986;59:569-77.

Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006;296:2832-8.

North American Menopause Society. The 2012 hormone therapy position statement of: The North American Menopause Society. Menopause 2012;19:257-71.

Pappa HM, Bern E, Kamin D, Grand RJ. Vitamin D status in gastrointestinal and liver disease. Curr Opin Gastroenterol 2008;24:176-83.

Levels and Safety

Cranney C, Horsely T, O’Donnell S, Weiler H, Ooi D, Atkinson S, et al. Effectiveness and safety of vitamin D. Evidence Report/Technology Assessment No. 158 prepared by the University of Ottawa Evidence-based Practice Center under Contract No. 290-02.0021. AHRQ Publication No. 07-E013. Rockville, MD: Agency for Healthcare Research and Quality, 2007.

Davis CD, Hartmuller V, Freedman M, Hartge P, Picciano MF, Swanson CA, Milner JA. Vitamin D and cancer: current dilemmas and future needs. Nutr Rev 2007;65:S71-S74.

Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad H, Weaver CM. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2011;96:1911-30.

Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr 2008;88:582S-6S.

Malone M. Recommended nutritional supplements for bariatric surgery patients. Ann Pharmacother 2008;42:1851-8.

Medscape.com. http://www.medscape.com/viewarticle/829508

National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (USA). Osteoporosis Handout on Health. NIH Publication No. 11-5158; 2011.

Wolpowitz D, Gilchrest BA. The vitamin D questions: how much do you need and how should you get it? J Am Acad Dermatol 2006;54:301-17.