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Vitamin D deficiency

Key learning points:

- Vitamin D assays may be inaccurate and imprecise

- Low vitamin D status may not be clinically apparent until it is severe

- Vitamin D derived from sunlight may have more benefits than vitamin D from supplements

Vitamin D deficiency is reportedly common worldwide1 and has been linked to an increased risk of a wide range of diseases.2 There has been a tendency to recommend high blood levels of vitamin D for optimum health,3 and such levels can generally only be achieved with supplementation. However, recent research is challenging much of the past “evidence” about vitamin D and its relationship with disease outcomes, as well as the level that is needed for good health.4,5 Furthermore, there is some evidence that vitamin D from supplements may not be as effective as vitamin D through sun exposure of the skin.

Types of vitamin D

The term vitamin D is often used generically to refer to the group of steroid chemicals that are part of the vitamin D pathway. It is clearer to use the accurate terminology; thus, vitamin D includes both ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3), while 25-hydroxyvitamin D (25(OH)D) is the form that is most commonly measured in the blood to test a person's vitamin D status (and includes both 25(OH)D2 derived from vitamin D2, and 25(OH)D3 derived from vitamin D3). The active form is 1,25-dihyroxyvitamin D (1,25(OH)2D), again including both 1,25(OH)2D2 and 1,25(OH)2D3.

The subscripted numbers following the D refer to variations in the side chains of the steroid molecule and those following the (OH), the number of hydroxyl groups attached to the molecule. In this article 25(OH)D concentrations are provided in nanomoles per litre (nmol/L), and the vitamin D content of food or supplements in micrograms (μg) [International Units (IU)].

The main source of vitamin D for much of the world's population is through the synthesis of vitamin D3 in skin exposed to sunlight. It is important to note that only exposure to shorter wavelengths of ultraviolet (UV) radiation, categorised as UV-B, can initiate synthesis of vitamin D3. On winter days in the UK, even when it is sunny, there may not be sufficient UV-B content in sunshine to initiate vitamin D synthesis. This means that no amount of time outdoors or skin exposed will result in vitamin D production. A small amount of vitamin D3 and vitamin D2 is present in food, e.g. fatty fish such as salmon, eggs, meat (vitamin D3) and mushrooms (vitamin D2) as well as in foods such as cereal and margarine that often have vitamin D added to them. Vitamin D supplements contain either vitamin D3 or vitamin D2; multivitamins commonly contain 5μg [200 IU] or 10 μg [400 IU] of vitamin D2 or vitamin D3.

Causes of vitamin D deficiency

The definition of vitamin D deficiency varies across different countries, but is most commonly either 6

The primary source of most of our vitamin D is the skin's exposure to UV radiation in the UV-B wavelengths. Intake in the diet or from supplements is a secondary source. This means that risk factors for vitamin D deficiency include:

1.Limited time outdoors: Those at increased risk include office workers, people who are institutionalised (e.g. elderly in care homes), those who are sun avoidant for any reason (e.g. a past history of skin cancer), and those at high risk of skin cancer who are taking photosensitising medications.

2.Limited skin exposure when outdoors: UV-B radiation does not penetrate through clothing or glass. Thus cultural norms of wearing clothes that cover the majority of the skin, preferences for fairer skin, particularly among some ethnic groups,7 and extreme sun protection will limit vitamin D production.

3.Insufficient levels of UV-B radiation when outdoors: In some locations, particularly those further from the Equator (including all of the UK), there may be insufficient UV-B radiation for vitamin D synthesis to occur from sun exposure of the skin, particularly during winter. In addition, at this time of year, it is often cold so a limited amount of skin is exposed. Midday is the best time to be outdoors to take advantage of any limited UV-B radiation that may be available.

4.Low dose of UV-B radiation to the relevant biological precursors: UV-B does not penetrate well into the skin and can be partly blocked, for example, by the thicker layer of melanin pigment in darker skin or assiduous application of sunscreen. Thus darker skinned people are at higher risk of vitamin D deficiency, particularly when UV-B levels are low. Usual use of sunscreen may decrease, but not completely block vitamin D production in the skin.

Combinations of these factors further increase the risk of vitamin D deficiency. Older people (more than 65 years of age) may make vitamin D less efficiently, but the evidence is mixed and the factors above may explain the lower 25(OH)D levels often seen in older people. Similarly, obese people are more likely to be vitamin D deficient than those of normal weight. This may be due to increased storage of vitamin D in fat, or behavioural factors that limit sun exposure, such as less time outdoors with skin exposed to the sun.

Low dietary intake is unlikely to be a major risk factor for deficiency as it is generally only a minor contributor to overall vitamin D status. Malabsorption disorders can reduce the absorption of oral forms of vitamin D. Nutrient requirements in the UK are described according to a number of metrics, including the reference nutrient intake (RNI), which represents the amount of the nutrient that is enough, or more than enough, for approximately 97.5% of the people in a group.5 For vitamin D, this is the intake that will maintain more than the minimum level of 25nmol/L. Based on the available data, a recent report proposes a RNI of 10μg [400 IU] per day for the UK general population aged four years and above, including pregnant women, and safe intake levels of 10 μg [400 IU]/day for children aged one to four years and 8.5-10 μg [340-400 IU]/day for infants aged 0 to 11 months.5 Of note, in the most recent National Diet and Nutrition Survey, the mean vitamin D intake was well below the RNI for all age groups, with dietary intake of the order of 2-4 μg [80-160 IU]/day, and mean intake from diet plus supplements of 2.3-5 μg [90-200 IU]/day.8

Signs and symptoms of vitamin D deficiency

Vitamin D deficiency is a silent disorder until it becomes severe. Infants with a prolonged severe deficiency may develop rickets, with symptoms of bone pain and signs including skeletal deformities such as knock knees or bow legs, bone pain or tenderness, and muscle weakness. In adults prolonged vitamin D deficiency can cause osteomalacia that presents as bone tenderness or pain in the spine, shoulders, ribs or pelvis, and/or muscle weakness. For less severe vitamin D deficiency, a good history focusing on the risk factors noted earlier, should alert the health professional that a patient is at high risk of being vitamin D deficient.

Many other disorders have been linked to low 25(OH)D levels, but, at this time the evidence remains inconclusive. In particular, although observational studies have shown a link between low 25(OH)D levels and increased disease, vitamin D supplementation has not been shown to be effective at reducing disease risks.

How is vitamin D deficiency diagnosed?

To the best of our current knowledge, the serum or plasma concentration of 25(OH)D is the best measure of vitamin D status. Some recent research has suggested that health effects may be more closely linked to levels of some of the other vitamin D metabolites, but at this stage it is speculative.

Treatment options for vitamin D deficiency

Severe vitamin D deficiency requires treatment with vitamin D supplementation. Tolerable upper limits for vitamin D long-term are:5

1.100μg [4000 IU]/day for adults and children aged 11-17 years.

2.50μg [2000 IU]/day for children aged one to 10 years.

3.25μg [1000 IU]/day for infants.

Doses for short-term treatment of severe deficiency may be higher. The treatment of vitamin D insufficiency is less clear cut and there should be consideration of the individual circumstances and the time of year. Sun exposure of the skin releases other chemicals in addition to vitamin D, and these may also have benefits for a person's health that are not achieved with vitamin D supplementation. Mild vitamin D insufficiency may be best managed by careful sun exposure, with short periods outdoors with as much skin exposed as possible. This is the most efficient pattern of sun exposure to gain the benefits and minimise the risks of skin cancers. Mild vitamin D insufficiency in winter, when UV-B levels are low, will generally improve in spring and summer.

Careful sun exposure in summer and autumn to attain 25(OH)D levels of around 80 nmol/L prior to winter will prevent vitamin D deficiency (8 Vitamin D supplementation is thought to be quite safe, with toxic effects (such as high blood calcium levels leading to calcium deposition in soft tissues, renal calculi and cardiovascular toxicity) being uncommon even with very high dose supplementation.

There is now very little evidence to support supplementation to reach very high 25(OH)D levels of 100nmol/L or more. Indeed there are some reports of U-shaped associations whereby both lower and higher 25(OH)D levels are associated with increased disease risks, including for all-cause mortality. Importantly, the active form of vitamin D works to increase the uptake of dietary calcium; adequate calcium intake is required in conjunction with vitamin D supplementation.


Vitamin D deficiency may be less common than it has been previously reported as a result of recent advances in the standardisation of vitamin D assays, but it is still a concern for the UK population. There is now a much better understanding of the risk factors for deficiency, and consequently, a decreasing need to test for vitamin D status.

People at a high risk of vitamin D deficiency and particularly those with a combination of risk factors should be treated with vitamin D supplementation. Additionally, they should be encouraged to seek some sun exposure - keeping in mind that short periods of sun exposure to a large area of skin is best for vitamin D production, and safest in terms of skin cancer risk.


National Diet and Nutrition Survey:

Scientific Advisory Committee on Nutrition:


1. Hilger J, Friedel A, Herr R, Rausch T, Roos F, Wahl DA, et al. A systematic review of vitamin D status in populations worldwide. British Journal of Nutrition 2014;111(1):23-45

2. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. The American Journal of Clinical Nutrition 2008;87(4):1080S-6S

3. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. The Journal of Clinical Endocrinology and Metabolism 2011;96(7):1911-30

4. Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Institute of Medicine of the National Academies, 2010

5. Scientific Advisory Committee on Nutrition. Draft Vitamin D and
Health report. United Kingdom: Scientific Advisory Committee on Nutrtion, 2015

6. Lucas R, Neale R. What is the optimal level of vitamin D? - Separating the evidence from the rhetoric. Australian Family Physician 2014;43(3):119-22

7. Guo S, Gies P, King K, Lucas RM. Sun exposure and vitamin D status as Northeast Asian migrants become acculturated to life in Australia. Photochemistry Photobiology 2014;90(6):1455-61

8. National Diet and Nutrition Survey: Results from Years 1-4 (combined) of the Rolling Programme (2008/2009-2011/12). Public Health England, 2014