Testing and treating vitamin D deficiency

Published in MedicineWise News

Date published: About this date

Clinical content may change after this date. This information is not intended as a substitute for medical advice from a qualified health professional. Health professionals should rely on their own expertise and enquiries when providing medical advice or treatment.

Increased interest in vitamin D deficiency, reports of its high prevalence in Australia and a suggested role in a range of health conditions has led to a surge in vitamin D testing and uncertainty about management. When is testing and treatment warranted? This News provides information on who is at risk of vitamin D deficiency, when vitamin D testing is of value and appropriate supplementation in those identified as being deficient.

Background

People obtain most of their vitamin D from the sun. When skin is exposed to sunlight it produces vitamin D3 (colecalciferolA). Production is influenced by the season, latitude, skin colour and skin exposure. Small amounts of vitamin D — as either vitamin D3 or vitamin D2 (ergocalciferol) — are consumed in the diet. Both vitamin D2 and D3 are converted by the liver to 25-hydroxyvitamin D (25-OHD) which circulates in the blood. This is further processed by the kidney to produce the active form of vitamin D, calcitriol (1,25-dihydroxyvitamin D). Assays measure 25-OHD to estimate vitamin D levels within individuals.

No consensus on optimal level of serum 25-OHD

Generally, serum 25-OHD levels > 50 nmol/L are agreed to indicate vitamin D adequacy.1-3 However, there is ongoing debate about the optimal level of serum 25-OHD.2,3

People with 25-OHD levels < 25 nmol/L are at increased risk of rickets or osteomalacia and are truly deficient.1,3,4 They should receive supplements.1

Parathyroid hormone levels, bone turnover and muscle weakness are higher in mild deficiency (serum 25-OHD 25–50 nmol/L).1 Some studies have shown a decrease in falls and fractures among older people (> 65 years) taking vitamin D and calcium supplements and Australian guidelines recommend 1000 IU of vitamin D daily to reduce fracture risk in the elderly. 1  The evidence for supplementation among younger people with mild deficiency is less clear with the US Institute of Medicine (IOM) pointing out that only some people are at risk of inadequacy and deficiency symptoms at levels between 30 nmol/L and 50 nmol/L. 2  The variability of vitamin D tests (see below) may also impact on decisions about recommending supplements in people with mild deficiency if they do not fall into a high-risk category (see Some groups are more likely to be deficient).

There is a lack of definitive evidence for any health benefit when serum 25-OHD levels are 75 nmol/L or above. There is an emerging possibility that serum levels above 125 nmol/L may have adverse health effects.2,3 Supplementation with the aim of achieving such high serum levels is not supported by evidence.

Vitamin D testing has limitations

There are a number of different tests used in Australia to determine vitamin D levels and there has been considerable variability between the tests and between laboratories.5-9 In some studies blood samples have been classified as adequate by one assay or laboratory but deficient by another assay or laboratory.7-9 New international standards and laboratory participation in external quality assessment programsB should improve these results.

Consider vitamin D testing in people with identified risk factors (see Some groups are more likely to be deficient). The value of testing community-dwelling people without risk factors is uncertain.

A. May also be spelt cholecalciferol.
B. International External Quality Assessment Scheme for Vitamin D (DEQAS) or Royal College of Pathologists of Australasia Association of Clinical Biochemists Quality Assurance Program (RCPA/AACB QAP).

Things to consider when requesting or interpreting vitamin D tests

Consider the time of year — serum levels vary with season. They are highest at the end of summer when people are most likely to be exposed to sunlight and lowest at the end of winter. Consider the skin colour and age of the individual and ask how they typically dress when outside. Ask questions about lifestyle — individuals who spend time outdoors, are physically active or are recreational walkers are less likely to have low vitamin D levels.10,11 If an individual is from one of the high risk groups they are more likely to be deficient.2

Moderate to severe deficiency is uncommon in the general population

Studies in community-dwelling members of the general Australian population consistently report mean 25-OHD levels > 50 nmol/L (adequate range) in winter and in summer (Table 1).11-17 Typically, less than 10% of study participants were moderately or severely deficient, although a substantial minority had vitamin D levels in the mildly deficient range (25–50 nmol/L).

Some groups are more likely to be deficient

While most Australians are likely to have adequate vitamin D levels, testing and supplementation is advisable in particular groups.

People who may benefit from testing, because they are at greater risk of being moderately or severely deficient are:

  • People who are housebound, particularly those over 65 years or resident in aged care facilities — prevalence of up to 77% reported in Australian facilities.1,18,19
  • People with naturally dark skin — prevalence of 44% among children from an east African background attending a Melbourne health clinic.20
  • People who cover themselves for religious or cultural reasons — prevalence of 68% in a Sydney study where three quarters of the women were veiled and 80% in a Melbourne study of women who were veiled or had darker skin.21,22

Others who may be at risk include people who:

  • use medicines that interfere with vitamin D metabolism (see Co-morbidities and interactions)
  • have malabsorption syndromes
  • have limited access to sunlight because of a chronic illness or disability or because of working conditions such as shift work
  • avoid the sun as they are at increased risk of skin cancers
  • are obese.1,15,23,24

Table 1. Reported 25-hydroxyvitamin D levels in Australian studies

Location
n
Mean 25-OHD level (nmol/L)
25-OHD < 50 nmol/L
25-OHD < 25 nmol/L
South-east Qld13,16
414 75 (summer), 55 (winter)
23%
8% (≤ 38 nmol/L)
Brisbane11 126 57 and 52C (winter)
42%
10%
Perth17 197 58
34%
Maryborough (Vic)12 113 54

Geelong14 861 81 (summer), 59 (winter)
30%
7% (< 28 nmol/L)
Tasmania15 262 53D
49%
9%
C. Mean for male and females, respectively.
D. Community control group only.

Everyday outdoor activity should ensure adequate vitamin D

Normal day-to-day outdoor activities should ensure adequate vitamin D production. In summer, short walks of less than 10 minutes around morning or afternoon tea time on most days should ensure adequate vitamin D (around 1000 IU) for people with moderately fair skin if the hands, face and arms are exposed. In winter longer periods of exposure may be needed, particularly in the southern states (e.g. 15 minutes at lunchtime in Sydney or 30 minutes at lunchtime in Hobart). People with darker skin are likely to need longer exposures in winter and summer.1

Advise people that prolonged sun exposure is counterproductive — it increases the risk of skin cancers and if an individual stays in the sun for too long, degrades the vitamin D produced in the skin.1,25,26 Further information about sun exposure can be found on the Cancer Council website.

Sunscreens use is unlikely to contribute to vitamin D deficiency

Theoretically, sunscreens can reduce vitamin D synthesis by > 95% but in an Australian randomised trial vitamin D levels rose similarly among people using a placebo cream every day and those using a sun protection factor (SPF) 17 sunscreen every day over summer.12 This is probably because people do not apply sunscreen to all of their exposed skin, do not use enough sunscreen or do not reapply as often as they should.2,12,27

Continue to advise people to use sun protection if they will be in the sun for an extended period of time and to avoid unprotected exposure in summer between 10 am and 2 pm (11 am and 3 pm during daylight saving).1

Treat moderate to severe deficiency with supplements

Australian consensus guidelines suggest that people diagnosed with moderate or severe vitamin D deficiency (serum 25-OHD < 25 nmol/L) should receive 3000 to 5000 IU of colecalciferol as a supplement per day for 6 to 12 weeks.1 Diet alone does not provide an adequate amount of vitamin D so ongoing supplements may be necessary for people at high risk of vitamin D deficiency.1

Consider recommending short periods of sun exposure, increased physical activity and improved dietary calcium intake to people with mild deficiency.1,28 Supplementation may be necessary in groups at risk or if such advice is impractical.

If you wish to re-test vitamin D levels, wait at least 3 months after starting supplementation.1

Most vitamin D supplements are available over-the-counter and contain colecalciferol. Supplements that contain colecalciferol alone are available as a 1000 IU dose. In supplements that combine colecalciferol with other active ingredients the amount of colecalciferol ranges from 100 IU to 1000 IU. Supplements containing 200 IU or less are insufficient to treat deficiency.1

Advise patients who require a supplement that multivitamins and halibut or cod liver oil capsules should not be used to treat vitamin D deficiency. Multivitamins contain amounts of vitamin D that are too low to treat deficiency while the dose of liver oil required to treat vitamin D deficiency may result in an overdose of vitamin A.29

Do not use calcitriol (the active form of vitamin D) to treat vitamin D deficiency, except for specific indications (e.g. renal failure). It has a narrow therapeutic index and carries a high risk of hypercalcaemia, and monitoring is required.1,29

Effectiveness, other than on bone health, is unproven

Until outcome driven randomised controlled trials are undertaken the importance of vitamin D in non-bone disease remains unproven.2 Studies reporting associations between low vitamin D levels and these diseases are often observational, have design limitations or are contradictory.

Co-morbidities and interactions

Vitamin D supplements are nearly always contraindicated in people with hypercalcaemiaE and should be used with caution in people with hyperphosphataemia.29 Vitamin D supplements may also interact with other medicines (Table 2).27,30

Toxicity and adverse effects are uncommon

Vitamin D toxicity is uncommon.4 Toxicity cannot occur through exposure to sunlight but can occur if excessive doses of vitamin D supplements are taken.27

Very large single doses of vitamin D may increase the risk of fractures. In a randomised trial conducted among older Australian women (≥ 70 years) those who took a single oral annual dose of 500 000 IU of colecalciferol were at greater risk of falls or fractures than women in the placebo groups.31

The recent US IOM review concluded that toxicity is unlikely in people taking up to 10 000 IU of vitamin D daily.2 However, it pointed to emerging evidence from observational studies of adverse health effects among people with 25-OHD above 125 nmol/L.2 For this reason, and because the benefits and risks of long-term supplementation are uncertain, the IOM recommended that the daily dose of vitamin D should not exceed 4000 IU.2

E. Specialist advice is necessary.

Table 2: Potential interactions between vitamin D and other medicines27,29,30

Drug/class
Effect / changes required
phenytoin, phenobarbital

Increases the metabolism of vitamin D, thereby reducing its effects and disturbing calcium metabolism.

Monitor treatment and increase vitamin D dose if necessary.
orlistat

Reduces the absorption of fat soluble vitamins.

Take vitamins, including vitamin D, 2 hours before or after taking orlistat.

thiazide diuretics

Has the potential to lower the urinary excretion of calcium increasing risk of hypercalcaemia.

Monitor serum calcium in people taking vitamin D (with or without calcium).

digoxin

Very large doses of vitamin D may increase serum calcium levels and can theoretically enhance the effects of digoxin which may increase the risk of arrhythmias.

Monitor serum calcium in people taking vitamin D and digoxin.

 

Help your patients understand more about vitamin D using the new NPS resources. Available in English, Arabic, Chinese, Dari, Farsi, Korean, Turkish and Vietnamese. Order these and other free resources from our health professional resources orders page.

External reviewers
Prof Michael Kimlin, Director, NHMRC Centre for Research Excellence in Sun and Health, Director, AusSun Research Lab, Queensland University of Technology

Professor Rebecca S Mason, Head, Physiology, Deputy Director, Bosch Institute, President, ANZ Bone and Mineral Society, University of Sydney

Reviewers

Dr John Dowden, Editor, Australian Prescriber

Dr Graham Emblem, General Practitioner, Toowoomba

Dr Sarah Gani, General Practitioner and Medical Educator, Blacktown

Benafsha Khairwala, Managing Editor, Journal of Pharmacy Practice and Research

A/Prof Jennifer Martin, Head, PA-Southside Clinical School

Deborah Norton, QUM Pharmacist, West Vic DGP

Simone Rossi, Managing Editor, Australian Medicines Handbook

Dr Guan Yeo, Clinical Education Consultant and General Practitioner, Berowra

References
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