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Rapid Responses: Rapid Responses published:
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Deficiency of sunlight and vitamin D
- Edward Hutchinson (13 June 2008)
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More evidence is needed before supplementation
- Miles D Witham (16 June 2008)
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Frustrations with Vitamin D treatments
- Avril Danczak (16 June 2008)
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Widespread severe vitamin D-deficiency in Scotland
- Helga M Rhein (17 June 2008)
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Vitamin D deficiency in Asylum seekers and refugees
- Anan Raghunath, Rena Downing, Jezz Thompson and Peter Campion (18 June 2008)
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Re: More evidence is needed before supplementation
- Eddie Vos (18 June 2008)
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Skin Cancer, Sunlight and Vitamin D Deficiency
- S. Alexander Holme, Dr Alexander V Anstey (23 June 2008)
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Vitamin D Deficiency In Psychiatric Inpatients
- John A Dent, Girija Kottalgi (23 June 2008)
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Unlicensed vitamin D can be prescribed if licenced high dosed vitamin D is unavailable
- Helga M Rhein (24 June 2008)
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Challenges in Prevention and treatment of Vitamin D deficiency.
- vijay bangar, Fisher JP, Haig R, Hungin APS (27 June 2008)
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Vitamin D deficiency
- Shirwan A. Mirza, MD, FACP, FACE (29 June 2008)
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Correcting vitamin D deficiency
- Sanjeev Patel, Ashok Bhalla, Karl Gaffney, Richard Keen, Abbas Ismail, Ira Pande, Jonathan Reeve, Jonathan Tobias (30 June 2008)
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Vitamin D Deficiency
- Mitchell Simson (3 July 2008)
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Edward Hutchinson, Patient Retired
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In "Circulating Vitamin D3 and 25-hydroxyvitamin D in Humans": Hollis, Wagner,Drezner, Binkley show only when circulating 25(OH)D levels are above 50ng 125nmol/l are the body's basic daily need met and surplus D3 can be stored. "Hypovitaminosis D in British adults at age 45y" Hyppönen, Power show half of the adult UK population had 25(OH)D concentrations <40nmol/L during the winter and spring and remain <75nmol/l throughout the year. "The urgent need to recommend an intake of vitamin D that is effective" (authors too numerous to list here) explains supplemental intake of 400 IU vitamin D3/d has only a modest effect on blood concentrations of 25(OH)D, raising them by 7–12 nmol/L, depending on the starting point. While 2000iu/daily/D3 may raise 25(OH)D from 50 to 80 nmol/L it will not and cannot raise 25(OH)D to attain and maintain levels between 125- 150nmol/l necessary to enable the body to build a reserve. "The case against ergocalciferol (vitamin D2) as a vitamin supplement" Houghton Vieth show many people do not use D2 as effectively as D3. Although Holick's paper "Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D." shows at low levels, using assured quality, D2 may be as effective as D3 in some individuals, while D3 remains cheaper and more effective the logic of using D2 rather than D3 remains suspect. Competing interests: None declared |
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Miles D Witham, Clinician Scientist, Ageing and Health University of Dundee, Ninewells Hospital, Dundee DD1 9SY
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Editor, Holick [1] is right to highlight the high prevalence of vitamin D insufficiency in many groups of people living at higher latitudes. However, the evidence base to support general supplementation, including aggressive fortification, does not currently exist. There are now indeed an impressive array of observational data that suggest that low vitamin D levels are associated with a wide variety of diseases, including diabetes, cardiovascular disease and cancer. This does not necessarily mean that intervention with vitamin D supplementation will improve health outcomes – witness the problems of hormone replacement therapy despite encouraging observational data, not to mention the lack of effect and possible harms surrounding vitamins A,E and beta-carotene supplementation [2]. Whilst traditional vitamin D toxicity may be unlikely even with relatively large doses of vitamin D, we cannot be sure that long-term vitamin D supplementation does not in fact cause some harms – and the case for benefits is far from proven. The recent WHI study of low-dose calcium and D supplementation [3] showed no change in risk of colorectal cancer, diabetes, stroke or cardiovascular disease, but did produce an increase in the number of renal stones. Recent observational data from the Framingham study [4] suggests that the risk of cardiovascular events may be lowest at 25 hydroxy D levels of around 60nmol/L, possibly increasing slowly at levels above this. The only way to resolve these uncertainties is to conduct large- scale, randomised controlled trials comparing different doses of vitamin D versus placebo. Only then will we be able to weigh up the balance of benefit and risk, decide which groups of people would gain net benefit, and thus make safe and sensible recommendations on vitamin D supplementation. Dr Miles D Witham
References: 1. Holick MF. Deficiency of sunlight and vitamin D. BMJ 2008; 336: 1318-9. 2. Bjelakovic G et al. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev 2008 Apr 16;(2):CD007176. 3. Hsia J et al. Calcium/vitamin D supplementation and cardiovascular events. Circulation 2007;115(7):846-54. 4. Wang TJ et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008;117(4):503-11. Competing interests: Dr Witham has received grant income from the Scottish Government, Chest Heart and Stroke Scotland, Diabetes UK and Heart Research UK to investigate the effects of vitamin D on the cardiovascular system |
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Avril Danczak, General Practitioner The Alexandra Practice, 365 Wilbraham Road Manchester M16 8NG
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I welcome the interest in Vitamin D deficiency as it is extremely common in our mixed inner city population, and many doctors seem unaware of the problem and fail to consider it in their differential diagnoses. I have commonly noticed Vitamin D deficiency in association with plantar fasciitis, fatigue,low mood,muscular pains in pregnancy and low birth weight,as well as the expected musculoskeletal pains, which can be non specific, assymetrical and without radiological or bone enzyme abnormalities. The children of mothers with low vitamin D levels commonly feed poorly and can be lethargic,unhappy toddlers even before they develop late signs of frank rickets.Symptoms are also common in at risk men..ie those with inadequate sunlight exposure. Asian populations have high rates of heart disease, diabetes and TB. These are all associated with Vitamin D deficiency, which is especially common in those communities. Fustratingly, suitable oral treatments have become unavailable in the last year and it can be hard to get sufficient replacement levels in many patients. There is no suitable daily supplement of Vitamin D alone listed in the BNF, and over the counter vitamins are usually mixtures, with doses of Vitamin D too low to replenish stores in the severely deficient patient.Preparations of Vitamin D for daily use contain calcium, which often causes constipation and hence poor adherence. High dose oral Ergocalciferol preparations are effective and popular with patients,but these have been not available in pharmacies locally for some time due to "manufacturing difficulties".No one seems to be responsible for ensuring supplies of Vitamin D are adequate. Injections are painful, use more staff time and require medical input. It is also fustrating that almost all the Vitamin D preparations contain gelatine, which makes them unsuitable for those who wish to observe Halal principles. Vitamin D deficiency is usually a whole family problem. All family members need encouragement to get sun exposure and take appropriate supplements. All health professionals need to be aware that Vitamin D metabolism is complex and linked to cancers, heart disease and diabetes. The reduction in all cause mortality seen with Vitamin D supplementation (referred to by Sievenpiper et al in their article BMJ 2008;336:1371-4) is not matched by statins.We spend millions ensuring that people get their statins, shouldnt we do the same for vitamin D? I remember debates about supplementing foods etc when I was a medical student 30 years ago. Isnt it time to be proactive about this problem, at all levels of the NHS? Competing interests: None declared |
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Helga M Rhein, General Practitioner Sighthill Health Centre, 380 Calder Road, Edinburgh EH11 4AU
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15 June 2008 I couldn’t agree more with Holick (BMJ, 14/6/2008, editorial, p.1318) and Sievenpiper et al (BMJ, 14/6/2008, Lesson of the week, p.1371) about the urgent need to highlight the neglected subject of vitamin D deficiency in the UK. We have found in our General Practice in Edinburgh a (to us) surprisingly high prevalence of gross vitamin D deficiency and continue to do so. The deficiency affects not only our South Asian patients but also a considerable number of those with white skin colour. The following are our yet unpublished figures from Sept 07: Between 2005 and 2007, bloods were taken from 99 patients, aged 15 to 85, suspected of having a possible vitamin D deficiency, those of South Asian origin or other ethnic minorities, those with vague musculo-skeletal symptoms or who are overweight, on anti-epileptic drugs, use sunscreen or make up, are house-bound or get little exposure to sun light. According to the definitions of most vitamin D researchers, insufficient vitamin D concentrations are those below 75 nmol/l. In our sample, there are only 2% with a sufficient vitamin D level. Levels below 25nmol/l are defined as severe deficiency, in our sample 47%. Hyppoenen et al have recorded similar figures for Scotland, Am J Clin Nutr, 2007.
Helga Rhein (GP) Sighthill Health Centre 380 Calder Road Edinburgh EH11 4AU helga.rhein@lothian.scot.nhs.uk Competing interests: None declared |
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Anan Raghunath, General Practitioner The Quays, Hull, East Yorkshire, Rena Downing, Jezz Thompson and Peter Campion
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We undertake clinical sessions in a specialist community GP unit that provides medical care for refugees and asylum seekers. The majority of such clients we deal with come from the Asian and middle-eastern countries. They often present with a multitude of physical and psychological symptoms many of which is taken to represent their traumatic past experiences in their own countries. In recent months there has been a both an increased request for as well as positive results of low 25-hydroxy vitamin-D levels in these patients presenting with non-specific symptoms of muscluo-skeletal pains and "somatisation disorders". The tests had been mainly instigated by one GP with experience of working abroad with similar patient groups. We feel that with increasing influx of ethnic minority groups in UK, there is now a case for routine testing of Vitamin D levels in these patients, particularly women and children, presenting to their GP with vague unexplained symptomatology. There is also a urgent need for primary care research in this area to both to raise awareness amogst health professionals of the rapid "re-emergence" of this clnical entity in UK and to help produce guidelines for diagnosis and management. Competing interests: None declared |
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Eddie Vos, maintains www.health-heart.org Sutton (Qc) Canada J0E 2K0
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Dr. Witham agrees there is "widespread deficiency"
and unlikely harm from "relatively large doses of vitamin D", and
likely benefit in many age-related diseases yet he proposes more and by
necessity extremely long-duration trials before recommending supplementation.
He cites examples of negative but non related nutrient or hormone studies as an excuse for NOT now taking steps to resolve this recognized deficiency.
Clearly, it is time to act if only on the basis of this one trial in an over age 65 U.K. population and where 22% of first fractures were prevented by vitamin D supplementation. This involved a total of 37.5 mg cholecalciferol, taken every 4 month as a 100,000 IU [2.5 mg D3] pill, during 5 years. Harm is hypothetical; the harm from bone fractures is a painful reality. Such trials would thus be unethical. While 50,000 IU pills may currently be hard to obtain in the U.K., in the U.S. 100 such pills are a simple $30 mail-order purchase [product source: Bio-Tech-Pharm.com] and where the taking of 1 pill every 2 months would reach the level of the above trial [cost ~$10/5 years], and go a long way resolving deficiency. Competing interests: None declared |
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S. Alexander Holme, Consultant Dermatologist Queen Margaret Hospital, Dunfermline. KY12 0SU, Dr Alexander V Anstey
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Sir, The BMJ editorial by Professor Michael Holick on Vitamin D deficiency highlights a dilemma for clinicians and public health physicians when advising patients and the public on sun exposure. [1] Too much sun is the main risk factor for skin cancer; on the other hand, too little sun may lead to vitamin D deficiency. Hollick has reported previously that white populations may become vitamin D deficient in winter and that only minimal exposure to ultraviolet (UV) radiation (5-10 minutes sun exposure three times a week of hands, arms and face) is required during spring, summer and autumn to reverse this. [2] The message from the articles by Hollick [1] and Sievenpiper [3] highlighting the consequences of vitamin D deficiency should not confuse the health promotion message emphasising the importance of UV protection to prevent skin cancer. Non-melanoma skin cancer is now the UK’s commonest malignancy with a steeply rising incidence, and malignant melanoma is the commonest cancer in the 15-34 year group. [4] In his editorial figure, Hollick suggests sunscreen use to be a cause of vitamin D deficiency. This is misleading as there is no convincing evidence to support this claim in normal populations not actively avoiding sunlight; although sunscreen use does appear to cause a modest reduction in 25-hydroxyvitamin D levels. [5,6] In cases where sunscreen use has been implicated in deficiency, other risk factors such as ethnic skin pigmentation, institutional residency, age or occlusive clothing, have also been present. Two recent publications have reported an additional risk factor for vitamin D deficiency to be the presence of severe photosensitivity such as occurs in erythropoietic protoporphyria or cutaneous lupus erythematosus. [7,8] It is individuals with risk factors for vitamin D deficiency, such as the Asian women described by Sievenpiper, who should be targeted for education or assessment, not the white population in whom the risk of skin cancer is higher. Dr S. Alex Holme FRCP, Consultant Dermatologist, Queen Margaret Hospital, Whitefield Road, Dunfermline. KY12 0SU Dr Alex V. Anstey MD FRCP Consultant Dermatologist, Director of Photodermatology Unit, Department of Dermatology, Cardiff University. CF14 4XN 1. Holick MF. Deficiency of sunlight and vitamin D. BMJ 2008; 336: 1318-9. 2. Hollick MF. Sunlight “D”llemma: risk of skin cancer or bone disease and muscle weakness. The Lancet 2001; 357: 4-6. 3. Sievenpiper JL, McIntyre EA, Verrill M, Quinton R, Pearce SHS. Unrecognised severe vitamin D deficiency. BMJ 2008; 336: 1371-4. 4. www.isdscotland.org/ cancer/allcancer types/incidenceandmortality 5. Marks R, Foley P, Jolley D et al. The effect of regular sunscreen use on vitamin D levels in an Australian population. Archives of Dermatology 1995; 131: 415-421. 6. Farrerons J, Barnadas M, Rodríguez J et al. Clinically prescribed sunscreen (sun protection factor 15) does not decrease serum vitamin D concentration sufficiently either to induce changes in parathyroid function or in metabolic markers. British Journal of Dermatology 1998; 139: 422-427. 7. Holme SA, Anstey AV, Badminton MN, Elder GH. Serum 25- hydroxyvitamin D in erythropoietic protoporphyria. British Journal of Dermatology 2008; 159: 211-213. 8. Renne J, Werfel T, Wittman M. High frequency of vitamin D deficiency among patients with cutaneous lupus erythematosus. British Journal of Dermatology 2008; doi: 10.1111/j.1365-2133.2008.08632: EPub ahead of Print. Competing interests: None declared |
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John A Dent, Consultant Psychiatrist West london Mental Health Trust UB1 3EU, Girija Kottalgi
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Dear Sir We read with interest the recent editorial regarding vitamin D deficiency and the consequences for both physical and mental health. A recent study on prevalence of vitamin D deficiency among our long term male psychiatric inpatients (n =17) has found severe vitamin D deficiency in 15 i.e. less than 25nmol/L 25 hyrdoxycholecalciferol (25OHD) and borderline deficiency in the remaining 2 patients (25 to 50 nmol/L 25OHD). Although this is a small study there is no reason to think that our patients are untypical of the urban psychiatric inpatient population in the UK. Our patients report that the oral formulation of vitamin D replacement is unpalatable due to it being a large chalky tablet. We have found that oral replacement with calcium ergocalciferol 400 to 800 units per day to be only partially effective even where compliance is supervised. Unfortunately the alternative of long acting intramuscular injection of 300,000 units, while effective, has not been available for the past three months due to lack of availability of supplies nationally in the UK. Yours sincerely Dr Girija Kottalgi ST2 West London Mental Health NHS Trust Dr John Dent Consultant Psychiatrist West London Mental Health NHS Trust Tiangga E, Gowda A, Dent J. Vitamin D deficiency in psychiatric in- patients and treatment wih daily supplement of calcium and ergocalciferol. In Press Psych. Bull 2008;32 Competing interests: None declared |
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Helga M Rhein, GP Sighthill Health Centre, 380 Calder Road, Edinburgh EH11 4AU
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John Dent, Girija Kottalgi and colleagues mention the present dearth in the UK of high dosed vitamin D tablets or injections to treat deficient patients. I had similar experiences some months ago but have now started prescibing unlicensed medication, with the agreement of local prescibing advisors, as I find it unacceptable to let people with osteomalacia go without treatment. Our local pharmacist located capsules of 20 000 IU Cholecalciferol ("Dekristol" from Germany). I prescribe about 20, initially, one to take every second day, check U+Es after the first week of taking them, in case of rare hypersensitivity, and re-check vitamin D concentration, PTH, U+Es, Ca, PO4 after the course is finished. Hope this can be of help to anyone wanting to treat osteo- malacic patients. Helga Rhein, GP Competing interests: None declared |
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vijay bangar, Consultant Physician Calderdale and Huddersfield Foundation Trust, Halifax, Wset Yorkshire, HX3 OPW, Fisher JP, Haig R, Hungin APS
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The article by Sievenpiper et al1 highlighted the lack of awareness of the severity of symptoms and methods of presentation of vitamin D deficiency (VDD) and the potential dangers of misdiagnosis. It also highlighted the excellent outcomes achievable with correct treatment. However, treatment is proving impossible at present and delivery systems are beset with confusion. Despite reference in the BNF2 and a review by Holick 3 there is a near impossible challenge in translating strategies into action. Sievenpiper et al 1 used intramuscular Vitamin D (IMVD) to treat their patients. IMVD is available in a 300,000 i.u. and 600,000 i.u. preparations containing vitamin d3 (ergocalciferol). It is well recognised that the number of patients with Vitamin D deficiency, requiring treatment doses, is huge, approaching 100% in the high risk populations (particularly migrants from the tropical world and their offspring) . IMVD is licensed in patients who have intestinal malabsorbtion or chronic liver disease2 . This excludes most of the patients in this group. Moreover, the manufacturer recommends that IMVD be administered using glass syringes, although many practitioners have reported use of IMVD using plastic syringes without any problem. Despite enquires with syringe manufacturers; we have not managed to obtain glass syringes. The use of IMVD in this population requires these issue to be addressed by the manufacturers and by regulatory bodies. As a fallback there is available an oral preparation of 250 mcg or 10,000 i.u (HDVD) of Vitamin d3 (ergocalciferol). This preparation can be used within licence although this is not very clear in the BNF. Holick 3 recommends 50,000 i.u. per week. Using HDVD 5 days per week, delivers a dose of 50,000 i.u. per week. In our locality (West Yorkshire) we developed a guideline using this approach at primary care level. However, the HDVD preparation has not been available since the start of this year and IMVD treatment but this also has been unavailable since February. We welcome the publicity drawn to the issue of Vitamin D deficiency by these articles. There are large populations in the United Kingdom who need treatment and prevention for this condition. We would urge the pharmaceutical authorities to clarify the issues around IMVD, and make suitable preparations available. We would also urge them to address the problem of non-availability of HDVD. Reference List (1) Sievenpiper JLMEAVM, Quinton R, Pearce S.H.S. Unrecognised severe vitamin D deficiency. BMJ 336, 1371-1374. 14-6-2008. (2) Vitamin d. British National Formulary 53, 513-514. 1-3-2007. (3) Holick MF. Vitamin D deficiency. New England Journal of Medicine 357, 266-281. 2008. Competing interests: None declared |
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Shirwan A. Mirza, MD, FACP, FACE, Private Practice New York, USA
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I am surprised that some of our colleagues still question the adequacy of the clinical evidence for the benefits of vitamin D. The reference range of 25 hydroxy vitamin D 75-150 nmol/l in Europe (32-100 ng/ml in the USA) is wide enough to prevent that. In my experience of treating more than 2000 patients with vitamin D deficiency in the cloudy upstate New York, you need to give almost 300,000-500,000 IU of vitamin D2 to raise 25, hydroxy vitamin D by 10 ng/ml. Intoxication with vitamin D ( a serum level of 375 nmol/l or 150 ng/ml)is nearly impossible when patients are given reasonable doses under medical supervision. This unfounded fear of vitamin D intoxication has been cited in European countries like Germany as a reason not to fortify milk with vitamin D. Vitamin D benefits mirror the widespread presence of vitamin D receptors in the body. Most people think that vitamin D impacts only the bones. If this was the case, why would you find vitamin D receptors in lymphocytes, brain, heart, blood vessels, prostate, colon, breasts, thyroid, ovaries, testicles, lungs ...? Many observational studies have clearly shown the anti-cancer effects of vitamin D, its favorable effects in preventing auto-immune disorders such as multiple sclerosis and type 1 diabetes. Vitamin D is crucial for muscle strength, hence the fatigue as a prominent symptom of vitamin D deficiency. Proximal myopathy is a cardinal feature of osteomalacia, which can lead to falls and fractures. If you want to see more patients with vitamin D deficiency, look in your own practice: those patients with fatigue, aches and pains, and proximal muscle weakness are very likely to be vitamin D deficient. Those patients who present with atypical chest pains, in whom cardiac causes have been ruled out, most likely have rib pains rather than the fashionable term "costochondritis" (press on the xiphoid process gently to see the exquisite tenderness. Those patients with tender bones (they don't like to be touched) are very likely to have vitamin D deficiency. Vitamin D is a public health problem. It is the duty of governments to revise the reference ranges of vitamin D to make it in line with the numbers mentioned by Dr. Holick. These governments should also update the required daily dose of vitamin D (1000-2000 IU of vitamin D3 a day). Dermatologists should soften their stance on sun exposure. 5-10 minutes of daily sun exposure is considered a judicious dose of sun rays for vitamin D production. 1. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266-8 2. Holick MF. Resurrection of vitamin D deficiency and rickets J. Clin. Invest; 2006: 116(8): 2062-2072 Competing interests: None declared |
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Sanjeev Patel, Consultant Physician SM51AA, Ashok Bhalla, Karl Gaffney, Richard Keen, Abbas Ismail, Ira Pande, Jonathan Reeve, Jonathan Tobias
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Vitamin D deficiency is common and based on epidemiological data is associated with many diseases as outlined by Holick in his recent editorial. Food fortification and other public health strategies may improve population vitamin D levels however there is still considerable debate about what constitutes a normal vitamin D level for human health, particularly so for non-skeletal benefits, such as reduction in cancers and autoimmune diseases. We would suggest that the concept of “tissue specific vitamin D deficiency” is important to consider, rather than one serum level being relevant for all organ systems. Only interventional studies will allow us to prevent and treat potential vitamin D associated diseases, with the confidence that we are achieving specific outcome goals, rather than correcting a nominal serum level of 25-vitamin D. There is also the major problem regarding availability of both ergocalciferol and cholecalciferol particularly in the UK. Ideally a number of preparations from more than one manufacturer should be available, with certificates of analyses, so that the actual dose of vitamin D per tablet is clear. Currently, as previous correspondents have described, treatment of high risk individuals is severely impeded and clinicians are having to make ad-hoc arrangements to import vitamin D preparations. Whilst this is possible, particularly in the hospital setting, community pharmacists will find it difficult to consistently hold supplies and usually this would be an unlicensed preparation. This surely needs concerted action by governments and regulatory bodies to ensure that supplies of vitamin D, preferably as cholecalciferol are available. Competing interests: None declared |
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Mitchell Simson, Assistant Professor of Internal Medicine UNM School of Medicine, Albuquerque, NM 87131
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Despite living in the sunny southwestern United States with sunshine about 300 days annually, I have found widespread Vitamin D deficiency in my general Internal Medicine population. About a year ago, I began to check Vit. D 25-OH levels on all my patients, no matter what age. I have seen significant deficiency in over 85% (ages 22 through 90). I can guarantee that any patient who works indoors (especially those who sit behind computers), and all patients with diabetes, arthritis and coronary disease have low levels. These have included middle-aged and elderly patients who have been taking routine calcium and vitamin D supplementation (~800 I.U. vitamin D daily). Many patients have required 2 rounds of 50,000 I.U. therapy to get themselves into the low normal range before daily supplementation can continue. One wonders about the amount and/or true bioavailability of the vitamin in such supplements. Competing interests: None declared |
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