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Taking vitamin D levels seriously

Dr Muhammad Haroon, Dr Mark J. Phelan and Dr Michael J. Regan explain the definition and causes of vitamin D deficiency and look at some Irish studies which have examined rates of vitamin deficiency here

Vitamin D deficiency is preventable and treatable. It can present with a spectrum of clinical manifestations, including non-specific musculoskeletal pain, weakness and fatigue. It is relatively common at northern latitudes and occurs when individuals have inadequate levels of the nutrient vitamin D.

In its fully evolved florid form, vitamin D deficiency causes rickets and osteomalacia. Symptoms of less florid hypovitaminosis D can be subtle and can go undiagnosed for many years – with dire consequences for bone health, at a minimum. Such patients can be misdiagnosed with fibromyalgia, chronic fatigue syndrome, myositis, systemic lupus erythematosus or other connective tissue diseases.

Suboptimal (i.e. inadequate) vitamin D can be associated with secondary hyperparathyroidism, increased bone turnover and secondary osteoporosis.

A potent inhibitor

Besides its well-defined role in maintaining musculoskeletal health, 1,25-dihydroxyvitamin D is a potent inhibitor of cellular growth, stimulator of insulin secretion, modulator of immune function and inhibitor of renin production. There are vitamin D receptors in muscle and the brain.

These facts could well explain the recent observations that vitamin D-deficient people are more prone to solid tumours, autoimmune diseases (e.g. multiple sclerosis and diabetes mellitus), hypertension and an increased risk of falls.

Let us now discuss ‘cut-off’ issues and terminology as they pertain to defining what constitutes a ‘normal’ vitamin D level. Specifically, we should address the terms ‘deficiency’, ‘inadequacy’ and ‘insufficiency’.

Most experts are now refining their concept of what constitutes vitamin D deficiency. Most are now using a higher reference range for what constitutes the cut-off for ‘normal’ vitamin D status and use simple terms when thinking about, talking about and researching vitamin D status.

Most now agree that hypovitaminosis D (i.e. vitamin D ‘deficiency’) should be defined as a 25-hydroxy (25-OH) vitamin D level ≤ 75nmol/L (i.e., ≤ 30ng/ml in the U.S.). In our group in Cork, we currently accept this cut-off and further subdivide our vitamin D deficient patients into mild, moderate, severe and very severely deficient groups. We use, and suggest, that one should solely use the term ‘deficient’ (or ‘not deficient’) when talking about 25-OH vitamin D status. Thankfully, worldwide now, the confusing and clinically useless terms ‘inadequacy’ and ‘insufficiency’ are appropriately being relegated to history.

Vitamin D is a steroid hormone that consists of two molecules, vitamin D2 (ergocalciferol, synthesized by plants) and vitamin D3 (cholecalciferol, synthesised in the skin). Both forms of the vitamin are used to fortify various foods and in over-the-counter supplements.

Vitamin D is further hydoxylated in the liver to 25-OH vitamin D. Both forms are metabolised to their respective 25-OH vitamin D forms. 25-OH vitamin D is the major circulating form of vitamin D. 25-OH vitamin D is metabolised in the kidneys by the enzyme 25-OH D-1α-hydroxylase to its active form, 1,25-dihydroxyvitamin D. The renal production of 1,25-dihydroxyvitamin D is tightly regulated by plasma parathyroid hormone (PTH) levels, serum calcium and phosphorus levels. Because of its long half-life, 25-OH vitamin D measurement is the only useful one to use for assessing vitamin D status and stores in any patient.

The measurement of 1,25(OH)2D concentrations can be misleading because compensatory rises in PTH due to hypovitaminosis D can cause increases in the concentration of 1,25(OH)2D through its action on kidneys.

Exposure to sunlight

Vitamin D can be acquired by exposure of skin to sunlight or ingestion of foods containing vitamin D. Only a few foods, primarily fish oils, egg yolks and liver, naturally contain substantial amounts of vitamin D.

In Europe, very few foods are supplemented with vitamin D. Consequently, most vitamin D is acquired by its synthesis in skin (from sun exposure). However, trying to get adequate vitamin D from this source is problematic as it increases the risk of melanoma.

Vitamin D deficiency has been described virtually everywhere on the planet. However, it is more prevalent in northern latitudes. Research has shown that adults in Europe, northern United States and Canada are particularly at risk. Groups at highest risk include elderly persons, housebound or institutionalised persons, African-Americans (and others with dark skin pigment) and adults who spend most of their time working indoors. There is significant seasonal variation in vitamin D status in healthy young adults, with the lowest concentrations occurring in winter and spring. One study in the Am J Clin Nutr (2002) revealed that women examined in the winter or spring were 2.4-3.6 times more likely to have hypovitaminosis D compared to women examined in the summertime.

Similar figures have been replicated in other studies. A 2005 systemic review by Gaugris et al. revealed that the prevalence of vitamin D inadequacy was 12.5 per cent to 76 per cent among osteoporotic women.

As alluded to earlier, receptors for 1,25 (OH) vitamin D have been identified in skeletal muscle tissue and a recent meta-analysis (2004) reported a 22 per cent decrease in falls associated with the use of vitamin D supplements.
In a review at the Boston Medical Centre, 32 per cent of the students and doctors (18–29 years of age) were vitamin D deficient at the end of the winter. One likely contributory explanation is that during the winter season, more ultra violet B photons are absorbed by the ozone layer even if people were outside in the open air. During winter months above the latitude of 37°, there are even more marked decreases in the number of ultraviolet B photons reaching the earth’s surface. Therefore, very little vitamin D3 is produced in the skin during the winter. The latitude in Ireland is significantly higher than this and we are likely to have very ineffective vitamin D exposure periods (even if outside) during the autumn and winter months.

Let us look at a few studies from Ireland: a 2004 food consumption survey carried out in Ireland has shown that a considerable proportion of Irish adults have very low dietary intakes of vitamin D and that they are largely dependent on sunlight to maintain adequate levels of vitamin D.

Another recent study in the European Journal of Clinical Nutrition (2005) showed that up to 36 per cent of Irish women (aged 51-69 years) had sub-optimal vitamin D status during winter time. A more recent study in the Ir J Med Sci. (2006) examined the vitamin D intake and status in young girls (11-13 years) and elderly women; the results found that young girls had very low vitamin D intake and very low levels of serum vitamin D compared to the elderly population.

In this latter study, it was suggested that the increased use of supplemental vitamin D in the elderly cohort might have explained the discrepancy in vitamin D levels. Our group at the Arthritis & Osteoporosis Centre, Division of Rheumatology, South Infirmary-Victoria University Hospital, Cork has a special clinical and research interest in vitamin D deficiency and bone health.

We have examined the prevalence of low vitamin D status in our outpatients. In 2007, we carried out a six-month study investigating the prevalence of vitamin D deficiency in all consecutive new patients seen in our rheumatology clinics at first visit (all referred by their GPs). The patients were recruited from January 1 to June 30, 2007. In total, 264 new patients were seen over this time-period and 231 consented to partake in the study.

The results of this study were presented as a poster abstract at this year’s annual European rheumatology meeting in Paris in June (EULAR) and as an oral/podium presentation at this year’s American College of Rheumatology (‘ACR’) annual meeting in San Francisco in October.

In this study, we found that 70 per cent of the cohort had hypovitaminosis D (≤53 nmol/L). Overall, 26 per cent had severe hypovitaminosis D (≤25 nmol/L) and 21 per cent of those who had low vitamin D had secondary hyperparathyroidism.

Twenty-four per cent of the patients were aged ≥65 years; 65 per cent of these elderly patients (≥65 years) were vitamin D deficient and 25 per cent were severely deficient. It was very interesting that in those aged <30 years of age, 78 per cent had vitamin D deficiency.

Our principal findings were a) that the prevalence of low vitamin D in the cohort of 231 new patients was extremely common, and b) that the age of the patient did not substantially influence whether they had vitamin D deficiency or not.

If we had used the cut-offs which we now use (in 2008), our figures would have been even more striking: 87 per cent of all new patents seen at our rheumatology clinics over a 6-month period would have had vitamin D deficiency with 25-OH vitamin D levels ≤ 75nmol/L (≤ 30ng/ml in the US).

In the context of rheumatologic diseases, among the research reports at this year’s ACR meeting, there were many abstracts showing a high prevalence of low vitamin D in patients with SLE, rheumatoid arthritis, juvenile arthritis and scleroderma.

Some abstracts suggested an association between low levels of vitamin D and greater inflammatory disease activity. Indeed, researchers from Johns Hopkins University, Baltimore, USA described that in women with rheumatoid arthritis (but not men), low serum vitamin D status had an independent association with physical functioning.

Conclusion

In conclusion, vitamin D deficiency represents a major health concern. Poor awareness of the condition exists among most clinicians despite the fact that excellent options for prevention and treatment are available.

In contrast to the popular belief that vitamin D deficiency is only a disease of the older, housebound, sunlight-deprived or institutionalised person – this is clearly not the case. Research from across the world has shown that it exists in all age groups, even children.

Physicians should have a high index of suspicion for this condition because, in the world of rheumatology, geriatrics and general practice, its recognition and management offers us the opportunity to optimise, at a minimum, bone health and muscle strength.

In the wider medical world, maximising vitamin D levels over many years may help delay the onset of diabetes mellitus, aid the immune system and help in tumour surveillance. It is time to take vitamin D seriously. Its time has come.

• Dr Muhammad Haroon, Rheumatology Specialist Registrar, Waterford Regional Hospital; with Dr Mark J. Phelan and Dr Michael J. Regan, Consultant Rheumatologists, Arthritis and Osteoporosis Centre, Department of Rheumatology, South Infirmary-Victoria University Hospital, Cork.

Posted in Nutrition on 05 December 2008
Tags: vitamins

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abortion, accupuncture, ACE inhibitors, acne, ADHD, alcohol, allergies, Alzheimer's, anaemia, anaethesia, anorexia, antibiotics, antidepressants, antihistamine, anxiety, appetite control, arthritis, ASCOT, aspirin, asthma, atherosclerosis, autism, autoantibodies, back pain, beta carotene, beta-blockers, bipolar disorder, birth, bleeding, blindness, blood pressure, body dysmorphic disorder, body mass, breast cancer, breast feeding, bronchitis, Caesarean section, calcium, cancer, carcinogens, carcinoma, cardiac syncope, cardiolgy, cataracts, cervical cancer, chemotherapy, child psychiatry, children, cholesterol, clinical trial, clopidogrel, Clostridium difficile, cognitive behavioural therapy, colectomy, colic, colorectal cancer, complementary and alternative therapies, contraception, COPD, coronary care, coronary stents, Crohn's, cystic fibrosis, defibrillator, dementia, depression, dermatology, diabetes management, diet, disability, DNA, Down's syndrome, eating disorders, echinacea, ECT, eczema, elderly people, endoscopy, epilepsy, erectile dysfunction, euthanasia, exercise, fat, fertility, fitness, flu pandemic, fluoxetine, folic acid, food labelling, fracture, fragile X syndrome, general surgery, genetics, gerontology, GIK infusion therapy, GORD, gout, haemodialysis, hearing, heart attack, heart disease, heart failure, heart health, hepatitis, HIV, hospital care, HPV, HRT, hyperglycaemia, hypertension, hypoglycaemia, IBD, ICU, incontinence, infant, infant mortality, infection, inflammatory bowel disease, influenza, invasive candidiasis, IQ, Irish Heart Foundation, irritable bowel syndrome, keyhole surgery, kidney disease, laser, learning difficulties, leukaemia, liver disease, lumbar disk herniation, lung cancer, lung disease, lymph nodes, macular degeneration, macular oedema, magnetic resonance imaging (MRI), malaria, malnutrition, Marfan syndrome, media, medical ethics, medical research, medication, meningitis, mental illness, metabolic syndrome, migraine, miscarriage, mortality rate, MRSA, multiple sclerosis (MS), NCHDs, nephrology, neurology, OAB, obesity, obstetrics, occupational health, ocular medicine, omega-3, opthalmology, oral cancer, organ transplantation, orthopaedics, osteoporosis, otolaryngology, ovarian cancer, paediatrics, pain management, pancreatic cancer, panic, Parkinson’s disease, patient safety, patient-physician communication, personality disorders, physiotherapy, plastic surgery, polio, practice, pre-eclampsia, pregnancy, preventative health care, probiotics, prostate cancer, psoriasis, psychiatric admission, psychiatry, psychotherapy, PTSD, public health, quality of life, radiology, radiotherapy, rectal cancer, reproductive health, research, resuscitation, rheumatoid arthritis, rheumatology, rhinitis, salt, SARS, schizophrenia, screening, seizures, self harm, sexual abuse, sexual health, sexually transmitted infections, SGA, sinusitis, skin cancer, sleep disorders, smoking, smoking ban, spinal injury, sports medicine, statins, stress, stroke, substance abuse, suicide, supplement, surgery, syncope, technology, teenagers, testosterone, thoracic surgery, thrombosis, thyroid cancer, tonsillectomy, tonsillitis, Tourette's syndrome, toxicology, travel medicine, tuberculosis, tumour angiogenesis, type 1 diabetes, type 2 diabetes, ulcer, ulcerative colitis, urinary incontinence, vaccine, vitamins, weight, WHO, women's health, World Health Assembly

«Previous article | Next article»

Taking vitamin D levels seriously

Dr Muhammad Haroon, Dr Mark J. Phelan and Dr Michael J. Regan explain the definition and causes of vitamin D deficiency and look at some Irish studies which have examined rates of vitamin deficiency here

Vitamin D deficiency is preventable and treatable. It can present with a spectrum of clinical manifestations, including non-specific musculoskeletal pain, weakness and fatigue. It is relatively common at northern latitudes and occurs when individuals have inadequate levels of the nutrient vitamin D.

In its fully evolved florid form, vitamin D deficiency causes rickets and osteomalacia. Symptoms of less florid hypovitaminosis D can be subtle and can go undiagnosed for many years – with dire consequences for bone health, at a minimum. Such patients can be misdiagnosed with fibromyalgia, chronic fatigue syndrome, myositis, systemic lupus erythematosus or other connective tissue diseases.

Suboptimal (i.e. inadequate) vitamin D can be associated with secondary hyperparathyroidism, increased bone turnover and secondary osteoporosis.

A potent inhibitor

Besides its well-defined role in maintaining musculoskeletal health, 1,25-dihydroxyvitamin D is a potent inhibitor of cellular growth, stimulator of insulin secretion, modulator of immune function and inhibitor of renin production. There are vitamin D receptors in muscle and the brain.

These facts could well explain the recent observations that vitamin D-deficient people are more prone to solid tumours, autoimmune diseases (e.g. multiple sclerosis and diabetes mellitus), hypertension and an increased risk of falls.

Let us now discuss ‘cut-off’ issues and terminology as they pertain to defining what constitutes a ‘normal’ vitamin D level. Specifically, we should address the terms ‘deficiency’, ‘inadequacy’ and ‘insufficiency’.

Most experts are now refining their concept of what constitutes vitamin D deficiency. Most are now using a higher reference range for what constitutes the cut-off for ‘normal’ vitamin D status and use simple terms when thinking about, talking about and researching vitamin D status.

Most now agree that hypovitaminosis D (i.e. vitamin D ‘deficiency’) should be defined as a 25-hydroxy (25-OH) vitamin D level ≤ 75nmol/L (i.e., ≤ 30ng/ml in the U.S.). In our group in Cork, we currently accept this cut-off and further subdivide our vitamin D deficient patients into mild, moderate, severe and very severely deficient groups. We use, and suggest, that one should solely use the term ‘deficient’ (or ‘not deficient’) when talking about 25-OH vitamin D status. Thankfully, worldwide now, the confusing and clinically useless terms ‘inadequacy’ and ‘insufficiency’ are appropriately being relegated to history.

Vitamin D is a steroid hormone that consists of two molecules, vitamin D2 (ergocalciferol, synthesized by plants) and vitamin D3 (cholecalciferol, synthesised in the skin). Both forms of the vitamin are used to fortify various foods and in over-the-counter supplements.

Vitamin D is further hydoxylated in the liver to 25-OH vitamin D. Both forms are metabolised to their respective 25-OH vitamin D forms. 25-OH vitamin D is the major circulating form of vitamin D. 25-OH vitamin D is metabolised in the kidneys by the enzyme 25-OH D-1α-hydroxylase to its active form, 1,25-dihydroxyvitamin D. The renal production of 1,25-dihydroxyvitamin D is tightly regulated by plasma parathyroid hormone (PTH) levels, serum calcium and phosphorus levels. Because of its long half-life, 25-OH vitamin D measurement is the only useful one to use for assessing vitamin D status and stores in any patient.

The measurement of 1,25(OH)2D concentrations can be misleading because compensatory rises in PTH due to hypovitaminosis D can cause increases in the concentration of 1,25(OH)2D through its action on kidneys.

Exposure to sunlight

Vitamin D can be acquired by exposure of skin to sunlight or ingestion of foods containing vitamin D. Only a few foods, primarily fish oils, egg yolks and liver, naturally contain substantial amounts of vitamin D.

In Europe, very few foods are supplemented with vitamin D. Consequently, most vitamin D is acquired by its synthesis in skin (from sun exposure). However, trying to get adequate vitamin D from this source is problematic as it increases the risk of melanoma.

Vitamin D deficiency has been described virtually everywhere on the planet. However, it is more prevalent in northern latitudes. Research has shown that adults in Europe, northern United States and Canada are particularly at risk. Groups at highest risk include elderly persons, housebound or institutionalised persons, African-Americans (and others with dark skin pigment) and adults who spend most of their time working indoors. There is significant seasonal variation in vitamin D status in healthy young adults, with the lowest concentrations occurring in winter and spring. One study in the Am J Clin Nutr (2002) revealed that women examined in the winter or spring were 2.4-3.6 times more likely to have hypovitaminosis D compared to women examined in the summertime.

Similar figures have been replicated in other studies. A 2005 systemic review by Gaugris et al. revealed that the prevalence of vitamin D inadequacy was 12.5 per cent to 76 per cent among osteoporotic women.

As alluded to earlier, receptors for 1,25 (OH) vitamin D have been identified in skeletal muscle tissue and a recent meta-analysis (2004) reported a 22 per cent decrease in falls associated with the use of vitamin D supplements.
In a review at the Boston Medical Centre, 32 per cent of the students and doctors (18–29 years of age) were vitamin D deficient at the end of the winter. One likely contributory explanation is that during the winter season, more ultra violet B photons are absorbed by the ozone layer even if people were outside in the open air. During winter months above the latitude of 37°, there are even more marked decreases in the number of ultraviolet B photons reaching the earth’s surface. Therefore, very little vitamin D3 is produced in the skin during the winter. The latitude in Ireland is significantly higher than this and we are likely to have very ineffective vitamin D exposure periods (even if outside) during the autumn and winter months.

Let us look at a few studies from Ireland: a 2004 food consumption survey carried out in Ireland has shown that a considerable proportion of Irish adults have very low dietary intakes of vitamin D and that they are largely dependent on sunlight to maintain adequate levels of vitamin D.

Another recent study in the European Journal of Clinical Nutrition (2005) showed that up to 36 per cent of Irish women (aged 51-69 years) had sub-optimal vitamin D status during winter time. A more recent study in the Ir J Med Sci. (2006) examined the vitamin D intake and status in young girls (11-13 years) and elderly women; the results found that young girls had very low vitamin D intake and very low levels of serum vitamin D compared to the elderly population.

In this latter study, it was suggested that the increased use of supplemental vitamin D in the elderly cohort might have explained the discrepancy in vitamin D levels. Our group at the Arthritis & Osteoporosis Centre, Division of Rheumatology, South Infirmary-Victoria University Hospital, Cork has a special clinical and research interest in vitamin D deficiency and bone health.

We have examined the prevalence of low vitamin D status in our outpatients. In 2007, we carried out a six-month study investigating the prevalence of vitamin D deficiency in all consecutive new patients seen in our rheumatology clinics at first visit (all referred by their GPs). The patients were recruited from January 1 to June 30, 2007. In total, 264 new patients were seen over this time-period and 231 consented to partake in the study.

The results of this study were presented as a poster abstract at this year’s annual European rheumatology meeting in Paris in June (EULAR) and as an oral/podium presentation at this year’s American College of Rheumatology (‘ACR’) annual meeting in San Francisco in October.

In this study, we found that 70 per cent of the cohort had hypovitaminosis D (≤53 nmol/L). Overall, 26 per cent had severe hypovitaminosis D (≤25 nmol/L) and 21 per cent of those who had low vitamin D had secondary hyperparathyroidism.

Twenty-four per cent of the patients were aged ≥65 years; 65 per cent of these elderly patients (≥65 years) were vitamin D deficient and 25 per cent were severely deficient. It was very interesting that in those aged <30 years of age, 78 per cent had vitamin D deficiency.

Our principal findings were a) that the prevalence of low vitamin D in the cohort of 231 new patients was extremely common, and b) that the age of the patient did not substantially influence whether they had vitamin D deficiency or not.

If we had used the cut-offs which we now use (in 2008), our figures would have been even more striking: 87 per cent of all new patents seen at our rheumatology clinics over a 6-month period would have had vitamin D deficiency with 25-OH vitamin D levels ≤ 75nmol/L (≤ 30ng/ml in the US).

In the context of rheumatologic diseases, among the research reports at this year’s ACR meeting, there were many abstracts showing a high prevalence of low vitamin D in patients with SLE, rheumatoid arthritis, juvenile arthritis and scleroderma.

Some abstracts suggested an association between low levels of vitamin D and greater inflammatory disease activity. Indeed, researchers from Johns Hopkins University, Baltimore, USA described that in women with rheumatoid arthritis (but not men), low serum vitamin D status had an independent association with physical functioning.

Conclusion

In conclusion, vitamin D deficiency represents a major health concern. Poor awareness of the condition exists among most clinicians despite the fact that excellent options for prevention and treatment are available.

In contrast to the popular belief that vitamin D deficiency is only a disease of the older, housebound, sunlight-deprived or institutionalised person – this is clearly not the case. Research from across the world has shown that it exists in all age groups, even children.

Physicians should have a high index of suspicion for this condition because, in the world of rheumatology, geriatrics and general practice, its recognition and management offers us the opportunity to optimise, at a minimum, bone health and muscle strength.

In the wider medical world, maximising vitamin D levels over many years may help delay the onset of diabetes mellitus, aid the immune system and help in tumour surveillance. It is time to take vitamin D seriously. Its time has come.

• Dr Muhammad Haroon, Rheumatology Specialist Registrar, Waterford Regional Hospital; with Dr Mark J. Phelan and Dr Michael J. Regan, Consultant Rheumatologists, Arthritis and Osteoporosis Centre, Department of Rheumatology, South Infirmary-Victoria University Hospital, Cork.

Posted in Nutrition on 05 December 2008
Tags: vitamins