Establishing Benefit from Vitamin D Supplementation - Adherence to Defined Criteria and Targeting of High-Risk Groups Essential?

BACKGROUND: Vitamin D is the one of the most common nutritional deficiencies worldwide, and insufficiency or deficiency can be associated with musculoskeletal and non-skeletal conditions such as cancer, cardiovascular disease and diabetes mellitus. OBJECTIVE: Recent data suggests that Vitamin D is relatively safe and toxicity is rarer than previously indicated. However, international guidelines regarding dosage and target plasma levels are conflicting. Moreover multiple well-designed studies of healthy older adults, unselected in terms of Vitamin D status, have revealed largely negative results (with the possible exception of older patients in care homes/hospitals) in terms of improvement in musculoskeletal and non-skeletal conditions to date. CONCLUSION: On that basis, it is suggested that future trials regarding Vitamin D supplementation should be carried out in high-risk groups. The use of published criteria for evaluating the effect of nutrients and targeting of individuals with Vitamin D insufficiency and deficiency for inclusion in such studies is also proposed. The identification of specific subgroups that will benefit from supplementation and replacement, and the establishment of a scientific basis for such therapy, should be possible with this approach.

Fulminant Skeletal Failure in a Centenarian: The Impact of Nutrition and Immobility.

This case describes a 103-year-old lady who presented from home with an incidental diagnosis of a left femoral fracture. She had no history of trauma and denied pain. She had a known diagnosis of osteoporosis, and sustained a fracture of the contralateral femur aged 93 which was managed conservatively. She was bed-bound with fixed contractures, poor oral intake and was non-compliant with prescribed calcium/vitamin D supplementation. Clinical biochemical measurements showed severe vitamin D deficiency and mild hypocalcaemia. Secondary hyperparathyroidism in the setting of an inappropriately normal phosphate suggested concurrent renal bone disease. Biomarkers of bone turnover were also consistent with bone remodelling. The history of prior fragility fractures, severe vitamin D deficiency and immobility supports a diagnosis of osteoporotic fracture, however other causes of spontaneous fracture were also considered. This case highlights the complexity of interpreting clinical biochemistry results in the setting of multi-morbidity and addresses the challenges of bone health management in the frail older person.

A review of vitamin D insufficiency and its management: a lack of evidence and consensus persists.

Vitamin D deficiency is the most common nutritional deficiency worldwide, however uncertainty persists regarding the benefits of vitamin D supplementation. Vitamin D is essential for calcium homeostasis, and has been linked to falls and fractures in older people. There are numerous risk factors for vitamin D deficiency, chief among them old age. Studies of vitamin D supplementation have given mixed signals, but over all there is evidence of benefit for those with risk factors for deficiency. International guidelines recommend vitamin D target levels of >25 to >80 nmol/l, best achieved by a daily dose of 800-1000 IU. Large bolus doses should be avoided. There are still unanswered questions regarding vitamin D supplementation and target levels. There is need for well designed and powered trials to achieve consensus.

Vitamin D Deficiency and Insufficiency Prevalence in the West of Ireland - A Retrospective Study.

OBJECTIVES: Vitamin D plays an important role in calcium homeostasis and is essential for normal bone growth and remodeling. Previous studies of acutely ill and institutionalized older women in Galway revealed that vitamin D insufficiency is extremely common. We aimed to evaluate age and gender-related rates of vitamin D insufficiency and deficiency in adult patients attending their General Practitioners in the same region. DESIGN: A retrospective cohort study. SETTING: General practices in Galway, a city located on the west coast of Ireland, latitude 53.17 North. PARTICIPANTS: A total of 15,708 consecutive blood samples from adults attending their General Practitioners between January 2013 and December 2014 were sent to the Clinical Biochemistry Laboratory in the University Hospital Galway for vitamin D level testing. 73% were from women. INTERVENTION: Data were collected and grouped according to age, sex and season. Vitamin D levels (25OHD) were categorised into deficiency (<25nmol/L), insufficiency (25-50nmol/L) and sufficiency ( >50nmol/L). MEASUREMENTS: Median and interquartile range were reported as vitamin D levels were not normally distributed. Descriptive statistics were performed using STATA/MP 13.1 for Mac. RESULTS: While vitamin D levels were sufficient in 56.4% (n=8,496), they were insufficient in 32.4% (n=4,891) and deficient in 11.2% (n=1,691). Of the deficient group, 19%( 325) had levels <15nmol/L consistent with profound deficiency. Men were more likely than women to be deficient (12% (n=489) vs. 10.9% (n=1,202)) and insufficient (38.0% (n=1,550) vs. 30.4% (n=3,341)) (p<0.01). Highest rates of deficiency were seen in those 81-97 years (19.4% (n=136)) and 18-40 years (13.8% (n=543)), the former group showing less seasonal variation. CONCLUSION: Overall prevalence of insufficiency is similar to those in national and European studies published recently. However, there is a high possibility that those most vulnerable to vitamin D deficiency were underrepresented in this cohort, when results from previous studies in the same region are considered. Further prospective studies are needed to guide treatment with supplementation of vitamin D for appropriate subgroups.

Iron status and restless legs syndrome in the elderly.

The relationship between iron status and the restless legs syndrome (RLS) was examined in 18 elderly patients with RLS and in 18 matched control subjects. A rating scale with a maximum score of 10 was used to assess the severity of RLS symptoms. Serum ferritin levels were reduced in the RLS patients compared with control subjects (median 33 micrograms/l vs. 59 micrograms/l, p < 0.01, Wilcoxon signed rank test); serum iron, vitamin B12 and folate levels and haemoglobin levels did not differ between the two groups. Serum ferritin levels were inversely correlated with the severity of RLS symptoms (Spearman's rho -0.53, p < 0.05). Fifteen patients with RLS were treated with ferrous sulphate for 2 months. RLS severity score improved by a median value of 4 points in six patients with an initial ferritin < or = 18 micrograms/l, by 3 points in four patients with ferritin > 18 micrograms/l, < or = 45 micrograms/l and by 1 point in five patients with ferritin > 45 micrograms/l, < 100 micrograms/l. Iron deficiency, with or without anaemia, is an important contributor to the development of RLS in elderly patients, and iron supplements can produce a significant reduction in symptoms.

Effect of prolonged nifedipine or captopril therapy on lymphocyte magnesium and potassium levels in hypertension.

The effect of prolonged treatment with calcium channel blockers on potassium and magnesium stores is uncertain. We measured lymphocyte and serum magnesium and potassium in 28 patients treated for hypertension for 6 months with nifedipine or captopril. There was no difference in serum or lymphocyte concentrations in the two groups compared to 45 healthy, normotensive controls. These results suggest that intracellular cation levels are maintained with prolonged therapy with calcium channel blockers.

Effect of captopril therapy on lymphocyte potassium and magnesium concentrations in patients with congestive heart failure.

Lymphocyte potassium and magnesium were measured before and 3 months after the introduction of captopril in 18 patients taking diuretics for congestive heart failure. Compared to 32 healthy controls, 9 patients who had been on potassium supplements plus frusemide had decreased baseline lymphocyte magnesium and potassium concentrations (p less than 0.01), in spite of similar plasma electrolyte levels. There was a significant (p less than 0.01) increase in both lymphocyte potassium and magnesium levels after 3 months' treatment with captopril and frusemide in these patients. Nine patients who had been taking a potassium-sparing combination diuretic also had an increase in lymphocyte magnesium (p less than 0.05) following the introduction of captopril. Increased intracellular potassium and magnesium may be one mechanism whereby angiotensin-converting enzyme inhibitors reduced arrhythmias and improve survival in patients with congestive heart failure.