Chronic vitamin D insufficiency impairs physical performance in C57BL/6J mice.

Vitamin D insufficiency (serum 25-OH vitamin D < 30 ng/ml) affects 70-80% of the general population, yet the long-term impacts on physical performance and the progression of sarcopenia are poorly understood. We therefore followed 6-month-old male C57BL/6J mice (n=6) consuming either sufficient (STD, 1000 IU) or insufficient (LOW, 125 IU) vitamin D3/kg chow for 12 months (equivalent to 20-30 human years). LOW supplemented mice exhibited a rapid decline of serum 25-OH vitamin D levels by two weeks that remained between 11-15 ng/mL for all time points thereafter. After 12 months LOW mice displayed worse grip endurance (34.6 ± 14.1 versus 147.5 ± 50.6 seconds, p=0.001), uphill sprint speed (16.0 ± 1.0 versus 21.8 ± 2.4 meters/min, p=0.0007), and stride length (4.4 ± 0.3 versus 5.1 ± 0.3, p=0.002). LOW mice also showed less lean body mass after 8 months (57.5% ± 5.1% versus 64.5% ± 4.0%, p=0.023), but not after 12 months of supplementation, as well as greater protein expression of atrophy pathway gene atrogin­1. Additionally, microRNA sequencing revealed differential expression of mIR­26a in muscle tissue of LOW mice. These data suggest chronic vitamin D insufficiency may be an important factor contributing to functional decline and sarcopenia.

A mouse model of vitamin D insufficiency: is there a relationship between 25(OH) vitamin D levels and obesity?

BACKGROUND: Vitamin D insufficiency (serum 25-OH vitamin D > 10 ng/ml and < 30 ng/ml) is prevalent in the obese (body mass index (BMI) > 30 kg/m2), yet relationships between the two are poorly understood. Objectives of this study include identification of the impact of obesity on reducing serum 25-OH vitamin D concentration, particularly in response to altered vitamin D3 supplementation, and to elucidate the longitudinal impact of serum 25-OH vitamin D on body mass index. METHODS: Twenty four-week-old lean and obese male C57BL/6 J mice were fed low, standard, or high levels of cholecalciferol supplementation and followed for 24 weeks. Longitudinal measurements include serum 25-OH and 1,25-(OH)2 vitamin D, intact PTH, and calcium concentrations, as well as BMI, bone density and body fat/lean mass. RESULTS: Baseline serum 25-OH concentrations were not different in lean and obese mice (lean 32.8 ± 4.4 ng/ml versus obese 30.9 ± 1.6 ng/ml p = 0.09). Lean mice receiving low supplementation exhibited rapid declines in serum 25-OH vitamin D concentrations, falling from 33.4 ± 5.4 ng/ml to 14.5 ± 3.4 ng/ml after 2 weeks, while obese mice declined at a lower rate, falling from 30.9 ± 1.5 to 19.0 ± 0.9 ng/ml within the same time period. Surprisingly, high vitamin D3 supplementation did not substantially increase serum vitamin D concentrations above standard supplementation, in either lean or obese mice. No differences in serum 1,25-(OH)2 vitamin D, intact parathyroid hormone (PTH) or serum calcium were observed between lean and obese mice within the same vitamin D supplementation group. Yet obese mice exhibited lower serum calcitriol, higher serum PTH, and lower bone mineral density (BMD) than did lean mice. Additionally, neither body mass index nor body fat % was significantly correlated with vitamin D concentrations. Interestingly, lean mice with high vitamin D supplementation consumed significantly more food than did lean mice with standard or low supplementation (14.6 ± 1.7 kcal/mouse/day versus 11.8 ± 1.4 and 12.3 ± 1.7 respectively, p < 0.0001 for both). CONCLUSIONS: Low cholecalciferol supplementation in both lean and obese mice significantly and sustainably reduces serum 25-OH vitamin D concentrations. Interestingly, obesity slowed the rate of decline. Over the period of the study, vitamin D insufficiency was not subsequently correlated with greater BMI/body fat, although lean mice with high supplementation consumed greater calories with no apparent BMI increase.

The response of elderly veterans to daily vitamin D3 supplementation of 2,000 IU: a pilot efficacy study.

OBJECTIVES: To determine the prevalence of hypovitaminosis D (serum 25-hydroxyvitamin D<32 ng/mL; HVD) in a population of elderly veterans and conduct a preliminary assessment of the efficacy of supplementation with cholecalciferol in correcting HVD. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: Geriatric clinic at the Bruce W. Carter Veterans Affairs Medical Center, Miami, Florida. PARTICIPANTS: Veterans aged 70 and older. INTERVENTION: Oral cholecalciferol 2,000 IU daily or placebo for 6 months. MEASUREMENTS: Serum calcium, 25-hydroxyvitamin D, parathyroid hormone, and 24-hour urinary calcium. RESULTS: Of the 34 participants who completed the study, 62% had HVD at baseline. In the treatment group, mean serum 25-hydroxyvitamin D level rose from 28.4±7.9 ng/mL at baseline to 42.7±10.5 ng/mL at the end of the trial, but levels remained less than 32 ng/mL in three of 17 (18%) of the participants. In the placebo group, the baseline level of 27.7±8.3 ng/mL remained unchanged (28.8±8.7 ng/mL). Supplementation did not alter serum or urinary calcium levels and did not result in any adverse events. CONCLUSION: These initial observations suggest that, in older veterans, cholecalciferol 2,000 IU daily for 6 months is generally safe and corrects HVD in most but not all individuals.

Treatment for osteoporosis in Australian residential aged care facilities: consensus recommendations for fracture prevention.

Older people living in residential aged care facilities (RACFs) are at considerably higher risk of suffering fractures than older people living in the community. When admitted to RACFs, patients should be assessed for fracture risk to ensure early implementation of effective fracture prevention measures. Routine or regular determination of calcium and phosphate serum levels in institutionalised older people is not indicated. Opinion is divided about the value of routine measurements of serum concentrations of 25-hydroxyvitamin D, parathyroid hormone and bone turnover markers. The non-pharmacological approach to fracture prevention includes multifactorial programs of falls prevention and the use of hip protectors. Vitamin D supplementation is recommended for all patients in RACFs. Dietary calcium intake should be optimised (1200-1500 mg per day is recommended) and supplementation offered to those with inadequate intake. The decision to prescribe calcium supplements should be guided by patients' tolerance, whether or not they have a history of kidney stones, and emerging data about its cardiovascular safety. Bisphosphonates are the first-choice pharmacological agents for fracture prevention in older persons at high risk. Intravenous administration is as efficient as oral and has the significant advantage of better adherence. Use of strontium ranelate has not been tested on people in RACFs, but evidence in the "old-old" (those aged 75 years and older) suggests it could be a therapeutic option for fracture prevention in this setting. In general, teriparatide should not be considered as a first-line treatment for fracture prevention, particularly for people in RACFs.

Some new food for thought: the role of vitamin D in the mental health of older adults.

Vitamin D, a multipurpose steroid hormone vital to health, has been increasingly implicated in the pathology of cognition and mental illness. Hypovitaminosis D is prevalent among older adults, and several studies suggest an association between hypovitaminosis D and basic and executive cognitive functions, depression, bipolar disorder, and schizophrenia. Vitamin D activates receptors on neurons in regions implicated in the regulation of behavior, stimulates neurotrophin release, and protects the brain by buffering antioxidant and anti-inflammatory defenses against vascular injury and improving metabolic and cardiovascular function. Although additional studies are needed to examine the impact of supplementation on cognition and mood disorders, given the known health benefits of vitamin D, we recommend greater supplementation in older adults.

Hypovitaminosis D: a widespread epidemic.

Vitamin D insufficiency is widespread, regardless of geographical location. It is particularly prevalent in the elderly and has far-ranging health consequences including: osteoporosis, falls, increased risk of cancer, and altered glucose and lipid metabolism. Increasing evidence strongly supports the benefits of vitamin D supplementation and also reveals that present recommendations are inadequate, especially for older individuals. Although additional studies are still needed to further optimize diagnostic and therapeutic approaches, physicians should consider prescribing cholecalciferol--at least 2000 international units (IU) per day--to all elderly patients. Oral cholecalciferol supplementation at that level is inexpensive, safe, and effective, and has great potential to improve the quality of life of the elderly.

Emerging therapies to treat frailty syndrome in the elderly.

Frailty syndrome (FS) has become increasingly recognized as a major predictor of co-morbidities and mortality in older individuals. Interventions with the potential to benefit frail elders include nutritional supplementation (vitamins D, carotenoids, creatine, dehydroepiandrosterone (DHEA), and beta-hydroxy-beta-methylbutyrate) and exercise modalities (tai chi and cobblestone walking). While these have not been explicitly tested for their impact on FS, vitamin D supplementation appears to offer significant promise in enhancing long-term health of the elderly. Exercise modalities such as tai chi and cobblestone walking, because of probable low risk and ease of participation, may also confer benefit. Additional studies are needed to investigate interventions that directly prevent, delay, and/or ameliorate frailty. Successful therapies may well involve multi-component approaches utilizing a combination of medication, nutritional supplementation, and exercise.