Vitamin D Abstracts 3

© 2012

Association of vitamin D deficiency with cognitive impairment in older women: cross-sectional study

         (Annweiler, Schott et al. 2010) Download

OBJECTIVE: The association between low serum 25-hydroxyvitamin D [25(OH)D] concentration and cognitive decline has been investigated by only a few studies, with mixed results. The objective of this cross-sectional population-based study was to examine the association between serum 25(OH)D deficiency and cognitive impairment while taking confounders into account. METHODS: The subjects, 752 women aged > or =75 years from the Epidemiologie de l'Osteoporose (EPIDOS) cohort, were divided into 2 groups according to serum 25(OH)D concentrations (either deficient, <10 ng/mL, or nondeficient, > or =10 ng/mL). Cognitive impairment was defined as a Pfeiffer Short Portable Mental State Questionnaire (SPMSQ) score <8. Age, body mass index, number of chronic diseases, hypertension, depression, use of psychoactive drugs, education level, regular physical activity, and serum intact parathyroid hormone and calcium were used as potential confounders. RESULTS: Compared with women with serum 25(OH)D concentrations > or =10 ng/mL (n = 623), the women with 25(OH)D deficiency (n = 129) had a lower mean SPMSQ score (p < 0.001) and more often had an SPMSQ score <8 (p = 0.006). There was no significant linear association between serum 25(OH)D concentration and SPMSQ score (beta = -0.003, 95% confidence interval -0.012 to 0.006, p = 0.512). However, serum 25(OH)D deficiency was associated with cognitive impairment (crude odds ratio [OR] = 2.08 with p = 0.007; adjusted OR = 1.99 with p = 0.017 for full model; and adjusted OR = 2.03 with p = 0.012 for stepwise backward model). CONCLUSIONS: 25-Hydroxyvitamin D deficiency was associated with cognitive impairment in this cohort of community-dwelling older women.


Vitamin D-mentia: randomized clinical trials should be the next step

            (Annweiler and Beauchet 2011) Download

Hypovitaminosis D is highly prevalent in the elderly. Its possible role in the pathogenesis of Alzheimer's disease (AD) is particularly important, as AD remains a public health concern with no current efficient treatment. Vitamin D administration could be a multitarget stabilizing treatment for AD since vitamin D simultaneously targets several factors leading to neurodegeneration through immunoregulatory, antioxidant and anti-ischemic actions, as well as the regulation of neurotrophic factors, acetylcholine neurotransmitter and clearance of amyloid beta peptide, and the avoidance of hyperparathyroidism. By preventing neuronal loss, the question is whether correcting hypovitaminosis D among older adults could also prevent AD-related cognitive decline. The cross-sectional associations between the vitamin D intakes--whether from diet, sun exposure or drug supplements--and cognition strengthened this hypothesis, but prevented the finding of a cause and effect link. Pre-post studies showed an improvement of cognition concomitant with the increase in 25-hydroxyvitamin D concentrations. One randomized trial found that supraphysiological doses of vitamin D were not better than physiological doses at improving cognition in AD. At this stage, only clinical trials testing vitamin D supplements versus placebo can further determine the impact of vitamin D administration on cognition and AD with higher levels of evidence.

The role of dietary calcium in the physiology of vitamin D toxicity: excess dietary vitamin D3 blunts parathyroid hormone induction of kidney 1-hydroxylase

            (Beckman, Johnson et al. 1995) Download

We studied the effects of dietary calcium (Ca) restriction and excess vitamin D3 on tissue 25-hydroxyvitamin D-1-hydroxylase (1-OHase) and 1,25(OH)2D/25-OH-D-24-hydroxylase (24-OHase) activities in rats. Effects were studied in four groups of rats, with each group receiving one of the following diets: a control diet consisting of normal Ca and normal vitamin D3 (NC), NC plus excess (75,000 IU/week) vitamin D3 (NCT), low Ca and normal vitamin D3 (LC), or LC diet with excess vitamin D3 (LCT). Rats fed the low-Ca diets (LC and LCT) had elevated plasma parathyroid hormone (PTH) concentrations, increasing > 3-fold relative to rats fed the normal Ca diets. The elevated concentrations of PTH in LCT rats did not result in increased plasma 1,25-dihydroxycholecalciferol [1,25(OH)2D3] (NC = 115 +/- 7 pg/ml; LCT = 99 +/- 11 pg/ml). Plasma 1,25(OH)2D in LC rats, however, was increased significantly (615 +/- 110, P = < 0.001). There were no differences in either plasma Ca or phosphorus between the LC and LCT groups. Dietary Ca restriction led to an 18-fold stimulation in renal 1-OHase activity in LC rats (P = < 0.01), while 1-OHase in the LCT rats was marginally but significantly elevated 2.3-fold (P = < 0.05). The ability of PTH to downregulate renal 24-OHase and the 1,25-dihydroxyvitamin D receptor (VDR) during prolonged Ca restriction remained intact, irrespective of vitamin D status. Also, the metabolic clearance rate for 1,25(OH)2D3 was enhanced by feeding excess vitamin D3, which was likely a result of the substantial elevations in intestinal (25-fold) and renal (46-fold) 24-OHase activities in the LCT and NCT groups, respectively. These data indicate that calcium restriction accompanied by excess vitamin D3 is attended by impaired responsiveness of renal 1-OHase to PTH and enhanced metabolic clearance of 1,25(OH)2D.

Comment on "vitamin D discovery outpaces FDA decision making"

            (Boucher 2008) Download

25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services

            (Buell, Dawson-Hughes et al. 2010) Download

BACKGROUND: Vitamin D deficiency has potential adverse effects on neurocognitive health and subcortical function. However, no studies have examined the association between vitamin D status, dementia, and cranial MRI indicators of cerebrovascular disease (CVD). METHODS: Cross-sectional investigation of 25-hydroxyvitamin D [25(OH)D], dementia, and MRI measures of CVD in elders receiving home care (aged 65-99 years) from 2003 to 2007. RESULTS: Among 318 participants, the mean age was 73.5 +/- 8.1 years, 231 (72.6%) were women, and 109 (34.3%) were black. 25(OH)D concentrations were deficient (<10 ng/mL) in 14.5% and insufficient (10-20 ng/mL) in 44.3% of participants. There were 76 participants (23.9%) with dementia, 41 of which were classified as probable AD. Mean 25(OH)D concentrations were lower in subjects with dementia (16.8 vs 20.0 ng/mL, p < 0.01). There was a higher prevalence of dementia among participants with 25(OH)D insufficiency (< or =20 ng/mL) (30.5% vs 14.5%, p < 0.01). 25(OH)D deficiency was associated with increased white matter hyperintensity volume (4.9 vs 2.9 mL, p < 0.01), grade (3.0 vs 2.2, p = 0.04), and prevalence of large vessel infarcts (10.1% vs 6.9%, p < 0.01). After adjustment for age, race, sex, body mass index, and education, 25(OH)D insufficiency (< or =20 ng/mL) was associated with more than twice the odds of all-cause dementia (odds ratio [OR] = 2.3, 95% confidence interval [CI] 1.2-4.2), Alzheimer disease (OR = 2.5, 95% CI 1.1-6.1), and stroke (with and without dementia symptoms) (OR = 2.0, 95% CI 1.0-4.0). CONCLUSIONS: Vitamin D insufficiency and deficiency was associated with all-cause dementia, Alzheimer disease, stroke (with and without dementia symptoms), and MRI indicators of cerebrovascular disease. These findings suggest a potential vasculoprotective role of vitamin D.


The paradoxical effects of vitamin D on type 1 mediated immunity

            (Cantorna, Yu et al. 2008) Download

Low vitamin D status is associated with an increased risk of Th1 mediated autoimmune diseases like inflammatory bowel disease. 1,25(OH)(2)D(3) treatments have been shown to suppress Th1 mediated immunity and protect animals from experimental autoimmunity. Th1 mediated immunity is important for clearance of a number of different infectious diseases. For tuberculosis 1,25(OH)(2)D(3) treatment is associated with decreased Th1 mediated immunity but increased bactericidal activity. Systemic candidiasis is unaffected by 1,25(OH)(2)D(3) treatment. The seemingly paradoxical effects of 1,25(OH)(2)D(3) and vitamin D on Th1 mediated autoimmunity versus infectious immunity point to a broad array of vitamin D targets in the immune system. The interplay of these vitamin D targets and their impact on the host-immune response then dictate the outcome.

Vitamin D and Gastric Secretion

         (Herting and Steenbock 1955) Download

Assessment and interpretation of circulating 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in the clinical environment

            (Hollis 2010) Download

The unique cis-triene structure of vitamin D and related metabolites makes it susceptible to oxidation, ultraviolet (UV) light-induced conformational changes, heat-induced conformational changes, and attacks by free radicals. Vitamin D(2) is much less bioactive than vitamin D(3) in humans. Metabolic activation and inactivation of vitamin D are well characterized and result in a plethora of metabolites, of which only 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) provide any clinically relevant information. 25(OH)D(2) and 25(OH)D(3) are commonly known as calcifediol and the 1,25(OH)(2)D metabolites as calcitriol. In this review the current state of the science on the clinical assessment of circulating 25(OH)D and 1,25(OH)(2)D is described.


1alpha,25-Dihydroxyvitamin D3 enhances cerebral clearance of human amyloid-beta peptide(1-40) from mouse brain across the blood-brain barrier

            (Ito, Ohtsuki et al. 2011) Download

ABSTRACT: BACKGROUND: Cerebrovascular dysfunction has been considered to cause impairment of cerebral amyloid-beta peptide (Abeta) clearance across the blood-brain barrier (BBB). Further, low levels of vitamin D are associated with increased risk of Alzheimer's disease, as well as vascular dysfunction. The purpose of the present study was to investigate the effect of 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3), an active form of vitamin D, on cerebral Abeta clearance from mouse brain. METHODS: The elimination of [125I]hAbeta(1-40) from mouse brain was examined by using the Brain Efflux Index method to determine the remaining amount of [125I]hAbeta(1-40) radioactivity after injection into the cerebral cortex. [125I]hAbeta(1-40) internalization was analyzed using conditionally immortalized mouse brain capillary endothelial cells (TM-BBB4). RESULTS: Twenty-four hours after intraperitoneal injection of 1,25(OH)2D3 (1 mug/mouse), [125I]hAbeta(1-40) elimination from mouse brain was increased 1.3-fold, and the level of endogenous Abeta(1-40) in mouse brain was reduced. These effects were observed at 24 h after i.p. injection of 1,25(OH)2D3, while no significant effect was observed at 48 or 72 h. Vitamin D receptor (VDR) mRNA was detected in mouse brain capillaries, suggesting that 1,25(OH)2D3 has a VDR-mediated genomic action. Furthermore, forskolin, which activates mitogen-activated protein kinase kinase (MEK), enhanced [125I]hAbeta(1-40) elimination from mouse brain. Forskolin also enhanced [125I]hAbeta(1-40) internalization in TM-BBB4 cells, and this enhancement was inhibited by a MEK inhibitor, suggesting involvement of non-genomic action. CONCLUSIONS: The active form of vitamin D, 1,25(OH)2D3, appears to enhance brain-to-blood Abeta(1-40) efflux transport at the BBB through both genomic and non-genomic actions. Compounds activating these pathways may be candidate agents for modulating Abeta(1-40) elimination at the BBB.


Can vitamin D delay the progression of ALS?

            (Karam and Scelsa 2011) Download

The pathogenesis of amyotrophic lateral sclerosis (ALS) is multifactorial and a treatment targeting only one aspect of the disease is unlikely to be beneficial. Vitamin D is safe and may delay progression of ALS by acting on several aspects of the disease. In this article we explore how vitamin D may promote VGEF, IGF-1 and axonal regeneration delaying ALS progression. In addition, we discuss how vitamin D may increase calcium binding protein in motor neuron cells conferring a greater resistance to the underlying disease process, as seen in the oculomotor nerve and Onuf's nucleus. Finally, we discuss vitamin D immunomodulator role, decreasing the reactive gliosis in ALS.

Could combating vitamin D deficiency reduce the incidence of autoimmune disease?

            (Kinder and Hagaman 2011) Download

Serum 25-hydroxyvitamin D concentration and cognitive impairment

         (Llewellyn, Langa et al. 2009) Download

Vitamin D may be of interest in the prevention of cognitive impairment, though previous findings are inconclusive. Participants were 1766 adults aged 65 years and older from the Health Survey for England 2000, a nationally representative population-based study. Cognitive impairment was assessed using the Abbreviated Mental Test Score. The cross-sectional relation of serum 25-hydroxyvitamin D quartiles to cognitive impairment was modeled using logistic regression. In all, 212 participants (12%) were cognitively impaired. Odds ratios (95% confidence intervals) for cognitive impairment in the first (8-30 nmol/L), second (31-44 nmol/L), and third (45-65 nmol/L) quartiles of serum 25-hydroxyvitamin D compared with the fourth (66-170 nmol/L) were 2.3 (1.4-3.8), 1.4 (0.8-2.4), and 1.1 (0.6-1.9), after adjustment for age, sex, education, ethnicity, season of testing, and additional risk factors for cognitive impairment (P for linear trend = .001). Our data suggest low serum 25-hydroxyvitamin D is associated with increased odds of cognitive impairment.

Vitamin D and risk of cognitive decline in elderly persons

         (Llewellyn, Lang et al. 2010) Download

BACKGROUND: To our knowledge, no prospective study has examined the association between vitamin D and cognitive decline or dementia. METHODS: We determined whether low levels of serum 25-hydroxyvitamin D (25[OH]D) were associated with an increased risk of substantial cognitive decline in the InCHIANTI population-based study conducted in Italy between 1998 and 2006 with follow-up assessments every 3 years. A total of 858 adults 65 years or older completed interviews, cognitive assessments, and medical examinations and provided blood samples. Cognitive decline was assessed using the Mini-Mental State Examination (MMSE), and substantial decline was defined as 3 or more points. The Trail-Making Tests A and B were also used, and substantial decline was defined as the worst 10% of the distribution of decline or as discontinued testing. RESULTS: The multivariate adjusted relative risk (95% confidence interval [CI]) of substantial cognitive decline on the MMSE in participants who were severely serum 25(OH)D deficient (levels <25 nmol/L) in comparison with those with sufficient levels of 25(OH)D (>/=75 nmol/L) was 1.60 (95% CI, 1.19-2.00). Multivariate adjusted random-effects models demonstrated that the scores of participants who were severely 25(OH)D deficient declined by an additional 0.3 MMSE points per year more than those with sufficient levels of 25(OH)D. The relative risk for substantial decline on Trail-Making Test B was 1.31 (95% CI, 1.03-1.51) among those who were severely 25(OH)D deficient compared with those with sufficient levels of 25(OH)D. No significant association was observed for Trail-Making Test A. CONCLUSION: Low levels of vitamin D were associated with substantial cognitive decline in the elderly population studied over a 6-year period, which raises important new possibilities for treatment and prevention.

Vitamin D and cognitive impairment in the elderly U.S. population

            (Llewellyn, Lang et al. 2011) Download

BACKGROUND: Recent European studies suggest that vitamin D deficiency may be associated with increased odds of cognitive impairment in older persons, although findings from the United States are equivocal. Our objective was to investigate the association between vitamin D deficiency and cognitive impairment in the elderly U.S. population. METHODS: Three thousand and three hundred twenty-five adults aged 65 years or more completed cognitive assessments, medical examinations, and physical performance measures and provided blood samples in the Third National Health and Nutrition Examination Survey, a nationally representative cross-sectional study of the U.S. noninstitutionalized population. We determined whether low levels of serum 25-hydroxyvitamin D (25(OH)D) were associated with increased odds of cognitive impairment using logistic regression models. Cognitive impairment was assessed using measures of immediate and delayed verbal memory, orientation, and attention (impairment was defined as the worst 10% of the distribution of combined scores). RESULTS: The multivariate adjusted odds ratios (95% confidence interval) of cognitive impairment in participants who were 25(OH)D insufficient (>/= 50 < 75 nmol/L), deficient (>/= 25 < 50 nmol/L), and severely deficient (<25 nmol/L) in comparison with those sufficient (>/= 75 nmol/L) were 0.9 (0.6-1.3), 1.4 (1.0-2.1), and 3.9 (1.5-10.4), respectively (p for linear trend = .02). Log-transformed levels of 25(OH)D were also significantly associated with the odds of cognitive impairment (p = .02). CONCLUSIONS: These findings suggest that vitamin D deficiency is associated with increased odds of cognitive impairment in the elderly U.S. population. Further exploration of a possible causal relationship between vitamin D deficiency and cognitive impairment is warranted.

The beneficial role of vitamin D in Alzheimer's disease

            (Lu'o'ng and Nguyen 2011) Download

Alzheimer's disease (AD) is the most common form of dementia in the elderly individuals and is associated with progressive neurodegeneration of the human neocortex. Patients with AD have a high prevalence of vitamin D deficiency, which is also associated with low mood and impaired cognitive performance in older people. Genetic studies have provided the opportunity to determine which proteins link vitamin D to AD pathology (ie, the major histocompatibility complex class II molecules, vitamin D receptor, renin-angiotensin system, apolipoprotein E, liver X receptor, Sp1 promoter gene, and the poly(ADP-ribose) polymerase-1 gene). Vitamin D also exerts its effect on AD through nongenomic factors, that is, L-type voltage-sensitive calcium channels, nerve growth factor, the prostaglandins, cyclooxygenase 2, reactive oxygen species, and nitric oxide synthase. In conclusion, vitamin D clearly has a beneficial role in AD and improves cognitive function in some patients with AD. Calcitriol, 1 alpha,25-dihydroxyvitamin D3, is best used for AD because of its active form of vitamin D(3) metabolite and its receptor in the central nervous system.

Vitamin D discovery outpaces FDA decision making

         (Marshall 2008) Download

The US FDA currently encourages the addition of vitamin D to milk and cereals, with the aim of reducing rickets in children and osteoporosis in adults. However, vitamin D not only regulates the expression of genes associated with calcium homeostasis, but also genes associated with cancers, autoimmune disease, and infection. It does this by controlling the activation of the vitamin D receptor (VDR), a type 1 nuclear receptor and DNA transcription factor. Molecular biology is rapidly coming to an understanding of the multiplicity of roles played by the VDR, but clinical medicine is having difficulty keeping up with the pace of change. For example, the FDA recently proposed a rule change that will encourage high levels of vitamin D to be added to even more foods, so that the manufacturers can claim those foods "reduce the risk of osteoporosis". The FDA docket does not review one single paper detailing the transcriptional activity of vitamin D, even though, on average, one new paper a day is being published on that topic. Nor do they review whether widespread supplementation with vitamin D, an immunomodulatory secosteroid, might predispose the population to immune dysfunction. This BioEssay explores how lifelong supplementation of the food chain with vitamin D might well be contributing to the current epidemics of obesity and chronic disease.

Clinical practice. Vitamin D insufficiency

            (Rosen 2011) Download

Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis

            (Tripkovic, Lambert et al. 2012) Download

BACKGROUND: Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 and D3 in the raising of serum 25-hydroxyvitamin D [25(OH)D]. OBJECTIVE: The objective of this article was to report a systematic review and meta-analysis of randomized controlled trials (RCTs) that have directly compared the effects of vitamin D2 and vitamin D3 on serum 25(OH)D concentrations in humans. DESIGN: The ISI Web of Knowledge (January 1966 to July 2011) database was searched electronically for all relevant studies in adults that directly compared vitamin D3 with vitamin D2. The Cochrane Clinical Trials Registry, International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials. RESULTS: A meta-analysis of RCTs indicated that supplementation with vitamin D3 had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with the effect of vitamin D2 (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a bolus dose (P = 0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation. CONCLUSIONS: This meta-analysis indicates that vitamin D3 is more efficacious at raising serum 25(OH)D concentrations than is vitamin D2, and thus vitamin D3) could potentially become the preferred choice for supplementation. However, additional research is required to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which this review was unable to verify.

Excess vitamin D and the ear

         (Walker and Bingham 2006) Download


Vitamin D insufficiency

            (Weiss and Litonjua 2011) Download

Vitamin D in the New Millennium

         (Wimalawansa 2012) Download

The incidence of vitamin D deficiency is rising worldwide, yet in the vast majority of patients, the condition remains undiagnosed and untreated. Current evidence overwhelmingly indicates that supplemental doses greater than 800 IU/day have beneficial effects on the musculoskeletal system, improving skeletal homeostasis, thus leading to fewer falls and fractures. Evidence is also accumulating on the beneficial effects of vitamin D on extraskeletal systems, such as improving immune health, autoimmune disorders, cancer, neuromodulation, diabetes, and metabolic syndrome. The cause-effect relationship of vitamin D deficiency with increasing incidences of nonskeletal disorders is being investigated. Published reports support the definition of sufficiency, serum levels of 25-hydroxyvitamin D [25(OH)D] greater than 30 ng/mL (75 nmol/L). To achieve this, most people need vitamin D supplementation ranging from 600 to 2000 IU/day; consumption up to of 5000 international units (IU) per day of vitamin D is reported as safe. Although light-skinned individuals need 1000 IU/day of vitamin D, elderly and dark-skinned individuals are likely to need approximately 2000 IU/day to maintain serum 25(OH)D levels greater than 30 ng/mL. Other vulnerable patients, such as the obese, those who have undergone bariatric surgery, and those with gastrointestinal malabsorption syndromes, may require higher doses of vitamin D to maintain normal serum levels and be healthy.


References

Annweiler, C. and O. Beauchet (2011). "Vitamin D-mentia: randomized clinical trials should be the next step." Neuroepidemiology 37(3-4): 249-58.

Annweiler, C., A. M. Schott, et al. (2010). "Association of vitamin D deficiency with cognitive impairment in older women: cross-sectional study." Neurology 74(1): 27-32.

Beckman, M. J., J. A. Johnson, et al. (1995). "The role of dietary calcium in the physiology of vitamin D toxicity: excess dietary vitamin D3 blunts parathyroid hormone induction of kidney 1-hydroxylase." Arch Biochem Biophys 319(2): 535-9.

Boucher, B. J. (2008). "Comment on "vitamin D discovery outpaces FDA decision making"." Bioessays 30(5): 508-9; author reply 510-1.

Buell, J. S., B. Dawson-Hughes, et al. (2010). "25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services." Neurology 74(1): 18-26.

Cantorna, M. T., S. Yu, et al. (2008). "The paradoxical effects of vitamin D on type 1 mediated immunity." Mol Aspects Med 29(6): 369-75.

Herting, D. C. and H. Steenbock (1955). "Vitamin D and gastric secretion." J Nutr 57(4): 469-82.

Hollis, B. W. (2010). "Assessment and interpretation of circulating 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in the clinical environment." Endocrinol Metab Clin North Am 39(2): 271-86, table of contents.

Ito, S., S. Ohtsuki, et al. (2011). "1alpha,25-Dihydroxyvitamin D3 enhances cerebral clearance of human amyloid-beta peptide(1-40) from mouse brain across the blood-brain barrier." Fluids Barriers CNS 8: 20.

Karam, C. and S. N. Scelsa (2011). "Can vitamin D delay the progression of ALS?" Med Hypotheses 76(5): 643-5.

Kinder, B. W. and J. T. Hagaman (2011). "Could combating vitamin D deficiency reduce the incidence of autoimmune disease?" Expert Rev Clin Immunol 7(3): 255-7.

Llewellyn, D. J., I. A. Lang, et al. (2011). "Vitamin D and cognitive impairment in the elderly U.S. population." J Gerontol A Biol Sci Med Sci 66(1): 59-65.

Llewellyn, D. J., I. A. Lang, et al. (2010). "Vitamin D and risk of cognitive decline in elderly persons." Arch Intern Med 170(13): 1135-41.

Llewellyn, D. J., K. M. Langa, et al. (2009). "Serum 25-hydroxyvitamin D concentration and cognitive impairment." J Geriatr Psychiatry Neurol 22(3): 188-95.

Lu'o'ng, K. V. and L. T. Nguyen (2011). "The beneficial role of vitamin D in Alzheimer's disease." Am J Alzheimers Dis Other Demen 26(7): 511-20.

Marshall, T. G. (2008). "Vitamin D discovery outpaces FDA decision making." Bioessays 30(2): 173-82.

Rosen, C. J. (2011). "Clinical practice. Vitamin D insufficiency." N Engl J Med 364(3): 248-54.

Tripkovic, L., H. Lambert, et al. (2012). "Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis." Am J Clin Nutr 95(6): 1357-64.

Walker, F. D. and B. J. Bingham (2006). "Excess vitamin D and the ear." Clin Otolaryngol 31(3): 238-9.

Weiss, S. T. and A. A. Litonjua (2011). "Vitamin D insufficiency." N Engl J Med 364(14): 1379; author reply 1380.

Wimalawansa, S. J. (2012). "Vitamin D in the new millennium." Curr Osteoporos Rep 10(1): 4-15.