DNC News

Vitamin D Update, Summer 2005


Subject: A short review of new research on Vitamin D


This is getting ridiculous. Vitamin D research is being published so quickly that it is hard to keep up. Recall from previous newsletters that in the last few years our entire perspective on the value of Vitamin D in human health has been turned upside down. We now know that a significant portion of our population is Vitamin D deficient and this predisposes us to cancer, heart disease, auto immune disease, including diabetes and MS, chronic pain and depression. Below is a short summaries of eleven new studies of interest on Vitamin D which have been published since May, 2005.



Daily intake of Vitamin D should be above 2,000 iu/day, closer to 4,000. July, 2005 [i]

[J Steroid Biochem Mol Biol. 2005 Jul 15;]


Vitamin D reverses inflammatory changes associated with age-related memory impairment. Researchers from Ireland demonstrated that vitamin D3 acts as an anti-inflammatory agent and turns old brains into young. This research suggests vitamin D may prevent, or even treat, age-related cognitive decline. August, 2005 [ii]

[ Biochem Soc Trans. 2005 Aug;33(Pt 4):573-7.]


Blood sugar is closely associated with vitamin D level.

Researchers in Australia added to the growing evidence that sun avoidance may have caused the epidemic of type 2 diabetes. The Australians' found that the higher your vitamin D level, the lower your blood glucose. June, 2005 [iii]

[ Clin Endocrinol (Oxf). 2005 Jun;62(6):738-41]


In July, a group from Minnesota found that 100% of elderly patients admitted for fragility fractures were vitamin D deficient despite the fact that half of them were taking vitamin D supplements. The authors found that women taking supplemental vitamin D had average levels of 16.4 ng/ml while women not taking supplements had levels of 11.9.ng/ml, both dangerously low. None of the 82 women got enough sun or took enough vitamin D to obtain a level of 40 ng/ml. These were fragility fractures, not fractures caused by unusual trauma. July, 2005 [iv]

[ Curr Med Res Opin. 2005 Jul;21(7):1069-74.]


Women with the lowest vitamin D levels had five times higher risk for breast cancer. Women with 25(OH)-vitamin D blood levels less than 20 ng/ml were five times more likely to be diagnosed with breast cancer than were women with levels above 60 ng/ml. May, 2005 [v]

[ Eur J Cancer. 2005 May;41(8):1164-9. Epub 2005 Apr 14.]


  Avoiding the sun doubles the risk of prostate cancer. The risk of avoiding the sun is clear, this time in another study with prostate cancer. However, the authors pointed out that sun exposure increases the risk of skin cancer and believed that proper vitamin D supplementation ”may be the safest solution to achieve an adequate vitamin D status.” June 2005 [vi]

[ Cancer Res. 2005 Jun 15;65(12):5470-9.]



South Korean researchers associated vitamin D deficiency with Parkinson's Disease. Actually, they showed that certain genetic malformations (VDR polymorphisms) are more likely in-patients with Parkinson's Disease, implying an association with vitamin D and Parkinsonism. June, 2005 [vii]

[ J Korean Med Sci. 2005 Jun;20(3):495-8.]


Researchers in England discovered that patients with chronic pain have phenomenally low vitamin D levels. The authors added to the evidence that severe vitamin D deficiency is associated with chronic pain. They found that 88% of their patients with chronic pain had levels less than 10 ng/ml. If they treated their patients, they did not report it. However, Swiss researchers recently treated chronic pain patients with vitamin D and reported the pain “disappeared” within one to three months in most of their patients. This is the second open study that showed adequate doses of vitamin D dramatically improve chronic pain. August, 2005 [viii]

[ Ann Rheum Dis. 2005 Aug;64(8):1217-9.]


Severe vitamin D deficiency is common in TB patients. The authors reviewed the impressive animal evidence that vitamin D can help treat TB. Then they reported that most of their immigrant TB patients had undetectable vitamin D levels. June, 2005 [ix]

[J Infect. 2005 Jun;50(5):432-7.]



Virtually all nephrologists give renal failure patients a vitamin D-like drug. Yet most renal failure patients are severely vitamin D deficient . Most Renal failure patients are vitamin D deficient despite taking vitamin D analogs. Most nephrologists prescribe activated vitamin D (calcitriol) or vitamin D analogs but not vitamin D. Calcitriol and vitamin D analogs do nothing to prevent vitamin D deficiency. Renal failure patients need both vitamin D and a calcitriol-like drug. Moreover, 400 units a day of vitamin D will not correct their deficiencies; they need up to 4,000 iu/day. June, 2005 [x]

[ [1] Am J Kidney Dis. 2005 Jun;45(6):1026-33. ]


The three best reasons why we should all maintain minimum Vitamin D levels of at least 32 ng/ml:

(a)    effectively suppresses PTH,

(b)    maximizes calcium absorption,

(c)    maximally improves glucose tolerance.

Some people, especially African Americans, will need to take 3,000 to 4,000 units every day to maintain healthy 25(OH)-vitamin D blood levels. July, 2005 [xi]

[ J Steroid Biochem Mol Biol. 2005 Jul 15]









[i] J Steroid Biochem Mol Biol. 2005 Jul 15; [Epub ahead of print]

The Vitamin D requirement in health and disease.


Heaney RP.


Creighton University , 601 N. 30th St., Suite 4841 Omaha , NE 68131 , USA .


Advances in Vitamin D nutritional physiology since publication of the DRIs in 1997 are briefly summarized. Available data indicate that (1) Vitamin D's canonical function, optimizing intestinal calcium absorption, is fully expressed at serum 25-hydroxyvitamin D (25OHD) concentration of approximately 80nmol/L; (2) elevated parathyroid activity, typical of aging populations, is minimized at the same 25OHD value and (3) osteoporotic fractures are reduced when serum 25OHD is raised to near 80nmol/L. Depending upon starting value, achieving 25OHD concentrations of 80 or higher may require a daily oral intake of 2200IU (55mug) or more in addition to prevailing cutaneous inputs. The tolerable upper intake level (TUIL), currently set at 2000IU (50mug)/day, is too low to permit optimization of Vitamin D status in the general population. Actual toxicity is not seen below serum 25OHD values of 250nmol/L, a value that would be produced only at continuing oral intakes in excess of 10,000IU (250mug)/day.


PMID: 16026981 [PubMed - as supplied by publisher]



[ii] Biochem Soc Trans. 2005 Aug;33(Pt 4):573-7.


Evidence that vitamin D(3) reverses age-related inflammatory changes in the rat hippocampus.


Moore ME, Piazza A, McCartney Y, Lynch MA.


Department of Physiology and Trinity College Institute of Neuroscience, Trinity College , Dublin 2, Ireland .


One of the major challenges in neuroscience is to identify the changes which accompany aging and which contribute to the well-documented age-related deterioration in cognitive function. This is a particular challenge in the light of the vast array of reported changes, which include morphological changes like synaptic and perhaps cell loss, alteration in membrane composition and the resultant changes in function of membrane proteins, modulation of the hypothalamo-pituitary axis, impaired calcium homoeostatic mechanisms, alteration in enzyme function and decreased neurotransmitter release. In the past few years, evidence suggesting that an aged brain exhibits signs of oxidative stress and inflammatory stress has been accumulating, and recent evidence using microarray analysis has added support to this view. In this paper, we provide evidence to suggest that vitamin D(3) acts as an anti-inflammatory agent and reverses the age-related increase in microglial activation and the accompanying increase in IL-1beta (interleukin-1beta) concentration.


PMID: 16042547 [PubMed - in process]



[iii] Clin Endocrinol (Oxf). 2005 Jun;62(6):738-41.

Relationship between fasting serum glucose, age, body mass index and serum 25 hydroxyvitamin D in postmenopausal women.


Need AG, O'Loughlin PD, Horowitz M, Nordin BE.


Division of Clinical Biochemistry, Institute of Medical and Veterinary Science, University of Adelaide , Adelaide , SA, Australia . allan.need@imvs.sa.gov.au


OBJECTIVE: Because it has been reported that vitamin D, given to mother or infant, can prevent type I diabetes in children, that diabetes is more common in adults with low serum vitamin D and that insulin secretion and action are related to vitamin D levels in healthy young adults we examined the relationship between serum vitamin D metabolites and fasting serum glucose in patients attending our outpatient clinics. DESIGN: Retrospective examination of convenience sample of postmenopausal women attending our osteoporosis clinics. PATIENTS: A total of 753 postmenopausal women attending a university hospital outpatient clinic and not on any treatment known to affect glucose metabolism. MEASUREMENTS: Body weight and height, serum 25-hydroxyvitamin D [25(OH)D], serum 1,25-dihydroxyvitamin D [1,25(OH)2D], serum PTH and fasting serum glucose. RESULTS: On simple correlation fasting serum glucose was a positive function of age (P < 0.05), weight (P < 0.001) and body mass index (BMI) (P < 0.001) and a negative function of serum 25(OH)D (P < 0.001), but it was not significantly related to either serum 1,25(OH)2D, PTH or creatinine. When fasting serum glucose was regressed simultaneously on age, BMI and 25(OH)D, glucose was still an inverse function of 25(OH)D (P = 0.006). CONCLUSIONS: Fasting serum glucose increased as 25(OH)D levels fell throughout the range of serum 25(OH)D measured but the greatest increase was observed in those with 25(OH)D below 40 nmol/l.


PMID: 15943837 [PubMed - indexed for MEDLINE]



[iv] Curr Med Res Opin. 2005 Jul;21(7):1069-74.

Prevalence of vitamin D inadequacy in a minimal trauma fracture population.


Simonelli C, Weiss TW, Morancey J, Swanson L, Chen YT.


HealthEast Osteoporosis Care, HealthEast Clinics, Woodbury , MN 55125 , USA . msciao@comcast.net


OBJECTIVE: The purpose of this analysis was to report the prevalence of vitamin D inadequacy in a population of adults with minimal trauma fractures. RESEARCH DESIGN AND METHODS: 82 adults (ages 52-97 with 63% age 80+) consecutively hospitalized with hip and extremity fractures between August 2001 and January 2002 were recruited from two St. Paul , MN hospitals. Patients came from independent living and assisted living facilities. Demographics, medical history and vitamin D supplementation were obtained by the medical record and self-report. Blood specimens were collected during hospitalization within 48 hours of admission. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were assessed using Diasorin 25-hydroxyvitamin D radioimmunoassay kit (RIA) at Mayo Clinic, Rochester , MN . Results were available for 78 patients and are included in the current analysis. RESULTS: Patients were 99% Caucasian, 63% >/=80 years and 78% female. 97% were admitted due to hip fracture. On admission, 50% reported using at least 400 IU per day of vitamin D through supplements (including multivitamins) and 13% of all patients were taking osteoporosis medication (3 estrogen, 5 alendronate, 1 etidronate, 1 raloxifene). The mean 25(OH)D concentration was 14.2 (SD 6.6) with a range of 5-39 ng/mL (8-38 ng/mL wintertime vales in Rochester , MN ). All but two of the 78 patients (97.4%) had 25(OH)D concentrations < 30 ng/mL and the majority (81%) of the patients had 25(OH)D concentrations < 20 ng/mL, including 21% < 9 ng/mL. Mean 25(OH)D concentrations were not substantially different by gender, age, or osteoporosis medication use. Patients who reported vitamin D supplementation >/= 400 IU/day had significantly greater mean 25(OH)D concentrations, albeit suboptimal, compared to those who did not (16.4 vs. 13.7 ng/mL; p = 0.002). CONCLUSIONS: Nearly all patients in this study hospitalized for fracture had vitamin D inadequacy. Significant opportunity exists to ensure adequate and persistent vitamin D intake in a high risk fracture patient population.


PMID: 16004675 [PubMed - in process]



[v] Eur J Cancer. 2005 May;41(8):1164-9. Epub 2005 Apr 14.


Plasma 25-hydroxy vitamin D concentrations, vitamin D receptor genotype and breast cancer risk in a UK Caucasian population.


Lowe LC, Guy M, Mansi JL, Peckitt C, Bliss J, Wilson RG, Colston KW.


Department of Cellular and Molecular Medicine, St. George's Hospital Medical School , Cranmer Terrace, London SW17 ORE , UK .


Low levels of 25-hydroxy vitamin D (25(OH)D) and polymorphisms in the vitamin D receptor gene (VDR) have been found separately to increase risk of breast cancer. The aim of this study was to determine whether low 25(OH)D levels, alone and in combination with BsmI VDR genotype, increased breast cancer risk in a United Kingdom (UK) Caucasian population. Breast cancer patients (n=179) and control women (n=179) were recruited and 25(OH)D levels measured by enzyme-linked immunosorbent assay (ELISA). VDR genotype was determined by polymerase chain reaction (PCR) and restriction enzyme digest. Analysis showed that subjects with 25(OH)D levels <50 nM and the bb BsmI VDR genotype are 6.82 times more likely to have breast cancer than subjects with levels of 25(OH)D>50 nM and either the BB or Bb genotype (95% confidence interval (CI) 2.31-14.7, P<0.001). This study indicates that low levels of circulating 25(OH)D, both alone and in combination with BsmI VDR genotype, may increase risk of breast cancer in a UK Caucasian population.


PMID: 15911240 [PubMed - indexed for MEDLINE]



[vi] Cancer Res. 2005 Jun 15;65(12):5470-9.

Sun exposure, vitamin D receptor gene polymorphisms, and risk of advanced prostate cancer.


John EM, Schwartz GG, Koo J, Van Den Berg D, Ingles SA.


Northern California Cancer Center , Fremont , California 94538 , USA . ejohn@nccc.org


Substantial experimental evidence indicates that the hormonal form of vitamin D promotes the differentiation and inhibits the proliferation, invasiveness, and metastasis of human prostatic cancer cells. Results from epidemiologic studies of vitamin D status and/or vitamin D receptor (VDR) polymorphisms and prostate cancer risk have been mixed. We conducted a population-based, case-control study of advanced prostate cancer among men ages 40 to 79 years from the San Francisco Bay area. Interview data on lifetime sun exposure and other risk factors were collected for 905 non-Hispanic White men (450 cases and 455 controls). Using a reflectometer, we measured constitutive skin pigmentation on the upper underarm (a sun-protected site) and facultative pigmentation on the forehead (a sun-exposed site) and calculated a sun exposure index from these measurements. Biospecimens were collected for 426 cases and 440 controls. Genotyping was done for VDR polymorphisms in the 5' regulatory region (Cdx-2), exon 2 (FokI), and the 3' region (TaqI and BglI). Reduced risk of advanced prostate cancer was associated with high sun exposure determined by reflectometry [odds ratio (OR), 0.51; 95% confidence interval (95% CI), 0.33-0.80] and high occupational outdoor activity (OR, 0.73; 95% CI, 0.48-1.11). Significant risk reductions with the high-activity alleles FokI FF or Ff, TaqI tt, and BglI BB genotypes and a nonsignificant reduction with Cdx-2 AG or AA genotype were observed in the presence of high sun exposure, with ORs ranging from 0.46 to 0.67. Our findings support the hypothesis that sun exposure and VDR polymorphisms together play important roles in the etiology of prostate cancer.


PMID: 15958597 [PubMed - indexed for MEDLINE]



[vii] J Korean Med Sci. 2005 Jun;20(3):495-8.


Association of vitamin D receptor gene polymorphism and Parkinson's disease in Koreans.


Kim JS, Kim YI, Song C, Yoon I, Park JW, Choi YB, Kim HT, Lee KS.


Department of Neurology, The Catholic University of Korea , Seoul .


1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3), which is the biologically active form of vitamin D, has anti-inflammatory effects and can prevent experimental Parkinson's disease (PD). 1,25(OH)2D3 exerts most of its actions only after it binds to its specific nuclear receptors. Eighty-five Korean patients with PD and 231 unrelated healthy individuals were evaluated to determine if vitamin D receptor gene (VDRG) BsmI polymorphisms were markers for the susceptibility to PD in Korean patients. Each polymorphism was detected using polymerase chain reaction (PCR)-based restriction analysis. In addition, the relationship between the BsmI polymorphisms and the clinical manifestations of PD was evaluated. Overexpression of the b allele (91.2 vs. 85.7%; p=0.069) and homozygote bb (84.7 vs. 72.7%; p=0.043) was found in the PD patients compared with the controls. These results show for the first time an association between PD and a VDRG polymorphism, which might be involved in the pathogenesis of PD, or in the linkage disequilibrium of the VDRG to another pathogenic gene locus.


PMID: 15953876 [PubMed - in process]



[viii] Ann Rheum Dis. 2005 Aug;64(8):1217-9.


An excess of widespread pain among South Asians: are low levels of vitamin D implicated?


Macfarlane GJ, Palmer B, Roy D, Afzal C, Silman AJ, O'Neill T.


Aberdeen Pain Research (Epidemiology) Group, Department of Public Health, School of Medicine, Polwarth Building Foresterhill, Aberdeen AB25 2ZD, Scotland. g.j.macfarlane@abdn.ac.uk


BACKGROUND: Anecdotal reports from rheumatologists in the United Kingdom suggest that patients from South Asian backgrounds are more likely to report widespread body pain. OBJECTIVE: To confirm the presence of an excess of widespread pain in South Asians, and to evaluate the relationship of their symptoms with levels of 25-OH vitamin D. METHODS: Two population studies involving over 3135 subjects were carried out in the North West and Midlands areas of England. RESULTS: The first study confirmed an excess of widespread pain among South Asians (OR = 1.6, 95% CI 1.3 to 2.1). The second smaller study conducted only among young women also showed a similar excess of widespread pain among South Asians (OR = 1.8, 95% CI 0.7 to 4.7) and found that low levels of 25-OH vitamin D (<10 ng/ml) were more common among those with widespread pain (OR = 3.5, 95% CI 0.4 to 31.0). CONCLUSIONS: Owing to the small numbers, the relationship between 25-OH vitamin D and widespread pain must be considered preliminary and requires further investigation. However, it may be one potentially treatable cause of widespread pain.


PMID: 16014682 [PubMed - in process]


[ix] J Infect. 2005 Jun;50(5):432-7.


Prevalence and associations of vitamin D deficiency in foreign-born persons with tuberculosis in London .


Ustianowski A, Shaffer R, Collin S, Wilkinson RJ, Davidson RN.


Department of Infection and Tropical Medicine, Lister Unit, Northwick Park Hospital , Harrow , Middlesex HA1 3UJ , UK . ustianowski@doctors.org.uk


OBJECTIVES: The incidence of tuberculosis (TB) is high amongst foreign-born persons resident in developed countries. Vitamin D is important in the host defence against TB in vitro and deficiency may be an acquired risk factor for this disease. We aimed to determine the incidence and associations of vitamin D deficiency in TB patients diagnosed at an infectious diseases unit in London , UK . METHODS: Case-note analysis of 210 unselected patients diagnosed with TB who had plasma vitamin D (25(OH)D3) levels routinely measured. Prevalence of 25(OH)D3 deficiency and its relationship to ethnic origin, religion, site of TB, sex, age, duration in the UK, month of 25(OH)D3 estimation and TB diagnosis were determined. RESULTS: Of 210 patients 76% were 25(OH)D3 deficient and 56% had undetectable levels. 70/82 Indian, 24/28 East African Asian, 29/34 Somali, 14/19 Pakistani and Afghani, 16/22 Sri Lankan and 2/6 other African patients were deficient (with 58, 17, 23, 9, 6 and 1 having undetectable levels, respectively). Only 0/6 white Europeans and 1/8 Chinese/South East Asians had low plasma 25(OH)D3 levels. Muslims, Hindus and Sikhs all had equivalent rates of deficiency though Hindus were more likely to have undetectable levels (odds ratio 1.87, 95% CI 1.27-2.76). There was no significant association between 25(OH)D3 level and site of TB or duration of residence in the UK . There was no apparent seasonal variation in either TB diagnosis or 25(OH)D3 level. CONCLUSIONS: 25(OH)D3 deficiency commonly associates with TB among all ethnic groups apart from white Europeans, and Chinese/South East Asians. Our data support a lack of sunlight exposure and potentially a vegetarian diet as contributors to this deficiency.


PMID: 15907552 [PubMed - indexed for MEDLINE]


[x] Am J Kidney Dis. 2005 Jun;45(6):1026-33.


Prevalence of calcidiol deficiency in CKD: a cross-sectional study across latitudes in the United States .


LaClair RE, Hellman RN, Karp SL, Kraus M, Ofner S, Li Q, Graves KL, Moe SM.


Department of Medicine, Indiana University School of Medicine, Indianapolis , IN , USA .


BACKGROUND: Recent Kidney Disease Outcomes Quality Initiative guidelines have raised concerns of 25-hydroxyvitamin D, or calcidiol, insufficiency and deficiency in patients with chronic kidney disease (CKD) not yet on dialysis therapy; however, no cross-sectional study across latitudes has been performed to support this assertion. METHODS: Baseline screening data from a prospective study were used to determine calcidiol levels in subjects with moderate to severe CKD not yet on dialysis therapy from 12 geographically diverse regions of the United States . Calcidiol deficiency is defined as levels less than 10 ng/mL (< 25 nmol/L), and insufficiency, as levels of 10 to 30 ng/mL (25 to 75 nmol/L). RESULTS: Two hundred one subjects with a mean age 65 +/- 13 years and calculated glomerular filtration rate (GFR) of 27 +/- 11 mL/min (0.45 mL/s) were evaluated. Overall mean calcidiol level was 19.4 +/- 13.6 ng/mL (48 +/- 34 nmol/L), with a range of 0 to 65 ng/mL (0 to 162 nmol/L). Only 29% and 17% of subjects with moderate and severe CKD had sufficient levels, respectively. Mean calcidiol levels were less than sufficient levels in all geographic locations tested. Multivariate analysis found log calcidiol level correlated with calcium level (P = 0.016), log calcitriol level (P = 0.024), sex (P = 0.041), geographic location (P = 0.045), and inverse intact parathyroid hormone level (P = 0.013), but not calculated GFR or phosphorous level. Calcidiol levels changed modestly in 18 patients who had calcidiol levels measured in winter and late summer after confirmed exposure to sunlight, with mean calcidiol levels of 17.9 +/- 11.7 to 21.2 +/- 10.0 ng/mL (45 +/- 29 to 53 +/- 25 nmol/L; P = 0.015). CONCLUSION: This cross-sectional cohort study found a high prevalence of calcidiol deficiency and insufficiency in patients with moderate and severe CKD not on dialysis therapy regardless of geographic location.


PMID: 15957131 [PubMed - in process]


[xi] J Steroid Biochem Mol Biol. 2005 Jul 15; [Epub ahead of print]


The Vitamin D requirement in health and disease.


Heaney RP.


Creighton University , 601 N. 30th St., Suite 4841 Omaha , NE 68131 , USA .


Advances in Vitamin D nutritional physiology since publication of the DRIs in 1997 are briefly summarized. Available data indicate that (1) Vitamin D's canonical function, optimizing intestinal calcium absorption, is fully expressed at serum 25-hydroxyvitamin D (25OHD) concentration of approximately 80nmol/L; (2) elevated parathyroid activity, typical of aging populations, is minimized at the same 25OHD value and (3) osteoporotic fractures are reduced when serum 25OHD is raised to near 80nmol/L. Depending upon starting value, achieving 25OHD concentrations of 80 or higher may require a daily oral intake of 2200IU (55mug) or more in addition to prevailing cutaneous inputs. The tolerable upper intake level (TUIL), currently set at 2000IU (50mug)/day, is too low to permit optimization of Vitamin D status in the general population. Actual toxicity is not seen below serum 25OHD values of 250nmol/L, a value that would be produced only at continuing oral intakes in excess of 10,000IU (250mug)/day.


PMID: 16026981 [PubMed - as supplied by publisher]

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