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Treatment and Epidemiologic Studies with Vitamin D

Higher levels of vitamin D or vitamin D supplementation have been associated with lower levels of asthma, bladder overactivity, breast cancer, colon cancer, lung cancer, non-Hodgkins lymphoma, prostate cancer, diabetes, falls and fractures in the elderly, heart disease deaths, high blood pressure, lung function, multiple sclerosis, muscle pain and muscle mass loss, osteoporosis, PMS, schizophrenia, tooth loss, and vaginal atrophy.  Huge amounts of research are finally being done on vitamin D and proving its importance.

Unfortunately, most Americans don't get enough sunlight and have inadequate vitamin D levels.  Some may also have genetic variants of the vitamin D receptor gene.  It appears sensible for everyone to take a daily vitamin D supplement of 1000 (children), 1000 (adult), to 2000 IU (elderly) depending upon age and condition.  I have found one study showing that individuals with receptor gene abnormalities benefit from vitamin D supplementation.  These abnormalities are fairly common and have been linked to many illnesses.  Since gene testing isn't readily available and is costly, it is yet another argument in favor of supplementation.  Current USDA recommendations are clearly inadequate.

Arthritis: Vitamin D Genetic Variants Increase Osteo Risk: In a genetic study of individuals with and without osteoarthritis, VDR gene polymorphisms appeared to play a role in the etiology of symmetrical hand OA. Moreover, the association between the VDR gene and OA may be modified by calcium intake. Solovieva, et al. Helsinki. Arthr Res Ther 2005 Dec 30;8(1):R20. 

Asthma May Increase Responsiveness to Steroids: Steroid treatment may work, at least in part, by inducing the T-cells of the immune system to synthesize a secreted signalling molecule, called IL-10. This molecule can inhibit the immune responses that cause the symptoms of allergic and asthmatic disease. Unlike T-cells from healthy individuals, or patients that respond to steroids, T-cells taken from patients who are steroid resistant do not produce IL-10 when cultured in vitro with the steroid, dexamethasone. However, the researchers found that when vitamin D3 was added to the culture medium along with dexamethasone, this defect was reversed. The researchers gave daily vitamin D3 supplements to people with asthma who were unresponsive to steroids for seven days. Blood tests showed the patients' T-cells were more responsive to dexamethasone after they had taken the supplement. Tak Lee, et al. King's College London, Journal of Clinical Investigation 12/9/05

Asthma May Be Slightly Higher in Infants Given Vitamin D: Allergen-induced secretion of Th2-type cytokines and IgE production are increased in mice treated with 1,25(OH)(2)D. The Northern Finland Birth Cohort of all born in 1966 found the prevalence of atopy and allergic rhinitis at age 31 years was somewhat higher in those who had received vitamin D supplementation regularly during the first year compared to others (OR 1.46, and OR 1.66). A similar association was observed for asthma (OR 1.35). Infant vitamin d supplementation and allergic conditions in adulthood: northern Finland birth cohort 1966. Hypponen E, Sovio U, et al. London, UK. Ann N Y Acad Sci. 2004 Dec;1037:84-95

Bladder Overactivity Lower with Higher Vitamin D, Potassium, Protein in Diet: A random sample of 6,371 women with a one year follow-up found that higher intakes of vitamin D (P = 0.008), protein (P = 0.03), and potassium (P = 0.05) were significantly associated with decreased risks of onset. Although overall the associations with vitamin B6 and niacin were not significant (P = 0.08 and P = 0.13), there was some evidence of a decreased risk of onset with higher intakes. Nutrient composition of the diet and the development of overactive bladder: A longitudinal study in women. Dallosso HM, McGrother CW, Matthews RJ, Donaldson MM. University of Leicester, UK. Neurourol Urodyn. 2004;23(3):204-10

Burn Injury Children Need Vitamin D Supplement: In a University of Texas, Galveston, authors report that severe burn injury is associated with vitamin D deficiency, low bone turnover, and abnormalities in calcium homoeostasis. Patients do not routinely receive vitamin D supplementation and sun exposure is currently not controlled. By analysis of skin biopsy samples for vitamin D3 precursors after exposure to ultraviolet B light, it was found that the conversion of 7-dehydrocholesterol to previtamin D3 was still reduced in children an average of 14 months after the burn. Low serum 25-hydroxyvitamin D concentrations were also found. Vitamin D supplementation should be given after burn injury. Lancet. 2004 Jan 24;363(9405):291-2

Cancer Levels Lowered by More Sunlight: Cancer (2002;94:1867-75) examined cancer mortality in the United States. Deaths from a range of cancers of the reproductive and digestive systems were approximately twice as high in New England as in the Southwest, despite a diet that varies little. There was a close inverse correlation between cancer mortality and the levels of ultraviolet B light. The likeliest mechanism is for a protective effect from sunlight producing more vitamin D. The same geographical trend affects Afro-Americans, whose overall cancer rates are significantly higher. Darker skinned people require more sunlight to synthesize vitamin D. The strongest inverse correlation is with breast, colon, and ovarian cancer. Other cancers apparently affected by sunlight include tumors of the bladder, uterus, esophagus, rectum, and stomach. Cancer (2002;94:272-81) looked at rates of breast cancer in 35 countries. That study attributed 25% of cases of breast cancer in Europe to insufficient exposure to ultraviolet B. The correlation between breast cancer and latitude in Europe became more clear when Scandinavia was removed from the analysis. Scandinavian get a large amount of vitamin D from fish consumption. 

Cancer of the Breast: Vitamin D and Calcium Appear to Markedly Reduce: For women ages 40-60 with screening mammograms, multivariate logistic regression found that for increasing vitamin D intake (<50, 50-99, 100-199, and >/=200 IU/d), for extensive densities were reduced by 49%, 63%, and 76% with increasing intake compared to the lowest group or adjusted ORs 1.00 (reference), 0.51, 0.37, and 0.24, respectively (P = 0.0005). For increasing calcium intake (<500, 500-749, 750-999, and >/=1,000 mg/d), adjusted ORs were 1.00, 0.63, 0.25, and 0.24 (P = 0.0006). This suggests that dietary vitamin D and calcium could reduce breast cancer risk possibly through influences on breast tissue morphology. Vitamin d, calcium, and mammographic breast densities. Berube S, Diorio C, et al. Quebec. Cancer Epidemiol Biomarkers Prev. 2004 Sep;13(9):1466-72

Cancer: Breast: Calcium Helped But Not Vitamin D: In 68,567 postmenopausal women followed for 9 years in the Cancer Prevention Study II Nutrition Cohort, 2,855 developed breast cancer. Women with the highest intake of dietary calcium (>1,250 mg/d) were at a lower risk of breast cancer than those reporting < or =500 mg/d [RR, 0.80; P(trend) = 0.02]; however, neither use of supplemental calcium nor vitamin D intake was associated with risk. Consumption starting at two or more servings of dairy products per day was likewise inversely associated with risk (RR, 0.81; P(trend) = 0.002, compared with <0.5 servings/d). Dairy, calcium, and vitamin D intake and postmenopausal breast cancer risk in the Cancer Prevention Study II Nutrition Cohort. McCullough ML, et al. American Cancer Society, Atlanta, GA. . Cancer Epidem Biomarker Prev 2005 Dec;14(12):2898-904. 

Cancer of the Breast: Low Vitamin D and Vitamin D Receptor Gene Polymorphism Increase Risk Together: 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. In a case-control study of breast cancer patients (n=179) and controls (n=179), women with 25(OH)D levels <50nM and the bb BsmI VDR genotype are 6.82 times more likely to have breast cancer than subjects with levels of 25(OH)D>50nM and either the BB or Bb genotype (P<0.001). Plasma 25-hydroxy vitamin D concentrations, vitamin D receptor genotype and breast cancer risk in a UK Caucasian population. Lowe LC, Guy M, et al. St. George's Hospital Medical School, London, UK. Eur J Cancer. 2005 May;41(8):1164-1169

Cancer of the Colon: Vitamin D Levels Lower: In a nested case-control study among women in the Nurses' Health Study, 193 colorectal cancer cases, ages 46-78, diagnosed up to 11 years after blood collection were matched with controls. Odds ratios (OR) for risk of colorectal cancer were calculated using conditional logistic regression adjusted for body mass index, physical activity, smoking, family history, use of hormone replacement therapy, aspirin use, and dietary intakes. Among women in the highest quintile (fifth) in vitamin D levels, the OR was 0.53 (p=.006)(a 47% decrease). The benefit from higher 25(OH)D concentrations was observed for cancers at the distal colon and rectum (P = 0.02) but was not evident for those at the proximal colon (P = 0.81). Plasma vitamin d metabolites and risk of colorectal cancer in women. Feskanich D, Ma J, Fuchs CS, Kirkner GJ, Hankinson SE, Hollis BW, Giovannucci EL. Harvard Medical Cancer Epidemiol Biomarkers Prev. 2004 Sep;13(9):1502-8

Cancer of the Colon: Vitamin D and Calcium Intake Not Related: In vivo and in vitro studies have suggested a protective role of calcium and vitamin D in the development of colorectal cancer. However, in a 10 year follow-up 39,876 women over age 44 and free of cardiovascular disease and cancer, 223 of developed colorectal cancer. Intakes of total calcium and vitamin D were not associated with risk of colorectal cancer. Intakes of calcium and vitamin D and risk of colorectal cancer in women. Lin J, Zhang SM, et al. Harvard. Am J Epidemiol. 2005 Apr 15;161(8):755-64.

Cancer of the Colon: Colon Polyps Less Likely with Higher Vitamin D Consumption: A Portland VA study of 3,100 men given screening colonoscopies found that those reported consuming over 645 IUs of vitamin D per day were 40% less likely to have advanced polyps compared to those consuming little or no vitamin D. The Odds Ratio of polyps with higher cereal fiber was OR = 0.95, NSAID use OR 0.66, smoking OR 1.85, 1st degree relative with colon cancer OR 1.6. Risk Factors for Advanced Colonic Neoplasia and Hyperplastic Polyps in Asymptomatic Individuals. Lieberman DA, Prindiville S, Weiss DG, Willett W. JAMA 2003 Dec 10;290(22):2959-2967. Similar: Cancer Epidemiol Biomarkers Prev. 2005 Feb;14(2):525-8.

Cancer of the Colon: Colon Adenomas Decreased by Calcium if Higher Vitamin D Levels: 803 patients with colorectal adenomas in a DB PC study were given calcium or placebo. Calcium was of no value for those with average or below vitamin D levels but had an RR (Risk Ratio) = 0.71 for those with above average vitamin D levels, i.e., a 29% decrease.  Those with high D levels did better only if on a calcium supplement. Vitamin D, calcium supplementation, and colorectal adenomas: results of a randomized trial. Grau MV, Baron JA, Sandler RS, Haile RW, Beach ML, Church TR, Heber D. J Natl Cancer Inst. 2003 Dec 3;95(23):1765-71. Ed: Calcium supplements are fine for women, but increase prostate cancer in men.

Cancer of the Colon: Colon Polyps: Vitamin D and Calcium Supplements Not Quite Significant Effect: In the 4-year Polyp Prevention Trial (PPT) randomized study of a high-fiber, high-fruit and vegetable, low-fat diet on the recurrence of adenomatous polyps in the large bowel, recurrence was found in 754 of the 1905 patients. There were no overall significant associations between adenoma recurrence and dietary calcium intake [OR for the 5th compared with the lowest quintile = 0.91], total calcium intake (OR = 0.86; P-trend = 0.20), or dietary vitamin D intake (OR = 0.93; P-trend = 0.43). Supplemental calcium and vitamin D use during follow-up also were inversely associated with adenoma recurrence (OR for any compared with no use = 0.82; and OR = 0.82). Slightly stronger associations were noted for the prevention of multiple recurrences. The association of calcium and vitamin d with risk of colorectal adenomas. Hartman TJ, Albert PS, et al. The Pennsylvania State University, PA; J Nutr. 2005 Feb;135(2):252-9

Cancer: Endometrial: Vitamin D and Calcium Lower Risk: In a case-control study of 85 cases of endometrial cancer and 629 controls, there was no association between EC risk and consumption of animal or vegetable proteins, saturated, monounsaturated, or polyunsaturated fat, although high intake of lactose (odds ratio [OR], 0.46, P = 0.004), vitamin D (OR, 0.38, P= 0.003), and calcium (OR, 0.39, P= 0.02) were inversely associated with EC. Dietary vitamin D and calcium may play an important role in the development of EC. Dietary factors and endometrial cancer risk. Results of a case-control study in Mexico. Salazar-Martinez E, et al. National Institute of Public Health, Cuernavaca, Mexico. Int J Gynecol Cancer. 2005 Sep-Oct;15(5):938-45.

Cancer: Lung: Vitamin D Linked to Improved Survival in Non-Small Cell Lung Cancer: Vitamin D may inhibit the development and progression of a wide spectrum of cancers. In a study of the associations of surgery season and vitamin D intake with recurrence-free survival (RFS) and overall survival in 456 early-stage non-small cell lung cancer patients, patients who had surgery in summer had a better RFS than those who had surgery in winter (HR= 0.75), with 5-year RFS rates of 53% vs. 40% (P = 0.10). Patients who had surgery during summer with the highest vitamin D intake had much better RFS (HR=0.33) than patients who had surgery during winter with the lowest vitamin D intake, with the 5-year RFS rates of 56% vs. 23%. Similar associations of surgery season and vitamin D intake with overall survival were also observed. Vitamin d is associated with improved survival in early-stage non-small cell lung cancer patients. Zhou W, et al. Harvard. . Cancer Epidemiol Biomarkers Prev. 2005 Oct;14(10):2303-9.

Cancer: Non-Hodgkin Lymphoma Lower with Sun: In a study of 704 adult victims of non-Hodgkin lymphoma (NHL) and 694 controls, the risk of NHL fell with increasing reported sun exposure hours. Relative to 1.0 for the lowest quarter of total sun exposure hours, the odds ratios (ORs) for successively higher quarters were 0.72, 0.66 and 0.65 (p=0.01). The association of sun exposure on nonworking days with NHL was stronger; OR for highest quarter 0.47 (p=0.0001). These associations appeared strongest in women and in childhood. Vitamin D might be the mechanism for the benefit. Sun exposure may protect against non-Hodgkin lymphoma: a case-control study. Hughes AM, Armstrong BK, et al. University of Sydney, Australia. Int J Cancer. 2004 Dec 10;112(5):865-71

Cancer of the Prostate: Onions, Vitamin D from Sunlight Linked to Lower Prostate Cancer; Meat Bad: Prostate cancer mortality rates for 32 European ethnic countries found the strongest risk factor for prostate cancer mortality was animal products, with the nonfat portion of milk and alcohol being somewhat weaker; the strongest risk reduction factors were onions, other protective vegetable products (excluding alcohol, oils, and sweeteners), and solar UV-B radiation (sunlight) exposure.  A multicountry ecologic study of risk and risk reduction factors for prostate cancer mortality. Grant WB. Eur Urol. 2004 Mar;45(3):271-9. 

Cancer of the Prostate: PSA Rise Markedly Slowed: When local treatments for prostate cancer fails, the prostate-specific antigen (PSA) rises in the absence of symptoms. Calcitriol has been shown to prolong the doubling time of PSA using near-toxic doses. Vitamin D (cholecalciferol) 2,000 IU/d, a biochemical precursor of calcitriol, in 15 patients resulted in 9 of the patients having PSA levels decreased or unchanged  for as long as 21 mo. The rate of PSA rise slowed after administration of cholecalciferol (P = 0.005) compared with that before cholecalciferol: a doubling time of 14.3 months prior to 25 mo after starting cholecalciferol. Only 1 failed to have an increase in PSA doubling time. There were no side effects reported Pilot study: potential role of vitamin D (Cholecalciferol) in patients with PSA relapse after definitive therapy. Woo TC, Choo R, et al. Toronto-Sunnybrook Regional Cancer Centre, Canada. Nutr Cancer. 2005;51(1):32-6.

Cancer of the Prostate: Linked to Low Vitamin D: Mortality rates from prostate cancer are significantly higher among African Americans than Caucasian Americans and are inversely related to the availability of ultraviolet (UV) radiation. Specific receptors for 1,25-dihydroxyvitamin D [1,25(OH)(2)D] are in human prostate cells; 1,25(OH)(2)D exerts prodifferentiating, antiproliferative, and antimetastatic effects on these cells; normal prostate cells express 1alpha-hydroxylase and synthesize their own 1,25(OH)(2)D. Thus, 1,25(OH)(2)D is an autocrine hormone in the prostate. Low levels of UV radiation/vitamin D are associated with an increased risk of prostate cancer in individual men.

Cancer of the Prostate: Sun Exposure Reduces Risk of Advanced Cases: In a case-control study of advanced prostate cancer among men ages 40 to 79 years of 905 European-Americans, 450 with cancer, skin pigmentation on the upper underarm compared to the forehead showed a 49% reduced risk of advanced prostate cancer  with high sun exposure (OR 0.51] and high occupational outdoor activity (OR, 0.73). 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. Sun exposure, vitamin D receptor gene polymorphisms, and risk of advanced prostate cancer. John FM. et al. Fremont, California. Cancer Res. 2005 Jun 15;65(12):5470-9.

Cancer of the Skin: Vitamin D Protective in Mice:  D3 (1,25(OH)(2)D(3)) protects human skin cells from ultraviolet radiation (UVR)-induced apoptosis. Researchers found a protective effect of Vitamin D compounds against DNA photodamage in vivo in hairless mice. Dixon KM, et al. University of Sydney, Australia. J Steroid Biochem Mol Biol. 2005 Jul 19

Depression More Common with Low Vitamin D in Secondary Hyperparathyroidism: 21 adults with secondary hyperparathyroidism without renal failure (serum calcium < 2.40 mmol/L, serum PTH > 6.4 pmol/L, and normal serum creatinine) and 63 control were compared. Those in the SHPT group had significantly impaired performance in 3 of 14 cognitive tests (Digit span forward, Stroop test part 1 and 2, and Word association test (FAS)) as compared with the controls, and also had a significantly higher depression score at the Beck Depression Inventory. A low level of serum 25-hydroxyvitamin D was significantly associated with a high depression score.

Depressed Women Have Lower Bone Density: In a study of 24 depressed women and 24 controls, the bone density in the women with past or current depression was was an average of 11% lower at the four different areas of bone measured. In addition, women with past or current depression had higher urinary cortisol excretion (71 vs. 51 micrograms per day, P=0.006), lower serum osteocalcin concentration (P=0.04), and lower urinary excretion of deoxypyridinoline (P=0.02). Bone mineral density in women with depression. Michelson D, Stratakis C, Hill L, Reynolds J, Galliven E, Chrousos G, Gold P. N Engl J Med. 1996 Oct 17;335(16):1176-81

Depression: Vitamin D: Seasonal Affective Disorder Helped: In a very small 15-patient randomized study, the eight patients given 100,000 I.U. of vitamin D supplementation one time showed a significant decrease in depression by 1 month follow-up but those given light therapy did not. Vitamin D status improved in both groups (74% vitamin D group, p < 0.005 and 36% phototherapy group, p < 0.01). Improvement in 25-OH D was significantly associated with improvement in depression scale scores (p=0.05). Baltimore. Vitamin D vs. broad spectrum phototherapy in the treatment of seasonal affective disorder. Gloth FM 3rd, Alam W, Hollis B. J Nutr Health Aging. 1999;3(1):5-7

Depression: Might Help Winter Depression : In a poorly done Australian DB PC study of 44 healthy adult lasting only 5 days (way too short), those receiving vitamin D 400 IU or 800 IU vs. placebo had an increase in positive mood and some decrease in negative affect. Vitamin D3 enhances mood in healthy subjects during winter. Lansdowne AT, Provost SC. Psychopharmacology (Berl). 1998 Feb;135(4):319-23

Depression: Vitamin D Tanning Spa Effect?: Steven R Feldman of Wake Forest published in J Amer Acad Derm a 6 week, 14 person study using tanning beds twice a week. One of the beds had a UV filter. Those using the bed giving out UV light tested more content and relaxed and 11 of 12 subjects preferred the UV bed without knowing of the difference. 7/13/04. Ed: UV light is the type of light that makes vitamin D.

Depressed Mood Not Helped by Vitamin D Supplement in Normal Women: A 1 year DB PC study found POMS scores for anxiety and depression highest in fall and lowest in spring and summer. Vitamin D at 400 IU/day for one year was of no benefit in reducing anxiety and depression in 250 females ages 43-72. Tufts University, Boston, Seasonal mood changes in 250 normal women. Harris S, Dawson-Hughes B, Psychiatr Res ’93;49:77. Ed: Since 400 IU of vitamin D is often inadequate at treating osteoporosis, 1000 IUs per day would have been a better test. Of course, vitamin D might help individuals with high levels of anxiety and depression more than those with average levels.

Diabetes in Children Markedly Reduced by Vitamin D 2000 IU Supplement: A Finnish study following 12,055 babies born in 1966 found those who were given the recommended 2000 IU of vitamin D supplement had an 88% reduced risk of developing diabetes (RR for regular vs no supplementation 0.12, and irregular vs no supplementation 0.16). Children who regularly took the recommended dose of vitamin D (2000 IU daily) had a RR of 0.22 compared with those who regularly received less than the recommended amount. Those who had rickets, a disease linked to vitamin D deficiency, in the first year of life had a three-fold risk of developing diabetes. Finland has the highest reported incidence of type 1 diabetes in the world. In north Finland, there are only two hours of sunlight, a key source of vitamin D, each day in December. BBC News 11/2/01 and Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM. Institute of Child Health, London, UK. Lancet. 2001 Nov 3;358(9292):1500-3.; Vitamin D status increases the expression of Type 1 diabetes in non-obese diabetic mice. Data in the mice, as well as human epidemiological data, point to the importance of preventing vitamin D deficiency in early childhood. Controlling this dietary factor could be an easy and safe way to reduce the incidence of Type 1 diabetes in subjects who are genetically at risk. Belgium. Diabetologia. 2004 Jan 31.

Diabetes in Children Reduced by Vitamin D Supplement: In a case-control study of 820 type 1 diabetics and 2335 controls from seven European countries, vitamin D supplementation in the early years was associated with a 33% decreased risk of Type I diabetes (OR 0.67). Vitamin D supplement in early childhood and risk for Type I (insulin-dependent) diabetes mellitus. The EURODIAB Substudy 2 Study Group. Diabetologia. 1999 Jan;42(1):51-4.

Diabetes: Vitamin D and Calcium Lower the Risk: In the Nurses' Health Study of 83,779 women who had no history of diabetes, cardiovascular disease, or cancer at baseline for the development of type 2 diabetes, during 20 years of follow-up, there were 4,843 new cases of type 2 diabetes. The relative risk (RR) of type 2 diabetes was 0.87 (p = 0.04) comparing the highest with the lowest category of vitamin D intake from supplements. The multivariate RRs of type 2 diabetes were 0.79 (p <0.001) comparing the highest with the lowest category of calcium intake from all sources and 0.82 (p <0.001) comparing the highest with the lowest category of calcium intake from supplements. A combined daily intake of >1,200 mg calcium and >800 IU vitamin D was associated with a 33% lower risk of type 2 diabetes with RR of 0.67 compared with an intake of <600 mg and 400 IU calcium and vitamin D. Vitamin d and calcium intake in relation to type 2 diabetes in women. Pittas AG, et al. Tufts-New England Medical Center. . Diab Care 2006 Mar;29(3):650-6.

Diabetes: Low Vitamin D Strongly Linked to Diabetes: Using nationwide U.S. Third National Health and Nutrition Examination Survey data of 6,228 adults, after djusting for sex, age, BMI, leisure activity, and quarter of year, the odds ratios for diabetes varied inversely (OR 0.25 for European-Americans and 0.17 for Mexican Americans) in the highest vitamin D quartile (25OHD > or =81.0 nmol/l) compared with the lowest (< or =43.9 nmol/l). This inverse association was not observed in African-Americans. Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey. Scragg R, Sowers M, Bell C. University of Auckland. Diabetes Care. 2004 Dec;27(12):2813-8

Diabetes: Low Vitamin D as Risk for Insulin Resistance and Metabolic Syndrome: In a study of 126 healthy, glucose-tolerant adults, univariate regression analyses showed that 25(OH)D concentration was positively correlated with the insulin sensitivity index (P < 0.0001) and negatively correlated with first phase insulin response (1stIR) (P = 0.0045) and second phase insulin response (2ndIR) (P < 0.0001). Multiple regression analyses confirmed an independent correlation between 25(OH)D concentration and ISI (P = 0.0007). An independent negative relation of 25(OH)D concentration with plasma glucose concentration was observed at fasting (P = 0.0258), 60 min (P = 0.0011), 90 min (P = 0.0011), and 120 min (P = 0.0007) during the oral-glucose-tolerance test. Subjects with hypovitaminosis D (<20 ng/mL) had a greater prevalence of components of metabolic syndrome than did subjects without hypovitaminosis D (30% compared with 11%; P = 0.0076). Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Chiu KC, Chu A, et al. University of California-Los Angeles. Am J Clin Nutr. 2004 May;79(5):820-5.

Diabetes: Vitamin D Supplement Helps Type 2 Diabetics: In a study of 10 type 2 diabetics on oral hypoglycemics compared to 17 controls, the diabetics were given vitamin D 1332 IU daily for one month. The mean plasma 25(OH)D level was 35.3 nmol/l at baseline, 70% of patients being vitamin D deficient. After one month, vitamin D levels increased by 76% with 70% of patients achieving normal levels. First phase insulin secretion (FPIS) increased significantly by 34%, while second phase increased 20%. There was a correlation between the change in FPIS and the change in 25(OH)D levels (p < 0.018). The results showed a decrease of 21% in insulin resistance after one month. The authors advocate adding vitamin D to the treatment plan of type 2 diabetics. The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients. Borissova AM, Tankova T, et al. University Hospital, Sofia, Bulgaria. Int J Clin Pract. 2003 May;57(4):258-61.

Diabetes: Low Vitamin D a Risk Factor for Glucose Intolerance: In a study of 142 elderly Dutchmen ages 70-88, 39% were deficient in vitamin D. After adjustment, the 1-hour glucose and area under the glucose curve during a standard 75-g oral glucose tolerance test were inversely associated with the vitamin D levels (r = -0.23, p < 0.01). After excluding newly diagnosed diabetics, total insulin concentrations during the test were also inversely associated with vitamin D levels (r = -0.18 to -0.23, p < 0.05). Hypovitaminosis D was a significant risk factor for glucose intolerance. Vitamin D, glucose tolerance and insulinaemia in elderly men. Baynes KC, Boucher BJ, et al. Royal London School of Medicine, UK. Diabetologia. 1997 Mar;40(3):344-7.

Diabetes: Vitamin D Receptor Gene Polymorphism Involved in Retinopathy: The vitamin D receptor (VDR) is extensively expressed in retina. The plasma concentration of 1,25-dihydroxyvitamin D3 has been inversely correlated with the severity of diabetic retinopathy (DR). The Taq I VDR polymorphism has been associated with severe DR. The Fok I VDR polymorphism is a T-to-C substitution in the first codon (f allele) abolishing the first translation initiation site and resulting in a peptide lacking 3 amino acids (F allele), which increases the transcriptional activity of VDR. 254 French adults with longstanding C-peptide-negative type 1 diabetes, 128 patients with absent/mild DR (control group) and 126 patients with preproliferative/proliferative DR (study group), were genotyped. The frequency of F allele was significantly higher in the control (66.4%) than in the study group (56%, OR=0.64, P = 0.016). In subjects with <25 yr of diabetes (median value, n = 134), this association was strongly increased (P = 0.0008).

Diabetes: Vitamin D Improved Diabetes in Diabetic Rats: Calcitriol improves streptozotocin-induced diabetes and recovers bone mineral density in diabetic rats. Del Pino-Montes J, et al. Universidad de Salamanca, Spain. Calcif Tissue Int. 2004 Dec;75(6):526-32.

Diabetes: Vitamin D Prevents Diabetes in Diabetic Prone Mice: Oral administration of 1,25-dihydroxyvitamin D3 completely protects NOD mice from insulin-dependent diabetes mellitus. Zella JB, et al. University of Wisconsin-Madison. Arch Biochem Biophys. 2003 Sep 1;417(1):77-80

Falls: Vitamin D Supplements and Calcium Reduce Risk in Women 46%, But Not in Men: In a DB PC 3-year supplementation with cholecalciferol-calcium of 199 men and 246 women age 65 or older and living at home, 55% of women and 45% of men reported at least 1 fall. Cholecalciferol 700 IU-calcium 500 mg/daily significantly reduced the risk of falling in women by 46%, but not in men (7%). Fall reduction was most pronounced in less active women (65%). Baseline 25-hydroxyvitamin D level did not modulate the treatment effect. Supplementation had a neutral effect in men independent of their physical activity level. Effect of cholecalciferol plus calcium on falling in ambulatory older men and women: a 3-year randomized controlled trial. Bischoff-Ferrari HA, et al. University Hospital Zurich, Switzerland. . Arch Int Med 2006 Feb 27;166(4):424-30.

F: Vitamin D Reduced Falling in Elderly 27%: In a 2-year, DB PC study of 149 elderly in hostels or nursing homes and with low normal (25-90) vitamin D levels, 665 falls occurred with vitamin D 1000 units/day vs. 890 falls with placebo, a 27% decrease. The risk of fracture decreased 31% (OR 0.69). Excluding 85 subjects whose vitamin D compliance was not greater than 50%, revealed a significant 37% reduction in the incident rate ratio for falls with vitamin D treatment, 0.63. 8 people needed to be treated for one year to prevent a fall occurring. University of Western Australia, Perth, Australia. J Am Geriatr Soc. 2005 Nov;53(11):1881-8.

Falls and Hip Fractures Reduced After Stroke: Vitamin D Increases Muscle Strength: In a 2-year DB PC study of 96 elderly women with poststroke hemiplegia, those given 1,000 IU ergocalciferol daily had a 59% reduction in falls (p = 0.003). There were increases in the relative number and size of type II muscle fibers and improved muscle strength in the vitamin D-treated group. Hip fractures occurred in 4 of 48 placebo group and 0 in 48 vitamin D(2) group during the 2-year study period (p = 0.049).  At baseline, serum 25-hydroxyvitamin D levels were in the deficient range (<10 ng/ml) in all patients; and vitamin D treatment enhanced serum 25-hydroxyvitamin D and1,25-dihydroxyvitamin D levels. Low-Dose Vitamin D Prevents Muscular Atrophy and Reduces Falls and Hip Fractures in Women after Stroke: A Randomized Controlled Trial. Sato Y, et al. Iizuka, Japan. Cerebrovasc Dis. 2005 Jul 27;20(3):187-192

Falls Reduced 22% in Elderly by Vitamin D:  Based on 5 random controlled trials involving 1,237 participants, vitamin D supplementation reduced the risk of falling by 22% (corrected OR, 0.78) compared with patients receiving calcium or placebo. From the pooled risk difference, the number needed to treat (NNT) was 15, or equivalently 15 patients would need to be treated with vitamin D to prevent 1 person from falling. Effect of Vitamin D on falls: a meta-analysis. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB, Bazemore MG, Zee RY, Wong JB. Harvard. JAMA. 2004 Apr 28;291(16):1999-2006

Falls in Elderly Increased with Vitamin D Deficiency; Supplement Helps: Leon Flicker, University of Western Australia in Perth found in a study of 1500 elderly women, average age 84, that severe vitamin D deficiency is common in Australia. Almost half in high-level residential care, though not bedridden, were severely deficient. A fifth of elderly women who were healthy enough to live in low-level residential care were also severely deficient. A doubling of vitamin D levels reducing their risk by 20% even when other risk factors, such as the use of sedatives, were taken into account. Journal of the American Geriatrics Society 12/2003;51:1533). Supplements reduced the number of falls and the number of breaks caused. The supplements only need to be given every few months because the body can store vitamin D.

Falls in Elderly Reduced by Vitamin D Supplement 800 IU: A DB PC study of 122 women over age 65 used 1200 mg/d calcium with or without vitamin D. It found a 49% decrease in falls over 3 months. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. Bischoff HA, Stahelin HB, Dick W, Akos R, Knecht M, Salis C, Nebiker M, Theiler R, Pfeifer M, Begerow B, Lew RA, Conzelmann M. J Bone Miner Res 2003 Feb;18(2):343-51

Falls: Hip Fractured Women Helped Best by Oral 800 IU: In a randomized study, 150 previously independent elderly women, recruited following surgery for hip fracture, were assigned to receive a single injection of 300,000 units of vitamin D(2), injected vitamin D(2) plus 1 g/day oral calcium, 800 units/day oral vitamin D(3) plus 1 g/day calcium, or no treatment. Follow-up was after one year with measurement of 25-hydroxyvitamin D, parathyroid hormone, bone mineral density, and falls. Vitamin D levels increased and parathyroid hormone was suppressed in all the actively treated groups, more so in the group receiving combined oral vitamin D and calcium. 20% of participants injected with vitamin D were deficient in 25-hydroxyvitamin D a year later. Bone mineral density showed small but statistically significant differences of up to 4.6% between actively treated groups and placebo. Relative risk of falling in the groups supplemented with vitamin D was 0.48 compared with controls, a 52% decrease. Age Ageing. 2004 Jan;33(1):45-51

Falls: Vitamin D Helps Standing and Walking in Elderly: In a population-based survey of 4,100 ambulatory U.S. adults over age 60, an 8-foot walk test compared subjects in the lowest and highest quintiles (fifths) of serum 25(OH)D; the quintile highest in vitamin D had an average decrease of 0.27 second vs. the lowest quintile [P < 0.001]. On the sit-to-stand test, the highest quintile had an average decrease of 0.67 second vs. the lowest [P = 0.017]. Most of the improvement occurred in subjects with 25(OH)D concentrations between 22.5 and approximately 40 nmol/L, but further improvement was seen in the range of 40-94 nmol/L. In both active and inactive ambulatory elderly, 25(OH)D concentrations between 40 and 94 nmol/L are associated with better musculoskeletal function in the lower extremities than are concentrations < 40 nmol/L. Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged > or =60 y. Bischoff-Ferrari HA, Dietrich T, Orav EJ, Hu FB, Zhang Y, Karlson EW, Dawson-Hughes B. Harvard. Am J Clin Nutr. 2004 Sep;80(3):752-8

Fracture Healing: Vitamin D Plus Calcium Helps in Elderly: In a 12-week DB PC study of 30 elderly women average age 78 with humerus fractures, those receiving oral 800 IU vitamin D(3) plus 1 g calcium had a positive effect on fracture healing over the first 6 weeks. The Effect of Calcium and Vitamin D(3) Supplementation on the Healing of the Proximal Humerus Fracture: A Randomized Placebo-Controlled Study. Doetsch AM, Faber J, Lynnerup N, Watjen I, Bliddal H, Danneskiold-Samsoe B. Frederiksberg Hospital, Copenhagen, Denmark. Calcif Tissue Int. 2004 May 27

Gingivitis: Higher Vitamin D Helps a Little: In 6700 never smokers ages 13-90 from the third National Health and Nutrition Examination Survey, when adjusted for subject- and site-specific covariates included age, sex, race-ethnicity, income, body mass index, diabetes, use of oral contraceptives and hormone replacement therapy among women, intake of vitamin C, missing teeth, full crown coverage, presence of calculus, frequency of dental visits, and dental examiner and survey phase, compared to those in the lowest 25(OH)D quintile, the highest 25(OH)D quintile were 20% less likely to bleed on gingival probing (P< 0.001). The association appeared to be linear over the entire 25(OH)D range, was consistent across racial or ethnic groups, and was similar among men and women as well as among users and nonusers of vitamin and mineral supplements. Association between serum concentrations of 25-hydroxyvitamin D and gingival inflammation. Dietrich T, et al. Boston University. . Am J Clin Nutr 2005 Sep;82(3):575-80.

Heart: Less Sunlight, More Heart Disease: Insufficient vitamin D status may contribute to the worldwide high prevalence of CVD. Geographic latitude, altitude, season, and the place of residence (urban or rural) are associated with CVD mortality. All these factors also have an influence on human UVB exposure and thus on vitamin D status. The first intervention trials indicate that vitamin D may suppress cardiovascular risk markers. More controlled clinical trials are needed to investigate whether optimal oral vitamin D supplementation is able to reduce CVD morbidity and mortality. Putting cardiovascular disease and vitamin D insufficiency into perspective. Zittermann A, et al. Ruhr University Germany. Br J Nutr. 2005 Oct;94(4):483-92.

Heart Deaths Lowered in Elderly Women by Vitamin D Supplements: The University of California at San Francisco studied 9,704 women aged 65 and older. Of these, 4,272 were taking vitamin D supplements. Over a period of nearly 11 years, 420 of the women died of coronary heart disease (CHD). Women who used vitamin D supplements had a 31% lower risk of heart disease death. Women with osteoporosis, a disease caused by loss of calcium from the bones, are more likely to die of CHD. BBC News 4/29/02

Heart Deaths Much Lower in Dialysis Patients Using Vitamin D Supplements: Renal failure results in deficiency of active vitamin D3. In a study of the risk of death among hemodialysis patients who were regular users (n = 162) and non-users (n = 80) of vitamin D3 for a follow-up of 61 months, the vitamin D users showed a 72% lower risk of death from cardiovascular disease than the non-users [HR 0.287, P = 0.003], whereas the risk for death from non-cardiovascular disease was not different. Lower risk for cardiovascular mortality in oral 1alpha-hydroxy vitamin D3 users in a haemodialysis population. Shoji T, et al. Osaka City University, Japan. Nephrol Dial Transplant. 2004 Jan;19(1):179-84.

Heart Failure Patients Had Lower Vitamin D Levels: Comparing 54 patients with chronic heart failure with 34 healthy people, researchers found that vitamin D levels were up to 50% lower in the blood of CHF patients. BBC News 2/18/03 and Journal of the American College of Cardiology. U Bonn

Heart: Vitamins D Plus K Appeared Better Than D Alone: In a DB PC 181-patient study, those on a mineral plus D plus vitamin K did best. Univ. Maastricht, Beneficial effects of vitamins D and K on the elastic properties of the vessel wall in postmenopausal women: a follow-up study. Thromb Haemost. 2004 Feb;91(2):373-80 

HIV Patients May Need Vitamin D Supplementation: In a lab study using intact cells, HIV-protease inhibitors (a standard medication in HIV treatment) markedly suppress the activities of 25- and 1alpha-hydroxylase, which are critical in 1,25(OH) D synthesis, while exerting mild inhibition of 24-hydroxylase, responsible for 1,25(OH) D catabolism. Defective 1,25(OH) D production caused by protease inhibitors could contribute to the bone demineralization in HIV patients. Washington Univ. AIDS. 2003 Mar 7;17(4):513-20

High Blood Pressure: Vitamin D and Sunlight May Help Prevent: The prevalence of hypertension in a population increases with distance north or south of the equator.  Ultraviolet light may contribute to geographic and racial blood pressure differences. Rostand SG. Hypertension 1997;30:150–6. Hypertension becomes less severe in subjects whose 25(OH)D concentrations are increased to >100 nmol/L through ultraviolet exposure. Krause R, Buhring M, Hopfenmuller W, Holick MF, Sharma AM. Ultraviolet B and blood pressure. Lancet 1998;352:709–10.

High Blood Pressure: Vitamin D Suppresses Renin and Hypertension: Vitamin D is a potent endocrine suppressor of renin biosynthesis. Mice lacking the Vitamin D receptor have elevated production of renin and angiotensin II, leading to hypertension, cardiac hypertrophy and increased water intake. These abnormalities can be prevented by treatment with an ACE inhibitor or AT(1) receptor antagonist. Vitamin D repression of renin expression is independent of calcium metabolism, the volume- and salt-sensing mechanisms and the Ang II feedback regulation. In normal mice, Vitamin D-deficiency stimulates renin expression, whereas injection of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] reduces renin synthesis. In cell cultures, 1,25(OH)(2)D(3) directly suppresses renin gene transcription by a VDR-dependent mechanism. Vitamin D: a negative endocrine regulator of the renin-angiotensin system and blood pressure. Li YC, Qiao G, Uskokovic M, Xiang W, Zheng W, Kong J. University of Chicago. J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):387-92

Hyperparathyroidism Helped: Vitamin D deficiency led to more severe bone disease, increased parathyroid tumor growth, and delayed postoperative recovery of parathyroid function in patients with primary hyperparathyroidism in an epidemiologic study. Correlations between Vitamin D Status and Biochemical/Clinical and Pathological Parameters in Primary Hyperparathyroidism. Ozbey N, et al. Istanbul University. World J Surg

Lungs: Strong Relationship Vitamin D and Pulmonary Function: Using data from the Third National Health and Nutrition Examination Cross-sectional Survey of 14,091 American adults, after adjustment for age, gender, height, body mass index, ethnicity, and smoking history, the mean FEV1 was 126 mL, and the mean FVC was 172 mL greater for the highest quintile of serum 25-hydroxy vitamin D level (> 85.7 nmol/L) compared with the lowest quintile (< 40.4 nmol/L; p < 0.0001). With further adjustment for physical activity, the intake of vitamin D supplements, milk intake, and the level of serum antioxidants, the mean difference between the highest and lowest quintiles of 25-hydroxy vitamin D was 106 mL for FEV1, and 142 mL for FVC (p < 0.0001). Relationship between serum 25-hydroxyvitamin d and pulmonary function in the third national health and nutrition examination survey. Black PN, et al. University of Auckland, New Zealand. . Chest 2005 Dec;128(6):3792-8.


Thomas E. Radecki, M.D., J.D.

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