Multiple Sclerosis Less with Fish, Cod Liver Oil, or Sun Exposure: In a study of 152 MS patients and 402 population controls born north of the arctic circle, increased outdoor activities during summer in early life were associated with a decreased risk of MS, most pronounced at ages 16-20 years (odds ratio (OR) 0.55, p = 0.001, adjusted for intake of fish and cod-liver oil). A protective effect of supplementation with cod-liver oil was suggested in the subgroup that reported low summer outdoor activities (OR 0.57, p = 0.072). Consumption of fish three or more times a week was also associated with reduced risk of MS (OR 0.55, p = 0.024). Outdoor activities and diet in childhood and adolescence relate to MS risk above the Arctic Circle . Kampman MT , et al. University Hospital of North Norway , Tromso , Norway . J Neurol 2007 Mar 21. Ed: Fish and cod liver oil are both high in vitamin D, which is also produced by sunlight striking the skin.

Multiple Sclerosis Protected Against by Vitamin D: In a Harvard study of 187,563 women in the Nurses' Health Study I and II who were followed for an average of 11 years with the diet assessed at baseline and updated every 4 years thereafter, 173 cases of MS were confirmed during follow-up. The highest quintile (1/5) in total vitamin D intake at baseline, when compared to those with the lowest intake, had a 33% lower risk of MS: RR 0.67 (p = 0.03). Intake of vitamin D from supplements was also inversely associated with risk of MS; the RR for women with intake of >or=400 IU/day vs. women with no supplemental vitamin D was 0.59 (p = 0.006). No association was found between vitamin D from food and MS incidence. Vitamin D intake and incidence of multiple sclerosis. Munger KL, Zhang SM, O'Reilly E, Hernan MA, Olek MJ, Willett WC, Ascherio A. Neurology. 2004 Jan 13;62(1):60-5.

Multiple Sclerosis Less Likely with Higher Vitamin D Levels: In a study of 150 military personnel with MS vs. 300 matched controls using blood samples from five years before the MS diagnosis, those with the highest vitamin D levels had a 62% lower risk of MS with the strongest benefit to those under age 20. (JAMA 296:2832, 2006).

Multiple Sclerosis: Vitamin D Might Help: 15 patients with relapsing-remitting MS and at least one clinical relapse within the previous 12 months received oral calcitriol (target dose: 2.5 microg/d) for 48 weeks. Dietary calcium was restricted to 800 mg/d. The on-study exacerbation rate (27%) was less than baseline. Four patients experienced five clinical relapses but only one patient worsened by >1 EDSS point. Brain MRI revealed enhancing lesions in five patients at baseline (33%) and in four (29%) at both 24 and 48 weeks. A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing-remitting multiple sclerosis. Wingerchuk DM, et al. Mayo Clinic,  Scottsdale , Arizona. . J Neurol Neurosurg Psychiatry. 2005 Sep;76(9):1294-6.

Multiple Sclerosis: Fetuses Developing During Sunny Months Have Less MS: In a study of 17,874 Canadian, 11,502 British, and 12,700 Danish and Swedish patients with multiple sclerosis, fewer (8.5%) people with MS were born in November and significantly more (9.1%) were born in May. Timing of birth and risk of multiple sclerosis: population based study. Willer CJ, Dyment DA, et al. University of Michigan. BMJ. 2005 Jan 15;330(7483):120. Ed: Infants born in November would have developed during the months of greatest sunlight and therefore highest vitamin D levels in the mothers, especially in the 4th to 6th months which are critical for nervous system development.  May is the opposite.

Multiple Sclerosis: Sun, Vitamin D Reduce Risk: Higher sun exposure when aged 6-15 years (average 2-3 hours or more a day in summer during weekends and holidays) was associated with a 69% decreased risk of multiple sclerosis (adjusted odds ratio 0.31) in a case control study of 136 cases and 272 controls in Tasmania. Higher exposure in winter seemed more important than higher exposure in summer. Greater actinic damage was also independently associated with a 68% decreased risk of multiple sclerosis (0.32). Administration of ultraviolet radiation or 1,25-dihydroxycholecalciferol, the active form of vitamin D-3, which is produced under the influence of ultraviolet radiation, has shown protective effects against the induction or progression of experimental allergic encephalomyelitis. A strong ecological association between regional levels of ultraviolet radiation and prevalence of multiple sclerosis is evident in Australia (r = -0.91). In a death certificate based case-control study, high residential or occupational exposure to sunlight was negatively associated with mortality from multiple sclerosis. A strong latitudinal gradient of prevalence of multiple sclerosis in Australia even among immigrants from the United Kingdom and Ireland (70% who migrated after age 15) suggests exposure later in life might also be important. Tasmania's latitude is 41-3°S and it has a high prevalence of multiple sclerosis at 75.6 per 100,000 population. BMJ 2003;327:316 8/9/03. Ed: Taking vitamin D is a lot easier than moving to the Equator.

Multiple Sclerosis: Increased Vitamin D Gene Variants: To investigate VDR gene variation using three intragenic restriction fragment length polymorphisms (Apa I, Taq I and Fok I) in an Australian MS case-control population, 104 Australian MS patients and 104 controls were studied. There was a significant difference of genotype distribution frequency between the case and control groups for the functional exon 9 VDR marker Taq I (p(Gen) = 0.016) and a stronger difference for the allelic frequency (p(All) = 0.0072). The Apa I alleles were also found to be associated with MS (p(All) = 0.04) but genotype frequencies were not significantly different from controls (p(Gen) = 0.1). The Taq and Apa variants are in very strong and significant linkage disequilibrium (D' = 0.96, P < 0.0001). The genotypic associations are strongest for the progressive forms of MS (SP-MS and PP-MS). Variation in the vitamin D receptor gene is associated with multiple sclerosis in an Australian population. Tajouri L, et al. Griffith University Gold Coast, Southport, Queensland, Australia. J Neurogenet. 2005 Jan-Mar;19(1):25-38.

Multiple Sclerosis: Vitamin D Low: In a study of 31 MS patients and 30 controls, BMD of the lumbar spine was nearly 1 SD lower in MS patients compared with the healthy reference population (Z scores). MS patients had significantly lower vitamin D levels (17.3 ng/ml vs 43.1 ng/ml; P < 0.001) compared to controls, and 19 patients (61%) had a serum level of vitamin D that was less than 20 ng/ml. Vitamin D deficiency and reduced bone mineral density in multiple sclerosis: effect of ambulatory status and functional capacity. Ozgocmen S, et al. Firat Universitesi, Elazig, Turkey. J Bone Miner Metab. 2005;23(4):309-13

Muscle Mass Decrease in Elderly Associated with Common Vitamin D Receptor Gene Change: In a University of Pittsburgh study of European-American men over age 57, muscle mass (fat-free mass) was found more than twice as deficient in the 38% of men with the FF vitamin D receptor gene vs. the 48% with the Ff gene pattern and 14% with the ff gene pattern. The increased risk of sarcopenia with RR = 2.17. J Gerontol A Biol Sci Med Sci. 2004 Jan;59(1):10-5. 

Muscle Mass Decreased in Dutch Elderly with Low Vitamin D: In adults over 64 in the Longitudinal Aging Study Amsterdam, grip strength (n = 1008) and arm and leg skeletal muscle mass (n = 331, using dual-energy x-ray absorptiometry) were measured at baseline and after a 3-year follow-up. Sarcopenia was defined as the lowest sex-specific 15th percentile of the cohort or a loss of grip strength greater than 40% or a loss of muscle mass greater than 3%. After adjustment for physical activity level, season of data collection, serum creatinine concentration, chronic disease, smoking, and body mass index, persons with low (<25 nmol/liter) baseline 25-OHD levels were 157% and 114% more likely to develop sarcopenia, compared with those with high (>50 nmol/liter) vitamin D levels. High PTH levels (usually caused by low vitamin D) were associated with an increased risk of sarcopenia: odds ratio = 1.71 based on grip strength, odds ratio = 2.35 based on muscle mass. J Clin Endocrinol Metab. 2003 Dec;88(12):5766-72; Ed: Vitamin D supplementation might help correct this very common problem and getting genetic testing is unreasonable expensive at the present time. However, a small DB PC study of 65 elderly men living in the community did not find any increased strength for vitamin D 1000 IU/day for 6 months. Maybe the study was too small or too short to detect the benefit. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. Visser M, Deeg DJ, Lips P; Longitudinal Aging Study Amsterdam.  J Am Geriatr Soc. 2003 Dec;51(12):1762-7

Muscle Pain Linked to Low Vitamin D in Minnesota: Of 150 patients screened with persistent, nonspecific musculoskeletal pain, 140 had unrecognized and untreated severe hypovitaminosis D including 55% of those under age 30. This risk extended to those considered at low risk for vitamin D deficiency: non-elderly, non-housebound, or nonimmigrant persons of either sex. Nonimmigrant women of childbearing age with such pain appear to be at greatest risk for misdiagnosis or delayed diagnosis. Seasons of the year did not affect vitamin D levels. Because osteomalacia is a known cause of persistent, nonspecific musculoskeletal pain, screen all outpatients with such pain for hypovitaminosis D. U Minn. Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain. Plotnikoff GA, Quigley JM. Mayo Clin Proc. 2003 Dec;78(12):1463-70. The direct effects of vitamin D on skeletal muscle cells include induction of transcription factors such as c-myc (genomic action), and activation of Ca channels, Src tyrosine kinase and MAP kinase (non-genomic action). Recent studies on VDR gene knockout mice reveal that VDR also regulates expression of the MyoD family of transcription factors in skeletal muscle. Thus, vitamin D and Ca appear to regulate proliferation, maturation and function of skeletal muscle through these complex actions. Endo et al. Univ Tokushima. Clin Calcium. 2003;13(7):905-7.

Musculoskeletal Pain Common Due to Vitamin D Deficiency and Easily Corrected: The deficiency of vitamin D is very common in the adults of all ages. It's even more prevalent among darker skinned people or those not getting sunshine. In an English rheumatology clinic, 78% of Asians from India vs. 58% of other patients had low vitamin D levels. When recognized, hypovitaminosis D3 is easily treatable. A study on osteomalacic myopathy (muscle pains and weakness) in veiled Arabic women in Denmark found that muscle strength returned to normal after six months' treatment. Musculoskeletal pain in female asylum seekers and hypovitaminosis D3. Gabrielle de Torrent de la Jara, Alain Pcoud, Bernard Favrat, University of Lausanne. BMJ  7/17/2004;329:156-157.

Muscle: Five cases of Severe Wheelchair-Bound Myopathy due to vitamin D Deficiency: Each was confined to a wheelchair because of weakness and immobility, one a 37-year-old African American with type 1 diabetes mellitus. All had been misdiagnosed. There was a proximal myopathy; diagnosed confirmed by low vitamin D and high parathyroid levels and  restoration of normal muscle strength in 4 to 6 weeks. Four became fully mobile and one partially. Severe myopathy associated with vitamin D deficiency in western New York. Prabhala A, Garg R, et al. State University of New York at Buffalo. Arch Intern Med. 2000 Apr 24;160(8):1199-203.

Nephotic Syndrome Children Low in Vitamin D: Serum 25-hydroxyvitamin D [25(OH)D] was measured in 94 healthy controls and in 41 children and teens with steroid-sensitive nephrotic syndrome in remission with vitamin D being deficient in most of the nephotic children (16.4 ng/ml vs. 23.9 ng/ml, P<0.001). The odds ratios (OR) of vitamin D insufficiency increased in SSNS subjects [OR 11.2], non-European-Americans [OR 12.9], older children [OR 1.20 per year], and winter months [OR 6.7]. Serum 25(OH)D concentrations were not associated with SSNS disease characteristics. Vitamin D insufficiency in steroid-sensitive nephrotic syndrome in remission. Weng FL, Shults J, et al University of Pennsylvania. Pediatr Nephrol. 2005 Jan;20(1):56-63.

Neurofibromatosis: Vitamin D Much Lower and Deficiency Associated with Damage: Neurofibromatosis 1 is a tumour suppressor gene syndrome characterized by multiple cutaneous and plexiform neurofibromas. Focal osseous abnormalities, short stature, and decreased bone mineral density are also frequent. Serum 25-hydroxyvitamin D concentrations in 55 NF1 patients and 58 healthy controls found vitamin D levels much lower in patients (14.0 vs. 31.4 ng/mL among healthy controls (p<<0.0001). The serum vitamin D concentration and number of dermal neurofibromas reported by NF1 patients were inversely correlated (Sp<0.00001). Vitamin D deficiency associated with number of neurofibromas in neurofibromatosis 1. Lammert M, et al. University Hospital Eppendorf, Germany. J Med Gen 2006 Mar 29.

Nursing Mothers: High Dose Vitamin D Recommended: Authors state that the recommended 400 IU/day of vitamin D is inadequate for nursing mothers and infants.  In a study of 18 nursing mothers, 2000 IU/day for 3 months raised the levels in the breast milk by 34.2 IU/L, while 4000 IU/d increased levels by 94.2 IU/L, which the authors thought were still better. Vitamin D requirements during lactation: high-dose maternal supplementation as therapy to prevent hypovitaminosis D for both the mother and the nursing infant. Hollis BW, Wagner CL. Medical University of South Carolina. Am J Clin Nutr. 2004 Dec;80. Ed: Low vitamin D in infants results in slower growth and reduced size. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1748S-51S. Vitamin D supplementation markedly reduces the risk of diabetes and schizophrenia in the children.

Obesity: Vitamin D Low in Obese: In a study of 302 adult women, serum intact parathyroid hormone was positively correlated with both the body mass index (BMI) (r = 0.42; P < 0.0001) and body fat mass (r = 0.37; P < 0.0001). Serum 25-hydroxy vitamin D was negatively correlated with BMI (r = -0.4; P < 0.0001) and body fat mass (r = -0.41; P < 0.0001). Serum 1,25-vit D was also negatively correlated with BMI (r = -0.26; P < 0.0001) and body fat mass (r = -0.25; P = 0.0001). Serum 1,25-vit D was significantly lower in obese than nonobese subjects (106 vs. 125 pmol/liter; P < 0.0001) in both Caucasian and African-American adults. The Relationship between Obesity and Serum 1,25-Dihydroxy Vitamin D Concentrations in Healthy Adults. Parikh SJ, Edelman M, et al. J Clin Endocrinol Metab. 2004 Mar;89(3):1196-9

Obesity: Vitamin D Receptor Polymorphisms Associated with Weight and Fat Mass: In a Swedish study of 175 healthy women ages 20-39, the polymorphic regions in the VDR gene (the poly A repeat and the BsmI SNP) found that individuals with shorter poly A repeat, ss and/or absence of the linked BsmI restriction site (BB) have higher hamstring strength (ss vs LL, P=0.02), body weight (ss vs LL, P=0.049) and fat mass (ss vs LL, P=0.04) compared with women with a longer poly A repeat (LL) and/or the presence of the linked BsmI restriction site (bb). Genetic variation in the human vitamin D receptor is associated with muscle strength, fat mass and body weight in Swedish women. Grundberg E, Brandstrom H, et al. Eur J Endocrinol. 2004 Mar;150(3):323-8.

Osteoporosis: Alfacalcidol Much Better than Vitamin D3: Due to strong feedback regulation, plain vitamin D is not activated in the kidney in vitamin-replete patients, while alfacalcidol, having been hydroxylated at position 1, bypasses regulation and increases available amounts of active D-hormone in different target tissues. In a 3-year DB study of 204 patients with established steroid-induced osteoporosis with or without vertebral fracture, those receiving 1 microg alfacalcidol plus 500 mg calcium per day had a 2.4% increase in lumbar spine bone mineral density vs. a -0.8% decrease for those on 1000 IU vitamin D3 plus 500 mg calcium (p < 0.0001) and a median increase at the femoral neck of 1.2% versus 0.8% (p < 0.006). The percentages with new vertebral fracture were 9.7% versus 24.8% (p = 0.005); and new nonvertebral fracture were 15% versus 25% (p = 0.081). The alfacalcidol group showed a substantially larger decrease in back pain than the plain vitamin D group (p < 0.0001). Only 3 patients in the alfacalcidol group and 2 patients in the vitamin D group had moderate hypercalcemia. Alfacalcidol versus plain vitamin D in the treatment of glucocorticoid/inflammation-induced osteoporosis. Ringe JD, et al. University of Cologne, Germany. . J Rheumatol Suppl. 2005 Sep;76:33-40.

Osteoporosis: Sun Exposure Reduced Fractures in Elderly:  In a randomized study, Alzheimer's disease (AD) patients were assigned to regular sunlight exposure (n = 132) or sunlight deprivation (n = 132) and followed for 1 year. Serum 25-OHD level increased by 2.2-fold in the sunlight-exposed group. Eleven patients sustained fractures in the sunlight-deprived group, and three fractures occurred among the sunlight-exposed group (p = 0.0362; odds ratio = 3.7). BMD increased by 2.7% in the sunlight-exposed group and decreased by 5.6% in the sunlight-deprived group (p < 0.0001). Serum 25-OHD level increased from 24.0 to 52.2 nM in the sunlight-exposed group. Amelioration of osteoporosis and hypovitaminosis d by sunlight exposure in hospitalized, elderly women with Alzheimer's disease: a randomized controlled trial. Sato Y, et al. Tagawa, Japan. J Bone Miner Res. 2005 Aug;20(8):1327-33

Osteoporosis: Vitamin D at 800 IU and 2000 IU Didn't Help: In a 3 year DB PC study of 208 African American postmenopausal women, 20 microg/d (800 IU) of vitamin D(3) and 2000 IU for the third year with all women receiving calcium supplements of 1200 to 1500 mg/d led to no significant differences in BMD between the active and control groups throughout the study. There was also no relationship between serum 25-hydroxyvitamin D levels attained and rates of bone loss. There was an increase in BMD of the total body, hip, and radius at 1 year in both groups. Over the 3 years, BMD declined at these sites by 0.26% to 0.55% per year. A randomized controlled trial of vitamin D3 supplementation in African American women. Aloia JF, et al. Winthrop University Hospital, Mineola, NY. Arch Intern Med. 2005 Jul 25;165(14):1618-23

Osteoporosis: Vitamin D 800 IU Helps: In a meta-analysis of double-blind RCTs of oral vitamin D supplementation (cholecalciferol, ergocalciferol) with or without calcium supplementation vs calcium supplementation or placebo in older persons (> or =60 years), five RCTs for hip fracture (n = 9294) and 7 RCTs for nonvertebral fracture risk (n = 9820) met inclusion criteria. All trials used cholecalciferol. A vitamin D dose of 700 to 800 IU/d reduced the relative risk (RR) of hip fracture by 26% and any nonvertebral fracture by 23%  vs calcium or placebo. No significant benefit was observed for RCTs with 400 IU/d vitamin D (2 RCTs with 3722 persons). Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. Bischoff-Ferrari HA, Willett WC, et al. Harvard. JAMA. 2005 May 11;293(18):2257-64.

Osteoporosis: Many Mothers and Infants Deficient with Larger Birth Weight and Lower Bone Mineral Content to Body Size: In a study of 50 mothers and infants, 46% of the mothers and 36% of the infants had a low plasma 25(OH)D concentration. Infants who were vitamin D deficient were larger at birth and follow-up. Absolute lumbar spine, femur and whole-body BMC were not different between infants with adequate vitamin D and those who were deficient, despite larger body size in the latter group. In the regression analysis, higher whole-body BMC was associated with greater gestational age and weight at birth as well as higher infant plasma 25(OH)D. Whether a return to normal vitamin D status, achieved through supplements or fortified infant formula, can reset the trajectory for acquisition of BMC requires investigation. Vitamin D deficiency and whole-body and femur bone mass relative to weight in healthy newborns. Weiler H, Fitzpatrick-Wong S, et al. University of Manitoba, Winnipeg. CMAJ. 2005 Mar 15;172(6):757-61. Ed: Larger birth weight is correlated with an increased risk of diabetes type I. Vitamin D supplementation of mothers while pregnant or infants considerably lowers the risk of diabetes. Thus, the larger birth weight in this study makes sense and is an unhealthy feature in this case.

Osteoarthritis: Vitamin D Protects Against Osteoarthritis: The probability that established osteoarthritis will progress to a more severe stage is reduced with better vitamin D nutritional status, based both on serum 25(OH)D concentrations and diet history. McAlindon TE, Felson DT, Zhang Y, et al. Relation of dietary intake and serum levels of vitamin D to progression of osteoarthritis of the knee among participants in the Framingham Study. Ann Intern Med 1996;125:353–9. The authors recommended that serum 25(OH)D should exceed 75 nmol/L in persons with osteoarthritis of the knee.

Osteoporosis: Vitamin K and D and Calcium Reduced Fractures by 86% in Alzheimer’s: In a DB PC 2-year study of 200 AD patients, those who received 45 mg menatetrenone (K-2), 1000 IU ergocalciferol (vitamin D) and 600 mg calcium daily for 2 years had BMD in the second metacarpals increase by 2.3% in the treated group and decrease by 5.2% in the untreated group (P < 0.0001). Serum levels of vitamin K2 and 25-hydroxyvitamin D increased by 285% and 148%, respectively, in the treated group. Twenty-two patients in the untreated group sustained nonvertebral fractures (15 with hip fractures, two fractures each at the distal forearm and the proximal femur, each one fracture at the proximal humerus, ribs, and pelvis), and three fractures (2 with hip fractures, one fracture at the proximal femur) occurred among the treated patients (P = 0.0003; odds ratio = 7.5). Menatetrenone and vitamin D2 with calcium supplements prevent nonvertebral fracture in elderly women with Alzheimer's disease. Sato Y, Kanoko T, et al. Japan. Bone. 2005 Jan;36(1):61-8.

Osteoporosis: Extra Vitamin D and Calcium May Have Helped in Cystic Fibrosis: Low bone mineral density (BMD) is prevalent in adults with cystic fibrosis. Patients were randomized to receive calcium 1 g+vitamin D 800 IU or placebo daily, in addition to their regular vitamin D supplements (900 IU/day). After 12 months, the treatment group (n=15) showed a reduced rate of bone loss compared with the control group (n=15) in the lumbar spine (mean difference 1.9%), total hip (mean difference 0.7%) and distal forearm (mean difference 1.7%). There was also a trend towards a reduction in bone turnover in the treatment group. Randomised double blind placebo controlled trial investigating the effect of calcium and vitamin D supplementation on bone mineral density and bone metabolism in adult patients with cystic fibrosis. Haworth CS, Jones AM, et al. Manchester, UK. J Cyst Fibros. 2004 Dec;3(4):233-6

Osteoporosis: Mothers Low in Vitamin D Affect Body Mineral Density of Offspring: In a 9-year follow-up study of 198 newborns, 31% mothers had insufficient and 18% had deficient circulating 25(OH)-vitamin D during late pregnancy. Low vitamin D in mothers during late pregnancy was associated with reduced whole-body (p=0.0088) and lumbar-spine (p=0.03) bone-mineral content in children at age 9 years. Both the estimated exposure to ultraviolet B radiation during late pregnancy and the maternal use of vitamin D supplements predicted maternal 25(OH)-vitamin D concentration (p<0.0001 and p=0.0110, respectively) and childhood bone mass (p=0.0267). Reduced concentration of umbilical-venous calcium also predicted reduced childhood bone mass (p=0.0286).  Vitamin D supplementation of pregnant women, especially during winter months, could lead to longlasting reductions in the risk of osteoporotic fracture in their offspring. Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study. Javaid MK, et al. University of Southampton, UK. Lancet 2006 Jan 7;367(9504):36-43.

Osteoporosis: High 5,000-10,000 Daily Dose Needed for 3 Months: In 38 postmenopausal osteopenic/osteoporotic women studied during winter and spring, all received 500 mg calcium/day. The median baseline 25 hydroxyvitamin D (25OHD) level was 36.25 nmol/l. After 3 months, 8% of the patients in the placebo group, 50% in the 5,000 IU/day group and 75% in the 10,000 IU/day group had 25OHD values above 85 nmol/l (34 ng/ml). Serum calcium remained within normal range during the follow-up. The oral dose of vitamin D(2) required to rapidly achieve adequate levels of 25OHD is much higher than the usual recommended vitamin D(3) dose (800 IU/day). Vitamin D(2) dose required to rapidly increase 25OHD levels in osteoporotic women. Mastaglia SR, et al. Universidad de Buenos Aires, Argentina. Eur J Clin Nutr 2006 Jan 4. Ed: Maintaining 10,000 IU longer could be toxic. I would be more patient.  Since I encourage vitamin K, also, such high doses should be needed.

Vitamin D2 400,000 IU Annually Reduced Fractures: All women over age 64 in Health District 20 were eligible for a prospective community intervention study. A vial containing 400,000 IU of oral vitamin D2 was offered to all in the winters of 2000-2001 and 2001-2002. 45-47% of eligible women accepted the vitamin D: 50-55% of women ages 60-70 years and 22-26% of those ages > 90 years. Women who had received vitamin D, with respect to women who had not, decreased by 17% (p = 0.056) and 25% (p = 0.005) in the 1st and 2nd years. Those over age 75 were the most helped. 25-OH vitamin D concentrations rose by 9 ng/ml over 4 months after administration (p < 0.0001) in 120 checked. Effect of oral vitamin D2 yearly bolus on hip fracture risk in elderly women: a community primary prevention study. Rossini M, Alberti V, et al. Regione Veneto, Italy. Aging Clin Exp Res. 2004 Dec;16(6):432-6.

Osteoporosis: Vitamin D 100,000 IU Every 4 Months Cuts Fractures and Death: In a DB PC study of 2,686 adults ages 65-79 living in community with 4.5 years of follow-up in England, there were 22% fewer fractures (RR 0.78) and 33% fewer in typical osteo sites (0.67) in the vitamin D group with a 10% decrease in mortality as well (16.7% vs. 18.4%)(RR 0.88; p=.18) although the decreased mortality was not statistically significant. The dosage used might still not have been high enough since there was only a minor decrease parathyroid hormone. Effect of four monthly oral vitamin D₃ (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. Daksha P Trivedi, Richard Doll, Kay Tee Kha. BMJ 2003;326:469 ( 1 March ). Chapuy reported that daily supplementation with vitamin D 800 IU and calcium reduced hip fractures by 30% over three years in a very large study of 3,270 elderly women. Some studies with just Vitamin D 400 IU/d not find benefit. 25-hydroxycalciferol, half-life 25 days. 

Osteoporosis: Vitamin D 400 IU with Calcium 500 Helps Deficient Women: In a DB PC 12 month study of 192 adults over age 65, even 400 IU of vitamin D had beneficial effects when added to calcium. Effects on bone mineral density of calcium and vitamin D supplementation in elderly women with vitamin D deficiency. Grados F, Brazier M, Kamel S, Duver S, Heurtebize N, Maamer M, Mathieu M, Garabedian M, Sebert JL, Fardellone P. Joint Bone Spine. 2003 Jun;70(3):203-8

Osteoporosis: Vitamin D and Calcium Helped Pre-Teen Girls: In a 12-month DB PC study of just 71 12-year-olds, 800 mg calcium carbonate and 400 IU vitamin D, no differences were found for age, weight, height, body mass index, pubertal maturation, or reported physical activity at enrollment or during the study. Average intakes during the study were 1524 mg calcium and 496 IU vitamin D (TX) versus 865 mg calcium and 160 IU vitamin D (C) per day. Trabecular bone mineral content increased 4% vs. a 1.6% decrease with placebo. BMD increased 1% vs. a 2% loss with placebo. Bone mass and density response to a 12-month trial of calcium and vitamin D supplement in preadolescent girls. Moyer-Mileur LJ, et al. University of Utah. J Musculoskelet Neuronal Interact. 2003 Mar;3(1):63-70.

Osteoporosis: Seasonal Bone Loss Reversed by Vitamin D and Calcium: In a random-assignment open study of 55 adults, half were given 500 IU oral vitamin D(3) and calcium 500 mg/day during the winter months. Before the supplement, both groups lost bone during the winter months. In the year of supplementation, the vitamin D group gained 0.3-0.9% lumbar and femoral bone while the control group continued to lose bone. Supplementation with oral vitamin d3 and calcium during winter prevents seasonal bone loss: a randomized controlled open-label prospective trial. Meier C, Woitge HW, Witte K, Lemmer B, Seibel MJ. University Sydney.

Osteoporosis: Vitamin D Injection Most Cost Effective: It costs only $1,500 per fracture prevented using Vitamin D injections for elderly females in nursing homes. Adding calcium increases cost per fracture prevented to $22,000. Cost-effectiveness of preventing hip fractures in the elderly population using vitamin D and calcium. Torgerson DJ, Kanis JA. QJM. 1995 Feb;88(2):135-9. Calcijex = calcitriol; paricalcitol (Zemplar)(D2); doxercalciferol (Hectorol)(D2)

Osteoporosis: Bone Mineral Density Not Helped by Vitamin D Supplement: A 1 year DB PC study using vitamin D 800 IU/d found no benefit of bone mineral density in 70 healthy women ages 24-70. The effect of season and vitamin D supplementation on bone mineral density in healthy women: a double-masked crossover study. Patel R, Collins D, Bullock S, Swaminathan R, Blake GM, Fogelman I. Osteoporos Int 2001;12(4):319-25. Ed: This is a very small study for a relatively short period of time with many participants who were not at high risk for osteoporosis due to being young.

Osteoporosis: Bone Mineral Density Not Helped by Vitamin D Supplement: In a DB PC study of 79 twin pairs in which one twin in each pair was given 800 IU/d, no benefit was found. A randomized controlled trial of vitamin D supplementation on preventing postmenopausal bone loss and modifying bone metabolism using identical twin pairs. Hunter D, Major P, Arden N, Swaminathan R, Andrew T, MacGregor AJ, Keen R, Snieder H, Spector TD. J Bone Miner Res 2000 Nov;15(11):2276-83. Ed: This is another very small study for a relatively short period of time with many participants who were not at high risk for osteoporosis due to being young.  Such studies are not good for detecting the benefits of vitamin D.  Larger studies for longer periods of time are better at measuring vitamin D’s benefit.

Osteoporosis: Vitamin D 10,000 IU/week No Benefit added to 1000 mg Calcium: Women, all age 56, in a 2 year DB of calcium or calcium plus vitamin D detected no vitamin D benefit. Am J Clin Nutr. 2003 May;77(5):1324-9. Ed: This study was too small.

Osteoporosis: High Dose Supplementation Recommended: Serum 25-hydroxyvitamin D3 [25(OH)D3] < 80 nmol/L are associated with reduced calcium absorption, osteoporosis, and increased fracture risk. For typical older individuals, supplemental oral intakes of approximately 1300 IU/d are required to reach the lower end of the optimal range. Functional indices of vitamin D status and ramifications of vitamin D deficiency. Heaney RP. Creighton University. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1706S-9S

PMS: Lower in Women with Higher Vitamin D Intake: In a case-control study within the prospective Nurses' Health Study II cohort of women aged 27 to 44 years and free from PMS at baseline, 1057 women developed PMS over 10 years of follow-up and 1968 women reporting no diagnosis of PMS and no or minimal menstrual symptoms. After adjustment for age, parity, smoking status, and other risk factors, women in the highest quintile of total vitamin D intake (median, 706 IU/d) had a relative risk of 0.59 compared with those in the lowest quintile (median, 112 IU/d) (P = .01). The intake of calcium from food sources was also inversely related to PMS; compared with women with a low intake (median, 529 mg/d), participants with the highest intake (median, 1283 mg/d) had a relative risk of 0.70 (P = .02 for trend). The intake of skim or low-fat milk was also associated with a lower risk (P<.001). Calcium and vitamin D intake and risk of incident premenstrual syndrome. Bertone-Johnson FR, et al. University of Massachusetts, Amherst. Arch Intern Med. 2005 Jun 13;165(11):1246-52.

Periodontal Disease: Vitamin D Might Prevent: Periodontal disease (PD) is a common chronic inflammatory disease causing tooth loss. Using data from the third National Health and Nutrition Examination Survey on 11,202 adults, after controlling for age, ethnicity, smoking, diabetes, poverty income ratio, body mass index, estrogen use, and gingival bleeding, 25(OH)D(3) concentrations were significantly and inversely associated with tooth attachment loss (AL) in men and women over 49. Compared with men in the highest 25(OH)D(3) quintile, those in the lowest quintile had a mean AL that was 0.39 mm higher; in women, the difference in AL between the lowest and highest quintiles was 0.26 mm. The BMD of the total femoral region was not associated with AL and did not mediate the association between 25(OH)D(3) and AL. Association between serum concentrations of 25-hydroxyvitamin D3 and periodontal disease in the US population. Dietrich T, Joshipura KJ, Dawson-Hughes B, Bischoff-Ferrari HA. Humboldt University of Berlin. Am J Clin Nutr. 2004 Jul;80(1):108-13

Pneumonia: Vitamin D and Breast Feeding Protective Against Childhood Pneumonia: Eighty Indian children under age five with severe lower respiratory infections were compared with 70 controls. Subclinical vitamin D deficiency (OR 0.09 is vitamin D > 22.5 nmol/l) and nonexclusive breastfeeding in the first 4 months of life (OR 0.42 if breastfed) were major significant risk factors for severe infection. Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5 y. Wayse V, Yousafzai A, Mogale K, Filteau S. University College London, UK. Eur J Clin Nutr. 2004 Apr;58(4):563-7

Pre-Eclampsia in Adult Women Less If Vitamin D Taken in Infancy: Using data on 2969 women born in the Northern Finland Birth Cohort 1966 of whom 68 (2.3%) had pre-eclampsia in their first pregnancy, the risk of pre-eclampsia was halved (OR 0.49) in participants who had received vitamin D supplementation regularly during the first year of life. This association was not affected by adjustment for own birth order, birth weight, gestational age, social class in 1966 and hospitalizations or pregnancy-induced hypertension of their mothers. Does vitamin D supplementation in infancy reduce the risk of pre-eclampsia? Hypponen E, et al. Institute of Child Health, London, UK. European Journal of Clinical Nutrition 31 January 2007.

Premee Teeth Problems Not Helped by High Vitamin D and Calcium in Very Small Study; Second Study Found Benefit: In a study of 32 preterm children and 64 control children, the prevalence of enamel defects in children born preterm was clearly higher as compared with controls in both the primary (78% vs. 20%, P<0.001) and permanent (83% vs. 36%, P<0.001) dentitions. Neither the mineral supplementation used nor a vitamin D dose of 1000 IU/day, as compared with a lower dose of 500 IU/day, reduced the prevalence of enamel defects in the primary or permanent dentitions. Finland, Univ Tampere, Enamel defects in primary and permanent teeth of children born prematurely. Aine L, Backstrom MC, Maki R, Kuusela AL, Koivisto AM, Ikonen RS, Maki M. J Oral Pathol Med. 2000 Sep;29(8):403-9; It is well known that breast milk contains too little calcium and phosphorus to enable intrauterine mineral accretion in preterm infants. Thus the main cause of metabolic bone disease of prematurity is an inadequate supply of calcium and phosphorus, not vitamin D deficiency, as long as a dose of 160-1000 IU/day is used as a supplement. Premee children receiving the higher vitamin D dose in the neonatal period had more mature permanent dentition than those receiving the lower dose, but mineral intake did not affect maturation of the permanent teeth. Dental maturation did not correlate with bone mineral status at age 10. Same authors. Arch Dis Child Fetal Neonatal Ed. 2000 Sep;83(2):F104-8

Rheumatoid Arthritis: Vitamin D Intake Associated with Lower Rates: In an 11-year follow-up of 29,300 Iowa women ages 55-69, where 158 developed rheumatoid arthritis, those with higher intakes of vitamin D in food or by supplements were 30% less likely to develop rheumatoid arthritis. Risk ratios were 0.72 and 0.66 for in food or via supplement. Univ Iowa, Linda Merlino, Arthritis Rheum. 2004:50:72-77. 

Rickets Due to Vitamin D Deficiency: Vitamin D-deficient rickets is uncommon but becoming more prevalent in the pediatric population. The author claims it is likely related to increases in breast-feeding. It should be considered in many clinical situations. Three cases of rickets presenting acutely to the emergency department are reported by the authors. Each child had a fracture initially arousing concern for child abuse, tetany, and hypocalcemic seizures.  In fact, there was no child abuse, but a vitamin D deficiency was found in each case. Pediatr Emerg Care. 2004 Feb;20(2):126-30

Schizophrenia: Vitamin D Supplement in Infancy Linked to Lower Schizophrenia in Males; 2000 IU Best: In a Finnish study of 9,114 newborns followed for 31 years, males given vitamin D supplements in the first year of life, either irregular or regular vitamin D supplements, had a 90% reduced risk of schizophrenia (Risk ratio (RR)=0.10) compared with no supplementation. In males, the use of at least 2,000 IU of vitamin D was associated with a reduced risk of schizophrenia (RR=0.23) compared to those on lower doses. There was no link for females or for other psychiatric difficulties for either sex. Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study. McGrath J, Saari K, et al. Schizophr Res. 2004 Apr 1;67(2-3):237-45. Ed: No one has studied whether vitamin D helps adults with schizophrenia.  While I would not expect these huge benefits, I personally think vitamin D supplementation is a very good idea.  In any case, developing diabetes was 700% more common in schizophrenic patients on medication in one study and vitamin D helps prevent diabetes. (VA study, 2004, 4.4% annual rate vs. 0.63% in normal population.)

Schizophrenia May be Increased by Vitamin D Deficiency in Infancy: People who develop schizophrenia in Europe and North America are more likely to be born in the spring, according to an article in the New Scientist. They are also roughly four times as likely to be born to Afro-Caribbean immigrants living in England as they are to have parents of other ethnic origins living in the same areas. Australian psychiatrist John McGrath found adult rats deprived of vitamin D from conception are more startled than normal by a loud noise preceded by a soft noise. He also found ventricles in the brains of vitamin-deprived baby rats are also unusually large, a feature seen in people with schizophrenia. A U.S. survey suggests serious vitamin D deficiency affects 12% of women of childbearing age. BBC News 2/7/02.

Schizophrenics' Mothers Tended to be Deficient in Vitamin D During Pregnancy: There was no statistically significant difference in levels using banked sera in third trimester maternal vitamin D in a very small sample of 26 cases and 51 controls. However, within the subgroup of Afro-Australian individuals (n = 21), there was a trend level difference in the predicted direction, i.e., lower vitamin D, more schizophrenia in the children after they grew up. Low maternal vitamin D as a risk factor for schizophrenia: a pilot study using banked sera. McGrath J, Eyles D, Mowry B, Yolken R, Buka S. Schizophr Res. 2003 Sep 1;63(1-2):73-8

Schizophrenia: In Utero or Infant Vitamin D Deficiency Affects Adult Brain in Rats: The brains of newborn rats from Vitamin D(3) deficient dams are larger than controls, have increased cell proliferation, larger lateral ventricles, and reduced cortical thickness. Brains from these animals also had reduced expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor. The brains of adult rats at 10 weeks of age after Vitamin D(3) deficiency until birth or weaning had larger lateral ventricles, reduced NGF protein content, and reduced expression of a number genes involved in neuronal structure, i.e. neurofilament or MAP-2 or neurotransmission, i.e. GABA-A(alpha4). Developmental Vitamin D(3) deficiency alters the adult rat brain. Feron F, Burne TH, et al. Griffith University, Brisbane, Australia. Brain Res Bull. 2005 Mar 15;65(2):141-8.

Senile Warts, Psoriasis, Vitiligo: Vitamin D Helped: Vitamin D(3) ointment is widely used for the therapy of inflammatory keratotic dermatoses such as psoriasis. Senile wart (seborrheic keratosis) is a benign tumor, which occurs mainly in the elderly. It has been treated with surgical procedures, freezing with liquid nitrogen, or laser therapy. In a study of topical vitamin D(3) ointments applied on senile warts once or twice a day, out of 116 cases treated for more than three months, 30% showed more than 80% of decreasing of tumor volume, 47% showed a 40-80% decrease, while 23% showed less or no decrease. The warts disappeared without any inflammatory change such as erythema or swelling and with no side-effects. New aspects on vitamin D3 ointment; treatment of senile warts with topical application of active forms of vitamin D3. Mitsuhashi Y. Yamagata University. Clin Calcium. 2004 Oct;14(10):141-4. Vitamin D Ointment also was thought to help vitiligo in an uncontrolled study. Clin Calcium. 2004 Oct;14(10):137-40

Systemic Lupus Erythematosis: Vitamin D Low: Possibly a Cause: Data from a population-based cohort of 123 recently diagnosed SLE patients and 240 controls showed lower 25(OH)D levels in cases compared to controls, which was statistically significant in Caucasians (p=0.04), controlling for age, sex, season, and smoking. 67% were vitamin D deficient, with mean levels significantly lower among African Americans (15.9 ng/ml) compared to Caucasians (31.3 ng/ml). Critically low vitamin D levels (<10 ng/ml) were found in 22 of the SLE cases, with presence of renal disease being the strongest predictor (OR 13.3, p<0.01) followed by photosensitivity (OR 12.9, p<0.01). Vitamin D deficiency in systemic lupus erythematosus. Kamen DL, et al. Medical University of South Carolina. . Autoimmune Rev 2006 Feb;5(2):114-7.

Smokers May Need Vitamin D: In a Danish study of 510 adults, half smokers, the smokers had significantly lower vitamin D levels (P=0.02) and parathyroid hormone levels (P<0.001). There was a negative effect of smoking on serum osteocalcin (P=0.01). The small differences in lifestyle between the two groups could not explain these findings. Smokers had small but significant reductions in bone mineral density. Eur J Clin Nutr. 1999 Dec;53(12):920-6

Stroke: Vitamin D Lower in Stroke Victims; Iron Lower in Heart Attacks and Strokes: In a population-based health survey of 755 adults ages 65-99 with 10 years follow-up, 130 had heart attacks and 70 had strokes. Low intake of vitamin D (p=0.011) and low serum levels of 1,25-dihydroxy-vitamin D (p=0.0053) were predictive of stroke when adjusted for age, gender, smoking and functional capacity. High dietary intakes of two flavonoids, luteolin (p=0.0096) and kaempferol (p=0.002) were associated with lowered risk of heart attack. Low serum levels of iron predicted both heart attack (p=0.013) and stroke (p=0.019). Dietary and serum vitamins and minerals as predictors of myocardial infarction and stroke in elderly subjects. Marniemi J, et al. National Public Health Institute, Turku, Finland. Nutr Metab Cardiovasc Dis. 2005 Jun;15(3):188-97; Similar: Stroke 2006 Jan;37(1):243-5

Tooth Loss and Osteoporosis Reduced by Vitamin D and Calcium Supplements: In a 3-year DB PC study of 145 men over age 64 with an additional 2 years of follow-up, participants took placebo or vitamin D plus calcium 1000 mg. Of the supplement group, 13% lost at least one tooth vs. 27% with placebo. OR = 0.4. Calcium and vitamin D supplements reduce tooth loss in the elderly. Krall EA, Wehler C, Garcia RI, Harris SS, Dawson-Hughes B. Am J Med 2001 Oct 15;111(6):452-6; Boston U 

Tooth Loss Linked to Bone Loss in Elderly: In a 7-year follow-up study of 189 healthy women, for each 1% per year decrement in bone mineral density, relative risks (RR) of losing a tooth were significantly elevated at the whole body (RR = 4.83), femoral neck (RR = 1.50), and spine (RR = 1.45). These results provide support for a role of systemic bone loss in the development of tooth loss among postmenopausal women. Tufts. Increased risk of tooth loss is related to bone loss at the whole body, hip, and spine. Krall EA, Garcia RI, Dawson-Hughes B. Calcif Tissue Int. 1996 Dec;59(6):433-7

Tooth Decay: Sunshine Lacking North Has More Multiple Sclerosis, Tooth Decay, Prostate and other Cancers: Mortality rates from multiple sclerosis have a well-proven north-south pattern, both within the United States and internationally. Mortality rates from prostate cancer show a similar pattern as does colon cancer, dental caries, and Parkinson's disease. Vitamin deficiencies caused by a lack of sunshine exposure may be the cause. Multiple sclerosis and prostate cancer: what do their similar geographies suggest? Schwartz GG. Neuroepidemiology. 1992;11(4-6):244-54

Tuberculosis: Vitamin D Blood Levels Lower in Infected: In an Indian study of 35 tuberculosis patients compared to 16 controls, the patients had very low vitamin D levels on average: controls (19.5 ng/ml) and patients (10.7 ng/ml)(p < 0.005) Even vitamin D levels in the control group was deficient according to standard values. Sunlight exposure was adequate in those with deficiency but there was reduced dietary intake of vitamin D. Authors speculate that the low vitamin D probably is playing a causal role. Tuberculosis and vitamin D deficiency. Sasidharan PK, Rajeev E, et al Calicut Medical College, Kerala. J Assoc Physicians India. 2002 Apr;50:554-8.

Vaginal Atrophy Helped by Vitamin D: In a study of 60 women with vaginal atrophy, those given vitamin D treatment had fewer signs of atrophy than those without treatment. Cell maturation index also favored vitamin D. The effects of postmenopausal Vitamin D treatment on vaginal atrophy. Yildirim B, Kaleli B, et al. Pamukkale University, Turkey. Maturitas. 2004 Dec 10;49(4):334-7. Ed: I couldn't tell if a cream or pills were used.

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

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