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Vitamin D, nervous system and aging. P. Tuohimaa, T. Keisala, A. Minasyan, J. Cachat and A. Kalueff. . Psychoneuroendocrinology, Volume 34, Supplement 1, December 2009, Pages S278-S286 NEUROACTIVE STEROIDS: EFFECTS AND MECHANISMS OF ACTION doi:10.1016/j.psyneuen.2009.07.003 This is a mini-review of vitamin D3, its active metabolites and their functioning in the central nervous system (CNS), especially in relation to nervous system pathologies and aging. The vitamin D3 endocrine system consists of 3 active calcipherol hormones: calcidiol (25OHD3), 1α-calcitriol (1α,25(OH)2D3) and 24-calcitriol (24,25(OH)2D3). The impact of the calcipherol hormone system on aging, health and disease is discussed. Low serum calcidiol concentrations are associated with an increased risk of several chronic diseases including osteoporosis, cancer, diabetes, autoimmune disorders, hypertension, atherosclerosis and muscle weakness all of which can be considered aging-related diseases. The relationship of many of these diseases and aging-related changes in physiology show a U-shaped response curve to serum calcidiol concentrations. Clinical data suggest that vitamin D3 insufficiency is associated with an increased risk of several CNS diseases, including multiple sclerosis, Alzheimer's and Parkinson's disease, seasonal affective disorder and schizophrenia. In line with this, recent animal and human studies suggest that vitamin D insufficiency is associated with abnormal development and functioning of the CNS. Overall, imbalances in the calcipherol system appear to cause abnormal function, including premature aging, of the CNS.

My doctor advised us to give Vitamin D to both our children, though our son is more than 4 year old. I decided to find out more about it. I surfed the Internet, read the description of the vitamin (here Canadian Pharmacy site https://www.canadapharmacy.com/ helped me a lot). Finally, I decided to give it to my children. But I didn't know, it is good for adults. Thanks for sharing this information, it is very useful for me!

Plasma 25-hydroxyvitamin d is associated with markers of the insulin resistant phenotype in nondiabetic adults. Liu E, Meigs JB, Pittas AG, McKeown NM, Economos CD, Booth SL, Jacques PF. J Nutr. 2009 Feb;139(2):329-34. Epub 2008 Dec 23. PMID: 19106328 doi:10.3945/jn.108.093831 After adjusting for age and sex, plasma 25(OH)D was positively associated with ISI(0,120), plasma adiponectin, and HDL cholesterol and inversely associated with plasma triacylglycerol, but these associations were no longer significant after further adjustment for BMI, waist circumference, and current smoking status. 25(OH)D and 2-h post-OGTT glucose were not associated. Among adults without diabetes, vitamin D status was inversely associated with surrogate fasting measures of insulin resistance. These results suggest that vitamin D status may be an important determinant for type 2 diabetes mellitus.

Vitamin D, aging, and cancer. Tuohimaa P. Nutr Rev. 2008 Oct;66(10 Suppl 2):S147-52. Review. PMID: 18844842 DOI: 10.1111/j.1753-4887.2008.00095.x Deficiency of the prohormone calcidiol (25OH vitamin D3) seems to be associated with several aging-related chronic diseases including cancer. Our results suggest that calcidiol is mainly responsible for differentiation homeostasis, whereas calcitriol might be more involved in calcium homeostasis. Therefore, an imbalance of calcidiol rather than calcitriol is a risk factor for cancer and chronic diseases. Calcidiol insufficiency, as well as insufficient solar exposure, is associated with increased risk of several solid cancers. Both a vitamin D3 deficiency and a high concentration of calcidiol may increase cancer risk. Similarly, aging phenomena show a U-shaped association with vitamin D bioactivity. Therefore, the chronic diseases and cancers related to aging might be prevented by an optimal concentration of serum calcidiol, which remains to be determined.

25(OH)D Serum levels decline with age earlier in women than in men and less efficiently prevent compensatory hyperparathyroidism in older adults. Maggio D, Cherubini A, Lauretani F, Russo RC, Bartali B, Pierandrei M, Ruggiero C, Macchiarulo MC, Giorgino R, Minisola S, Ferrucci L. J Gerontol A Biol Sci Med Sci. 2005 Nov;60(11):1414-9. PMID: 16339327 Conclusions. These findings suggest that the age-associated fall of serum 25(OH)D starts earlier in women than in men and that higher levels of 25(OH)D are required in older compared to younger persons to avoid the age-associated compensatory hyperparathyroidism.

"From 1955 to 1990, all infants in East Germany received 600,000 IU of Vitamin D every three months for a total of 3,600,000 IU at age 18 months. With the 400 IU/day recommendation of the American Pediatric Association in mind, I ran across this amazing paper while surfing Medline for Vitamin D. According to this paper, all infants in the German Democratic Republic (East Germany) received dangerously high doses of Vitamin D every three months in their doctors office. The policy was in place for 35 years. The first 600,000 IU dose was given at three months and then every three months until the child was 18 months of age. This works out to an average of 6,000 IU per day (actually, for several technical reasons it is not equivalent) for 18 months. The authors collected blood before the dose and then 2 weeks after the quarterly dose to obtain 25(OH)D, 1,25(OH)D, and calcium levels on a total of 43 infants. Before the first dose, at 3 months of age, the average infant was extremely deficient (median 25(OH)D of 7 ng/ml). Two weeks after the first dose the average 25(OH)D level was 120 ng/ml, the second dose 170 ng/ml, the third dose, 180 ng/ml, the fourth dose, 144 ng/ml, the fifth dose, 110 ng/ml and after the sixth and final dose, 3.6 million total units, at age 18 months, the children had mean levels of 100 ng/ml. That is, by the 15 and 18 month doses, the children were beginning to effectively handle these massive doses. The highest level recorded in any of the 43 infants was 408 ng/ml at age 9 months, two weeks after the third 600,000 IU dose. Thirty-four percent of the infants had at least one episode of hypercalcemia but only 3 had an elevated serum 1,25(OH)D. The authors reported that all the infants appeared healthy, even the infant with a level of 408 ng/ml, that is, no clinical toxicity was noted in any of these infants."

Association between depressive symptoms and 25-hydroxyvitamin D in middle-aged and elderly Chinese. Pan A, Lu L, Franco OH, Yu Z, Li H, Lin X. J Affect Disord. 2009 Nov;118(1-3):240-3. Epub 2009 Feb 27. PMID: 19249103 doi:10.1016/j.jad.2009.02.002 Conclusions Depressive symptoms are not associated with 25(OH)D concentrations in middle-aged and elderly Chinese. Further prospective studies are required to determine whether they are correlated.

Prospective study of serum 25(OH)-vitamin D concentration and risk of oesophageal and gastric cancers. Chen W, Dawsey SM, Qiao YL, Mark SD, Dong ZW, Taylor PR, Zhao P, Abnet CC. Br J Cancer. 2007 Jul 2;97(1):123-8. Epub 2007 Jun 5. PMID: 17551495 We prospectively examined the relation between pretrial serum vitamin D status and risk of oesophageal and gastric cancers among subjects who developed cancer over 5.25 years of follow-up, including 545 oesophageal squamous cell carcinomas (ESCC), 353 gastric cardia adenocarcinomas, 81 gastric noncardia adenocarcinomas, and an age- and sex-stratified random sample of 1105 subjects. We found no associations for gastric cardia or noncardia adenocarcinoma. Among subjects with low vitamin D status, higher serum 25(OH)D concentrations were associated with significantly increased risk of ESCC in men, but not in women. Further refinements of the analysis did not suggest any factors, which could explain this unexpected result. In conclusion, we found a direct association between higher serum 25(OH)D concentration and increased risk of ESCC in men but not women in a large population-based prospective cohort study from rural China. We found no association with risk of gastric cardia or noncardia adenocarcinoma in either sex. Greater than 50% of our cohort had an inadequate serum 25(OH)D concentration, yet higher concentrations were associated with increased risk of ESCC compared to lower concentrations.

Optimal vitamin D status attenuates the age-associated increase in systolic blood pressure in white Americans: results from the third National Health and Nutrition Examination Survey. Judd SE, Nanes MS, Ziegler TR, Wilson PW, Tangpricha V. Am J Clin Nutr. 2008 Jan;87(1):136-41. PMID: 18175747 Conclusions: SBP is inversely associated with serum vitamin D concentrations in nonhypertensive white persons in the United States. This observation provides a rationale for studies on the potential effects of vitamin D supplementation as a method to reduce SBP in persons at risk of hypertension.

Age-related changes in the 25-hydroxyvitamin D versus parathyroid hormone relationship suggest a different reason why older adults require more vitamin D. Vieth R, Ladak Y, Walfish PG. J Clin Endocrinol Metab. 2003 Jan;88(1):185-91. PMID: 12519850 This study shows that all age groups exhibit a high prevalence of 25(OH)D insufficiency and secondary hyperparathyroidism. Older adults are just as efficient in maintaining 25(OH)D, but they need more vitamin D to produce the higher 25(OH)D concentrations required to overcome the hyperparathyroidism associated with their diminishing renal function

Association between 25-hydroxyvitamin D levels and cognitive performance in middle-aged and older European men. Lee DM, Tajar A, Ulubaev A, Pendleton N, O'Neill TW, O'Connor DB, Bartfai G, Boonen S, Bouillon R, Casanueva FF, Finn JD, Forti G, Giwercman A, Han TS, Huhtaniemi IT, Kula K, Lean ME, Punab M, Silman AJ, Vanderschueren D, Wu FC; EMAS study group. J Neurol Neurosurg Psychiatry. 2009 Jul;80(7):722-9. Epub 2009 May 21. PMID: 19460797 doi:10.1136/jnnp.2008.165720 Conclusion: In this study, lower 25(OH)D levels were associated with poorer performance on the DSST. Further research is warranted to determine whether vitamin D sufficiency might have a role in preserving cognitive function in older adults.

The association of solar ultraviolet B (UVB) with reducing risk of cancer: multifactorial ecologic analysis of geographic variation in age-adjusted cancer mortality rates. Grant WB, Garland CF. Anticancer Res. 2006 Jul-Aug;26(4A):2687-99. PMID: 16886679 CONCLUSION: These results provide additional support for the hypothesis that solar UVB, through photosynthesis of vitamin D, is inversely-associated with cancer mortality rates, and that various other cancer risk-modifying factors do not detract from this link. It is thought that sun avoidance practices after 1980, along with improved cancer treatment, led to reduced associations in the latter period. The results regarding solar UVB should be studied further with additional observational and intervention studies of vitamin D indices and cancer incidence, mortality and survival rates.

"DALLAS, Jan. 8 - The same vitamin D deficiency that can result in weak bones now has been associated with an increased risk of cardiovascular disease, Framingham Heart Study researchers report in Circulation: Journal of the American Heart Association. "Vitamin D deficiency is associated with increased cardiovascular risk, above and beyond established cardiovascular risk factors," said Thomas J. Wang, M.D., assistant professor of medicine at Harvard Medical School in Boston, Mass. "The higher risk associated with vitamin D deficiency was particularly evident among individuals with high blood pressure." In a study of 1,739 offspring from Framingham Heart Study participants (average age 59, all Caucasian), researchers found that those with blood levels of vitamin D below15 nanograms per milliliter (ng/mL) had twice the risk of a cardiovascular event such as a heart attack, heart failure or stroke in the next five years compared to those with higher levels of vitamin D."

Association between vitamin D and age-related macular degeneration in the Third National Health and Nutrition Examination Survey, 1988 through 1994. Parekh N, Chappell RJ, Millen AE, Albert DM, Mares JA. Arch Ophthalmol. 2007 May;125(5):661-9. PMID: 17502506

Severe vitamin D deficiency in Swiss hip fracture patients. Bischoff-Ferrari HA, Can U, Staehelin HB, Platz A, Henschkowski J, Michel BA, Dawson-Hughes B, Theiler R. Bone. 2008 Mar;42(3):597-602. Epub 2007 Nov 28. PMID: 18180211 BACKGROUND: Most clinical guidelines for the prevention of hip fractures recommend 800 IU vitamin D per day. This dose shifted serum 25-hydroxyvitamin D levels (25(OH)D) in previous studies to between 60 and 100 nmol/l. AIM: To measure 25(OH)D levels and prevalence of vitamin D supplementation in individuals age 65+ with acute hip fracture. METHODS: 222 consecutive hip fracture patients were investigated over a 12 month period. Mean age of patients was 86 years and 77% were women. RESULTS: Mean serum 25(OH)D levels were low among hip fracture patients admitted from home (34.6 nmol/l), from assisted living (27.7 nmol/l), and from nursing homes (24 nmol/l). Severe vitamin D deficiency below 30 nmol/l was present in 60%, 80% were below 50 nmol/l, and less than 4% reached desirable levels of at least 75 nmol/l. Consistently, only 10% of hip fracture patients had any vitamin D supplementation on admission to acute care with significantly higher 25(OH)D levels among individuals supplemented with 800-880 IU/day (63.5 nmol/l). Controlling for age and gender, vitamin D supplementation, type of dwelling, and season were independently and significantly associated with 25(OH)D levels. CONCLUSION: These data provide evidence that current guidelines for the prevention of hip fractures need further effort to be translated into clinical practice.

Urgent action needed to improve vitamin D status among older people in England! Hirani V, Tull K, Ali A, Mindell J. Age Ageing. 2009 Nov 23. [Epub ahead of print] PMID: 19934073 CONCLUSIONS: poor vitamin D status of older people continues to be a public health problem in England. Hypovitaminosis D is associated with many risk factors and poor health outcomes. There is now an urgent need for a uniform policy on assessment and dietary supplementation of vitamin D in older people to prevent poor vitamin D status and its negative consequences

25-hydroxyvitamin D, IGF-1, and metabolic syndrome at 45 years of age: a cross-sectional study in the 1958 British Birth Cohort. Hyppönen E, Boucher BJ, Berry DJ, Power C. Diabetes. 2008 Feb;57(2):298-305. Epub 2007 Nov 14. PMID: 18003755 doi: 10.2337/db07-1122 CONCLUSIONS-Serum 25(OH)D is inversely associated with metabolic syndrome, whereas the inverse association with IGF-1 was found only among those without hypovitaminosis D. These results suggest that metabolic syndrome prevalence is the lowest when both 25(OH)D and IGF-1 are high.

Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study. Javaid MK, Crozier SR, Harvey NC, Gale CR, Dennison EM, Boucher BJ, Arden NK, Godfrey KM, Cooper C; Princess Anne Hospital Study Group. Lancet. 2006 Jan 7;367(9504):36-43. Erratum in: Lancet. 2006 May 6;367(9521):1486. PMID: 16399151 doi:10.1016/S0140-6736(06)67922-1 Interpretation Maternal vitamin D insufficiency is common during pregnancy and is associated with reduced bone-mineral accrual in the offspring during childhood; this association is mediated partly through the concentration of umbilical venous calcium. Vitamin D supplementation of pregnant women, especially during winter months, could lead to longlasting reductions in the risk of osteoporotic fracture in their offspring.

Vitamin D-Related Changes in Physical Performance: A Systematic Review. Annweiler C, Schott AM, Berrut G, Fantino B, Beauchet O. J Nutr Health Aging. 2009;13(10):893-898. PMID: 19924350 Conclusions: The findings show that the association between vitamin D and physical performance remains controversial. Observational studies and clinical trials yielded divergent results, which highlights the complex and to date still poorly understood association between serum vitamin D concentration or vitamin D supplementation and physical performance.

An estimated 50% to 60% of older people have suboptimal vitamin D levels, which is a problem that could affect more than bone health. Recent cross-sectional studies have also shown an association between low vitamin D levels and cardiovascular disease, hypertension, and metabolic syndrome. In a long-term prospective study from Germany, researchers assessed whether 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were associated with all-cause and cardiovascular mortality among more than 3000 consecutive patients (mean age, 62) referred for coronary angiography.

Association between depressive symptoms and 25-hydroxyvitamin D in middle-aged and elderly Chinese. Pan A, Lu L, Franco OH, Yu Z, Li H, Lin X. J Affect Disord. 2009 Feb 25. [Epub ahead of print] PMID: 19249103 doi:10.1016/j.jad.2009.02.002