Vitamin D

An acknowledged benefit of exposure to ultraviolet radiation is synthesis of vitamin D in human skin. Here we have defined a standard vitamin D dose based upon recommended requirements for vitamin D, and present a web-based tool that enables the user to calculate associated exposure times for any time and place ( http://nadir.nilu.no/~olaeng/fastrt/VitD_quartMED.html). The recommended UV exposure times depends on latitude, time, total ozone, clouds, aerosols, surface reflectivity and altitude all of which can be specified by the user. A simpler version for non-experts is available at http://nadir.nilu.no/~olaeng/fastrt/VitD-ez_quartMED.html

An acknowledged benefit of exposure to ultraviolet radiation is synthesis of vitamin D in human skin. Here we have defined a standard vitamin D dose based upon recommended requirements for vitamin D, and present a simplified web-based tool that enables the user to calculate associated exposure times for any time and place ( http://nadir.nilu.no/~olaeng/fastrt/VitD-ez_quartMED.html). This www page is a simplified version of the more complex web tool ( http://nadir.nilu.no/~olaeng/fastrt/VitD_quartMED.html). The simplified www page is convenient for users unfamiliar to radiative transfer modelling, because the model input is limited and more intuitive.

Simulations of ultraviolet irradiances, doses and indices at the Earth's surface at user specified UV wavelengths. A simpler version for non-experts is available at http://nadir.nilu.no/~olaeng/fastrt/fastrt-ez.html

Relationships between 25-Hydroxyvitamin D Levels and Plasma Glucose and Lipid Levels in Pediatric Outpatients. Johnson MD, Nader NS, Weaver AL, Singh R, Kumar S. J Pediatr. 2009 Nov 17. [Epub ahead of print] PMID: 19926097 Conclusions Low 25(OH) D levels in children and adolescents are associated with higher plasma glucose and lower HDL concentrations.

Vitamin D and breast cancer. Bertone-Johnson ER. Ann Epidemiol. 2009 Jul;19(7):462-7. Epub 2009 Feb 20. Review. PMID: 19230714 Though the relationship between vitamin D and breast cancer remains unclear, a growing body of evidence suggests that vitamin D may modestly reduce risk. A large number of in vitro studies indicate that vitamin D can inhibit cell proliferation and promote apoptosis and cell differentiation in breast tumor tissue. Results from analytic studies of sunlight exposure and dietary intake have been inconsistent but together generally support a modestly protective role of vitamin D, at least in some population subgroups. Studies using blood vitamin D metabolites to assess vitamin D status may be less prone to misclassification than those of diet and sunlight exposure. Overall, the two prospective and four case-control studies of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D tend to support a protective effect in older women. The relationship between common vitamin D receptor polymorphisms and risk remains unclear. Many questions about this relationship clearly remain, including the utility of assessing vitamin D through diet and sunlight exposure, the relationship between plasma metabolites, and the potential modifying effects of age, menopausal status and tumor characteristics. Given that vitamin D status is modifiable, additional prospective studies are necessary to determine if vitamin D may have important potential for breast cancer prevention.

"Osteoporoosin tiedetään olevan pääasiassa D-vitamiinin ja auringon valon puutesairaus. Afrikasassa osteoporoosi on tuntematon ja mitä pohjoisemmaksi tullaan sitä enemmän on luuston haurastumista ja murtumia. Lonkkamurtumia ei Afrikassa juuri tunneta ja murtumien määrä kasvaa samanikäisellä väestöllä monisatakertaisesti tänne pohjoiseen tultaessa. Nyt on selvinnyt että jo äidin raskauden aikainen D-vitamiinin saanti on tärkeää lapsen tulevalle luuntiheydelle. Ne brittiäidit, jotka käyttivät D-vitamiinivalmisteita sekä ne äidit,jotka synnyttivät kesällä saivat vahvempiluisia jälkeläisiä ja ero näkyi vielä 9 vuoden iässä. "

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.

Aurinko, D-vitamiini ja sydäntaudit liittyvät toisiinsa. On väärin syyttää kolesterolia ja ruokavaliota sydän- ja verisuonitaudeista, sanoo englantilainen gastroenterologi David Grimes Machesterin yliopistosta. Hän on tutkinut yli 20 vuotta sydän- ja valtimotautien esiintymistä eri väestöissä, ja nyt hän on julkaissut aiheesta 642-sivuisen perusteellisen kirjan ´Vitamin D and Cholesterol´. Sen mukaan sepelvaltimotaudin pääasiallinen syy on auringonvalon ja D-vitamiinin puute, eikä suinkaan kolesteroli ja rasvainen ruoka. Tohtori Grimes sai kimmokkeen alkaa tutkia auringonvalon, veren D-vitamiinin ja sydäntautien yhteyksiä havaittuaan, että Englantiin muuttaneet aasialaiset sairastuivat sydäntauteihin sitä enemmän, mitä pohjoisemmaksi he asettuivat asumaan. Pohjoiseen muuttaneet aasialaiset sairastuivat useammin kuin Etelä-Englantiin muuttaneet, ruokavaliosta riippumatta. Grimes selvitti kuinka paljon aurinkoisia päiviä eri paikkakunnilla oli ja kuinka paljon asukkaat saivat aurinkoa, ja hän vertasi lukuja sairaustilastoihin. Yhteys oli selvä: Sydänpotilailla on "leveysastetauti" (latitude sickness). Lenkki on D-vitamiini, päätteli Grimes. Sen pääasiallinen lähdehän ihmiskunnalle on auringovalo; ruoasta saamme vain hyvin mitättömän pienen määrän päivittäin, 5-7 mikrogrammaa (µg). Tarve voi olla jopa 100 µg, minkä useimmat maahanmuuttajat olivat saaneet helposti päivittäin auringosta lähtömaissaan.

"We are fond of grumbling about Britain's grey skies, but there may be a good medical reason for doing so. It seems the dreary weather is bad for our hearts - worse, even, than raised cholesterol and an unhealthy diet. That's the controversial claim being made by Dr David Grimes, a gastroenterologist from Blackburn. He's been gazing at the sky for 20 years for clues about why his patients get more sick than those in the south of the country. And what he's found turns key assumptions about heart disease on their head. 'It's not diet or cholesterol levels that raise your risk of heart disease,' he claims. 'It's where you live. People in the north are more likely to be ill because they get less sunshine Basically they are suffering from 'latitude' sickness. The link is vitamin D. While we get some from our diet, the main source is the sun - sunlight converts a compound in the skin into vitamin D, so the amount you make is directly related to the amount of sunshine you get. In a new book Dr Grimes argues the higher the level of vitamin D in your blood, the lower your risk of heart disease and a range of other illnesses. If he's right, what we need is not diet and lifestyle advice, but food fortified with vitamin D. For years the vitamin was thought to be useful only for preventing rickets. So how does he treat them? 'You can do it with diet,' he says 'One Bangladeshi woman eats oily fish every day and now has a vitamin D blood level of 40. 'We give supplements of 1,000 international units (IU) a day or we can give an injection of 300,000 IU that lasts for a year. 'The patients respond well,' says Grimes 'but what's needed is a proper controlled, long-term trial and who is going to fund that? Not a drug company.'"

Serum vitamin D concentration and prostate cancer risk: a nested case-control study. Ahn J, Peters U, Albanes D, Purdue MP, Abnet CC, Chatterjee N, Horst RL, Hollis BW, Huang WY, Shikany JM, Hayes RB; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Project Team. J Natl Cancer Inst. 2008 Jun 4;100(11):796-804. Epub 2008 May 27. PMID: 18505967 doi:10.1093/jnci/djn152 CONCLUSION: The findings of this large prospective study do not support the hypothesis that vitamin D is associated with decreased risk of prostate cancer; indeed, higher circulating 25(OH)D concentrations may be associated with increased risk of aggressive disease. In summary, results from this large prospective study of men who underwent standardized prostate cancer screening in the context of a screening trial do not support the hypothesis that higher serum vitamin D status is associated with decreased risk of prostate cancer. The study showed no association of vitamin D level with nonaggressive disease; however, it raises the possibility that higher vitamin D level may be associated with increased risks for aggressive disease, although a clear monotonic dose-response relationship was lacking. Along with recent reports of adverse associations for higher vitamin D status and risk of pancreatic (32) and esophageal (33,34) cancer, caution should be taken in recommending high doses of vitamin D or sunlight exposure to the general public for prostate cancer prevention. Future analyses are warranted to confirm these results and to further clarify the effects of vitamin D on aggressive prostate cancer.

Vitamin D receptor (VDR) gene polymorphisms and haplotypes, interactions with plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and prostate cancer risk. Mikhak B, Hunter DJ, Spiegelman D, Platz EA, Hollis BW, Giovannucci E. Prostate. 2007 Jun 15;67(9):911-23. PMID: 17440943 DOI: 10.1002/pros.20570 RESULTS No association was found between these SNPs or their associated haplotypes and all PC subtypes except that haplotype 2 (A-f-b) with Cdx2 A, Fok1 f, and Bsm1 b alleles and haplotype 3 (A-F-B) with Cdx2 A, Fok1 F and Bsm1 B alleles compared to the most common haplotype (A-F-b), were associated with reduced risk of aggressive PC (high stage or Gleason sum 7; P = 0.02), both with two alleles suspected of being low risk. Carriers of the variant Cdx2 A allele who were deficient in plasma 25-hydroxyvitamin D (15 ng/ml) compared to non-carriers with normal 25-hydroxyvitamin D, had a lower risk of total and poorly differentiated PCs (Gleason sum 7) (P for interaction = 0.02 and 0.04, respectively). Plasma 1,25-dihydroxyvitamin D deficiency (26 pg/ml) was associated with a threefold risk of poorly differentiated PC (P for interaction = 0.01) when comparing carriers of the Cdx2 A allele to non-carriers with normal 1,25-dihydroxyvitamin D. CONCLUSION In this population of men, none of the VDR polymorphisms studied was associated with susceptibility to PC. Carriers of the variant Cdx2 A allele with low plasma 25-hydroxyvitamin D may experience a reduction in risk of total and poorly differentiated prostate cancers compared to non-carriers with adequate 25-hydroxyvitamin D.

A prospective nested case-control study of vitamin D status and pancreatic cancer risk in male smokers. Stolzenberg-Solomon RZ, Vieth R, Azad A, Pietinen P, Taylor PR, Virtamo J, Albanes D. Cancer Res. 2006 Oct 15;66(20):10213-9. PMID: 17047087 Higher vitamin D concentrations were associated with a 3-fold increased risk for pancreatic cancer (highest versus lowest quintile, >65.5 versus <32.0 nmol/L: OR, 2.92; 95% CI, 1.56-5.48, Ptrend = 0.001) that remained after excluding cases diagnosed early during follow-up. Contrary to expectations, subjects with higher prediagnostic vitamin D status had an increased pancreatic cancer risk compared with those with lower status. Our findings need to be replicated in other populations and caution is warranted in their interpretation and implication. Our results are intriguing and may provide clues that further the understanding of the etiology of this highly fatal cancer. In conclusion, contrary to expectation, subjects with higher 25(OH)D concentrations were at greater risk for pancreatic cancer compared with those with lower concentrations in our prospective study with long-term follow-up. Caution is warranted in the interpretation and implication of our findings, however, as vitamin D inadequacy is an important public health problem and adequate status is desirable to prevent bone and other diseases (5). Our results, however, are intriguing and may provide clues that further the understanding of the etiology of this highly fatal cancer.

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.

Fish, vitamin D, and flavonoids in relation to renal cell cancer among smokers. Wilson RT, Wang J, Chinchilli V, Richie JP, Virtamo J, Moore LE, Albanes D. Am J Epidemiol. 2009 Sep 15;170(6):717-29. Epub 2009 Aug 3. PMID: 19651663 doi:10.1093/aje/kwp178 These results suggest that the flavonoid quercetin may prevent renal cell cancer among male smokers. The possible risk associated with fish intake warrants further investigation before conclusions may be drawn.

Serum 25(OH)-vitamin D concentration and risk of esophageal squamous dysplasia. Abnet CC, Chen W, Dawsey SM, Wei WQ, Roth MJ, Liu B, Lu N, Taylor PR, Qiao YL. Cancer Epidemiol Biomarkers Prev. 2007 Sep;16(9):1889-93. PMID: 17855710 doi: 10.1158/1055-9965.EPI-07-0461 Background: Squamous dysplasia is the precursor lesion for esophageal squamous cell carcinoma, and nutritional factors play an important role in the etiology of this cancer. Previous studies using a variety of measures for vitamin D exposure have reached different conclusions about the association between vitamin D and the risk of developing esophageal cancer. Conclusions: Higher serum 25(OH)D concentrations were associated with significantly increased risk of squamous dysplasia. No obvious source of measured or unmeasured confounding explains this finding. In conclusion, we found that a higher serum 25(OH)D concentration was associated with an increased risk of esophageal squamous dysplasia, the precursor lesion for ESCC. This finding concurs with our previous prospective study which found that higher vitamin D status was associated with increased risk of incident ESCC in this same population. These unexpected findings suggest that further studies of the association of vitamin D and digestive tract cancers are needed before the effect of vitamin D in different populations can be elucidated.

"I discussed in my last post how Dr Vieth has a model of tissue 1,25(OH)2D synthesis and degradation in which the level of active substance is pretty well independent of blood vitamin D level, provided the level is either rising or stable. I think it is also worth pointing out that he is talking, hypothetically, about tissue 1,25(OH)2D, not plasma level... As we know, almost nothing is known about tissue 1,25(OH)2D control. By Vieth's hypothesis tissue 1,25(OH)2D is OK so long as there is at least SOME vitamin D present in plasma and the level dose not vary too much. Obviously there is a level below which you can have as much of the enzyme for converting vitamin D to the active form as you like, if there is no vitamin D in your blood you can't make any 1,25(OH)2D in your tissues, or in your kidneys for export to your blood to control calcium levels. At the lower extremes we have rickets and osteomalacia. These are clear cut, unarguable markers of vitamin D deficiency, in the absence of confounding factors (there are a few)."

The vitamin D-antimicrobial peptide pathway and its role in protection against infection. Gombart AF. Future Microbiol. 2009 Nov;4:1151-65. PMID: 19895218 Vitamin D deficiency has been correlated with increased rates of infection. Since the early 19th century, both environmental (i.e., sunlight) and dietary sources (cod liver) of vitamin D have been identified as treatments for TB. The recent discovery that vitamin D induces antimicrobial peptide gene expression explains, in part, the 'antibiotic' effect of vitamin D and has greatly renewed interest in the ability of vitamin D to improve immune function. Subsequent work indicates that this regulation is biologically important for the response of the innate immune system to wounds and infection and that deficiency may lead to suboptimal responses toward bacterial and viral infections. The regulation of the cathelicidin antimicrobial peptide gene is a human/primate-specific adaptation and is not conserved in other mammals. The capacity of the vitamin D receptor to act as a high-affinity receptor for vitamin D and a low-affinity receptor for secondary bile acids and potentially other novel nutritional compounds suggests that the evolutionary selection to place the cathelicidin gene under control of the vitamin D receptor allows for its regulation under both endocrine and xenobiotic response systems. Future studies in both humans and humanized mouse models will elucidate the importance of this regulation and lead to the development of potential therapeutic applications

"Defensins are small cysteine-rich cationic proteins found in both vertebrates and invertebrates. They are active against bacteria, fungi and many enveloped and nonenveloped viruses. They consist of 18-45 amino acids including six (in vertebrates) to 8 conserved cysteine residues. Cells of the immune system contain these peptides to assist in killing phagocytized bacteria, for example in neutrophil granulocytes and almost all epithelial cells. Most defensins function by binding to microbial cell membrane, and once embedded, forming pore-like membrane defects that allow efflux of essential ions and nutrients

"D-vitamiini näyttäisi suojaavan keskushermoston rappeutumissairauksilta. Viime vuosien aikana on saatu lisävalaistusta normaaliin elimistön vanhenemiseen, kun on selvinnyt, että vanhenemista jarruttavan hormonin (FGF-23) vaikutus perustuu D-vitamiiniin. Sekä koe-eläimillä että ihmisillä on todettu, että FGF-23 jarruttaa D-vitamiinin hormonaalisten muotojen tuottoa. Siten FGF-23:n toimintaa häiritsevät mutaatiot saavat aikaan D-vitamiinin yliaktiivisuuden ja nopeuttavat vanhenemista. Tamperelainen tutkimusryhmä on juuri ilmestyneessä arvostetussa Psychoneuroendocrinology-lehdessä osoittanut, että sekä D-vitamiinin yliaktiivisuus että sen vaikutuksen puutos nopeuttavat fysiologista vanhenemista. Tutkimusryhmä on jo aikaisemmin raportoinut, että eturauhassyövän riski on pienimmillään, kun seerumin D-vitamiinipitoisuus on normaali, mutta riski lisääntyy sekä matalilla että korkeilla veripitoisuuksilla. Sairastumisriski noudattaa U-muotoista riippuvuutta D-vitamiinin veripitoisuudesta. Tällainen U-muotoinen riippuvuus D-vitamiinista näyttäisi olevan melko yleistä, koska sellainen ilmenee myös kokonaiskuolleisuudessa, sydänkuolleisuudessa ja luuston haurastumisessa. On mahdollista, että oikealla D-vitamiinin annostelulla voitaisiin lykätä monien kroonisten sairauksien alkamista jopa vuosilla myöhemmäksi. Tällaisia sairauksia ovat eräät yleiset syövät, sokeritauti, verisuonten kalkkeutuminen, verenpainetauti, keskushermoston rappeutumissairaudet, astma, autoimmuunisairaudet ja osteoporoosi."

"D-vitamiini parantaa yli 65-vuotiaiden ihmisten elämänlaatua ja ehkäisee ennenaikaista sydänkuolemaa, ilmenee Amerikan geriatriyhdistyksen lehden julkaisemasta tutkimuksesta. Myös Suomen THL julkaisi vastikään raportin, jonka mukaan seerumin vähäinen D-vitamiinin pitoisuus liittyi sydäntauteihin ja -kuolemiin. Seerumin D-vitamiinin pitoisuus (25-0HD eli S-D-25), joka on pienempi kuin 25 nmol/l, liittyy suurentuneeseen sydäntautien ja kuoleman riskiin, kirjoittavat amerikkalaiset tutkijat. Heidän aineistonsa käsitti 3408 yli 65-vuotiasta miestä ja naista, joiden terveydentilaa seurattiin Third National Health and Nutrition Examination Survey (NHANES III) -tutkimuksessa. Keskimäärin 7,3 vuoden seuruun aikana kuoli 1493 (44 %) tutkituista. Vähän yli puolet (767) kuolemista johtui sydänkohtauksista."