Tidsskr Nor Lægeforen 2005; 125: 330
Jeg ser meg nødt til å sitere større biter av enkelte artikler.
Kunnskapen om vitamin D har lenge vært økt, at det har med mer å gjøre enn bare ”index disease”, en sykdom per mangel, altså mer enn rakitt og osteomalaci.
Dessverre har ikke dagens lærebøker fått med seg dette, det så jeg tydelig da jeg sjekket pensumbøkene i sykepleie. Det strakk seg fra irrelevant til uvitende til direkte feil.
En eldre utgave av Geriatri i praksis av Laake nevnte bare calcitriol, mens konsensus er at vitamin D-status måles med nivået av 25-(OH)D (lagerformen av vitamin D3, calcidiol). Men han har rett i å anbefale kalsiumtilskudd, 1-1,5 gram samt vitamin D 800 IE 20µg. Det som er feil er at han sier at man ikke skal glemme at calcigran inneholder en signifikant mengde (100IE) D-vitamin per måleskje. Han sier at det kan oppstå hyperkalsemi ved flere D-vitaminpreparater og tran samtidig. Nå er det 400 IE i en nesten full spiseskje tran (5ml) og til sammen utgjør dette da 30µghvis jeg teller i tablett calcigran forte for 400 IE vitamin D. Flytende calcigran fant jeg ikke.
I en nyere utgave (2002) står stort sett det samme, men med tilføyelsen at de på tiuraziddiuretika (som kom tilbake på markedet nylig etter ALLHAT-studien) kan få for høye calsiumverdier, samt at sammenhengen calcitonin og PTH i osteoporose er uklar og at vitamin D-metabolitter er normale i osteoporose. Han ser fremdeles på feil metabolitt. Det brukes en del spalteplass på bentetthetsmålinger og annet innviklet og dyrt stoff.
Dette er godt under høyeste inntak som offisielt er 50µg, og har vært det siden 1960. det ville vært bedre å sitere 50µg og ikke skrive at flere D-vitaminpreparater ikke skal tas samtidig fordi det oppfattes som ufravikelig og absolutt. Man må sammenholde det med data for giftighet , og det går i gram-nivå, ikke µg.
Nå har nyere forskning funnet ut at det trengs enda mer enn disse 30µg for å heve et nivå på 50nmol/l til disse 80nmol/ liter hvor PTH ikke er forhøyet lenger, nemlig 33µg og det er nærliggende å trekke den slutningen at produsenten av kalktablettene med vitamin D nettopp har tilstrebet et optimalt vitamin-D-nivå hos pasientene:
http://www.ajcn.org/cgi/content/full/80/6/1706S Heaney: Functional indices of vitamin D status and ramifications of vitamin D deficiency
Presented at the conference "Vitamin D and Health in the 21st Century: Bone and Beyond," held in Bethesda, MD, October 9–10, 2003
Although the index diseases for vitamin D deficiency have long been considered to be rickets (for children) and osteomalacia (for adults), there has been a growing conviction that less severe degrees of deficiency may also produce skeletal disease. The canonical function of vitamin D is facilitation of the active transport component of intestinal calcium absorption, and there has never been any evidence suggesting that absorption is optimal at vitamin D concentrations just sufficient to prevent rickets or osteomalacia.
On the basis of his extensive experience with histomorphometric analysis of adult bone samples, in 1990 Parfitt (2) introduced an heuristically important reconceptualization of the bone disease attributable to vitamin D deficiency, for which he coined the term hypovitaminosis D osteopathy. He identified 3 stages of disease, related to increasing degrees of vitamin D depletion. In stage 1, the only detectable pathophysiologic change was reduced intestinal absorption of calcium, with consequent diminution of skeletal calcium reserves and accompanying osteoporosis. In biopsies, the bone in stage 1 showed no evidence of osteomalacia. In stage 2 hypovitaminosis D, there was decreased intestinal calcium absorption and decreased bone mass, as in stage 1, but in biopsies there was identifiable early osteomalacia, ie, increased surface coverage by osteoid and decreased mineral apposition rates. Patients with stage 2 disease exhibited no clinical or laboratory chemical signs of osteomalacia. Their only clinical manifestation was reduced bone mass, ie, osteoporosis. In stage 3 hypovitaminosis D, there was continued hypoabsorption of calcium and osteomalacia was evident clinically, biochemically, and histologically.
The importance of this reconceptualization is that it clearly demarcated the traditional index disease for vitamin D deficiency as constituting only the most extreme degree of deficiency. It was proposed that lesser degrees produced osteoporosis, which is silent until fractures occur, as has long been recognized. Therefore, the presence of osteoporosis and its connection to vitamin D status would have gone unrecognized.
Given the absence of reliable 25(OH)D3 values for the patients who contributed biopsy samples for his analysis, Parfitt (2) was unable to relate quantitatively his 3 stages to specific values for what the FNB would designate subsequently as the functional indicator. Nevertheless, Parfitt's work made clear that the then-current recommended dietary allowance for adults (200 IU/d), which was just sufficient to prevent clinical osteomalacia, was insufficient to protect against stage 1 or 2 hypovitaminosis D osteopathy. It is only now possible to assign, at least tentatively, specific serum 25(OH)D3 concentrations to the boundary between stage 1 disease and normal conditions and to estimate the input of vitamin D needed to reach such concentrations.
It is generally recognized that serum 25(OH)D3 concentrations of < 20 nmol/L are associated with clinical osteomalacia among adults. Most laboratory reference ranges, in contrast, extend from lower limits of 37.5 or 40 nmol/L to somewhat more than 100 or 120 nmol/L. The range between 20 nmol/L (the rickets/osteomalacia threshold) and the lower end of the reference range has usually been termed vitamin D insufficiency, in recognition of its presumed inadequacy for optimal functioning of the vitamin D and calcium economies. (The avoidance of the term deficiency for values in this range reflects the usually implied but common premise in nutritional science that inadequate intake of any nutrient causes only one disease; therefore, if patients did not have osteomalacia, they could not be "deficient.")
Clear quantitative evidence of the relationship of serum 25(OH)D3 concentrations to calcium absorptive function has emerged only recently. Heaney et al (13) and Barger-Lux and Heaney (14), in 2 companion studies, showed that fractional calcium absorption increased with serum 25(OH)D3 concentrations within the reference range, up to 80 nmol/L, and plateaued above that level.
These recently published studies clearly establish that there is malabsorption of calcium and increased fracture risk at serum 25(OH)D3 concentrations below 80 nmol/L. These findings are precisely what would be predicted for Parfitt's hypovitaminosis D osteopathy, stages 1 and 2, and provide quantitative referents not available to Parfitt when he proposed his classification scheme for vitamin D-related disease. Furthermore, these findings underscore the disturbing implications of elevated PTH concentrations at 25(OH)D3 concentrations of < 80 nmol/L
It has been a common professional experience that administration of vitamin D in amounts in the range of the current adequate intakes (defined by the FNB as 200–600 IU/d) does not produce an appreciable increase in measured serum 25(OH)D3 concentrations, which suggests either inadequate potency of the preparations used or greater need than implied in the concept of adequate intakes. Therefore, my colleagues and I (18) attempted to quantify both the daily utilization of vitamin D and the amount required to produce any desired increase in serum 25(OH)D3 concentrations. In this analysis, which was performed among healthy adults with average serum 25(OH)D3 concentrations in the middle of the reference range, we ascertained that daily utilization of vitamin D approximated 4000 IU (100 µg) and that, at equilibrium, serum 25(OH)D3 concentrations increased by 0.7 nmol/L for every 1 µg (40 IU) of vitamin D3 taken orally as a regular daily dose.
The antifracture trial by Trivedi et al (17) demonstrated an increase of almost exactly 1 nmol/L per 1 µg/d. By taking a value in the middle of the observed range of slopes (eg, 0.9 nmol/L per 1 µg/d), it can be calculated that the recommended daily intake for adults 50–70 y of age (400 IU) would be expected to increase serum 25(OH)D3 concentrations by only 9 nmol/L (3.6 ng/mL).
The initial step is to establish the vitamin D status of the individual (or group of individuals) being treated; only measurement of serum 25(OH)D3 concentrations can provide the baseline data on which prophylactic or therapeutic dosing can be based. For example, with 0.9 nmol/L per 1 µg/d being taken as the approximate operative slope, a patient with an untreated serum 25(OH)D3 concentration of 50 nmol/L would require a daily dose of 33 µg ( 1300 IU) to reach and maintain a serum 25(OH)D3 concentration of 80 nmol/L. This hypothetical starting value, 50 nmol/L, is almost exactly the measured concentration for the untreated subjects in our absorption study (13) and in the antifracture trial by Trivedi et al (17).
Nå var vi ved 33µg, noe som må oppfattes som giftig hos alle som ikke vet bedre når de leser hva Laake skriver om overdosering. Tredobbeldoseringen som han advarer mot, er nettopp nesten den dosen man trenger.
Heaney skriver at 250µg/dag ove mange måneder gir hypercalcemi, og vitamin D-council skriver at dyreforsøk angir at 21 mg/kg er dødelig dose.
Neste bok på pensum:
Karoliussen Smebye eldre, aldring og sykepleie
De sier som rett er, at eldre er mer påkledd og at omdanningen i huden går dårligere for eldre. De sier korrekt at målet er mengen 25(OH)D men sier ikke noe om at de eldre må faktisk testes hvert år. De sier at Nes og Thørner harmålt vitamin D hos eldre og at eldre som ikke får tilskudd, har lave verdier.
Men så detter de helt av.
De sier at vitamin D må dekkes gjennom kosten mest mulig (er ikke mulig hvis man ikke spiser mølje veldig hyppig og drikker tranen i mølje, det fins ingen andre kilder som gir 33µg om dagen og vitaminisert lettmelk inneholder kun 0,4µg/dl) og at i de tilfeller (altså alle tilfeller ifølge mitt resonnement) hvor det gis tilskudd , skal en vise forsiktighet med doseringen. ”Vitamin D er et toksisk stoff, og gapet mellom anbefalt daglig inntak og giftig dose er ikke særlig stort”.
Da titter vi på siden til venstre, hvor det er en hendig tabell. Nedre grense for inntak står det, og det er listet opp hele 2,5µg vitamin D både for menn og kvinner. Det er tabellen fra den gang statens ernæringsråd.
Hva skal en sykepleier da tenke om giftig dose som skal ikke være så langt fra anbefalt dose? Hun vil da huske Laake og være uvillig til å gi noen mer enn en calcigran- tablett som alene inneholder 10µg vitamin D. Jeg synes denne boken er ubrukelig uten en nærmere innføring i hva toxisk dos er , og at 33µg trengs for å heve nivået fra 50nmol/l til 80 nmol/l, og at man må måle vitamin D-status hvert år hos eldre.
De nye anbefalingene fra statens råd for ernæring og fysisk aktivitet er forresten hevet til 10µg for mennesker over 60 år, men den tabellen med nedre inntak har fremdeles 2,5µg for vitamin D.
|
1998 Oct 20;118(25):3929-31. |
[Vitamin D deficiency among hospitalized
and home-bound elderly][Article in Norwegian]
Mowe
M, Bohmer
T, Haug
E.
Medisinsk avdeling, Aker sykehus, Oslo.
Vitamin D status, measured
as serum calcidiol concentration, was studied in a group of 273 recently hospitalised
patients at Aker University Hospital and compared to a group of 98 persons living
in their own homes, all living in Oslo and all above 70 years of age. We found
lower serum calcidiol concentrations in the hospital group than among people
living in their own homes, in men as well as in women (mean +/- SD, 40.4 nmol/l
+/- 23.2 vs 59.6 nmol/l +/- 28.9 in men and 37.5 nmol/l +/- 22.6 vs 48.5 +/-
20.3 in women). 34% of the men and 49% of the women in the hospital group had
vitamin D deficiency (se. calcidiol < 20 nmol/l). There was no seasonal
variation in the hospitalised group; the group living at home did show seasonal
variations, with highest levels in late autumn (62.2 nmol/l) and lowest levels
in February (42.7 nmol/l). The low levels of calcidiol concentration may contribute
to the high prevalence of hip-fracture among elderly in Oslo
Og hva hvis man går ut ifra 80nmol/l? Da må vel de fleste her ha vitamin D-mangel.
http://www.tidsskriftet.no/pls/lts/PA_LT.VisSeksjon?vp_SEKS_ID=1095304
Kosttilskudd eller ikke?
…Undersøkelser av et utvalg av eldre i Oslo-området viser høygradig vitamin D-mangel hos 20 % av de eldre kvinnene, både hjemmeboende og sykehusinnlagte. Under 50 % hadde tilfredsstillende vitamin D-status (5, 6). Vitamin D er viktig for beinsystem og muskelfunksjon (7)….
http://www.tidsskriftet.no/pls/lts/PA_LT.VisSeksjon?vp_SEKS_ID=1142624
T. Bøhmer svarer:
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Tidsskr Nor Lægeforen 2005; 125: 330 |
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Carl Ditlef Jacobsen savner i min oversikt at «blodprøveanalyser kan avsløre mangeltilstander eller - helst det motsatte…». De råd jeg gir, er nettopp basert på blod- og serumanalyser, uten at jeg så det som vesentlig å presentere dette i innlegget.
Vitamin D-mangel er uttalt hos 10 % av sykehusinnlagte og hjemmeboende eldre, og vitamin D-konsentrasjonen er lavere enn ønskelig hos 50 % av samme gruppe (1, 2). Mangel på vitamin B6 (pyridoksalfosfat) og andre B-vitaminer er vanlig hos geriatriske pasienter (3). Vitamin C-konsentrasjonen er redusert hos et stort antall sykehusinnlagte og hjemmeboende eldre (3 - 5). I en studie var matinntaket hos eldre kvinner, både hjemmeboende og sykehusinnlagte, på gjennomsnittlig 1 750 kcal (6). Halvparten hadde derfor et kaloriinntak under dette og får ikke dekket minimumsbehovet for mineraler og sporelementer fra kosten uten ekstra tilskudd.
Den frykt enkeltpersoner fra det basalernæringsmessige miljø har for forgiftningsfaren ved høye vitamindoser, spesielt gjelder det de fettløselige, synes ikke å være noe klinisk problem. A-vitaminforgiftning får man ved å spise mye isbjørnlever. Gjør du det? Tolerable doser for vitamin D ligger kanskje 20 ganger over det anbefalte.
http://edrv.endojournals.org/cgi/content/full/22/4/477
C. Side effects and risks
The usually recommended doses of vitamin D3 are 400 or 800 IU/d. These doses are safe, and side effects are virtually nonexistent. The tolerance is quite high because the conversion into 1,25-(OH)2D3 is under tight feed-back control. Higher doses seldom are necessary, but 100,000 to 300,000 IU by mouth or per injection have been used once every 6 months or once yearly because of the ease of administration, obviating the need of checking compliance (192, 211, 212). In these studies, hypercalcemia was not observed. However, hypercalcemia has been observed in an older patient with a dose of 2000 IU/d (213) and in one patient receiving a single oral dose of 600,000 IU (214). Although practical, high doses may not be as safe as low doses. In addition, deep intramuscular injections carry some bleeding risk especially in combination with coumarin or acetylsalicylic acid therapy.
så godt som alle tenåringsjenter har verdier under 50nmol/L. Nedre grense for adekvat går ved 80 nmol/L
Vitamin D supplementation with 400 to 800 IU/d does not influence renal function or serum cholesterol concentration, and hypercalcemia has not been reported (56). High doses when given daily or weekly may cause vitamin D intoxication leading to bone resorption, bone loss, hypercalcemia, hypercalciuria, and renal functional impairment. However, graded oral dosing of vitamin D3 up to 50,000 IU/d for 8 weeks did not cause hypercalcemia (215). The occurrence of vitamin D intoxication is rather unpredictable, and it may occur even after years. Vitamin D intoxication may also result from over-the-counter dietary supplements which may contain several thousands of units vitamin D per daily dose (216). In vitamin D intoxication, the offending metabolite probably is 25(OH)D, which may bind to the VDR (217, 218). Alternatively, the serum 1,25-(OH)2D concentration may be increased, causing increased bone resorption that can be blocked by bisphosphonate infusion (219). The free serum 1,25-(OH)2D may also be increased because the high quantity of 25(OH)D may displace 1,25-(OH)2D from the vitamin D binding protein, thereby increasing its free concentration (220).
Another rare problem is an increased conversion of 25(OH)D to 1,25-(OH)2D, which may occur in granulomatous diseases such as sarcoidosis, tuberculosis, or malignant lymphoma (221). Vitamin D supplementation might cause an increase of serum 1,25-(OH)2D and hypercalcemia in these cases.
http://www.nutrition.org/cgi/content/abstract/135/2/317
Symposium: Vitamin D Insufficiency: A Significant Risk Factor in Chronic Diseases and Potential Disease-Specific Biomarkers of Vitamin D Sufficiency
Circulating 25-Hydroxyvitamin D Levels Indicative of Vitamin D Sufficiency: Implications for Establishing a New Effective Dietary Intake Recommendation for Vitamin D
Bruce W. Hollis
Departments of Pediatrics, Biochemistry, and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425
To whom correspondence should be addressed. E-mail: hollisb@musc.edu.
It has been more than 3 decades since the first assay assessing circulating 25-hydroxyvitamin D [25(OH)D] in human subjects was performed and led to the definition of "normal" nutritional vitamin D status, i.e., vitamin D sufficiency. Sampling human subjects, who appear to be free from disease, and assessing "normal" circulating 25(OH)D levels based on a Gaussian distribution of these values is now considered to be a grossly inaccurate method of identifying the normal range. Several factors contribute to the inaccuracy of this approach, including race, lifestyle habits, sunscreen usage, age, latitude, and inappropriately low dietary intake recommendations for vitamin D. The current adult recommendations for vitamin D, 200–600 IU/d, are very inadequate when one considers that a 10–15 min whole-body exposure to peak summer sun will generate and release up to 20,000 IU vitamin D-3 into the circulation. We are now able to better identify sufficient circulating 25(OH)D levels through the use of specific biomarkers that appropriately increase or decrease with changes in 25(OH)D levels; these include intact parathyroid hormone, calcium absorption, and bone mineral density. Using these functional indicators, several studies have more accurately defined vitamin D deficiency as circulating levels of 25(OH)D 80 nmol or 32 µg/L. Recent studies reveal that current dietary recommendations for adults are not sufficient to maintain circulating 25(OH)D levels at or above this level, especially in pregnancy and lactation.
http://www.ajcn.org/cgi/content/abstract/77/1/204
Original Research Communication Heaney et al. 2003
Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol1,2,3
Robert P Heaney, K Michael Davies, Tai C Chen, Michael F Holick and M Janet Barger-Lux
1 From Creighton University, Omaha (RPH, KMD, and MJB-L), and Boston University (TCC and MFH).
Background: The cholecalciferol inputs required to achieve or maintain any given serum 25-hydroxycholecalciferol concentration are not known, particularly within ranges comparable to the probable physiologic supply of the vitamin.
Objectives: The objectives were to establish the quantitative relation between steady state cholecalciferol input and the resulting serum 25-hydroxycholecalciferol concentration and to estimate the proportion of the daily requirement during winter that is met by cholecalciferol reserves in body tissue stores.
Design: Cholecalciferol was administered daily in controlled oral doses labeled at 0, 25, 125, and 250 µg cholecalciferol for 20 wk during the winter to 67 men living in Omaha (41.2° N latitude). The time course of serum 25-hydroxycholecalciferol concentration was measured at intervals over the course of treatment.
Results: From a mean baseline value of 70.3 nmol/L, equilibrium concentrations of serum 25-hydroxycholecalciferol changed during the winter months in direct proportion to the dose, with a slope of 0.70 nmol/L for each additional 1 µg cholecalciferol input. The calculated oral input required to sustain the serum 25-hydroxycholecalciferol concentration present before the study (ie, in the autumn) was 12.5 µg (500 IU)/d, whereas the total amount from all sources (supplement, food, tissue stores) needed to sustain the starting 25-hydroxycholecalciferol concentration was estimated at 96 µg (3800 IU)/d. By difference, the tissue stores provided 78–82 µg/d.
Conclusions: Healthy men seem to use 3000–5000 IU cholecalciferol/d, apparently meeting > 80% of their winter cholecalciferol need with cutaneously synthesized accumulations from solar sources during the preceding summer months. Current recommended vitamin D inputs are inadequate to maintain serum 25-hydroxycholecalciferol concentration in the absence of substantial cutaneous production of vitamin D.
http://www.ajcn.org/cgi/content/full/77/1/204
Without attaching particular significance to any given serum 25(OH)D concentration, it is nevertheless useful to select one such concentration so as to estimate the daily vitamin D input needed to achieve or sustain it. For this purpose, we selected 80 nmol/L, a figure near which serum PTH bottoms out (5,14,15). For a person with a starting value such as 50 nmol/L, the target increase would be 30 nmol/L, and, as the data in Figures 2 and 3B make clear, this increase would in turn require an additional input from all sources of 43 µg (1700 IU)/d. The standard error of the slope of the relation, derived from the data plotted in Figures 2 and 3B, produces a 95% CI for this estimate of 33 to 65 µg (1320, 2600 IU)/d. If maintenance of the assumed basal concentration of 50 nmol/L required input in the same proportion, the total daily input needed to maintain a concentration of 80 nmol/L would be about 114 µg/d (4600 IU/d). The 95% CI around this estimate extends from 88 to 175 µg (3520, 7000 IU). Even at the lower bound of the CI, this estimate is high in relation to current assumptions about vitamin D. Nevertheless, our point estimate is very close to the one produced by Vieth (16) in a recent analysis of the vitamin D literature.
As noted in the Results section, 12.5 µg/d is the approximate oral input required to maintain serum 25(OH)D at zero change, at least from starting values in the range we observed (70 nmol/L). ...
Both Vieth (16) and Holick (18) estimated that a single whole-body minimum erythema dose of solar radiation to the skin produces an input of 10 000 IU (250 µg) cholecalciferol, ...
Since 25(OH)D measurement became available clinically, it has been the common experience of clinicians and investigators that the standard multivitamin preparation (nominally containing 400 IU/dose unit) produced often imperceptible changes in measured serum 25(OH)D. Our present results confirm, in a general way, the relative smallness of the response to inputs in the range of the currently recommended oral vitamin D inputs (1). Using the slope for actual dose (ie, 0.70 nmol • L-1 • µg-1 • d-1), one can readily calculate that a dose such as 400 IU/d would elevate serum 25(OH)D3 by 7.0 nmol/L. Given the between assay variability of the methods for measuring serum 25(OH)D, it is unlikely that changes this small would be regularly detectable in individual persons. .....
For example, if a 70-y-old person’s sole source of vitamin D were the 600 IU/d recommended by the FNB (1), the data presented in this paper indicate that such an amount would be sufficient to sustain a 25(OH)D3 concentration in the range of only 12.5 nmol/L, a value generally recognized as subnormal and probably consistent with osteomalacia. ...
Several groups have reached the same conclusion, namely that, without appreciable cutaneous synthesis, current cholecalciferol input recommendations are inadequate . ....
We agree completely with Vieth (9) that the evidence available today indicates that a value of 2000 IU/d for the tolerable upper input level is too low. As already noted, the data presented here indicate an average daily need perhaps twice that amount. Note that, in our study, 20 wk of supplementation at 5500 and 11 000 IU/d, starting from a status of relative vitamin D repletion, produced no elevation of serum calcium above the upper limits of normal in any subject. Note also that the highest mean 25(OH)D3 values reached were 160 and 220 nmol/L, respectively. ...
http://jcem.endojournals.org/cgi/content/abstract/90/2/707
In conclusion, in healthy older men and women, a calcium intake within the range usually consumed and recommended does not appear to have an important effect on the rise in serum 25(OH)D levels that occurs in response to daily doses of 800 IU (20 µg) of vitamin D3. Moreover, only 21% of these subjects reached a 25(OH)D level of 32ng/ml (80 nmol/L) in the wintertime after 3 months of supplementation.
http://www.ajcn.org/cgi/content/abstract/80/6/1735S
Weaver
..Upper levels of vitamin D intake were set at 50 µg/d (2000 IU/d) for all ages. Some individuals would require higher levels than these to achieve serum 25-hydroxyvitamin D concentrations for optimal calcium absorption. So much new information on vitamin D and health has been collected since the requirements were set in 1997 that this nutrient is likely the most in need of revised requirements. ...
http://pediatrics.aappublications.org/cgi/content/abstract/116/3/e453
forgiftning av et barn med 600 000 IE per dag , ingen varige mèn. Blodverdien var da 470 ng/mL
cholecalciferol-council.com newsletter gjenfortelling av historien:
” This month we learned how much it takes to sicken a child. Doctors at the University of
Maryland School of Medicine report a case of accidental overdose of ergocalciferol - a vitamin
D like drug.
Pediatrics. 2005 Sep;116(3):e453-6.
(Ergocalciferol is not vitamin D; it is a vitamin D analog whose patent expired years ago.
Trader Joe’s sells it as a vegetarian vitamin D. It is usually obtained by radiating fungi, a fact
the health food crowd ignores. Ergocalciferol does not occur naturally in the human body, nor
do its numerous metabolic byproducts. It was nice to see the authors refer to ergocalciferol as
a vitamin D analog. Ergocalciferol is not vitamin D. Cholecalciferol is vitamin D.)
Anyway, mom was giving her 32-lb son a liquid preparation of ergocalciferol made in Latin
America. The direction stated adults should take one drop (2,500 units) per day but mom
mistakenly gave junior four bottles (2,400,000 units or 60 mg) over four days. The child
developed abdominal pain, mild high blood pressure, and high blood calcium but made an
uneventful recovery once the correct diagnosis was made.”
http://www.ajcn.org/cgi/content/abstract/69/5/842
http://www.cholecalciferol-council.com/
Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety
Reinhold Vieth
http://www.tidsskriftet.no/pls/lts/PA_LT.VisSeksjon?vp_SEKS_ID=97720
legetidsskriftet om barnematdirektivet fra EU, angående påbudt tilsetting av vitamin D i grøt . Da vil det bli enten 13 eller 38 µg vitamin D alt etter mengden grøt, som er høyere enn anbefalt grense på 25µg 1000IE. Dette var 2000, grensen kan ha gått opp siden. Anbefalt totalt inntak er 10µg ifølge artikkelen.
se NOAEL på side 18 i pdf fra Statens råd for ernæring, det er bare oppgitt NOAEL for voksne. De kaller det "Øvre grense for inntak av visse næringsstoffer for voksne, angitt per person og dag. De øvre grensene skal ikke brukes som anbefalte nivåer for inntak. De representerer øvre inntaksgrenser over lang tid hvor det er liten sannsynlighet for at det oppstår uønskede effekter hos mennesker."
islandsk studie viser at bare 500 mg kalsium trengs hvis man har nok vitamin D
japanske kvinner tar inn mye mindre kalsium enn skandinaviske men har mye høyere vitamin D-inntak, og har 30% færre benbrudd Calvo, Whiting, Barto Symposium Vitamin D insufficiency 2004 (via google scholar)
http://www.ajcn.org/cgi/content/full/80/3/752
Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged 60 y1,2,3
Heike A Bischoff-Ferrari, Thomas Dietrich, E John Orav, Frank B Hu, Yuqing Zhang, Elisabeth W Karlson and Bess Dawson-Hughes
http://edrv.endojournals.org/cgi/content/full/22/4/477
Vitamin D Deficiency and Secondary Hyperparathyroidism in the Elderly: Consequences for Bone Loss and Fractures and Therapeutic Implications Paul Lips
vanlig inntak er ca 100 IE 2,5µg per dag i Europa men mer i Skandinavia
The very low serum 25(OH)D in patients with hip fracture might be partly due to trauma. Serum DBP was lower in patients with hip fracture than in controls (86). However, the free 25(OH)D index, (ratio 25(OH)D/DBP), an estimate for the free serum 25(OH)D concentration, was also lower in patients with hip fracture than in controls (3.0 ± 1.6 vs. 4.6 ± 2.0, P < 0.001) indicating real vitamin D deficiency.
Nå har vi blitt tutet ørene fulle med at vi får i oss nok D-vitamin her i landet, og at den høye insidensen av brudd på lårhalsen er en gåte.
a vitamin D supplement of 400 or 800 IU/d increased serum 25(OH)D from 24 to 65 or 75 nmol/liter, respectively
Dette er 10 og 20µg, og 75 nmol/l er egentlig ikke høyt nok siden PTH først slutter å være forhøyet ved 80nmol/L.
Dette stemmer godt med konklusjonen ellers fra andre kilder om at man trenger mer enn anbefalt dose for å kunne ta opp kalsium bedre slik at bentettheten bedres.
More prospective epidemiological studies on risk factors for osteoporotic fractures including vitamin D deficiency are underway, e.g., the European Prospective Osteoporosis Study, the Rotterdam Study, and the Longitudinal Aging Study Amsterdam
Vitamin D deficiency is associated with muscle weakness. Muscle contraction and relaxation are abnormal in vitamin D deficiency, and these are corrected by vitamin D independently of changes in mineral levels
Interesting observations have been made in American blacks compared with whites. The incidence of hip fractures is considerably lower in black than in white people Biochemical markers of bone turnover, such as serum osteocalcin, suggested a higher bone turnover in blacks than in whites (161) or a similar turnover
http://www.ajcn.org/cgi/content/full/78/5/912
Thus, thiamine was linked to beriberi, niacin to pellagra, vitamin D to rickets, iodine to goiter, etc. Although it was soon recognized that most of the nutrients concerned played key roles in the metabolism of many tissues, the index disease for each nutrient was implicitly or explicitly considered to reflect the most vulnerable process or most sensitive tissue. This may explain why nutrient intake recommendations today are still largely pegged to the prevention of the index diseases for specific nutrients. The presumption has been that if the intake of the nutrient is sufficient to prevent the expression of the index disease, then the intake is, ipso facto, adequate for the functioning of the total organism. But this approach overlooks 2 additional possibilities. First, there may be long-term consequences of lesser degrees of deficiency that nevertheless operate through a mechanism similar to that inducing the index disease. Second, entirely different metabolic mechanisms may be involved. If the disease latency period were prolonged, then these mechanisms would probably be missed; or if they were recognized, they would probably be attributed to nonnutritional causes. Calcium and vitamin D each illustrate both possibilities.
As recently as 1989, the British Medical Journal could carry a two-part review that concluded that low calcium intake played no role in the development of osteoporosis (3, 4).
The vitamin D requirements are pegged to the prevention of stage-3 deficiency, and there still remains a presumption that if one does not have rickets or osteomalacia, then one has sufficient vitamin D. This position is no longer tenable, not just for the theoretical reasons just outlined, but because a rapidly growing body of evidence indicates malfunctioning and morbidity, which are correctable with vitamin D, in persons who do not have the index disease. For example, increasing serum 25-hydroxyvitamin D [25(OH)D] concentrations from 50 nmol/L to 80 nmol/L (both values within the usual reference range) improves calcium absorption efficiency by nearly two-thirds (21) and reduces osteoporotic fracture risk by one-third (22). Thus, it is now incontrovertible that vitamin D deficiency that is less extreme than that required to produce rickets or osteomalacia nevertheless produces disease, although of a long-latency character.
Because the endocrine function is driven by PTH, it is relatively independent of serum 25(OH)D concentrations, which explains why calcitriol concentrations may well be entirely normal in patients with florid osteomalacia.
Only relatively recently has reliable measurement of serum 25(OH)D concentrations been available, and most of the physiology of vitamin D had been worked out before that time and thus was unconnected to specific levels of vitamin D repletion. For example, although the Food and Nutrition Board had no difficulty in identifying 25(OH)D as the functional indicator for vitamin D status, they were not able, with the data that existed at that time, to assign numerical values to the lower limit of the normal range or to assign cutoff values for various vitamin D activities (6). As a result, current measurements are usually related to laboratory "reference" ranges (which is inevitably circular inasmuch as such ranges record what is observed in people who are considered "normal" only because they do not have recognizable rickets or osteomalacia).
The studies to which I just alluded (21, 22), together with a large body of data relating PTH concentrations to circulating 25(OH)D concentrations (eg, see references 30 and 31), indicate that the lower end of an acceptable normal range must be 80 nmol/L. (By contrast, the lower end of most reference ranges is closer to 40 nmol/L.) In recent years, nutritional scientists have referred to values <20 nmol/L as "deficient" (because they were reproducibly associated with osteomalacia or rickets), values above 80 as "normal," and values in between as "insufficient," without a clear consensus as to where the boundary might lie between "insufficient" and "normal." From the standpoint of the calcium economy, it now seems clear from the studies just cited that, at least for people living in the United Kingdom and North America, values <80 nmol/L are deficient. The awkward term insufficiency ought to be dropped. Its use simply reflected the point made earlier that the index disease for vitamin D was osteomalacia or rickets. If one had it, one was "deficient"; and if one did not, one could not be "deficient."
http://www.ajcn.org/cgi/content/full/80/6/1706S
Functional indices of vitamin D status and ramifications of vitamin D deficiency
Robert P Heaney
The publication in 2003 of a large British vitamin D intervention study provided a crucial piece of needed evidence. With a placebo-controlled, randomized design, Trivedi et al (17) administered 100,000 IU of vitamin D3 every 4 mo (averaging 800 IU/d), for 5 y, to 2686 healthy British participants 65–85 y of age. Serum 25(OH)D3 concentrations were measured for a subset of the cohort and averaged 53 nmol/L for the placebo group and 74 nmol/L for the vitamin D-treated group. The risk of all fractures was reduced by 22% among the supplement-treated individuals, and typical osteoporotic fractures, taken as a group, were reduced by 33%. As in the absorptive study by Heaney et al (13), the mean treated and untreated serum 25(OH)D3 concentrations in the British study were well within the reference range; in fact, the 2 studies spanned nearly the same range of values (50 and 53 nmol/L for the untreated subjects in the 2 studies and 74 and 86 nmol/L for the treated subjects).
It has been a common professional experience that administration of vitamin D in amounts in the range of the current adequate intakes (defined by the FNB as 200–600 IU/d) does not produce an appreciable increase in measured serum 25(OH)D3 concentrations, which suggests either inadequate potency of the preparations used or greater need than implied in the concept of adequate intakes.
For example, with 0.9 nmol/L per 1 µg/d being taken as the approximate operative slope, a patient with an untreated serum 25(OH)D3 concentration of 50 nmol/L would require a daily dose of 33 µg (1300 IU) to reach and maintain a serum 25(OH)D3 concentration of 80 nmol/L. This hypothetical starting value, 50 nmol/L, is almost exactly the measured concentration for the untreated subjects in our absorption study (13) and in the antifracture trial by Trivedi et al (17).
To complicate the matter further, several authors (26, 27) pointed out that some of the better-established methods failed to detect 25(OH)D2 with the same efficiency as 25(OH)D3. Because vitamin D3 (cholecalciferol) is the normal animal form of the vitamin and because cutaneous synthesis is the predominant source of total vitamin D for most individuals, this analytic defect is not likely to have serious consequences for assessment of vitamin D status among untreated patients. However, the only high-potency therapeutic vitamin D preparation available in the United States is ergocalciferol (vitamin D2), and no vitamin D3 preparation with a unit strength of > 2000 IU is available. The existing 25(OH)D3 assays may therefore be unable to help clinicians monitor responses to treatment with therapeutic vitamin D2.
http://www.ajcn.org/cgi/content/full/80/2/264
Why "Vitamin D" is not
a hormone, and not a synonym for 1,25-dihydroxy-vitamin D, its analogs or deltanoids.
Vieth R.
Department of Laboratory Medicine and Pathobiology, University of Toronto and
Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ont., Canada
M5G 1X5. rvieth@mtsinai.on.ca
Official nutrition committee reports in both North America and Europe now state
that Vitamin D is more of a hormone than a nutrient. These statements are wrong,
and do not reflect the definitions of either vitamin or hormone. Researchers
often compound the problem by referring to calcitriol or other deltanoids as
"Vitamin D". These things have serious consequences: (1) The literature
is burdened by an ongoing confusion that presumes that the reader will somehow
"know" what the writer refers to by "Vitamin D". (2) Medical
practitioners not familiar with the ambiguities administer Vitamin D inappropriately
when calcitriol or a deltanoid analog would be correct, or vice versa. (3) Attempts
to promote Vitamin D nutrition are hindered by alarmist responses justifiably
associated with the widespread administration of any hormone. Vitamin D is a
vitamin in the truest sense of the word, because "insufficient amounts
in the diet may cause deficiency diseases". The term, prohormone, is not
relevant to the Vitamin D system, but 25-hydroxy-Vitamin D (calcidiol) is appropriately
described as a prehormone, i.e. a glandular secretory product, having little
or no inherent biologic potency, that is converted peripherally to an active
hormone.
Prospects for vitamin D receptor modulators as candidate drugs for cancer and (auto)immune diseases.
The effect of conventional vitamin D(2) supplementation on serum 25(OH)D concentration is weak among peripubertal Finnish girls: a 3-y prospective study.
(10µg vitamin D2 gjorde nesten ikke noe for å øke blodverdiene)
Half of the patients with an acute hip fracture suffer from hypovitaminosis D: a prospective study in southeastern Finland.
|
Scand J Rheumatol Suppl. 1996;103:75-8; discussion 79-80. |
Prevention of hip fractures by correcting calcium and vitamin D insufficiencies in elderly people.
Nutrient content of served food, nutrient intake and nutritional status of residents with dementia in a finnish nursing home.
A high prevalence of hypovitaminosis D in Finnish medical in- and outpatients.
|
1982 Aug;17(2):189-94. |
Serum levels of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D and parathyroid hormone in patients with femoral neck fracture in southern Finland.
Newsletter http://www.cholecalciferol-council.com/ Toxicity of vitamin D
“Although there are documented cases of pharmacological overdoses from ergocalciferol,
the only documented case of pharmacological, not industrial, toxicity
from cholecalciferol
we could find in the literature was intoxication from over-the-counter
supplement called
Prolongevity. [8] On closer inspection, it seemed more like an industrial
accident but is
interesting because it gives us some idea of the safety of cholecalciferol.
The capsules
consumed contained up to 430 times the amount of cholecalciferol
contained on the
label (2,000 IU). The man had been taking between 156,000 to 2,604,000
IU of
cholecalciferol a day (equivalent to between 390 and 6,500 of the
400 unit capsules) for
two years. He recovered uneventfully after the proper diagnosis,
treatment with steroids
and sunscreen.”
It is true that a few people may have problems with high calcium due to undiagnosed
vitamin D hypersensitivity syndromes such as primary hyperparathyroidism,
granulomatous disease or occult cancers but a blood calcium level, a PTH, a
25(OH)D
and calcitriol level should help clarify the cause of the hypersensitivity.
kill half the animals) for cholecalciferol in dogs is about 88 mg/kg
(3,520,000 IU/kg). 4]
This would be equivalent to a 110-pound adult taking 176,000,000
IU or 440,000 of
the 400 unit cholecalciferol capsules!
Vitamin D hypersensitivity syndromes are often mistaken for vitamin D toxicity.
The
most common is primary hyperparathyroidism. Other syndromes occur when abnormal
tissue subverts the kidney's normal regulation of endocrine calcitriol production.
Aberrant tissues, usually granulomatous, convert 25(OH)D into calcitriol causing
high
blood calcium. The most common such condition is sarcoidosis, oat cell carcinoma
of
the lung and non-Hodgkin's lymphoma but other illness can cause the syndrome
and
they can occur while the patient’s 25(OH)D levels are normal or even low. For
that
reason, while rare, it is advisable to seek a knowledgeable physician's care
when
repleting your vitamin D system, especially if you are older, have sarcoidosis,
cancer or
other granulomatous diseases. In such high-risk patients, periodic monitoring
of 25(OH)
D levels and serum calcium will alert the physician to the need to do more tests,
such as
calcitriol or PTH, and take further action.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3008525&query_hl=11&itool=pubmed_DocSum
|
1986 Mar;15(2):77-83. |
Seasonal changes in the biochemical indices of vitamin D deficiency in the elderly: a comparison of people in residential homes, long-stay wards and attending a day hospital.
High prevalence of hypovitaminosis D among free-living postmenopausal women referred to an osteoporosis outpatient clinic in northern Italy for initial screening.
Teenage girls and elderly women living in northern Europe have low winter vitamin D status.
http://www.nature.com/ejcn/journal/v54/n8/abs/1601065a.htm
Vitamin D deficiency and bone health in healthy adults in Finland: could this be a concern in other parts of Europe?
Effect of oral vitamin D2 yearly bolus on hip fracture risk in elderly women: a community primary prevention study.
Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients.
Occult vitamin D deficiency in postmenopausal US women with acute hip fracture.
The new 1997 Dietary Reference Intake guidelines from the National Institutes of Health recommend 400 IU of vitamin D supplement daily for individuals from age 51 through 70 years and 600 IU daily for those older than 70 years. Supplements of about 800 IU of vitamin D per day and calcium may be necessary to attenuate bone loss in the winter and to reduce fractures.
Vitamin D, parathyroid hormone levels and bone mineral density in community-dwelling older women: The Rancho Bernardo Study.
….However, after the threshold vitamin D level of 120 nmol/l, all PTH values were below 65 ng/l.
|
Lancet. 1995 Jul 22;346(8969):207-10. |
Serum vitamin D concentrations among elderly people in Europe.
|
Public Health Nutr. 2004 Apr;7(2):327-35. |
Vitamin D status of middle-aged
women at 65-71 degrees N in relation to dietary intake and exposure to ultraviolet
radiation.
Brustad M, Alsaker E, Engelsen O, Aksnes L, Lund
E.
Institute of Community Medicine, University of Tromso, N-9037 Tromso, Norway.
Magritt.Brustad@ism.uit.no
Vitamin D intake was a significant predictor of 25(OH)D
Conclusions:Increased ingestion of marine food items that provide vitamin D should be promoted and further studies should be carried out to investigate vitamin D status in arctic populations in relation to both UV exposure and traditional food sources.
|
J Neurol. 2005 Nov 14; [Epub ahead of print] |
Neuropsychological function in
relation to serum parathyroid hormone and serum 25-hydroxyvitamin D levels The
Tromso study.
Jorde
R, Waterloo
K, Saleh
F, Haug
E, Svartberg
J.
Department of Internal Medicine, Institute of Clinical Medicine, University
of Tromso, Tromso, Norway.
There are receptors for parathyroid hormone (PTH) and 1,25-dihydroxyvitamin
D in the brain, and there are clinical and experimental data indicating that
PTH and vitamin D may affect cerebral function. In the present study 21 subjects
who both in the 5(th) Tromso study and at a follow-up examination fulfilled
criteria for secondary hyperparathyroidism (SHPT) without renal failure (serum
calcium < 2.40 mmol/L, serum PTH > 6.4 pmol/L, and normal serum creatinine)
and 63 control subjects were compared with tests for cognitive and emotional
function. 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 (BDI) (items 1-13).
In a multiple linear regression model, a high serum PTH level was significantly
associated with low performance at the Digit span forward, Stroop test part
1 and 2, and Digit Symbol tests. A low level of serum 25-hydroxyvitamin D was
significantly associated with a high depression score. In conclusion, a deranged
calcium metabolism appears to be associated with impaired function in several
tests of neuropsychological function.
Dette gjelder depresjon.
Ellers er vitamin D involvert i blodtrykk, immunsystemet bl.a. autoimmune sykdommer og kreft.
Søk på vitamin D på Medline og det er mange artikler om andre ting mangel på Vitamin D er invlovert i
http://www.tidsskriftet.no/pls/lts/PA_LT.VisSeksjon?vp_SEKS_ID=97720 om barnematdirektivet
lim inn referansen ” Seelig MS. Vitamin D and cardiovascular, renal, and brain damage in infancy and childhood. Ann NY Acad Sci 1969; 147: 539 – 82” i google og opp kommer EU-dokumentet
http://europa.eu.int/comm/food/fs/sc/scf/out157_en.pdf Tolerable upper intake level of vitamin D
http://www.tidsskriftet.no/pls/lts/PA_LT.VisSeksjon?vp_SEKS_ID=1019441 oppgir at europeiske anbefalinger for vitamin D- tilskudd er op til 25µg og at finske målinger antyder at 10µg kan gi tilfredsstillende vitamin D-status. Jeg har ikke lest referansen.
http://www.tidsskriftet.no/pls/lts/PA_LT.VisSeksjon?vp_SEKS_ID=1188579
Kalsium og vitamin D forebygger ikke brudd
|
Tidsskr Nor Lægeforen 2005; 125: 1304 |
Tilskudd av kalsium og vitamin D3 ser ikke ut til å minske risikoen for lårhalsbrudd hos eldre kvinner. En randomisert kontrollert studie publisert i BMJ konkluderer med dette etter å ha fulgt 3 300 britiske kvinner over 70 år med en eller flere risikofaktorer for lårhalsbrudd. Som risikofaktorer regnes blant annet tidligere brudd, lav kroppsvekt, røyking og generelt dårlig helse. Kvinnene ble delt i to grupper, hvor kvinnene i den ene gruppen fikk råd om hvordan de unngår fall, samt tilskudd av 1 000 mg kalsium og 800 IE (20 g) vitamin D3 daglig. Kontrollgruppen fikk kun en brosjyre om kosthold, samt råd om hvordan de unngår fall. Kvinnene ble fulgt opp over en periode på gjennomsnittlig to år. I løpet av denne perioden var antall brudd lavere enn forventet i begge gruppene, men det var ingen forskjell mellom gruppene. Forskerne fant ingen bevis for at tilskudd av kalsium og vitamin D3 reduserer risikoen for beinbrudd som følge av fall. De fant heller ikke bevis for bedret livskvalitet.
Jeg leste artikkelen artikkelen i bmj. De har ikke målt vitamin D-status og heller ikke PTH i denne studien, noe som jeg synes er oppsiktsvekkende. Heanley skriver at man i teori må opp i 33µg, hvis utgangspunktet var 50nmol/l og i praksis må man da måle 25(OH)D. Artikkelen bekrefter nettopp at 20µg ikke er nok. Forresten henviser de til en norsk studie som jeg ikke har lest.