cholecalciferol should be an integral part of effective osteoporosis management

8/13/2019 Cholecalciferol Should Be an Integral Part of Effective Osteoporosis Management

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Cholecalciferol should be an integral

part of effective osteoporosis

management

We evaluated the effect of supplementation withcholecalciferol (excluding the potential effect of calcium

supplementation) on the risk of fall and fracture, primarily in

postmenopausal women, using a systematic literature review

of MEDL!E, EM"#$E, "%$$ and the &ochrane Data'ase

of $ystematic eviews There is a trend towards a

reduction in the risk of fall among patients treated

with cholecalciferol alone compared with placebo,

suggesting that cholecalciferol should be an integral

part of effective osteoporosis management.

(*rom the Evidence esearch +nit, Macclesfield, +, Merck

- &o nc, Whitehouse $tation, !ew .ersey, +$#, and

!ottingham &ity /ospital, !ottingham, +)

&holecalciferol, or 0itamin D1, is usually derived from

lanolin in sheep2s wool Except for a synthetic 0itamin D1

precursor currently given only to poultry (3), and 0itamin

D1 purportedly produced 'y lichen (1), we have not 'een

aware of an all4plant4'ased 0itamin D1 5he 06 wascurious to learn a'out the cholecalciferol that $ource of Life

said was produced 'y mushrooms

0itamin D deficiency is a common condition that affects a

significant num'er of #ustralians 0itamin D is important in


2/43

the maintenance of 'one health, and deficiency leads to

osteomalacia and contri'utes to fragility fractures

Deficiency has also 'een implicated in a wide variety of

extra4skeletal conditions 0itamin D can 'e easily assessed in

patients 'y measuring serum 374hydroxyvitamin D

eplacement of vitamin D needs to 'e tailored for each

patient and depends on the severity of the deficiency

5oxicity is unlikely with vitamin D when it is administered as

cholecalciferol as it has a wide safety window5he ade8uacy

of replacement should 'e monitored and in cases of

persistently low concentrations, mala'sorptive conditions

(especially coeliac disease) should 'e excluded

Meta'olism and function of vitamin D

5he two main forms are vitamin D1 (cholecalciferol) and

vitamin D3 (ergocalciferol) (see *ig 9) 5hese are

transported to the liver and meta'olised to 374

hydroxyvitamin D1 and 374hydroxyvitamin D3 which are thema:or circulating forms of vitamin D and are measured in

most assays # second hydroxylation takes place in the

kidney to form 9,374dihydroxyvitamin D1, also known as

calcitriol, and 9,374dihydroxyvitamin D3 5hese are the

activated forms of vitamin D and have three main functions;

• enhancing a'sorption of calcium and phosphate from

the small intestine

• inhi'iting parathyroid hormone synthesis and secretion

• mineralising the 'one matrix


3/43

&holecalciferol is produced industrially for use in vitamin

supplements and to fortify foods 'y the ultraviolet

irradiation of araphrasing a more detailed

explanation,?@A cholesterol is extracted from wool grease and

wool wax alcohols o'tained from the cleaning of wool after

shearing 5he cholesterol undergoes a four step process to

make


4/43


5/43

meta'olism to determine causal associations that can 'e

su'se8uently used as endpoints for validation in randomiCed

clinical trials (&5)

t is well esta'lished that insufficient 8uantities of the vitamin contri'ute to osteopenia, osteomalacia, and

osteoporosis /owever, there is so much new interest in

I'onelessI applications of vitamin D that the topic was

featured in the .une, 3BB1 eader=s Digest (9)

0itamin D was first isolated from tuna fish oil in 9G1@, and

synthesiCed in 9G73 t is a prohormone sterol which the

'ody manufactures, given sunlight, from


6/43

evidence that D1 is more efficiently utiliCed in chicks (F) and,

more to the point, in humans I5he assumption that vitamins

D3 and D1 have e8ual nutritional value is pro'a'ly wrong

and should 'e reconsideredI (7)

5here are two commercial sources of natural vitamin D1;

fish liver oil and an oil extracted from wool If a la'el lists

=vitamin D1 (cholecalciferol)= then it is from wool oil 5his is

considered a vegetarian source (the animal is not harmed,

:ust sheared), 'ut not vegan *ish liver oil will 'e in

parentheses if it is the sourceI (@) #nimals can o'tain vitamin D from licking their fur, and in humans, rickets can

'e successfully treated 'y ru''ing cod liver oil into the skin

Dosage

As with all vitamins, there is ongoing and ever-

protracted debate about vitamin D's safety and

effectiveness. In the end, the issue really boils downto dosage. ecause vitamin D can be made in the

body, given sufficient sunlight, it has been

considered more of a hormone than a vitamin. This

terminology is likely to pre!udice any consideration

of megadoses, and that is unfortunate. "overnment-

sponsored #tolerable# or #safe upper limits# $%&

for vitamin D have been established, perhaps based

as much on speculation as on available facts. (or

babies under one year, that #upper limit# is ),*** I%

$+ mcg per day. (or everyone else, including

pregnant and nursing women, it is +,*** I% $*

mcg per day. $ These #safe upper limits# may be


7/43

ecessively conservative. /ieth et al write, #The )**-

microg0d $1,*** I%0day dosage of vitamin D2

effectively increased +$34D to high-normal

concentrations in practically all adults and serum

+$34D remained within the physiologic range5

therefore, we consider )** microg vitamin D20d

$1,*** I%0day to be a safe intake.# $6

/itamin D has sometimes been regarded as the most

potentially dangerous vitamin. In his +**) article

#/itamin Toicity,# 7ark 8osenbloom, 7D, writesthat, for vitamin D, #Acute toic dose is not

established, and chronic toic dose is more than

*,*** I%0day in adults. In children, 1** I%0day is

potentially toic. A wide variance in potential

toicity eists.# There were no fatalities cited. $9

There are numerous symptomatic warnings before

serious toic effects occur. 7erck says, #The firstsymptoms are anoreia, nausea, and vomiting,

followed by polyuria, polydipsia, weakness,

nervousness, and pruritus. $:ventually renal

function is impaired. . . 7etastatic calcifications

may occur, particularly in the kidneys. In "reat

ritain, so-called hypercalcemia in infancy with

failure to thrive has occurred with a daily vitamin Dintake of * to ;g $+*** to 2*** I%.# $)*

Though the details and duration of intake are not

stated, a body-weight comparison suggests that if an

infant weighed )* pounds, that would be the dose


8/43

e


9/43

very strong, yet very different terms that are often

used interchangeably by critics of vitamin

supplementation. 7ost overdoses are not toic, and

most toicities are not fatal.

3ther benefits of vitamin D supplementation are

implicated epidemiologically@ prevention of some

cancers, osteoarthritis progression, multiple

sclerosis, and hypertension. Total-body sun

eposure easily provides the e


10/43

1* #Toic# in this particular instance must mean

#death,# as this figure is presumably based on the

% :nvironmental >rotection Agency's published

oral &D* for female rats of =)9 mg0kg $+*. ** to

=** mcg is the eA's &D * for mallards is greater than

+*** mg0kg, more than three times that for female

rats.

:ven if such figures were not directly applicable to

human beings, vitamin D must remain one of the

most non-toic substances imaginable. It might be

speculated that at least some of the recent increase

of interest in vitamin D analogs is due, in part, topatent- and profit-driven attempts to chemically

sidestep the presumed dangers of high doses of

inepensive, natural vitamin D. If the vitamin is

non-toic, incentive to develop pharmaceutical

analogs largely disappears.

There are, of course, some reasonable cautions withits use. >ersons with hyperparathyroidism,

lymphoma, lupus erythematosus, tuberculosis,

sarcoidosis, kidney disease, or those taking digitalis,

calcium channel-blockers, or thiaEide diuretics,


11/43

should have physician supervision before and while

taking etra vitamin D. 4yperparathyroidism has

been successfully managed with *,*** to +**,***

I% of vitamin D daily $+). Fhen employing large

doses of vitamin D, periodic testing is highly

advisable.

/ITA7IC D@ Deficiency, Diversity and Dosage

by Andrew F. aul

$8eprinted with permission from the ?ournal of3rthomolecular 7edicine, +**25 /ol. )6, Cumbers 2

and 1, p. )91-+*1.

#/itamin D deficiency is a ma!or unrecogniEed

health problem.# $7ichael (. 4olick, 7.D., oston

%niversity 7edical Genter

There have been many papers published on vitamin

D. A 7edline search for #vitamin D# will yield over

2+,*** matches. It is well established that

insufficient


12/43


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wool. #If a label lists 'vitamin D2 $cholecalciferol'

then it is from wool oil. This is considered a

vegetarian source $the animal is not harmed, !ust

sheared, but not vegan. (ish liver oil will be in

parentheses if it is the source.# $= Animals can

obtain vitamin D from licking their fur, and in

humans, rickets can be successfully treated by

rubbing cod liver oil into the skin.

&3C"-T:87 A(:TH

As with all vitamins, there is ongoing and ever-

protracted debate about vitamin D's safety and

effectiveness. In the end, the issue really boils down

to dosage. ecause vitamin D can be made in the

body, given sufficient sunlight, it has been

considered more of a hormone than a vitamin. This

terminology is likely to pre!udice any consideration

of megadoses, and that is unfortunate. "overnment-

sponsored #tolerable# or #safe upper limits# $%&

for vitamin D have been established, perhaps based

as much on speculation as on available facts. (or

babies under one year, that #upper limit# is ),*** I%

$+ mcg per day. (or everyone else, including

pregnant and nursing women, it is +,*** I% $*mcg per day. $ These #safe upper limits# may be

ecessively conservative. /ieth et al write, #The )**-

microg0d $1,*** I%0day dosage of vitamin D2

effectively increased +$34D to high-normal


14/43

concentrations in practically all adults and serum

+$34D remained within the physiologic range5

therefore, we consider )** microg vitamin D20d

$1,*** I%0day to be a safe intake.# $6

/itamin D has sometimes been regarded as the most

potentially dangerous vitamin. In his +**) article

#/itamin Toicity,# 7ark 8osenbloom, 7D, writes

that, for vitamin D, #Acute toic dose is not

established, and chronic toic dose is more than

*,*** I%0day in adults. In children, 1** I%0day ispotentially toic. A wide variance in potential

toicity eists.# There were no fatalities cited. $9

The 7erck 7anual's assessment is somewhat

different@ #/itamin D )*** ;g $1*,*** I%0day

produces toicity within ) to 1 months in infants,

and as little as ;g $2,*** I%0day can produce

toicity over years. Toic effects have occurred in

adults receiving +,** ;g $)**,*** I%0day for

several months.# $)*

The 7erck 7anual's lowest #toicity# figure for

#infants# of 2,*** I% is substantially higher than Dr.8osenbloom's #potentially toic# figure of 1** I%

for presumably older and larger #children.#

#>otentially toic# is very different than #toic.#

7oreover, #toic# is very different than #death.# The


15/43

choice to use the word #toic# may serve to convey a

false impression of immediate and mortal danger.

There are numerous symptomatic warnings before

serious toic effects occur. 7erck says, #The first

symptoms are anoreia, nausea, and vomiting,

followed by polyuria, polydipsia, weakness,

nervousness, and pruritus. $:ventually renal

function is impaired. . . 7etastatic calcifications

may occur, particularly in the kidneys. In "reat

ritain, so-called hypercalcemia in infancy with

failure to thrive has occurred with a daily vitamin D

intake of * to ;g $+*** to 2*** I%.# $)*

Though the details and duration of intake are not

stated, a body-weight comparison suggests that if an

infant weighed )* pounds, that would be the dose

e


16/43

mistake had been corrected.

This is not an isolated instance. As recently as ?uly,

+**2, the website of a ma!or university medical

school $)+ made the same mistake of stating

milligrams $mg instead of micrograms $mcg. This

abbreviation error, amounting to a difference of

three orders of magnitude, was present no fewer

than si times in a single article. 3ne of the medical

school's statements read, #The upper limit of safety

for vitamin D established by the (ood and Cutritionoard of the Institute of 7edicine is + mg $)***

I% daily for infants and * mg $+*** I% for

children and adults.# Actually, + mg would be one

million I%0day, and * mg is two million I%0day.

7ark Twain's advice comes to mind@ #e careful in

reading health books. Hou may die of a misprint.#

>erhaps it is a testament to the safety of vitamin Dthat there has never been a report of any reader

deaths from medical school-induced

hypervitaminosis. Additionally, if nutrition tetbook

and medical school proofreaders can confuse

milligrams with micrograms, then certainly the

public can. This may serve as a practical eample of

the advantage of using International %nits in

discussing and labeling the fat-soluble vitamins.

It is instructive to note that as far back as )929,

some truly enormous doses of vitamin D were in


17/43

fact found to be far less deadly than one might

epect. In several countries, most infants, including

preemies, survived +**,*** to as many as =**,***

units of vitamin D given in a single in!ected or oral

dose. These are incredibly high


18/43

supplementation. 7ost overdoses are not toic, and

most toicities are not fatal.

Gurrent % Daily 8eference Intakes $D8I for

vitamin D are@

Infants *-)+ months, +** I% $ micrograms

7ales and females )-* years, +** I% $ mcg

)-* years, 1** I% $)* mcg

) years and older, =** I% $) mcg

>regnant or nursing women, +** I% $ mcg $

(ormerly, the % 8DA for vitamin D was only mcg

$+** I% for older adults. The present

recommendations are an improvement. 4owever,

there is evidence that even three times the D8I for

an adult is inade


19/43

Gurrent widely-publiciEed government

recommendations are probably inadeh.D., writes,#(or adults, the -microgram $+** I% vitamin D

recommended dietary allowance may prevent

osteomalacia in the absence of sunlight, but more is

needed to help prevent osteoporosis and secondary

hyperparathyroidism. 3ther benefits of vitamin D

supplementation are implicated epidemiologically@

prevention of some cancers, osteoarthritis

progression, multiple sclerosis, and hypertension.

Total-body sun eposure easily provides the

e


20/43

These figures, high though they may seem, may

actually be fairly conservative. The Cutrition Desk

8eference, econd :dition $)9 states that, for

vitamin D, #The threshold for toicity is ** to =**

micrograms per kilogram body weight per day.# $p

1* #Toic# in this particular instance must mean

#death,# as this figure is presumably based on the

% :nvironmental >rotection Agency's published

oral &D* for female rats of =)9 mg0kg $+*. ** to

=** mcg is the eA's &D * for mallards is greater than

+*** mg0kg, more than three times that for female

rats.

:ven if such figures were not directly applicable to

human beings, vitamin D must remain one of the

most non-toic substances imaginable. It might be

speculated that at least some of the recent increase

of interest in vitamin D analogs is due, in part, to

patent- and profit-driven attempts to chemically

sidestep the presumed dangers of high doses of

inepensive, natural vitamin D. If the vitamin is

non-toic, incentive to develop pharmaceutical

analogs largely disappears.


21/43

There are, of course, some reasonable cautions with

its use. >ersons with hyperparathyroidism,

lymphoma, lupus erythematosus, tuberculosis,

sarcoidosis, kidney disease, or those taking digitalis,

calcium channel-blockers, or thiaEide diuretics,

should have physician supervision before and while

taking etra vitamin D. 4yperparathyroidism has

been successfully managed with *,*** to +**,***

I% of vitamin D daily $+). Fhen employing large

doses of vitamin D, periodic testing is highly

advisable.

D:(IGI:CGH

/itamin D deficiency is, of course, to found in

people who do not take supplements, who receive

little sun eposure, and who do not drink vitamin D

fortified milk. A recent study $++ indicates that

about a


22/43


23/43


24/43

studies have found that when older individuals take

vitamin D supplements, they have less of a tendency

to sway while standing or walking, and may

therefore be less likely to fall.# $+2

M+L5>LE $&LE%$$

>ersons with multiple sclerosis typically are vitamin D

deficient and demonstrate dramatically reduced 'one mass

+nsurprisingly, such 'one loss appears to 'e directly caused 'y insufficient vitamin D (F@) and can I'e safely and

inexpensively corrected 'y the routine use of vitamin D

supplementsI (F


25/43

suscepti'le individuals with early intervention strategies that

provide ade8uate levels of hormonally active 9,374

dihydroxyvitamin D1 or its analogsI (FJ) Dr /ayes adds

that Inheriting genetic risk factors for multiple sclerosis

(M$) is not sufficient to cause this demyelinating disease of

the central nervous systemH exposure to environmental risk

factors is also re8uiredI (FG)

n a review article, I0itamin D $upplementation in the *ight

#gainst Multiple $clerosis (7B), #shton * Em'ry credits >

6old'erg (79, 73) with 'eing the first to propose that vitaminD is an important factor in the development of M$ 6old'erg

Ipostulated that such a close correspondence 'etween low

sunlight and M$ was due to low vitamin D production in the

population 6old'erg also showed that within areas of low

sunlight (eg !orway) differences in M$ prevalence could 'e

explained 'y dietary factors which affect vitamin D

production $uch factors include the amount of fish eaten(increases vitamin D) and the amount of grains consumed

(reduces vitamin D levels due to the action of phytates) 5o

explain how vitamin D levels were related to M$, 6old'erg

proposed that genetically suscepti'le individuals may need

larger than normal amounts of vitamin D during myelin

formation and that insufficient vitamin D during childhood

might result in defective myelin which would 'e suscepti'le

to 'reakdown in later life 6old'erg=s ideas were completely

ignored 'y medical researchersI

#t least at the time they were Eventually it was


26/43

demonstrated that vitamin D hormone could prevent or halt

not only an animal form of M$ (71, 7F) 'ut there had 'een a

clinical study (77) showing that vitamin D, along with

calcium and magnesium, reduced the relapse rate in humans

with multiple sclerosis *rederick lenner, MD, reported

success using vitamin and mineral therapy for multiple

sclerosis over thirty years ago (7@, 7


27/43

psoriasis has 'een successfully treated, not only with vitamin

D analogues, 'ut with topical vitamin D1 (@J) 0itamin D

deficiency may 'e a contri'uting cause of inflammatory

'owel disease, and might 'e an effective treatment (@G)

%ver 7B years ago, lupus vulgaris (tu'erculosis of the skin)

was reported successfully treated with 97B,BBB + of vitamin

D daily for six to eight months (


28/43

supplementation is mandatory

6overnment recommended dietary intakes of 3BB to @BB

+day are too low, according to the weight of clinical

evidence 6overnment Itolera'leI or Isafe upper intake

levelsI (+L) of 9,BBB to 3,BBB +day are likewise too low,

and largely unsupported 'y toxicological evidence #n

optimum health recommendation of 9,BBB to F,BBB +day,

in total from all sources, is not unreasona'le for the vast

ma:ority of healthy adults Effective therapeutic levels for

illness may 'e far higher When high doses are used,appropriate testing and monitoring is recommended t

would 'e unreasona'le to deny a therapeutic trial of vitamin

D in cases of multiple sclerosis, scleroderma, psoriasis,

congestive heart failure, hypertension, and various forms of

cancer

Excessive avoidance of sunlight, and sensational 'ut

unscientific dread of relatively high4dose vitamin D side

effects does more than merely set the stage for a population

of rickety children and fracture4ridden elderly

%verestimates and outright misstatements of vitamin D=s

Ipotential toxicityI open new marketing avenues for the

development of vitamin D4like drugs, a commercial

opportunity that the pharmaceutical industry has notoverlooked

%! D#!6E$ #!D D%$#6E; # &%!&L+D!6


29/43

&%MME!5

/ypervitaminosis articles are popular with the media,

sometimes even making it into the pages of the Wall $treet

.ournal %n #pril 1B, 9GG3, David $tipp reported that

'etween 9GGB and 9GG3, Ia series of patients with vitamin D

overdoses 'egan turning up at "oston hospitalsI %ne of

these patients su'se8uently died from drug complications,

and the case went to court (J3) IEssentially, this was a

product lia'ility action against the producer of dairy

products, specifically milk which contained excessiveamounts of 0itamin D 5he plaintiff=s decedent purportedly

suffered from elevated levels of 0itamin D in her

'loodstream which re8uired medication which in turn

allegedly compromised her immune system, leading to her

deathI (J1) 5his is the one and only vitamin D4related death

could find confirmation of anywhere, and even this one was

not directly due to the vitamin, 'ut rather to side effects ofmedication

# physiology text'ook later stated that I#t least 9G cases of

vitamin D toxicity were reported in the "oston area during

9GG3 $ymptoms included fatigue, weight loss, and

potentially severe damage to the kidneys and cardiovascular

system 5he pro'lems resulted from drinking milk fortified with vitamin D Due to pro'lems at one dairy, some of the

milk sold had over 31B,BBB units of vitamin D per 8uart

instead of the usual FBB units per 8uart 5he incident

highlighted the need for 8uality control in the production,


30/43

and care in the consumption, of vitamin supplementsI (JF)

$uch a conclusion is inaccurate 5he incident might :ust as

well 'e taken to 'e an unintentional proof of vitamin safety,

even in ridiculously high overdosage situations t is certainly

noteworthy that 7JB times the normal amount of vitamin D

produced, at most, one alleged fatality over a two4year

period *urthermore, there was a total of fewer than two

doCen toxicity reports, for the entire "oston metropolitan

area, after large num'ers of people had 'een ingesting close

to a 8uarter of a million units of vitamin D per liter of milkday after day, month after month, for up to two years 5his

'orders on the extraordinary Events such as this

demonstrate that the margin for error with vitamin D is very

large indeed 5hough the news reported a'out the vitamin=s

toxicity, the real story was the vitamin=s safety 5he scientific

literature confirms the vitamin=s value

eferences cited;

9 *reinkel $ 5he healing vitamin eader=s Digest .une,

3BB1

3 http;wwwi'l4ham'urgcomprodmg99B39mhtm

1 nt . &ircumpolar /ealth 7G; 3@413 3BBB

http://www.ibl-hamburg.com/prod/mg_11021_m.htmhttp://www.ibl-hamburg.com/prod/mg_11021_m.htmhttp://www.ibl-hamburg.com/prod/mg_11021_m.htm


31/43

F http;wwwcy'erlipidorgvitdvitdBBB9htm

7 /M 5rang, DE &ole, L# u'in, # >ierratos, $ $iu and

0ieth Evidence that vitamin D1 increases serum 374

hydroxyvitamin D more efficiently than does vitamin D3

#merican .ournal of &linical !utrition, 0ol @J, J7F4J7J,

9GGJ

@ http;wwwvitamercomfa8tspygeumhtml

hosphorus,

Magnesium, 0itamin D, and *luoride $tanding &ommittee

on the $cientific Evaluation of Dietary eference ntakes,

*ood and !utrition "oard, nstitute of Medicine, &hapter ress, Washington, D& 9GGG

J 0ieth , &han >&, Mac*arlane 6D Efficacy and safety of

vitamin D1 intake exceeding the lowest o'served adverse

effect level #m . &lin !utr *e'H


32/43


33/43


34/43


35/43

doses of vitamin D3 in the treatment of anticonvulsant

osteomalacia #cta !eurol $cand 7B;@194@F9 9G


36/43

1@ reiter $, $chwartC >, irkman /! .r, &harlton >#,

&alikoglu #$, Davenport ML !utritional rickets in #frican

#merican 'reast4fed infants . >ediatr #ugH91u'lic /ealth

$ervice, *e'ruary, 9GG9

FB *luoridation of Water &hemical and Engineering !ews,

0ol @@, #ugust 9, 9GJJ, p 3@4F3

F9 Wortsman . et al Decreased 'ioavaila'ility of vitamin D

in o'esity #m . &lin !ut


37/43

F1 ey $W, Mar'le M $tudies link sun exposure to

protection against cancer &ancer Weekly >lus !ovem'er 9u'lications npress http;wwwsunlightdorg

F@ &osman *, !ieves ., omar L, *errer 6, /er'ert .,

*ormica &, $hen 0, Lindsay *racture history and 'one

loss in patients with M$ !eurology %ctH 79(F);99@947 9GGJ

F


38/43

7B Em'ry #* 0itamin D supplementation in the fight

against multiple sclerosis http;wwwdirect4

msorgvitamindhtml #ccessed .uly, 3BB1

79 6old'erg > Multiple $clerosis; vitamin D and calcium as

environmental determinants of prevalence >art 9; $unlight,

dietary factors and epidemiology ntern . Environmental

$tudies, v @, p 9G43, *leming M and >icard E Multiple $clerosis;

Decreased relapse rate through dietary supplementation

http://www.direct-ms.org/vitamind.htmlhttp://www.direct-ms.org/vitamind.htmlhttp://www.direct-ms.org/vitamind.htmlhttp://www.direct-ms.org/vitamind.htmlhttp://www.direct-ms.org/vitamind.html


39/43

with calcium, magnesium and vitamin D Medical

/ypotheses, v 39, p 9G143BB 9GJ@

7@ $mith L/ &linical 6uide to the +se of 0itamin &

>ortland, %; Life $ciences >ress, 9GJJ, p F34O71

7ressH 391431


40/43

autoimmune diseasesA Dtsch Med Wochenschr *e'

3JH93J(G);FFB4@ ?#rticle in 6ermanA 3BB1

@3 ostand $6 +ltraviolet light may contri'ute to

geographic and racial 'lood pressure differences

/ypertension 1B(3 pt 9);97B497@ 9GGressH 9GGG p F31

@F Pittermann #, $chleithoff $$, 5enderich 6, "erthold /,

orfer , $tehle > Low vitamin D status; a contri'uting

factor in the pathogenesis of congestive heart failureN . #m

&oll &ardiol .an 9HF9(9);9B7493 3BB1

@7 !ishio , Mukae $, #oki $, toh $, onno !, %Cawa ,$atoh , atagiri 5 &ongestive heart failure is associated

with the rate of 'one loss . ntern Med #prH371(F);F1G4F@

3BB1

@@ >rice D, $tanford L&, "raden D$, E'eid M, $mith .&

/ypocalcemic ickets; #n +nusual &ause of Dilated

&ardiomyopathy >ediatr &ardiol .un @, 3BB1

@


41/43

of skin involvement using non4invasive techni8ues esults

of an open prospective trial #cta Derm 0enereolH rescott * 5he 0itamins in Medicine,

third edition Milwaukee, W; Lee *oundation p 7


42/43

9,374dihydroxyvitamin D1 is mediated 'y mutual modulation

of receptor expression Eur . &ancer 1F;399G43937 9GGJ

once E&, 6onCaleC Lira4

Lira 6, Escudero4De los ios > !utritional determinants of

epithelial ovarian cancer risk; a case4control study in Mexico

%ncology @1(3);9794


43/43

, et al +se of cod liver oil

during pregnancy associated with lower risk of 5ype

dia'etes in the offspring Dia'etologia F1;9BG149BGJ 3BBB

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cholecalciferol should be an integral part of effective osteoporosis management

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