2009-03 vitamin d deficiency - bioscientia.de · 3 cancer (breast, colon, prostate) vitamin d...
TRANSCRIPT
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No. 2/2010
October 2010
Vitamin D deficiency
An important marker
in preventive diagnostics
Peter J. Kuhl and Hans-Georg Lambrecht
Vitamin D promotes absorption of calcium from
the intestine and inhibits excretion via the
kidneys. It also promotes bone mineralization
and is thus necessary for healthy bones. In
addition to this, vitamin D is important for cell
differentiation and proliferation, for modulation
of the immune system, and for other metabolic
processes.
Vitamin D is not a vitamin in the true sense,
but a hormone.
Unlike vitamins, which are only obtained from
food, the biologically active hormone 1,25-
dihydroxyvitamin D3 is synthesized from
precursors by the body itself as a result of
exposure to the UV-B fractions of sunlight.
Since the intermediate, 25-hydroxyvitamin D3
(vitamin D3 (25-OH)), is the main storage form
in the human body, it is this metabolite that
should be used for determining total vitamin D
status [1, 2].
In the period from February to April, roughly
60% of the German population has vitamin D
deficiency, and even in summer the figure is
about 40% (Fig. 1).
nnnnnnnn Causes and classification of
vitamin D deficiency
Insufficient synthesis of vitamin in the winter
months is due to the low angle of the sun’s
rays and to the fact that many people spend
less time in the sun.
For people who go outside for about 30
minutes between 8:00 and 18:00 each day and
keep their hands and face uncovered while
they are out, the daily requirement of vitamin D
2
is 200 IU (5 µg). People who do not go outside
for as long or who do not go out at all have a
daily requirement of about 1000 IU vitamin D.
Severe vitamin D deficiency exists when
values are < 10 ng/ml and moderate to mild
deficiency is present when values are
10-20 ng/ml. Vitamin D levels are sufficient
when values are above 20-30 ng/ml [1].
Fig. 1: Seasonal pattern of 25-OH vitamin D3 levels.
Results of the Bochum postmenopausal study on the seasonal course of 25-hydroxyvitamin D3.
Investigation of a random sample of 1055 early-postmenopausal women between 45-65 years of age.
Pfeilschifter J: 2008 Osteology Conference, Hanover
nnnnnnnn Possible connection between
vitamin D deficiency and various
clinical pictures
“Recent studies show the importance of
vitamin D in the prevention of diseases. The
basis of this is the finding that vitamin D
receptors exist in nearly every cell. They are
able to convert the inactive 25-hydroxyvitamin
D circulating in the blood into the active 1,25-
hydroxyvitamin D. It thus appears that, in
addition to its classical role in bone
metabolism, vitamin D performs a further
function in numerous different diseases. Low
concentrations of vitamin D may be
associated with an increasing risk of chronic
diseases, cancer, and autoimmune diseases
and even cardiovascular disorders” (Fig. 3).
Osteoporosis, muscle weakness or muscle pain, and fibromyalgia
Low blood concentrations of vitamin D may
encourage the development of osteoporosis
through the metabolic effect on calcium
metabolism in postmenopausal women
especially [1, 3].
Diabetes
A predisposition to type 1 and type 2 diabetes
appears to be promoted by vitamin D
deficiency [3, 11]. Vitamin D receptors have
been detected both on beta cells of the
pancreas and on immune cells.
Epidemiological studies have shown an
association between vitamin D deficiency at a
young age and the subsequent development
of type 1 diabetes [11].
Proportion of population (in %) with concentration < 20 ng/ml
Month of the year
3
Cancer (breast, colon, prostate)
Vitamin D receptors are found in various
tissues, such as the prostate, the mammary
gland, and the colon. Vitamin D inhibits cell
proliferation and induces cell differentiation. A
connection between the relative risk of
colorectal cancer and vitamin D levels has
been demonstrated. Study results indicate
that higher vitamin D concentrations have a
positive effect in prostate and breast cancer
[1, 3, 8].
A good supply of vitamin D is important in the
prevention of bowel cancer. At a serum
concentration of 37 ng/ml the incidence of
cancer of the colon was half that observed at
less than 6 ng/ml [14].
Autoimmune diseases (e.g. multiple
sclerosis)
Vitamin D is an immunomodulator [1, 7, 8].
Data from a study from 2004 support the
hypothesis that vitamin D can reduce the risk
of multiple sclerosis [1, 9, 10].
Cardiovascular diseases
Vitamin D receptors are found on smooth-
muscle cells and the endothelium of the blood
vessels, among other places. This suggests
that vitamin D deficiency has a role in the
pathogenesis of vascular diseases [1, 3, 12].
Vitamin D probably has an effect on the renin-
angiotensin system and thus, indirectly, on
blood pressure [13].
For example, in the Health Professionals
Follow-Up Study, the risk of a myocardial
infarction was 2.4 times higher in men with
vitamin D deficiency (25-OH-vitamin D
< 15 ng/ml) than in men of the same age with
adequate levels of the vitamin (levels over
30 ng/ml) [15].
nnnnnnnn Optimal blood levels of
vitamin D3 (25-OH)
Scientists recommend a blood vitamin D3 (25-
OH) level of > 75 nmol/l (> 30 ng/ml) (Fig. 2)
[3, 4, 5].
The optimal ranges are:
Up to 50 years of
age
between 20 and 70
ng/ml
From approx. 50
years of age
between 25 and 70
ng/ml
From approx. 70
years of age
between 30 and 70
ng/ml
In many people, supplementing the diet with
400 IU (international units, 40 IU corresponds
to 1 µg) as recommended by the Deutsche
Gesellschaft für Ernährung [German
Nutritional Society] is not enough to achieve
the minimum blood concentration [6, 7] and
thereby ensure a preventive effect.
Experts therefore recommend that the vitamin D supply be checked by measuring
the vitamin D3 (25-OH) level. Such a
procedure is also recommended by
Cannell and Hollis [4]. Sample require-ment: 1 ml Serum.
It is often assumed that patients who
regularly take vitamin D products will have
adequate levels of vitamin D, but in many
instances this is not actually the case! [1]
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Fig. 2: The optimal serum level of vitamin D3 (25-OH) starts at 75 nmol/l.
Relative risk (RR) of fractures and colon cancer as a function of the vitamin D3 25-OH concentration. Broken lines represent the
connection between vitamin D3 25-OH concentration and bone density, and function of the lower extremities (measured using
the so-called 8-foot (2.4 m) walk test). Continuous lines relate to the left axis, broken lines to the right axis. Fig. modified
according to Bischoff-Ferrari et al. 2006 [3]. Factor for converting conventional unit of vitamin D3 (25-OH) concentration [ng/ml]
into SI unit [nmol/l]: 2.496 [5].
nnnnnnnn Prevention by regular measurement
of vitamin D levels
Vitamin D3 (25-OH) should be measured before
and after treatment is started, particularly in
patients who are in an at-risk group.
It is necessary to make sure that:
���� the vitamin D level from normal sources
is adequate
or
���� oral intake of vitamin D compensates an
existing deficiency
The following patients are particularly at risk:
���� The elderly
���� Postmenopausal women
���� Pregnant women
���� People with a dark complexion
���� Anyone who spends too little time
outdoors or covers up too much
���� Patients with chronic kidney disease
���� Patients with malabsorption syndrome
Vitamin D levels can be measured all year
round.
If the vitamin D level is at the lower limit
(below 30 ng/ml) at the first measurement,
measurement should be repeated between
January and April, as serum vitamin D3 (25-
OH) levels are at their lowest and parathyroid
hormone levels are at their highest after the
winter months. If a deficiency is detected and
a vitamin D supplement given (see, in this
regard, the recommendations of the
Deutsche Gesellschaft für Ernährung (DGE)
[German Nutritional Society] for example), a
check should be carried out after 4 months at
the earliest.
Bone density (g/cm2)
Fracture (RR)
Colon cancer (RR)
Rela
tive r
isk
5
Fig. 3: General significance of vitamin D3 for the various organ systems [16].
Contact: www.bioscientia.com
nnnnnnnn References:
1) Holick MF. Vitamin D Deficiency N Engl J Med.
2007;357:266-81. Review
2) Packungsbeilage Vitamin D3 (25-OH). Roche
Diagnostics.
3) Bischoff-Ferrari HA. Estimation of optimal serum
concentrations of 25-hydroxyvitamin D for multiple
health outcomes. Am J Clin Nutr. 2006;84:18-28.
4) Cannell JJ and Hollis BW. Use of Vitamin D in clinical
practice. Alt Med Rev. 2008;13:6-20.
5) SI Units for Clinical Data, Umrechnungsfaktoren:
http: / /www.unc.edu /~rowlett /units /scales
/clinical_data.html
6) Holick MF et al. Vitamin D2 Is as Effective as Vitamin
D3 in Maintaining Circulating Concentrations of 25-
Hydroxy-vitamin D. J Clin Endocrinol Metab.
2008;93:677–681
7) DeLappe E et al. Vitamin D insufficiency in older
female community-dwelling acute hospital
admissions and the response to supplementation.
Eur J Clin Nutr. 2006;60(8):1009-1015
8) Lappe JM., et al. Vitamin D and calcium
supplementation reduces cancer risk: results of a
randomized trial. Am J Clin Nutr. 2007;85:1586-91.
9) Munger KL, Lynn IL, Hollis BW, et al. Serum 25-
Hydroxyvitamin D Levels and Risk of Multiple
Sclerosis. JAMA. 2006;296:2832-7.
10) Deutsche Multiple Sklerose Gesellschaft
Bundesverband e.V. http://www.dmsg.de
/multiplesklerose-
news/inde.php?kategorie=forschung&cnr=31&anr=7
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11) Mathieu C., et al. Vitamin D and diabetes.
Diabetologia. 2005;48:1247-57.
12) Wang TJ., et al. Vitamin D deficiency and risk of
cardiovascular disease. Circulation. 2008;117:503-11.
13) Martini LA., et al. Vitamin D and blood pressure
connection: update on epidemiologic, clinical and
mechanistic evidence. Nutrition Reviews
2008;66:291-297
14) Am J Prev Med 32, 2007, 21
15) Arch Intern Med 168, 2008, 1174
16) M. F. Holick, M.Jenkins. Schützendes Sonnenlicht.
Haug-Verlag, MVS Medizinverlage Stuttgart, 2005
Sun
Skin Liver
Kidneys
Health of cells andHealth of cells andHealth of cells andHealth of cells and immune simmune simmune simmune systemystemystemystem
Prostate cells Breast cells
1,25 vitamin D
(active vitamin D)
Intestinal cells Immune
cells
Cardiovascular healthCardiovascular healthCardiovascular healthCardiovascular health
Regulates blood pressure
and can lower the risk of
hyper-tension, stroke, heart
attack and heart failure
Pancreatic healthPancreatic healthPancreatic healthPancreatic health
Improves insulin production
and can prevent diabetes
Bone healthBone healthBone healthBone health
Health of calcium
metabolism
Muscle metabolism
Salmon
Diet
Vitamin D-enriched milk/
orange juice
1,25 Vitamin D (active vitamin D)
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