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Medical Forum / General / Nutrition / March 2007

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Vitamin D status predicts physical performance and its decline in older persons

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Matti Narkia - 12 Mar 2007 18:07 GMT
The Dutch study

Wicherts IS, van Schoor NM, Boeke AJ, Visser M, Deeg DJ, Smit J, Knol
DL, Lips P.
Vitamin D status predicts physical performance and its decline in
older persons.
J Clin Endocrinol Metab. 2007 Mar 6; [Epub ahead of print]
PMID: 17341569 [PubMed - as supplied by publisher]
<http://jcem.endojournals.org/cgi/content/abstract/jc.2006-1525v1>
<http://jcem.endojournals.org/cgi/rapidpdf/jc.2006-1525v1> (koko
teksti PDF-tiedostona),

just published online, found that low vitamin D status is common in
older persons and associated with poorer physical performance and a
greater decline in physical performance. Below the abstract of this
study:

   "Context: Vitamin D deficiency is common among older people,
   and can cause mineralization defects, bone loss, and muscle
   weakness. Objective: To investigate the association of serum
   25-hydroxyvitamin D (25-OHD) concentration with current
   physical performance and its decline over 3 years among
   elderly. Design: Cross-sectional and longitudinal design (3
   years follow-up) within the Longitudinal Aging Study
   Amsterdam. Setting: An age- and sex-stratified random sample
   of the Dutch older population. Other participants: Subjects
   included 1234 men and women (aged 65yr and older) for cross-
   sectional analysis, and 979 (79%) persons for longitudinal
   analysis. Main Outcome Measure(s): physical performance (sum
   score of the walking test, chair stands, and tandem stand)
   and decline in physical performance. Results: serum 25-OHD
   was associated with physical performance after adjustment for
   age, gender, chronic diseases, degree of urbanization, BMI,
   and alcohol consumption. Compared with individuals with serum
   25-OHD levels above 30ng/ml, physical performance was poorer
   in participants with serum 25-OHD<10ng/ml (B= -1.69; 95%
   confidence interval[CI]= -2.28; -1.10), and with serum 25-OHD
   10-20ng/ml (B= -0.46; 95%CI=-0.90;-0.03). After adjustment
   for confounding variables, participants with 25-OHD<10ng/ml
   and 25-OHD 10-20ng/ml had significantly higher odds ratios
   (OR) for 3-year decline in physical performance ([OR=2.21;
   95%CI=1.00- 4.87] and [OR=2.01; 95%CI=1.06-3.81]), compared
   with participants with 25-OHD>/=30ng/ml. The results were
   consistent for each individual performance test. Conclusions:
   Serum 25-OHD concentrations <20ng/ml are associated with
   poorer physical performance and a greater decline in physical
   performance in older men and women. Because almost 50% of the
   population had serum 25-OHD<20ng/ml, public health strategies
   should be aimed at this group."

Signature

Matti Narkia

CliffMacgillivray - 12 Mar 2007 20:42 GMT
> just published online, found that low vitamin D status is common in
> older persons and associated with poorer physical performance and a
> greater decline in physical performance. Below the abstract of this
> study:

*gasp* So old people that are too frail to go outside into the sunlight
have low vitamin D levels!?!? I think that being too frail to go outside
leads to the vitamin D deficiency and not the other way around.
Jim Chinnis - 12 Mar 2007 20:58 GMT
CliffMacgillivray <nospam@fake-email.net> wrote in part:

>> just published online, found that low vitamin D status is common in
>> older persons and associated with poorer physical performance and a
[quoted text clipped - 4 lines]
>have low vitamin D levels!?!? I think that being too frail to go outside
>leads to the vitamin D deficiency and not the other way around.

Right. I also think the "discovery" of lower vit D in those with diabetes
type 2 is similar: they got diabetes (many of them) because they didn't go
out and bike/walk/run/swim enough and they got low vit D because they didn't
go out and bike/walk/run/swim enough.
--
Jim Chinnis  Warrenton, Virginia, USA  jchinnis@alum.mit.edu
Susan - 12 Mar 2007 21:18 GMT
> Right. I also think the "discovery" of lower vit D in those with diabetes
> type 2 is similar: they got diabetes (many of them) because they didn't go
> out and bike/walk/run/swim enough and they got low vit D because they didn't
> go out and bike/walk/run/swim enough.

Or they got it because they live in a climate where part of the year
it's difficult and/or dangerous to be out, and little sun is out, too.
Or they did all those things with their skin covered by clothing and
SPF, and with sunglasses on.

Susan
Jim Chinnis - 12 Mar 2007 21:31 GMT
Susan <nevermind@nomail.com> wrote in part:

>x-no-archive: yes
>
[quoted text clipped - 9 lines]
>
>Susan

Why would that make diabetics lower in vitamin d than non-diabetics?
--
Jim Chinnis  Warrenton, Virginia, USA  jchinnis@alum.mit.edu
Susan - 12 Mar 2007 21:56 GMT
> Why would that make diabetics lower in vitamin d than non-diabetics?
> --

For one thing, vitamin D is miscategorized as a vitamin; it's a steroid,
a secosteroid to be exact.

Higher insulin levels inhibit steroidogenesis, which is what your body
does to synthesize steroids.  Type 2 starts out with hypersecretion of
insulin, and later treatments either sensitize to insulin (more is
bioavailable) or cause DMs to excrete more so they can eat all the
starch and sugar the ADA advice tells them to.

Just one other possibility in what I think is a more complex equation.

Susan
Jim Chinnis - 12 Mar 2007 22:39 GMT
Susan <nevermind@nomail.com> wrote in part:

>x-no-archive: yes
>
[quoted text clipped - 13 lines]
>
>Susan

Thank you! Good insights, I'd say.
--
Jim Chinnis  Warrenton, Virginia, USA  jchinnis@alum.mit.edu
Susan - 12 Mar 2007 22:44 GMT
> Thank you! Good insights, I'd say.
> --

You know me; full of insights.

Often wrong, never in doubt.  ;-)

Susan
Juhana Harju - 12 Mar 2007 23:09 GMT
: x-no-archive: yes
:
:: Why would that make diabetics lower in vitamin d than non-diabetics?
:
: For one thing, vitamin D is miscategorized as a vitamin; it's a
: steroid, a secosteroid to be exact.

I suggest that you read this article by Reinhold Vieth.

http://www.direct-ms.org/pdf/VitDVieth/Vit%20D%20not%20a%20Hormone%20Vieth.pdf

Signature

Juhana

Matti Narkia - 12 Mar 2007 23:42 GMT
>CliffMacgillivray <nospam@fake-email.net> wrote in part:
>
[quoted text clipped - 11 lines]
>out and bike/walk/run/swim enough and they got low vit D because they didn't
>go out and bike/walk/run/swim enough.

That's logical, but I don't think that the observation of relatively
high prevalence of low vitamin D status among type 2 diabetes patients
was a main point of this study. IMHO it was the association of low
vitamin D status within this population with increased
atherosclerosis. An excerpt from the abstract:

   "In multivariate regression analysis, low 25(OH)D
   concentrations independently predicted carotid IMT (P <
   0.001) in people with type 2 diabetes after adjustment for
   classical risk factors, diabetes duration, HbA1c, calcium,
   renal function tests, inflammatory markers, use of
   medications, and presence of the metabolic syndrome"

As for the relation between low vitamin D status and type 2 diabetes,
I take a couple of IMHO interesting quotes from

Zittermann A.
Vitamin D in preventive medicine: are we ignoring the evidence?
Br J Nutr. 2003 May;89(5):552-72. Review.
PMID: 12720576 [PubMed - indexed for MEDLINE]
<http://www.ingentaconnect.com/content/cabi/bjn/2003/00000089/00000005/art00002?t
oken=00531a0783f6da2dd5264f65263a3d4f58762f467c405847447b23442f7b317b763b6b674c7
a2d1245d
>
(full text available from that page)

   "Experimental studies have demonstrated that a reduction in
   vitamin D activity can result in both increased insulin
   resistance and reduced insulin secretion (Boucher, 1998).
   Epidemiological data have shown a four- to five-fold higher
   prevalence of non-insulin-dependent diabetes in dark-skinned
   Asian immigrants in comparison with British Caucasians
   indicating that low vitamin D status may contribute to the
   pathogenesis of diabetes (McKeigue et al. 1992). Moreover, in
   elderly subjects the subgroup with the lowest tertile of
   25(OH)D levels had a significantly higher blood glucose
   increase and higher blood insulin increase after an oral
   glucose-tolerance test in comparison with the subgroup with
   the highest tertile of 25(OH)D levels (Baynes et al. 1997).
   Data indicate that vitamin D insufficiency may result in
   insulin resistance. Results are in line with the suggestion
   that enhanced levels of TNF-alpha, a cytokine with is
   inversely related to 25(OH)D and calcitriol (see p. 560),
   promote insulin resistance (Hotamisligil & Spiegelman, 1994).

   [...]

   It should be mentioned that hypertension, cardiovascular
   diseases, and diabetes mellitus are often associated with
   obesity. Obese subjects have an increased risk for low
   circulating 25(OH)D levels (Bell et al. 1985; Wortsman et al.
   2000) due to the storage of vitamin D and 25(OH)D in adipose
   tissue (Wortsman et al. 2000). The alterations in vitamin D
   metabolism of obese subjects in comparison with lean subjects
   are also associated with functional alterations such as
   elevated PTH levels (Bell et al. 1985; Wortsman et al. 2000).
   Obesity might thus contribute to insufficient circulating
   25(OH)D levels."

Signature

Matti Narkia

Matti Narkia - 13 Mar 2007 00:50 GMT
>>CliffMacgillivray <nospam@fake-email.net> wrote in part:
>>
[quoted text clipped - 67 lines]
>    Obesity might thus contribute to insufficient circulating
>    25(OH)D levels."

Here a few more references about the relation between low vitamin D
status and insulin resistance or type 2 diabetes

Pittas AG, Harris SS, Stark PC, Dawson-Hughes B.
The Effects of Calcium and Vitamin D Supplementation on Blood Glucose
and Markers of Inflammation in Non-diabetic Adults.
Diabetes Care. 2007 Feb 2; [Epub ahead of print]
PMID: 17277040 [PubMed - as supplied by publisher]
<http://care.diabetesjournals.org/cgi/content/abstract/dc06-1994v1>

   "Conclusions. In healthy older adults with impaired fasting
   glucose, supplementation with calcium and vitamin D may
   attenuate increases in glycemia and insulin resistance that
   occur over time. However, our findings should be considered
   hypothesis generating and need to be confirmed in randomized
   trials specifically designed for the outcomes of interest."

Mathieu C, Gysemans C, Giulietti A, Bouillon R.
Vitamin D and diabetes.
Diabetologia. 2005 Jul;48(7):1247-57. Epub 2005 Jun 22. Review.
PMID: 15971062 [PubMed - indexed for MEDLINE]
DOI: 10.1007/s00125-005-1802-7
<http://www.springerlink.com/content/q21433360tv03407/>

   "Vitamin D deficiency predisposes individuals to type 1 and
   type 2 diabetes, and receptors for its activated
   form - 1alpha,25-dihydroxyvitamin D3 - have been identified in
   both beta cells and immune cells. Vitamin D deficiency has
   been shown to impair insulin synthesis and secretion in
   humans and in animal models of diabetes, suggesting a role in
   the development of type 2 diabetes. Furthermore,
   epidemiological studies suggest a link between vitamin D
   deficiency in early life and the later onset of type 1
   diabetes. In some populations, type 1 diabetes is associated
   with certain polymorphisms within the vitamin D receptor
   gene. In studies in nonobese diabetic mice, pharmacological
   doses of 1alpha,25-dihydroxyvitamin D3, or its structural
   analogues, have been shown to delay the onset of diabetes,
   mainly through immune modulation. Vitamin D deficiency may,
   therefore, be involved in the pathogenesis of both forms of
   diabetes, and a better understanding of the mechanisms
   involved could lead to the development of preventive
   strategies."

Chiu KC, Chu A, Go VL, Saad MF (2004)
Hypovitaminosis D is associated with insulin resistance and beta cell
dysfunction.
Am J Clin Nutr 79:820-825
<http://www.ajcn.org/cgi/content/full/79/5/820>

   "CONCLUSIONS: The data show a positive correlation of 25(OH)D
   concentration with insulin sensitivity and a negative effect
   of hypovitaminosis D on beta cell function. Subjects with
   hypovitaminosis D are at higher risk of insulin resistance
   and the metabolic syndrome. Further studies are required to
   explore the underlying mechanisms.

   [...]

   Our data show that, in glucose-tolerant subjects, 25(OH)D
   concentration has a positive relation to insulin sensitivity
   and a negative effect on beta cell function. These relations are
   independent of confounding factors. Therefore,
   hypovitaminosis D is a risk factor for type 2 diabetes and
   the metabolic syndrome. Although there is to date no report
   on both of these associations in a single study such as the
   current study, separate reports have shown the association of
   hypovitaminosis D with insulin resistance (16) and beta cell
   dysfunction (8).

   [...]

   To our knowledge, the current study is the first to show the
   relation of 25(OH)D concentration to insulin sensitivity and
   secretion by using a hyperglycemic clamp technique in a group
   of healthy, glucose-tolerant subjects. We also observed that
   hypovitaminosis D is a risk factor for the metabolic
   syndrome. Extrapolation from the observations in the current
   study suggests that increasing 25(OH)D from 10 to 30 ng/mL
   can improve insulin sensitivity by 60%, from 3.8128 to 6.1176
   (micromol/L) * m^(-2) * min^(-1) * (pmol/L)^(-1). This improvement
   in insulin resistance could potentially eliminate the burden on
   beta cells and reverse abnormal glucose tolerance. Furthermore,
   the 60% improvement in insulin sensitivity that results from
   vitamin D treatment indicates that that treatment is more
   potent than either troglitazone or metformin treatment (54%
   and 13% improvement in insulin sensitivity, respectively;
   36). The modest effect of vitamin D on insulin sensitivity in
   individual persons may translate into a dramatic effect in
   the population as a whole because of the high prevalence of
   hypovitaminosis D, which, in a large population, carries an
   attributable risk for type 2 diabetes and the metabolic
   syndrome. Although a review of the literature suggests non-
   calcium-mediated effects, the underlying molecular mechanism
   remains to be elucidated."

Signature

Matti Narkia

Matti Narkia - 12 Mar 2007 23:18 GMT
>> just published online, found that low vitamin D status is common in
>> older persons and associated with poorer physical performance and a
[quoted text clipped - 4 lines]
>have low vitamin D levels!?!? I think that being too frail to go outside
>leads to the vitamin D deficiency and not the other way around.

A good point, and because this was an epidemiological study, no causal
conclusions can be drawn. Certainly not going out will lead to a low
vitamin D status, if supplements are not used. Still, the study claims
that the association of low vitamin D status with poorer physical
performance and its greater decline remained significant after
adjustment for number of chronic diseases and physical activity. From
the discussion chapter of the study:

   "This study clearly shows that physical performance is not
   only associated with vitamin D status cross-sectionally, but
   that vitamin D status is also associated with decline over
   time in physical performance. Compared with the reference
   group (25-OHD >= 30 ng/ml), participants with levels up to 20
   ng/ml had significantly lower scores for physical
   performance, and had higher odds for decline in physical
   performance. This was significant after adjustment for age,
   gender, number of chronic diseases, degree of urbanization,
   BMI, alcohol consumption, and physical activity."

Signature

Matti Narkia

Matti Narkia - 13 Mar 2007 11:34 GMT
>>> just published online, found that low vitamin D status is common in
>>> older persons and associated with poorer physical performance and a
[quoted text clipped - 23 lines]
>    gender, number of chronic diseases, degree of urbanization,
>    BMI, alcohol consumption, and physical activity."

References about the relation between vitamin D status and muscle
function and physical performance:

Gloth FM III, Smith CE, Hollis BW, Tobin JD.
Functional improvement with vitamin D replenishment in a cohort of
frail, vitamin D-deficient older people.
J Am Geriatr Soc 1995;43:1269-71.
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=7
594162&dopt=Abstract
>

   "CONCLUSIONS: In this cohort of homebound older people,
   improvement in vitamin D status was associated with functional
   improvement as measured by the FEFA questionnaire."

Verhaar HJ, Samson MM, Jansen PA, de Vreede PL, Manten JW, Duursma SA.
Muscle strength, functional mobility and vitamin D in older women.
Aging (Milano). 2000 Dec;12(6):455-60.
PMID: 11211956 [PubMed - indexed for MEDLINE]
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra
ctPlus&list_uids=11211956
>

   "Six months of treatment with alphacalcidol led to
   significant improvements (compared to the controls) in values
   of isometric knee extensor strength (left leg: 14.6% +/-
   5.7%. p=0.03; right leg: 11.5% +/- 5.0%, p=0.02) (mean +/-
   SEM). The achievements in the timed "Up & Go" test and 2-
   minute walking test did not improve in the alphacalcidol
   group compared to the controls after 6 months. However,
   within the vitamin D-deficient group, 6 months of
   alphacalcidol treatment led to a significant increase in the
   walking distance over 2 minutes (increase from 137.6 +/- 12.6
   to 151.3 +/- 11.2 meters, p=0.03). The controls, with normal
   vitamin D levels, did not exhibit improvements in performance
   of any of the tests over a period of 6 months. Summarized,
   alphacalcidol seems to improve muscle strength and walking
   distance over 2 minutes in vitamin D-deficient older women."

Ziambaras K, Dagogo-Jack S.
Reversible muscle weakness in patients with vitamin D deficiency.
West J Med 1997;167:435?9.
<http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9426489>
<http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1304730&blobtype=pdf>

   "We report on two patients who presented with significant
   proximal muscle weakness, one with vitamin D malabsorption
   and one with dietary vitamin D deficiency. A search for
   inflammation or other causes of myopathy was negative. Muscle
   biopsy in one patient revealed type IIB fiber atrophy. Once
   normal serum 25-hydroxyvitamin D3 levels were restored, both
   patients experienced gradual muscle strength improvement and
   reversal of proximal myopathy within 6 months.

   [...]
   
   The ultimate proof of the diagnosis of vitamin D-deficient
   muscle weakness rests on the response to therapy. Improvement
   in muscle strength has been observed as early as after a
   week,5 but usually within one to two months,14,15 of
   treatment with pharmacologic doses of vitamin D. Treatment is
   required for several months, however, for complete recovery
   of muscle strength.13,15"

Glerup H, Mikkelsen K, Poulsen L, et al.
Hypovitaminosis D myopathy without biochemical signs of osteomalacic
bone involvement.
Calcif Tissue Int 2000;66:419?24.
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=1
0821877&dopt=Abstract
>

   "Hypovitaminosis D myopathy is a prominent symptom of vitamin
   D deficiency, and severely impaired muscle function may be
   present even before biochemical signs of bone disease
   develop. Full normalization of hypovitaminosis D myopathy
   demands high-dose vitamin D treatment for 6 months or more.
   Our findings indicate that serum levels of ALP cannot be used
   in the screening for hypovitaminosis D myopathy. Assessment
   of s-25OHD is the only reliable test."

Prabhala A, Garg R, Dandona P.
Severe myopathy associated with vitamin D deficiency in western New
York.
Arch Intern Med 2000; 160:1199-203
<http://archinte.ama-assn.org/cgi/content/abstract/160/8/1199>

   "Five cases of severe myopathy associated with vitamin D
   deficiency are described. Each patient was confined to a
   wheelchair because of weakness and immobility. Two were
   elderly, 1 was a 37-year-old African American with type 1
   diabetes mellitus, 1 was being treated for carcinoid
   syndrome, and 1 was severely malnourished due to poor oral
   intake. In each, weakness had previously been attributed to
   other causes, including old age, concomitant diabetic
   neuropathy, or general debility. Correct diagnosis was made
   initially by a high index of suspicion, following the
   demonstration of clinical proximal myopathy; confirmation was
   made by the demonstration of low 25-hydroxyvitamin D and
   elevated parathyroid hormone concentrations. Treatment with
   vitamin D caused a resolution of body aches and pains and a
   restoration of normal muscle strength in 4 to 6 weeks. Four
   patients became fully mobile and had normal 25-hydroxyvitamin
   D concentrations, and the fifth also became mobile. In the 4
   fully recovered cases, parathyroid hormone levels on follow-
   up were lower but still elevated. This finding suggests a
   degree of autonomy of parathyroid secretion known to occur in
   cases of long-standing vitamin D deficiency. Myopathy, due to
   chronic vitamin D deficiency, probably contributes to
   immobility and ill health in a significant number of patients
   in the northern United States. An awareness of this condition
   may significantly improve mobility and quality of life in
   patient populations vulnerable to vitamin D deficiency."

Endo I, Inoue D, Mitsui T, Umaki Y, Akaike M, Yoshizawa T, Kato S,
Matsumoto T.
Deletion of vitamin D receptor gene in mice results in abnormal
skeletal muscle development with deregulated expression of
myoregulatory transcription factors.
Endocrinology. 2003 Dec;144(12):5138-44. Epub 2003 Aug 13.
PMID: 12959989 [PubMed - indexed for MEDLINE]
<http://endo.endojournals.org/cgi/content/full/144/12/5138>

   "These results suggest that VDR plays a physiological role in
   skeletal muscle development, participating in temporally
   strict down-regulation of myoregulatory transcription
   factors. The present study can form a molecular basis of VDR
   actions on muscle and should help further establish the
   physiological roles of VDR in muscle development as well as
   pharmacological effects of vitamin D on muscle functions."

Pfeifer M, Begerow B, Minne HW.
Vitamin D and muscle function.
Osteoporos Int. 2002 Mar;13(3):187-94. Review.
PMID: 11991436 [PubMed - indexed for MEDLINE]
DOI: 10.1007/s001980200012
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra
ctPlus&list_uids=11991436
>

Staud R.
Vitamin D: more than just affecting calcium and bone.
Curr Rheumatol Rep. 2005 Oct;7(5):356-64. Review.
PMID: 16174483 [PubMed - indexed for MEDLINE]
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra
ctPlus&list_uids=16174483
>

   "Clinical consequences related to low vitamin D levels
   include not only osteomalacia, osteoporosis, and rickets, but
   also neuro-muscular dysfunction and fractures. Falls related
   to neuromuscular dysfunction lead to 40% of all nursing home
   admissions and are the largest single cause of injury-related
   deaths in elderly people.
   
   [...]
   
   It is well established that vitamin D deficiency not only has
   serious consequences for bone health, but also for other
   organ systems. Previous studies have shown that vitamin D
   supplementation reduces the number of fractures and directly
   improves neuromuscular function, thus helping to prevent
   falls and subsequent fractures."

Boonen S, Bischoff-Ferrari HA, Cooper C, Lips P, Ljunggren O, Meunier
PJ, Reginster JY.
Addressing the musculoskeletal components of fracture risk with
calcium and vitamin D: a review of the evidence.
Calcif Tissue Int. 2006 May;78(5):257-70. Epub 2006 Apr 21. Review.
PMID: 16622587 [PubMed - indexed for MEDLINE]
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=R
etrieve&dopt=abstractplus&list_uids=16622587
>
<http://www.springerlink.com/content/w786x2mjm3276ggk/>

   "Additionally, calcium and vitamin D supplementation
   significantly improves body sway and lower extremity
   strength, reducing the risk of falls."

Zittermann A.
Vitamin D in preventive medicine: are we ignoring the evidence?
Br J Nutr. 2003 May;89(5):552-72. Review.
PMID: 12720576 [PubMed - indexed for MEDLINE]
<http://tinyurl.com/249efc> (full text available from that page)

   "It has been assumed already at the beginning of the 20th
   century that severe vitamin D deficiency results in a
   disturbed muscle metabolism (Ritz et al. 1980). Animal
   studies have demonstrated that the aktinomyosin content of
   myofibrills is reduced during experimental rickets (Stroder &
   Arensmeyer, 1965). Moreover, vitamin D deficiency can impair
   intracellular Ca metabolism in muscle cells. The Ca content
   of mitochondria isolated from vitamin D-depleted chicks is
   low (Pleasure et al. 1979) and Ca uptake into the
   sarcoplasmic reticulum is reduced during vitamin D deficiency
   (Curry et al. 1983). Patients with osteomalacia suffer from
   muscle weakness and have low serum levels of muscle enzymes
   (Ritz et al. 1980; Rimaniol et al. 1994). Supplementation
   with 357 or 1250 mcg vitamin D/d or 50 mcg 25(OH)D/d for 1 to 2
   months was able to normalize muscle strength in patients with
   myopathy (Rimaniol et al. 1994; Ziambaras & Dagogo-Jack,
   1997). Sub-clinical myopathy may even occur at serum 25(OH)D
   levels of 10-50 nmol/l (Peacock, 1995). In line with this
   assumption, leg extension power was positively correlated
   with serum 25(OH)D levels in elderly males and with serum
   calcitriol levels in the whole group of males and females.
   The males had mean 25(OH)D levels of 90 (sd 87.5) nmol/l and
   the females had mean 25(OH)D levels of 68 (sd 53) nmol/l
   (Bischoff et al. 1999b) indicating that a large number of
   subjects had an insufficient vitamin D status. A recent study
   has brought forward evidence that a low vitamin D status also
   contributes to the pathogenesis of congestive heart failure,
   a disease resulting in cardiac muscle weakness due to
   impaired myocardial contractility. Circulating levels of NT-
   proANP, a biochemical indicator of congestive heart failure
   severity, were inversely correlated with serum 25(OH)D levels
   (r2 0.16, P>0.001; Zittermann et al. 2003).

   Supplemental studies have demonstrated that doses of 0.5 mcg
   calitriol/d or 10 mcg vitamin D/d had no effects on parameters
   of muscle function (Table 4). A daily supplement of very high
   doses of vitamin D and also doses of 20 mcg vitamin D/d could,
   however, significantly improve muscle function in subjects
   with low initial 25(OH)D levels (Table 4). It should also be
   mentioned that in both intervention trials the 20 mcg vitamin
   D/d was combined with a daily supplement of 1 200 mg Ca.
   Probably, the combined effect of 20 mcg vitamin D with high
   doses of oral Ca was responsible for the beneficial effects
   in these studies."
   
Mowe M, Haug E, Bohmer T.
Low serum calcidiol concentration in older adults with reduced
muscular function.
J Am Geriatr Soc 1999;47:220-6.
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=9
988294&dopt=Abstract
>

   "CONCLUSIONS: Older people with reduced muscle function often
   had reduced levels of calcidiol serum concentration. Low
   levels of calcidiol were not associated with signs of general
   undernutrition, such as low body mass, or with reduced arm-
   muscle circumference or triceps skinfold thickness. This
   finding may suggest a physiological role for calcidiol in
   muscle function. Reduced muscle strength increased disability
   in our older subjects, which may be improved by vitamin D
   supplementation in vitamin D-deficient subjects.

   [...]
   
   Our findings may be clinically relevant to the
   musculoskeletal health in the aged, because vitamin D
   insufficiency has been shown to be associated with lower
   muscle strength and increased falling tendency in adults.
   Conversely, supplement of native vitamin D or treatment with
   active vitamin D has been reported to improve muscle
   functions and protect from falling events and falling-
   associated fractures (29, 30, 31, 32, 33). Whether the
   beneficial effects of vitamin D treatment occur via direct
   VDR actions on skeletal muscle cells or indirect mechanisms
   remains unclear. Interestingly, however, abnormal expression
   of MyoD family members and MHC isoforms has been reported in
   various models of immobilization and denervation (34, 35, 36,
   37, 38). Considering the plasticity and highly adaptive
   nature of muscle fibers, it is conceivable that reprogramming
   and adaptations of muscle fibers may occur under various
   pathological conditions, particularly in elderly patients,
   and that these processes may be modulated by VDR-dependent
   vitamin D actions.
   
   In summary, we have shown that VDR gene deleted mice exhibit
   abnormal skeletal muscle development. These abnormalities
   occur independently of secondary metabolic changes such as
   hypocalcemia and hypophosphatemia and are accompanied by
   deregulated expression of myogenic transcription factors and
   MHC isoforms. These effects appear to involve direct vitamin
   D actions on muscle through VDR, because similar effects were
   reproduced by treatment of VDR-positive myoblastic cells with
   1,25(OH)2D in vitro. The present study can form a molecular
   basis of VDR actions on muscle and should help further
   establish the physiological roles of VDR in muscle
   development as well as pharmacological effects of vitamin D
   on muscle functions."
   
Solomon AM, Bouloux PM.
Modifying muscle mass - the endocrine perspective.
J Endocrinol. 2006 Nov;191(2):349-60. Review.
PMID: 17088404 [PubMed - indexed for MEDLINE]
<http://joe.endocrinology-journals.org/cgi/content/full/191/2/349>

   "Calcium, vitamin D and phosphate levels all impact on muscle
   function most notably in deficiency states such as the
   myopathy seen in osteomalacia. This has been confirmed as a
   histological atrophy of muscle, predominantly type II fibres
   and is exacerbated by ageing (Janssen et al. 2002).
   Polymorphisms of the vitamin D receptor and vitamin D
   knockout models have a significant muscle phenotype (Demay
   2003). Vitamin D null mice have smaller muscle fibres and
   raised levels of MRFs. These changes are reversed by
   treatment with vitamin D (Endo et al. 2003). Vitamin D-
   receptor polymorphisms associated with body composition and
   muscle strength have been reported in men and women. One
   study assessing older men showed variation in the vitamin D-
   receptor FokI polymorphism (Roth et al. 2004), with a
   different polymorphism linked with muscle strength in a
   further study of older women (Geusens et al. 1997). In a
   longitudinal study looking at sarcopenia in older men and
   women, low vitamin D was linked with increased risk (by
   approximately x2) of reduced muscle mass and strength. a
   similar relationship was found with raised parathyroid
   hormone levels (Visser et al. 2003). In functional terms,
   several trials have examined the relationship between vitamin
   D status and falls; these have been recently reviewed
   (Mosekilde 2005)."

Janssen HCJP, Samson MM, Verhaar HJJ.
Vitamin D deficiency, muscle function, and falls in elderly people.
Am J Clin Nutr 2002;75:611-5.
<http://www.ajcn.org/cgi/content/full/80/2/496>

   "In conclusion, vitamin D deficiency is a condition that may
   cause muscle weakness in elderly persons. Although only a few
   intervention studies with vitamin D have been conducted in
   elderly people, the available evidence indicates that vitamin
   D supplementation preserves muscle strength and functional
   ability in high-risk groups, eg, frail, mostly homebound
   elderly people. Additional research, preferably by means of
   controlled randomized trials, is needed to confirm these
   findings."

Visser M, Deeg DJ, Lips P.
Low vitamin D and high parathyroid hormone levels as determinants of
loss of muscle strength and muscle mass (sarcopenia): the Longitudinal
Aging Study Amsterdam.
J Clin Endocrinol Metab 2003;88:5766?72.
<http://jcem.endojournals.org/cgi/content/abstract/88/12/5766>

   "After adjustment for physical activity level, season of data
   collection, serum creatinine concentration, chronic disease,
   smoking, and body mass index, persons with low (<25
   nmol/liter) baseline 25-OHD levels were 2.57 (95% confidence
   interval 1.40-4.70, based on grip strength) and 2.14
   (0.73-6.33, based on muscle mass) times more likely to
   experience sarcopenia, compared with those with high (>50
   nmol/liter) levels. High PTH levels (>=4.0 pmol/liter) were
   associated with an increased risk of sarcopenia, compared
   with low PTH (<3.0 pmol/liter): odds ratio = 1.71 (1.07-2.73)
   based on grip strength, odds ratio = 2.35 (1.05-5.28) based
   on muscle mass. The associations were similar in men and
   women. The results of this prospective, population-based
   study show that lower 25-OHD and higher PTH levels increase
   the risk of sarcopenia in older men and women."

Bishoff HA, Stahelin HB, Urscheler N, et al.
Muscle strength in the elderly: its relation to vitamin D metabolites.
Arch Phys Med Rehabil 1999;80:54?8.
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=9
915372&dopt=Abstract
>

   "CONCLUSION: Muscle strength declined with age in ambulatory
   elderly people and showed modest, but significant, positive
   correlation with 1,25(OH)2 vitamin D in both sexes and with
   25(OH)D in male subjects. Therefore vitamin D deficiency
   appears to contribute to the age-related loss of muscle
   strength, which might be more pronounced in institutionalized
   elderly people with a high prevalence of vitamin D
   deficiency."

Bischoff-Ferrari HA, Dietrich T, Orav EJ, Hu FB, Zhang Y, Karlson EW,
Dawson-Hughes B.
Higher 25-hydroxyvitamin D concentrations are associated with better
lower-extremity function in both active and inactive persons aged > or
=60 y.
Am J Clin Nutr. 2004 Sep;80(3):752-8.
PMID: 15321818 [PubMed - indexed for MEDLINE]
<http://www.ajcn.org/cgi/content/full/80/3/752>

   "BACKGROUND: Vitamin D may improve muscle strength through a
   highly specific nuclear receptor in muscle tissue.
   
   [...]
   
   CONCLUSION: In both active and inactive ambulatory persons
   aged > or =60 y, 25(OH)D concentrations between 40 and 94
   nmol/L are associated with better musculoskeletal function in
   the lower extremities than are concentrations < 40 nmol/L."

Szulc P, Duboeuf F, Marchand F, Delmas PD.
Hormonal and lifestyle determinants of appendicular skeletal muscle
mass in men: the MINOS study.
Am J Clin Nutr. 2004 Aug;80(2):496-503.
PMID: 15277176 [PubMed - indexed for MEDLINE]
<http://www.ajcn.org/cgi/content/full/80/2/496>

   "CONCLUSION: In elderly men, low physical activity, tobacco
   smoking, thinness, low testosterone (AFTC and FTI), and
   decreased 25(OH)D concentrations are risk factors for
   sarcopenia."

Zamboni M, Zoico E, Tosoni P, et al.
Relation between vitamin D, physical performance, and disability in
elderly persons.
J Gerontol A Biol Sci Med Sci 2002;57:M7?11
<http://biomed.gerontologyjournals.org/cgi/content/abstract/57/1/M7>

   "Conclusions. In community-dwelling elderly women, 25(OH)D is
   related to muscular function and reported disability. Because
   of the high prevalence of hypovitaminosis D in the elderly
   population, this association seems to be clinically
   relevant."

J. R Sharkey, C. Giuliani, P. S Haines, L. G Branch, J.
Busby-Whitehead, and N. Zohoori
Summary measure of dietary musculoskeletal nutrient (calcium, vitamin
D, magnesium, and phosphorus) intakes is associated with
lower-extremity physical performance in homebound elderly men and
women
Am. J. Clinical Nutrition, April 1, 2003; 77(4): 847 - 856.
<http://www.ajcn.org/cgi/content/full/77/4/847>

See also the link

<http://heartscanblog.blogspot.com/search?q=vitamin+d>

provided by RArmant for the references aboty the relation between
vitamin D status and physical performance.

Signature

Matti Narkia

Matti Narkia - 13 Mar 2007 16:12 GMT
>>>> just published online, found that low vitamin D status is common in
>>>> older persons and associated with poorer physical performance and a
[quoted text clipped - 26 lines]
>References about the relation between vitamin D status and muscle
>function and physical performance:

See also

Vitamin D
Micronutrient Information Center - Linus Pauling Institute
<http://lpi.oregonstate.edu/infocenter/vitamins/vitaminD/>

   "Vitamin D deficiency causes muscle weakness and pain in
   children and adults. Muscle pain and weakness was a prominent
   symptom of vitamin D deficiency in a study of Arab and Danish
   Moslem women living in Denmark (20). In a cross-sectional
   study of 150 consecutive patients referred to a clinic in
   Minnesota for the evaluation of persistent, nonspecific
   musculoskeletal pain, 93% had serum 25(OH)D levels indicative
   of vitamin D deficiency (21). A randomized controlled trial
   found that supplementation of elderly women with 800 IU/day
   of vitamin D and 1,200 mg/day of calcium for three months
   increased muscle strength and decreased the risk of falling
   by almost 50% compared to supplementation with calcium alone
   (22)."

References mentioned in above excerpt:

20.  Bringhurst FR, Demay MB, Kronenberg HM. Mineral Metabolism. In:
Larson PR, Kronenberg HM, Melmed S, Polonsky KS, eds. Larsen: Williams
Textbook of Endocrinology: Elsevier; 2003:1317-1320.

21.  Plotnikoff GA, Quigley JM. Prevalence of severe hypovitaminosis D
in patients with persistent, nonspecific musculoskeletal pain. Mayo
Clin Proc. 2003;78(12):1463-1470.
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
4661675&dopt=Abstract
>

22.  Bischoff HA, Stahelin HB, Dick W, et al. Effects of vitamin D and
calcium supplementation on falls: a randomized controlled trial. J
Bone Miner Res. 2003;18(2):343-351.
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
2568412&dopt=Abstract
>

   "Musculoskeletal function improved significantly in the
   Cal+D-group (p = 0.0094). A single intervention with vitamin
   D plus calcium over a 3-month period reduced the risk of
   falling by 49% compared with calcium alone. Over this short-
   term intervention, recurrent fallers seem to benefit most by
   the treatment. The impact of vitamin D on falls might be
   explained by the observed improvement in musculoskeletal
   function."

Signature

Matti Narkia

RArmant - 12 Mar 2007 21:13 GMT
Vitamin D appears to help reverse atherosclerosis. See --
http://heartscanblog.blogspot.com/search?q=vitamin+d
 
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