Mixed Picture for Vitamin D Status in Frail Elderly

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Both high and low levels of vitamin D were associated with frailty in

elderly study participants, suggesting a more complex relationship between

vitamin D and health status than has been commonly thought, researchers

said.

There was a U-shaped relationship between measures of frailty and serum

levels of 25-hydroxyvitamin D (25-OH-D) in more than 6,000 women older than

68 in the Study of Osteoporotic Fractures, conducted by e Ensrud, MD,

MPH, of the University of Minnesota in Minneapolis, and colleagues.

Among those with serum levels of at least 30 ng/mL -- the standard upper

limit of normal -- the multivariate odds ratio for frailty was 1.32 (95% CI

1.06 to 1.63*)*, the researchers reported in the December issue of the *Journal

of Clinical Endocrinology & Metabolism*.

The increased risk was similar to that seen in participants with serum

25-OH-D below 15 ng/mL (multivariate OR 1.47, 95% CI 1.19 to 1.82).

On the other hand, among participants who weren't frail at baseline, only

low 25-OH-D levels were associated with adverse outcomes during the study's

average of 4.5 years of follow-up.

Previous studies of vitamin D status and frailty " have assumed a linear

inverse association " between them, the researchers noted.

Ensrud and colleagues suggested that their findings highlight the importance

of prospective, randomized trials of vitamin D supplements before they can

be recommended for individuals with serum 25-OH-D levels already in or above

the normal range.

In an accompanying editorial, two independent researchers said that, in the

interim, the most prudent approach in elderly patients is to use supplements

when necessary to achieve serum 25-OH-D levels in the normal range of 20 to

30 ng/mL.

Those levels can reasonably be accepted as " safe as well as efficacious, "

wrote Clifford J. Rosen, MD, of Maine Medical Center in Scarborough, Maine,

and JoAnn Manson, MD, DrPH, of Brigham and Women's Hospital in Boston.

The multicenter study was a longitudinal project that began in 1986 with an

original enrollment of some 9,700 women 65 and older. After six years,

surviving participants were invited for a detailed follow-up examination.

Another such exam was offered at year 10.

Ensrud and colleagues focused on 6,307 participants who attended the year

six exam, considered the baseline in the current analysis. Of those women,

4,551 were not frail* *and completed the year 10 exam or were known to have

died.

Frailty was assessed on five criteria: body weight loss of at least 5% since

the previous exam, grip strength in the lowest quintile, self-reported

lethargy, walking speed in the lowest quintile, and weekly walking duration

in the lowest quintile.

Participants with poor scores on at least three components were considered

to be frail. Those with indications of frailty on one or two components were

classified as intermediate.

At baseline, 35% of the women were considered robust, 48% were in the

intermediate stage, and the remaining 17% were already frail.

The researchers determined that no single component of the frailty index

appeared to drive the overall relationship between frailty classification

and 25-OH-D levels. All five components were increased in those with levels

below 15 ng/mL, and three of the five -- body shrinkage, gait slowness, and

low activity level -- were increased in those with higher than normal

levels.

Participants could take vitamin D if they wished, and 42% chose to do so.

More than two-thirds of women with 25-OH-D levels of 30 ng/mL or more were

taking supplements, versus 49% of those in the normal range and 15% of those

with levels below 15 ng/mL.

These data raise the possibility that women who were already frail might

have tried to compensate by taking supplements, thereby accounting for the

increased rate of baseline frailty seen in those with higher 25-OH-D levels.

However, Ensrud and colleagues noted, the U-shaped relationship between

frailty status and 25-OH-D levels was also apparent in the participants not

taking supplements, as well as in the entire cohort.

Among the 4,551 participants not frail at baseline, 16% were classed as

frail at their next exam and 9.5% had died.

Levels of 25-OH-D that were out of the normal range showed small to modest,

mostly nonsignificant relationships with incident frailty or death in

multivariate analysis.

The largest effects were seen for death in participants with low 25-OH-D.

The adjusted odds ratio for death versus survival was 1.40 in patients with

25-OH-D below 15 ng/mL (95% CI 1.04 to 1.88).

When 25-OH-D was categorized in quartiles, the risk of death was increased

in the two lowest quartiles relative to the third by about 40% to 50%.

There was also a trend toward increased risk of death or frailty versus

classification as robust or intermediate in the two lower quartiles.

High 25-OH-D levels, defined as either 30 ng/mL or more or as the highest

quartile, did not appear associated with increased risk of incident frailty

or death.

Although Ensrud and colleagues were able to adjust for such factors as age,

body mass index, smoking, education, and comorbidities in their

calculations, they acknowledged that unmeasured confounders may still have

been present.

Other limitations included the study's exclusion of nonwhite women and the

nonrandom use of vitamin D supplements.

The National Institutes of Health supported the study.

Study authors and the editorialists declared they had no financial conflicts

of interest.

*Primary source: *Journal of Clinical Endocrinology & Metabolism

Source reference:

Ensrud K, et al " Circulating 25-hydroxyvitamin D levels and frailty status

in older women " *J Clin Endocrinol Metab* 2010; 95:

5266-5273.<http://jcem.endojournals.org/cgi/content/abstract/95/12/5266>

*Additional source:* Journal of Clinical Endocrinology & Metabolism

Source reference:

Rosen C, et al " Frailty: A D-ficiency syndrome of aging? " *J Clin Endocrinol

Metab* 2010; 95: 5210-5212.

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