Differences in vitamin D status between countries in young adults and the elderly

Differences in Vitamin D Status Between Countries in Young Adults and the Elderly MALACHIJ. MCKENNA, M.D., M.R.c.P.I., F.A.c.P., DbnLaoghaire.

To compare vitamin D status between countries in young adults and in the elderly. MATER~ANDmo~Reportsonvitamin D statue (as assesM by serum 25-hydroxyvitamin D) from 1971 to 1990 were reviewed. Studies were grouped according to geographic regions: North America (including Canada and the United States); Scandinavia (including Denmark, Finland, Norway, and Sweden); and Central and Western Europe (including Belgium, France, Germany, Ireland, The Netherlands, Switzerland, and the United Kiugdom). RESULTS: Vitamin D status varies with the season in young adults and in the elderly, and is lower during the winter in Europe than in both North America and Scandinavia. Oral vitamin D intake is lower in Europe than in both North America and Scandinavb~ Hypovitaminosis D and related abnormalities in bone chemistry are most common in elderly residents in Europe but are reported in all elderly populations. CONCLUSIONS: The vitamin D status in young adults and the elderly varies widely with the country of residence. Adequate exposure to summer sunlight is the mntial means to ample supply, but oral intake augmented by both fortification and supplementation is necessary to maintain baseline stores. AlI countries should adopt a fortification policy. It seems likely that the elderly would benefit additionahy from a daily supplement of 10 gg of vitamin D. PURPOSE:

lreland

itamin D is derived from skin and from oral intake. It is accepted that the major source of vitamin D is exposure of skin to the ultraviolet B rays contained in sunlight [l]. A number of factors influence skin production of vitamin Ds, namely, terrestrial solar irradiation, aging, melanin content of skin, and sunscreen usage [2,3]. At subtropical latitudes, there is no attenuation of vitamin D production during the winter; in low latitudes, cutaneous production continues throughout the winter but at reduced capacity; and, at high latitudes, there is no production for 4 to 6 months of the year [2]. Oral intake comprises vitamin D-rich foods, fortified foods, and supplementation. Natural sources of vitamin D are limited [4]. Milk is fortified with vitamin D in the United States and Canada, but this is not mandatory in European countries. A lack of vitamin D, termed privational vitamin D deficiency, predisposes at first to secondary hyperparathyroidism, accompanied by accelerated bone loss, and subsequently to osteomalacia, a disorder of defective bone mineralization manifested by pain, deformity, and fracture of bone [5,6]. Given the global differences in ultraviolet radiation and in dietary sources of vitamin D, disparities in vitamin D status should be evident between different regions of the world. Many studies on vitamin D status, using serum 25-hydroxyvitamin D [25(OH)D], have been reported over the past 2 decades [l]. Although regional differences have occasioned comment, no analysis has been reported. The purpose of this report is to compare studies of vitamin D status in young adults and the elderly worldwide, and to examine the consequences of differences in vitamin D status with regard to privational vitamin D deficiency.

V

MATERIALSAND METHODS

From the Department of Endocrinology and Diabetes, St. Vincent’s Hospital, Dublin, Ireland, and the Department of Medicine, St. Michael’s Hospital, Dun Laoghaire, Co. Dublin, Ireland. Dr. McKenna received financial support from Our Lady’s Manor, Dalkey, Ireland, and from the Robert and June Gurwin Research Fund, Henry Ford Hospital, Detroit, Michigan. Requests for reprints should be addressed to Malachi J. McKenna, M.D., Department of Medicine, St. Michael’s Hospital, Lr. George’s Street, Don Laoghaire, Co. Dublin, Ireland. Manuscript submitted July 2.1991, and accepted in revised form January 28, 1992.

Data Identification In a review of the literature using computerized bibliographic retrieval programs, Index Medicus, and personal files, 117 studies of vitamin D status from 27 regions were identified between 1971 and 1990 (Table I): 34 studies on the elderly alone, 42 on young adults alone, and 41 on both [7-1231. Criteria for Review of Reports Regarding different methodologies for assay of serum 25(OH)D, comparisons of results between July 1992 The American Journal of Medicine

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VITAMIN D STATUS IN ADULTS / McKENNA TABLE I List of Reportsof Vitamin D Status From Different Countries

canltry Antarctic f71 Arctic (Canadian) f81 Australia f91 Belgium [IO-121 Canada f13-161 Czechoslovakia [171 Denmark 118-221 Finland f23-261 France [27-301 Germany [31-331 Hong Kong f341 Ireland [35-371 Israel f38-431 Italy I441 Japan f451 Mexico f461 Netherlands [47-511 New Zealand I521 Norway [53,541 Puerto Rico [551 Saudi Arabia [56,571 South Africa I581 Sweden [591 Switzerland 160,611 United Kingdom [20,62-941 United States [95-1231 Zaire f121

No. of Studies Young Adults Elderly 1

-

1 7

7 3

:

1

1

3”

: 3

i : 2 4

: 6 i 1

-

1

4

2

1

:

1 2 1

:

Statistical Analysis

Comparison betweenmultiple groupswas made by one-wayanalysisof variance;if a significant differencewasnoted, then comparisonsbetweenindividual groupsweremade using the Bonferroni correction for multiple comparisons. Where appropriate, Student’s t-test was used for paired comparisons.p valuesrefer to two-sided tests;values below 0.05 were consideredto be significant.

1 2 2;

:i

1

11 -

different laboratorieshaveyielded acceptablefindings provided that a preparative chromatographic step was employed [20,35,91,124,125]. The following criteria for the comparison of studies were established: (1) that all serum 25(OH)D assaysincluded a preparatory chromatographic step; (2) that the time of the year was recorded so as to permit comparisonof results with referenceto the seasonof study; and (3) that a description of age, health, and residencewas given. Analysis of Vitamin D Status

It wasapparenton analysisof data from different countriesthat there were similarities betweencontiguous countries.In order to facilitate the analysis of trends in vitamin D status, countries were groupedaccording to regions:North America (including Canadaand the United States);Scandinavia (including Denmark, Finland, Norway, and Sweden);and Central and WesternEurope (including Belgium, France, Germany,Ireland, The Netherlands, Switzerland, and the United Kingdom). Studies comprised white patients only in these grouped comparisons.As regards elderly studies, groupsweresubdividedfurther into healthy elderly personsresiding at home and institutionalized elderly persons.Most studiesof seasonalvariation in serum 25(OH)D levelshavereported peakvaluesin late summer and lowest values in late winter. 70

Therefore, the year was divided into four time periods-late winter (January, February, March); late spring (April, May, June); late summer (July, August, September);and late fall (October,November, December)-spring and fall valuesweresubsequently combined. Studies from each geographic region were collated into eachof the time periods. Trends were examinedwith respectto: (1) vitamin D status as assessedby serum 25(OH)D; (2) oral vitamin D intake; and (3) frequency of hypovitaminosis D and of bone disease.

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RESULTS Vitamin D Status

In young adults, overt changesin vitamin D status wereseenthroughout the year,with the highest valuesbeingreachedin late summer and the lowest valuesin late winter (Figure 1). Significant differenceswerenoted betweengroupsduring winter (p
VITAMIN

Young Adults 26(OH)D

nmol/l

1

IN ADULTS

/ McKENNA

Healthy Elderly 26(OH)D

nmol/l

A

1

A

D STATUS

m

WINTER

m

BPRlRLL

1.::: SUMMER

/

120 100

80 60

I

40

00

/

7

40 20

I 20

I / NAMER

/ WAND

/ EUROPE

Figure 1. Mean of the average serum 25(OH)D levels in young adults reported during winter, spring-fall combined, and summer from studies collated according to geographic region: North America [15,95,97,98,103,106,110,112,120,121], Scandinavia [19-23,25,53,54], and Europe [10,20,28,30,32,

0 N AMER

SCAND

EUROPE

Flgure 2. Mean of the average serum 25(OH)D levels in healthy elderly reported during winter, spring-fall combined, and summer from studies collated according to geographic region: North America [103.110,112.118], Scandinavia [18,24,26,54,59], and Europe [29,30.37,56,63,67,68, 75,77,87,89,93].

35,37,47,61-66,80,82,84,89,90].

During a 2-month period of solar deprivation in a nuclearsubmarine,a declinein serum25(OH)D was noted [65]. In astronauts participating in the Skylab program, a slight decline in serum 25(OH)D levels was noted despite an oral intake of 12.5 Fg/day [lOO].In Japaneseresearchers(n = 3) at the Antarctic (69” south), very low serum 25(OH)D levels were found without any seasonalvariation [7]. At the other end of the globein Tromso (70° north), serum 25(OH)D had a mean seasonalincrement of 34 nmol/L in light-skinned populations [53]. With regardto racial differencesin youngadults, Mexican-American and African-American adults had lower levels than age-matchedwhite control subjects [109,121,123].In the Asian population in Great Britain, levelswere much lower than in comparable controls [65],just as Z&ians living in Belgium had lower valuesthan white control subjects [12]. In Germany, Turkish immigrants had lower levels than seenin the native population [33]. In Saudi Arabia, racial differenceswerealsoseen,with native personshaving lower levels than immigrant whites but higher levelsthan immigrants from Africa [57].The conversewasseenin the CanadianArctic, where native Inuits had higher levels of serum 25(OH)D than white residentswhen studied at the

end of winter [8]. This was explained by dietary customs,asthe Inuits consumedlargequantities of fish and seal livers. In the community-dwelling elderly, trends were similar to thoseof youngeradults but not asmarked (Figure 2). Differencesbetweengroupswerenoted for spring/fall (p = 0.03) but not for winter (p = 0.11)or summer (p = 0.69).When groupswereanalyzed regardlessof season,significant differences werenoted (F = 5.9,p = 0.008),and Europeanvalues were significantly lower than both Scandinavian and North American values. In the healthy elderly living in Israel, valuesweresimilar to those of comparableNorth Americans.Healthy elderly in Auckland, New Zealand (37” south), had similar values in the spring compared with comparable groups in North America [52]. Reports on institutionalized elderly were groupedaccordingto region only as a consequence of the limited number of studiesthat wereconducted during specificseasons,but onewould not expect much seasonalchange [4,83]. Regional patterns were consonant with those seen in young adults (Figure 3). Significant differencesbetweenregions werenoted (p
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VITAMIN D STATUS IN ADULTS / McKENNA

Oral Vitamin

Institutionalized Elderly

1

D Intake

mcald

26(OH)D nmoVl 10

eoT-

Reoommended Intake -1 I

I

6

6

a

4

2

:

N AMER

EUROPE

Figure 3. Mean of the average serum 25(OH)D levels in institutionalized elderly reported throughout the year from studies collated according to geographic region: North America [13,16.104.112,118,119], Scandinavia [26,54,59], and Europe [11,28,30.37,51,66,67,70,72,74,75,82,83,85,89, 92-941.

0 N AMER Figure 4. Mean of the average vitamin D intake in young adults and the elderly reported from studies collated according to geographic region: North America [1,13,95,98, 103,110.114,120,123], Scandinavia [18,20,26], and Europe [11,12,20,37,50,63,66,71,74-77,83,87,89,92,128-131].

Residents in North America and Scandinavia, American values, and Scandinavian values were both youngand old, are more apt to take vitamin D lower than North American values. supplementsthan their counterpartsin Europe. In Great Britain and Ireland, lessthan 15%of the elOral Vitamin D Intake derly take supplements[37,66,87];in North AmeriThirty-one studies that recordeddata on oral intake of vitamin D in young adults (n = 16) and the ca, about 30% of the young and the elderly take supplements [110,112,118,120]; and, in Denmark, elderly (n = 22) were reviewed [128-1311(Figure 4). Estimates included intake from natural sources, about 50% of the inhabitants take supplements fortified foodstuffs,and supplements.Regionaldif- [18,19].Also, inhabitants in Scandinaviancountries ferencesin intake were seen.When data on young havea high intake of natural sourcesof vitamin D, adults and the elderly were combined, significant such as oily fish [26]. differences were noted between the groups (p
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jects have low values in the winter, but less than 5% have low levels throughout the remainder of the year [14,24,103,112,114,118]. In Europe, the frequency of hypovitaminosis D in the winter ranges from 8% to 60% [11,32,61,63,90]. In Israel, nearly one third of healthy elderly persons have low levels during spring [39]. In the institutionalized elderly population, the prevalence of hypovitaminosis D varies from 3% to 23% in North America, from 70% to 100% in Europe, and up to 60% in Israel [37,39,65,66,90,93,94,104,112,118]. Women are represented in greater proportion than men in most studies, and they tend to have lower levels [103]. In the elderly, hypovitaminosis D is associated with an elevation in the serum alkaline phosphatase level [30,37,51]. In North America, a seasonal change in alkaline phosphatase is seen, with the peak during the winter when vitamin D stores are apt to be depleted [ 1031. Only marked depression in serum 25(OH)D levels to below 5 nmol/L is associated with decreases in serum calcium, phosphate, and calcium-phosphate product [4]. In the elderly, elevated serum parathyroid hormone levels are seen commonly [30,85]. In North America, a seasonal vacillation is observed in vitamin D-deplete postmenopausal women but not in vitamin D-replete subjects [120].

COMMENTS It is accepted that skin generation of vitamin D by the direct action of summer sunlight is the main source of vitamin D in humans. This comparison of studies from the medical literature suggests an important role for oral vitamin D intake in sustaining vitamin D stores during the winter period of obligatory solar deprivation. The magnitude of the seasonal fluctuation in serum 25(OH)D is less in North America and Scandinavia than in other European countries. A dietary factor must be responsible for the disparity during wintertime, when there is no skin production of the vitamin. Oral vitamin D intake-from natural sources, fortified food, and supplements-is higher in Scandinavia and North America than in Europe, both for young adults and the elderly. For elderly populations, in particular, the primacy of exogenous vitamin D in the maintenance of adequate baseline vitamin D stores throughout the year is strongly emphasized. Hypovitaminosis D per se does not imply that bone disease is present but does identify a high-risk status [ 11. Hypovitaminosis D describes the finding of a low circulating level of serum 25(OH)D, whereas vitamin D deficiency implies the existence of an anatomic, physiologic, or biochemical abnormality that can be corrected by administration of vitamin D in nonpharmacologic doses [l] . Hypovitaminosis D must precede a state of vitamin D deficiency. An

inaccurate use of terminology is to qualify vitamin D deficiency as being nutritional in origin [l]. This is erroneous for two reasons: first, the two sources of the vitamin are not considered by this usage; second, the inference is that oral intake in an individual subject is deficient, whereas it is the dietary sources of the region that are inadequate [6]. It is more correct to use other terms such as “privational,” “ simple,” or “extrinsic” [5]. Osteomalacia, an accumulation of unmineralized bone matrix (termed osteoid) as a consequence of failure in mineralization, is a pathologic disease that ensues when hypovitaminosis D persists for a protracted period of time [5,6]. The histologic evolution of bone disease due to vitamin D deficiency has been elucidated recently based upon knowledge of the relationship between osteoid accumulation and tetracycline-based kinetics. Secondary hyperparathyroidism is the initial event at the bone level [132,133]. There is an increase in osteoid volume, an increase in the bone formation rate, and an increase in osteoclastic activity [5,133]. Unless a tetracycline-based measurement is made, the histologic findings could be construed as being consistent with osteomalacia-a common custom in older studies [134]. It is during this initial stage that permanent bone loss occurs [132]; there is an increase in cortical porosity and a reduction in cortical width due to loss of bone at the endocortical surface. In time, the osteoid seam increases in thickness coincident with prolongation in the mineralization lag time; a state of defective mineralization prevails, consonant with the traditional definition of osteomalacia. Hypovitaminosis D osteopathy, encompassing secondary hyperparathyroidism and osteomalacia as judged by biochemical and histologic studies, is clearly evident in all elderly populations, especially European [135-1391. Available modes of prevention are threefold: oral vitamin D supplementation; increased exposure to ultraviolet light, either natural or artificial; and increased fortification of foodstuffs with vitamin D [l]. For many years, vitamin D supplements have been recommended for the elderly and others at risk [140]. Conflicting opinions are held on the efficacy and safety of low-dose supplementation [1,3,140-1431. It is contended by some that the oral route as a means of supplying vitamin D is either ineffective or unproven, unnatural, and potentially dangerous [142,143], whereas others suggest that vitamin D intake from all sources in the elderly should be 15 rgld to 20 kg/d, about 100% above the usual recommended daily intake [1,4]. The response to continuous supplementation with low-doses of parent vitamin D, in terms of serum 25(OH)D levels, reaches a plateau by 3 to 6 months [51,144]. Three studies of long-term lowJuly 1992 The American Journal of Medlclne

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dose supplementation from Europe (each using 20 pg of vitamin Ds or vitamin Ds) report mean values that are remarkably similar (ranging from 73 to 78 nmol/L), and values remain below maximum levels seen in young adults [30,51,144]. An alternative to continuous low-dose replacement is single highdose therapy (2,006 pg to 15,609 c(g) repeated on a yearly or a biannual basis [17,145-1481. Whenever hypercalcemia has been noted with vitamin D supplementation, this outcome has been explained by contemporaneous conditions such a primary hyperparathyroidism [51,149,150]. Skin synthesis of vitamin D in elderly people may be enhanced by exposure to artificial ultraviolet light [82], but provision of fluorescent lighting in wards has resulted in inconsistent responses [70,83,92,151,152] and can be associated with complications-namely skin burns, keratoconjunctivitis, and cataracts. Advising the elderly to spend more time outdoors is to be encouraged but is hardly practical for the most infirm and thus the most at risk. Those elderly who venture outdoors, unlike their younger counterparts, often take protective action to avoid sunlight either by use of clothing and sunscreens, or simply by just avoiding the direct path of the sunlight. In addition, there are valid concerns about photoaging and skin cancer. In all countries, natural dietary sources of the vitamin do not readily permit intake of recommended amounts, i.e., 5.0 to 10.0 pg daily. Fortification of a foodstuff with a nutrient is a public health measure aimed at increasing intake of that nutrient in the general population. In North America, household milk is fortified with vitamin D. The quantity added to a quart of milk is 10 pg of vitamin D. At this level of fortification, one pint of milk per day would provide approximately half the recommended daily intake of vitamin D for housebound individuals. Dunnigan and colleagues [92] in Scotland have conducted the only comprehensive trial of fortification. Elderly residents of a long-stay hospital received either the usual diet or fortified food: margarine (2.4 pg/d), butter (2.4 pg/d), or milk (4.2 rgld). Compared with baseline, use of fortified foods led to an increase in serum 25(OH)D in three of four groups, but none reached significance. In control patients, the mean serum 25(OH)D level decreased. By comparison, in patients who received a daily supplement of 10 rg of vitamin D, a threefold rise in the serum 25(OH)D level occurred. The relationship between 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)sD], the most potent metabolite, is complex. The concentration of serum 1,25(OH)sD, which is under tight metabolic control, is only influenced by vitamin D status if there is substrate deficiency [l]. In young adults, a seasonal change in 1,25(OH)zD is not seen [22,102]. In the 74

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early stages of vitamin D depletion, serum 1,25(OH)sD levels are likely to be normal or even high, rather than low, as secondary hyperparathyroidism counters substrate deficiency [14,54]. In severe depletion, serum 1,25(OH)zD levels are low [94]. Vitamin D therapy did not result in any change in serum 1,25(OH)sD levels in North American studies of nursing home residents without vitamin D depletion [16,153]. In Europe, supplementation of vitamin D-deplete subjects has shown a rise in serum 1,25(OH)sD, which appears to be pronounced in those with hypovitaminosis D [ll]. The exact level of serum 25(OH)D above which the production of 1,25(OH)sD is no longer influenced by substrate but subject only to physiologic signals is unknown; it may exceed 75 nmol/L [154]. In conclusion, vitamin D status in young adults and the elderly varies widely with country of residence. Although adequate exposure to summer sunlight is the essential means to ample supply, oral intake augmented by both food fortification and vitamin supplementation is necessary to maintain baseline stores during wintertime. Governments of countries where foodstuffs fortified with vitamin D are in short supply should be enjoined to consider a more comprehensive policy. Greater availability of vitamin D through fortification of food does not abrogate physicians and health care professionals from contemplating supplementation in specific circumstances. Supplementation, in contrast to fortification, which is a means to provide a minimal supply for the general population, is a substitute for skin supply. Since the prevalence of hypovitaminosis D is unacceptably high in the elderly from all regions studied, low-dose vitamin D supplements (about 10 rg daily) should be administered to all elderly persons. Continuous low-dose vitamin D supplementation is a simple, safe, and efficacious mode of prevention.

ACKNOWLEDGMENT I wish to thank A.M. Parfitt. Freaney, Ph.D., St. Vincent’s

M.D., Henry Ford Hospital, Detroit, MI, and R. Hospital, Dublin, Ireland, for helpful discussions.

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