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Estimación de Requerimientos de Vit D en Adultos Sanos - Am J Clin Nutr 2008 PDF
Estimación de Requerimientos de Vit D en Adultos Sanos - Am J Clin Nutr 2008 PDF
adults1–3
Kevin D Cashman, Tom R Hill, Alice J Lucey, Nicola Taylor, Kelly M Seamans, Siobhan Muldowney,
Anthony P FitzGerald, Albert Flynn, Maria S Barnes, Geraldine Horigan, Maxine P Bonham, Emeir M Duffy, JJ Strain,
Julie MW Wallace, and Mairead Kiely
Am J Clin Nutr 2008;88:1535– 42. Printed in USA. © 2008 American Society for Nutrition 1535
1536 CASHMAN ET AL
panel assumed that there was no cutaneous synthesis of vitamin DRI panel (5). Randomization was centralized, computer-
D through sun exposure (5). The European Union (EU) dietary generated, stratified by center, and adjusted for age (20 –30 or
recommendation [population reference intake (PRI)] for vitamin 쏜30 – 40 y) and sex. The vitamin D3 capsules and matching
D in adults ranges from 0 to 10 g/d to account for the widely placebo capsules were produced by Banner Pharmacaps (Til-
varying latitudes in which EU citizens live (35–70 oN) (16). burg, Netherlands) and were identical in appearance and taste.
The aim of the present study was to perform a randomized The vitamin D3 content of the capsules was independently con-
controlled intervention study in adults (aged 20 – 40 y) by using firmed by laboratory analysis (Consultus Ltd, Glanmire, Ire-
supplemental intakes (0, 5, 10, and 15 g/d) of vitamin D3 land). Compliance was assessed by capsule counting. An a priori
throughout the winter to establish the distribution of dietary decision was made to include only those subjects whose com-
requirements for the maintenance of nutritional adequacy of vi- pliance exceeded 85%. The allocation remained concealed until
tamin D during late winter, as indicated by serum 25(OH)D the final analyses, and all data were reported by persons who
concentrations ranging from 욷25 nmol/L to 욷80 nmol/L. In were blinded to the allocation scheme.
addition, the effect of summer sunshine exposure (and the re- The study was carried out in 2 locations: Cork, Ireland (latitude
sulting tissue vitamin D stores) on these dietary requirements was 51 °N), and Coleraine, Northern Ireland, United Kingdom (lat-
assessed. itude 55 °N). A 2-center approach was chosen because of the
differences in summer weather patterns and cloud cover between
the 2 centers and because the 2 centers, which are separated by 4 °
SUBJECTS AND METHODS of latitude, provide a geographic spread that covers a sizeable
area of Ireland and the United Kingdom. [Data from the NDNS
Subjects show that mean serum 25(OH)D concentrations in older adults
A total of 245 apparently healthy adults were recruited to this were 앒10 nmol/L lower in the northern part of the United King-
however, men had significantly (P 쏝 0.006) higher intakes of the proportion of men to women, in sun exposure preferences, in
vitamin D and calcium than did women [3.8 (2.4 –5.8) and 3.3 mean habitual dietary vitamin D or calcium intake, or in mean
(1.7–5.0) g/d, respectively, for vitamin D; 1128 (857–1485) preintervention serum 25(OH)D, PTH, or albumin-corrected cal-
and 803 (587–1045) mg/d, respectively, for calcium), which was cium concentrations among the treatment groups (Table 2).
TABLE 1
Baseline characteristics of the subjects who entered the intervention study1
Treatment group
Placebo 5 g vitamin D/d 10 g vitamin D/d 15 g vitamin D/d
(n ҃ 57) (n ҃ 48) (n ҃ 57) (n ҃ 53) P2
Habitual dietary vitamin D (g/d) 3.4 (2.0–5.0)3 4.3 (2.2–5.7) 3.5 (2.3–4.7) 3.6 (1.8–5.8) 0.856
Habitual dietary calcium (mg/d) 924 (694–1197) 905 (655–1314) 976 (681–1286) 1014 (744–1387) 0.600
Summer sun exposure preferences (%)
Sun avoider 12.5 12.5 8.9 17.0
Some sun exposure 50.0 50.0 46.4 49.1
Frequent sun exposure 37.5 37.5 44.6 34.0 0.885
Serum 25(OH)D (nmol/L)
Before intervention4 65.7 (58.4–94.1) 60.0 (50.0–89.7) 72.2 (55.7–91.9) 75.9 (55.9–89.3) 0.623
After intervention5,6 37.4 (31.4–47.9)a 49.7 (44.6–60.0)b 60.0 (51.0–69.1)c 69.0 (59.1–84.2)d 쏝0.0001
Serum PTH (ng/mL)
Before intervention4 49.7 (32.9–62.1) 46.9 (34.0–70.3) 43.1 (35.6–57.9) 38.4 (29.0–50.3) 0.145
After intervention5,6 56.2 (41.3–67.8)a 52.0 (35.9–67.9)a 50.5 (41.1–69.4)a 43.0 (33.1–62.0)b 0.060
1
PTH, parathyroid hormone; 25(OH)D, 25-hydroxyvitamin D. Values in a row with different superscript letters are significantly different, P 쏝 0.05.
2
One-factor ANOVA followed by Tukey’s test.
3
Median; interquartile range in parentheses (all such values), used in the case of nonnormally distributed variables.
respectively; P 쏝 0.0001). In contrast, calcium intake at end- serum 25(OH)D concentrations 쏜25 nmol/L in 50% of the
point did not differ significantly (P ҃ 0.5) among the 4 groups adults] could not be estimated because, at the lowest vitamin D
(data not shown). intake (0.1 g), the serum 25(OH)D concentrations in the 50th
There was a significant (P 쏝 0.0001) effect of treatment on percentile were 34.5 nmol/L. Data on sun preference also were
mean postintervention serum 25(OH)D concentrations, with incorporated into the model; the vitamin D intakes that main-
clear dose-related increments with increasing supplemental vi- tained serum 25(OH)D concentrations of 욷25 nmol/L in 97.5%
tamin D3 (Table 2). There was no significant difference in mean of the sample were 7.2, 8.8, and 12.3 g/d in those who reported
postintervention serum albumin– corrected calcium concentra- often having sunshine exposure, those who sometimes had sun-
tions among the treatment groups (8.6 앐 0.3, 8.7 앐 0.3, 8.6 앐 0.3, shine exposure, and sunshine avoiders, respectively. The vitamin
and 8.6 앐 0.3 mmol/L in the placebo and 5, 10, and 15 g vitamin D intakes that maintained serum 25(OH)D concentrations above
D/d groups, respectively; P ҃ 0.526) and no significant change 2 other commonly suggested cutoffs in 97.5% of the sample were
over time (P for time ҂ treatment ҃ 0.336). None of the subjects 26.1, 27.7, and 31.0 g/d (for 욷50 nmol/L) and 38.9, 40.6, and
had hypercalcemia. There was a trend (P ҃ 0.06) for postinter- 43.9 g/d (for 욷80 nmol/L) in those who reported often having
vention serum PTH concentration to be affected by treatment,
and post hoc analysis showed a significantly (P ҃ 0.009) lower
mean concentration in the group receiving 15 g/d than in the
group receiving placebo (Table 2). However, the treatment ҂
time interaction in repeated-measures ANOVA was not signifi-
cant (P ҃ 0.274) for the effect of vitamin D supplementation on
serum PTH concentrations.
sunshine exposure, those who sometimes had sunshine exposure, value to 2.5 g/d and then doubled it to achieve an AI of 5.0 g/d
and sunshine avoiders, respectively. (5). Working from a lack of data in men, the panel also made an
Whereas a serum 25(OH)D concentration of 쏝25 nmol/L has assumption that the AI for men would be similar to that for
been used by several authorities as the traditional indicator of women (5). The findings of the present study suggest that a
adequacy for vitamin D (1, 5, 15, 16), several other biochemical vitamin D intake of approximately twice the AI is required by
cutoffs for serum 25(OH)D, ranging from 37.5 to 80 nmol/L, healthy white men and women at latitudes of 앒50 oN to maintain
have been suggested (6 –9, 24). The 50th, 90th, 95th, and 97.5th 25(OH)D at these concentrations (앒30 nmol/L).
percentile estimates for vitamin D intake, obtained by using a In setting the AI, the US DRI panel also assumed that there was
range of alternative indicators of adequacy for vitamin D status, no cutaneous synthesis of vitamin D through sun exposure (5).
are shown in Table 3. This is true in winter, and, whereas summertime dermal synthesis
can be viewed as a supplement (“top-up”) to help generate win-
DISCUSSION tertime tissue stores of vitamin D, individual variation is likely to
be high, which makes summertime dermal synthesis an unreli-
The RDA for nutrients is generally established as the average able contributor to vitamin D status. In the current study, sun
daily intake level that is sufficient to meet the nutrient require- exposure preference was assessed as a surrogate for tissue stores;
ment for nearly all (97–98%) persons in a life-stage and sex group as expected, whereas most people liked some (앒50%) or a lot
(1, 5). Uncertainty and gaps in the available data about the rela- (앒38%) of sun, 앒12% of subjects were sun avoiders. One might
tive contribution of sunshine and diet to vitamin D status and
expect this minority of subjects to have the highest dietary re-
vitamin D requirements for health maintenance have presented
quirement for vitamin D in winter as a consequence of their low
international authorities with considerable difficulty in setting
tissue stores. In fact, the vitamin D intake required to maintain
dietary requirements for vitamin D. An approach that prioritizes
serum 25(OH)D concentrations in late winter above 25 nmol/L
TABLE 3
Estimated dietary requirements for vitamin D at selected percentiles in 215 men and women aged 20 – 40 y to maintain serum 25-hydroxyvitamin D
关25(OH)D兴 concentrations above selected biochemical cutoffs during winter1
g/d
Serum 25(OH)D 쏜25 nmol/L — 2.7 (0.0, 4.7) 5.9 (3.6, 8.0) 8.7 (6.5, 11.1)
Serum 25(OH)D 쏜37.5 nmol/L 2.3 (0.0, 4.2) 13.8 (12.1, 15.9) 17.0 (14.8, 19.9) 19.9 (17.2, 23.5)
Serum 25(OH)D 쏜50 nmol/L 10.2 (8.9, 11.4) 21.7 (19.3, 25.0) 25.0 (21.9, 29.1) 28.0 (24.2, 32.8)
Serum 25(OH)D 쏜80 nmol/L 23.1 (21.0, 26.0) 34.8 (30.4, 40.6) 38.3 (33.0, 44.8) 41.1 (35.4, 48.7)
1
All values are estimate; 95% CI in parentheses. Results were based on a log-linear model of serum 25(OH)D as a function of vitamin D intake; the 95%
CIs were calculated by using a bias-corrected bootstrap based on 10 000 replications.
2
The vitamin D intake value that will maintain serum 25(OH)D concentrations in 50% of 20 – 40-y-old adults above the indicated cutoff during winter.
DIETARY VITAMIN D REQUIREMENT IN HEALTHY ADULTS 1541
Survey data from the UK NDNS showed that up to 20% of UK accuracy with which we can estimate the dietary requirement to
adults 19 –34 y old (whose median vitamin D intake was 2.5 achieve such high serum 25(OH)D concentrations. To absolutely
g/d) have plasma 25(OH)D concentrations of 쏝25 nmol/L confirm that our recommended intakes can achieve 25(OH)D
(14), which underscores our findings. We acknowledge that cu- concentrations in the range of 50 to 80 nmol/L, a wintertime
taneous vitamin D synthesis during summer months probably intervention study using higher doses of vitamin D (at least
offsets the dietary requirement for vitamin D that would ensure 20 – 40 g/d) would be required.
adequacy during wintertime. However, it is worth noting that the In conclusion, to ensure that the needs of 쏜97.5% of 20 – 40-
percentage of the population with unprotected sun exposure may y-old persons are met in relation to vitamin D status during
be rapidly declining, as a consequence of public education cam- winter, 8.7 g vitamin D/d is required to maintain serum
paigns in relation to skin cancer (27). 25(OH)D concentrations above the most conservative threshold
In the current analysis, we placed strong emphasis on using a of adequacy (ie, 25 nmol/L).
cutoff of 25 nmol/L for serum 25(OH)D on the basis that con-
The authors’ responsibilities were as follows: MK, JMWW, AF, MPB,
centrations of 앒20 –27.5 nmol/L are considered to be consistent EMD, JJS, and KDC: the conception of work and are grant holders; TRH, NT,
with vitamin D deficiency and rickets or osteomalacia (1, 28), AJL, KMS, GH, MSB, JMWW, MK, and KDC: the execution of the study;
and the 25 nmol/L threshold has been in use to date by various SM, NT, TRH, GH, AJL, and MB: sample analysis; and all authors: data
important authorities (1, 5, 15, 16). However, we also reported analysis and writing of the manuscript. None of the authors had a personal or
dietary requirements for vitamin D in the current sample of white financial conflict of interest.
20 – 40-y-old persons by using several other serum 25(OH)D
cutoffs (37.5, 50, and 80 nmol/L) (6, 7). The rationale for these
alternative definitions of adequacy for vitamin D in relation to REFERENCES
skeletal and nonskeletal health benefits has been detailed else- 1. UK Department of Health. Nutrition and bone health: with particular
18. Andersen R, Molgaard C, Skovgaard LT, et al. Teenage girls and elderly 26. Matsuoka LY, Wortsman J, Hollis BW. Use of topical sunscreen for the
women living in northern Europe have low winter vitamin D status. Eur evaluation of regional synthesis of vitamin D3. J Am Acad Dermatol
J Clin Nutr 2005;59:533– 41. 1990;22:772–5.
19. Webb AR, Kline L, Holick MF. Influence of season and latitude on the 27. Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vita-
cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston min D sufficiency: implications for establishing a new effective dietary
and Edmonton will not promote vitamin D3 synthesis in human skin. intake recommendation for vitamin D. J Nutr 2005;135:317–22.
J Clin Endocrinol Metab 1988;67:373–78. 28. Specker BL, Ho ML, Oestreich A, et al. Prospective study of vitamin D
20. Lucey AJ, Paschos GK, Cashman KD, Martínéz JA, Thorsdottir I, Kiely supplementation and rickets in China. J Pediatr 1992;120:733–9.
M. Influence of moderate energy restriction and seafood consumption on 29. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human
bone turnover in overweight young adults. Am J Clin Nutr 2008;87: serum 25-hydroxycholecalciferol response to extended oral dosing with
1045–52. cholecalciferol. Am J Clin Nutr 2003;77:204 –10.
21. Collins A. Development and validation of methods for the measurement 30. Weaver CM, Fleet JC. Vitamin D requirements: current and future. Am J
of micronutrient intakes relevant to bone health. Doctoral dissertation.
Clin Nutr 2004;80(suppl):1735S–9S.
The National University of Ireland, Cork, 2006.
31. Byrne PM, Freaney R, McKenna MJ. Vitamin D supplementation in the
22. Hill T, Collins A, O’Brien M, Kiely M, Flynn A, Cashman KD. Vitamin
elderly: review of safety and effectiveness of different regimes. Calcif
D intake and status in Irish postmenopausal women. Eur J Clin Nutr
2005;59:404 –10. Tissue Int 1995;56:518 –20.
23. Cashman KD, Hill TR, Cotter AA, et al. Low vitamin D status adversely 32. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to
affects bone health parameters in adolescents. Am J Clin Nutr 2008;87: prevent hip fractures in elderly women. N Engl J Med 1992;327:1637–
1039 – 44. 42.
24. Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson- 33. Krall EA, Sahyoun N, Tannenbaum S, Dallal GE, Dawson-Hughes B.
Hughes B. Estimation of optimal serum concentrations of 25- Effect of vitamin D input on seasonal variations in parathyroid hormone
hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 2006; secretion in postmenopausal women. N Engl J Med 1989;321:1777– 83.
84:18 –28. 34. Kyriakidou-Himonas M, Aloia JF, Yeh JK. Vitamin D supplementation
25. Kinyamu HK, Gallagher JC, Balhorn KE, Petranick KM, Rafferty KA. in postmenopausal black women. J Clin Endocrinol Metab 1999;84:
3988 –90.