Micronutrientes

VITAMINAS E MINERAIS

Nutrição no Exercício Físico e Desporto Pedro Carrera Bastos, 2013

COMPOSIÇÃO DO CORPO HUMANO
Elementos gasosos Proporção no corpo
humano
Oxigénio 65%
Hidrogénio 10%
Nitrogénio 3%
Subtotal 78%
Minerais
Carbono 18.5%
Cálcio 1.2%
Fósforo 1.0%
Potássio, Enxofre, Sódio, Cloro, 1.2%
Magnésio
Vitaminas e outros nutrientes 0.1%
Total 100%

Colgan, M. Sports nutrition guide – Minerals, vitamins & antioxidants for athletes. Apple Publications, 2002

FONTES DE NUTRIENTES

Nutrientes Fontes
Oxigénio Ar e água
Hidrogénio Ar e água
Carbono Base estrutural de todos os
alimentos
Nitrogénio Proteínas
Restantes elementos Distribuição heterogénea em
vários alimentos


VITAMINAS E OUTROS NUTRIENTES

Vitaminas Vitaminas Outros
hidrossolúveis Lipossolúveis micronutrientes
Vitamina B1 Vitamina A Colina
Vitamina B2 Vitamina D Betaína
Vitamina B3 Vitamina E PABA
Vitamina B5 Vitamina K Fitonutrientes
Vitamina B6
Vitamina B12
Ácido Fólico
Biotina
Vitamina C


MINERAIS
Macrominerais Microminerais
Cálcio Ferro
Fósforo Zinco
Potássio Cobre
Enxofre Iodo
Sódio Crómio
Cloro Selénio
Magnésio Manganês
Molibdénio
Sílicio
Boro
Vanádio
Flúor
Cobalto
Arsénico, Estanho e Níquel

Stipanuk. MH. Biochenical, Physiological, Molecular aspects of Human Nutrition. Saunders, 2006

–1 –1
as
96
. A central
see
tween
–1
as
A. central
94

tral

1,25(OH)2D3

Vitamina D3
86

25OHD3

86,97,98
. α

,97,98
. 86,97,98
. 99
α
α
Hart PH, et al. Nature Rev Immun 2011;11:584–596

Ca
Duodeno: 8-10%
Ceco e Cólon: % pequena
Íleo: Maior parte

Ca

Duodeno: 8-10%
Ceco e Cólon: % pequena
Íleo: Maior parte

Christakos S. Arch Biochem Biophys. 2012 Jul 1;523(1):73-6

Ca

Ca

Ca

Ca

Ca

Christakos S. Arch Biochem Biophys. 2012 Jul 1;523(1):73-6

Ca
TRPV6

Ca

Ca

Ca
TRPV6

Ca

Figure 2. Comparing the Risk of the Risk of Hip and Nonvertebral Fractures Between Vitamin D (700-800 IU/d) and Control
re 2. Forest PlotsForest Plots ComparingHip and Nonvertebral Fractures Between Vitamin D (700-800 IU/d and 400IU/d and 400 IU/d) and Con
ps Groups

Hip Fracture
Hip Fracture Nonvertebral Fracture
Nonvertebral Fracture

Source
Fracture Prevention With
Favors Vitamin D Favors Control
Source
Favors Vitamin D
Favors Control

Vitamin D Supplementation
Source Source
Vitamin D 700-800 IU/d 700-800 IU/d
Vitamin D Vitamin D 700-800 IU/d D 700-800 IU/d
Vitamin

17 Pfeifer et al,15 2000
Chapuy et al,17 Chapuy et al, 2002 Pfeifer et al,15 2000
A Meta-analysis of Randomized Controlled Trials
2002

Chapuy et al,17 2002
12
Chapuy et al,12 Chapuy et al,
1994 1994
Heike A. Bischoff-Ferrari, MD, MPH Chapuy et al,12 1994
Context The role and dose of oral vitamin D supplementation in nonvertebral f
18 Walter C. Willett, DrPH ture Dawson-HughesDawson-Hughes well 14 1997
prevention have not been et al, established.
Trivedi et al,18 2003 et al, 2003
Trivedi et al,14 1997
John B. Wong, MD Objective To estimate the effectiveness of vitamin D supplementation in prev
Trivedi et 18
Trivedi et nonvertebral al, 2003 in older persons.
18
Edward Giovannucci, ScD ing hip and al, 2003 fractures
Pooled Pooled Thomas Dietrich, MPH Data Sources A systematic review of English and non-English articles using MEDL
Pooled Pooled
and the Cochrane Controlled Trials Register (1960-2005), and EMBASE (1991-20
Bess Dawson-Hughes, MD Additional studies were identified by contacting clinical experts and searching bibl

F
0.2 0.2
0.5 1.0 0.5 1.0 5.0 5.0 0.2 0.5 0.2 1.0 0.5 1.0 5.0 5.
raphies and abstracts presented at the American Society for Bone and Mineral Rese
RACTURES CONTRIBUTE SIGNIFI- (1995-2004). Search terms included randomized controlled trial (RCT), controlled c
cantly to morbidity and mortal- cal trial, random allocation, double-blind method, cholecalciferol, ergocalciferol,
Vitamin D 400 Vitamin D 400 IU/d
IU/d
ity of older persons. Hip frac- Vitamin D 400 humans, elderly, falls, and bone density.
hydroxyvitaminIU/d fractures, IU/d
Vitamin D 400 D,
tures increase exponentially Study Selection Only double-blind RCTs of oral vitamin D supplementation (c
Meyer et al,16 2002 et al,16 2002
Meyer Meyer et al,16 2002Meyer et al,16 2002
with age so that by the ninth decade of lecalciferol, ergocalciferol) with or without calcium supplementation vs calcium sup
life, an estimated 1 in every 3 women mentation or placebo in older persons (Ն60 years) that examined hip or nonverte
and 1 in every 6 men will have sus- fractures were included.
tained a hip fracture.1 With the aging Data ExtractionLips et al,13 1996 extraction of articles by 2 authors using predef
Lips et al,13 1996 et al,13 1996
Lips Lips et al,13 1996 Independent
of the population, the number of hip data fields, including study quality indicators.
fractures is projected to increase world- Data Synthesis All pooled analyses were based on random-effects models. Five R
wide.2 The consequences of hip frac- for hip fracture (n=9294) and 7 RCTs for nonvertebral fracture risk (n=9820) met
Pooled Pooled Pooled
tures are severe: 50% of older persons inclusion criteria. All trials used cholecalciferol. Heterogeneity among studies for both
Pooled
have permanent functional disabili- and nonvertebral fracture prevention was observed, which disappeared after pooling R
0.2 15% to 25% require long-term 5.0 low-dose (400 IU/d) and higher-dose0.2 1.0 D 0.5
ties,0.5
0.2 1.0 0.5 1.0 5.0 with 0.2 0.5 vitamin (700-800 IU/d), separately.5.
1.0 5.0 A
nursing home care, CI) Risk (95%20% die 2tamin D dose of 700 to 800 IU/d reduced the relative riskCI) Risk (95% CI) by 26%
Relative Risk (95% and 10% to CI)
Relative
JAMA.
005;293:2257-‐2264

Relative Risk (95% (RR) of hip fracture
Relative
within 1 year.3-6 Besides the personal RCTs with 5572 persons; pooled RR, 0.74; 95% confidence interval [CI], 0.61-0.88)
es represent relative risks (RRs) and size(RRs) and sizeproportionalis proportionalthe the size of the fracture by95%represent 95% confidenceTrials are sortedTrials are so
Squares represent relative risks of squares is of squares to the size ofany trials. Error bars represent bars confidence with 6098 persons; pooled RR, 0.77; 9
to nonvertebral trials. Error 23% (5 RCTs intervals (CIs). intervals (CIs). by
burden, hip fractures account for sub- 12,17,18 12,17,18

Holick
MF.
J
Clin
Invest.
2006
Aug;116(8):2062-‐72

×

3, Vol 78 Musculoskeletal Pain and Severe Hypovitaminosis D 1463

vere Hypovitaminosis D in Patients
Nonspecific Musculoskeletal Pain Vol 78
Mayo Clin Proc, December 2003, Musculoskeletal Pain and

F, Original Article
MD, MTS, AND JOANNA M. QUIGLEY, BA

mine the prevalence of hypovita- whom were younger than 30 years. Five patients, 4 of whom
care outpatients with persistent, were aged 35 years or younger, had vitamin D serum levels
Prevalence of Severe Hypovitaminosis D in Patients
etal pain syndromes refractory to below the level of detection. The severity of deficiency was
disproportionate by age for young women (P<.001), by sex
ds: In this cross-sectional study, for East African patients (P<.001), and by race for African
With Persistent, Nonspecific Musculoskeletal Pain
consecutively between February
h persistent, nonspecific muscu-
American patients (P=.006). Season was not a significant
factor in determining vitamin D serum levels (P=.06).
mmunity University Health Care • Conclusion: All patients with persistent, nonspecific
iliated inner city primary care musculoskeletal pain are at high risk for the consequences
nn (45 north). Immigrant (n=83) of unrecognized and untreated severe hypovitaminosis D.
G REGORYto A. P
) persons of both sexes, aged 10 LOTNIKOFF , MD, MTS, J
AND OANNA
This risk extends to those considered at low risk for vita- M. QUIGLEY, BA
ethnic groups were screened for min D deficiency: nonelderly, nonhousebound, or nonimmi-
25-hydroxyvitamin D levels were grant persons of either sex. Nonimmigrant women of
unoassay. childbearing age with such pain appear to be at greatest
• Objective: To misdiagnosis or delayed diagnosis. Because osteo-
can American, East African, His-
dian patients, 100% had deficient
risk for determine the prevalence of hypovita-
malacia is a known cause of persistent, nonspecific muscu-
whom were younger than 30 ye
ng/mL). Of all patients, 93% (140/D in primary screening all outpatients with such pain for
minosis loskeletal pain, care outpatients with persistent, were aged 35 years or younger,
nonspecific musculoskeletal pain standard practicerefractory to
of vitamin D (mean, 12.08 ng/mL; hypovitaminosis D should be syndromes in clinical below the level of detection. Th
, 11.18-12.99 ng/mL). Nonimmi- care.
standard therapies.
evels as deficient as immigrants Mayo Clin Proc. 2003;78:1463-1470 disproportionate by age for yo
• Patients and Methods:of In thisCI = confidence interval; study,
n D in men were as deficient as in
tients, 28% (42/150) had severely
ANOVA = analysis variance; cross-sectional for East African patients (P<.0
150 patients presented consecutively between February
ls (≤8 ng/mL), including 55% of
PTH = parathyroid hormone American patients (P=.006). S

Clin Rheumatol (2007) 26:1895–1901
DOI 10.1007/s10067-007-0603-4

ORIGINAL ARTICLE

Hypovitaminosis D in female patients with chronic
low back pain
Ahmed Lotfi & Ahmed M. Abdel-Nasser &
Ahmed Hamdy & Ahmed A. Omran &
Mahmoud A. El-Rehany

Received: 7 October 2006 / Revised: 4 March 2007 / Accepted: 5 March 2007 / Published online: 22 March 2007
# Clinical Rheumatology 2007

Abstract Chronic low back pain (LBP) is an extremely had significantly lower 25 OHD levels (p<0.05)
common problem in practice, where it is often labeled significantly higher PTH (p<0.05) and ALP (p<0.
idiopathic. No sufficient studies have been conducted to than controls, although there were no significant g
analyze the contribution of hypovitaminosis D to the eti- differences in calcium and phosphorus. Hypovitaminos

International Journal of Rheumatic Diseases 2010; 13: 340–346

ORIGINAL ARTICLE

Association between nonspecific skeletal pain and vitamin
D deficiency
Behzad HEIDARI,1 Javad Shokri SHIRVANI,1 Alireza FIROUZJAHI,2 Parnaz HEIDARI3 and
Karim O. HAJIAN-TILAKI4
1
Deparment of Medicine, Division of Rheumatology, 2Deparment of Pathology and Laboratory Medicine, Rouhani Hospital, Babol
University of Medical Sciences, Babol, 3Faculty of Medicine, Islamic Azad University, Tehran and 4Department of Social Medicine,
Babol University of Medical Sciences, Babol, Iran

Abstract
Background: Deficiency of vitamin D has been reported in patients with many types of musculoskeletal pain.

RECEPTORES EM VÁRIAS CÉLULAS

Catelicidina

Holick
MF.
J
Clin
Invest.
2006
Aug;116(8):2062-‐72

Lipopolysaccharide
or tuberculosis
TLR-2/1 tubercle Cytokine regulation

Activated T lymphocyte
VDR-RXR

Increased Tuberculosis
tubercle Immunoglobulin
cathelicidin
synthesis
Increased VDR
Increased 1-OHase 1,25(OH)2D
Activated B lymphocyte

25(OH)D

1-OHase

1,25(OH)2D
VDR–RXR
24-OHase
25(OH)D
>30 ng/ml Calcitroic
Acid Enhances p21 and p27
Inhibits angiogenesis
Induces apoptosis

1-OHase
VDR–RXR 1-OHase 1,25(OH)2D Increased
1,25(OH)2D insulin
Decreased
Decreased
parathyroid renin
hormone
Holick M. NEJM 2007;357:266-81.

Parathyroid
hormone regulation Blood pressure regulation Blood sugar control

Figure 2. Metabolism of 25-Hydroxyvitamin D to 1,25-Dihydroxyvitamin D for Nonskeletal Functions.

Virology Journal 2008, 5:29

VITAMINA D E GRIPE

25
cr
N = 104 Placebo vs 104 Vit D ex
20 m
15 th
a
10
se
5 of
0
Winter Spring Summer Autumn
In
Placebo 800 IU/d 2000 IU/d
ap
Figure
season 2
Incidence of reported cold/influenza symptoms according to In
Incidence ofJJ, Zasloff M, Garland CF, Scragg R, Giovannucci E. Virol symptoms
Cannell reported cold/influenza J. 2008 Feb 25;5:29.
lu
according to season. The 104 subjects in the placebo m

Diabetologia (2008) 51:1391–1398 1393

45
Sardinia, Italy

40

Finland

35

Aberdeen, UK
Diabetes incidence rate per 100,000

30
Prince Edward Island,
Sweden
Canada

25
Canterbury, New Zealand Alberta,
Canada Norway

Oxford,
Tierra del Fuego, Argentina 72
20 77 UK
Kuwait

Puerto Rico Plymouth, 40
61 64 UK
Alabama, 71
15 US Virgin Islands
USA 48
New South Wales, Lux .
97 68 49 The Netherlands
Australia
45 50 44
10 Montevideo, 3 38 Estonia
Uruguay 2 62 43
52 Lithuania
67
Sao Paulo, Brazil 63 Latvia
Bogota, Dominica
Cordoba, Argentina 31 39 59 36
Columbia Sudan 8 4
5 80 5 Oran,
65 Wielkopolska,
82 Barbados Algeria Poland
Cuba 9 32 33
Santiago, Chile 87 7 29 34 23 16 10
88 90 25 17 21
0
–60 –50 –40 –30 –20 –10 0 10 20 30 40 50 60 70
Latitude (º)
Fig. 1 Age-standardised incidence rates of type 1 diabetes per Madeira Island, Portugal; 64. Portalegre, Portugal; 65. Bucharest,
100,000 boys <14 years of age, by latitude, in 51 regions worldwide, Romania; 67. Slovakia; 68. Catalonia, Spain; 71. Leicestershire, UK;
2002. Data points are shown by dots; names shown adjacent to the 72. Northern Ireland, UK; 77. Allegheny, PA, USA; 80. Avellaneda,

MS) IS 25-hydroxyvitamin D levels either by 2
mmon partment of Defense Serumsome as yet Multiple sclerosis cases were identified through
Repository. unknown effect on vita- 3
ses in Army and Navy physical disabilitymetabolismfor 1992 through 2004, and diagnoses collection
min D databases or, more likely, by Age at first serum sample
ecting Serum 25-Hydroxyvitamin D Levels
were confirmed by medicalchanges in behavior—because heat matched to 2 con- (%) unless o
record review. Each case (n=257) was *Data are expressed as No.
trols by age, sex, race/ethnicity, and dates of blood collection. Vitamin“Methods”to 100% of text forof mis
commonly exacerbates MS symp- ‡See D status was
†Does not total because
States
vailing and Risk of Multiple Sclerosis
estimated by averaging 25-hydroxyvitamin D levels of 2 or more serum samples col-
lected before the date of initial multiple sclerosis symptoms.
section defini

ne dis- Kassandra L. Munger, MSc
Main Outcome Measures Odds ratios of multiple sclerosis evidence suggests thatcon- D Among W
Context Ratios of MS and experimental associated with high
Figure. Odds Epidemiologicalby Quantile of Serum 25-Hydroxyvitaminlevels of vi-
ent or Lynn I. Levin, PhD, MPH
tinuous or categorical levels (quantilespotent immunomodulator, may decrease the risk of multiple25-
tamin D, a
or a priori–defined this hypothesis. of serum sclerosis. There
categories)
are no prospective studies addressing
nflam- Bruce W. Hollis, PhD
hydroxyvitamin D within each racial/ethnic group.
3.0
Whites
Objective To examine whether levels of 25-hydroxyvitamin D are associated with
tion of Noel S. Howard, MD
Results AmongDrPH (148 cases, multiple sclerosis. the risk of multiple sclerosis signifi-
Alberto Ascherio, MD, whites risk of
296 controls),

M
cantly decreased with increasing levelsSetting, and military personnelD (oddsnested case-control studythe De-
Design,
ofmillion US Participants Prospective, serum samples for a in among
25-hydroxyvitamin who have ratio [OR] stored
1.36
al dis- ULTIPLE SCLEROSIS (MS) IS more than 7 1.07 1.07
50-nmol/L increase in 25-hydroxyvitaminDefense Serum Repository. Multipleinterval, 0.36-0.97). through
among the most common partment of 1.0 0.59; 95% confidence sclerosis cases were identified
1 D,
crease In categorical analyses using the lowest quintile (Ͻ63.3 nmol/L) as the 1992 through the ORs diagnoses
neurological diseases in Army and Navy physical disability databases0.74 reference, 2004, and
for 0.75

Odds Ratio
titude, young adults, affecting were confirmed by medical record review.(P=.02 (n = 257) was across to 2 con-
Each case
for each subsequent quintile were 0.57, 0.57, 0.74, and0.57 dates of blood collection. Vitamin D status was
0.57 0.38 for trend
matched
trols by age, sex, race/ethnicity, and
uator.3 350 000 individuals in the United States estimated by averaging 25-hydroxyvitamin D levels of 2 or more serum samples col-
quintiles). Only the OR for the highest quintile, corresponding to 0.40 25-hydroxyvitamin D
0.38
and 2 million worldwide.1 Prevailing lected before the date of initial multiple sclerosis symptoms.
0.30 0.30
utes to thought higher thanautoimmune dis- was significantly different from 1.00 (OR, 0.38; 95% con-
levels is that MS is an 99.1 nmol/L,
in MS fidence interval, 0.19-0.75; or Main Outcome Measures Odds ratios of multiple sclerosis risk was with con-
tinuous or categorical
relation with multiple sclerosis associated
order whereby an unknown agent P=.006). The inverse levels (quantiles or a priori–defined categories) of serum 25-
0.19
agents triggers astrong for 25-hydroxyvitamin D levels measured before age 20 years. Among
particularly T cell–mediated inflam- hydroxyvitamin=D within each racial/ethnic group.
ple of matory attack, causing demyelination of P .02 for Trend
blacks and Hispanics (109 cases, 218 0.1 Among whites (148 cases, 296 controls), the risk of multiplelev- signifi-
Resultscontrols), who had lower 25-hydroxyvitamin D sclerosis
ports a central nervous system tissue.2
els than whites, nothe global dis- associations between vitamin D and84.9-99.1 99.2-152.9 ratio [OR] for a
A striking feature of
15.2-63.2 63.3-75.3 75.4-84.8
significant cantly decreased with increasing levels of 25-hydroxyvitamin D (odds risk
multiple sclerosis
ne po- were found.
Quintile of 25-Hydroxyvitamin D, nmol/L
50-nmol/L increase in 25-hydroxyvitamin D, 0.59; 95% confidence interval, 0.36-0.97).
9 tribution of MS is a multifold increase In categorical analyses using the lowest quintile (Ͻ63.3 nmol/L) as the reference, the ORs
a po- in incidence with increasing latitude, forCases subsequent quintile were 0.57, 0.57, 0.74, and 0.3818
each 41 29 27 33 (P=.02 for trend across C
ts hor- Conclusion The results of ourquintiles).suggest that60 highest63
both north and south of the equator. 3 study Only56 OR for the circulating 57
Controls the high quintile, corresponding60 25-hydroxyvitamin D
levels of vitamin D
to C
Genetic predisposition contributes to levelsmultiple 99.1 nmol/L, was significantly different from 1.00 (OR, 0.38; 95% con-
are associated with a lower risk of higher than sclerosis.
mental this variation,4 but the change in MS bars indicate 95% confidence intervals. inverse relation with multiple sclerosis risk was
Error fidence interval, 0.19-0.75; P=.006). The
JAMA. 2006;296:2832-2838 www.jama.com
(EAE), risk with migration among people of particularly strong for 25-hydroxyvitamin D levels measured before age 20 years. Among
e food common ancestry5 strongly supports a blacks and Hispanics (109 Association. All rights reserved.
©2006 American Medical cases, 218 controls), who had lower 25-hydroxyvitamin D lev-
els than whites, no significant associations between vitamin D and multiple sclerosis risk

RISCO RELATIVO DE QUEDAS AJUSTADO PARA A
IDADE EM 124 IDOSOS

NÍVEL IDEAL DE 25OHD PARA ÓPTIMA FUNÇÃO MUSCULAR
NOS MEMBROS INFERIORES

the growt
Prostate cell inhibit pr
1α,25(OH)2D3 25(OH)D3
Review line that
TRENDS in Endocrinology and Metabolism Vol.14 No.9 November 2003

to the SV
Mitochondria DU145 ce
1α-OHase
Vitamin D and prostate cancer 25(OH)D3 1α,25(OH)2D3
of 24-OHa
of Liaroz
prevention and treatment 24-hydrox
half-life o
Tai C. Chen and Michael F. Holick
Nucleus 1a,25(OH
1α,25(OH)D3
University School of Medicine, Boston, MA 02118, USA
and in cel
Vitamin D, Skin and Bone Research Laboratory, Section of Endocrinology, Diabetes and Nutrition, Department of Med

VDR RXR
might be
Human prostate cells contain receptors for 1a,25-dihy- and prodifferentiation activities of 1a,25(OH
droxyvitamin D, the active form of vitamin D. Prostate Apoptotic
analogs in prostate cells in vitro and in vivo [
Gene transcription we summarize recent findings of: (1
cancer cells respond to vitamin D3 with increases in Here Under so
differentiation and apoptosis, and decreases in prolifer- ation between vitamin D deficiency, UVR expo
ation, invasiveness and metastasis. These findings risk of prostate cancer; (2) the mechanism of a
induces 1
strongly support the use of vitamin D-based therapies Cell-cycle arrest
Apoptosis Differentiation action; (3) the identification of terminal
1a-OHase in
for prostate cancer and/or as a second-line therapy CDK2, p21, p27, p53, the evaluation of anti
Bcl-2, Bcl-XL, Mcl-1 PSA, AR if and its implications; (4)
BAG1L, deprivation fails. The association between Ki67, E-Cadherin 2D3 and itsnick in pro
androgen XIAP, cIAP1 activity of 1a,25(OH) analogs end
either decreased sun exposure or vitamin D deficiency
cIAP2 risk of prostate cancer at an earlier culture, in animal models and inassociation be
and the increased controversy that surrounds the
clinical trials
cytometri
age, and with a more aggressive progression, indicates Blutt et
polymorphism and the risk of prostate cancer
that adequate vitamin D nutrition should be a priority
TRENDS in Vitamin D Metabolism
LNCaP c
for men of all ages. Here we summarize recent advancesEndocrinology &deficiency, UV exposure and the
in epidemiological and biochemical studies of the endo- prostate cancer downregu
crine and autocrine systems associated with vitamin D An association between vitamin D deficiency a

453
death Table 3 The estimated relationship between serum calcidiol and death
arately from prostate cancer among patients receiving hormone therapy (n ¼ 97)

III RR Model I Model II Model III
CI) Variables RR (95%CI) RR (95%CI) RR (95%CI)

Calcidiol (nmol lÀ1)
Low (<
50)
1.00 (ref) 1.00 (ref) 1.00 (ref)
Medium (50-‐80)
0.39 (0.19 – 0.81) 0.35 (0.17 – 0.73) 0.18 (0.07 – 0.46)
– 0.77) High (>
80)
0.29 (0.12 – 0.68) 0.20 (0.08 – 0.50) 0.09 (0.03 – 0.27)
– 0.43)
Group status 0.08 (0.04 – 0.16) 0.06 (0.02 – 0.13)
– 0.10)
Age (1 year) 1.00 (0.94 – 1.03)

Clinical Studies
– 1.03)
Functional status
Good 1.00 (ref)
Less good 1.19 (1.04 – 1.61)
– 5.06)
– 25.7) Differentiation gradea
High 1.00 (ref)
Moderate 0.85 (0.23 – 3.18)
Low 5.63 (1.42 – 22.3)
– 1.50) a British Journal of Cancer (2009) 100, 450 – 454
Differentiation grade of tumour tissue; WHO three-grade system.
& 2009 Cancer Research UK All rights reserved 0007 – 0920/09 $32.00
www.bjcancer.com

VITAMIN D FOR CANCER PREVENTION
470 Garland et al.
arland et al. AEP Vol. AEP No. 7 No. 7
19, Vol. 19,
TAMIN D FOR VITAMIN D FOR CANCER PREVENTION
CANCER PREVENTION July 2009: 468–483 468–483
July 2009:

1.0 1.0
1.0 1.0 0.93 0.95
0.93 1.0 0.95
0.93 0.9 p trend = 0.02
p trend = 0.02
0.9
0.9
0.8 0.8
0.8 0.8
0.7 0.68 0.8
0.68
Relative risk

0.7

Relative risk
0.6 0.6
0.7

Relative risk
0.6 0.5
Relative risk

RR=0.44

Relative risk
0.4 0.6 RR = 0.28 0.5 0.4 RR=0.44 0.6
RR = 0.28 p < 0.05 RR=0.28
0.4 0.3
0.2 p < 0.05
0.3 0.2 RR=0.28
0.5
0.20
0.4 0.08 0.1 RR = 0.28 0.11
0.0
0.2
0.20 0.4
0.08
< 62.5 nmol/L > 62.5 nmol/L 0.1 p < 0.05
< 50 nmol/L 50 to <80 nmol/L0.11 > 80 nmol/L

FIGURE 1. Relative risk of breast cancer mortality, by baseline FIGURE 3. Relative risk of colon cancer mortality, by baseline
0.3
< 62.5 nmol/L > 62.5 nmol/L
serum 25(OH)D concentration, divided at the median,
0.2 1988–2000. (Source: Drawn from data in serum nmol/L 50 to <80 nmol/L > 80 nmol/L
< 50 25(OH)D concentration, in tertiles, NHANES cohort,
NHANES III cohort,
E 1. Relative risk of breast cancer mortality, by baseline FIGURE 3. Relative (Source: Drawn from data in Freedman et al. [56].) 0.2
1988-2000. risk of colon cancer mortality, by baseline
Freedman et al. [56].) divided at the median,
25(OH)D concentration, serum 25(OH)D concentration, 0.08in tertiles, NHANES cohort,
ES III cohort, 1988–2000. (Source: Drawn from data in 25(OH)D and0.1
1988-2000. (10) found that physicians whoseet al. [56].)
by quantiles of serum 25(OH)D provided a clear linear dose-
(Source: Drawn from data in Freedman
n et al. [56].) 0.0 1,25(OH)2D levels were both below the median,
response gradient (61) (Fig. 4). A serum 25(OH)D level
tiles of serum than 38 ng/mL (95 a clear<(top quintile)
62.5 nmol/L asso-
greater25(OH)D providednmol/L)linear dose- was (10) found that of 28 ng/mL (70 nmol/L) and 1,25(OH)2D of
25(OH)D physicians whose 25(OH)D and
> 62.5 nmol/L
ciated with an odds ratio of 0.45 (95% CI 0.28–0.69), cor- 32 pg/mL (77 pmol/L) had twice the incidence of aggressive
e gradient (61) (Fig. 4). A serum 25(OH)D level 1,25(OH)2D levels were both below the median,
risk Relative risk of 25(OH)D prostateng/mL (odds ratioby and 1,25(OH) p ! 0.05) as
responding to 55% lower1. of colorectal cancer compared
FIGURE quintile) was asso- breast cancercancer (70 nmol/L) the median. 2D of FIGURE
of 28 mortality,
2.1, 95% CI 1.2–3.4,
baseline
than 38to individuals with 25(OH)D of less than 16 ng/mL (40
ng/mL (95 nmol/L) (top men whose levels were above
serum 25(OH)D concentration, divided case-control incidence ofKaiser Foundation 25(
with an nmol/L) (bottom quintile) CI 0.28–0.69), cor-
odds ratio of 0.45 (95% (61). 32 pg/mL (77In a nested at the study of 90 aggressive serum
pmol/L) had twice the median,
prostate cancer (odds controls 95% CI 1.2–3.4, p ! 0.05) of serum
NHANES III cohort, 1988–2000. (Source: ratio 2.1,matched on age, race, and dayas 1988-2000
ing to 55% lower risk of colorectal cancer compared cases and 91Drawn from data in
viduals with 25(OH)D of less et al. [56].) (40 men whose levels were above the median. of prostate cancer was
storage, the estimated relative risk
Prostate Freedman than 16 ng/mL
Cancer In a nested (not signiﬁcant) in men inKaiser Foundation serum
0.41 case-control study of 90 the top quartile of
) (bottom quintile) (61).
Observational studies of the inverse association of prediag- and 91 controls metabolites, speciﬁcally, 25(OH)Dserum than
cases vitamin D matched on age, race, and day of greater

AEP Vol. 19, No. 7
July 2009: 468–483
470 Garland et al.
arland et al. AEP Vol. AEP No. 7 No. 7
19, Vol. 19,
TAMIN D FOR VITAMIN D FOR CANCER PREVENTION
CANCER PREVENTION July 2009: 468–483 468–483
July 2009:

1.0 1.0 0.95
1.0 0.95
0.93 1.0 0.95
0.93 0.9 p = 0.02
0.9 0.9 p trend = 0.02= 0.02trend
p trend
0.8 0.8
0.8 0.68
0.7
0.8 0.68
Relative risk

0.7

Relative risk
0.6 0.6

Relative risk
0.7 0.6 0.5 0.68
RR=0.44
0.4 RR = 0.28
Relative risk

0.5 0.4 RR=0.44
0.6 RR = 0.28 p < 0.05
0.4 0.3 RR=0.28
0.2 p < 0.05 0.2 RR=0.28
0.5 0.3
RR=0.44 0.20
0.08 0.1 0.11
0.2
0.20
0.0
< 62.5 nmol/L
0.4 0.08 > 62.5 nmol/L 0.1 < 50 nmol/L 50 to <80 nmol/L0.11 > 80 nmol/L

0.3 > 62.5 nmol/L
FIGURE 1. Relative risk of breast cancer mortality, by baseline FIGURE 3. Relative risk ofRR=0.28 mortality, by baseline
colon cancer
< 62.5 nmol/L
serum 25(OH)D concentration, divided at the median, serum nmol/L 50 to <80 nmol/L > 80 nmol/L
< 50 25(OH)D concentration, in tertiles, NHANES cohort,

E 1. Relative risk of breast cancer mortality, by baseline from data in
NHANES III cohort, 1988–2000. (Source: Drawn
0.2 FIGURE 3. Relative (Source: Drawn from data in Freedman et al. [56].)
1988-2000. risk of colon cancer mortality, by baseline
Freedman et al. [56].) divided at the median,
25(OH)D concentration, 0.20
serum 25(OH)D concentration, in tertiles, NHANES cohort,
ES III cohort, 1988–2000. (Source: Drawn from data in
0.1 1988-2000. (10) found that physicians whoseet al. [56].)
(Source: Drawn from data in Freedman 25(OH)D and
by quantiles of serum 25(OH)D provided a clear linear dose-
n et al. [56].) 0.11
response gradient (61) (Fig. 4). A serum 25(OH)D level 1,25(OH)2D levels were both below the median,
greater25(OH)D providednmol/L)linear dose- was (10) found that of 28 ng/mL (70 nmol/L) and 1,25(OH)2D of
than 38 ng/mL (95 a clear (top quintile) asso- 25(OH)D physicians whose 25(OH)D and
L of serum with an odds ratio of 0.45 (95% CI 0.28–0.69), cor- 50 to <80 nmol/L
tiles
ciated
< 50 nmol/L 32 pg/mL (77 pmol/L) had 80 nmol/L
> twice the incidence of aggressive
e gradient (61) (Fig. 4). A serum 25(OH)D level 1,25(OH)2D levels were both below the median,
responding to 55% lower risk of colorectal cancer compared prostate cancer (odds ratio 2.1, 95% CI 1.2–3.4, p ! 0.05) as
by baseline (95 nmol/L) (top quintile) Relative risk(40 colon cancer(70 nmol/L) and 1,25(OH)2D of
FIGURE 3. than 16
than 38to individuals with 25(OH)D of lesswas asso- ng/mL of
ng/mL 25(OH)D men whose levels were above the median.
of 28 ng/mL mortality, by baseline
with an nmol/L) (bottom serum CI 0.28–0.69), cor- 32 pg/mL (77 pmol/L) had twice the incidence of aggressive
median, of 0.45 (95% (61).
odds ratio quintile) 25(OH)D concentration, In a tertiles, NHANES 90 Kaiser Foundation
in nested case-controlCI 1.2–3.4,cohort, of
study of
p ! 0.05)
prostate cancer (odds ratio 2.1,matched on age, race, and dayas serum
95%
ing to 55% lower risk of colorectal cancer compared cases and 91 controls
m data in 1988-2000. (Source: Drawn whose levels wereestimated relativeet al. prostate cancer was
viduals with 25(OH)D of less than 16 ng/mL (40 men from data in above the median. of [56].)
storage, the Freedman risk
Prostate Cancer In a nested (not signiﬁcant) in men inKaiser Foundation serum
0.41 case-control study of 90 the top quartile of
) (bottom quintile) (61).
Observational studies of the inverse association of prediag- and 91 controls metabolites, speciﬁcally, 25(OH)Dserum than
cases vitamin D matched on age, race, and day of greater

Best Practice & Research Clinical Endocrinology & Metabolism 25 (2011) 681–691

Contents lists available at ScienceDirect

Best Practice & Research Clinical
Endocrinology & Metabolism
journal homepage: www.elsevier.com/locate/beem

13

Why the minimum desirable serum 25-hydroxyvitamin D
level should be 75 nmol/L (30 ng/ml)
Reinhold Vieth, Ph.D., F.C.A.C.B., Professor a, b, c, *
a
Department of Nutritional Sciences, University of Toronto, Canada
b
Department of Laboratory Medicine and Pathobiology, University of Toronto, Canada
c
Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave, Toronto, Ontario, Canada M5G 1X5

Keywords:
The Institutes of Medicine (IOM) recently revised the recom-
mended dietary allowances (RDA) for vitamin D, to maintain

RELAÇÃO ENTRE INGESTÃO CÁLCIO E NÍVEIS SÉRICOS DE 25OHD

Ingestão
de
300
mg
Cálcio

Heaney R P Am J Clin Nutr 2008;88:541S-544S
©2008 by American Society for Nutrition

[Dermato-Endocrinology 1:4, 207-214; July/August 2009]; ©2009 Landes Bioscience

Review

In defense of the sun
An estimate of changes in mortality rates in the United States if mean serum 25-hydroxyvitamin D
levels were raised to 45 ng/mL by solar ultraviolet-B irradiance

William B. Grant

Sunlight, Nutrition and Health Research Center (SUNARC); San Francisco, CA USA

Key words: cancer, cardiovascular diseases, melanoma, respiratory infections, skin cancer, vitamin D, ultraviolet-B

Emerging scientific evidence strongly supports the beneficial rates of other diseases such as type 2 diabetes mellitus,9,10 coronary
role of vitamin D in reducing the risk of incidence and death heart disease (CHD)11 and congestive heart failure.12
from many chronic and infectious diseases. This study esti- Let us put vitamin D production into the context of human
mates increases in melanoma and nonmelanoma skin cancer history on Earth. The human species originated in the eastern
mortality rates and decreases in chronic and infectious disease portion of tropical Africa. Skin pigmentation in that region was
mortality rates in the US from the standpoint of approximately very dark to protect against the adverse effects of solar UVR,
doubling population doses of solar UVB to increase mean primarily free radical production and DNA damage leading to
serum 25-hydroxyvitamin D levels from 16 ng/mL for black melanoma and other skin cancer.13 Because UVB doses were
Americans and 25 ng/mL for white Americans to 45 ng/mL. high and clothes were not worn, sufficient UVB penetrated the

The n e w e ng l a n d j o u r na l of m e dic i n e

droxylase Circulation
review article

Medical Progress

Vitamin D Deficiency
Michael F. Holick, M.D., Ph.D.

O
rom the Department of Medicine, Sec- nce foods were fortified with vitamin d and rickets appeared
ion of Endocrinology, Nutrition, and Di- to have been conquered, many health care professionals thought the major
betes, the Vitamin D, Skin, and Bone
Research Laboratory, Boston University Reference range
health problems resulting from vitamin D deficiency had been resolved. How-
Medical Center, Boston. Address reprint ever, rickets can be considered the tip of the vitamin D–deficiency iceberg. In fact,
<20 ng/ml
equests to Dr. Holick at Boston University
School of Medicine, 715 Albany St., M-1013, 20–100 ng/ml
vitamin D deficiency remains common in children and adults. In utero and during >150 ng/ml
childhood, vitamin D deficiency can cause growth retardation and skeletal deformi-
Boston, MA 02118, or at mfholick@bu.edu.
ties and may increase the risk of hip fracture later in life. Vitamin D deficiency in adults
etabolite)
N Engl J Med 2007;357:266-81.
opyright © 2007 Massachusetts Medical Society.
can precipitate or exacerbate osteopenia and osteoporosis, cause osteomalacia and
muscle weakness, and increase the risk of fracture.
Deficiency Preferred range Intoxication
The discovery that most tissues and cells in the body have a vitamin D receptor and
that several possess the enzymatic machinery to convert the primary circulating form
of vitamin D, 25-hydroxyvitamin D, to the active form, 1,25-dihydroxyvitamin D, has
30–60 ng/ml
provided new insights into the function of this vitamin. Of great interest is the role
it can play in decreasing the risk of many chronic illnesses, including common can-
cers, autoimmune diseases, infectious diseases, and cardiovascular disease. In this
review I consider the nature of vitamin D deficiency, discuss its role in skeletal and
_ nonskeletal health, and suggest M. NEJM 2007;357:266-81. and treatment.
Holick strategies for its prevention

S ource s a nd Me ta bol ism of V i ta min D

Webb AR, Kline L, Holick MF. J Clin Endocrinol Metab. 1988 Aug;67(2):373-8.

RADIAÇÃO UV E VITAMINA D

68
Défice de Vitamina D 6 ou + meses/ano


. .   . 
Vitamina D todo o ano



Figure 1. The potential for synthesis of previtamin D3 in lightly pigmented human skin computed from annual average UVMED. The highest annual
values for UVMED are shown in light violet, with incrementally lower values in dark 2000 Jul;39(1):57-106 shades of blue, orange, green and gray
Jablonski NG, Chaplin G. J Hum Evol. violet, then in light to dark
(64 classes). White denotes areas for which no UVMED data exist. Mercator projection. In the tropics, the zone of adequate UV radiation throughout
the year (Zone 1) is delimited by bold black lines. Light stippling indicates Zone 2, in which there is not suﬃcient UV radiation during at least one month
of the year to produce previtamin D3 in human skin. Zone 3, in which there is not suﬃcient UV radiation for previtamin D3 synthesis on average for

Sunlight, UV-Radiation, Vitamin D and Skin Cancer 5

Figure 3. Influence of season, time of day in July and latitude on the synthesis of previtamin
D3 in Boston (42°N)-o-, Edmonton (52°N)-n-, Bergen (60°) - ^ - . The hour is the end of the
one hour exposure time in July. Holick copyright 2007 with permission.

cells in the kidneys. l,25(OH)2D is responsible for the maintenance of calcium homeostasis and
bone health by increasing the efficiency ofExp Med Biol.calcium absorption, stimulating osteoblast
Holick MF. Adv
intestinal 2008;624:1-15.
function and increase bone calcium resorption. It also enhances the tubular resorption of calcium
in the kidneys (Fig. 5).

Epidemiol. Infect. (2006), 134, 1129–1140. f 2006 Cambridge University Press
doi:10.1017/S0950268806007175 Printed in the United Kingdom

Epidemiol. Infect. (2006), 134, 1129–1140. f 2006 Cambridge University Press
REVIEW ARTICLE
doi:10.1017/S0950268806007175 Printed in the United Kingdom
Epidemic influenza and vitamin D
REVIEW ARTICLE

J. J. C A N N E L L 1*, R. V IE T H 2, J. C. U M H A U 3, M. F. H O L IC K 4, W. B. G R A N T 5, 1131
S. M A D R O N I C H 6, C. F. G A R LA N D 7 A N D E. G I O V A N N U C C I 8
1
Atascadero State Hospital, 10333 El Camino Real, Atascadero, CA, USA
2
J. J. C A NNHospital, PathologyT H 2Laboratory Medicine,, Department of IC K 4, W. B. GR A NT 5,
Mount Sinai E L L 1*, R. V IE and , J. C. UM H A U 3 M. F. H O L Medicine, Toronto, Ontario,
ess despite being a 35
Canada
S. M A D R O N I C H 6, C. F. G A R LA ND 7 A N D E. G I O V A N N U C C I 8
3
Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism,
mmune population National Institutes of Health, 10333 El Camino Real, Atascadero, CA, USA
1
4
2
Atascadero State Hospital, Bethesda, MD
Departments of Medicine and Physiology, Boston University School of Medicine, Boston, MA, USA
Mount Sinai Hospital, Pathology and Laboratory Medicine, Department of Medicine, Toronto, Ontario,
rates increased in 30
5
SUNARC, San Francisco, CA, USA
Canada
25(OH)D (ng/ml)

6
3 Atmospheric Chemistry Division, National Center for Atmospheric Research, Boulder, CO, USA
7
Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism,
Department of Family and Preventive Medicine, University of California San Diego, La Jolla, CA, USA
gressively lower in National Institutes of Health, Bethesda, MD
8
4 Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, USA
25Departments of Medicine and Physiology, Boston University School of Medicine, Boston, MA, USA
5
SUNARC, San Francisco, CA, USA
ng until the winter (Accepted 5 August 2006, first published Center for Atmospheric Research, Boulder, CO, USA
6

7
Atmospheric Chemistry Division, National online 7 September 2006)
Department of Family and Preventive Medicine, University of California San Diego, La Jolla, CA, USA
mmunity outbreaks 20
8
Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, USA
SUMMARY

eaked for several (Accepted 5Edgar Hope-Simpson proposed that a ‘ seasonal stimulus ’ intimately associated with
In 1981, R. August 2006, first published online 7 September 2006)
15
solar radiation explained the remarkable seasonality of epidemic influenza. Solar radiation triggers
e higher in the sky S U M M A R Y vitamin D production in the skin ; vitamin D deficiency is common in the winter,
robust seasonal
and activated vitamin D, 1,25(OH)2D, a steroid hormone, has profound effects on human
influenza virtually 10
In 1981, R.1,25(OH)2D acts as an immune system a ‘seasonal stimulus ’ intimately associated with
immunity. Edgar Hope-Simpson proposed that modulator, preventing excessive expression
solar radiation explained the remarkable seasonality of burst ’ potential of macrophages. Perhaps
of inflammatory cytokines and increasing the ‘ oxidative epidemic influenza. Solar radiation triggers
stice. Clinical case robust seasonal vitamin D production Jan. skin ; vitamin of potentMayJune JulyAug.
Aug. Sep. Oct.Nov.Dec. in the Feb. Mar.Apr. anti-microbial in the winter,
most importantly, it dramatically stimulates the expression D deficiency is commonpeptides,
Month
and activated neutrophils,1,25(OH)2D,natural killer cells, and in epithelialeffects on human
which exist in vitamin D, monocytes, a steroid hormone, has profound cells lining the
a increased from immunity. 1,25(OH)2Dthey play a immune system modulator, preventinginfection. Volunteers
respiratory tract where acts as an major role in protecting the lung from excessive expression
of inflammatory cytokines and influenza virus ‘oxidative burst ’ potentialfever and serological
inoculated with live attenuated increasing the are more likely to develop of macrophages. Perhaps
again in the days Fig. 3. Seasonal variation of 25(OH)D levels in a popu-
evidence of an immune response in the winter. Vitamin D deficiency predisposes children to
most importantly, it dramatically stimulates the expression of potent anti-microbial peptides,
which exist infections. Ultraviolet radiation (either from artificial sources or cells lining the reduces
respiratory in neutrophils, monocytes, natural killer cells, and in epithelial from sunlight)
n though a much lation-based sample of inhabitants of a small southern
respiratory tractviral respiratory infections, as does cod liver the (which contains vitamin D). An
the incidence of where they play a major role in protecting oil lung from infection. Volunteers
German town, aged 50–80 years. (Reproduced/amended
inoculated with live attenuated influenza D reducesmore likely to of respiratory and serological
interventional study showed that vitamin virus are the incidence develop fever infections in
pulation had virus- evidence of an immune response in D, or lack of it, may D deficiency predisposes children to ’.
children. We conclude that vitamin the winter. Vitamin be Hope-Simpson’s ‘ seasonal stimulus
with respiratory infections. Ultraviolet of Springer artificial sourcesand sunlight) reduces
kind permission radiation (either from Science or from Business
ning of the lethal the incidence of viral respiratory infections, as does cod liver oil (which contains vitamin D). An
Media, R O D U CstudyNS.H., 1998.)D reduces the incidence of respiratory infections in might
I N T Scharla, TIO … the characteristic microbe of a disease be a
interventional showed that vitamin symptom instead of a cause.
e beginning of its children. wishes to investigate medicine properly of it, may be Hope-Simpson’s ‘seasonal stimulus ’. Bernard Shaw
Whoever We conclude that vitamin D, or lack should
proceed thus : in the first place to consider the seasons of the
George

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