Transcript Slide 1

Vitamin D:
Tilting the Odds in your Favor
D
D
D
Karen Rafferty, RD, LMNT
Owner, Nutrition Science Resource
Iowa Dietetic Association
Annual Meeting
November 5, 2009
Scope of presentation
I.
Skeletal and non-skeletal
functions of vitamin D
II.
Optimal vitamin D status
III. Treatment strategies: sources
and amounts of vitamin D
The function of vitamin D
In the mid 1990s, the IOM revisited the
nutrient intake recommendations for the
bone-related nutrients
Vitamin D was one of the five
re-evaluated – 1997 DRI (AI)
The function of vitamin D
What we knew:
 Vitamin D prevented rickets
 The RDA for vitamin D was sufficient
to afford protection
 Vitamin D was important for calcium
absorption
Functional indicator of vitamin D




0
Blood level of vitamin D
Serum 25(OH)D
1 ng/ml (= 2.5 nmol/L) – clinical
1 nmol/L (= .4 ng/ml) – research
25
50
75
10
20
30
ng/ml
ng/ml
ng/ml
(nmol/L)
100
125
150
The function of vitamin D
What we didn’t know:
 Was there a connection between
vitamin D status and any other
(non-skeletal) disease?
 What is the optimal serum 25(OH)D
level?
 What is the dose-response?
Evidence base
Disease
Status of Evidence
osteoarthritis/RA
falls/neuromuscular function
multiple sclerosis
fibromyalgia
type I diabetes
insulin sensitivity
cardiovascular disease
periodontal disease
various cancers
tuberculosis
hypertension
+
++++
++
++
++
++
++
++
++++
+++
++
Evidence base
Prevention of
rickets/osteomalacia
0
25
(nmol/L)
50










75
calcium absorption
falls/neuromuscular function
multiple sclerosis
fibromyalgia
type I diabetes
insulin sensitivity
cardiovascular disease
periodontal disease
various cancers
tuberculosis
?
100
reference range “normal”
125
150
Vitamin D schemes
endocrine
kidney
1,25(OH)2D3
skin
diet
D3
gut
CaAb
liver
25(OH)D3
periphery
autocrine
1,25(OH)2D3
various
tissues
cell
signals
Vitamin D & Ca absorption
ABSORPTION
FRACTION
0.4
0.3
+68%
0.2
0.1
 34 postmenopausal women
 studied twice, one
yr apart (Spring)
 given vitamin D one
year & not the
other
0.0
0
25
(nmol/L)
50
75
100
125
150
reference range “normal”
Heaney RP et al
JACN 2003; 22:142-146
Vitamin D & Ca absorption
Bischoff et al.
(2003); JBMR
18:3243–51
Barger-Lux et al.
(2002); JCEM
87:4952–56
Heaney et al.
(2003); JACN
22:142–46
ABSORPTION FRACTION
0.5
0.4
0.3
0.2
0.1
0.0
0
20
40
60
80
100
120
140
160
SERUM 25(OH)D (nmol/L)
Heaney RP
Am J Clin Nutr 2008;88:541S-544S
Vitamin D & Ca absorption
Bischoff et al.
(2003); JBMR
18:3243–51
Barger-Lux et al.
(2002); JCEM
87:4952–56
Heaney et al.
(2003); JACN
22:142–46
ABSORPTION FRACTION
0.5
calcium absorption is
suboptimal
in the lower half of
the reference range
0.4
0.3
0.2
usual laboratory
reference range
0.1
0.0
0
20
40
60
80
100
120
140
160
SERUM 25(OH)D (nmol/L)
Heaney RP
Am J Clin Nutr 2008;88:541S-544S
Vitamin D & fractures
(hip, forearm, spine)
FRACTURE RELATIVE RISK
1.0




–33%
0.8
0.6
N = 2,686
ages 65–85
5 yr RCT
Vit D  800
IU/d
0.4
0.2
0.0
0
25
50
75
100
125
150
(nmol/L)
Trivedi DP et al
BMJ 2003; 326:469
Vitamin D & falling
1.0
–49%
0.8
Fall Risk
 122 women
 age: 63–99
 DB-RCT
 Ca 1200 mg/d
 Ca + 800 IU Vit D
 12 week duration
 25(OH)D 30 nmol/L
at baseline
0.6
0.4
0.2
0.0
Ca only
Ca + D
Bischoff et al
JBMR 2003; 18:343-351
Vit D & neuromuscular function
Performance Score
 1359 men & women;
mean age 75.5
 Amsterdam longitud.
aging study
 neuromuscular
performance
measured on a scale
of 0 to 12 (higher is
better)
9
8
7
6
5
4
3
2
1
0
0
25<25
(nmol/L)
25–50 50–75
50
>75
75
SERUM 25(OH)D
100
125
150
Wicherts et al.
JBMR. 2005.
Vit D & neuromuscular function
Assessing muscle function:
1. 8–foot walk test
2. Sit–to–stand test
Accurately predict disability
Bischoff et al
AJCN 2004; 80:752-758
Vit D & nursing home admissions
Visser et al
AJCN 2006:616-622
Vitamin D & mortality
Visser, M. et al
ACJN 2006: 616-622
Vit D & endocrine functions
Raising serum 25(OH)D
from 50 nmol/L to > 80 nmol/L :
 improves calcium absorption
 improves neuromuscular function
 reduces fracture risk and falls
 reduces nursing home admissions
0
25
(nmol/L)
50
75
100
125
150
Vit D – expanded scheme
endocrine
skin
liver
D3
25(OH)D3
kidney
gut
1,25(OH)2D3
CaBP
periphery
autocrine
CU
ORC
1,25(OH)2D3
various
tissues
cell
signals
Vit D & autocrine functions
 cell proliferation
 cell differentiation
 apoptosis
 immune response
 inflammation
Autocrine action
25(OH)D
~ 200 genes
have VDREs
VDRE
Transcription
Vitamin D & Cancer
Altoona 150 mi
Vitamin D & Cancer
 1179 healthy women
 aged 66.7
 four year trial
 three treatment groups:
 control (placebo)
 Ca (1400–1500 mg/d)
 Ca plus D3 (1100 IU/d)
 baseline 25(OH)D: 72 nmol/L
 achieved 25(OH)D: 96 nmol/L
Lappe J et al
AJCN 2007
Vitamin D & Cancer
1.00
Fraction Cancer-Free
96 nmol/L
Ca+D
0.98
0.96
Ca-only
0.94
Placebo
72 nmol/L
0.92
0.90
0
1
2
3
Time (yrs)
4
5
Lappe J et al
AJCN 2007
UV-B & breast cancer mortality
36
32
(cases/100,000/yr)
Mortality Rate – US
34
US breast CA
deaths (1970 –
1994) vs. solar
UV exposure
30
28
26
24
22
20
18
16
14
3
4
5
6
7
8
9
10
11
UV-B Exposure (kJ/m2)
Grant WB
Cancer 2002; 94:1867
Vitamin D & prostate cancer
2.5
2.0
RELATIVE RISK
 13 yr
longitudinal
study
 19,000 men
 149 cases
prostate CA
1.5
1.0
0.5
0.0
Ahonen et al, 2000
CancerCauses&Control 11:847-852
1
2
3
25(OH)D QUARTILES
4
Vitamin D & prostate cancer
2.5
2.0
RELATIVE RISK
those below the
median 25(OH)D
level were 70%
more likely to
develop prostate
CA than those
above
1.5
1.0
0.5
0.0
Ahonen et al, 2000
CancerCauses&Control 11:847-852
1
2
3
25(OH)D QUARTILES
4
Vitamin D & colon cancer
Odds Ratios of Colon CA
risk of incident
colon CA, as a
function of
baseline 25(OH)D
in the Women’s
Health Initiative
Study
3.0
2.5
2.0
1.5
1.0
0.5
0.0
< 31
31–42
42–58
>58
Serum 25(OH)D (nmol/L)
UV-B and cancer risk
“…relative immunity to cancer
is a direct effect of sunlight…”
Apperly FL
Cancer Research Vol 1, No1 (1941)
1934-1938 health statistics
Vitamin D and MS
37º N
Percent national average incidence:
40–70%
70–100%
Vitamin DCU
100–130%
130–160%
160–190%
190–220%
ORC
modified from: http://mscenter.ucsf.edu/
Vitamin D & Influenza
35
30
25
70%
20
15
10
 208 African-American
postmenopausal
women
 3 yr DB-RCT
 placebo or vit D3
 800 IU/d – 2 yrs
 2000 IU/d – 3rd yr
 BL 25(OH)D: 47 nmol/L
5
0
0
25
(nmol/L)
Placebo
50
Vitamin D
75
100
125
150
Age related change Blood pressure
mm Hg/year
Vitamin D & Blood pressure
0
0.6
0.5
20%
0.4
0.3
0.2
0.1
0.0
25
(nmol/L)
 NHANES III survey
 N=7,699 men
and women
 >18 years
 Non-hypertensive
50
<50
>80
75
25(OH)D nmol/L
100
125
150
Vitamin D & disease risk
Heaney RP
J Nutr 2008;138:1591-1595
Copyright ©2008 American Society for Nutrition
Vitamin D & disease risk










Prevention of
rickets/osteomalacia
0
25
(nmol/L)
50
75
?
calcium absorption
falls/neuromuscular function
multiple sclerosis
fibromyalgia
type I diabetes
insulin sensitivity
cardiovascular disease
periodontal disease
various cancers
tuberculosis
100
reference range “normal”
125
150
Vitamin D & disease risk
Prevention of
rickets/osteomalacia
Optimal for Ca
endocrine related
functions
Reduced relative
risk of cancer
Reduced
periodontal
disease
Lowered BP
Reduced flu
0
25
(nmol/L)
50
75
100
reference range “normal”
125
150
Prevalence of Vit. D deficiency
NHANES-III
 women
 aged 60–79
 summer
 northern states
Nebraska
 women
 aged 55–79
 adjusted year round
 41º N latitude
RELATIVE FREQUENCY
0.025
0.020
0.015
77%
10%
0.010
68%
0.005
4%
0.000
0
Vitamin DCU
20
40
60
80
100
120
140
25(OH)D (nmol/L)
ORC
Looker et al., Bone 2002; 30:771–77
Prevalence of Vit. D deficiency
Yetley EA
AJCN 2008;88:558S-564S
Copyright ©2008 The American Society for Nutrition
Prevalence of Vit. D deficiency
Eastern Nebraska &
NHANES III white
women aged 60+
Prevention of
rickets/
osteomalacia
0
25
(nmol/L)
NHANES III
Black women
age 10+
50
Outdoor agricultural
workers in the tropics
Optimal for health
related functions
75
100
reference range “normal”
Life guards at
end of summer
125
150
Sources of vitamin D
?
Body D3
stores
25(OH)D
Fish as a Vitamin D source
6
Mahi
5
Haddock
4
Cod
3
Farmed Salmon
2
Wild salmon
1
0
0
200
400
600
800
1000
1200
Vitamin D IU/3.5oz
Lu et al. JBMR 2006
Meat as a Vitamin D source
4
Beef
3
Pork muscle
2
Pork fat
1
0
0
20
40
60
80
100
Vitamin D IU/3.5 oz.
Armas et al.
unpublished data
Milk as a Vitamin D source




Skim milk (Fat Free)
1% milk (Low Fat)
2% milk (Reduced Fat)
Vitamin D (Whole milk)
Cheese as a Vitamin D source ?
HC
HC–D+
UC
UC–D+
200 IU/d *
68%
89%
20%
52%
400 IU/d †
16%
43%
< 1%
1%
0
0
0
0
> 2000 IU/d (UL)
Percentage of 149
teenage girls on
High Calcium (HC)
or Usual Calcium
(UC) diets, who met
the AI for Vit. D
* 1997 IOM Vitamin D AI
†
2008 AAP Vitamin D recommendation for all children through age 18
D+ = Vitamin D content of diet if all dairy foods were fortified with
vitamin D at the same level as fluid milk (100 IU vitamin D per 300 mg Ca)
Rafferty et al.
unpublished data
Vitamin D Supplements
Combinations:
Multi-vitamins
typical: 400 IU
Ca plus D
Fosamax plus D (400 IU/d)
Pure vitamin D3 (often hard to find)
1,000 IU Douglas Labs
Vitamin D Supplements
25
D2 vs. D3
single oral dose
50,000 IU
D2 or D3
n = 10 in each
group
 25(OH)D (nmol/L)




20
15
D3
10
5
0
-5
D2
-10
0
5
10
15
20
TIME (days)
Armas et al., 2004
25
30
Vitamin D and UV-B sunlight
At risk for low vitamin D levels:
 Northern climates, winter months
 Elderly
 Dark skinned
 Sunscreen users
 House bound/nursing home
Vitamin D & latitude
41º N
37º N
No UV-B sunrays October – March
ORCsun exposure April – September
10 – 15DCU
min/day
Vitamin
modified from: http://mscenter.ucsf.edu/
Vitamin D & latitude
225
 41% body surface
exposure for 38 hrs/wk
for 14 wks
 varying degrees of
skin pigmentation
200
25(OH)D (nmol/L)
 26 male outdoor
workers
175
150
125
100
75
50
25
0
Late
summer
Armas L. et al. 2007
J Am Acad Dermatol 57:588.
Late
winter
Vitamin D and aging
SERUM D3 (ng/mL)
40
30
 whole body exposure
of 0.032J/cm2
(~1MED)
20
 young: age 20–30
old: age 62–80
Old
Young
10
0
0
1
2
3
4
5
TIME (days)
6
7
Holick et al
Lancet 1989
Vitamin D and aging
(g/6.25 cm2)
7- DEHYDROCHOLESTEROL
9
8
7
6
–50%
5
4
 surgically
obtained skin
samples
 Caucasian pts.
3
2
1
0
0
20
40
60
AGE
80
100
McLaughlin & Holick
JCI 1985 76:1536–38
Vitamin D and skin color
 72 males and females
 19-49 yrs
 Various skin tones
 90% skin exposed to
UVB 3x weekly for 4 weeks
HOUV-A II UV light booth (National Biological Corp.)
Vitamin D and skin color
60
50
40
2x
Darker skinned
subjects required
twice as much UVB
light to raise Vitamin
D levels as lighter
skinned subjects
Minutes of July noon sun
70
30
20
10
0
Dark
Light
Armas L. et al. 2007
J Am Acad Dermatol 57:588
Vitamin D and sun-screen
 SPF 8 reduces
Vitamin D
production by 95%
25
20
95 %
 SPF 15 reduces
Vitamin D
production by 99%
Rise in Vitamin D3 Concentrations
ng/mL
30
15
10
5
0
No SPF
SPF 8
Matsuoka JCEM 1987
WHO annual global disease
burden due to UVR exposure
 1.6 million Disability Adjusted Life Yrs
due to UVR over exposure
 3.3 billion Disability Adjusted Life Yrs
due to UVR under exposure
x 2000
Lucas RM
Int J Epidemiology 2008
Vitamin D dose response
D3 dose
(IU/d)
 66 males
 aged 38.7 yr
( 11.2 )
 dosed with vit
D3 from
October –
February
25(OH)D (nmol/L)
250
10,000
200
5,000
150
100
1,000
0
50
0
0
Ilahi M. et al 2008
Am J Clin Nutr 87:688.
20
40
60
80
100
TIME (days)
120
140
160
Vitamin D dose response




Vitamin D3
100,000 IU
by mouth
one time
Serum 25(OH)D (nmol/L)
110
100
90
80
70
60
0
Ilahi M. et al 2008
Am J Clin Nutr 87:688.
20
40
60
Time (days)
80
100
120
Vitamin D dose response
150 IU ↑ 25(OH)D levels ≈ 1 ng/ml
150 IU raises 25(OH)D ~
1000 IU raises 25(OH)D ~
1500 IU raises 25(OH)D ~
2000 IU raises 25(OH)D ~
2.5 nmol/L
17 nmol/L
25 nmol/L
33 nmol/L
Clinical Recommendations
Baseline values
62-80 nmol/L
37-62 nmol/L
< 37nmol/L
Dose
1,000 IU/daily
2,000 IU/daily
3,000 IU/daily
Safety at high doses
 in our experiments, doses of 5,000–10,000
IU/d in healthy adults for 4–5 months have
not:


elevated serum Ca
elevated urine Ca
 further, these doses reproduce 25(OH)D
levels frequently found at end of summer in
outdoor workers – at which levels no
hyperabsorption of calcium occurs
Serum 25(OH)D (nmol/L)
Safety at high doses
1,800
1,600
no toxicity
below
30,000
1,400 IU/d
15 studies of adults
receiving vitamin D
supplementation
(means)
1,200
1,000
8 studies reporting
toxicity (individual
values)
800
600
400
no toxicity below 500
nmol/L (200 ng/mL)
200
0
1,000
10,000
100,000
1,000,000
Vitamin D Intake (IU/day)
10,000,000
Safety at high doses
UL: 10,000 IU/d
Hathcock et al.,2007
AJCN 85:6–18
CONCLUSIONS
 vitamin D sufficiency can no longer be
defined as the mere absence of rickets
 vitamin D acts in multiple systems
 serum 25(OH)D levels below 80
nmol/L are not adequate for optimal
health outcomes
 inputs from all sources combined
(needed to sustain 80 nmol/L) are in
the range of ~ 2,000 – 4,000 IU/day
Ask physician to include serum
vitamin D with scheduled blood work
Thank You