Holick Vitamin D - for Andrew Weil...

THE D-LIGHTFULVITAMIN

FOR HEALTHMichael F. Holick

Boston University Medical Center

Teaching Goals1. How to Dx Vitamin D Deficiency

A. Which Vitamin D metaboliteshould be ordered?

2. How to Tx Vitamin D DeficiencyA. Vitamin D2 vs Vitamin D3

3. What are the non-calcemic Benefits of Vitamin D?

Institute of MedicineIOM

Agency for Healthcare Research

AndQuality

Depended onRandomized Controlled Trials

RCTs

AHRQ

Ignored Association Studies

AI for Vitamin D

1997 0-50 yrs

50-70 yrs

70+ yrs

200 IU

400 IU

600 IU Need at L

east 1000 -2

000IU/d IOM RDA UL0-0.5 YEARS0.5-1 YEARS

400 IU/D 10001500

1-8 YEARS9-12 YEARS

600 IU/D 25003000

13-70YEARS 600IU/D 400070+YEARS 800IU/D 4000

Consultant and SpeakerBayerQuest DiagnosticsMerckP&G,Aventis, WarnerNational Dairy CouncilAmgenNovartis

8

And SupportFrom The

Sun

How much calcium do we need ?Who is at

Risk for

Vitamin D Deficiency

???

RICKETS

OSTEOMALACIADM,MS,RA,

HBP,CHDINFECTIONS

CANCER

VITAMIN D DEFICIENCY

OUR SKIN WAS DESIGNED

TO MAKEVITAMIN D

Do you know why I became

hypopigmented ????????

Rachitic PelvisNormal Female

Pelvis

HOW DO YOU MAKEVITAMIN D ????

7-DHC

HO

Vitamin D3HO

ΔH

CH2

PreD3

HO

Solar UV Radiation Can I make Too muchVitamin D

?????

ΔH

7-DHC

HO

PreD3

HO

Vitamin D3

HO

UV

Lumisterol3

HO H

Tachysterol3

OH

H3C

UV

UV

Suprasterol I

OH

Transvitamin D3

OH

Suprasterol II

HO

UVUV

UV

CH2

YOU CANNOT BECOMEVITAMIN D TOXIC FROM

SUN EXPOSURE

OCTOBER 1, 1918 NOVEMBER 12, 1918

UVR 1 Hr2/WK FOR6 WEEKS

1931 US GOVERNMENTPROVIDED RECOMMENDATIONSFOR SUN EXPOSURE

DermatologySocieties

FOR 40 YEARS ARE YOUSURE?????

WHAT WILL HAPPEN IF MYCHILDREN GO OUT WITHOUTSUNSCREEN ?

STEENBOCK 1920s

VITAMIN Dis

ESSENTIALFOR

BONE HEALTH

Case #1 • 7 month Old Female

• Muscle Weakness

• Tetanic seizures

• Serum calcium 4.2mg%•

BOSTON MEDICAL CENTER

MY DOCTOR SAIDBREAST MILK PROVIDESALL THE NUTRITIONMY INFANT NEEDS.

42

THERE IS LITTLE VITAMIN D

BREAST MILK

~ 25 IU/L

IS VITAMIN D DEFICIENCYA COMMON PROBLEM

FOR PREGNANT WOMEN??????

44

BOSTON MEDICAL CENTER

40 MOTHERS AND THEIR INFANTSAT BIRTH

MEASURED VITAMIN D STATUS25-HYDROXYVITAMIN D

45

70% MTVDRANK

2.3 GLASSESMILK/D

Daily Intake Vitamin D~600 IU

76% Mothers

Vitamin D Deficient

81% Newborns25(OH)D < 20NG/ML

IOM600 IU/d

47

Strong, inverse relation between maternal 25(OH)D at <22 weeks and risk of preeclampsia

Adjusted OR (95% CI) associated with a 50-nmol/l decline in 25(OH)D:

2.4 (1.1, 5.4))

20 ng/ml

Bodnar et al 07

RISK PREECLAMPSIA

49

Poster title: Maternal Vitamin D Status and Cesarean Birth: Is There a Connection?Session time: 4276.0: Tuesday, November 06, 2007: 4:30 PM-5:30 PM 0 20 40 60 80

Mother’s 25(OH)D ng/ml

Probability C-Section

Risk C-section

400 %

I NEED 1000 IU VITAMIN D/DAYTO PROVIDE ENOUGH VITAMIN D

FOR ME & MY INFANT

52

HOW MUCH VITAMIN D DOES MY MOM NEED TO PROVIDEME WITH ADQUATE VITAMIN D

??????

4000 IU/D

American Academy PediatricsBeginning at Birth

AllINFANTS need400 IU Vitamin D/d

Infants400-800 IU/d

Pregnant & LactatingWomen

2000 IU/d

55

What is a CommonSymptom of Vitamin D Deficiency ??????

Night Sweating !!!

And VAGINITIS

IOM RDA UL

1-70YEARS 600IU/D 4000

No Need To Increase Intake Pregnancy

orLactation

Case #2 • 1 Year Old Female

• Muscle Weakness

• Boney Deformities

• Failure to Thrive Osteomalacia

RX Rickets

?

We need Calcium &

Vitamin D for Strong Bones

& Teeth

IOMYou can get your

Vitamin D from Diet

Vitamin D is Rare in Foods

Dairy Fortified with Vitamin D

100 IU/Serving

100 IUof

VITAMIN D8 OZ GLASS

Did you KnowMushrooms

Make Vitamin D?????

UV-B Exposed Portabellas have 387 IU vitamin D per raw 84 gram serving.

Shrooms’ plant sterol - ergosterol -converts to vitamin D when exposed to light.

Growers can expose mushrooms to UV light to increase vitamin D levels.

UM,UM GOODUM,UM GOOD

73

BUT I EAT FISH

OILY FISHSALMON

HOW MUCH?????

5-7 Times/Week

500-1000 IU/3.5 oz

100-250 IU/3.5 oz

10-25% VIT D in FARMEDVS

WILD CAUGHT SALMON

SUMMER

UVB

PRODUCE VITAMIN D

WINTERUVB

NO VITAMIN D

???????

Jul A ug Sep Oct A pr M ay JunN ov D ec Jan F eb M ar

0

2

4

6

M onth

Seasonal Effect on Cutaneous Vitamin D Synthesis in Boston

Vitamin D Synthesis %

Webb et al

Nov-Feb0%

Can You Make Any??????

CannotMake

Vitamin DIn

WinterAbove32 N

Jul Aug Sep O ct Apr M ay JunNov Dec Jan Feb M ar

0

2

4

6

M onth

Seasonal Effect on Cutaneous Vitamin D Synthesis in EDMONTON

Vitamin D Synthesis %

Webb et al

OCT-APRIL0%

85

Great for RomanceNot for Vitamin D

10am-3pm

-1 0 1 2 3 4 5 6 7 8 9 1 01 11 21 31 41 50

5

1 0

1 5

2 0

2 5

3 0

3 5

Days

Se

rum

Co

nc

en

tra

tio

n

of

Vit

am

in D

(n

g/m

l)

Holick, 1987

Without Sunscreen

With Sunscreen

SPF30 99%

UVBUVB

Vitamin D3

Vitamin D3

~1%

SPF-30 -99%

90-95% of our Vitam in D com es from Exposure to Sunlight

HOW MUCH

SUNEXPOSURE????????????

Exposure to

1 Minimum Erythemal

Dose

~20,000 IU Vitamin D3

Does Sunlight ReallyProvide us with

Vitamin D

???????

Brot et al, Brit J Nutr (2001), 86, Suppl. 1, S97-S103

SUMMER

WINTER

Did You KnowObesity Causes

Vitamin D Deficiency?

Wow !!!

50

40

30

20

10

0Seru

m V

itam

in D

3 (n

mol

/L)

NormalWeight

*

Obese BM I>30

**

Serum Vitamin D Levels After ExposureOf Non-obese And Obese Adults To TSame Amount Of Ultraviolet Radiation

55%

4-320ng/gVitamin D Both

D2&D3

Rx Obese pts need

2-3 X vitamin D 50,000 IU vitamin D/wk

Recommendation in Boston

5 to 15 Minutes Sunlight 2-3X/wk LEGS

ARMS

5-15 MINUTES THEN

SUNPROTECTION

Time (days)

Vit

amin

D (n

g/m

l)

Effect of UVB on Serum Vitamin D Levels in Caucasian and Black Subjects

0 5 1 0 1 5 2 00

1 02 03 04 05 06 07 0

Vit

amin

D (n

g/m

l)

54 mJ/cm2

Time (days)

0 5 1 0 1 5 2 00

1 02 03 04 05 06 07 0

320 mJ/cm2

Black

Black

Caucasian

5-10 X

CAUCASIAN

0 5 1 0 1 5 2 00

1 02 03 04 05 06 07 0

54 mJ/cm2 BLACK

60 ng/ml

30 ng/ml

0 ng/ml

30-50% African Americans

Vitamin D Deficient

How Do You KnowWhat Your Vitamin D

Status Is ?????????

1,25(OH)2D

Serum 25(OH)Dis

the barometerfor

vitamin Dstatus

Excess

NormalDeficient

55 ng/ml

10 ng/ml

25(OH)DH

N

L

Normal

Deficient10 ng/ml

25(OH)D

L

CU ORC

111

SERUM 25(OH)D (nmol/L)0 25 50 75 100 125 150 175 200

SERU

M iP

TH (p

g/m

L)

0

20

40

60

80

100

120

140

25(OH)D & SERUM iPTH*

10 20 30 40 50

25(OH)D ng/ml

PTH

pg/

ml 30-40 ng/ml

Chapuy et alCU ORC

112

VITAMIN D STATUS & THE Ca ECONOMY

· 31 women· age: 63.2 + 9.3

· studied 2x – 1 yr apart in Spring

· given 10 μg 25(OH)D/day (D+)

or· no treatment (D–)

25(OH)D

D+ D–

nm

ol/

L0

20

40

60

80

100

+65%

25(O

H)D

ng/

ml

20

30

10

40

+D -DHeaney et al 2004

32 ng/ml

ExcessNormative

20-100 ng/ml

Deficient

>100 ng/ml

<20 ng/ml

25(OH)D

Preferred30-60 ng/ml

Did you know25(OH)D

Assay Most ordered AssayIn US

What does 25(OH)D2 & 25(OH)D3mean ?????

Should I just use thetotal ??

Use Total25(OH)D

Is Vitamin DDeficiency

a Health Problemfor

adults 50+ yrs?????

0

40

20

60

80

% o

f vo

lunt

eers

< 2

0 ng

/ml 25

(OH)D

Percent ADULTS>50 YRS who were vitamin D Deficient <20 ng/ml in August

White

30%

Black

84%

Hispanic

42%

Sunlight Deprivation > 65 years

25(OH)D < 10 ng/ml

In

54% community dwellers

38% nursing home

Gloth et al JAMA, 1995

Vitamin D DeficiencyIs an

unrecognizedepidemic

inadults 50+ yrs

CDC 42%

AFRICAN AMERICAN WOMENIN US AGES 15-49Y <15NG/ML

VITAMIN D DEFICIENT

37%

BMC MEDICAL STUDENTSAND RESIDENTS 18-29 y?????????????????????????VITAMIN D INSUFFICIENT

????% VITAMIN D

INSUFFICIENT

0

10

20

30

18-29(n=69) (n=69

Inci

denc

e of

Vita

min

D

Insu

ffici

ency

(%)

% VITAMIN D INSUFFICIENT <20ng/mlBMC RESIDENTS & STUDENTS

32% END WINTER

Tangpricha et al Am J Med 2002

4% END SUMMER0

20

40

60

80

100

120

Sep-00 Mar-01 Sep-01 Mar-02 Sep-02 Mar-03

Date

25(O

H)D

(nm

ol/L

)

0

1

0

20

3

0

40

48% D-DEFICIENT<20 ng/mlEND OF WINTER

MAINE GIRLS AGES 9-11

SULLIVAN,ROSEN,HOLICK

25

(OH

)D N

G/M

L

0

20

40

60

80

100

120

Sep-00 Mar-01 Sep-01 Mar-02 Sep-02 Mar-03

Date

25(O

H)D

(nm

ol/L

)

0

1

0

20

3

0

40

SULLIVAN,ROSEN,HOLICK 2002

25(O

H)D

NG

/

17% D-DEFICIENT<20 ng/ml

END OF SUMMER

MAINE GIRLS AGES 9-11

52% D-deficient

<20 ng/ml

1-5 yrs 50 %< 30 ng/ml

6-11 yrs 70 %< 30 ng/ml


• Osteomalacia

• Osteoporosis• 2º HPTH

Subclinical


PRECIPITATES &

EXACERBATES OSTEOPOROSIS

Symptoms• Generalized bone pain

• Muscle aches

• Isolated bone pain

40-60% OSTEOMALACIA

25(OH)D<5ng/ml

25(OH)D = 35ng/ml

23%

Non-immigrant and Immigrant SubjectsSerum 25-Hydroxyvitamin D Levels (ng/ml) in

35

30

25

20

15

10

5

0Non-immigrant Subjects Immigrant Subjects

150 aged 10-65 yrsBone & Muscle Pains

93% Vitamin D Deficient

Subjects With Undetectable 25-Hydroxyvitamin D

Rx NSAID, intermittent narcotic agents,SSRI, TCA, Cardiovascular

Dysthymia/MDD,DJD refractory to surgery, angina refractory to PTCASomatoform D/O?

Severe non-radicularlow back pain, intermittent chest pain,depressed mood, insomnia, weakness

AA58Male

OTC NSAID, SSRI,Neuroleptic agent

MDD/PTSDDiffuse MSK pain,fatigue, insomnia, headache, weakness

EastAfrican

35Female

OTC NSAID,Pre-natal vitaminsInsulin

Pregnancy 3rd T.Gestational DM

Severe non-radicularLBP, fatigue, depressed mood, insomnia, weakness

AA27Female

OTC and Rx NSAIDs, TCA

Dysthymia, stress reaction

Diffuse MSK pain,Fatigue, insomnia

Asian26Female

OTC and Rx NSAIDs

Dysthymia, non-DJD low back pain

Non-radicular LBP, weakness, fatigue

Cauc23 Female

MedicationsDiagnosesSymptomsRaceAge/Sex

VITAMIN D DEFICIENT

WHY DO YOU HAVE PAIN WITH

OSTEOMALACIA

???????

IT IS THE JELLO

PHENOMENON

!!!!!!!!!!!!!!!!!!!!!

142

Priemel et al.100% > 30 ng/ml

Holick There is TOOMuch scatterFor the PTH

Plateau!!!

Serum 25(OH)D (ng/mL)

20 25 30 35 40 45 50 55

OV/

BV (%

)

0

1

2

3

4

5

6IOM>20

Priemel>30 ng/ml

IOM25(OH)D > 20 ng/ml97.5 % no evidence

OSTEOMALACIA

25(OH)D> 30 ng/ml= no Osteomalacia!

151

78 Y/O MMUSCLE WEAKNESS

ATROPHY, DENERVATION

+EMG

+NCS 152

ALSSymptoms resolved

Rx VITAMIN Dprogressive painless muscle weakness with muscle atrophy,which manifests like lower motor neuron diseaseand improves after vitamin D supplementation

153 154

Time to Stand vs 25(OH)D Levels

Bischoff-Ferreri et al

~20-40 ng/ml

155 156

DID YOU KNOWVDR IS IN

SKELETAL MUSCLE!!!

157

VITAMIN D IS GOOD FOR

MUSCLE STRENGTH

158

72% Less Falls800 IU/d 5 months

159

28-32 ng/ml

JCEM 2007 160

WHITE

Mex Am

BLACK

~20-40 ng/ml

162

163

0 6 12 18 24 30 360

2

4

6

8

10

12

14

Month

Cum

ulat

ive

Inci

denc

e (%

)

After Dawson-Hughes, NEJM 1997

Incidence of Non-Vertebral Fractures in Men & Women >65yrs

Placebo

500 mg Ca 700 IU D

~58%

164

25(OH)D > 30 ng/ml

↑Muscle strength, ↑balance,

↑lower extremity function↑ BMD

↓Fall risk ↓ Fxs

TREAT VITAMIN D DEFICIENCY

50,000 IU VITAMIN D2

ONCE/WEEK

8 WEEKS

6000 IU/d

Cut in halfAdd Milk etc

MAINTAIN VITAMIN D SUFFICIENCY

50,000 IU VITAMIN D

ONCE/ 2WEEKS3000 IU/d

DEFICIENT

INSUFFICIENT

SUFFICIENT

0

20

30

40

50

60

70

0 72Time (Months)

Me

an

25(O

H)D

(n

g/d

L)

20 ng/ml

40 ng/ml6 yrs

MEAN 25(OH)D LEVELS IN PATIENTS RECEIVING 50,000 IU VITAMIN D2 EVERY 2 WEEKS FOR 6 YRS

3000 IU/d

Pietras Arch Int Med 2009 R2D2

IS D3REALLY MORE

EFFECTIVETHAN D2

????

C3PO

10

15

20

25

30

35Mean Serum Total 25(OH)D Levels

Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 7 Week 8 Week 9 Week 10 Week 11 Week 12

25

(OH

)D L

eve

l (n

g/m

l)

P=0.45

P=0.63

P=0.45

P=0.75P=0.65

P=0.27

P=0.59P=0.17 P=0.71

P=0.45 P=0.30

P=0.54

Time (weeks)

PLACEBO

1000 IU D2

1000 IU D3

Time (weeks)

Me

an 2

5(O

H)D

Levels

(ng/m

l)

0.00

2.00

4.00

6.00

8.00

10.00

12.00

14.00

16.00

1 2 3 4 5 6 7 8 9 10 11 12

Mean Serum 25(OH)D2 and 25(OH)D3 in Subjects receiving Vitamin D2

1000 IU D2

25(OH)D2

25(OH)D3

173

1000 IU Vitamin D3/d

or500 IU Vitamin D3

+500 IU Vitamin D2/d

Ch

ang

e in

Se

rum

25

(OH

)D L

eve

ls (

ng

/ml)

Time (weeks)

1 2 3 4 5 6 7 8 9 10 11 12

32

30

28

26

24

22

20

18

1000 IU D2

500 IU D2+500 IU D3

Ch

ang

e in

Se

rum

25

(OH

)D L

eve

ls (

ng

/ml)

Time (weeks)

1 2 3 4 5 6 7 8 9 10 11 12

32

30

28

26

24

22

20

18

1000 IU Vitamin D

Sufficient

No one was sufficient

WILL YOU BECOME VITAMIN D

INTOXICATED????

,ELEVATEDCa,Pi,25(OH)D

CALCIFY BLOOD

VESSELS &KIDNEYS

CU ORC

177

SAFETY AT HIGH DOSES· 33 males· aged 38.7 yr

(± 11.2 )· dosed with

vit D3 from October thru February

· 5,000 & 10,000 IU/d

Pre Post

SERU

M C

ALCI

UM (m

g/dL

)

8.0

8.5

9.0

9.5

10.0

10.5

11.0

Vieth et al 1998

10,000 IU/dIs Safe

1 MILLION IUVITAMIN D/DAY

1000 IU/TSP

KOUTIA et al NEJM 20002

Ca= 15.2 mg/dl

25(OH)D= 520 ng/ml

IT IS DIFFICULT

TO BECOMEVITAMIN D

INTOXICATED

WHO IS AT RISK FOR VITAMIN DDEFICIENCY????????

H o w m u c h c a l c i u m d o w e n e e d ?

EVERYONE

!!!!!!!!!!!!!!!

WHY SHOULDI CARE ??????

Skin

1,25(OH)2D3

25(OH)D3

Liver

25-OHase

Kidney

1α-OHase

VDR

VDR

VDR

VDR

VDR VDR

VDR

VDR

VDRVDR

VDRVDR

VDRVDR

VDR

VDREVERY TISSUE AND CELL HAS A VDR

Suda et al 1979 RX -1,25(OH)2D3

1915 8X more likely to

DieWorked Indoors

Colon Cancer M ortality Rates

1970-80 in W hite Fem alesHighest 10% for Colon Cancer Mortality

Garland & Garland. Intern J Epid. 1980

Colon Cancer M ortality Rates1970-1994

Inverse Relationshipbetween 25(OH)D Levels & Risk of Colon Cancer

Garland et al 1989

195

50% PROJECTED REDUCTION25(OH)D = 40 ng/ml



50% PROJECTED REDUCTIONWITH 480 IU/D

50% PROJECTED REDUCTIONCOLON CANCER WITH 1000 IU/D

Garland et al 2005

I HATE TAKING CALCIUM & VITAMIN DEVERY DAY

60 %Did not follow

Protocol

<12 ng/ml

253%

INVASIVE COLORECTALCANCER

8 years

Breast Cancer Mortality Inversely Correlates with Mean Solar Radiation

Breast Cancer Mortality Inversely Correlates with Mean Solar Radiation

After Garland et al., Preventive Med, 1990

Solar radiation(calories per square centimeter)

250 300 350 400 450 500 550

Bre

ast c

ance

r mor

talit

yra

te p

er 1

00,0

00

20

22

24

26

28

30

32

34

PhoenixHonolulu

TampaFort Worth

El PasoAlbequerque

San AntonioLexington

Oklahoma City

Salt Lake CityMiamiNashville

Lincoln

San Diego

OmahaAtlanta

Los AngelesBrookhaven

Omaha

New Orleans

IndianapolisLong Island

Columbus

CambridgeWashington D.C.

Cleveland

Boston

Seattle

Pittsburgh

Lynn, MAChicago

New York MORTALITY

25(OH)D = 48 ng/ml

50% LOWER RISK

By looking at the latitudinal variation ofbreast cancer mortality rates in Europe,and controlling for diet, Grant foundthat lack of UV-B from sunlight accountsfor perhaps 25% of the breast cancermortality ratesin northern Europe. 47,800 MEN

INCREASEDDECREASEDRISK

43% LOWER RISK> 400 IU/d

Premature Mortality due to Cancer with Insufficient UV-B, White Males, U.S., 1970-1994, vs. July 1992 DNA-Weighted UV-B Radiation

UV-B (kJ/m2)

3 4 5 6 7 8 9 10 11

Mor

talit

y R

ate

(cas

es/1

00,0

00/y

ear)

-10

0

10

20

30

W. Grant 2002

MORTALITY

INCREASE SUN EXPOSURE

WHITE MALES & FEMALES

y = 0.2238x + 25.905R2 = 0.1888

30

32

34

36

38

40

42

40 45 50 55 60 65

Rate (Cases per 100,000)

Latit

ude

(Deg

rees

N)

r = 0.44

latitude versus the number of all individuals diagnosed with colon cancer independent of race in the state of California.

COLON CANCER IN CALIFORNIA

INCREASE LATITUDE

MORTALITY

San Diego

San Francisco

223 224

Kaplan-Meier plot showing association of UVR exposure and age at diagnosis with prostate cancer

Age at diagnosis (years)

Pro

porti

on tu

mor

free

Lowest quartile

cumulative exposure

1.00

0.75

0.50

0.25

09080706050

C. J. Luscombe et al, The Lancet Vol 358 Num 9282, 2001

Upper three quartiles of exposure

3-5 YEARS

Lappe et al AJCN 2007

60%LESS

CANCERS1179 PM WOMEN1200MG Ca +- D3ALL CANCERS

YEARS 0-4

1100 IU D3

Girls 10-19 yrs most sun 69%

Women 20-29 yrs most sun 51%

Women 45-54 yrs most sun 0.0%Cancer Epi Biomarkers & Prev 07

25(OH)D

1,25(OH)2D

This is a REAL

CONUNDRUM!!!!!!!!!

1-OHase

25(OH)D 1,25(OH)2D

Autocrine Regulation of Cell Growth

Control of cell growth

CALCITROIC ACID

INACTIVE

Colon Cell

Gene Transcription

Apoptosis

Bcl-2Bcl-XLMcl-1

BAG1LXIAPcIAP1cIAP2

DifferentiationMATURATION

Nucleus

Cell-cycle Arrest

CDK2, p21, p27, p53Ki67, E-Cadherin

25(OH)D>30 ng/ml

RXRVDR

1-OHaseMitochondria

1,25(OH)2D3

1,25(OH)D3

~ 2000 Genes Affected

By 1,25(OH)2D236

ACTIVATED MACROPHAGES

Metabolize 25(OH)D3 to 1,25(OH)2D3

25(OH)D3 1,25(OH)2D3

Adams et al JCEM 1987

1849

Brompton Hospital Records, 38 1849

Codliver oil - Rx Tuberculosis

25(OH)D

1,25(OH)2D

Death

19K

Da

Cathelicidin mRNA

TB

1-OHase mRNA

1-OHase

Cathelicidin

TLR2/1MACROPHAGE

Liu et al Science 2006

Why is fluSeason alwaysIn the WINTER

???????

1981 Edgar Hope-SimpsonSuggested a “SEASONAL STIMULUS”

Jan-Mar

Jan-Mar25(OH)D

winter

32 ng/ml

12 ng/ml

Aloia et al 2007

2000 IU/D

90% URIs

25(OH)D=38 ng/ml 2X

Influenza A + School Children

Placebo 18.6%

+1200 IU Vitamin D 10.8%

Type 1 Diabetes/100,000Boys<14 yrs

10X

15X

Garland et al 2008

Hypponen et al. Lancet 2001

Annual age-adjusted incidence rates of type 1 diabetes, children < 14 years old, per 100,000 population, Finland, 1965-2005

15

25

35

45

55

65

1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010

Year

Inci

denc

e ra

te 1964RecommendedVitamin D intakeReduced from4500 to 2000 IU/d

Beta-ISLET CELL1,25(OH)D3

VDR +VDR +

Insulin+

Metabolic Syndrome & Type 2 Diabetes

Ca<500 mg

> 1200 mg

< 400 IU

> 800 IU

D D+

Ca

0.67

RR

Typ

e 2

DM R

R 33%

Ca > 1200 MG+

VIT D > 800 IU

Pittas et al JCEM 07

Scragg et al Diabetes Care 27:2813;04

DIABETES INVERSELY RELATED

SERUM 25(OH)D

WHITES-NH 75%

MEXICAN-AM 83%

BLACKSNO EFFECT

North-South Gradient in Mortality from MS

100%MS 35

Vitamin D Intake (>400IU/D) Inversely Related To MS

In Women

41%

Vitamin D Intake (>400IU/D) Inversely Related To RA

In Women

44%

OSTEOARTHRITIS

Rostand 1979Reported

Inverse ReationshipBetween

BP & Latitude

Association between Latitude

andBlood

Pressure

Hypertension 1997; 30:150-156262

263

PVD & 25(OH)D

80%

>29 ng/ml

PVD vs 25(OH)D Quality Heath Care Worldwide

ABBOTTRENAL GLOBALDevelopment

264

Vitamin D deficiency in humansis associated with heart failure.

RXRDNA binding

RNA Pol IICoReg

VDR

VDR

B

VDRERNA Pol II

Suppression of Renin Transcription by VDR

Activation

VDRRXR

↓ Renin

Blood Pressure

LVH

ReninRenin TGACCT TGACCT

Atherosclerosis,Inflammation,

oxidative stress

> 200 Genes inHeart & Vessels

RXR

First MI >50% Increase Associated

With Vitamin D Deficiency

Arch Int Med 2008

28 ng/ml

8-13 ng/ml

All108%

CV122%

What are the consequences of

Vitamin D Deficiency on

Our health ???

2.4 X HBP2.5 X Elevated BS4 X Metablolic Syndrome

50 Million TeensDeficient/Insufficient 49 NT Blacks 16 yrs

400 vs 2000 IU/d 4 Mos

25(OH)D 11 to 24 ng/ml 400 IU/d

25(OH)D 11 to 34 ng/ml 2000 IU/d

Significant Decrease inArterial Wall Stiffness

Dong et al JCEM 95;2010

All Cause MortalityDecreased 7%On 528 IU Vitamin D

IOMIncrease mortality 25(OH)D> 30 ng/ml

ADEQUATE VITAMIN D

IS NECESSARY FROM BIRTH-

DEATH

IS A DISEASE OF NEGLECT

VITAMIN D THERE IS NOWA MOUNTAIN OFEVIDENCE LINKINGVITAMIN D DEFICIENCY

WITH CANCER RISK & MORTALITY

AUTOIMMUNE DISEASESTYPE 1 DIABETESHYPERTENSIONTYPE 2 DIABETES

!!!!!

100 IU VITAMIN D3RAISES 25(OH)D

BY ONLY

1NG/ML.

CHILDREN & ADULTS HAVE

25(OH)D ~18 -25 ng/ml

Seru

m 2

5(O

H)D

Leve

ls (

ng

/ml)

Time (weeks)

1 2 3 4 5 6 7 8 9 10 11 12

32

30

28

26

24

22

20

18

1000 IU vitamin D/d

Sufficient

No one was sufficient

Conquer

Vitamin D

Deficiency

What is theBest

Source ofVitamin D

?

HOLICK HOW DO YOU GET

THE MESSAGE OUT ??????

MAY 04

I DO NOT ADVOCATETANNING !!!!!!!!!!!!

ANCESTORS APPRECIATION OF THESUN FOR ITS LIFE GIVING BENEFITS

UNENLIGHTENED DERMATOLOGISTSVIEW OF THE SUN’S EFFECT ON HEALTH

Galileo recanted IMPRISIONED FOR THE REST OF HIS LIFE

InquisitorsNEED

Large RCTs

Agency for Astronomical Research

AndQuality

AARQ

Need more Randomized Controlled

AstronomicalTrialsRCATs

!!!!!!!!!!!!!!!!!!!

AARQ

Need more Randomized Controlled

AstronomicalTrials

!!!!!!!!!!!!!!!!!!!

RCATs

Instituted Hand WashingPrevent Maternal & Infant

Mortality

Commited himselfInsane Asylum

Died Infection

ALWAYS WEARA SUNSCREEN

DERMATOLOGIST ADVISING ABOUT SUN EXPOSURE

NEVER BE EXPOSED

TO THE SUN !!!!!!!!!!!!!!!!!!!

Slip, Slap, Slop

87% < 20 ng/ml

87% Vitamin D Deficient end of Summer

Australian dermatologist

Schizoprehenia

Vitamin D DeficiencyAssociated with:

DepressionDementia

25(OH)D <10 ng/ml

RR=31%

YOU CAN GET IT FROM

DIET !!!

YOU CANNOT GET IT FROM

DIET

00If you and your familyare not taking at least

1000-2000 IU/dYou are

Vitamin D Insufficient

316

WHAT IS YOUR 25(OH)D LEVEL

????????

+ 2000 IU Vitamin D3+ MTV=400 IU+ 3 glasses milk += 300 IUMy Total Vitamin D= 2700 IU/d

My 25(OH)D = 52 ng/mlVitamin D Deficiency

Is TheMost COMMON

Medical Condition

VITAMIN D DEFICIENCYCAUSES CONSEQUSUN SUNSCREEN

MELANINLATITUDEWINTER

MALABSORPTIONCrohn’s Whipple’sCystic FibrosisCeliacLiver disease

Hepatic Failure

Renal FailureNephrotic syndrome

Obesity

MEDICATIONS AntiseizureGlucocorticoidsRifampinHAARTSt John’s Wart

SchizophreniaDepression

FEV1

Wheezingillnesses

Muscle weaknessMuscle aches

OsteoporosisOsteomalaciaRickets

AutoimmuneType 1 DiabetesMSCrohn’sRA

AODMSyndrome X

HBPCHD

CANCERColonBreastProstateetc.

INFECTIONSURITB

Osteoarthritis

X

Holick NEJM July 07

There Is NoDownside

To IncreasingVitamin D Intake !!!!

We NeedSensible

Sun &

Vitamin D Supplementation

Recommendations !!!!!!!!

You Do Not Need To Be A Genius To Know

This is NOT

HYPOTHESIS

Do we need toScreen everyoneFor their 25(OH)D level???????????????

No !!!!!!!

But YesBMI>30

MalabsorptionMeds/AEs., Glc

Sarcoidosis

April 1, 2010

DrHolick.com

IOM RDA UL0-0.5 YEARS0.5-1 YEARS

400 IU/D 10001500

1-8 YEARS9-12 YEARS

600 IU/D 25003000

13-70YEARS 600IU/D 400070+YEARS 800IU/D 4000

Adequate Intake 0-1 YEAR 600-1000 IU/D

1-12 YEAR 1000-2000 IU/D13+ YEARs1500-2000 IU/D

Obesity 2-3 Times more

SAFE UPPER LIMIT

0-1 YEAR 2000 IU/D1-12 YEAR 5000 IU/D13+ YEARs 10,000 IU/D DrHolick.com

Holick Vitamin D - for Andrew Weil...

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