THE D-LIGHTFUL VITAMIN FOR HEALTH Michael F. Holick Boston University Medical Center Teaching Goals 1. How to Dx Vitamin D Deficiency A. Which Vitamin D metabolite should be ordered? 2. How to Tx Vitamin D Deficiency A. Vitamin D2 vs Vitamin D3 3. What are the non-calcemic Benefits of Vitamin D? Institute of Medicine IOM Agency for Healthcare Research AHRQ And Quality Depended on Randomized Controlled Trials RCTs Ignored Association Studies AI for Vitamin D 0-50 yrs 50-70 yrs 70+ yrs 1997 200 IU 400 IU 600 IU Need at Least 1000-2000IU/d IOM RDA UL 0-0.5 YEARS 0.5-1 YEARS 1-8 YEARS 9-12 YEARS 400 IU/D 1000 1500 600 IU/D 2500 3000 13-70YEARS 600IU/D 4000 70+YEARS 800IU/D 4000
Consultant and Speaker Bayer Quest Diagnostics Merck P&G,Aventis, Warner National Dairy Council Amgen Novartis And Support From The Sun 8 Who is at How much calcium do we need? Risk for Vitamin D Deficiency??? RICKETS VITAMIN D DEFICIENCY OSTEOMALACIA DM,MS,RA, INFECTIONS HBP,CHD CANCER
OUR SKIN WAS DESIGNED TO MAKE VITAMIN D Do you know why I became hypopigmented???????? Normal Female Pelvis Rachitic Pelvis
HOW DO YOU MAKE VITAMIN D???? HO Solar UV Radiation HO 7-DHC PreD 3 ΔH Can I make Too much Vitamin D????? HO CH2 Vitamin D 3 HO 7-DHC UV HO PreD 3 UV Tachysterol 3 Vitamin D 3 ΔH CH2 HO HO H UV UV UV UV H 3 C OH Lumisterol 3 YOU CANNOT BECOME HO OH VITAMIN D TOXIC OH FROM Suprasterol II Transvitamin D 3 Suprasterol I SUN EXPOSURE
UVR 1 Hr 2/WK FOR 6 WEEKS OCTOBER 1, 1918 NOVEMBER 12, 1918 Dermatology Societies FOR 40 YEARS ARE YOU SURE????? 1931 US GOVERNMENT PROVIDED RECOMMENDATIONS FOR SUN EXPOSURE
WHAT WILL HAPPEN IF MY CHILDREN GO OUT WITHOUT SUNSCREEN? STEENBOCK 1920s VITAMIN D is ESSENTIAL FOR BONE HEALTH Case #1 7 month Old Female Muscle Weakness Tetanic seizures Serum calcium 4.2mg%
BOSTON MEDICAL CENTER MY DOCTOR SAID BREAST MILK PROVIDES ALL THE NUTRITION MY INFANT NEEDS. THERE IS LITTLE VITAMIN D BREAST MILK ~ 25 IU/L 42
IS VITAMIN D DEFICIENCY A COMMON PROBLEM FOR PREGNANT WOMEN?????? BOSTON MEDICAL CENTER 40 MOTHERS AND THEIR INFANTS AT BIRTH MEASURED VITAMIN D STATUS 25-HYDROXYVITAMIN D 44 Daily Intake Vitamin D ~600 IU 70% MTV DRANK 2.3 GLASSES MILK/D 45 76% Mothers IOM 600 IU/d 81% Newborns 25(OH)D < 20NG/ML Vitamin D Deficient 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: RISK PREECLAMPSIA 2.4 (1.1, 5.4)) 20 ng/ml Bodnar et al 07 47
Probability C-Section Risk C-section 400 % 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 49 I NEED 1000 IU VITAMIN D/DAY TO PROVIDE ENOUGH VITAMIN D FOR ME & MY INFANT HOW MUCH VITAMIN D DOES MY MOM NEED TO PROVIDE ME WITH ADQUATE VITAMIN D?????? 4000 IU/D 52 American Academy Pediatrics Beginning at Birth All INFANTS need 400 IU Vitamin D/d Infants 400-800 IU/d Pregnant & Lactating Women 2000 IU/d
Night Sweating!!! What is a Common Symptom of Vitamin D Deficiency?????? And VAGINITIS 55 IOM RDA UL 1-70YEARS 600IU/D 4000 No Need To Increase Intake Pregnancy or Lactation Case #2 1 Year Old Female Muscle Weakness Boney Deformities Failure to Thrive RX Rickets? Osteomalacia
We need Calcium & Vitamin D for Strong Bones & Teeth IOM You can get your Vitamin D from Diet Vitamin D is Rare in Foods Dairy Fortified with Vitamin D 100 IU/Serving Did you Know Mushrooms Make Vitamin D????? 100 IU of VITAMIN D 8 OZ GLASS
Shrooms plant sterol - ergosterol - converts to vitamin D when exposed to light. Growers can expose mushrooms to UV light to increase vitamin D levels. UV-B Exposed Portabellas have 387 IU vitamin D per raw 84 gram serving. UM,UM GOOD
BUT I EAT FISH OILY FISH SALMON HOW MUCH????? 73 500-1000 IU/3.5 oz 5-7 Times/Week 100-250 IU/3.5 oz 10-25% VIT D in FARMED VS WILD CAUGHT SALMON
UVB UVB WINTER SUMMER PRODUCE VITAMIN D NO VITAMIN D??????? Vitam in D Synthesis% Seasonal Effect on Cutaneous Vitamin D Synthesis in Boston 6 4 2 0 Webb et al Can You Make Any?????? Nov-Feb 0% Jul A ug Sep Oct N ov D ec J an F eb M ar A pr M ay Jun Month Cannot Make Vitamin D In Winter Above 32 N Seasonal Effect on Cutaneous Vitamin D Synthesis in EDMONTON Vitam in D Synthesis % 6 4 2 0 Webb et al OCT-APRIL 0% Jul Aug Sep O ct Nov Dec Jan Feb M ar Apr M ay Jun M onth
Great for Romance Not for Vitamin D 10am-3pm 85 Serum Concentration of Vitamin D (ng/ml) 35 30 25 20 15 10 5 0 Without Sunscreen SPF30 99% With Sunscreen -1 0 1 2 3 4 5 6 7 8 9 101112131415 Holick, 1987 Days UVB UVB SPF-30-99% 90-95% ofour Vitam in D com es from Exposure to Sunlight Vitamin D 3 Vitamin D3 ~1%
HOW MUCH SUN EXPOSURE???????????? Exposure to 1 Minimum Erythemal Dose ~20,000 IU Vitamin D 3 Does Sunlight Really Provide us with Vitamin D??????? SUMMER WINTER Brot et al, Brit J Nutr (2001), 86, Suppl. 1, S97-S103
Did You Know Obesity Causes Vitamin D Deficiency? Wow!!! Serum Vitamin D Levels After Exposure Of Non-obese And Obese Adults To T Same Amount Of Ultraviolet Radiation * 55% Serum Vitamin D 3 (nmol/l) 50 40 30 20 10 0 Normal Weight ** Obese BM I>30 Rx Obese pts need 2-3 X vitamin D 50,000 IU vitamin D/wk 4-320ng/g Vitamin D Both D2&D3 Recommendation in Boston 5 to 15 Minutes Sunlight 2-3X/wk ARMS LEGS 5-15 MINUTES THEN SUNPROTECTION Vitamin D (ng/ml) 7 0 6 0 5 0 4 0 3 0 2 0 1 0 0 Effect of UVB on Serum Vitamin D Levels in Caucasian and Black Subjects 0 5 1 0 1 5 2 0 54 mj/cm 2 CAUCASIAN 60 Caucasian ng/ml Time (days) 320 mj/cm 2 Vitamin D (ng/ml) 7 0 6 0 5 0 4 0 3 0 2 0 1 0 54 mj/cm 2 0 7 0 6 0 5 0 4 0 3 0 2 0 1 0 0 BLACK 0 ng/ml Black 0 5 1 0 1 5 2 0 Black 5-10 X 30 ng/ml 0 5 1 0 1 5 2 0 Time (days)
30-50% African Americans Vitamin D Deficient How Do You Know What Your Vitamin D Status Is????????? 1,25(OH)2D Serum 25(OH)D is the barom eterfor vitamin D status H 55 ng/ml 10 ng/ml 25(OH)D L Excess Norm al Deficie nt N
25(OH)D L 10 ng/ml Normal Deficient 25(OH)D & SERUM ipth* Chapuy et al PTH pg/ml SERUM ipth (pg/ml) 140 120 100 80 60 40 20 0 30-40 ng/ml 0 25 50 75 100 125 150 175 200 10 20 30 40 50 SERUM 25(OH)D (nmol/l) CU ORC 25(OH)D ng/ml 111 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 ) CU Heaney et al 2004 ORC 25(OH)D ng/ml 40 30 20 nmol/l 10 25(OH)D 100 80 60 40 20 0 32 ng/ml +65% D+ D +D -D 112 25(OH)D >100 ng/ml Normative 20-100 ng/ml <20 ng/ml Excess Preferred 30-60 ng/ml Deficient Did you know 25(OH)D Assay Most ordered Assay In US
What does 25(OH)D2 & 25(OH)D3 Use mean Total????? Should 25(OH)D I just use the total?? Is Vitamin D Deficiency a Health Problem for adults 50+ yrs????? Percent ADULTS>50 YRS who were vitamin D Deficient <20 ng/ml in August % of volunteers < 20 ng/ml 25(OH)D 80 60 40 20 0 30% White 42% Hispanic 84% Black Sunlight Deprivation > 65 years 25(OH)D < 10 ng/ml In 54% community dwellers 38% nursing home Gloth et al JAMA, 1995 Vitamin D Deficiency Is an unrecognized epidemic in adults 50+ yrs
CDC 42% AFRICAN AMERICAN WOMEN IN US AGES 15-49Y <15NG/ML VITAMIN D DEFICIENT BMC MEDICAL STUDENTS AND RESIDENTS 18-29 y????????????????????????? VITAMIN D INSUFFICIENT 37%????% VITAMIN D INSUFFICIENT % VITAMIN D INSUFFICIENT <20ng/ml BMC RESIDENTS & STUDENTS Incidence of Vitamin D Insufficiency (%) 30 20 10 0 18-29 (n=69) (n=69 Tangpricha et al Am J Med 2002 32% END WINTER 4% END SUMMER 25(OH)D NG/ML 25(OH)D (nmol/l) MAINE GIRLS AGES 9-11 120 0 10 20 30 40 100 80 60 40 20 0 48% D-DEFICIENT <20 ng/ml END OF WINTER Sep-00 Mar-01 Sep-01 Mar-02 Sep-02 Mar-03 SULLIVAN,ROSEN,HOLICK Date 25(OH)D (nmol/l) NG/ 120 0 10 20 30 40 100 80 60 40 20 0 MAINE GIRLS AGES 9-11 17% D-DEFICIENT <20 ng/ml END OF SUMMER Sep-00 Mar-01 Sep-01 Mar-02 Sep-02 Mar-03 SULLIVAN,ROSEN,HOLICK 2002 Date
52% D-deficient <20 ng/ml 6-11 yrs 70 %< 30 ng/ml 1-5 yrs 50 %< 30 ng/ml Vitamin D Deficiency Osteomalacia 2º HPTH Osteoporosis Subclinical Vitamin D Deficiency PRECIPITATES & EXACERBATES OSTEOPOROSIS
Symptoms Generalized bone pain Isolated bone pain Muscle aches 40-60% OSTEOMALACIA 25(OH)D<5ng/ml 23% 25(OH)D = 35ng/ml
Serum 25-Hydroxyvitamin D Levels (ng/ml) in Non-immigrant and Immigrant Subjects 35 150 aged 10-65 yrs 30 Bone 25 & Muscle Pains 20 15 10 5 0 Non-immigrant Subjects Immigrant Subjects 93% Vitamin D Deficient 58 Male Subjects With Undetectable 25-Hydroxyvitamin D Age/Sex 23 Female 26 Female 27 Female 35 Female Race Cauc Asian AA East African AA Symptoms Non-radicular LBP, weakness, fatigue Diffuse MSK pain, Fatigue, insomnia Severe non-radicular LBP, fatigue, depressed mood, insomnia, weakness Diffuse MSK pain, fatigue, insomnia, headache, weakness Severe non-radicular low back pain, intermittent chest pain,depressed mood, insomnia, weakness Diagnoses Dysthymia, non- DJD low back pain Dysthymia, stress reaction Pregnancy 3 rd T. Gestational DM MDD/PTSD Dysthymia/MDD, DJD refractory to surgery, angina refractory to PTCA Somatoform D/O? Medications OTC and Rx NSAIDs OTC and Rx NSAIDs, TCA OTC NSAID, Pre-natal vitamins Insulin VITAMIN D DEFICIENT OTC NSAID, SSRI, Neuroleptic agent Rx NSAID, intermittent narcotic agents, SSRI, TCA, Cardiovascular IT IS THE JELLO PHENOMENON!!!!!!!!!!!!!!!!!!!!! WHY DO YOU HAVE PAIN WITH OSTEOMALACIA??????? 142
Priemel et al. 100% > 30 ng/ml OV/BV (%) 6IOM 5>20 4 3 2 1 Priemel >30 ng/ml Holick There is TOO Much scatter For the PTH Plateau!!! 0 20 25 30 35 40 45 50 55 Serum 25(OH)D (ng/ml) IOM 25(OH)D > 20 ng/ml 97.5 % no evidence OSTEOMALACIA 25(OH)D> 30 ng/ml= no Osteomalacia!
78 Y/O M MUSCLE WEAKNESS ATROPHY, DENERVATION +EMG ALS Symptoms resolved Rx VITAMIN D +NCS and improves after vitamin D supplementation 151 152 progressive painless muscle weakness with muscle atrophy, which manifests like lower motor neuron disease Time to Stand vs 25(OH)D Levels ~20-40 ng/ml 153 154 Bischoff-Ferreri et al DID YOU KNOW VDR IS IN SKELETAL MUSCLE!!! 155 156
VITAMIN D IS GOOD FOR MUSCLE STRENGTH 72% Less Falls 800 IU/d 5 months 157 158 28-32 ng/ml JCEM 2007 159 160 WHITE ~20-40 ng/ml Mex Am BLACK 162
Incidence of Non-Vertebral Fractures in Men & Women >65yrs 25(OH)D > 30 ng/ml Cumulative Incidence (%) 14 12 10 After Dawson-Hughes, NEJM 1997 8 6 4 500 mg Ca 700 2 IU D 0 0 6 12 18 24 30 36 Month Placebo ~58% 163 Muscle strength, balance, lower extremity function Fall risk BMD Fxs 164 TREAT VITAMIN D DEFICIENCY 50,000 IU VITAMIN D2 6000 IU/d ONCE/WEEK 8 WEEKS Cut in half Add Milk etc MAINTAIN VITAMIN D SUFFICIENCY 50,000 IU VITAMIN D 3000 IU/d ONCE/ 2WEEKS
MEAN 25(OH)D LEVELS IN PATIENTS RECEIVING 50,000 70 IU VITAMIN D2 EVERY 2 WEEKS FOR 6 YRS Mean 25(OH)D (ng/dl) 60 50 40 30 20 SUFFICIENT 20 ng/ml 40 ng/ml 6 yrs 3000 IU/d INSUFFICIENT DEFICIENT 0 0 72 Pietras Arch Int Med 2009 Time (Months) C3PO R2D2 IS D3 REALLY MORE EFFECTIVE THAN D2???? 25(OH)D Level (ng/ml) 35 30 25 20 15 10 Mean Serum Total 25(OH)D Levels P=0.27 P=0.65 P=0.75 P=0.45 P=0.63 P=0.45 1000 IU D3 P=0.45 P=0.30 P=0.54 P=0.59 P=0.17 P=0.71 Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 7 Week 8 Week 9 Week 10 Week 11 Week 12 Time (weeks) 1000 IU D2 PLACEBO Mean 25(OH)D Levels (ng/ml) 16.00 14.00 12.00 10.00 8.00 6.00 4.00 Mean Serum 25(OH)D 2 and 25(OH)D 3 in Subjects receiving Vitamin D 2 25(OH)D3 25(OH)D2 1000 IU D2 2.00 0.00 1 2 3 4 5 6 7 8 9 10 11 12 Time (weeks) 1000 IU Vitamin D3/d or 500 IU Vitamin D3 + 500 IU Vitamin D2/d 173 Change in Serum 25(OH)D Levels (ng/ml) 32 30 28 26 24 22 20 18 1000 IU D2 500 IU D2+500 IU D3 1 2 3 4 5 6 7 8 9 10 11 12 Time (weeks)
Change in Serum 25(OH)D Levels (ng/ml) 32 30 28 26 24 22 20 18 Sufficient 1000 IU Vitamin D No one was sufficient 1 2 3 4 5 6 7 8 9 10 11 12 Time (weeks) WILL YOU BECOME VITAMIN D INTOXICATED????,ELEVATED Ca,Pi,25(OH)D CALCIFY BLOOD VESSELS &KIDNEYS SAFETY AT HIGH DOSES 33 males aged 38.7 yr (± 11.2 ) dosed with vit D 3 from October thru February 5,000 & 10,000 IU/d 10,000 10.5 IU/d 10.0 9.5 Is Safe 9.0 8.5 8.0 Pre Post CU ORC Vieth et al 1998 SERUM CALCIUM (mg/dl) 11.0 177 1 MILLION IU VITAMIN D/DAY 1000 IU/TSP Ca= 15.2 mg/dl 25(OH)D= 520 ng/ml IT IS DIFFICULT TO BECOME VITAMIN D INTOXICATED KOUTIA et al NEJM 20002
WHO IS AT RISK FOR VITAMIN D DEFICIENCY???????? H o w m u c h ca l ciu m d o w e n e e d? EVERYONE!!!!!!!!!!!!!!! WHY SHOULD I CARE?????? Skin Liver 25-OHase 25(OH)D 3 Kidney 1α-OHase 1,25(OH) 2 D 3 VDR VDR VDR VDR VDR VDR VDR VDR VDR VDR VDR VDR VDR VDR VDR VDR EVERY TISSUE AND CELL HAS A VDR Suda et al 1979 RX -1,25(OH)2D3
1915 8X more likely to Die Worked Indoors Colon Cancer Mortality Rates 1970-80 in W hite Fem ales Highest 10% for Colon Cancer Mortality Garland & Garland. Intern J Epid. 1980 Colon C ancer Mortality Rates 1970-1994
Inverse Relationship between 25(OH)D Levels & Risk of Colon Cancer Garland et al 1989 50% PROJECTED REDUCTION 25(OH)D = 40 ng/ml 50% PROJECTED REDUCTION 25(OH)D = 27 ng/ml 195 50% PROJECTED REDUCTION 25(OH)D = 38 ng/ml
50% PROJECTED REDUCTION WITH 480 IU/D 50% PROJECTED REDUCTION COLON CANCER WITH 1000 IU/D Garland et al 2005
I HATE TAKING CALCIUM & VITAMIN D EVERY DAY 60 % Did not follow Protocol 253% <12 ng/ml 8 years INVASIVE COLORECTAL CANCER Breast Cancer Mortality Inversely Correlates with Mean Solar Radiation Breast cancer mortality rate per 100,000 34 New York M 32 O Chicago Lynn, MA Cleveland R Washington D.C. 30 Cambridge T Boston Columbus A Pittsburgh 28 Los Angeles L New Orleans Seattle Brookhaven Long Island Atlanta I Indianapolis Omaha 26 T Omaha San Diego Y Lincoln 24 Nashville Miami Salt Lake City El Paso Albequerque Oklahoma City 22 San Antonio Lexington Fort Worth Tampa Phoenix Honolulu 20 250 300 350 400 450 500 550 After Garland et al., Preventive Med, 1990 Solar radiation (calories per square centimeter) 50% LOWER RISK 25(OH)D = 48 ng/ml
By looking at the latitudinal variation of breast cancer mortality rates in Europe, and controlling for diet, Grant found that lack of UV-B from sunlight accounts for perhaps 25% of the breast cancer mortality rates in northern Europe. 47,800 MEN DECREASED INCREASED RISK 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 30 WHITE MALES & FEMALES Mortality Rate (cases/100,000/year) 20 10 0 INCREASE SUN EXPOSURE MORTALITY -10 3 4 5 6 7 8 9 10 11 W. Grant 2002 UV-B (kj/m 2 ) COLON CANCER IN CALIFORNIA 42 y = 0.2238x + 25.905 40 R 2 = 0.1888 r = 0.44 San Francisco Latitude (Degrees N) 38 36 34 32 San Diego INCREASE LATITUDE MORTALITY 30 40 45 50 55 60 65 Rate (Cases per 100,000) latitude versus the number of all individuals diagnosed with colon cancer independent of race in the state of California.
Kaplan-Meier plot showing association of UVR exposure and age at diagnosis with prostate cancer Proportion tumor free 1.00 3-5 YEARS 0.75 Upper three quartiles of 0.50 exposure Lowest 0.25 quartile cumulative 0 exposure 50 60 70 80 90 Age at diagnosis (years) 223 C. J. Luscombe et al, The Lancet Vol 358 Num 9282, 2001 224 1100 IU D3 YEARS 0-4 1179 PM WOMEN 1200MG Ca +- D3 ALL CANCERS 60% LESS CANCERS Girls 10-19 yrs most sun 69% Women 20-29 yrs most sun 51% Lappe et al AJCN 2007 Women 45-54 yrs most sun 0.0% Cancer Epi Biomarkers & Prev 07
1,25(OH)2D 25(OH)D This is a REAL CONUNDRUM!!!!!!!!! Autocrine Regulation of Cell Growth 25(OH)D CALCITROIC ACID INACTIVE 1-OHase 1,25(OH) 2 D Control of cell growth
25(OH)D>30 ng/ml Colon Cell Mitochondria 1-OHase 1,25(OH) 2 D ~ 2000 Genes 3 Affected Nucleus Bcl-2 1,25(OH)D Bcl-X L Mcl-1 VDR RXR Gene Transcription BAG1L XIAPBy 1,25(OH)2D 3 Apoptosis Cell-cycle ciap1 Arrest ciap2 Differentiation CDK2, p21, p27, p53 MATURATION Ki67, E-Cadherin 236 ACTIVATED MACROPHAGES Metabolize 25(OH)D 3 to 1,25(OH) 2 D 3 25(OH)D 3 1,25(OH) 2 D 3 Adams et al JCEM 1987 1849 Codliver oil - Rx Tuberculosis Brompton Hospital Records, 38 1849
19KDa TLR2/1 MACROPHAGE 25(OH)D 1-OHase 1-OHase mrna Liu et al Science 2006 1,25(OH) 2 D Cathelicidin Death TB Cathelicidin mrna Why is flu Season always In the WINTER??????? 1981 Edgar Hope-Simpson Suggested a SEASONAL STIMULUS Jan-Mar 32 ng/ml Jan-Mar 25(OH)D winter 12 ng/ml 2000 IU/D 90% URIs Aloia et al 2007
Influenza A + School Children 25(OH)D=38 ng/ml 2X Placebo 18.6% +1200 IU Vitamin D 10.8% Type 1 Diabetes/100,000 Boys<14 yrs 15X 10X Garland et al 2008 Annual age-adjusted incidence rates of type 1 diabetes, children < 14 years old, per 100,000 population, Finland, 1965-2005 65 55 Incidence rate 45 35 1964 Recommended Vitamin D intake Reduced from 4500 to 2000 IU/d 25 Hypponen et al. Lancet 2001 15 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 Year
Beta-ISLET CELL 1,25(OH)D3 VDR + VDR + + Insulin Metabolic Syndrome & Type 2 Diabetes RR Type 2 DM D < 400 IU > 800 IU 0.67 D + Ca > 1200 mg Ca <500 mg RR 33% Ca > 1200 MG + VIT D > 800 IU Pittas et al JCEM 07 North-South Gradient in Mortality from MS Scragg et al Diabetes Care 27:2813;04 DIABETES INVERSELY RELATED SERUM 25(OH)D 100% MS 35 WHITES-NH 75% MEXICAN-AM 83% BLACKS NO EFFECT Vitamin D Intake (>400IU/D) Inversely Related To MS In Women 41% Vitamin D Intake (>400IU/D) Inversely Related To RA In Women 44%
Quality Heath Care Worldwide OSTEOARTHRITIS Rostand 1979 Reported Inverse Reationship Between BP & Latitude Association between Latitude and Blood Pressure Hypertension 1997; 30:150-156 262 PVD vs & 25(OH)D 80% Vitamin D deficiency in humans is associated with heart failure. ABBOTT RENAL GLOBAL Development >29 ng/ml 263 264
Suppression of Renin Transcription by VDR Activation RXRVDR VDRE RXR VDR Renin TGACCT Renin DNA binding RNA Pol II RNA Pol II CoReg B VDRRXR TGACCT > 200 Genes in Renin Heart & Vessels Atherosclerosis, Inflammation, oxidative stress Blood Pressure LVH First MI >50% Increase Associated With Vitamin D Deficiency What are the consequences of Vitamin D Deficiency on 28 ng/ml Our health??? All 108% CV 122% 8-13 ng/ml Arch Int Med 2008 50 Million Teens Deficient/Insufficient 2.4 X HBP 2.5 X Elevated BS 4 X Metablolic Syndrome 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 in Arterial Wall Stiffness Dong et al JCEM 95;2010
IOM Increase mortality 25(OH)D> 30 ng/ml All Cause Mortality Decreased 7% On 528 IU Vitamin D ADEQUATE VITAMIN D IS NECESSARY FROM BIRTH- DEATH VITAMIN D IS A DISEASE OF NEGLECT THERE IS NOW A MOUNTAIN OF EVIDENCE LINKING VITAMIN D DEFICIENCY WITH CANCER RISK & MORTALITY AUTOIMMUNE DISEASES TYPE 1 DIABETES HYPERTENSION TYPE 2 DIABETES!!!!!
100 IU VITAMIN D3 RAISES 25(OH)D BY ONLY 1NG/ML. CHILDREN & ADULTS HAVE 25(OH)D ~18-25 ng/ml Serum 25(OH)D Levels (ng/ml) 32 30 28 26 24 22 20 Sufficient 1000 IU vitamin D/d No one was sufficient 18 1 2 3 4 5 6 7 8 9 10 11 12 Time (weeks)
Conquer Vitamin D Deficiency What is the Best Source of Vitamin D?
HOLICK HOW DO YOU GET THE MESSAGE OUT?????? MAY 04 I DO NOT ADVOCATE TANNING!!!!!!!!!!!! ANCESTORS APPRECIATION OF THE SUN FOR ITS LIFE GIVING BENEFITS
UNENLIGHTENED DERMATOLOGISTS VIEW OF THE SUN S EFFECT ON HEALTH Inquisitors NEED Large RCTs Galileo recanted IMPRISIONED FOR THE REST OF HIS LIFE Agency for Astronomical Research And Quality AARQ AARQ Need more Randomized Controlled Astronomical Trials RCATs!!!!!!!!!!!!!!!!!!! Need more Randomized Controlled Astronomical Trials!!!!!!!!!!!!!!!!!!! RCATs
Instituted Hand Washing Prevent Maternal & Infant Mortality Commited himself Insane Asylum ALWAYS WEAR A SUNSCREEN Died Infection DERMATOLOGIST ADVISING ABOUT SUN EXPOSURE
Slip, Slap, Slop NEVER BE EXPOSED TO THE SUN!!!!!!!!!!!!!!!!!!! Australian dermatologist 87% < 20 ng/ml 87% Vitamin D Deficient end of Summer Vitamin D Deficiency Associated with: Schizoprehenia Depression Dementia 25(OH)D <10 ng/ml RR=31%
YOU CAN GET IT FROM DIET!!! YOU CANNOT GET IT FROM DIET 00 If you and your family are not taking at least 1000-2000 IU/d You are Vitamin D Insufficient WHAT IS YOUR 25(OH)D LEVEL???????? 316 + 2000 IU Vitamin D3 + MTV=400 IU + 3 glasses milk += 300 IU My Total Vitamin D= 2700 IU/d My 25(OH)D = 52 ng/ml Vitamin D Deficiency Is The Most COMMON Medical Condition
CAUSES SUN SUNSCREEN MELANIN LATITUDE WINTER MEDICATIONS X Antiseizure Glucocorticoids Rifampin Hepatic Failure HAART St John s Wart Renal Failure Nephrotic syndrome MALABSORPTION Crohn s Whipple s Cystic Fibrosis Celiac Liver disease VITAMIN D DEFICIENCY Obesity Schizophrenia Depression INFECTIONS URI TB HBP CHD FEV1 Wheezing illnesses AODM Syndrome X Muscle weakness Muscle aches Osteoporosis Osteomalacia Rickets Osteoarthritis CONSEQU Autoimmune Type 1 Diabetes MS Crohn s RA CANCER Colon Breast Prostate etc. There Is No Downside To Increasing Vitamin D Intake!!!! Holick NEJM July 07 We Need Sensible Sun & Vitamin D Supplementation Recommendations!!!!!!!! This is NOT HYPOTHESIS Do we need to Screen everyone For their 25(OH)D level??????????????? You Do Not Need To Be A Genius To Know No!!!!!!! But Yes BMI>30 Malabsorption Meds/AEs., Glc Sarcoidosis April 1, 2010 DrHolick.com
IOM RDA UL 0-0.5 YEARS 0.5-1 YEARS 1-8 YEARS 9-12 YEARS 400 IU/D 1000 1500 600 IU/D 2500 3000 13-70YEARS 600IU/D 4000 70+YEARS 800IU/D 4000 Adequate Intake 0-1 YEAR 600-1000 IU/D 1-12 YEAR 1000-2000 IU/D 13+ YEARs1500-2000 IU/D Obesity 2-3 Times more SAFE UPPER LIMIT 0-1 YEAR 2000 IU/D 1-12 YEAR 5000 IU/D 13+ YEARs 10,000 IU/D DrHolick.com