A brief review about the role of vitamin D in health and disease. Most of the content in these slides were taken from another author with some editing to custom it for the purpose of general physician workshop scientific material. Some figures were our own data in our hospital

1. Rachmat Gunadi Wachjudi
email :email :
konsultan.reumatologi@gmail.comkonsultan.reumatologi@gmail.com
 Lahir diLahir di GGarut,arut, 16-1-195516-1-1955
 PendidikanPendidikan ::
 SD-SMA :SD-SMA : GGarutarut
 Dokter umum: FK UNSRIDokter umum: FK UNSRI PPalembangalembang
 Internist: FK UNPADInternist: FK UNPAD / RSHS B/ RSHS Bandungandung
 Fellowship : Royal Perth & Sir Charles Gairdner HospitalFellowship : Royal Perth & Sir Charles Gairdner Hospital
 Subspesialis Reumatologi : FK UI / RSCM JakartaSubspesialis Reumatologi : FK UI / RSCM Jakarta
 Pekerjaan
 Divisi Reumatologi & Autoimun RSDivisi Reumatologi & Autoimun RS DDrr HHasanasan SSadikin Bandungadikin Bandung
 Organisasi
 IDIIDI,, PAPDIPAPDI,, IRA, PEROSIIRA, PEROSI,, PERALMUNIPERALMUNI,, PESLIPESLI,, APLARAPLAR

2. Vitamin DVitamin D
in health and diseasein health and disease
Rachmat Gunadi WachjudiRachmat Gunadi Wachjudi
Department of internal Medicine UNPADDepartment of internal Medicine UNPAD

3. OverviewOverview
 Vitamin D receptors found in gut, bone, brain, breast,Vitamin D receptors found in gut, bone, brain, breast,
prostate, lymphocytes, placenta, and other tissuesprostate, lymphocytes, placenta, and other tissues
 Routine screening is appropriateRoutine screening is appropriate
 Safe up to 4000iu/d without monitoringSafe up to 4000iu/d without monitoring
 Safe up to 10,000iu/d with monitoringSafe up to 10,000iu/d with monitoring
 Supplementation helpful in:Supplementation helpful in:
 DM, metabolic syndrome, CAD, depression, autoimmuneDM, metabolic syndrome, CAD, depression, autoimmune
diseases, various cancers, HTN, osteoporosis, osteoarthritis,diseases, various cancers, HTN, osteoporosis, osteoarthritis,
pain, MS, epilepsy, elderly fall prevention, PCOS, pregnancy &pain, MS, epilepsy, elderly fall prevention, PCOS, pregnancy &
lactation, periodontal disease, URI and influenza, andlactation, periodontal disease, URI and influenza, and
decreasing all-cause mortalitydecreasing all-cause mortality

4. Conversion of Vitamin D to the activeConversion of Vitamin D to the active
formform
Cholesterol from
diet
7 dehydrocholesterol in the skin
Sunlight converts 7-
dehydrocholesterol to
previtamin D3
Cholecalciferol
(Previtamin D3)
The liver converts previtamin D to 25-
hydroxyvitamin D which appears in
circulation.
25-hydroxyvitamin D
(circulating form)
The kidneys and other tissues
convert it to an active form of
1,25-dihydroxyvitamin D1,25-dihydroxyvitamin D
(active form)

5. Clinical RelevanceClinical Relevance
 Coronary artery diseaseCoronary artery disease
 HypertensionHypertension
 Diabetes Type I andDiabetes Type I and
Type 2Type 2
 OsteoarthritisOsteoarthritis
 DepressionDepression
 EpilepsyEpilepsy
 Polycystic OvariesPolycystic Ovaries
 Musculoskeletal PainMusculoskeletal Pain
 Autoimmune DiseaseAutoimmune Disease
 Multiple SclerosisMultiple Sclerosis
 CancersCancers
 Falls in the ElderlyFalls in the Elderly
 Pregnancy and LactationPregnancy and Lactation

6. LaboratoryLaboratory
AssessmentAssessment
 25-OH-Vitamin D level is the appropriate test25-OH-Vitamin D level is the appropriate test
 Typical labeled normal range is 8-40ng/mlTypical labeled normal range is 8-40ng/ml
 Population basedPopulation based
 Optimal range for best health is 40-65ng/mlOptimal range for best health is 40-65ng/ml
 Based on epidemiologic assessment of normalBased on epidemiologic assessment of normal
levels in tropical humanslevels in tropical humans
 Based on physiologic changes, increases in PTH,Based on physiologic changes, increases in PTH,
and clinical disease states associated with levelsand clinical disease states associated with levels
under 40ng/mlunder 40ng/ml

7. Heart DiseaseHeart Disease
 MI risk doubles in pts with 25OHVitDMI risk doubles in pts with 25OHVitD
levels < 34ng/mllevels < 34ng/ml
 Scragg et al. Int J Epidemiol. 1990;19(3):559.Scragg et al. Int J Epidemiol. 1990;19(3):559.
 CHF pts have much lower 25OHVitDCHF pts have much lower 25OHVitD
levels than controlslevels than controls
 Zitterman et al. J Am Coll Cardiol. 2003;41:105.Zitterman et al. J Am Coll Cardiol. 2003;41:105.
 Deaths from CAD more common inDeaths from CAD more common in
winterwinter
 Scragg. Int J Epidemiol. 1981;10(4):337.Scragg. Int J Epidemiol. 1981;10(4):337.

8. CancerCancer
 Modulates the transcription of severalModulates the transcription of several
oncogenes involved with cell differentiation andoncogenes involved with cell differentiation and
proliferationproliferation
 C-myc, c-fos, c-sisC-myc, c-fos, c-sis
 Inverse relationship b/t sun exposure and cancerInverse relationship b/t sun exposure and cancer
mortalitymortality
 Grant. Cancer. 2002;94(6):1867.Grant. Cancer. 2002;94(6):1867.
 Apperly. Cancer Res. 1941;1:191.Apperly. Cancer Res. 1941;1:191.

9. Calcitriol and CNSCalcitriol and CNS
functionfunction
 Vit D Modulates neurotransmitter andVit D Modulates neurotransmitter and
neurological functionneurological function
 Anticonvulsant and antidepressant effectAnticonvulsant and antidepressant effect
 Landsdowne et al. Psychopharmacology.Landsdowne et al. Psychopharmacology.
1998;135.1998;135.
 Christiansen et al. Br Med J.Christiansen et al. Br Med J.
1974;2(913):258.1974;2(913):258.

10. Heart DiseaseHeart Disease
 1,739 individuals without cardiovascular disease1,739 individuals without cardiovascular disease
 Baseline 25-OH-Vitamin D levels were assessed andBaseline 25-OH-Vitamin D levels were assessed and
participants were followed for a mean of 5.4 years.participants were followed for a mean of 5.4 years.
 Compared to having a level >15ng/mlCompared to having a level >15ng/ml
 25-(OH)D < 10 ng/mL - 80% greater risk of having a25-(OH)D < 10 ng/mL - 80% greater risk of having a
cardiovascular incidentcardiovascular incident
 25 (OH)D of 10-15 ng/mL - 53% increased risk25 (OH)D of 10-15 ng/mL - 53% increased risk
 The authors concluded vitamin D deficiency isThe authors concluded vitamin D deficiency is
positively correlated with incident cardiovascularpositively correlated with incident cardiovascular
disease.disease.
 Wang TJ, Pencina MJ, Booth Sl, et al. Vitamin D deficiency andWang TJ, Pencina MJ, Booth Sl, et al. Vitamin D deficiency and
risk of cardiovascular disease.risk of cardiovascular disease. CirculationCirculation 2008;117:503-511.2008;117:503-511.

11. HypertensionHypertension
 BP higher in winterBP higher in winter
 BP higher with increasing latitudeBP higher with increasing latitude
 BP higher with darker skin pigmentationBP higher with darker skin pigmentation
 HTN pts given UV light treatments 3 times perHTN pts given UV light treatments 3 times per
week for 6 weeks had Vit D level increases ofweek for 6 weeks had Vit D level increases of
162% and saw mild decreases in BP162% and saw mild decreases in BP
 Krause et al. Lancet. 1998;352(9129):709.Krause et al. Lancet. 1998;352(9129):709.
 Small doses of Vit D (800iu) for 8 weeksSmall doses of Vit D (800iu) for 8 weeks
decreased BP and pulse ratedecreased BP and pulse rate
 Pfeifer et al. J Clin Endocrinol Metab. 2001;86(4):258.Pfeifer et al. J Clin Endocrinol Metab. 2001;86(4):258.

12. HypertensionHypertension
 StudiesStudies
 BP is reduced significantly by ultraviolet radiationBP is reduced significantly by ultraviolet radiation
comparable to about oral intake of 3,000 IU ofcomparable to about oral intake of 3,000 IU of
vitamin D a dayvitamin D a day
 Krause R, Bohring M, Hopfenmhller W, Holick MF, Sharma AKrause R, Bohring M, Hopfenmhller W, Holick MF, Sharma A
 BP not routinely reduced by small amounts ofBP not routinely reduced by small amounts of
vitamin Dvitamin D
 Scragg R, Khaw KT, Murphy S: Effect of winter oral vitamin DScragg R, Khaw KT, Murphy S: Effect of winter oral vitamin D

13. Diabetes Type 1Diabetes Type 1
 Study with > 10,000 peopleStudy with > 10,000 people
 Supplementation of infants and children withSupplementation of infants and children with
Vit D 2000iu/day decreased incidence of DMVit D 2000iu/day decreased incidence of DM
type 1 by 80%type 1 by 80%
 Hypponen et al. Lancet. 2001;358(9292):1500.Hypponen et al. Lancet. 2001;358(9292):1500.
 Cod liver studies also show significantCod liver studies also show significant
reduction of incidence of Type I DMreduction of incidence of Type I DM

14. Diabetes Type 2Diabetes Type 2
 Low Vit D levels assoc with insulinLow Vit D levels assoc with insulin
resistance and Beta-cell dysfunctionresistance and Beta-cell dysfunction
 Postprandial glucose and insulinPostprandial glucose and insulin
sensitivitysensitivity
 Better in healthy adults with highest Vit DBetter in healthy adults with highest Vit D
levelslevels
 Chiu. Am J Clin Nutr. 2004;79:820.Chiu. Am J Clin Nutr. 2004;79:820.

15. Diabetes Type 2Diabetes Type 2
 Metformin improves insulin sensitivity byMetformin improves insulin sensitivity by
13%13%
 Highest Vit D levels associated with 60%Highest Vit D levels associated with 60%
improvement in insulin sensitivityimprovement in insulin sensitivity
 Chiu. Am J Clin Nutr. 2004;79:820.Chiu. Am J Clin Nutr. 2004;79:820.
 Small trial of 10 women with DM Type 2Small trial of 10 women with DM Type 2
 Vit D 1332iu per day x 30 daysVit D 1332iu per day x 30 days
 21% increase in insulin sensitivity21% increase in insulin sensitivity
 Borrisova et al. Int J Clin Pract. 2003;57(4):258.Borrisova et al. Int J Clin Pract. 2003;57(4):258.

16. Upper RespiratoryUpper Respiratory
Infection and InfluenzaInfection and Influenza
 Three-year RCT of 208 African-American postmenopausal womenThree-year RCT of 208 African-American postmenopausal women
(who are at great risk of vitamin D deficiency)(who are at great risk of vitamin D deficiency)
 Vitamin D 800iu/day for Years 1-2 and 2000iu/day Year 3Vitamin D 800iu/day for Years 1-2 and 2000iu/day Year 3
 In the three years of the study 34 patients reported cold and fluIn the three years of the study 34 patients reported cold and flu
symptoms,symptoms,
 8 in the supplemented group8 in the supplemented group
 26 in the placebo group (p<0.002).26 in the placebo group (p<0.002).
 Participants who got a placebo had a 300% greater risk of havingParticipants who got a placebo had a 300% greater risk of having
a cold or flu, and that vitamin D supplementation provided a highlya cold or flu, and that vitamin D supplementation provided a highly
significant protective effect.significant protective effect.
 Aloia JF. Epidemic influenza and vitamin D.Aloia JF. Epidemic influenza and vitamin D. Epidemiol InfectEpidemiol Infect
2007;135:1095-1096.2007;135:1095-1096.

17. OsteoarthritisOsteoarthritis
 Framingham dataFramingham data
 Knee OA advanced most quickly in patientsKnee OA advanced most quickly in patients
with 25OHVitD < 36ng/mlwith 25OHVitD < 36ng/ml
 McAlindon et al. Ann Intern Med. 1996;125(5):353.McAlindon et al. Ann Intern Med. 1996;125(5):353.
 Hip OA advanced most quickly in patientsHip OA advanced most quickly in patients
with 25OHVitD < 30 ng/mlwith 25OHVitD < 30 ng/ml
 Lane et al. Arthritis Rheum. 1999;42(5):854.Lane et al. Arthritis Rheum. 1999;42(5):854.

18. DepressionDepression
 Seasonal Affective DisorderSeasonal Affective Disorder
 Single dose 100,000 iu Vit D superior to lightSingle dose 100,000 iu Vit D superior to light
therapy for one monththerapy for one month
 Gloth et al. J Nutr Health Aging. 1999;3(1):5.Gloth et al. J Nutr Health Aging. 1999;3(1):5.
 Vit D 400-800iu per day associated withVit D 400-800iu per day associated with
improved mood within 5 daysimproved mood within 5 days
 Landsdowne et al. Psychopharmacology.Landsdowne et al. Psychopharmacology.
1998;135.1998;135.

19. Mental IllnessMental Illness
ComorbiditiesComorbidities
 Mental Illness and Vitamin D deficiencyMental Illness and Vitamin D deficiency
share similar comorbiditiesshare similar comorbidities
 Cardiac mortality, DM type I and II,Cardiac mortality, DM type I and II,
osteoporosis, MS, rheumatoid arthritis, HTNosteoporosis, MS, rheumatoid arthritis, HTN

20. EpilepsyEpilepsy
 Seizures can be first sign of Vit D defSeizures can be first sign of Vit D def
 Johnson, Willis. Med J Aust. 2003;178(9):467.Johnson, Willis. Med J Aust. 2003;178(9):467.
 Hypovitaminosis D decreases SeizureHypovitaminosis D decreases Seizure
thresholdthreshold
 Several anticonvulsantsSeveral anticonvulsants
 Interfere with renal calcitriol formationInterfere with renal calcitriol formation
 Induce hepatic clearance of calcitriolInduce hepatic clearance of calcitriol
 May cause iatrogenic seizures via iatrogenicMay cause iatrogenic seizures via iatrogenic
hypovitaminosis Dhypovitaminosis D
 Ali et al. Ann Pharmacother. 2004;38(6):1002.Ali et al. Ann Pharmacother. 2004;38(6):1002.

21. EpilepsyEpilepsy
 Placebo controlled pilot studyPlacebo controlled pilot study
 4000-16000iu/day of Vit D24000-16000iu/day of Vit D2
 Decrease in seizure frequencyDecrease in seizure frequency
 Christiansen et al. Br Med J. 1974;2(913):258.Christiansen et al. Br Med J. 1974;2(913):258.

22. Polycystic OvaryPolycystic Ovary
SyndromeSyndrome
 Small study of 13 PCOS ptsSmall study of 13 PCOS pts
 9 of 13 w/ Vit D deficiency9 of 13 w/ Vit D deficiency
 Ca 1500mg/day + Vit D2 50,000iu/weekCa 1500mg/day + Vit D2 50,000iu/week
 9 of 9 pts with normalization of menses9 of 9 pts with normalization of menses
and/or fertility within 3 monthsand/or fertility within 3 months
 Thys-Jacobs S. Steroids. 1999;64(6):430.Thys-Jacobs S. Steroids. 1999;64(6):430.

23. PainPain
 Study with 150 pts with persistent, nonspecificStudy with 150 pts with persistent, nonspecific
musculoskeletal pain at Mayo clinicmusculoskeletal pain at Mayo clinic
 93% had Vit D deficiency93% had Vit D deficiency
 Plotnikoff, Quigley. Mayo Clin Proc. 2003;78(12):1463.Plotnikoff, Quigley. Mayo Clin Proc. 2003;78(12):1463.
 Children w/ limb pain improved in 3 monthsChildren w/ limb pain improved in 3 months
 Low Back PainLow Back Pain
 83% of 299 LBP pts had Vit D def83% of 299 LBP pts had Vit D def
 5000-10,000iu/day5000-10,000iu/day
 Decrease in pain medication in nearly 100% after 3 monthsDecrease in pain medication in nearly 100% after 3 months
 Al Faraj, Al Mutairi. Spine 2003;28(2):177.Al Faraj, Al Mutairi. Spine 2003;28(2):177.

24. Autoimmune DiseaseAutoimmune Disease
 Vitamin D insufficiency in:Vitamin D insufficiency in:
 50% of pts w/ fibromyalgia + SLE50% of pts w/ fibromyalgia + SLE
 Huisman et al. J Rheumatol. 2001;28(11):2535.Huisman et al. J Rheumatol. 2001;28(11):2535.
 58% Japanese F’s with Graves Disease58% Japanese F’s with Graves Disease
 Yamashita et al. Endocr J. 2001;48(1):63.Yamashita et al. Endocr J. 2001;48(1):63.
 73% Austrian pts w/ Ankylosing Spondilitis73% Austrian pts w/ Ankylosing Spondilitis
 Falkenbach et al. Wien Klin Wochenschr.Falkenbach et al. Wien Klin Wochenschr.
2001;113(9):3282001;113(9):328
 RheRheuumatoid Arthtritismatoid Arthtritis
 Cantorna.Proc Soc Exp Biol Med. 2000;223(3):230Cantorna.Proc Soc Exp Biol Med. 2000;223(3):230

25. PainPain
 Study with 150 pts with persistent,Study with 150 pts with persistent, nonspecificnonspecific
musculoskeletal pmusculoskeletal pain at Mayo clinicain at Mayo clinic
 93% had Vit D deficiency93% had Vit D deficiency
 Plotnikoff, Quigley. Mayo Clin Proc. 2003;78(12):1463.Plotnikoff, Quigley. Mayo Clin Proc. 2003;78(12):1463.
 Children w/ limb pain improved in 3 monthsChildren w/ limb pain improved in 3 months
 Low Back PainLow Back Pain
 83% of 299 LBP pts had Vit D def83% of 299 LBP pts had Vit D def
 5000-10,000iu/day5000-10,000iu/day
 Decrease in pain medication in nearly 100% after 3 monthsDecrease in pain medication in nearly 100% after 3 months
 Al Faraj, Al Mutairi. Spine 2003;28(2):177.Al Faraj, Al Mutairi. Spine 2003;28(2):177.

26. AutoimAutoimmunitymunity
Genetic Hormonal Environment
Polymorphism
VDR Prohormon UV
Gen Bsml

27. Autoimmune diseaseAutoimmune disease
progressionprogression
Disease activity
Low vitamin D

30. Peran vitamin D (25-hydroxyvitamin D, [25(OH)D] )
pada autoimun.11-17
 Metabolit aktif vitamin D (1,25- dihydroxyvitamin D, [1,25(OH)2D] )
berikatan dengan reseptornya (vitamin D receptor, VDR) yang
terdapat pada berbagai jaringan tubuh seperti saluran cerna,
ginjal, tulang, kelenjar paratiroid, kulit dan sel imun.
 Peran vitamin D dalam sistem imun 
 memperbaiki fungsi kemotaksis dan fagositosis makrofag,
 menginduksi aktivitas sel T regulator ( regulatory T cells, T reg),
 menginhibisi diferensiasi dan proliferasi sel B
 menginhibisi pembentukan antibodi.
 Secara invivo dan invitro, vitamin D memperbaiki inflamasi dan
abnormalitas imun pada SLE.12-20

31. Multiple SclerosisMultiple Sclerosis
 48% of MS pts are Vit D deficient48% of MS pts are Vit D deficient
 Mahon. J Neuroimmunol. 2003;134(1-2):128.Mahon. J Neuroimmunol. 2003;134(1-2):128.
 MS rare near equatorMS rare near equator
 Zittermann A. Br J of Nutr. 2003;89:552-572Zittermann A. Br J of Nutr. 2003;89:552-572
 5,000iu/d plus Ca 1000mg and Mag5,000iu/d plus Ca 1000mg and Mag
600mg decreased the relapse rate in MS600mg decreased the relapse rate in MS
patients – no side effectspatients – no side effects
 Goldberg P. Medical Hypothesis. 1986;21:193-200Goldberg P. Medical Hypothesis. 1986;21:193-200

32. InflammationInflammation
 Vit D injections averaging 547iu/day x 2-5Vit D injections averaging 547iu/day x 2-5
years – 23% decrease in CRPyears – 23% decrease in CRP
 Timms et al. QJM. 2002;95:787.Timms et al. QJM. 2002;95:787.
 25(OH)Vit D level should be checked in any25(OH)Vit D level should be checked in any
patient with any inflammatory conditionpatient with any inflammatory condition
 Michael Hollick, PhD, MD Professor of Medicine,Michael Hollick, PhD, MD Professor of Medicine,
Dermatology, Physiology and BioPhysics, Director of theDermatology, Physiology and BioPhysics, Director of the
General Clinical Research Center and Director of the BoneGeneral Clinical Research Center and Director of the Bone
Health Care Clinic at Boston University Medical CenterHealth Care Clinic at Boston University Medical Center
 Vit D supp in pts w/ prolonged clinical illnessVit D supp in pts w/ prolonged clinical illness
saw decreases in IL-6 and CRPsaw decreases in IL-6 and CRP
 Van den Berghe et al. J Clin Endocrinol Metab.Van den Berghe et al. J Clin Endocrinol Metab.
2003;88(10):4623.2003;88(10):4623.

33. CancerCancer
 Vitamin D levels inversely correlated to colonVitamin D levels inversely correlated to colon
cancer mortality (but not to all cancer mortality)cancer mortality (but not to all cancer mortality)
 Freedman et al. J Natl Cancer Inst. 2007. 99(21):1563.Freedman et al. J Natl Cancer Inst. 2007. 99(21):1563.
 47,800 men over 14 years –47,800 men over 14 years –
10 ng/ml rise in Vitamin D level of associated w/10 ng/ml rise in Vitamin D level of associated w/
 17% reduction in cancer incidence17% reduction in cancer incidence
 29% reduction in all cancer mortality29% reduction in all cancer mortality
 45% reduction in GI cancer mortality45% reduction in GI cancer mortality
 Giovanucchi et al. J Natl Cancer Inst. 2006. 98(7):428.Giovanucchi et al. J Natl Cancer Inst. 2006. 98(7):428.

34. CancerCancer
 Long-term study of 50,000 men at HarvardLong-term study of 50,000 men at Harvard
School of Public Health suggests vitamin DSchool of Public Health suggests vitamin D
may reduce the risk of all cancers by at leastmay reduce the risk of all cancers by at least
30 percent.30 percent.
 Giovannucci. J Natl Cancer Inst. 2006 Apr 5:98(7):428.Giovannucci. J Natl Cancer Inst. 2006 Apr 5:98(7):428.
 Decreased sunlight assoc with increasedDecreased sunlight assoc with increased
cancer mortalitycancer mortality
 Breast, colon, cancer, prostate, bladder, esophagus,Breast, colon, cancer, prostate, bladder, esophagus,
kidney, lung, pancreas, rectum, stomach, uterus,kidney, lung, pancreas, rectum, stomach, uterus,
non-Hodgkin’s Lymphomanon-Hodgkin’s Lymphoma
 Grant. Cancer. 2002;94(6):1867.Grant. Cancer. 2002;94(6):1867.

35. Falls in the ElderlyFalls in the Elderly
 Vit D receptors in skeletal muscleVit D receptors in skeletal muscle
 Bischoff HA, et al. Histochem J 2001;33:19.Bischoff HA, et al. Histochem J 2001;33:19.
 Vit D deficiency reported to affect predominantly theVit D deficiency reported to affect predominantly the
weight-bearing antigravity muscles of the lower limb,weight-bearing antigravity muscles of the lower limb,
which are necessary for postural balance and walkingwhich are necessary for postural balance and walking
Glerup H et al. Calcif Tissue Int 2000;66:419.Glerup H et al. Calcif Tissue Int 2000;66:419.
 Significant correlation between serum 25(OH)D3Significant correlation between serum 25(OH)D3
concentration and the occurrence of falls in elderlyconcentration and the occurrence of falls in elderly
reported in literature.reported in literature.
 Mowé M et al. J Am Geriatr Soc 1999;47:220Mowé M et al. J Am Geriatr Soc 1999;47:220
 Stein MS et al. J Am Geriatr Soc 1999;47:1195Stein MS et al. J Am Geriatr Soc 1999;47:1195

36. Falls in the ElderlyFalls in the Elderly
 STOP/IT (Sites Testing Osteoporosis Prevention andSTOP/IT (Sites Testing Osteoporosis Prevention and
Intervention Treatments) trialIntervention Treatments) trial
 489 women randomly assigned to receive estrogen,489 women randomly assigned to receive estrogen,
calcitriol, both estrogen and calcitriol, or a placebo for 3calcitriol, both estrogen and calcitriol, or a placebo for 3
years.years.
 The increase in bone density was twice as large withThe increase in bone density was twice as large with
estrogen as with calcitriol.estrogen as with calcitriol.
 The subjects w/ calcitriol had fewer fractures from falls thanThe subjects w/ calcitriol had fewer fractures from falls than
did the group who took estrogen (odds ratio: 0.78 and 0.94,did the group who took estrogen (odds ratio: 0.78 and 0.94,
respectively).respectively).
 Improvement in lower extremity muscle strength andImprovement in lower extremity muscle strength and
balance with vitamin D supplementation thought to explainbalance with vitamin D supplementation thought to explain
the reduced number of fall-related fractures.the reduced number of fall-related fractures.
 Dawson-Hughes et al. N Engl J Med 1997;337:670Dawson-Hughes et al. N Engl J Med 1997;337:670

37. PregnancyPregnancy
 Vit D2 100,000 iu/day throughout pregnancyVit D2 100,000 iu/day throughout pregnancy
associated with no fetal abnormalitiesassociated with no fetal abnormalities
 Current recommendation of 200-400iu per dayCurrent recommendation of 200-400iu per day
inadequateinadequate
 Hollis & Wagner recommend up to 4000iuHollis & Wagner recommend up to 4000iu
 Pre-eclamsia and SGA babies associated withPre-eclamsia and SGA babies associated with
Vit D deficiencyVit D deficiency
 Halhali et al. J Clin Endocrin & Met 2000. 85(5), 1828-Halhali et al. J Clin Endocrin & Met 2000. 85(5), 1828-
1833 .1833 .

38. LactationLactation
 Breast-feeding mothers need 4,000 unitsBreast-feeding mothers need 4,000 units
of vitamin D a day in order to maintainof vitamin D a day in order to maintain
adequate infant Vit D status.adequate infant Vit D status.
 2,000 iu/day was not effective.2,000 iu/day was not effective.
 Wagner CL, et al. Pediatr Res 2003.Wagner CL, et al. Pediatr Res 2003.
 Hollis et alHollis et al. Am J Clin Nutr. Am J Clin Nutr 2004;80(suppl):1752S–2004;80(suppl):1752S–
8S.8S.
 Basile et al. Breastfeeding Medicine. March 1,Basile et al. Breastfeeding Medicine. March 1,
2006, 1(1): 27-352006, 1(1): 27-35

39. LactationLactation
 25-OH-D content of maternal milk responsible25-OH-D content of maternal milk responsible
for vitamin D concentrations of serum offor vitamin D concentrations of serum of
exclusively breast-fed infantsexclusively breast-fed infants
 Cancela et al. J Endocrinol. 1986 Jul;110(1):43-50.Cancela et al. J Endocrinol. 1986 Jul;110(1):43-50.
 Hypovitaminosis D common in summer inHypovitaminosis D common in summer in
exclusively breast-feeding infants and theirexclusively breast-feeding infants and their
mothersmothers
 Dawodu et al. J Pediatr. 2003 Feb;142(2):169Dawodu et al. J Pediatr. 2003 Feb;142(2):169
 Breastfed infants should be given Vit D 1000iuBreastfed infants should be given Vit D 1000iu
 Increase this to 2000iu in family hx of DM type 1Increase this to 2000iu in family hx of DM type 1

40. Periodontal DiseasePeriodontal Disease
 Periodontal attachment loss inverselyPeriodontal attachment loss inversely
associated with 25-OH-Vitamin D levelsassociated with 25-OH-Vitamin D levels
in adults > 50yrs oldin adults > 50yrs old
 DietrichDietrich Am J Clin Nutr. 2004 Jul;80(1):108-13.Am J Clin Nutr. 2004 Jul;80(1):108-13.

41. Medical InpatientsMedical Inpatients
 290 medical inpatients in Boston290 medical inpatients in Boston
screenedscreened
 57% with Vitamin D < 15ng/ml57% with Vitamin D < 15ng/ml
 Thomas et al. N Engl J Med 1998;338(12):777-83Thomas et al. N Engl J Med 1998;338(12):777-83
 Separate Finish studySeparate Finish study
 40-70% medical patients deficient40-70% medical patients deficient

42. Lake Almanor ClinicLake Almanor Clinic
 T Archie - unpublished case series of over 90T Archie - unpublished case series of over 90
patients with range of diagnoses (40 degpatients with range of diagnoses (40 deg
latitude)latitude)
 25OHVitD levels checked Sept 04-Jan 0725OHVitD levels checked Sept 04-Jan 07
 HTN, chronic kidney disease, osteoarthritis,HTN, chronic kidney disease, osteoarthritis,
depression, SAD, musculoskeletal pain,depression, SAD, musculoskeletal pain,
autoimmune disease, CHF, DM, overweight, CVA,autoimmune disease, CHF, DM, overweight, CVA,
elevated CRP, healthy pregnancy, screeningelevated CRP, healthy pregnancy, screening
 All but 5 patients had levels below 40ng/mlAll but 5 patients had levels below 40ng/ml
 95% incidence among this group95% incidence among this group
 Common to see level 12-25ng/mlCommon to see level 12-25ng/ml

43. ToxicityToxicity
 No credible evidence of toxicity at Vit DNo credible evidence of toxicity at Vit D
levels <150ng/mllevels <150ng/ml
 No evidence for toxicity at doses ofNo evidence for toxicity at doses of
10,000iu/d indefinitely10,000iu/d indefinitely
 Vieth R. Am J Clin Nutr. 1999;69Vieth R. Am J Clin Nutr. 1999;69
 Indicator of direct Vit D toxicityIndicator of direct Vit D toxicity
 Elevated serum calcium - AND -Elevated serum calcium - AND -
 25OHVitD > 90ng/ml25OHVitD > 90ng/ml
 Berkow. Merck Manual. 1987:928.Berkow. Merck Manual. 1987:928.

44. ToxicityToxicity
 Toxicity rare and requires long-termToxicity rare and requires long-term
administration of at least 40,000iu/day inadministration of at least 40,000iu/day in
infants (or 100,000iu/d in adults) for severalinfants (or 100,000iu/d in adults) for several
monthsmonths
 Berkow. Merck Manual. 1987:928.Berkow. Merck Manual. 1987:928.
 Toxicity sx’s appear with level >125ng/mlToxicity sx’s appear with level >125ng/ml
 Anorexia, nausea, vomiting, weakness,Anorexia, nausea, vomiting, weakness,
nervousness, pruritis, polyuria, polydipsia, renalnervousness, pruritis, polyuria, polydipsia, renal
impairment, soft tissue calcificationsimpairment, soft tissue calcifications
 Holick. Am J Clin Nutr. 2001;73(2):288.Holick. Am J Clin Nutr. 2001;73(2):288.

45. SupplementingSupplementing
 Physiologic requirement 3000-5000iu/dayPhysiologic requirement 3000-5000iu/day
 Vitamin D deficiencyVitamin D deficiency
 <20ng/ml (some authors believe this should be<20ng/ml (some authors believe this should be
<30ng/ml – and some labs have cut off at 32ng/ml)<30ng/ml – and some labs have cut off at 32ng/ml)
 Vitamin D insufficiencyVitamin D insufficiency
 <40ng/ml<40ng/ml
 PTH levels increase at 30-40ng/mlPTH levels increase at 30-40ng/ml
 Elderly men and women shown to have increasingElderly men and women shown to have increasing
PTH levels at Vit D levels <45ng/mlPTH levels at Vit D levels <45ng/ml

46. SupplementingSupplementing
 Optimal goal is 40-65ng/mlOptimal goal is 40-65ng/ml
 Humans living near the equator have mean serumHumans living near the equator have mean serum
25(OH)D levels of more than 40 ng/ml25(OH)D levels of more than 40 ng/ml
 Solar input equivalent to about 4,000 IU of vitamin DSolar input equivalent to about 4,000 IU of vitamin D
a daya day
 Linhares et al. Am J Clin Nutr. 1984:39(4):625-630Linhares et al. Am J Clin Nutr. 1984:39(4):625-630
 American lifeguards, working in swimsuits, haveAmerican lifeguards, working in swimsuits, have
even higher 25(OH)D levels (64 ng/ml), in spite ofeven higher 25(OH)D levels (64 ng/ml), in spite of
temperate latitudes.temperate latitudes.
 Holmes R, Kummerow F. J Amer Coll Nutr. 1983;2:173.Holmes R, Kummerow F. J Amer Coll Nutr. 1983;2:173.

47. Supplementing inSupplementing in
ObesityObesity
 Double the Vitamin D dosage in theDouble the Vitamin D dosage in the
patient with obesitypatient with obesity
 Excessive adipose tissue absorbsExcessive adipose tissue absorbs
Vitamin D and decreases bioavailabilityVitamin D and decreases bioavailability
by 57%by 57%
 Wortsman et al. Am J Clin Nutrition, 2000: 72 (3),Wortsman et al. Am J Clin Nutrition, 2000: 72 (3),
690-693690-693

48. SupplementingSupplementing
 ReplacementReplacement
 4000-10,000iu per day for 5-9 months4000-10,000iu per day for 5-9 months
 Baseline supplementationBaseline supplementation
 Infants 1000iu/dayInfants 1000iu/day
 Children 2000iu/dayChildren 2000iu/day
 Adults 2000iu - 4000iu/dayAdults 2000iu - 4000iu/day
 Pregnancy and Lactation 4000iu/dayPregnancy and Lactation 4000iu/day

49. SupplementationSupplementation
 Serum levels plateau after 3-4 months ofSerum levels plateau after 3-4 months of
daily supplementationdaily supplementation
 Heaney. Am J Clin Nutr. 2003;77(1):204.Heaney. Am J Clin Nutr. 2003;77(1):204.
 Therefore, be prepared to increaseTherefore, be prepared to increase
supplementation if necessary.supplementation if necessary.

50. SupplementationSupplementation
 Cod Liver Oil (concern is Vit A toxicityCod Liver Oil (concern is Vit A toxicity
depending on dose)depending on dose)
 Vitamin D3 (cholecalciferol)Vitamin D3 (cholecalciferol)
 Highest single dose available 5000iu per softgelHighest single dose available 5000iu per softgel
(Pure Encapsulations). 1000iu – Life Extension(Pure Encapsulations). 1000iu – Life Extension
SourceSource
 Preferred sourcePreferred source
 Capsule can be opened into milk for infantsCapsule can be opened into milk for infants
 Vitamin D2 (ergocalciferol)Vitamin D2 (ergocalciferol)
 Available as 50,000iu given every 1-2 weeksAvailable as 50,000iu given every 1-2 weeks
 Less effective for conversion to calcitriolLess effective for conversion to calcitriol

51. MonitoringMonitoring
 25-OH-Vit D levels and serum calcium25-OH-Vit D levels and serum calcium
 Re-check every 2-4 months when starting withRe-check every 2-4 months when starting with
levels below 35ng/ml.levels below 35ng/ml.
 Re-check every 1-2 months when levels overRe-check every 1-2 months when levels over
35ng/ml until levels plateau.35ng/ml until levels plateau.
 Consider continuing age-appropriateConsider continuing age-appropriate
supplementing with infrequent monitoringsupplementing with infrequent monitoring

52. Repeating theRepeating the
OverviewOverview
 Vitamin D receptors found in gut, bone, brain,Vitamin D receptors found in gut, bone, brain,
breast, prostate, lymphocytes, placenta, andbreast, prostate, lymphocytes, placenta, and
other tissuesother tissues
 Routine screening is appropriate at Lat >35degRoutine screening is appropriate at Lat >35deg
 Safe up to 4000iu/d without monitoringSafe up to 4000iu/d without monitoring
 Safe up to 10,000iu/d with monitoringSafe up to 10,000iu/d with monitoring
 Supplementation helpful in:Supplementation helpful in:
 DM, metabolic syndrome, CAD, depression, autoimmuneDM, metabolic syndrome, CAD, depression, autoimmune
diseases, various cancers, HTN, osteoporosis,diseases, various cancers, HTN, osteoporosis,
osteoarthritis, pain, MS, epilepsy, elderly fall prevention,osteoarthritis, pain, MS, epilepsy, elderly fall prevention,
PCOS, pregnancy & lactation, periodontal dz, URI/fluPCOS, pregnancy & lactation, periodontal dz, URI/flu
prevention, all-cause mortalityprevention, all-cause mortality

53. Thank youThank you