Vitamin D: Current Research Vitamin D: Current Research and Recommendations and Recommendations Across the Life SpanAcross the Life Span

Seema Desai, MS, RD, LDN, CNSD Kerry Harwood, MSN, RN

Vitamin D OverviewVitamin D Overview

It is a fat soluble vitamin.It is a fat soluble vitamin. Not just a vitamin it is a prehormoneNot just a vitamin it is a prehormone Found in some food and made in the body Found in some food and made in the body

after exposure to UV raysafter exposure to UV rays Major biological function is to maintain Major biological function is to maintain

normal blood levels of Ca and Po4normal blood levels of Ca and Po4 Other tissues like macrophages, prostrate Other tissues like macrophages, prostrate

tissue also have vit D receptortissue also have vit D receptor

History of Vitamin DHistory of Vitamin D Existed over 500 million yearsExisted over 500 million years Industrial revolution : rickets Industrial revolution : rickets Cod liver oil: common folklore medicine Cod liver oil: common folklore medicine Discovery of Vit D as the antirachitic factor in cod liver Discovery of Vit D as the antirachitic factor in cod liver

oil(1920)oil(1920) Discovery of conversion of 7-dehydrocholesterol in the skin Discovery of conversion of 7-dehydrocholesterol in the skin

to vit D (1937)to vit D (1937) Antirachitic property in foodAntirachitic property in food Fortification of food with vitamin D was patentedFortification of food with vitamin D was patented Complete eradication of rickets in USComplete eradication of rickets in US US public service issuing warnings about sun-induced US public service issuing warnings about sun-induced

health riskhealth risk Over next 30 yrs skin cancer hazard of excessive sun Over next 30 yrs skin cancer hazard of excessive sun

exposure became well establishedexposure became well established

Structure of Vitamin DStructure of Vitamin D

Endocrine, paracrine and intracrine Endocrine, paracrine and intracrine functions of Vitamin Dfunctions of Vitamin D

Vitamin D Across the LifespanVitamin D Across the Lifespan

Factors influencing accumulation of Factors influencing accumulation of bone minerals:bone minerals:– HeredityHeredity– GenderGender– DietDiet– Physical activityPhysical activity– Endocrine statusEndocrine status– Maternal vitamin D statusMaternal vitamin D status

Maternal Vitamin D StatusMaternal Vitamin D Status

Association of low intake of milk and vit D Association of low intake of milk and vit D during pregnancy with decreased birth during pregnancy with decreased birth weightweight..

C.A. Mannion, Katherine Gray-Donald, kristine G. Koski. CMAJ C.A. Mannion, Katherine Gray-Donald, kristine G. Koski. CMAJ April 25, 2006April 25, 2006

-Women between ages 19-45yrs-Women between ages 19-45yrs

-In Calgary-In Calgary

-</= 250 ml of milk = low birth weight-</= 250 ml of milk = low birth weight

-milk or vit D independent predictor of BW-milk or vit D independent predictor of BW

-1 cup milk = 41 gm increase in BW-1 cup milk = 41 gm increase in BW

-1 Mcg increase in dietary vit D = 11 gm increase in -1 Mcg increase in dietary vit D = 11 gm increase in BWBW

Maternal vitamin D….Maternal vitamin D….

Maternal vitamin D status during pregnancy Maternal vitamin D status during pregnancy and childhood bone mass at age 9yrs.and childhood bone mass at age 9yrs.

M.K. Javaid, SR Crozeir at al. Lancet Jan 7 2006M.K. Javaid, SR Crozeir at al. Lancet Jan 7 2006

-198 children born in 1991-92 in South Hampton UK-198 children born in 1991-92 in South Hampton UK-children were followed up at age 9yrs-children were followed up at age 9yrs-31% mother had insufficient and 18% had deficient -31% mother had insufficient and 18% had deficient

serum vit D during late pregnancyserum vit D during late pregnancy-decrease vit D in mothers = decrease bone mineral -decrease vit D in mothers = decrease bone mineral

content in children at age 9 yrscontent in children at age 9 yrs-mother’s exposure to UV rays and use of vit d -mother’s exposure to UV rays and use of vit d

predicted vit d and childhood bone masspredicted vit d and childhood bone mass

Breastfed infantsBreastfed infants

Vitamin D deficiency in breastfed infants in Vitamin D deficiency in breastfed infants in Iowa.Iowa.

Ekhard E. Ziegler, Bruce w. Hollis, Steven E Nelson and Janice Ekhard E. Ziegler, Bruce w. Hollis, Steven E Nelson and Janice M. Jeter. Pediatrics 2006M. Jeter. Pediatrics 2006-84 breastfed infants-84 breastfed infants-blood samples and dietary records were taken-blood samples and dietary records were taken-35 infants were unsupplemented -35 infants were unsupplemented -49 infants were either supplemented with formula or vit D-49 infants were either supplemented with formula or vit D-10% were vit D deficient -10% were vit D deficient -Marked seasonal affect more so in the unsupplemented -Marked seasonal affect more so in the unsupplemented groupgroup-mainly but not exclusively during winter and occurred in -mainly but not exclusively during winter and occurred in light and dark skinned infantslight and dark skinned infants

Healthy adolescentsHealthy adolescents

Prevalence of vitamin D deficiency among healthy Prevalence of vitamin D deficiency among healthy adolescents.adolescents.

Catherine M Gordon, Kerrin C. DePeter, Henry A. Feldman, Estherann Grace, Catherine M Gordon, Kerrin C. DePeter, Henry A. Feldman, Estherann Grace, Jean Emans. Arch pediatr Adolesc med June 2004Jean Emans. Arch pediatr Adolesc med June 2004-307 healthy adolescents 11-18 yrs, -307 healthy adolescents 11-18 yrs, -annual physical between july 2001-june 2003-annual physical between july 2001-june 2003-Data collected on age, sex, ethnicity, Ht, wt, exercise, medical hx diet-Data collected on age, sex, ethnicity, Ht, wt, exercise, medical hx diet-Blood samples were drawn at the end of the visit-Blood samples were drawn at the end of the visit

-24.1% of the participants were vit D deficient-24.1% of the participants were vit D deficient-highest prevalence in African American-highest prevalence in African American-Most prevalent during winter-Most prevalent during winter-no difference in prevalence between girls and boys-no difference in prevalence between girls and boys-+ correlation between soft drink consumption and vit D deficiency-+ correlation between soft drink consumption and vit D deficiency-inverse correlation between vit D deficiency and milk and cold cereal -inverse correlation between vit D deficiency and milk and cold cereal consumption consumption

Young girls in southern USYoung girls in southern US

Serum 25-hydroxy vitamin D concentration in girls Serum 25-hydroxy vitamin D concentration in girls aged 4-8 y living in the southeastern United aged 4-8 y living in the southeastern United

States.States. Stein et al.. Am J clinical nutrition 2006 Stein et al.. Am J clinical nutrition 2006

-168 prepubertal girls 4-8 yrs old-168 prepubertal girls 4-8 yrs old

-120 non-Hispanic white-120 non-Hispanic white

-48 non-Hispanic black-48 non-Hispanic black

-Oct 1997-Oct 2000 at U of GA-Oct 1997-Oct 2000 at U of GA

-with in 1 wk of blood draw bone scan, anthropometric -with in 1 wk of blood draw bone scan, anthropometric measure dietary intake, and physical activity were assessedmeasure dietary intake, and physical activity were assessed

https://docme.mc.duke.edu/ada/index.asp

o Mean vitaminD, Calcium and multivitamin Mean vitaminD, Calcium and multivitamin use was higher in white girls than in blackuse was higher in white girls than in black

o Both races had mean dietary vitamin D Both races had mean dietary vitamin D intake above adequate levelsintake above adequate levels

o Race and season strongest predictor of vit D Race and season strongest predictor of vit D statusstatus

o Black girls had lower mean vit D valueBlack girls had lower mean vit D valueo Vitamin D value were significantly higher in Vitamin D value were significantly higher in

summer than in winter summer than in winter o Living at low latitude does not entirely Living at low latitude does not entirely

prevent poor vitamin D statusprevent poor vitamin D status

Milk Allergies and vitamin D Milk Allergies and vitamin D deficiencydeficiency

Milk allergy and vitamin D deficiency rickets: a common Milk allergy and vitamin D deficiency rickets: a common disorder associated with an uncommon disease. Case disorder associated with an uncommon disease. Case ReportReport

Joyce w. Yu at el…Joyce w. Yu at el…Annals of allergy, asthma and immunology…April 2006Annals of allergy, asthma and immunology…April 2006

-Case report of Vit D deficiency rickets in 2 yr old boy with-Case report of Vit D deficiency rickets in 2 yr old boy withmilk allergymilk allergy-BF for 6-7 months-BF for 6-7 months-failed trail of cows milk formula-failed trail of cows milk formula-drank 500-700ml of fruit juice with no vit D and Ca -drank 500-700ml of fruit juice with no vit D and Ca supplementationsupplementation-18 months of age started to regress-18 months of age started to regress-Lab values: Vit D of 8 mmol/l, Ca: 1.98 mmol/l, alk phos:-Lab values: Vit D of 8 mmol/l, Ca: 1.98 mmol/l, alk phos:-2,822u/l-2,822u/l

o Discharged taking 4000IU of vit D, 200mg Discharged taking 4000IU of vit D, 200mg calcitriol, and 300mg elemental Cacalcitriol, and 300mg elemental Ca

o 2 weeks later was able to stand, and his lab 2 weeks later was able to stand, and his lab values were improved.values were improved.

AdultsAdults

Vitamin D Deficiency in Vitamin D Deficiency in Hospitalized PatientsHospitalized Patients

Vitamin D Deficiency in Vitamin D Deficiency in Renal Transplant PatientsRenal Transplant Patients

Vitamin D Inadequacy in Vitamin D Inadequacy in Post-Menopausal WomenPost-Menopausal Women

Vitamin D and CancerVitamin D and Cancer

May influence both incidence and May influence both incidence and mortalitymortality

Linked with GI cancer, prostate and Linked with GI cancer, prostate and breast cancers, lymphomas, breast cancers, lymphomas, endometrial and lung cancersendometrial and lung cancers

Something New Under the Sun?Something New Under the Sun?

Apperly FL. Apperly FL. The relation of solar The relation of solar radiation to cancer mortality in North radiation to cancer mortality in North

America. America.

Cancer Research.1941(1):191-195Cancer Research.1941(1):191-195

1979 - 19811979 - 1981

Vitamin D receptors found in Vitamin D receptors found in malignant melanoma cells and malignant melanoma cells and myeloid leukemia cellsmyeloid leukemia cells

1,25(OH)1,25(OH)22D inhibited melanoma cell D inhibited melanoma cell proliferation and induced myeloid proliferation and induced myeloid cell differentiationcell differentiation

Northern vs. Southern U.S.Northern vs. Southern U.S.

1 – 2 extra skin cancer deaths (per 100,000)

30 – 40 extra deaths for other major cancers (per 100,000)

19981998

Serum levels of 1,25(OH)Serum levels of 1,25(OH)22D are D are tightly controlled by the kidneys & tightly controlled by the kidneys & don’t vary by sun exposure so how don’t vary by sun exposure so how could vitamin D contribute to the could vitamin D contribute to the north-south gradients and African-north-south gradients and African-American excess in cancer rates?American excess in cancer rates?

Non-renal cells discovered to Non-renal cells discovered to hydroxylate 25(OH)D and synthesize hydroxylate 25(OH)D and synthesize 1,25(OH)1,25(OH)22D locally.D locally.

Vitamin D & CancerVitamin D & Cancer

Environmental: sunlight & dietEnvironmental: sunlight & diet– Calcitriol (hormonal form of vitamin D) Calcitriol (hormonal form of vitamin D)

controls the differentiation of many cells controls the differentiation of many cells that possess vitamin D receptors (VDR)that possess vitamin D receptors (VDR)

– Induce cell differentiation and apoptosis Induce cell differentiation and apoptosis of cancer cells while inhibiting cell of cancer cells while inhibiting cell proliferation, angiogenesis, and proliferation, angiogenesis, and metastasismetastasis

Genetic: VDR polymorphismsGenetic: VDR polymorphisms

June, 2007 American Journal of June, 2007 American Journal of Clinical NutritionClinical Nutrition

Women who regularly took vitamin Women who regularly took vitamin D3 and calcium had a 60% reduction D3 and calcium had a 60% reduction in all-cancer incidence compared in all-cancer incidence compared with a group taking placebo and a with a group taking placebo and a 77% reduction when the analysis was 77% reduction when the analysis was confined to cancers diagnosed after confined to cancers diagnosed after the first 12 months.the first 12 months.

Lung cancerLung cancer

1,25(OH)1,25(OH)22D:D: inhibits proliferation and induces inhibits proliferation and induces

differentiation of lung cancer cell differentiation of lung cancer cell lines (Higashimoto, et al., 1996, lines (Higashimoto, et al., 1996, Guzey, et al., 1998)Guzey, et al., 1998)

inhibits metastatic growth and inhibits metastatic growth and locoregional recurrence of lung locoregional recurrence of lung cancer cells in mice (Wiers, et al., cancer cells in mice (Wiers, et al., 2000)2000)

Lung cancerLung cancer

456 patients with early stage NSCLC456 patients with early stage NSCLC– Median age – 69Median age – 69– 96% Caucasian96% Caucasian

Data collection:Data collection:– Season of surgerySeason of surgery– Food frequency questionnaireFood frequency questionnaire– Recurrence free survival (RFS)Recurrence free survival (RFS)– Overall survival (OS)Overall survival (OS)

Zhou, et al., 2005Zhou, et al., 2005

Lung cancerLung cancer

Patients who had surgery during Patients who had surgery during summer with the highest vitamin D summer with the highest vitamin D intake had better RFS that patients intake had better RFS that patients who had surgery during winter with who had surgery during winter with the lowest vitamin D intake.the lowest vitamin D intake.

Similar associations were seen for Similar associations were seen for overall survival.overall survival.

Zhou, et al., 2005Zhou, et al., 2005

Lung cancer Lung cancer

Insert survival graph from Zhou article Insert survival graph from Zhou article herehere

Breast cancerBreast cancer

1,25(OH)1,25(OH)22D:D: inhibits cell proliferation, induces inhibits cell proliferation, induces

differentiation & apoptosis, and inhibits differentiation & apoptosis, and inhibits angiogenesis in normal and breast cancer angiogenesis in normal and breast cancer cells (Colston, et al, 1989, Saez, et al, cells (Colston, et al, 1989, Saez, et al, 1993, Mantell, et al., 2000)1993, Mantell, et al., 2000)

suppresses high-fat diet-induced suppresses high-fat diet-induced mammary tumorigenesis in rats (Jacobson, mammary tumorigenesis in rats (Jacobson, et al., 1989, Xue, 1999)et al., 1989, Xue, 1999)

Breast cancerBreast cancer Inverse association between vitamin D & Inverse association between vitamin D &

calcium intake and breast densitycalcium intake and breast density Inconclusive results in studies looking at Inconclusive results in studies looking at

VDR genetic polymorphisms and breast VDR genetic polymorphisms and breast cancercancer

Inverse association between high sunlight Inverse association between high sunlight exposure and breast cancer riskexposure and breast cancer risk

Association may be stronger for Association may be stronger for premenopausal than postmenopausal premenopausal than postmenopausal women due to interactions between women due to interactions between vitamin D, the VDR, estrogen and insulin-vitamin D, the VDR, estrogen and insulin-like growth factor-I (IGF-I)like growth factor-I (IGF-I)

Cui & Rohan, 2006Cui & Rohan, 2006

Breast cancerBreast cancer

Case-control study – 972 women with Case-control study – 972 women with newly-diagnosed breast cancer & newly-diagnosed breast cancer & 1,135 healthy controls1,135 healthy controls

Interviews regarding vitamin D-Interviews regarding vitamin D-related exposures, e.g. outdoor related exposures, e.g. outdoor activities, use of sunscreen, dietary activities, use of sunscreen, dietary contributionscontributions

Knight, 2007Knight, 2007

Breast cancerBreast cancer

More frequent sun exposure during More frequent sun exposure during adolescence was associated with a adolescence was associated with a 35% reduction in breast cancer risk 35% reduction in breast cancer risk later in lifelater in life

Lower risk also linked to cod liver oil Lower risk also linked to cod liver oil and milk intake > 10 glasses / weekand milk intake > 10 glasses / week

Milder protection seen for people age Milder protection seen for people age 20 – 2920 – 29

No protection for people over age 45No protection for people over age 45

Breast cancerBreast cancer

Epidemiologic study of different regions of Epidemiologic study of different regions of Norway, each with a different annual UV Norway, each with a different annual UV exposureexposure

Prognosis 15 – 25% better for women Prognosis 15 – 25% better for women diagnosed / treated in the summer vs. diagnosed / treated in the summer vs. winterwinter

<get this article: Breast Cancer Research <get this article: Breast Cancer Research and Treatment, May>Knight , 2007and Treatment, May>Knight , 2007

Endometrial cancerEndometrial cancer

Is ultraviolet B irradiance inversely Is ultraviolet B irradiance inversely associated with incidence rates of associated with incidence rates of endometrial cancer: an ecological endometrial cancer: an ecological

study of 107 countries.study of 107 countries.

Mohr, et al, 2007Mohr, et al, 2007

Endometrial cancerEndometrial cancer

Objective: perform an ecological Objective: perform an ecological analysis of the relationship between analysis of the relationship between low levels of ultraviolet B irradiance low levels of ultraviolet B irradiance and age-standardized incidence rates and age-standardized incidence rates of endometrial cancer by country, of endometrial cancer by country, controlling for known confounderscontrolling for known confounders

Endometrial cancerEndometrial cancer 107 countries:107 countries:

– UVB irradianceUVB irradiance– cloud covercloud cover– intake of energy from animal sourcesintake of energy from animal sources– proportion overweightproportion overweight– skin pigmentationskin pigmentation– cigarette consumptioncigarette consumption– health expenditure health expenditure – total fertility rates total fertility rates

vs. age-standardized incidence of vs. age-standardized incidence of endometrial cancerendometrial cancer

Endometrial cancerEndometrial cancer

Association found between Association found between endometrial cancer incidence rates endometrial cancer incidence rates and:and:– Low UVB irradianceLow UVB irradiance– High intake of energy from animal High intake of energy from animal

sources (sources ( IGF-I?) IGF-I?)– Per capital health expenditurePer capital health expenditure– Proportion of population overweightProportion of population overweight

Pancreatic cancerPancreatic cancer

Prospectively collected diet and lifestyle Prospectively collected diet and lifestyle datadata– Nurses’ Health Study – 75,427 womenNurses’ Health Study – 75,427 women– Health Professionals Follow-up Study – 46,771 Health Professionals Follow-up Study – 46,771

menmen Pancreatic cancer risk 41% lower among Pancreatic cancer risk 41% lower among

those who consumed > 600 IU of vitamin those who consumed > 600 IU of vitamin D / day vs. those who consumed < 150 IU / D / day vs. those who consumed < 150 IU / dayday

Skinner, et al., 2006Skinner, et al., 2006

Cancer SurvivalCancer Survival

Summer / Fall (vs. Winter / Summer / Fall (vs. Winter / Spring) diagnosis associated with Spring) diagnosis associated with improved survival in:improved survival in:– Colorectal cancerColorectal cancer– Hodgkin’s lymphomaHodgkin’s lymphoma– NSCLCNSCLC– Breast cancerBreast cancer

Cancer SurvivalCancer Survival

Intermittent sun exposure Intermittent sun exposure associated with increased survival associated with increased survival following a diagnosis of melanomafollowing a diagnosis of melanoma

Berwick, et al., 2005Berwick, et al., 2005

Type 2 DiabetesType 2 Diabetes

Altered vitamin D and calcium Altered vitamin D and calcium homeostasis may play a role in homeostasis may play a role in development of type 2 diabetesdevelopment of type 2 diabetes

Low serum levels of 25(OH)D are Low serum levels of 25(OH)D are associated with impaired pancreatic associated with impaired pancreatic ββ cell function and insulin resistance cell function and insulin resistance

High calcium intake is inversely High calcium intake is inversely associated with body weightassociated with body weight

Type 2 DiabetesType 2 Diabetes

Nurses’ Health Study – 83,779 Nurses’ Health Study – 83,779 women (98% Caucasian)women (98% Caucasian)

Daily intake of >1,200 mg calcium Daily intake of >1,200 mg calcium & >800IU vitamin D was & >800IU vitamin D was associated with a 33% lower risk associated with a 33% lower risk of type 2 diabetes compared with of type 2 diabetes compared with an intake of <600 mg calcium & an intake of <600 mg calcium & <400 IU vitamin D<400 IU vitamin D

Pittas, et al., 2006Pittas, et al., 2006

Type 1 DiabetesType 1 Diabetes

Birth-cohort study in Finland – all women Birth-cohort study in Finland – all women due to give birth in 1966 enrolleddue to give birth in 1966 enrolled

10,366 children born alive and followed to 10,366 children born alive and followed to one year; 81 diagnosed with Type 1 one year; 81 diagnosed with Type 1 diabetesdiabetes

Children who regularly took recommended Children who regularly took recommended dose of vitamin D (2000 IU) had a RR of dose of vitamin D (2000 IU) had a RR of 0.22 compared with those who did not.0.22 compared with those who did not.

Children suspected of having rickets had a Children suspected of having rickets had a RR of 3.0 compared with those not RR of 3.0 compared with those not suspected.suspected.

Hopponen, et al., 2001Hopponen, et al., 2001

Metabolic SyndromeMetabolic Syndrome

Third National Health & Nutrition Third National Health & Nutrition Examination Survey (NHANES III)Examination Survey (NHANES III)– 8,421 men and non-pregnant women > 8,421 men and non-pregnant women >

20 years of age and had fasted 20 years of age and had fasted >> 8 hrs 8 hrs Unadjusted prevalence of metabolic Unadjusted prevalence of metabolic

syndrome - 21.9%syndrome - 21.9%

Metabolic SyndromeMetabolic Syndrome

After adjustments for known risk factors, After adjustments for known risk factors, odd of metabolic syndrome decreased odd of metabolic syndrome decreased progressively across increasing progressively across increasing concentrations of 25(OH)Dconcentrations of 25(OH)D

Relative risk compared with bottom Relative risk compared with bottom quintile of vitamin D level:quintile of vitamin D level:– 22ndnd quintile – 0.85 quintile – 0.85– 33rdrd quintile – 0.75 quintile – 0.75– 44thth quintile – 0.62 quintile – 0.62– 55thth quintile – 0.46 quintile – 0.46

Ford, et al., 2005Ford, et al., 2005

Pulmonary / COPDPulmonary / COPD

• Third National Health & Nutrition Third National Health & Nutrition Examination Survey (NHANES III)Examination Survey (NHANES III)• 14,000 subjects14,000 subjects• Dose-response correlation between Dose-response correlation between

percent predicted FEVpercent predicted FEV11 and FVC values and FVC values and circulating 25(OH)Dand circulating 25(OH)D

• Plausibility: vitamin D shown to prevent Plausibility: vitamin D shown to prevent experimental inflammatory diseases in experimental inflammatory diseases in mice including allergic asthmamice including allergic asthma

Black, et al., Chest, 2005Black, et al., Chest, 2005

Congestive Heart FailureCongestive Heart Failure

RCT of vitamin D + calcium vs. RCT of vitamin D + calcium vs. placebo + calcium x 9 months in placebo + calcium x 9 months in subjects with CHFsubjects with CHF– 93 subjects completed study93 subjects completed study– Anti-inflammatory cytokine interleukin Anti-inflammatory cytokine interleukin

10 significantly higher10 significantly higher– Suppressed release of TNF-Suppressed release of TNF-αα– No difference in survival but blood levels No difference in survival but blood levels

not optimizednot optimizedSchleithoff, et al., 2006Schleithoff, et al., 2006

HypertensionHypertension

Prospectively followed two cohorts:Prospectively followed two cohorts:– Nurses’ Health Study – 1198 womenNurses’ Health Study – 1198 women– Health Professionals Follow-up Study – Health Professionals Follow-up Study –

613 men613 men Relative risk of hypertension:Relative risk of hypertension:

– < 15 ng/mL vs < 15 ng/mL vs >> 30 ng/mL 25(OH)D 30 ng/mL 25(OH)D Men: RR = 6.13Men: RR = 6.13Women: RR = 2.67Women: RR = 2.67

StrokeStroke

Chronic Kidney DiseaseChronic Kidney Disease

Multiple SclerosisMultiple Sclerosis

Osteo- & Rheumatoid ArthritisOsteo- & Rheumatoid Arthritis

Where do we go from here?Where do we go from here?

Routine screeningRoutine screening

Rectify deficiency / insufficiencyRectify deficiency / insufficiency Maintain levels through a patient-Maintain levels through a patient-

specific combination of diet, specific combination of diet, supplementation, and sun exposuresupplementation, and sun exposure

RecommendationsRecommendations

Annual testing of 25(OH)DAnnual testing of 25(OH)D Consider time of year in testingConsider time of year in testing

– Lowest levels generally towards Lowest levels generally towards end of winter, early springend of winter, early spring

Vitamin D AssessmentVitamin D Assessment

Lab assays are available to measure both Lab assays are available to measure both 25(OH)D and 1,25-D.25(OH)D and 1,25-D.

25(OH)D closely reflects total amount of 25(OH)D closely reflects total amount of vit D produced in the skin and from dietvit D produced in the skin and from diet

D2 and D3: have similar biological activityD2 and D3: have similar biological activity Both D2 and D3 should be measuredBoth D2 and D3 should be measured DO NOT USE - 1,25-D. This can often be DO NOT USE - 1,25-D. This can often be

normal with vit D deficiencynormal with vit D deficiency

Goals in Maintaining Goals in Maintaining Vitamin D LevelsVitamin D Levels

1.1. Prevent disease of deficiency – Prevent disease of deficiency – rickets, osteomalaciarickets, osteomalacia

2.2. Prevent complications of Prevent complications of insufficiency – impaired calcium insufficiency – impaired calcium absorption and increased bone absorption and increased bone resorptionresorption

3.3. Minimize risks of future disease – Minimize risks of future disease – cancer, cardiopulmonary diseases, cancer, cardiopulmonary diseases, diabetes, other immune-related diabetes, other immune-related diseasesdiseases

25(OH)D concentration25(OH)D concentration

To prevent deficiency disease – To prevent deficiency disease – > 25 nmol / L> 25 nmol / L

To prevent complications of To prevent complications of insufficiency – insufficiency – >> 50 nmol/L 50 nmol/L

For maximum bone health and For maximum bone health and prevention of chronic disease – prevention of chronic disease – 75 – 100 nmol/L75 – 100 nmol/L

Who is at greatest risk?Who is at greatest risk? Low dietary intake: BF infants, children who do not drink Low dietary intake: BF infants, children who do not drink

fortified milkfortified milk Malabsorption syndromeMalabsorption syndrome Severe liver diseaseSevere liver disease Kidney diseaseKidney disease DrugsDrugs Higher latitudesHigher latitudes People who spend little time outsidePeople who spend little time outside Older adultsOlder adults Decreased sun exposure due to cultural reasonsDecreased sun exposure due to cultural reasons Races with high skin melanin levelsRaces with high skin melanin levels

SupplementationSupplementation

Supplementation (adults)Supplementation (adults)

To correct deficiency: 50,000 IU To correct deficiency: 50,000 IU vitamin D weekly x 8 weeks, vitamin D weekly x 8 weeks, reassess and repeat if necessaryreassess and repeat if necessary

Supplementation (peds)Supplementation (peds)

To correct deficiency To correct deficiency

IOM RecommendationsIOM Recommendations (AI) (AI)AgeAge ChildrenChildren MenMen WomenWomen PregnancPregnanc

yylactationlactation

Birth-13 Birth-13 yrsyrs

5mcgs5mcgs

=200IU=200IU

14-14-18yrs18yrs

55

200IU200IU55

200 IU200 IU55

200IU200IU55

200IU200IU

19-5019-50

YrsYrs55

200200

IUIU

55

200 IU200 IU55

200 IU200 IU55

200 IU200 IU

51-7051-70

YrsYrs1010

400 IU400 IU1010

400 IU400 IU

71+71+ 1515

600 IU600 IU1515

600 IU600 IU

Do recommendations reflect the Do recommendations reflect the state of the science?state of the science?

‘ ‘Our studies in children (3 – 16 years Our studies in children (3 – 16 years of age) in Edmonton, Alberta, show of age) in Edmonton, Alberta, show that 200 IU daily is not even that 200 IU daily is not even adequate for maintaining levels now adequate for maintaining levels now considered mildly to moderately considered mildly to moderately deficient (40 nmol/L), let alone deficient (40 nmol/L), let alone optimum (80 nmol/L).’optimum (80 nmol/L).’

A.B. Jones, Canadian Family Physician, 2006A.B. Jones, Canadian Family Physician, 2006

Do recommendations reflect the Do recommendations reflect the state of the science?state of the science?

‘ ‘Oral doses currently consumed in the US Oral doses currently consumed in the US (an estimated mean of 320 IU / day) are (an estimated mean of 320 IU / day) are far too low, and the designation of the far too low, and the designation of the 2000 IU/day dosage as safe by NAS 2000 IU/day dosage as safe by NAS provides latitude to the community to provides latitude to the community to increase intakes to levels required to increase intakes to levels required to reduce risk of cancer, with essentially no reduce risk of cancer, with essentially no likelihood of adverse effects.’likelihood of adverse effects.’

Grant and Gorham, International J of Epidemiology, 2006Grant and Gorham, International J of Epidemiology, 2006

Do recommendations reflect the Do recommendations reflect the state of the science?state of the science?

‘… ‘…the present recommended the present recommended allowance for vitamin D – 400 IU – for allowance for vitamin D – 400 IU – for individuals aged 50 – 70 years is individuals aged 50 – 70 years is inadequate even to maintain skeletal inadequate even to maintain skeletal health and is probably too low for health and is probably too low for meaningful anticancer effects.’meaningful anticancer effects.’

Schwartz & Blot, J National Cancer Institute, 2006Schwartz & Blot, J National Cancer Institute, 2006

National Academy of ScienceNational Academy of Science Tolerable Upper Intake Levels Tolerable Upper Intake Levels

Pediatrics 0 – 12 months – Pediatrics 0 – 12 months – 1000 IU / Day1000 IU / Day

All others – All others – 2000 IU / Day2000 IU / Day

USDHHS Dietary Guidelines for USDHHS Dietary Guidelines for America - 2005America - 2005

Special groups – elderly and Special groups – elderly and individuals with dark skin – individuals with dark skin – 1,000 IU / day1,000 IU / day

Maintenance (adults)Maintenance (adults)

To maintain recommended levels: To maintain recommended levels: 800 - 1000 IU / day if not getting 800 - 1000 IU / day if not getting enough sun exposure to maintain enough sun exposure to maintain vitamin D levels or 50,000 IU 1-2 vitamin D levels or 50,000 IU 1-2 times monthlytimes monthly

North American Conference North American Conference on Vitamin Don Vitamin D

“ “to minimize the health risks to minimize the health risks associated with UVB radiation associated with UVB radiation exposure while maximizing the exposure while maximizing the potential benefits of optimum potential benefits of optimum vitamin D status, {dietary} vitamin D status, {dietary} supplementation and small amounts supplementation and small amounts of sun exposure are the preferred of sun exposure are the preferred methods of obtaining vitamin D.” methods of obtaining vitamin D.”

Consensus statement, 2006Consensus statement, 2006

How much sun?How much sun?

Depends on:Depends on:– AgeAge– Amount of vitamin D obtained from dietAmount of vitamin D obtained from diet– Skin darknessSkin darkness– Sunshine intensitySunshine intensity

How much sun?How much sun?

Significant skin exposureSignificant skin exposure– Face, neck, arms, handsFace, neck, arms, hands– Arms, legsArms, legs

Adequate sun strengthAdequate sun strength TimeTime

– 25% of the time it would take to cause 25% of the time it would take to cause pinkness of the skin (Caucasians)pinkness of the skin (Caucasians)

– People with dark skin require People with dark skin require significantly more sun exposuresignificantly more sun exposure

Holick, 2004Holick, 2004

Food Sources of Vitamin DFood Sources of Vitamin D Cod liver oil – 1 TBSCod liver oil – 1 TBS Salmon 3.5 oz.Salmon 3.5 oz. Mackerel 3.5 oz.Mackerel 3.5 oz. Tuna, canned, in oil, 3 oz.Tuna, canned, in oil, 3 oz. Sardines 3.5 oz.Sardines 3.5 oz. Milk (fortified) 8 oz.Milk (fortified) 8 oz. Ready to eat cereal Ready to eat cereal

(fortified) ¾ - 1 cup(fortified) ¾ - 1 cup Egg 1 wholeEgg 1 whole Liver, 3.5 oz.Liver, 3.5 oz. Cheese, swiss 1 oz.Cheese, swiss 1 oz.

1,360 IU1,360 IU 360360 345345 200200 250250 9898 4040

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