Vitamin D and Calcium New Research – New Recommendations? · Vitamin D and Calcium New Research – New Recommendations? will begin at the top of the hour Audio for today’s presentation

Vitamin D and CalciumNew Research – New Recommendations?

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NUTRI-BITES®

Webinar Series

November 5, 2015

Presenter:

Robert P. Heaney, MD, FACP, FASNJohn A. Creighton University Professor

& Professor of MedicineCreighton University Osteoporosis Research Center

Moderator:James M. Rippe, MD – Leading cardiologist, Founder and Director,

Rippe Lifestyle Institute

Approved for 1 CPE (Level 2) by the Commission on Dietetic Registration, credentialing agency for the Academy of Nutrition and Dietetics.

NUTRI-BITES®

Webinar Series

Vitamin D and CalciumNew Research - New Recommendations?

ConAgra Foods Science Institute With a mission of:

Promoting dietary and related choices affecting wellness

by linking evidence-based understanding

with practice

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certificate will be emailed and available on this webinar’s page at www.ConAgraFoodsScienceInstitute.com within 2 days.

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The presenter will answer questions at the end of this webinar. Please submit questions by using the ‘Chat’ dialogue box on your computer screen.

Today’s Faculty

Robert P. Heaney, MD, FACP, FASNJohn A. Creighton University Professor

& Professor of MedicineCreighton University Osteoporosis Research Center

Moderator:James M. Rippe, MD – Leading cardiologist, Founder and Director, Rippe Lifestyle Institute

Learning Objectives Recall the principal roles vitamin D and calcium serve in the

human body Describe how nutrients – and vitamin D in particular – are

like preventive maintenance of a complex machine Describe some of the consequences of inadequate intake of

each nutrient List the principal sources of vitamin D and calcium Recall the optimal intake/input of each nutrient, with

emphasis on differing needs at different life stages

NUTRI-BITES®

Webinar SeriesVitamin D and Calcium: New Research-New Recommendations

VITAMIN D AND CALCIUM

New Research –New Recommendations ?

Robert P. Heaney, MD, FACP, FASN

Creighton University Osteoporosis Research Center

Two fundamentally different ways of approaching nutrients:

micro-nutrients macro-nutrients



needed for the proper running of the biochemical apparatus of all living cells; think: preventive maintenance



needed for body structures;think: extracellular fluid

volume or bone mass

needed for the proper running of the biochemical apparatus of all living cells; think: preventive maintenance



Vitamin D



Calcium

Vitamin D


micro-nutrients macro-nutrientsexcept for the classical

deficiency diseases: don’t expect miracles don’t look for dramatic

disease cures

Two fundamentally different ways of approaching nutrients


look instead for longer life expectancy better functional life

CU ORC

TWO FRAMEWORKS:The nutrient requirement

Risk assessment Physiology

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THE NUTRIENT REQUIREMENT:

Two Frameworks


Avoidance of some disease

outcome

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THE NUTRIENT REQUIREMENT:Two Frameworks


Avoidance of some disease

outcome

Support of cell function

The physiological approach must inevitably produce a higher estimate of the requirement than the disease avoidance approach:

the questions are different the goals are different the endpoints are different

CU ORC

THREE PHYSIOLOGICAL CRITERIA an example of a physiologically based

requirement would be an intake that: calls for the least day-to-day adaptation or

compensation

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THREE PHYSIOLOGICAL CRITERIA examples of a physiologically based

requirement would be : an intake that calls for the least day-to-day

adaptation or compensation an intake to which the human body has been

adapted by natural selection

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THREE PHYSIOLOGICAL CRITERIA examples of a physiologically based

requirement would be : an intake that calls for the least day-to-day

adaptation or compensation an intake to which the human body has been

adapted by natural selection an intake that is needed to support one or

more essential physiological functions

Vitamin D

CU ORC

RECOMMENDATION DISCORDANCE

Ages 51–70: IOM 2010 Endo Soc 2010 Am Ger Soc 2014 GrassrootsHealth

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RECOMMENDATION DISCORDANCE

Ages 51–70: IOM 2010 Endo Soc 2010 Am Ger Soc 2014 GrassrootsHealth

Daily Input (IU)RDA/AI TUIL

600 4,0001,500–2,000 10,000

4,000 --4,000–5,000 ––

Minimizing the need for compensation

low Ca absorption

low Ca absorptionelevated PTH production


elevated1,25(OH)2Dproduction



Ca absorption



Ca absorption



Ca absorption

Elevated PTH is an index of Ca and/or vitamin D inadequacy



Ca absorption

Elevated PTH is an index of Ca and/or vitamin D inadequacy

The rise in PTH doesn’t cause us to consume more Ca, but it does cause us to absorb more, thus tending to close the loop

CU ORC

THE SETPOINT CRITERION

Serum 25(OH)D (ng/mL)0 10 20 30 40 50 60

Seru

m P

TH (pg

/mL)

0

20

40

60

80

100

120

data from NHANES 2003-2006

N = 14,681 Ginde etal., J.

Endocrinol. Invest. (2011)

CU ORC


Serum 25(OH)D (ng/mL)0 10 20 30 40 50 60

Seru

m P

TH (pg

/mL)

0

20

40

60

80

100

120




CU ORC


Serum 25(OH)D (ng/mL)0 10 20 30 40 50 60

Seru

m P

TH (pg

/mL)

0

20

40

60

80

100

120 With a physiological criterion, “normal” vitamin D status would be a 25(OH)D concentration that required little or no compensatory PTH response under basal conditions.




Compensation is metabolically costly and often takes a toll in other organ systems.

Compensation is metabolically costly and often takes a toll in other organ systems.

Over the course of the evolution of human physiology, natural selection would have favored organisms that did not have to compensate for what the environment provided.

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SCORECARD

Criterion Serum 25(OH)Dminimal adaptation ~ 48–52 ng/mLancestral statusphysiological support

Matching the ancestral intake

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NATIVE AFRICANS* Masai

(pastoralists) Hadza (hunter-

gatherers)

* Luxwolda et al., BJN 2011

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NATIVE AFRICANS* Masai (pastoralists) diet differs from the

ancestral, but latitude, skin pigmentation, and skin exposure are the same as ancestral


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NATIVE AFRICANS* Hadza (hunter-

gatherers) diet, latitude, skin

exposure, and skin pigmentation are all ancestral

they have been called “the last of the first”


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NATIVE AFRICANS*

Maasai Hadzabe

Seru

m 2

5(O

H)D

(nm

ol/L

)

0

25

50

75

100

125

150

175


CU ORC

NATIVE AFRICANS*

Maasai Hadzabe

Seru

m 2

5(O

H)D

(nm

ol/L

)

0

25

50

75

100

125

150

175


Ancestral

CU ORC

NATIVE AFRICANS*

Maasai Hadzabe

Seru

m 2

5(O

H)D

(nm

ol/L

)

0

25

50

75

100

125

150

175


IOM

Ancestral

CU ORC

NATIVE AFRICANS*

Maasai Hadzabe

Seru

m 2

5(O

H)D

(nm

ol/L

)

0

25

50

75

100

125

150

175


IOM

Endocrine Society

Ancestral

CU ORC

SCORECARD

Criterion Serum 25(OH)Dminimal adaptation ~ 48–52 ng/mLancestral status ~ 46 ng/mLphysiological support

Just because ancestral humans averaged ~115 nmol/L doesn’t mean that modern humans need that much.

Just because ancestral humans averaged ~115 nmol/L doesn’t automatically mean that modern humans need that much.

But that’s the best starting point in determining the requirement, the burden of

proof should fall on those who say lower 25(OH)D values are adequate (and safe).

the question of adequacy must be: Will lower levels support critical physiological activities?

Supporting a critical physiological function

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LACTATION FACTS human milk is capable of providing all the vitamin D

(cholecalciferol) an infant needs

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(cholecalciferol) an infant needs but only if the mother has native vitamin D

(cholecalciferol) in her blood

CU ORC



(cholecalciferol) in her blood cholecalciferol crosses from the blood into the milk,

but 25(OH)D does not

CU ORC




but 25(OH)D does not so maternal serum cholecalciferol is the key variable

CU ORC




but 25(OH)D does not so serum cholecalciferol is the key variable its concentration begins to rise only after the hepatic

25-hydroxylase is approximately saturated, and that corresponds to a serum 25(OH)D above 100 nmol/L (40 ng/mL)

Serum Vitamin D3 (nmol/L)0 50 100 150 200 250

Seru

m 2

5(O

H)D

(nm

ol/L

)

0

50

100

150

200

250

300

THE D3-25(OH)D RELATIONSHIP*

* Heaney et al., (2008) AJCN 87:1730-37

Y = 0.433X + 87.8(1 – e-0.468X)


Seru

m 2

5(O

H)D

(nm

ol/L

)

0

50

100

150

200

250

300


* Heaney et al., (2008) AJCN 87:1730-37

Y = 0.433X + 87.8(1 – e-0.468X)

note the steep rise in 25(OH)D over very little change in serum D3,reflecting 1st

order kinetics


Seru

m 2

5(O

H)D

(nm

ol/L

)

0

50

100

150

200

250

300


* Heaney et al., (2008) AJCN 87:1730-37

Y = 0.433X + 87.8(1 – e-0.468X)

note the steep rise in 25(OH)D over very little change in serum D3,reflecting 1st

order kinetics

saturation of the 25-hydroxylase occurs here


* Heaney et al., (2008) AJCN 87:1730-37

Y = 0.433X + 87.8(1 – e-0.468X)


Seru

m 2

5(O

H)D

(nm

ol/L

)

0

50

100

150

200

250

300


* Heaney et al., (2008) AJCN 87:1730-37

Y = 0.433X + 87.8(1 – e-0.468X)


Seru

m 2

5(O

H)D

(nm

ol/L

)

0

50

100

150

200

250

300

this is the maternal 25(OH) D value that corresponds with the D3 level needed to ensure adequate D3 in breast milk

Serum Vitamin D3 (nmol/L)

0 20 40 60 80 100

Seru

m 2

5(O

H)D

(nm

ol/L

)

0

50

100

150

200

250

300

RELATIONSHIP OF D3 & 25D

this is the IOM value for adequacy; note that the D3concentration is too low to permit any transfer into milk

CU ORC

25(OH)D LEVELS IN NURSING INFANTS*

Treatment Group

Infa

nt 2

5(O

H)D

(nm

ol/L

) a

t 7 m

onth

s po

stpa

rtum

0

20

40

60

80

100

120

140400 IU/d, infant only

6400 IU/d, nursing mother only

*Hollis, Wagner, et al. (2015)

CU ORC

SUMMARY vitamin D remains a nutrient of concern

in pregnant women in babies in utero in infants

low perinatal vitamin D status leads to several late-life consequences

serum 25(OH)D levels should be maintained at 40 ng/mL or above

CU ORC

SCORECARD

Criterion Serum 25(OH)Dminimal adaptation ~ 48–52 ng/mLancestral status ~ 46 ng/mLphysiological support ~ 48–60 ng/mL

Calcium

Calcium&

Bone Health

Bone Health and OsteoporosisA Report of the Surgeon General

“Calcium has been singled out as a majorpublic health concern today because it is critically important to bone health and the average American consumes levels of calcium that are far below the amount recommended for optimal bone health.”

October 14, 2004



October 14, 2004



October 14, 2004



October 14, 2004

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CONSENSUS CONFERENCES

three NIH Consensus Development Conferences had specifically recommended Ca supplements: 1984 – Osteoporosis 1994 – Optimal Ca Intake 2000 – Osteoporosis

CU ORC

DANGERS WITH CALCIUM?

haven’t there been some papers suggesting increased CVD risk with Ca supplements?

Yes, but these papers have been thoroughly

refuted and, as it turns out, high Ca intakes are actually associated with reduced all-cause mortality

CU ORC

DIET CALCIUM AND MORTALITY 23,366 Swedish men 10-yr prospective

study 2358 deaths highest Ca intake

tertile compared to lowest

Kaluza et al., Am J Epidemiol2010, 171:801–7

CU ORC





0.0

0.2

0.4

0.6

0.8

1.0

All-cause CVD Cancer

Hazard Ratio

CU ORC





0.0

0.2

0.4

0.6

0.8

1.0

All-cause CVD Cancer

Hazard Ratio

CU ORC

Ca AND HIP FRACTURE*

*after Chapuy et al., (1992) NEJM 327:1637–1642

TIME (months)

0 6 12 18CU

MU

LA

TIV

E P

RO

BA

BIL

ITY

OF H

IP F

RA

CT

UR

E

0.00

0.03

0.06

0.09placebo

Ca + Vit D

CU ORC



TIME (months)

0 6 12 18CU

MU

LA

TIV

E P

RO

BA

BIL

ITY

OF H

IP F

RA

CT

UR

E

0.00

0.03

0.06

0.09placebo

Ca + Vit D

CU ORC



Ca + Vit D Placebo

18

MO

NT

H C

HA

NG

E I

N B

MD

AT

TH

E H

IP(%

)

-8

-6

-4

-2

0

2

4

TIME (months)

0 6 12 18CU

MU

LA

TIV

E P

RO

BA

BIL

ITY

OF H

IP F

RA

CT

UR

E

0.00

0.03

0.06

0.09placebo

Ca + Vit D

CU ORC



Ca + Vit D Placebo

18

MO

NT

H C

HA

NG

E I

N B

MD

AT

TH

E H

IP(%

)

-8

-6

-4

-2

0

2

4

TIME (months)

0 6 12 18CU

MU

LA

TIV

E P

RO

BA

BIL

ITY

OF H

IP F

RA

CT

UR

E

0.00

0.03

0.06

0.09placebo

Ca + Vit D

CU ORC



Ca + Vit D Placebo

18

MO

NT

H C

HA

NG

E I

N B

MD

AT

TH

E H

IP(%

)

-8

-6

-4

-2

0

2

4

TIME (months)

0 6 12 18CU

MU

LA

TIV

E P

RO

BA

BIL

ITY

OF H

IP F

RA

CT

UR

E

0.00

0.03

0.06

0.09placebo

Ca + Vit D

CU ORC



Ca + Vit D Placebo

18

MO

NT

H C

HA

NG

E I

N B

MD

AT

TH

E H

IP(%

)

-8

-6

-4

-2

0

2

4

TIME (months)

0 6 12 18CU

MU

LA

TIV

E P

RO

BA

BIL

ITY

OF H

IP F

RA

CT

UR

E

0.00

0.03

0.06

0.09

500 mg Ca/d

placebo

Ca + Vit D

CU ORC



Ca + Vit D Placebo

18

MO

NT

H C

HA

NG

E I

N B

MD

AT

TH

E H

IP(%

)

-8

-6

-4

-2

0

2

4

TIME (months)

0 6 12 18CU

MU

LA

TIV

E P

RO

BA

BIL

ITY

OF H

IP F

RA

CT

UR

E

0.00

0.03

0.06

0.09

1700 mg Ca/d

placebo

Ca + Vit D

CU ORC

CALCIUM, VIT D, & FRACTURE

TIME ON STUDY (months)

0 10 20 30FIRS

T N

ON

-VER

TEBR

AL F

RACT

URE

(Cum

ulat

ive

inci

denc

e –

%)0

2

4

6

8

10

12

14

*Dawson-Hughes et al., NEJM 1997:337:670-6

Ca + Vit D

placebo

176 men; 213women

ages > 65treatment:

Ca 500 mg + Vit D 700 iu

CU ORC



0 10 20 30FIRS

T N

ON

-VER

TEBR

AL F

RACT

URE

(Cum

ulat

ive

inci

denc

e –

%)0

2

4

6

8

10

12

14

*Dawson-Hughes et al., NEJM 1997:337:670-6

Ca + Vit D

placebo –55%

176 men; 213women

ages > 65treatment:

Ca 500 mg + Vit D 700 iu

What is the mechanism by which calcium & vitamin D reduce fractures in these

studies?

high bone remodeling activity makes bones fragile

high bone remodeling activity makes bones fragile

Calcium & vitamin D reduce fractures in these studies by

reducing the elevated rates of remodeling typically found in

post-menopausal women

CU ORC

RESTORING PRE-MENOPAUSAL RATES

the importance of restoring premenopausal rates of remodeling is shown by the fact that potent bisphosphonates produce the same reduction in fracture risk in patients who experience no change in BMD as in those who show an increase in BMD

CU ORC



the bone-sparing effect of bisphosphonates is of minor importance, despite the fact that bone sparing is generally considered the basis for their effect

CU ORC



the bone-sparing effect of bisphosphonates is of minor importance, despite the fact that bone sparing is generally considered the basis for their effect

REMODELING & STRESS RISERS



region of increased stress

REMODELING & FRAGILITY



CU ORC

TRABECULAR FRACTURES

CU ORC


CU ORC


CU ORC


CU ORC


Healed or healing micro-fractures are painless. They can greatly reduce trabecular bone strength.

CU ORC

REMODELING REDUCERS nutrients

Ca (with vitamin D) endocrines

estrogen or estrogen agonists (e.g., genistein)

pharmaceuticals bisphosphonates RANK ligand antagonists & other resorption

inhibitors

CU ORC



0 10 20 30FIRS

T N

ON

-VER

TEBR

AL F

RACT

URE

(Cum

ulat

ive

inci

denc

e –

%)0

2

4

6

8

10

12

14

Dawson-Hughes et al., NEJM 1997:337:670-6

Ca + Vit D

placebo –55%

the effect beginsimmediately because

remodelingreduction beginsimmediately

CU ORC



0 10 20 30FIRS

T N

ON

-VER

TEBR

AL F

RACT

URE

(Cum

ulat

ive

inci

denc

e –

%)0

2

4

6

8

10

12

14


Ca + Vit D

placebo –55%



CU ORC



0 10 20 30FIRS

T N

ON

-VER

TEBR

AL F

RACT

URE

(Cum

ulat

ive

inci

denc

e –

%)0

2

4

6

8

10

12

14


Ca + Vit D

placebo –55%



CU ORC

SUMMARY – VITAMIN D vitamin D is essential for adequate

functioning of virtually all body systems inadequate vitamin D status predisposes

to various chronic diseases optimal status is achieved when serum

25(OH)D is between 40 and 60 ng/mL this requires an all-source input of

~5000 IU/d

SUMMARY – CALCIUM

Calcium is still important in 2015 optimal intake : 1200–1800 mg/d

preferably from dairy bone protection is due largely to

reduction of excess bone remodeling

CU ORC

Take away messages. . . .

Most Americans have inadequate intakes of both vitamin D and Ca.

Foods are the best sources for the needed Ca

But vitamin D needs can best be met by a combination of sun exposure and supplements

CU ORC

ADDITIONAL RESOURCES Vitamin D:

Baggerly C. et al. (2015) Sunlight & Vitamin D: Necessary for Public Health J Am Coll Nutr

Heaney RP & Armas LAG (2015) Quantifying the Vitamin D Economy. Nutr Rev

Calcium: Surgeon General’s Report: Bone Health &

Osteoporosis (2004) Heaney RP (2003) Is the paradigm shifting? Bone

Thank you . . .

Questions?

Based on this webinar the participant should be able to: Recall the principal roles vitamin D and calcium serve in the

human body Describe how nutrients – and vitamin D in particular – are

like preventive maintenance of a complex machine Describe some of the consequences of inadequate intake of

each nutrient List the principal sources of vitamin D and calcium Recall the optimal intake/input of each nutrient, with

emphasis on differing needs at different life stages

NUTRI-BITES®

Webinar SeriesVitamin D and Calcium: New Research-New Recommendations

ConAgra Foods Science Institute Nutri-Bites® Webinar details

A link to obtain your Continuing Education Credit certificate will be emailed within 2 days

Today’s webinar will be available to download within 2 days at: www.ConAgraFoodsScienceInstitute.com

For CPE information: [email protected]

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Dietary Supplements:Basics, Beliefs and Benefits

Johanna Dwyer, D.Sc., R.D.Professor of Medicine and Community Health

Tufts University School of Medicine and Professor of Nutrition

Friedman School of Nutrition Science and PolicyDate: February 4, 2016

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Vitamin D and Calcium New Research – New Recommendations? · Vitamin D and Calcium New Research – New Recommendations? will begin at the top of the hour Audio for today’s presentation