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VITAMIN D: REDISCOVY

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Title: VITAMIN D: REDISCOVY


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VITAMIN D DEFICIENCY REDISCOVERYPart I- The
Science Behind The RediscoveryPart II- Options
For Putting The Science Into Practice
  • David A. McCarthy, MD
  • Donald L. Clark, MD
  • Family Physicians of OFallon
  • OFallon, Illinois
  • USAFP Meeting, Orlando, FL
  • April 6, 2009

4
Evidenced Based CME
  • Supplementation with Vitamin D reduces all cause
    mortality- Level A
  • http//www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID
    12007008358
  • Vitamin D supplementation reduces hip fractures-
    Level A
  • http//www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID
    12005008239
  • Vitamin D supplementation reduces risk of falls
    by greater than 20 - Level A
  • http//www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID
    12004008298

5
Game Plan
  • Don- Play By Play
  • Dave- Color Commentary
  • Disclosures- Neither Dr. McCarthy or Dr. Clark
    have any personal financial or commercial
    interests to disclose
  • Acknowledgements Vitamin D Council,
    Grassroots Health

6
Learning Objectives
  • The Participant will be able to
  • 1)Recall the science of Vitamin D in terms of its
    production and major physiologic actions.
  • 2)Understand the high prevalence of Vitamin D
    deficiency in all ages, racial and ethnic groups,
    and populations.
  • 3) Accurately interpret Vitamin D testing.
  • 4) Find the words that work in counseling
    patients on Vitamin D status
  • 5) Understand the daily and weekly dosing options
    of Vitamin D
  • 6)Understand how to put Vitamin D management to
    use in daily practice

7
Vitamin D Deficiency
  • PART I THE SCIENCE BEHIND THE REDISCOVERY

8
Reframing Vitamin D as a Hormone
  • Definition of a Hormone
  • 1)Chemical Substance
  • 2) Formed in one part of the body
  • 3) Carried in the blood to other organ or part
  • 4) Can alter the function or structure of one or
    many organs or parts

9
Vitamin D meets This Definition
  • Chemical Substance Cholecalciferol (Vitamin D3)

10
Formed in Organ of the Body -Skin
280-320 nm-UVB
Skin- Pro D3-?Vit D3
Oral Intake of D3
Liver
Calcidiol- 25 OH Vit D- biologically inert
Kidney-historically Other tissues-modern era
1,25 OH Vit D- biologically active
11
Carried in the Blood stream
  • 25 OH Vitamin D, inert storage form of Vitamin D
  • Carried on Vitamin D binding protein (VDBP)
  • Converted to 1, 25 OH Vitamin D
  • (by alpha 1 hydroxylase)
  • Goes to specific sites where it combines with
    Vitamin D receptor (VDR)
  • Reference Holick MF, J. Cell Biochem 2003 Feb 1
    88(2) 296-307. Bickle D, J.Clin Endo Metab 2009
    Jan 94(1) 26-34. Holick MF. NEJM 2007 July 19,
    357(3) 266-82.

12
THE BIG PICTURE
  • Vitamin D Receptors
  • Regulation of Apoptosis
  • Genetic up and down regulation
  • Effect on Renin Angiotensin System

13
Vitamin D Receptor Location
14
Apoptosis
  • Mechanism- orderly birth and death of cells
  • Necrosis abnormal death of cells

15
How Vitamin D can suppress Cancer
  • Augmenting apoptosis
  • Suppressing cancer angiogenic factors
  • Tightening cell cohesion
  • Up-regulates TNF alpha (Tumor necrosis factor)
    genesdose dependent
  • Reference Bouillion. J.Steroid Biochem Mol Biol.
    2006 Dec 102(1-5) 156-62. Shany et al.
    Steroids.2001 March-May 66(3-5) 319-25 Zhang
    et al. J. Biol. Chem. 2005 Oct 21 280(42)
    35458-68.

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Gene Regulation
  • Mechanism-up regulation, down regulation-i.e. MS
  • Reference http//www.plosgenetics.org/article/in
    fodoi/10.1371/journal.pgen.1000369

1,25 OH Vit D
VDR
Down regulates cytokine production
No Vit D
VDR
Up regulates cytokine production attacks myelin
18
Multiple Sclerosis and Vitamin D Levels
19
Vitamin D Receptor Effects
  • Exposure of Vitamin D receptor to
    lipopolysaccharide, macrophages, monocytes
  • Up regulation of production of 1,25 OH Vit D
  • Production of Antimicrobial Peptides (AMPs)
  • Production of cathelicidin et al
  • Production of specific cytokines in presence or
    absence of Vitamin D
  • Reference Tian-Tian Wang et al. J Immunol.2004
    173 2909-2912. Tavera-Mendoza, White. Scientific
    American. November 2007 62-72.

20
Implications- Areas
  • Inflammatory Conditions
  • A) Allergies
  • B) Asthma
  • C) Immune disorders
  • a. Multiple Sclerosis
  • b. Rheumatoid Arthritis
  • c. Thyroid disorders
  • d. Crohns Disease
  • e. Psoriasis/Eczema
  • D) Infectious Diseases
  • Tuberculosis
  • Influenza/ Cold viruses
  • E) Fibromyalgia/Chronic Pain

21
Influenza
  • There is a Reason for the Season
  • On the Epidemiology of Influenza (Cannell et
    al)
  • 28 Feb 2008 Virology Journal (free online)
  • Edgar Hope-Simpson, British heroic FP
  • Hippocrates, Greek heroic FP

22
Influenza Season Vitamin D Deficiency Season
  • Higher Levels of influenza are associated with
    low levels of Vitamin D
  • Reference Cannell JJ et. al. "Epidemic Influenza
    and Vitamin D" Epidemiol Infect 2006 Sept.7 1-12

23
Influenza and Vitamin D Levels
Flu
Flu
24
Australian Heroes
  • One Time IM Vitamin D vs. Flu vaccine
  • Med J Aust. 2005 Jul 4183(1)4-5.
  • Aboriginal osteoporosis and viral infections
  • Int J Epidemiol. 2008 Jun37(3)654-67.

25
Osteoporosis
  • Not due to a deficiency of Fosamax
  • Building bone is a team effort
  • Osteoblasts AND osteoclasts
  • Half life of Fosamax
  • Do not use if hypocalcemic and until Vitamin D
    deficiency has been addressed
  • How to build better bone- with better building
    blocks
  • The three 3s of bone
  • 3 hormones
  • 3 vitamins
  • 3 minerals

26
The Renin Angiotensin System
Renin
VITAMIN D
ACE
27
Mechanism of Vitamin Ds Effect on Renin
  • Vitamin D down regulates genetic production of
    Renin
  • Reference Li YC, J. Cell Biochem 2003 Feb 1
    88(2) 327-31.

VDR
RXR
Down regulates production of Renin
28
Vitamin D Deficiency Syndrome (VDDS)
  • Low Level of 25 OH Vit. D lt 25 ng/mL
  • Presence of at least two of following conditions
  • Osteoporosis
  • Heart Disease
  • Hypertension
  • Autoimmune disease
  • Chronic fatigue
  • Cancer
  • Allergies
  • Asthma
  • Psoriasis or Eczema
  • Recurrent infections

29
Vitamin D Testing
  • Measure 25 OH Vitamin D
  • Normal- obtained by population measurement,
  • 30-80 ng/mL
  • Deficient- lt20 ng/mL
  • Insufficient- lt35 ng/mL
  • Optimal- 80 ng/mL /- 10 (speakers opinion)
  • Targets are moving upward!

30
Prevalence
  • Doctors32 (deficient)
  • Medical Students42 (deficient)
  • African American Women-child bearing age 42
  • Pregnant women76 (insufficient)
  • Young Girls 48 (deficient)
  • Elderly 80 (insufficient)
  • Obese 80 (insufficient)
  • Residents of Southwest Illinois70 (insufficient)

31
Why the High Rate of Deficiency?
  • Location, latitude
  • Sunscreen
  • Skin pigmentation
  • -reason for health care disparity?
  • Clothes covering skin
  • Uniforms?, Burqas?
  • Aging skin
  • Ozone in atmosphere
  • Lack of adequate dietary sources

32
Prevalence- Number needed to Screen
33
Vitamin D Toxicity
  • Data show that no toxicity exists at levels below
    200 ng/mL, less than 30,000 IU per day
  • Symptoms- related to hypercalcemia
  • Nausea, vomiting, anorexia, calcifications in
    kidneys
  • Measure serum calcium with serum 25 OH Vit D

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Vitamin D Deficiency
  • Part II- Options for Putting The Science Into
    Practice

37
What Would You Like to Know?
38
Practical Options
  • To Test or Not to Test
  • Risk - Benefit Ratio
  • Treat to Target- blood level or clinical
    resolution
  • D2 vs. D3 (Ergocalciferol vs. Cholecalciferol)
  • How much D? 1000 IU/ 25 lbs body weight
  • Dosing Options- Daily, Weekly
  • Problems with Compliance
  • Practical Management

39
Words That Work
  • Avoid Panacea Paradox
  • Opportunistic Association
  • Sunlight does not make Vitamin D UV light does
  • Ask Basic Biology Questions
  • Do you seek or avoid summer Sun?
  • Sunscreen?
  • Drink milk daily? 100 IU / 8 oz.
  • Do you take vitamins? 200-400 IU
  • Do you live around here? 37 degrees North (St.
    Louis)

40
The Two Minute Drill
  • One Less Liver Transplant
  • Out of Their Wheelchairs and Dancing
  • Rheumatoid Arthritis and Family History of Breast
    Cancer
  • Sick of Sickling
  • Atmospheric Science Is Ozone a Shield or an
    Obstacle?
  • Helping Soldiers and Sailors avoid MS Harvards
    Contribution
  • The Telegraph in England
  • Was Sunscreen designed by an Evil Scientist?
  • How Mac Learned to Love Studying for the Boards
  • Educating the Governor and the Hollywood Director

41
One Less Liver Transplant
  • Patient RF, 45 y.o. male
  • Hx Sarcoidosis, Ascites, Liver Failure, Chronic
    Bronchitis, Allergic Rhinitis
  • Clinical Course
  • 2004- LFTs elevated, workup negative for Cancer,
    diagnosed with Sarcoidosis
  • 2006- LFTs worse, referred to transplant list,
    developed umbilical hernia, too risky for
    surgery
  • 2006, Nov.- admitted with ascites
  • 2007, May- Very Fatigued 25 OH Vit D 15
    started on D2, 50,000 IU twice a week
  • 2007, June- Still Fatigued, D level 54
  • 2007, July- Getting energy, started on 4000 IU
    D3, LFTs improving

42
One Less Liver Transplant
  • Clinical Course- Cont.
  • 2007, Aug.- Feeling Better, LFTs improving,
    increased to 10,000 IU D3 per day
  • 2007, Dec.- More strength, able to participate
    in ADLs
  • 2008, May- Can I stop my immunosuppressive drugs
    now?

43
Labs- RF
44
Out of Their Wheelchairs and Dancing- Patient 1-
LJ
  • Patient LJ, 66 y.o male
  • Hx Retired USAF, Management Analyst Family Hx.
    of Cardiac disease, father MI, Brother, sister
    CABG
  • Clincal Presentation/Hx chest pain, leg pain,
    myalgias, waves of paroxysmal pain all over body
  • Course of evaluation/Tx
  • 2001- first symptoms documented, cardiac workup
    negative, had OMT- helped some
  • 2002-2007 multiple specialists, Neuro. Rheum.,
    Ortho, Neurosurg.,Cardio.- no conclusive
    recommendations, multiple pain meds tried,
    nothing really helped
  • 2004, Oct.- Mayo Clinic evaluation, no conclusive
    cause for his pain
  • 2004-2007- Pain Management, still has problem,
    pain comes and goes, in motorized wheelchair due
    to pain

45
Out of Their Wheelchairs and Dancing- Patient 1-
LJ
  • 2007, April 25 OH Vit D 34 began D2, 50,000 IU
    per week, pain began to subside
  • 2007, June- attended Vitamin D talk at church by
    DLC, increased to 5000 IU of D3 daily, 25 OH
    level- 54
  • 2007, Dec pain improving, increased to 10,000
    IU per day, not using wheelchair
  • 2008 March- Dancing with wife at Mardi Gras party
  • 2008 April- 25 OH Vit D 87
  • 2008, Aug.- Hip replacement surgery
  • I have more good days than bad days, I just keep
    dancing

46
Out of Their Wheelchairs and Dancing- Patient 2-
JMC
  • JMC, 69 y.o. female
  • Hx Retired Nurse, Dance Teacher, Lived in
    Michigan with husband, retired to Florida because
    she Felt so much better in the sun.
  • Clinical Hx Hypothyroidism, fibromyalgia, HTN,
    obesity, degenerative arthritis pain continually
    worsened, chiropractic care helped some, pain
    became so bad, had to use motorized wheelchair to
    do normal daily functioning, shoulder replacement
    surgery for degenerative changes

47
Out of Their Wheelchairs and Dancing- Patient 2-
JMC
  • Vitamin D Hx.
  • 2007, Summer Talked with son (MD) about Vitamin
    D Deficiency ,started 500-1000 IU of Vitamin D3
    daily
  • 2007,July- Gastric Banding Surgery- increased to
    2000 IU of D3, lost approx. 100 lbs by 1/1/08
  • 2008, Jan.- Increased to 5,000 IU D3 daily- pain
    diminished, no fibromyalgia flairs
  • Stopped using wheelchair, more energy
  • Increased to 10,000 IU D3 per day, Started tap
    dancing classes for senior citizens in retirement
    community

48
Out of Their Wheelchairs and DancingJMC
  • Recently increased to 15,000 IU D3 per day
  • Currently teaching tap 7 hours per week,
    shopping, able to visit her children, travel
  • Now telling all her friends and relatives about
    the benefits of Vitamin D

49
Rheumatoid Arthritis and Family History of Breast
Cancer
  • Patient JAC, 47 y.o female
  • Hx Diffuse joint pains, fatigue, started in her
    teens, progressed to low back, hands, feet, grew
    up in Cleveland, OH, RF, ANA 1320 in 2002
    NSAID use, Methotrexate- nothing helped, worse in
    the winter
  • Family Hx Mother died metastatic Breast CA age
    55, Mat. Aunt- Breast CA, Father, stroke age 65
  • Clinical Course began Vitamin D3, 10,000 IU per
    day in May 2007 (No 25 OH Vit D levels)
  • Improvements Much improved joint and back pain,
    very short, less frequent colds, improved energy
  • I can feel the days that I forget my Vitamin D

50
HDL Improvement- No Changes in diet or
exercise-JAC
51
Sick of Sickling
  •  
  •   21 y/o  dark complexion African American male
    with lifelong history of sickle cell anemia. 
    Crises 2-3 times per month lasting 7-8 days each
    and requiring narcotics Aleve.  Missing school
    and work often.  Intolerant of dairy products, 
    no vitamin intake,  hates the heat so he stays
    out of the sun.  When asked, he notes his crises
    are less frequent and less intense late in the
    summer I wish I could feel like that all year
    long.
  • May 2007 -25-OH vitamin D level (lt7 ng/ml - 
    undetectable) Started on D3 50,000 IU once per
    week (on Sunday)
  • July 2007 -  Crises now only 2-3 days and less
    intense -  less frequent.  Much improved. 
    Changed to D3 -  3 x 1,000 3,000 IU daily
    25-OH Vitamin D level 58 ng/ml
  • August 2007 crises now last a few hours rather
    a week.   Still  3,000 IU daily
  • October 2007 increased to D3 50,000 IU once
    per week  (average 7,000 IU daily) for patient
    convenience and to see if higher blood level
    improved his SCDz.
  • March 2008 25-OH Vitamin D level 68 ng/ml
    Increased to 2 x 5,000 10,000 daily
  • Nov 2008 -  started on supplemental magnesium No
    pain for over one month
  • 25-OH Vitamin D level 78 ng/ml 

52
Sick of Sickling
  • As the rest of the family joined the practice
  • Mom initial D level of 19 ng/ml  -  now  76
    ng/ml
  •  
  • Dad initial D level of 15 ng/ml -  now 88 ng/ml
  •  
  • Sister (12 y/o)  - initial D level of 37 ng/ml 
    in July 2007
  • Did not take the supplemental D
  • Feb 2008   complaining of fatigue
  • 25-OH Vitamin D level 19 ng/ml started
    D3 50,000 q7d
  • That night pt notes 102 temp, body aches,
    headache and a cough takes her brothers D3
    50,000 IU capsule
  • Mom calls the next day to inform me of the flu
    like illness -  patient seen that day with a
    strong positive rapidflu test -  started on
    amantadine -  patient was afebrile and notes that
    she was already feeling much better after the 1 x
    50,000 50,000 dose -  advised her to take
    50,000 daily for two additional days ( 150,000
    load)
  • Then return to 50,000 once weekly on Sundays

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Helping Soldiers and Sailors avoid MS Harvards
Contribution
  • Munger, et al, JAMA, 2006 Dec 20, 296(23)
    2832-2838
  • Serum 25 OH D Levels and Risk of Multiple
    Sclerosis
  • Design Case-Control Study, 7 million USA and USN
    personnel serum samples in DOD Repository,
    physical disability databases 1992-2004
  • Odds of Having MS decreased with higher 25 OH Vit
    D levels
  • Greater than 40 ng/mL 62 lower risk of
    developing Multiple Sclerosis

54
Atmospheric Science- Is Ozone a Shield or an
Obstacle?
  •  
  • About 7 of solar radiation is UVB . Less than 1
    of solar radiation on Earth is UVB
  • The reason is Ozone- stratospheric and at ground
    level
  • Stratospheric Ozone is not uniform least at
    Equator, more at the poles  Ground level Ozone is
    in industrial metropolitan regions
  • In Nature, Ozone is produced by solar radiation
    energizing atmospheric oxygen at the Equator
  • Ozone rises slowly to the stratosphere then moves
    with the winds poleward
  • Ozonosphere varies with season in Northern
    Hemisphere -  thickest in March, thinnest in
    September
  • UVB reaching Earth is determined by season due to
    ozone variation and tilt of the Earth (with
    higher levels of radiation when perpendicular to
    the Sun) Midday
  • Our skins ability to produce Vitamin D varies
    greatly with time of the day and season of the
    year by latitude.
  • Check your zip code on weather.com during the day

55
Sunscreen Designed by an Evil Scientist?
  • Vitamin D converted at 290 nm (UVB)
  • PABA blocks 270 290 nm
  • PABA- SPF 15- reduces D production 98
  • PABA does not block UVA at all
  • Melanoma range peak- 360 nm (UVA)

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The Telegraph in England
  • The Lincolnshire Telegraph- Camilla Sutcliffe,
    January 27, 2009
  • FREE VITAMIN D SUPPLEMENTS ARE NOW BEING HANDED
    OUT TO EXPECTANT MOTHERS- 18 months after a
    shock report revealed 56 cases of rickets in
    Blackburn with Darwen.
  • HEALTH BOSSES reintroduced the supplements for
    toddlers after the 2007 report revealed Blackburn
    had four times the number of children suffering
    the painful bone-softening condition than Burnley
    and Pendle, where the vitamin had been given out.
  • It is hoped the supplements for mothers will give
    babies bones an extra boost.
  • Vitamin D is essential for healthy bone growth,
    but is unique in coming mainly from sunlight.
  • Dr Ellis Friedman, director of public health for
    NHS East Lancashire, said the supplements were
    vitally important for the South Asian community,
    as dark skin and Muslim requirements for clothing
    to cover limbs meant CATCHING THE SUN was even
    harder.
  • Almost all of East Lancashires recorded cases of
    rickets have been in Asian children.

60
The Telegraph in England
  • Katherine Burn, a GP at NHS Blackburn with
    Darwen, said If pregnant women have low Vitamin
    D levels, they can pass the deficiency on to
    their child. "New mothers need to recharge their
    Vitamin D levels, particularly if breast feeding.
  • In climates such as ours, it can be very
    difficult to get enough Vitamin D, especially in
    winter and for people with dark or pigmented
    skin.
  • By maintaining healthy Vitamin D levels during
    pregnancy you can help give your child the best
    possible start. Tablets for women also contain
    Vitamin C and folic acid.
  • Vitamin D drops can be given to children from as
    early as one month old and are given free of
    charge from health visitors as part of a 2-week
    visit. The vitamin drops will also give the baby
    essential vitamin A and vitamin C. Doctors advise
    that these supplements should continue until your
    child is 5-years-old.
  • Chairman of Blackburn with Darwen Councils
    HEALTH SCRUTINY COMMITTEE Roy Davies said We
    have to do these things to try and get these
    children healthy.
  • The supplements for children have been a
    success, and I hope pregnant women will continue
    to do everything they can to keep themselves and
    their babies healthy.

61
How I Learned to Love Studying for the Boards
  • My Board Strategies
  •  
  • 1981 -  Initial boards  -  no courses, didnt
    study            
  • 1987 -  Staff FP Offutt (4), followed Flight
    Medicine (2)
  •             Two week course, then four
    months of study     
  • 1993 -  Chief of Hospital Services (3), 
    Commander (3)
  •             One week course, then three
    months of study   
  • 2000 -  USAF Ambulatory Care (4), Private
    Practice (3)
  •             One week course, then two
    months of study      
  • 2007 -  Private Practice (7)
  •             One week course, then three
    months of study
  •             Checking Google after each
    section to learn
  •              About Vitamin D      
    (5050)                              
  •   
  • How many questions were on Vitamin D in 2007  - 
    one 

62
The Governor and the Hollywood Director
  •  
  • Primary Goal  educate key community leaders in
  •                                  Southwestern
    Illinois
  •  
  • Method  The OFallon Forum on Health Care
    Redesign
  •   
  • Secondary Goal  educate a key elected official
  •  
  • Method  studied the 19 Presidential candidates (
    D R )
  • Selected one who had
  • (1) a compelling vision of health care
  • (2) a long list of health care accomplishments
  • (3) the potential to be a future national
    leader
  •  

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The Governor and the Hollywood Director
  • Assemble the speakers
  •   Governor Huckabee  -  An American Health
    Care System
  •   Dave Racer Understanding the Uninsured
  •   Dave McCarthy- Reducing the Costs of
    Health Care, Now

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Governor and the Hollywood Director
  • Now we needed a person to keep The Forum on
    course. So, if you want a Navigator with an agile
    mind who loves science and talks about health
    care Who is the natural pick?

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Summary
  • Vitamin D is a hormone that helps to regulate
    many systems
  • Absence of it is directly associated with many
    disorders
  • Improving its levels shows improvement in many
    disorders
  • Vitamin D management is implementable in primary
    care practice
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