VITAMIN D: REDISCOVY

1
(No Transcript)
2
(No Transcript)
3
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.

16
(No Transcript)
17
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

34
(No Transcript)
35
(No Transcript)
36
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

53
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)

56
(No Transcript)
57
(No Transcript)
58
(No Transcript)
59
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
•  

63
(No Transcript)
64
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

65
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?

66
(No Transcript)
67
(No Transcript)
68
(No Transcript)
69
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