The Story of Vitamin D, and the Debacle of Human Health Impact that has unfolded over the past 50 years, as we allowed the population necessary levels to collapse. For individuals, parents, families, mothers - don't miss this understanding - this is probably the most important single factor for your health and longevity.
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D is for Debacle - The Sun, Vitamin D, 25(OH)D and Health
1. “D” is for DebacleThe Crucial Story of 25(OH)D
www.thefatemperor.com
2014 Ivor Cummins BE(Chem) CEng MIEI
2. A Thank-You to Some Experts:
Prof. Michael HolickEndocrinologist and Professor of Medicine, Physiology and Biophysics. Currently director at Boston University Medical Center. Internationally recognized expert on all aspects of vitamin D.
Dr. Edward GorhamAssociate Professor in the Department of Family and Preventive Medicine at the University of California
Prof. Robert P Heaney Clinical Endocrinologist, Professor of Medicine and John A. Creighton University Professor Emeritus, Creighton University School of Medicine. Internationally recognized expert on vitamin D.
Dr. Cedric F Garland AdjtProf. Family and Preventative Medicine, Division of Epidemiology, University of San Diego. Internationally recognized expert on the disease implications of vitamin D.
Dr. Chris Masterjohn
PhD in Nutritional Science and Assistant Professor of Health and Nutrition Sciences at Brooklyn College.
Dr. Bruce Hollis PhD
Professor of Pediatrics, Biochemistry and Molecular Biology at The Medical University of South Carolina as well as the Director of Pediatric Nutritional Sciences. Vitamin D research for the past 35 years and has published >200 peer reviewed articles.
Prof. Reinhold Vieth
Professor in the Department of Nutritional Sciences, and the Department of Laboratory Medicine and Pathobiology, University of Toronto.Internationally recognized expert on the clinical nutrition of vitamin D as well as its pharmacology and safety.
Dr. David Grimes
consultant Gastroenterologist at Blackburn Hospital in the UK. Expert in Vitamin D for the developing foetusand the implications for infections, diabetes, heart disease, liver disease and Crohn'sdisease.
3. Prelude
1.The Centrality of the Sun
2.25(OH)D –The Creation
3.25(OH)D –The Power
4.25(OH)D –The Human Cost
5.Anatomy of a Debacle
6.The Solution
Epilogue
Q&A
The “D”ebacleContent:
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
4. Prelude
1.The Centrality of the Sun
2.25(OH)D –The Creation
3.25(OH)D –The Power
4.25(OH)D –The Human Cost
5.Anatomy of a Debacle
6.The Solution
Epilogue
Q&A
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
6. Prelude –Critical Human Hormone
D3 –The Hormone Precursor
2014 Ivor Cummins BE(Chem) CEng MIEI
•“Vitamin” D3 (Cholecalciferol) is the hormone- precursor molecule required to synthesize 25(OH)D
•This is the crucial element provided mostly by UVB light on skin, but can be taken in supplement form & diet
7. •25(OH)Dis the pre-hormone substrate.
•Is produced in the Liver from D3 Cholecalciferol
•Enabled us to leave the seas, and a lot more besides
•Is used all over the body for critical functions
•An analogy might be “Ammunition Pack”
Prelude –Critical Human Hormone
25(OH)D –The Pre-Hormone
D3 –The Hormone Precursor
2014 Ivor Cummins BE(Chem) CEng MIEI
•“Vitamin” D3 (Cholecalciferol) is the hormone- precursor molecule required to synthesize 25(OH)D
•This is the crucial element provided mostly by UVB light on skin, but can be taken in supplement form & diet
8. •25(OH)Dis the pre-hormone substrate.
•Is produced in the Liver from D3 Cholecalciferol
•Enabled us to leave the seas, and a lot more besides
•Is used all over the body for critical functions
•An analogy might be “Ammunition Pack”
•1,25 (OH)2 Dis the active Hormone
•Is produced in the Kidney and elsewhere from 25(OH)D
•Is at 1000x lower concentration than 25(OH)D
•An analogy might be “precision bullet”
1,25 (OH)2 D –The Active Form
Prelude –Critical Human Hormone
25(OH)D –The Pre-Hormone
D3 –The Hormone Precursor
2014 Ivor Cummins BE(Chem) CEng MIEI
•“Vitamin” D3 (Cholecalciferol) is the hormone- precursor molecule required to synthesize 25(OH)D
•This is the crucial element provided mostly by UVB light on skin, but can be taken in supplement form & diet
10. 2014 Ivor Cummins BE(Chem) C(Eng) MIEI
Prelude –The Implications of Low…
USA
25(OH)D
Distribution
(NHANES III Seasonal Sampling)
11. ~70% of US Population Insufficient
( 15 Years Previously was ~50% )
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
Prelude –The Implications of Low…
USA
25(OH)D
Distribution
(NHANES III Seasonal Sampling)
12. 2014 Ivor Cummins BE(Chem) C(Eng) MIEI
~70% of US Population Insufficient
( 15 Years Previously was ~50% )
Prelude –The Implications of Low…
Requires
Engineering
USA
25(OH)D
Distribution
(NHANES III Seasonal Sampling)
13. Requires
Engineering
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
RICKETS
Prelude –The Implications of Low…
USA
25(OH)D
Distribution
(NHANES III Seasonal Sampling)
14. Prelude
1.The Centrality of the Sun
2.25(OH)D –The Creation
3.25(OH)D –The Power
4.25(OH)D –The Human Cost
5.Anatomy of a Debacle
6.The Solution
Epilogue
Q&A
2014 Ivor Cummins BE(Chem) CEng MIEI
15. Skin Pigmentation Hypotheses –to ~40kYrs ago
Evolutionary
Drivers
LOSS OF BODY HAIR (~1M Yrsago)
•Striding Bipedalism
•Sweat Gland System
•Whole Body Cooling
•Critical Brain Cooling
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
~1 million years…
16. Skin Pigmentation Hypotheses –to ~40kYrs ago
Evolutionary
Drivers
•Skin generally non- pigmented
•Hairlessareas pigmented
•Sun Protection Robust Overall
•Vitamin D accessed via Grooming, as for dogs etc
•Captive animals require D Supplementation!
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
LOSS OF BODY HAIR (~1M Yrsago)
•Striding Bipedalism
•Sweat Gland System
•Whole Body Cooling
•Critical Brain Cooling
~1 million years…
17. Skin Pigmentation Hypotheses –to ~40kYrs ago
Evolutionary
Drivers
•Skin generally non- pigmented
•Hairlessareas pigmented
•Sun Protection Robust Overall
•Vitamin D accessed via Grooming, as for dogs etc
•Captive animals require D Supplementation!
Hair Loss –Key Downside:
•Human Origin had Equatorial Sun
•Ubiquitous powerful UV penetrates to Blood Vessels and damages Folate (photolysis)
•Lack of folate causes Neural Tube Birth Defects
•Other Reproductive Impacts from excessive UV
•Also need to protect hugely increased Sweat Gland System from damage
And 25(OH)D Synthesis?
•Equatorial Sun still provides adequate amounts of UV in spite of pigmented skin
•Engineering “Tradeoff” thus achieved
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
LOSS OF BODY HAIR (~1M Yrsago)
•Striding Bipedalism
•Sweat Gland System
•Whole Body Cooling
•Critical Brain Cooling
~1 million years…
18. Skin Pigmentation Hypotheses –to ~40kYrs ago
Evolutionary
Drivers
•Skin generally non- pigmented
•Hairlessareas pigmented
•Sun Protection Robust Overall
•Vitamin D accessed via Grooming, as for dogs etc
•Captive animals require D Supplementation!
Hair Loss –Key Downside:
•Human Origin had Equatorial Sun
•Ubiquitous powerful UV penetrates to Blood Vessels and damages Folate (photolysis)
•Lack of folate causes Neural Tube Birth Defects
•Other Reproductive Impacts from excessive UV
•Also need to protect hugely increased Sweat Gland System from damage
And 25(OH)D Synthesis?
•Equatorial Sun still provides adequate amounts of UV in spite of pigmented skin
•Engineering “Tradeoff” thus achieved
2014 Ivor Cummins BE(Chem) CEng MIEI
LOSS OF BODY HAIR (~1M Yrsago)
•Striding Bipedalism
•Sweat Gland System
•Whole Body Cooling
•Critical Brain Cooling
~1 million years…
19. Skin Pigmentation Hypotheses –to ~40kYrs ago
Evolutionary
Drivers
•Skin generally non- pigmented
•Hairlessareas pigmented
•Sun Protection Robust Overall
•Vitamin D accessed via Grooming, as for dogs etc
•Captive animals require D Supplementation!
Hair Loss –Key Downside:
•Human Origin had Equatorial Sun
•Ubiquitous powerful UV penetrates to Blood Vessels and damages Folate (photolysis)
•Lack of folate causes Neural Tube Birth Defects
•Other Reproductive Impacts from excessive UV
•Also need to protect Homo Sapiens’ hugely increased Sweat Gland System from damage
And 25(OH)D Synthesis?
•Equatorial Sun still provides adequate amounts of UV in spite of pigmented skin
•Engineering “Tradeoff” thus achieved
2014 Ivor Cummins BE(Chem) CEng MIEI
LOSS OF BODY HAIR (~1M Yrsago)
•Striding Bipedalism
•Sweat Gland System
•Whole Body Cooling
•Critical Brain Cooling
~1 million years…
20. Skin Pigmentation Hypotheses –to ~40kYrs ago
Evolutionary
Drivers
•Skin generally non- pigmented
•Hairlessareas pigmented
•Sun Protection Robust Overall
•Vitamin D accessed via Grooming, as for dogs etc
•Captive animals require D Supplementation!
Hair Loss –Key Downside:
•Human Origin had Equatorial Sun
•Ubiquitous powerful UV penetrates to Blood Vessels and damages Folate (photolysis)
•Lack of folate causes Neural Tube Birth Defects
•Other Reproductive Impacts from excessive UV
•Also need to protect Homo Sapiens’ hugely increased Sweat Gland System from damage
And 25(OH)D Synthesis?
•Equatorial Sun still provides adequate amounts of UV in spite of pigmented skin
2014 Ivor Cummins BE(Chem) CEng MIEI
LOSS OF BODY HAIR (~1M Yrsago)
•Striding Bipedalism
•Sweat Gland System
•Whole Body Cooling
•Critical Brain Cooling
~1 million years…
21. Skin Pigmentation Hypotheses –to ~40kYrs ago
Evolutionary
Drivers
•Skin generally non- pigmented
•Hairlessareas pigmented
•Sun Protection Robust Overall
•Vitamin D accessed via Grooming, as for dogs etc
•Captive animals require D Supplementation!
Hair Loss –Key Downside:
•Human Origin had Equatorial Sun
•Ubiquitous powerful UV penetrates to Blood Vessels and damages Folate (photolysis)
•Lack of folate causes Neural Tube Birth Defects
•Other Reproductive Impacts from excessive UV
•Also need to protect Homo Sapiens’ hugely increased Sweat Gland System from damage
And 25(OH)D Synthesis?
•Equatorial Sun still provides adequate amounts of UV in spite of pigmented skin
•Engineering “Trade-off” thus achieved
2014 Ivor Cummins BE(Chem) CEng MIEI
LOSS OF BODY HAIR (~1M Yrsago)
•Striding Bipedalism
•Sweat Gland System
•Whole Body Cooling
•Critical Brain Cooling
~1 million years…
24. Evolutionary
Drivers
•Skin Heavily Pigmented
•Protection Robust Overall
•Vitamin D synthesis adequate
•Trade-off Optimised
Trade-offs change with Latitude:
•Studies strongly link availableUV on Earth’s surface to indigenous Skin Coloration
•Increasing Loss of Vitamin D Synthesis as we leave Equator –combined with poor nutrition, Rickets and many other issues ensue –we’ll look at those shortly
•In Northern Hemisphere particularly severe effect
•Acknowledgement: alternative hypotheses suggest many things: “simply lost pigmentation because unneeded” etc)
2014 Ivor Cummins BE(Chem) CEng MIEI
Migration from Equator
•Increasing weakness of UVB
•Use of Clothing increases
•Adaptive Pressure Deployed
•Fishing Ability Offsets
Skin Pigmentation Hypotheses –~30-40k Yrsto present
<40k years…
25. Evolutionary
Drivers
•Skin Heavily Pigmented
•Protection Robust Overall
•Vitamin D synthesis adequate
•Trade-off Optimised
Trade-offs change with Latitude:
•Studies strongly link availableUV on Earth’s surface to indigenous Skin Coloration
•Increasing Loss of Vitamin D Synthesis as we leave Equator –combined with poor nutrition, Rickets and many other issues ensue –we’ll look at those shortly
2014 Ivor Cummins BE(Chem) CEng MIEI
Migration from Equator
•Increasing weakness of UVB
•Use of Clothing increases
•Adaptive Pressure Deployed
•Fishing Ability Offsets
Skin Pigmentation Hypotheses –~30-40k Yrsto present
<40k years…
26. Evolutionary
Drivers
•Skin Heavily Pigmented
•Protection Robust Overall
•Vitamin D synthesis adequate
•Trade-off Optimised
Trade-offs change with Latitude:
•Studies strongly link availableUV on Earth’s surface to indigenous Skin Coloration
•Increasing Loss of Vitamin D Synthesis as we leave Equator –combined with poor nutrition, Rickets and many other issues ensue –we’ll look at those shortly
•In Northern Hemisphere particularly severe effect
•Acknowledgement: alternative hypotheses suggest many things: “simply lost pigmentation because unneeded” etc)
2014 Ivor Cummins BE(Chem) CEng MIEI
Migration from Equator
•Increasing weakness of UVB
•Use of Clothing increases
•Adaptive Pressure Deployed
•Fishing Ability Offsets
Skin Pigmentation Hypotheses –~30-40k Yrsto present
<40k years…
27. Evolutionary
Drivers
•Skin Heavily Pigmented
•Protection Robust Overall
•Vitamin D synthesis adequate
•Trade-off Optimised
Trade-offs change with Latitude:
•Studies strongly link availableUV on Earth’s surface to indigenous Skin Coloration
•Increasing Loss of Vitamin D Synthesis as we leave Equator –combined with poor nutrition, Rickets and many other issues ensue –we’ll look at those shortly
•In Northern Hemisphere particularly severe effect
•Note: alternative hypotheses suggest many things: “simply lost pigmentation because unneeded” etc
2014 Ivor Cummins BE(Chem) CEng MIEI
Migration from Equator
•Increasing weakness of UVB
•Use of Clothing increases
•Adaptive Pressure Deployed
•Fishing Ability Offsets
Skin Pigmentation Hypotheses –~30-40k Yrsto present
<40k years…
28. Evolutionary
Drivers
•Skin Heavily Pigmented
•Protection Robust Overall
•Vitamin D synthesis adequate
•Trade-off Optimised
Trade-offs change with Latitude:
•Studies strongly link availableUV on Earth’s surface to indigenous Skin Coloration
•Increasing Loss of Vitamin D Synthesis as we leave Equator –combined with poor nutrition, Rickets and many other issues ensue –we’ll look at those shortly
•In Northern Hemisphere particularly severe effect
•Note: alternative hypotheses suggest many things: “simply lost pigmentation because unneeded” etc
•But Timeframe and Logic indicate Key Driver, & emerging hypotheses suggest Sun is critical beyond D
2014 Ivor Cummins BE(Chem) CEng MIEI
Migration from Equator
•Increasing weakness of UVB
•Use of Clothing increases
•Adaptive Pressure Deployed
•Fishing Ability Offsets
Skin Pigmentation Hypotheses –~30-40k Yrsto present
<40k years…
29. Human Evolutionary Environment:
Assmann G, Schulte H. Am J Cardiol. 1992;70:733–737.
We originally evolved in an intense UVB environment –part of our design
Migration over millennia drove commensurate skin pigmentation adaptation
Tradeoff: Between UV Excess (e.g. Folate), and adequate synthesis of 25(OH)D
Key Takeaways:
2014 Ivor Cummins BE(Chem) CEng MIEI
32. Why is Breast Milk now D Deficient?
MIMIC EVOLUTIONARY SUN
Mother: 6400 IU/day
Baby: Only Breast Milk
MODERN REALITY
Mother: 400 IU/day Supplement
Baby: 300 IU/day Supplement
2014 Ivor Cummins BE(Chem) CEng MIEI
33. Why is Breast Milk now D Deficient?
MIMIC EVOLUTIONARY SUN
Mother: 6400 IU/day
Baby: Only Breast Milk
MODERN REALITY
Mother: 400 IU/day Supplement
Baby: 300 IU/day Supplement
2014 Ivor Cummins BE(Chem) CEng MIEI
34. Why is Breast Milk now D Deficient?
MIMIC EVOLUTIONARY SUN
Mother: 6400 IU/day
Baby: Only Breast Milk
MODERN REALITY
Mother: 400 IU/day Supplement
Baby: 300 IU/day Supplement
2014 Ivor Cummins BE(Chem) CEng MIEI
35. Why is Breast Milk now D Deficient?
MIMIC EVOLUTIONARY SUN
Mother: 6400 IU/day
Baby: Only Breast Milk
MODERN REALITY
Mother: 400 IU/day Supplement
Baby: 300 IU/day Supplement
2014 Ivor Cummins BE(Chem) CEng MIEI
36. Why is Breast Milk now D Deficient?
MIMIC EVOLUTIONARY SUN
Mother: 6400 IU/day
Baby: Only Breast Milk
MODERN REALITY
Mother: 400 IU/day Supplement
Baby: 300 IU/day Supplement
37. Why is Breast Milk now D Deficient?
“MIMIC EVOLUTIONARY SUN”
Mother: 6400 IU/day
Baby: Only Breast Milk
MODERN REALITY
Mother: 400 IU/day Supplement
Baby: 300 IU/day Supplement
2014 Ivor Cummins BE(Chem) CEng MIEI
38. Why is Breast Milk now D Deficient?
MIMIC EVOLUTIONARY SUN
Mother: 6400 IU/day
Baby: Only Breast Milk
MODERN REALITY
Mother: 400 IU/day Supplement
Baby: 300 IU/day Supplement
2014 Ivor Cummins BE(Chem) CEng MIEI
39. Why is Breast Milk now D Deficient?
MIMIC EVOLUTIONARY SUN
Mother: 6400 IU/day
Baby: Only Breast Milk
MODERN REALITY
Mother: 400 IU/day Supplement
Baby: 300 IU/day Supplement
2014 Ivor Cummins BE(Chem) CEng MIEI
40. Why is Breast Milk now D Deficient?
MIMIC EVOLUTIONARY SUN
Mother: 6400 IU/day
Baby: Only Breast Milk
MODERN REALITY
Mother: 400 IU/day Supplement
Baby: 300 IU/day Supplement
2014 Ivor Cummins BE(Chem) CEng MIEI
V5=
~620
V5=
~70
41. Why is Breast Milk now D Deficient?
MIMIC EVOLUTIONARY SUN
Mother: 6400 IU/day
Baby: Only Breast Milk
MODERN REALITY
Mother: 400 IU/day Supplement
Baby: 300 IU/day Supplement
Thus with Mediocre Nutrition in Northern Latitudes, we needed to rapidly devolve
Pigmentation to enhance D3 synthesis for Infant Needs
2014 Ivor Cummins BE(Chem) CEng MIEI
V5=
~620
V5=
~70
45. Prelude
1.The Centrality of the Sun
2.25(OH)D –The Creation
3.25(OH)D –The Power
4.25(OH)D –The Human Cost
5.Anatomy of a Debacle
6.The Solution
Epilogue
Q&A
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
46. 2014 Ivor Cummins BE(Chem) CEng MIEI
How This Most Critical Hormone is Made
7 DeHydroxyCholesterol
Primary Source is Sun UVB
(Sunscreen Prevents Synthesis)
47. 2014 Ivor Cummins BE(Chem) CEng MIEI
How This Most Critical Hormone is Made
7 DeHydroxyCholesterol
Cholecalciferol
(“Vitamin” D3)
Primary Source is Sun UVB
Catalyzes “Cholesterol” to D3
(Sunscreen Prevents Synthesis)
48. 2014 Ivor Cummins BE(Chem) CEng MIEI
How This Most Critical Hormone is Made
7 DeHydroxyCholesterol
D3/D2
Supplements
Cholecalciferol
(“Vitamin” D3)
Dietary contribution is limited
Primary Source is Sun UVB
Catalyzes “Cholesterol” to D3
(Sunscreen Prevents Synthesis)
Dietary Fatty Fish, Organ Meats, etc
49. How This Most Critical Hormone is Made
7 DeHydroxyCholesterol
D3/D2
Supplements
Cholecalciferol
(“Vitamin” D3)
Dietary Fatty Fish, Organ Meats, etc
Dietary contribution is limited
Liver then makes 25(OH)D
Primary Source is Sun UVB
Catalyzes “Cholesterol” to D3
(Sunscreen Prevents Synthesis)
21stCentury Science:
In-Cell Local 1,25 D Production on Demand
2014 Ivor Cummins BE(Chem) CEng MIEI
25(OH)D !
50. How This Most Critical Hormone is Made
7 DeHydroxyCholesterol
D3/D2
Supplements
Cholecalciferol
(“Vitamin” D3)
Dietary Fatty Fish, Organ Meats, etc
25(OH)D !
Dietary contribution is limited
Liver then makes 25(OH)D
25(OH)D is The KEY METRIC
Primary Source is Sun UVB
Catalyzes “Cholesterol” to D3
(Sunscreen Prevents Synthesis)
21stCentury Science:
In-Cell Local 1,25 D Production on Demand
2014 Ivor Cummins BE(Chem) CEng MIEI
51. How This Most Critical Hormone is Made
7 DeHydroxyCholesterol
D3/D2
Supplements
Cholecalciferol
(“Vitamin” D3)
Dietary Fatty Fish, Organ Meats, etc
25(OH)D !
1,25 D
Dietary contribution is limited
Liver then makes 25(OH)D
25(OH)D is The KEY METRIC
Kidney then makes 1,25
DihydroxyVitamin D
Primary Source is Sun UVB
Catalyzes “Cholesterol” to D3
(Sunscreen Prevents Synthesis)
21stCentury Science:
In-Cell Local 1,25 D Production on Demand
2014 Ivor Cummins BE(Chem) CEng MIEI
52. How This Most Critical Hormone is Made
7 DeHydroxyCholesterol
D3/D2
Supplements
Cholecalciferol
(“Vitamin” D3)
Dietary Fatty Fish, Organ Meats, etc
25(OH)D !
1,25 D
1,25 is ACTIVE Form of D
Dietary contribution is limited
Liver then makes 25(OH)D :
25(OH)D is The KEY METRIC
Kidney then makes 1,25
DihydroxyVitamin D
Primary Source is Sun UVB
Catalyzes “Cholesterol” to D3
(Sunscreen Prevents Synthesis)
21stCentury Science:
In-Cell Local 1,25 D Production on Demand
2014 Ivor Cummins BE(Chem) CEng MIEI
53. How This Most Critical Hormone is Made
7 DeHydroxyCholesterol
D3/D2
Supplements
Cholecalciferol
(“Vitamin” D3)
Dietary Fatty Fish, Organ Meats, etc
25(OH)D !
1,25 D
1,25 is ACTIVE Form of D
Dietary contribution is limited
Liver then makes 25(OH)D
25(OH)D is The KEY METRIC
Kidney then makes 1,25
DihydroxyVitamin D
Primary Source is Sun UVB
Catalyzes “Cholesterol” to D3
(Sunscreen Prevents Synthesis)
21stCentury Science:
In-Cell Local 1,25 D Production on Demand
20th Century
Science: Mainly CaRegulation
2014 Ivor Cummins BE(Chem) CEng MIEI
54. How This Most Critical Hormone is Made
7 DeHydroxyCholesterol
D3/D2
Supplements
Cholecalciferol
(“Vitamin” D3)
Dietary Fatty Fish, Organ Meats, etc
25(OH)D !
1,25 D
1,25 is ACTIVE Form of D
Dietary contribution is limited
Liver then makes 25(OH)D
25(OH)D is The KEY METRIC
Kidney then makes 1,25
DihydroxyVitamin D
1,25 does far more than Ca++ regulation !!!
Primary Source is Sun UVB
Catalyzes “Cholesterol” to D3
(Sunscreen Prevents Synthesis)
21stCentury Science:
In-Cell Local 1,25 D Production on Demand
20th Century
Science: Mainly CaRegulation
2014 Ivor Cummins BE(Chem) CEng MIEI
55. What the Most Critical Hormone Regulates
ValdivielsoJ M et al. Am J PhysiolRenal Physiol2009;297:F1502-F1509
Low 25(OH) D Invites in:
Cancer (esp. Colon/Breast)
TB/Influenza/Infections General
Various Blood Disorders
T1 (and T2) Diabetes
Osteomalacia/Osteoporosis
Asthma / Autoimmune Diseases
Multiple Sclerosis
Heart Disease in General
Thyroid Issues / Chronic Fatigue
Inflammation
Obesity/Hypertension
Metabolic Syndrome
Pre & Post Natal Issues
2014 Ivor Cummins BE(Chem) CEng MIEI
56. What the Most Critical Hormone Regulates
ValdivielsoJ M et al. Am J PhysiolRenal Physiol2009;297:F1502-F1509
Low 25(OH) D Invites in:
Cancer (esp. Colon/Breast)
TB/Influenza/Infections General
Various Blood Disorders
T1 (and T2) Diabetes
Osteomalacia/Osteoporosis
Asthma / Autoimmune Diseases
Multiple Sclerosis
Heart Disease in General
Thyroid Issues / Chronic Fatigue
Inflammation
Obesity/Hypertension
Metabolic Syndrome
Pre & Post Natal Issues
2014 Ivor Cummins BE(Chem) CEng MIEI
57. Prelude
1.The Centrality of the Sun
2.25(OH)D –The Creation
3.25(OH)D –Control System Criticality
4.25(OH)D –The Consequences
5.Anatomy of a Debacle
6.The Solution
Epilogue
Q&A
2014 Ivor Cummins BE(Chem) CEng MIEI
58. Central Control System of the Human Machine
UNIQUE
DNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
59. Central Control System of the Human Machine
35
TRILLION
CELLS
!
UNIQUE
DNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
60. Central Control System of the Human Machine
35
TRILLION
CELLS
!
UNIQUE
DNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
61. Central Control System of the Human Machine
35
TRILLION
CELLS
!
BLOOD
SERUM 25(OH)D
25(OH)D
UNIQUE
DNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
62. Central Control System of the Human Machine
35
TRILLION
CELLS
!
BLOOD
SERUM 25(OH)D
25(OH)D
1,25 D
UNIQUE
DNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ON
DEMAND
63. Central Control System of the Human Machine
35
TRILLION
CELLS
!
VDR
RXR
BLOOD
SERUM 25(OH)D
25(OH)D
1,25 D
UNIQUE
DNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ON
DEMAND
64. Central Control System of the Human Machine
35
TRILLION
CELLS
!
VDR
RXR
BLOOD
SERUM 25(OH)D
25(OH)D
1,25 D
+SAFETYSWITCH
UNIQUE
DNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ON
DEMAND
65. Central Control System of the Human Machine
35
TRILLION
CELLS
!
VDR
RXR
BLOOD
SERUM 25(OH)D
1,25 D
VDR
RXR
VDRE
25(OH)D
1,25 D
+SAFETYSWITCH
UNIQUE
DNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ON
DEMAND
66. Central Control System of the Human Machine
35
TRILLION
CELLS
!
VDR
RXR
BLOOD
SERUM 25(OH)D
1,25 D
VDR
RXR
VDRE
25(OH)D
1,25 D
+SAFETYSWITCH
UNIQUE
DNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ON
DEMAND
67. Central Control System of the Human Machine
35
TRILLION
CELLS
!
VDR
RXR
BLOOD
SERUM 25(OH)DTranscription!!
1,25 D
VDR
RXR
VDRE
25(OH)D
1,25 D
+SAFETYSWITCH
UNIQUE
DNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ON
DEMAND
68. Central Control System of the Human Machine
35
TRILLION
CELLS
!
VDR
RXR
BLOOD
SERUM 25(OH)DTranscription!!
1,25 D
VDR
RXR
VDRE
25(OH)D
1,25 D
+SAFETYSWITCHSAFETYSWITCH
UNIQUE
DNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ON
DEMAND
69. Central Control System of the Human Machine
35
TRILLION
CELLS
!
VDR
RXR
BLOOD
SERUM 25(OH)DTranscription!!
1,25 D
VDR
RXR
VDRE
25(OH)D
1,25 D
+SAFETYSWITCHSAFETYSWITCH
UNIQUE
DNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ON
DEMAND
70. Central Control System of the Human Machine
35
TRILLION
CELLS
!
VDR
RXR
BLOOD
SERUM 25(OH)DTranscription!!
1,25 D
VDR
RXR
VDRE
25(OH)D
1,25 D
+SAFETYSWITCHSAFETYSWITCH
UNIQUE
DNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ON
DEMAND
CRITICAL PROTEINS
e.g. CATHELICIDIN
71. Central Control System of the Human Machine
35
TRILLION
CELLS
!
VDR
RXR
BLOOD
SERUM 25(OH)DTranscription!!
1,25 D
VDR
RXR
VDRE
25(OH)D
1,25 D
+SAFETYSWITCHSAFETYSWITCH
UNIQUE
DNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ON
DEMAND
CRITICAL PROTEINS
e.g. CATHELICIDINReplication!!
72. Central Control System of the Human Machine
35
TRILLION
CELLS
!
VDR
RXR
BLOOD
SERUM 25(OH)DTranscription!!
1,25 D
VDR
RXR
VDRE
Blood Pressure
Cancer
Heart Disease
MS, TB, Flu
Asthma
T1 Diabetes
T2 Diabetes
Obesity
Met Syndrome
Alzheimers
25(OH)D
1,25 D
+SAFETYSWITCHSAFETYSWITCH
UNIQUE
DNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ON
DEMAND
CRITICAL PROTEINS
e.g. CATHELICIDINReplication!!
76. Prelude
1.The Centrality of the Sun
2.25(OH)D –The Creation
3.25(OH)D –The Power
4.25(OH)D –The Consequences
5.Anatomy of a Debacle
6.The Solution
Epilogue
Q&A
2014 Ivor Cummins BE(Chem) CEng MIEI
77. Survival Outcome for low 25(OH)D reminiscent of Smokers VsNon-Smokers
Doesn’t Prove Causality
Summary:
HEART and GENERAL MORBIDITY
Relation of Vitamin D Deficiency to Cardiovascular Risk Factors, Disease Status, and Incident Events in a General Healthcare Population
Jeffrey L. Anderson, MDa,b,*, Heidi T. May, PhD, MSPHa, Benjamin D. Horne, PhD, MPHa,c,
Tami L. Bair, BSa, Nathaniel L. Hall, MDa,b, John F. Carlquist, PhDa,b, Donald L. Lappé, MDa, and
Joseph B. Muhlestein, MDa,b, for the Intermountain Heart Collaborative (IHC) Study Group
(Am J Cardiol2010;106:963–968)
Population 25(OH)D Levels
Adequate
>30ng/ml
36.4%
V. Low <16
16.7%
Low
16-30 ng/ml
46.4%
2014 Ivor Cummins BE(Chem) CEng MIEI
Majority Population Insufficient
Remember D is a proxy for Sun(!)
>30
16-30
<16
78. Vitamin D and Cardiovascular Disease
Carl J. Lavie, MD, John H. Lee, MD, Richard V. Milani, MD
(J Am CollCardiol2011;58:1547–56)
Survival trends stronger than Non-Smoker versus Smoker
Dose-Response Relationship with Accelerated Effect in lowest Quartile
Key Takeaways:
2014 Ivor Cummins BE(Chem) CEng MIEI
CVD and All Cause Death
79. Assmann G, Schulte H. Am J Cardiol. 1992;70:733–737.
Incidence Rate Average of 6 Studies, consistent association throughout
Key Takeaways:
COLON CANCER –Incidence Rate
2014 Ivor Cummins BE(Chem) CEng MIEI
55% reduction in Colon
Cancer Risk associated with 38ng/ml 25(OH)D
Odds Ratio of Colorectal Cancer
P trend <0.0001
COLON CANCER INCIDENCE
10
20
40
30
80. Assmann G, Schulte H. Am J Cardiol. 1992;70:733–737.
Incidence Rate Average of 6 Studies, consistent association throughout
Mortality strongly associated with 25(OH)D levels, but multi-factor phenomenon
Key Takeaways:
COLON CANCER –Incidence Rate
2014 Ivor Cummins BE(Chem) CEng MIEI
55% reduction in Colon
Cancer Risk associated with 38ng/ml 25(OH)D
Odds Ratio of Colorectal Cancer
P trend <0.0001
COLON CANCER INCIDENCE
COLON CANCER MORTALITY
RR = 0.28
RR = 0.44
Relative risk
10
20
40
30
P trend =0.02
81. Strong, Linear association –& D mechanism directly tied to cell proliferation
Key Takeaways:
BREAST CANCER -Mortality
Vitamin D and prevention of breast cancer: Pooled analysis (2007)
Cedric F. Garland,, Edward D. Gorhama, Sharif B. Mohra, William B. Grant b,EdwardL. Giovannucci, Martin Lipkin, Harold Newmarke, Michael F. Holick, Frank C. Garland
Journal of Steroid Biochemistry & Molecular Biology 103 (2007) 708–711
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
P trend <0.001
R2= 0.9
50% lower risk
with 48 ng/ml
82. Strong, Linear association –& D mechanism directly tied to cell proliferation
Key Takeaways:
BREAST CANCER -Mortality
Vitamin D and prevention of breast cancer: Pooled analysis (2007)
Cedric F. Garland,, Edward D. Gorhama, Sharif B. Mohra, William B. Grant b,EdwardL. Giovannucci, Martin Lipkin, Harold Newmarke, Michael F. Holick, Frank C. Garland
Journal of Steroid Biochemistry & Molecular Biology 103 (2007) 708–711
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
P trend <0.001
R2= 0.9
50% lower risk
with 48 ng/ml
P trend <0.002
R2= 0.94
50% lower risk
with 52 ng/ml
83. Association is Dramatic, and mechanism’s available.
Key Takeaways:
BREAST CANCER -Mortality
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
Where would you rather be?
BREAST CANCER MORTALITY
RR = 0.28
P <0.05
84. Enormous body of evidence linking MS to 25(OH)D Status
MULTIPLE SCLEROSIS
2014 Ivor Cummins BE(Chem) CEng MIEI
Contribution of vitamin D insufficiency to the
pathogenesis of Multiple Sclerosis
Ther AdvNeurolDisord
(2013) 6(2) 81–116
DOI: 10.1177/
1756285612473513
Ireland
53O N
85. Enormous body of evidence linking MS to 25(OH)D Status:
MULTIPLE SCLEROSIS
2014 Ivor Cummins BE(Chem) CEng MIEI
25(OH)D Interacts with risk of MS from conception thru life via different mechs
Contribution of vitamin D insufficiency to the
pathogenesis of Multiple Sclerosis
Ther AdvNeurolDisord
(2013) 6(2) 81–116
DOI: 10.1177/
1756285612473513
NO
MS
MS
86. MULTIPLE SCLEROSIS
Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study
BMJ VOLUME 327 9 AUGUST 2003 bmj.com
N=136 MS Cases (in their 30’s) vs273 Matched Controls
Summary:
2014 Ivor Cummins BE(Chem) CEng MIEI
87. MULTIPLE SCLEROSIS
Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study
BMJ VOLUME 327 9 AUGUST 2003 bmj.com
N=136 MS Cases (in their 30’s) vs273 Matched Controls
Summary:
2014 Ivor Cummins BE(Chem) CEng MIEI
Consistent Dose-Response Benefit primarily for exposure age 6-10 and 10-16
P<0.01 for trend
88. MULTIPLE SCLEROSIS
Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study
BMJ VOLUME 327 9 AUGUST 2003 bmj.com
N=136 MS Cases (in their 30’s) vs273 Matched Controls
Summary:
2014 Ivor Cummins BE(Chem) CEng MIEI
Even more marked when Actinic Damage was used as independent measure
P<0.01 for trend
P<0.01 for trend
Consistent Dose-Response Benefit primarily for exposure age 6-10 and 10-16
89. MULTIPLE SCLEROSIS
Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study
BMJ VOLUME 327 9 AUGUST 2003 bmj.com
N=136 MS Cases (in their 30’s) vs273 Matched Controls
Summary:
2014 Ivor Cummins BE(Chem) CEng MIEI
Even more marked when Actinic Damage was used as independent measure
Conclusion: UVB and/or D critical for Adaptive Immune System Development
P<0.01 for trend
P<0.01 for trend
Consistent Dose-Response Benefit primarily for exposure age 6-10 and 10-16
MS
MS
90. Prelude
1.The Centrality of the Sun
2.25(OH)D –The Creation
3.25(OH)D –The Power
4.25(OH)D –The Consequences
5.Anatomy of a Debacle
6.The Solution
Epilogue
Q&A
2014 Ivor Cummins BE(Chem) CEng MIEI
91. Correctly executed, difference controlled to be primarily D and Ca.
Key Takeaways:
ALL CANCER MORTALITY (Experiment)
Baseline 25(OH)D = 29ng/ml
1100 IU Vitamin D + 1450 Ca/ day
Randomized Control Trial
N = 1179 Healthy Women
2014 Ivor Cummins BE(Chem) CengMIEI
Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial
92. Correctly executed, difference controlled to be primarily D and Ca.
Key Takeaways:
ALL CANCER MORTALITY (Experiment)
Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial
Baseline 25(OH)D = 29ng/ml
1100 IU Vitamin D + 1450 Ca/ day
Randomized Control Trial
N = 1179 Healthy Women
2014 Ivor Cummins BE(Chem) CengMIEI
Clear impact on Cancer and Overall mortality, especially with 1stYear removed
93. TYPE 1 DIABETES
2014 Ivor Cummins BE(Chem) CEng MIEI
The most common serious chronic disease in children, esp. in Northern Latitude
94. TYPE 1 DIABETES -Finnish Study
Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study
THE LANCET • Vol 358 • November 3, 2001
N=12,055 Births in 1966, Supplementation 1styear of life, follow-up to 1997
Summary:
2014 Ivor Cummins BE(Chem) CEng MIEI
95. TYPE 1 DIABETES -Finnish Study
Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study
THE LANCET • Vol 358 • November 3, 2001
N=12,055 Births in 1966, Supplementation 1styear of life, follow-up to 1997
Summary:
2014 Ivor Cummins BE(Chem) CEng MIEI
Note: Vitamin D known to prevent Type 1 Diabetes in animals
96. TYPE 1 DIABETES -Finnish Study
Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study
THE LANCET • Vol 358 • November 3, 2001
N=12,055 Births in 1966, Supplementation 1styear of life, follow-up to 1997
Summary:
2014 Ivor Cummins BE(Chem) CEng MIEI
Adjusted for Social Status, Birth Weight, Growth Rate etc.
Note: Vitamin D known to prevent Type 1 Diabetes in animals
97. TYPE 1 DIABETES -Finnish Study
Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study
THE LANCET • Vol 358 • November 3, 2001
N=12,055 Births in 1966, Supplementation 1styear of life, follow-up to 1997
Summary:
2014 Ivor Cummins BE(Chem) CEng MIEI
Adjusted for Social Status, Birth Weight, Growth Rate etc.
Note: Vitamin D known to prevent Type 1 Diabetes in animals
98. TYPE 1 DIABETES -Finnish Study
Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study
THE LANCET • Vol 358 • November 3, 2001
N=12,055 Births in 1966, Supplementation 1styear of life, follow-up to 1997
Summary:
2014 Ivor Cummins BE(Chem) CEng MIEI
Adjusted for Social Status, Birth Weight, Growth Rate etc.
Note: Vitamin D known to prevent Type 1 Diabetes in animals
99. TYPE 1 DIABETES -Finnish Study
Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study
THE LANCET • Vol 358 • November 3, 2001
N=12,055 Births in 1966, Supplementation 1styear of life, follow-up to 1997
Summary:
2014 Ivor Cummins BE(Chem) CEng MIEI
Adjusted for Social Status, Birth Weight, Growth Rate etc.
Note: Vitamin D known to prevent Type 1 Diabetes in animals
Conclusion Clear –Verified Vitamin D critical for Immune System Development
100. 2014 Ivor Cummins BE(Chem) CEng MIEI
FINLAND GUIDELINE VIT D vsType1 Diabetes Incidence in <15 Year Olds
Northern Latitude, very poor UVB. Supplement Strategy collapsed since 1950’s
Summary:
Incidence of Type 1 Diabetes in Finland
JAMA July 24/31, 2013 Volume 310, Number 4
TYPE 1 DIABETES -Supplementation History?
IU/Day VitD
101. 2014 Ivor Cummins BE(Chem) CEng MIEI
FINLAND GUIDELINE VIT D vsType1 Diabetes Incidence in <15 Year Olds
Northern Latitude, very poor UVB. Supplement Strategy collapsed since 1950’s
Summary:
Incidence Rate studied for 1978 onwards, & some Trend Messing about…
Incidence of Type 1 Diabetes in Finland
JAMA July 24/31, 2013 Volume 310, Number 4
TYPE 1 DIABETES -Supplementation History?
10
20
30
40
50
60
70
IU/Day VitD
102. 2014 Ivor Cummins BE(Chem) CEng MIEI
FINLAND GUIDELINE VIT D vsType1 Diabetes Incidence in <15 Year Olds
Northern Latitude, very poor UVB. Supplement Strategy collapsed since 1950’s
Summary:
Conclusion: Not quite clear? Questioned. Supplemented Dairy acknowledged.
Incidence Rate studied for 1978 onwards, & some Trend Messing about…
Incidence of Type 1 Diabetes in Finland
JAMA July 24/31, 2013 Volume 310, Number 4
D-fortified
Dairy
TYPE 1 DIABETES -Supplementation History?
IU/Day VitD
10
20
30
40
50
60
70
103. Incidence of Type 1 Diabetes in Finland
JAMA July 24/31, 2013 Volume 310, Number 4
Remove the inappropriate inferences, and plot a natural curve
EngineeringStyle Summary:
2014 Ivor Cummins BE(Chem) CEng MIEI
FINLAND GUIDELINE VIT D vsType1 Diabetes Incidence in <15 Year Olds
D-fortified
Dairy
TYPE 1 DIABETES -Supplementation History?
IU/Day VitD
10
20
30
40
50
60
70
104. Incidence of Type 1 Diabetes in Finland
JAMA July 24/31, 2013 Volume 310, Number 4
Remove the inappropriate inferences, and plot a natural curve
EngineeringStyle Summary:
2014 Ivor Cummins BE(Chem) CEng MIEI
Add in the earlier historical data from another source that had it…
FINLAND GUIDELINE VIT D vsType1 Diabetes Incidence in <15 Year Olds
Diabetes December 2002 vol. 51 no. 12 3353-3361
The Rise of Childhood Type 1 Diabetes in the 20th Century
D-fortified
Dairy
TYPE 1 DIABETES -Supplementation History?
IU/Day VitD
10
20
30
40
50
60
70
105. Incidence of Type 1 Diabetes in Finland
JAMA July 24/31, 2013 Volume 310, Number 4
Remove the inappropriate inferences, and plot a natural curve
EngineeringStyle Summary:
2014 Ivor Cummins BE(Chem) CEng MIEI
Conclusion: -go figure.
Diabetes December 2002 vol. 51 no. 12 3353-3361
The Rise of Childhood Type 1 Diabetes in the 20th Century
FINLAND GUIDELINE VIT D vsType1 Diabetes Incidence in <15 Year Olds
Add in the earlier historical data from another source that had it…
D-fortified
Dairy
TYPE 1 DIABETES -Supplementation History?
IU/Day VitD
10
20
30
40
50
60
70
106. Strong Hypothesis that Flu Outbreaks are mediated by 25(OH)D levels
Summary:
INFLUENZA –Seasonal Triggering
Hypponen E, Power C: HypovitaminosisD in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors
Am J Clin Nutr 2007, 85: 860–868
2014 Ivor Cummins BE(Chem) CEng MIEI
107. Strong Hypothesis that Flu Outbreaks are mediated by 25(OH)D levels
Summary:
INFLUENZA –Seasonal Triggering
Hypponen E, Power C: HypovitaminosisD in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors
Am J Clin Nutr 2007, 85: 860–868
Latitude Simultaneity, Transfer Dynamics, etc
2014 Ivor Cummins BE(Chem) CEng MIEI
108. INFLUENZA –Seasonal Triggering
2014 Ivor Cummins BE(Chem) CEng MIEI
16
20
24
28
32
25(OH)D ng/ml
0
5
10
15
20
% Respiratory Infection
Month
Season
0
5
10
15
20
% Respiratory Infection
Berry DJ, Hesketh K, Power C, et al. (2011) Vitamin D status has a liner association with seasonal infections and lung function in British adults.
Br J Nutr106, 1433–1440
109. 208 randomised individuals to placebo or 800 IU/day of D3 over 2 years
Key Takeaways:
INFLUENZA –Hospital Experiment
Re: epidemic Influenza and vitamin D
AloiaJF, Li-Ng M: Epidemic influenza and vitamin D. EpidemiolInfect 2007; 135: 1095–1096
Cannellet al. VirologyJournal 2008 5:29 doi:10.1186/1743-422X-5-29.
2014 Ivor Cummins BE(Chem) CEng MIEI
Increased to 2000 IU/day in 3rdYear
110. 208 randomised individuals to placebo or 800 IU/day of D3 over 2 years
Key Takeaways:
Re: epidemic Influenza and vitamin D
AloiaJF, Li-Ng M: Epidemic influenza and vitamin D. EpidemiolInfect 2007; 135: 1095–1096
Cannellet al. VirologyJournal 2008 5:29 doi:10.1186/1743-422X-5-29.
2014 Ivor Cummins BE(Chem) CEng MIEI
Increased to 2000 IU/day in 3rdYear
INFLUENZA –Hospital Experiment
111. 208 randomised individuals to placebo or 800 IU/day of D3 over 2 years
Key Takeaways:
Re: epidemic Influenza and vitamin D
AloiaJF, Li-Ng M: Epidemic influenza and vitamin D. EpidemiolInfect 2007; 135: 1095–1096
Cannellet al. VirologyJournal 2008 5:29 doi:10.1186/1743-422X-5-29.
2014 Ivor Cummins BE(Chem) CEng MIEI
Increased to 2000 IU/day in 3rdYear
25(OH)D acts via multiple mechanisms as discussed
INFLUENZA –Hospital Experiment
112. 208 randomised individuals to placebo or 800 IU/day of D3 over 2 years
Key Takeaways:
Re: epidemic Influenza and vitamin D
AloiaJF, Li-Ng M: Epidemic influenza and vitamin D. EpidemiolInfect 2007; 135: 1095–1096
Cannellet al. VirologyJournal 2008 5:29 doi:10.1186/1743-422X-5-29.
2014 Ivor Cummins BE(Chem) CEng MIEI
Increased to 2000 IU/day in 3rdYear
25(OH)D acts via multiple mechanisms as discussed
Very few studies done (and mouse/rat/dog lack the VDR for this mechanism, so much data is worthless…)
INFLUENZA –Hospital Experiment
113. 2014 Ivor Cummins BE(Chem) CEng MIEI
The Bottom Line: “Mechanisms From pre-Cradle to Grave”
114. Prelude
1.The Centrality of the Sun
2.25(OH)D –The Creation
3.25(OH)D –The Power
4.25(OH)D –The Consequences
5.Anatomy of a Debacle
6.The Solution
Epilogue
Q&A
2014 Ivor Cummins BE(Chem) CEng MIEI
115. Witness An Unfolding Catastrophe….
NHANES III (1988-1994)
SERUM 25(OH)D: % >30ng/ml
10
20
30
40
50
NHANES (2001-2004)
117. 2014 Ivor Cummins BE(Chem) CEng MIEI
European Journal of Clinical Nutrition (2012)
doi:10.1038/ejcn.2012.78
Vitamin D and the scientific calcium dogma:
understanding the ‘Panacea’ of the sun
Pineal Hormone
Vitamin D
SKIN
118. 2014 Ivor Cummins BE(Chem) CEng MIEI
Vitamin D and the scientific calcium dogma:
understanding the ‘Panacea’ of the sun
European Journal of Clinical Nutrition (2012)
doi:10.1038/ejcn.2012.78
Pineal Hormone
Vitamin D
SKIN
119. 2014 Ivor Cummins BE(Chem) CEng MIEI
USA
25(OH)D
Distribution
~70% of US Population Insufficient
( 15 Years Previously was ~50% )
< 32ng/ml > 32ng/ml
Recall Where We Are Now…..
Vitamin D and the scientific calcium dogma:
understanding the ‘Panacea’ of the sun
European Journal of Clinical Nutrition (2012)
doi:10.1038/ejcn.2012.78
Pineal Hormone
Vitamin D
SKIN
120. 2014 Ivor Cummins BE(Chem) CEng MIEI
Vitamin D and the scientific calcium dogma:
understanding the ‘Panacea’ of the sun
European Journal of Clinical Nutrition (2012)
doi:10.1038/ejcn.2012.78
Recall Where We Are Now…..
Pineal Hormone
Vitamin D
SKIN
121. The Skin Cancer / Melanoma Hysteria
J Am AcadDermatol. 2006 Feb;54(2):301-17
2014 Ivor Cummins BE(Chem) CEng MIEI
330
340
350
360
360
370
380
390
400
Blue is UV-B zone that enables Vitamin D Synthesis (and Cholesterol Sulphate)
122. The Skin Cancer / Melanoma Hysteria
J Am AcadDermatol. 2006 Feb;54(2):301-17
2014 Ivor Cummins BE(Chem) CEng MIEI
330
340
350
360
360
370
380
390
400
Red is zone that enables tan protection, and warning Erythema (Sunburn)
Blue is UV-B zone that enables Vitamin D Synthesis (and Cholesterol Sulphate)
123. The Skin Cancer / Melanoma Hysteria
J Am AcadDermatol. 2006 Feb;54(2):301-17
2014 Ivor Cummins BE(Chem) CEng MIEI
330
340
350
360
360
370
380
390
400
Green is zone that theoretical modelling suggests “Cosmetic” Skin Cancers
Red is zone that enables tan protection, and warning Erythema (Sunburn)
Blue is UV-B zone that enables Vitamin D Synthesis (and Cholesterol Sulphate)
124. The Skin Cancer / Melanoma Hysteria
J Am AcadDermatol. 2006 Feb;54(2):301-17
2014 Ivor Cummins BE(Chem) CEng MIEI
330
340
350
360
360
370
380
390
400
UV-A is currently deemed the primary driver of Cutaneous Malig. Melanoma
Green is zone that theoretical modelling suggests Squamous Skin Cancer
Red is zone that enables tan protection, and warning Erythema (Sunburn)
Blue is UV-B zone that enables Vitamin D Synthesis (and Cholesterol Sulphate)
~95% of Terrestrial UV Energy is from UVA. And it sails thru Ozone, and even Glass
125. The Skin Cancer / Melanoma Hysteria
J Am AcadDermatol. 2006 Feb;54(2):301-17
2014 Ivor Cummins BE(Chem) CEng MIEI
330
340
350
360
360
370
380
390
400
Green is zone that theoretical modelling suggests Squamous Skin Cancer
Red is zone that enables tan protection, and warning Erythema (Sunburn)
Blue is UV-B zone that enables Vitamin D Synthesis (and Cholesterol Sulphate)
UV-A is currently deemed the primary driver of Cutaneous Malig. Melanoma
Squamous and Basal cell Skin Cancers?
-<0.5% Mortality)
USA: ~2k deaths/yr
Melanoma Zone –Serious Stuff
USA: ~9k deaths/yr
126. The Skin Cancer / Melanoma Hysteria
J Am AcadDermatol. 2006 Feb;54(2):301-17
2014 Ivor Cummins BE(Chem) CEng MIEI
So who’s the idiot? (a) Evolution Itself, or (b) how humans have interpreted it??
330
340
350
360
360
370
380
390
400
Green is zone that theoretical modelling suggests Squamous Skin Cancer
Red is zone that enables tan protection, and warning Erythema (Sunburn)
Blue is UV-B zone that enables Vitamin D Synthesis (and Cholesterol Sulphate)
UV-A is currently deemed the primary driver of Cutaneous Malig. Melanoma
Squamous and Basal cell Skin Cancers?
-<0.5% Mortality)
USA: ~2k deaths/yr
Melanoma Zone –Serious Stuff
USA: ~9k deaths/yr
Sunscreens Effective
Most Sunscreens Not Effective
127. MELANOMA Versus Sun Exposure History
Eur J Cancer. Mar 2011; 47(5): 732–741
“Relationship between sun exposure and melanoma risk for tumors in different body sites in a large case-control study in a temperate climate”
N=960 MelanomaVictim Study:
2014 Ivor Cummins BE(Chem) CEng MIEI
128. MELANOMA Versus Sun Exposure History
Eur J Cancer. Mar 2011; 47(5): 732–741
“Relationship between sun exposure and melanoma risk for tumors in different body sites in a large case-control study in a temperate climate”
N=960 MelanomaVictim Study:
2014 Ivor Cummins BE(Chem) CEng MIEI
Healthy Sun Exposure, LOWER Risk
129. MELANOMA Versus Sun Exposure History
Eur J Cancer. Mar 2011; 47(5): 732–741
“Relationship between sun exposure and melanoma risk for tumors in different body sites in a large case-control study in a temperate climate”
N=960 MelanomaVictim Study:
2014 Ivor Cummins BE(Chem) CEng MIEI
Healthy Sun Exposure, LOWER Risk
130. MELANOMA Versus Sun Exposure History
Eur J Cancer. Mar 2011; 47(5): 732–741
“Relationship between sun exposure and melanoma risk for tumors in different body sites in a large case-control study in a temperate climate”
N=960 MelanomaVictim Study:
2014 Ivor Cummins BE(Chem) CEng MIEI
Healthy Sun Exposure, LOWER Risk
131. MELANOMA Versus Sun Exposure History
Eur J Cancer. Mar 2011; 47(5): 732–741
“Relationship between sun exposure and melanoma risk for tumors in different body sites in a large case-control study in a temperate climate”
N=960 MelanomaVictim Study:
2014 Ivor Cummins BE(Chem) CEng MIEI
Healthy Sun Exposure, LOWER Risk
Strong Correlation to 25(OH)D Observed
This Effect Applied to BOTH Skin Types
132. MELANOMA Versus Sun Exposure History
Eur J Cancer. Mar 2011; 47(5): 732–741
“Relationship between sun exposure and melanoma risk for tumors in different body sites in a large case-control study in a temperate climate”
N=960 MelanomaVictim Study:
2014 Ivor Cummins BE(Chem) CEng MIEI
Healthy Sun Exposure, LOWER Risk
Strong Correlation to 25(OH)D Observed
One of many Studies illustrating this effect
This Effect Applied to BOTH Skin Types
133. MELANOMA Versus Sun Exposure History
Eur J Cancer. Mar 2011; 47(5): 732–741
“Relationship between sun exposure and melanoma risk for tumors in different body sites in a large case-control study in a temperate climate”
Strong Correlation to 25(OH)D Observed
One of many Studies illustrating this effect
N=960 MelanomaVictim Study:
Healthy Sun Exposure, LOWER Risk
This Effect Applied to BOTH Skin Types
2014 Ivor Cummins BE(Chem) CEng MIEI
The Real Risk Factors?
134. MELANOMA Versus Sun Exposure History
Eur J Cancer. Mar 2011; 47(5): 732–741
“Relationship between sun exposure and melanoma risk for tumors in different body sites in a large case-control study in a temperate climate”
Strong Correlation to 25(OH)D Observed
One of many Studies illustrating this effect
N=960 MelanomaVictim Study:
Healthy Sun Exposure, LOWER Risk
This Effect Applied to BOTH Skin Types
2014 Ivor Cummins BE(Chem) CEng MIEI
The Real Risk Factors?
Significant Sun Burning Incidents
135. MELANOMA Versus Sun Exposure History
Eur J Cancer. Mar 2011; 47(5): 732–741
“Relationship between sun exposure and melanoma risk for tumors in different body sites in a large case-control study in a temperate climate”
Strong Correlation to 25(OH)D Observed
One of many Studies illustrating this effect
N=960 MelanomaVictim Study:
Healthy Sun Exposure, LOWER Risk
Light Skin; Freckles; Red Hair – Propensity to Burn
The Real Risk Factors?
Significant Sun Burning Incidents
This Effect Applied to BOTH Skin Types
2014 Ivor Cummins BE(Chem) CEng MIEI
136. SUNSCREENS: A Counter-Intuitive Twist
Int. J. Cancer: 87, 145–150 (2000)
“SUNSCREEN USE AND MALIGNANT MELANOMA”
N=571 Cutaneous Malignant Melanoma, Versus N=913 Healthy Controls:
2014 Ivor Cummins BE(Chem) CEng MIEI
HR
137. SUNSCREENS: A Counter-Intuitive Twist
Int. J. Cancer: 87, 145–150 (2000)
“SUNSCREEN USE AND MALIGNANT MELANOMA”
N=571 Cutaneous Malignant Melanoma, Versus N=913 Healthy Controls:
Generally Higher Risk of Cancer with increased sunscreen use
2014 Ivor Cummins BE(Chem) CEng MIEI
HR
138. SUNSCREENS: A Counter-Intuitive Twist
Int. J. Cancer: 87, 145–150 (2000)
“SUNSCREEN USE AND MALIGNANT MELANOMA”
N=571 Cutaneous Malignant Melanoma, Versus N=913 Healthy Controls:
Generally Higher Risk of Cancer with increased sunscreen use
this also applied after adjustment for Skin, Exposure Frequency and Duration
2014 Ivor Cummins BE(Chem) CEng MIEI
HR
139. SUNSCREENS: A Counter-Intuitive Twist
Int. J. Cancer: 87, 145–150 (2000)
“SUNSCREEN USE AND MALIGNANT MELANOMA”
UVA Mechanism, Lack of UVA Protection, Vitamin D and OverExpHighlighted
N=571 Cutaneous Malignant Melanoma, Versus N=913 Healthy Controls:
Generally Higher Risk of Cancer with increased sunscreen use
this also applied after adjustment for Skin, Exposure Frequency and Duration
2014 Ivor Cummins BE(Chem) CEng MIEI
HR
141. The Bottom Line: All Cause Mortality
Journal of Internal Medicine: doi: 10.1111/joim.12251
“Avoidance of sun exposure is a risk factor for all-cause mortality: results from the Melanoma in Southern Sweden cohort”
N=29,518 Swedish Women: Prospective Study with 20 Year Follow-Up
2014 Ivor Cummins BE(Chem) CEng MIEI
142. The Bottom Line: All Cause Mortality
Journal of Internal Medicine: doi: 10.1111/joim.12251
“Avoidance of sun exposure is a risk factor for all-cause mortality: results from the Melanoma in Southern Sweden cohort”
N=29,518 Swedish Women: Prospective Study with 20 Year Follow-Up
All-Cause Mortality was Halvedin UPPER Quartile of Sun Exposure
2014 Ivor Cummins BE(Chem) CEng MIEI
~2x Mortality Rate Throughout
143. The Bottom Line: All Cause Mortality
Journal of Internal Medicine: doi: 10.1111/joim.12251
“Avoidance of sun exposure is a risk factor for all-cause mortality: results from the Melanoma in Southern Sweden cohort”
N=29,518 Swedish Women: Prospective Study with 20 Year Follow-Up
All-Cause Mortality was Halvedin UPPER Quartile of Sun Exposure
this applied after adjustment for Co-Morbidity, Smoking, Education, Income etc
2014 Ivor Cummins BE(Chem) CEng MIEI
~2x Mortality Rate Throughout
144. The Bottom Line: All Cause Mortality
Journal of Internal Medicine: doi: 10.1111/joim.12251
“Avoidance of sun exposure is a risk factor for all-cause mortality: results from the Melanoma in Southern Sweden cohort”
Dose-Response Relationship seen throughout
N=29,518 Swedish Women: Prospective Study with 20 Year Follow-Up
All-Cause Mortality was Halvedin UPPER Quartile of Sun Exposure
this applied after adjustment for Co-Morbidity, Smoking, Education, Income etc
2014 Ivor Cummins BE(Chem) CEng MIEI
~2x Mortality Rate Throughout
145. The Bottom Line: All Cause Mortality
Journal of Internal Medicine: doi: 10.1111/joim.12251
“Avoidance of sun exposure is a risk factor for all-cause mortality: results from the Melanoma in Southern Sweden cohort”
Dose-Response Relationship seen throughout
N=29,518 Swedish Women: Prospective Study with 20 Year Follow-Up
All-Cause Mortality was Halvedin UPPER Quartile of Sun Exposure
this applied after adjustment for Co-Morbidity, Smoking, Education, Income etc
2014 Ivor Cummins BE(Chem) CEng MIEI
~2x Mortality Rate Throughout
25(OH)D indeed Cited, but there are other benefits of Sun
146. 2014 Ivor Cummins BE(Chem) MIEI
Prelude
1.The Centrality of the Sun
2.25(OH)D –The Creation
3.25(OH)D –The Power
4.25(OH)D –The Consequences
5.Anatomy of a Debacle
6.The Solution
Epilogue
Q&A
147. Optimising 25(OH)D –Synergy and Interaction
LOW25(OH)D
<32 ng/ml
Blood Pressure
Cancer
Heart Disease
MS, TB, Flu
Asthma
T1 Diabetes
T2 Diabetes
Obesity
Met Syndrome
Alzheimers
Lack of SUN Exposure
Low Fat
Diet
Low Calcium
Diet
Racial factors & Genetics
148. Optimising 25(OH)D –Synergy and Interaction
LOW25(OH)D
<32 ng/ml
Blood Pressure
Cancer
Heart Disease
MS, TB, Flu
Asthma
T1 Diabetes
T2 Diabetes
Obesity
Met Syndrome
Alzheimers
Lack of SUN Exposure
Low Fat
Diet
Low Calcium
Diet
HIGH25(OH)D
>60? ng/ml
Excess SUN Exposure LG
Excess D3Supplements
Racial factors & Genetics
AND
/OR
Low
VitK2
Excessive
Calcification?
149. Optimising 25(OH)D –Synergy and Interaction
LOW25(OH)D
<32 ng/ml
Blood Pressure
Cancer
Heart Disease
MS, TB, Flu
Asthma
T1 Diabetes
T2 Diabetes
Obesity
Met Syndrome
Alzheimers
Healthy Sun Exposure
UVB/UVA Ratio
Lack of SUN Exposure
Low Fat
Diet
Low Calcium
Diet
OPTIMUM25(OH)D
32-50 ng/ml
Fat-Nutrient Dense Diet
Oily Fish, Cod Liver, Pate, etc
CorrectD3Supplements
HIGH25(OH)D
>60? ng/ml
Excess SUN Exposure LG
Excess D3Supplements
Racial factors & Genetics
AND
AdequateCalcium
AND
/OR
AdequateVitA
AdequateVitK2
Excessive
Calcification?
Low
VitK2
150. Optimising 25(OH)D –Synergy and Interaction
LOW25(OH)D
<32 ng/ml
Blood Pressure
Cancer
Heart Disease
MS, TB, Flu
Asthma
T1 Diabetes
T2 Diabetes
Obesity
Met Syndrome
Alzheimers
Lack of SUN Exposure
Low Fat
Diet
Low Calcium
Diet
OPTIMUM25(OH)D
32-50 ng/ml
Fat-Nutrient Dense Diet
Oily Fish, Cod Liver, Pate, etc
CorrectD3Supplements
HIGH25(OH)D
>60? ng/ml
Excess SUN Exposure LG
Excess D3Supplements
Racial factors & Genetics
AND
AdequateCalcium
AND
/OR
AdequateVitA
AdequateVitK2
Immune Function
Bone Strength
Disease Protection
Cancer Resistance
Vigour & Longevity
Healthy Sun Exposure
UVB/UVA Ratio
Excessive
Calcification?
Low
VitK2
151. 2014 Ivor Cummins BE(Chem) MIEI
Prelude
1.The Centrality of the Sun
2.25(OH)D –The Creation
3.25(OH)D –The Power
4.25(OH)D –The Consequences
5.Anatomy of a Debacle
6.The Solution
Epilogue
Q&A
152. Epilogue –Respecting Evolution and Science
•Levels should be in 32-50ng/ml range (80-120nmol/L)
2014 Ivor Cummins BE(Chem) CEng MIEI
•“Short Shadow” Sun Exposure Without Burning is key
•Supplements: D3: new upper guideline is 4000 IU/day*
•Oily Fish, Organ Meats, Fortified Dairy etc. will help…
25(OH)D
153. Epilogue –Respecting Evolution and Science
•Levels should be in 32-50ng/ml range (80-120nmol/L)
2014 Ivor Cummins BE(Chem) CEng MIEI
•“Short Shadow” Sun Exposure Without Burning is key
•Supplements: D3: new upper guideline is 4000 IU/day*
•Oily Fish, Organ Meats, Fortified Dairy etc. will help…
•Calciumis critical and works in tandem with 25(OH)D
•Too low is more likely than too high these days…
•Plenty Cheese/Yogurt/Milk, Sardines, Dark Leafy Greens.
•Supplements –medical guidance.
25(OH)D
154. Epilogue –Respecting Evolution and Science
•Levels should be in 32-50ng/ml range (80-120nmol/L)
2014 Ivor Cummins BE(Chem) CEng MIEI
•“Short Shadow” Sun Exposure Without Burning is key
•Supplements: D3: new upper guideline is 4000 IU/day*
•Oily Fish, Organ Meats, Fortified Dairy etc. will help…
•Calciumis critical and works in tandem with 25(OH)D
•Too low is more likely than too high these days…
•Plenty Cheese/Yogurt/Milk, Sardines, Dark Leafy Greens.
•VitaminK2 is key, possibly the most important besides D.
•Supplements –medical guidance.
•Activates Matrix GLA Protein, for Calcium Management
•Highly interactive with Vitamin D & Ca–need keep K2 high
•Butter/Cheeses, Natto, Chicken Legs, Egg Yolks, Liver, etc
25(OH)D
155. Epilogue –Respecting Evolution and Science
•Levels should be in 32-50ng/ml range (80-120nmol/L)
2014 Ivor Cummins BE(Chem) CEng MIEI
•“Short Shadow” Sun Exposure Without Burning is key
•Supplements: D3: new upper guideline is 4000 IU/day*
•Oily Fish, Organ Meats, Fortified Dairy etc. will help…
•Calciumis critical and works in tandem with 25(OH)D
•Too low is more likely than too high these days…
•Plenty Cheese/Yogurt/Milk, Sardines, Dark Leafy Greens.
•VitaminK2 is key, possibly the most important besides D.
•Supplements –medical guidance.
•Activates Matrix GLA Protein, for Calcium Management
•Highly interactive with Vitamin D & Ca–need keep K2 high
•VitaminA also important -highly interactive with Vitamin D
•D/A Ratio is source of problem when low –balance needed.
•Sweet potato, carrots, Dark Leafy Greens, Dairy/Butter/Yolk
•Butter/Cheeses, Natto, Chicken Legs, Egg Yolks, Liver, etc
25(OH)D
156.
157. A Thank-You to some Experts:
Prof. Michael HolickEndocrinologist and Professor of Medicine, Physiology and Biophysics. Currently director at Boston University Medical Center. Internationally recognized expert on all aspects of vitamin D.
Dr. Edward GorhamAssociate Professor in the Department of Family and Preventive Medicine at the University of California
Prof. Robert P Heaney Clinical Endocrinologist, Professor of Medicine and John A. Creighton University Professor Emeritus, Creighton University School of Medicine. Internationally recognized expert on vitamin D.
Dr. Cedric F Garland AdjtProf. Family and Preventative Medicine, Division of Epidemiology, University of San Diego. Internationally recognized expert on the disease implications of vitamin D.
Dr. Chris Masterjohn
PhD in Nutritional Science and Assistant Professor of Health and Nutrition Sciences at Brooklyn College.
Dr. Stephanie Seneff
Senior Research Scientist at MIT.
BS (Biophysics), MS/EE and Ph.Din Electrical Engineering and Computer Science MIT.
Prof. Reinhold Vieth
Professor in the Department of Nutritional Sciences, and the Department of Laboratory Medicine and Pathobiology, University of Toronto.Internationally recognized expert on the clinical nutrition of vitamin D as well as its pharmacology and safety.
DrGrimes
ccccc.
162. 2014 Ivor Cummins BE(Chem) CEng MIEI
Coronary Vascular Disease
Vitamin D and Cardiovascular Disease
Carl J. Lavie, MD, John H. Lee, MD, Richard V. Milani, MD
(J Am CollCardiol2011;58:1547–56)
Coronary Vascular Disease strongly linked to admission level 25(OH)D
Synergy with Blood Pressure, also mitigated by Sun Exposure
Summary:
163. Colon Cancer has one of the strongest associations with 25(OH)D levels
Key Takeaways:
COLON CANCER –Survival Rate
2014 Ivor Cummins BE(Chem) CEng MIEI
164. Key Takeaways:
BREAST CANCER MORTALITY –A Null Result??
Calcium Plus Vitamin D Supplementation and the Risk of Breast Cancer
J NatlCancer Inst2007;100: 1581 –1591
“Homeopathic” Dose used
Only 400 IU / day to D Group
~50% of BOTH Groups taking D in Supplements throughout trial (D levels not disclosed)
2014 Ivor Cummins BE(Chem) CEng MIEI
165. Null Response: Dosage near-irrelevant, poorly executed and controlled.
Key Takeaways:
BREAST CANCER MORTALITY –A Null Result??
Calcium Plus Vitamin D Supplementation and the Risk of Breast Cancer
J NatlCancer Inst2007;100: 1581 –1591
“Homeopathic” Dose used
Only 400 IU / day to D Group
~50% of BOTH Groups taking D in Supplements throughout trial (D levels not disclosed)
2014 Ivor Cummins BE(Chem) CEng MIEI
166. Null Response: Dosage near-irrelevant, poorly executed and controlled.
Key Takeaways:
BREAST CANCER MORTALITY –A Null Result??
Calcium Plus Vitamin D Supplementation and the Risk of Breast Cancer
J NatlCancer Inst2007;100: 1581 –1591
“Homeopathic” Dose used
Only 400 IU / day to D Group
~50% of BOTH Groups taking D in Supplements throughout trial (D levels not disclosed)
2014 Ivor Cummins BE(Chem) CEng MIEI
Supplemental Data and Subgroup Analysis tells a story…let’s dig, shall we?
167. 2014 Ivor Cummins BE(Chem) CengMIEI
BREAST CANCER MORTALITY –A Deeper Dive
How did the Intervention Affect Subgroups?
Borderline
Significant
Estimated D Intake
Non-Supplement Users Subgroup with poor VitD intake showed signal
168. 2014 Ivor Cummins BE(Chem) CengMIEI
BREAST CANCER MORTALITY –A Deeper Dive
How did the Intervention Affect Subgroups?
Statistically
Significant
Estimated D Intake
Borderline
Significant
Estimated D Intake
Non-Supplement Users Subgroup with poor VitD intake showed signal
Supplement Users Subgroup with poor VitD Intake showed signal
169. 2014 Ivor Cummins BE(Chem) CengMIEI
BREAST CANCER MORTALITY –A Deeper Dive
Non-Supplement Users Subgroup with poor VitD intake showed signal
Supplement Users Subgroup with poor CaIntake showed signal
Supplement Users Subgroup with poor VitD Intake showed signal
Statistically
Significant
Statistically
Significant
Estimated D Intake
Estimated CaIntake
Borderline
Significant
Estimated D Intake
How did the Intervention Affect Subgroups?
170. 2014 Ivor Cummins BE(Chem) CengMIEI
BREAST CANCER MORTALITY –A Deeper Dive
Conclusion: Engineering Signal There, but study is otherwise Near-Worthless
Statistically
Significant
Statistically
Significant
Estimated D Intake
Estimated CaIntake
Borderline
Significant
Estimated D Intake
Non-Supplement Users Subgroup with poor VitD intake showed signal
Supplement Users Subgroup with poor CaIntake showed signal
Supplement Users Subgroup with poor VitD Intake showed signal
How did the Intervention Affect Subgroups?
171. Sunlight UVB is the Primary Source of Human 25(OH)D
….and a lot more, as recent understanding grows.
2014 Ivor Cummins BE(Chem) CEng MIEI
173. Land Mass in Southern Hemisphere retains high UVB year-round.
Annual Adequacy of UVB for Synthesis?
2014 Ivor Cummins BE(Chem) CEng MIEI
174. What the Most Critical Hormone Regulates
ValdivielsoJ M et al. Am J PhysiolRenal Physiol2009;297:F1502-F1509
Low 25(OH) D Invites in:
Cancer (esp. Colon/Breast)
TB/Influenza/Infections General
Various Blood Disorders
T1 (and T2) Diabetes
Osteomalacia/Osteoporosis
Asthma / Autoimmune Diseases
Multiple Sclerosis
Heart Disease in General
Thyroid Issues / Chronic Fatigue
Inflammation
Obesity/Hypertension
Metabolic Syndrome
Pre & Post Natal Issues
2014 Ivor Cummins BE(Chem) CEng MIEI
175. Central Control System of the Human Machine
2014 Ivor Cummins BE(Chem) CEng MIEI ↑↑CATHELICIDIN
176. The Centrality of the Sun
2014 Ivor Cummins BE(Chem) CEng MIEI
….A Profound Evolutionary Paradigm
HEALTHY
Sun Exposure
But NO
BURNING!
177. The Centrality of the Sun
2014 Ivor Cummins BE(Chem) CEng MIEI
….A Profound Evolutionary Paradigm
HEALTHY
Sun Exposure
But NO
BURNING!
D
Synthesis
Plus
Cholesterol
178. The Centrality of the Sun
2014 Ivor Cummins BE(Chem) CEng MIEI
….A Profound Evolutionary Paradigm
HEALTHY
Sun Exposure
But NO
BURNING!
D
Synthesis
Plus
Cholesterol
Cholesterol
Sulfate
Plus
Cholesterol / Sulfur
179. The Centrality of the Sun
2014 Ivor Cummins BE(Chem) CEng MIEI
….A Profound Evolutionary Paradigm
HEALTHY
Sun Exposure
But NO
BURNING!
D
Synthesis
Plus
Cholesterol
Cholesterol
Sulfate
Plus
Cholesterol / Sulfur
Health
+Longevity
180. The Centrality of the Sun
2014 Ivor Cummins BE(Chem) CEng MIEI
….A Profound Evolutionary Paradigm
HEALTHY
Sun Exposure
But NO
BURNING!
D
Synthesis
Plus
Cholesterol
Cholesterol
Sulfate
Plus
Cholesterol / Sulfur
Health
+Longevity
B.S. degree in Biophysics in 1968
M.S. and E.E. degrees in Electrical Engineering in 1980
Ph.Ddegree in Electrical Engineering and Computer Science in 1985
(All from MIT)
MIT Senior Research Scientist who has spent 3 decades
at the intersection Of Biology and Computation
181. Supplementation started in December, which was rather late; still:
Key Takeaways:
INFLUENZA –Japanese Schoolchildren
Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren
Mitsuyoshi Urashima, TakaakiSegawa, Minoru Okazaki, ManaKurihara, YasuyukiWada, and Hiroyuki Ida
Am J Clin Nutr 2010;91:1255–60.
2014 Ivor Cummins BE(Chem) CEng MIEI
182. Supplementation started in December, which was rather late; still:
Key Takeaways:
INFLUENZA –Japanese Schoolchildren
Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren
Mitsuyoshi Urashima, TakaakiSegawa, Minoru Okazaki, ManaKurihara, YasuyukiWada, and Hiroyuki Ida
Am J Clin Nutr 2010;91:1255–60.
2014 Ivor Cummins BE(Chem) CEng MIEI
In a (rare) experiment, D3 supplements reduced Influenza A by >40%
183. Supplementation started in December, which was rather late; still:
Key Takeaways:
INFLUENZA –Japanese Schoolchildren
Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren
Mitsuyoshi Urashima, TakaakiSegawa, Minoru Okazaki, ManaKurihara, YasuyukiWada, and Hiroyuki Ida
Am J Clin Nutr 2010;91:1255–60.
2014 Ivor Cummins BE(Chem) CEng MIEI
In a (rare) experiment, D3 supplements reduced Influenza A by >40%
Marked in Children not receiving existing supplements –reduction of ~ 65%
184. Supplementation started in December, which was rather late; still:
Key Takeaways:
INFLUENZA –Japanese Schoolchildren
Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren
Mitsuyoshi Urashima, TakaakiSegawa, Minoru Okazaki, ManaKurihara, YasuyukiWada, and Hiroyuki Ida
Am J Clin Nutr 2010;91:1255–60.
2014 Ivor Cummins BE(Chem) CEng MIEI
In a (rare) experiment, D3 supplements reduced Influenza A by >40%
Marked in Children not receiving existing supplements –reduction of ~ 65%
Asthma attacks significantly reduced also (no trial has ever assessed this)
185. 2014 Ivor Cummins BE(Chem) CengMIEI
BREAST CANCER MORTALITY –A Deeper Dive
Summary:
Conclusion: Engineering Signal There, but study is otherwise Near-Worthless
Non-Supplement Users Subgroup with poor VitD intake showed signal
Supplement Users Subgroup with poor CaIntake showed signal
Supplement Users Subgroup with poor VitD Intake showed signal
188. Hypothesis Summary from 2009 FDA Paper
US Food and Drug Administration, Center for Devices and Radiological Health
“Increased UVA exposures and decreased ..Vitamin D3 levels may be responsible for increasing incidence of melanoma”
•Outdoor workers generally have 2x the 25(OH)D of indoor workers
2014 Ivor Cummins BE(Chem) CEng MIEI
•Higher incidence of CMM in Indoor versus outdoor workers
•Melanoma patients have significantly lower blood 25(OH)D levels
•UVB-absorbing sunscreens promote the growth of melanoma in mice
•UVB-absorbing sunscreen users have significantly higher melanoma rates
•All-year tan is protective, and associated with 3-9 times the UV Dose
•No “critical period” for burns to increase CMM risk (e.g. in childhood)
•Childhood outdoor activity (excl. burns) decrease melanoma incidence
•Melanoma patients who receive regular sun live longer than those who don’t
•UVA promotes mice tumors after initiation, and causes twice as many
•Calcitrioldecreases Stage II Carcinogenesis in Vivo, not Stage I
189. Making D and burning / Cancer Q
J Am Acad
Dermatol. 2006 Feb;54(2):301-17
Red is erythema (Sunburn)
Green is Math Simulation for Squamous Skin Cancer Promotion
Primary Source is Sun UVB
Blue is 25(OH)D Production
(Sunscreen Prevents Synthesis)
Figure 4.4 –Caption of original article: Cutaneous vitamin D synthesis cannot be dissociated from harmful effects ofUVradiation. Dashed and dotted line (blue) shows spectrum of previtaminD3 formation obtained from plotting reciprocal of photoenergy(1/w cm_2). Dashed line ( green) represents both action spectrum of induction ofsquamouscell carcinoma in human beings mathematically derived from experimental data obtained from murineskin, and wavelength dependence of induction of DNA damage, in this case cyclobutanepyrimidine dimers, inhuman skin (adapted121). Solid line (red) shows erythema action spectrum from human skin (m2/J) (adapted 26).
Note that peaks of these 3 curves all occur within UVB spectrum (290-320 nm) (dashed gray lines). (FromWolpowicz& Gilchrest, The vitamin D questions: how much do you need and how should you get it? J Am AcadDermatol. 2006 Feb;54(2):301-17. With permission).
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
190. Future “Biochemistry for Life” Topics:
•25 HydroxyVitamin D
The history, latest science, and significant mortality implications of this critical agent
•Omega 6 Vegetable Oils
The interesting story of how a machine lubricant became a health food –but should have stayed in the machine….
•Insulin –a Billion Years in Service
The evolutionary importance and critical functionality of Insulin, increasingly dysfunctional and pathogenic in our modern environment
•Keto-Adaptation
Living in an advantaged metabolic state –it’s much more than simply having an edge
2013 Ivor Cummins BE(Chem) MIEI
191. cccc
Key Takeaways:
COLON CANCER –New Discovery in 2000’s ?
2014 Ivor Cummins BE(Chem) C(Eng) MIEI