“D” is for DebacleThe Crucial Story of 25(OH)D
www.thefatemperor.com2014 Ivor Cummins BE(Chem) CEng MIEI
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 Adjt Prof. Family and Preventative Medicine, Division of Epidemiology, University of San Diego. Internationally recognized expert on the disease implications of vitamin D.
Dr. Chris MasterjohnPhD in Nutritional Science and Assistant Professor of Health and Nutrition Sciences at Brooklyn College.
Dr. Bruce Hollis PhDProfessor 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 ViethProfessor 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 Grimesconsultant Gastroenterologist at Blackburn Hospital in the UK. Expert in Vitamin D for the developing foetus and the implications for infections, diabetes, heart disease, liver disease and Crohn's disease.
Prelude
1. The Centrality of the Sun2. 25(OH)D – The Creation3. 25(OH)D – The Power4. 25(OH)D – The Human Cost5. Anatomy of a Debacle6. The Solution
Epilogue
Q&A
The “D”ebacle Content:
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
Prelude1. The Centrality of the Sun2. 25(OH)D – The Creation3. 25(OH)D – The Power4. 25(OH)D – The Human Cost5. Anatomy of a Debacle6. The Solution
Epilogue
Q&A
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
The Literature is Exploding
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
• 25(OH)D is 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
• 25(OH)D is 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 D is 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
Prelude – The Implications of Low…
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
Prelude – The Implications of Low…
USA25(OH)D
Distribution(NHANES III Seasonal Sampling)
~70% of US Population Insufficient ( 15 Years Previously was ~50% )
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
Prelude – The Implications of Low…
USA25(OH)D
Distribution(NHANES III Seasonal Sampling)
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
~70% of US Population Insufficient ( 15 Years Previously was ~50% )
Prelude – The Implications of Low…
RequiresEngineering
USA25(OH)D
Distribution(NHANES III Seasonal Sampling)
RequiresEngineering
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
RICKETS
Prelude – The Implications of Low…
USA25(OH)D
Distribution(NHANES III Seasonal Sampling)
Prelude
1. The Centrality of the Sun2. 25(OH)D – The Creation3. 25(OH)D – The Power4. 25(OH)D – The Human Cost5. Anatomy of a Debacle6. The Solution
Epilogue
Q&A
2014 Ivor Cummins BE(Chem) CEng MIEI
Skin Pigmentation Hypotheses – to ~40kYrs ago
EvolutionaryDrivers
LOSS OF BODY HAIR (~1M Yrs ago)• Striding Bipedalism• Sweat Gland System• Whole Body Cooling• Critical Brain Cooling
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
~1 million years…
Skin Pigmentation Hypotheses – to ~40kYrs ago
EvolutionaryDrivers
• Skin generally non-pigmented
• Hairless areas 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 Yrs ago)• Striding Bipedalism• Sweat Gland System• Whole Body Cooling• Critical Brain Cooling
~1 million years…
Skin Pigmentation Hypotheses – to ~40kYrs ago
EvolutionaryDrivers
• Skin generally non-pigmented
• Hairless areas 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 damageAnd 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 Yrs ago)• Striding Bipedalism• Sweat Gland System• Whole Body Cooling• Critical Brain Cooling
~1 million years…
Skin Pigmentation Hypotheses – to ~40kYrs ago
EvolutionaryDrivers
• Skin generally non-pigmented
• Hairless areas 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 damageAnd 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 Yrs ago)• Striding Bipedalism• Sweat Gland System• Whole Body Cooling• Critical Brain Cooling
~1 million years…
Skin Pigmentation Hypotheses – to ~40kYrs ago
EvolutionaryDrivers
• Skin generally non-pigmented
• Hairless areas 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 damageAnd 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 Yrs ago)• Striding Bipedalism• Sweat Gland System• Whole Body Cooling• Critical Brain Cooling
~1 million years…
Skin Pigmentation Hypotheses – to ~40kYrs ago
EvolutionaryDrivers
• Skin generally non-pigmented
• Hairless areas 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 damageAnd 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 Yrs ago)• Striding Bipedalism• Sweat Gland System• Whole Body Cooling• Critical Brain Cooling
~1 million years…
Skin Pigmentation Hypotheses – to ~40kYrs ago
EvolutionaryDrivers
• Skin generally non-pigmented
• Hairless areas 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 damageAnd 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 Yrs ago)• Striding Bipedalism• Sweat Gland System• Whole Body Cooling• Critical Brain Cooling
~1 million years…
Skin Pigmentation Hypotheses –~30-40k Yrs to present
EvolutionaryDrivers
2014 Ivor Cummins BE(Chem) CEng MIEI
Migration from Equator• Increasing weakness of UVB• Use of Clothing increases• Adaptive Pressure Deployed• Fishing Ability Offsets
<40k years…
EvolutionaryDrivers
• Skin Heavily Pigmented
• Protection Robust Overall
• Vitamin D synthesis adequate
• Trade-off Optimised
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 Yrs to present
<40k years…
EvolutionaryDrivers
• Skin Heavily Pigmented
• Protection Robust Overall
• Vitamin D synthesis adequate
• Trade-off Optimised
Trade-offs change with Latitude:• Studies strongly link available UV 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 Yrs to present
<40k years…
EvolutionaryDrivers
• Skin Heavily Pigmented
• Protection Robust Overall
• Vitamin D synthesis adequate
• Trade-off Optimised
Trade-offs change with Latitude:• Studies strongly link available UV 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 Yrs to present
<40k years…
EvolutionaryDrivers
• Skin Heavily Pigmented
• Protection Robust Overall
• Vitamin D synthesis adequate
• Trade-off Optimised
Trade-offs change with Latitude:• Studies strongly link available UV 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 Yrs to present
<40k years…
EvolutionaryDrivers
• Skin Heavily Pigmented
• Protection Robust Overall
• Vitamin D synthesis adequate
• Trade-off Optimised
Trade-offs change with Latitude:• Studies strongly link available UV 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 Yrs to present
<40k years…
EvolutionaryDrivers
• Skin Heavily Pigmented
• Protection Robust Overall
• Vitamin D synthesis adequate
• Trade-off Optimised
Trade-offs change with Latitude:• Studies strongly link available UV 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 Yrs to present
<40k years…
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
Luxwolda and Muskiet,Submitted Manuscript
60
MAASAI MEDIAN 25(OH)D = 42ng/ml
MAASAIBANTU
20
40
30
50
25
(OH
)D n
g/m
l
Wyoming Woman Athletes 25(OH)D
0
40
20
60
100
80
25
(OH
)D (
ng
/ml)
120
Why is Breast Milk now D Deficient?MIMIC EVOLUTIONARY SUN
Mother: 6400 IU/dayBaby: Only Breast Milk
MODERN REALITYMother: 400 IU/day Supplement
Baby: 300 IU/day Supplement
2014 Ivor Cummins BE(Chem) CEng MIEI
Why is Breast Milk now D Deficient?MIMIC EVOLUTIONARY SUN
Mother: 6400 IU/dayBaby: Only Breast Milk
MODERN REALITYMother: 400 IU/day Supplement
Baby: 300 IU/day Supplement
2014 Ivor Cummins BE(Chem) CEng MIEI
Why is Breast Milk now D Deficient?MIMIC EVOLUTIONARY SUN
Mother: 6400 IU/dayBaby: Only Breast Milk
MODERN REALITYMother: 400 IU/day Supplement
Baby: 300 IU/day Supplement
2014 Ivor Cummins BE(Chem) CEng MIEI
Why is Breast Milk now D Deficient?MIMIC EVOLUTIONARY SUN
Mother: 6400 IU/dayBaby: Only Breast Milk
MODERN REALITYMother: 400 IU/day Supplement
Baby: 300 IU/day Supplement
2014 Ivor Cummins BE(Chem) CEng MIEI
Why is Breast Milk now D Deficient?MIMIC EVOLUTIONARY SUN
Mother: 6400 IU/dayBaby: Only Breast Milk
MODERN REALITYMother: 400 IU/day Supplement
Baby: 300 IU/day Supplement
Why is Breast Milk now D Deficient?“MIMIC EVOLUTIONARY SUN”
Mother: 6400 IU/dayBaby: Only Breast Milk
MODERN REALITYMother: 400 IU/day Supplement
Baby: 300 IU/day Supplement
2014 Ivor Cummins BE(Chem) CEng MIEI
Why is Breast Milk now D Deficient?MIMIC EVOLUTIONARY SUN
Mother: 6400 IU/dayBaby: Only Breast Milk
MODERN REALITYMother: 400 IU/day Supplement
Baby: 300 IU/day Supplement
2014 Ivor Cummins BE(Chem) CEng MIEI
Why is Breast Milk now D Deficient?MIMIC EVOLUTIONARY SUN
Mother: 6400 IU/dayBaby: Only Breast Milk
MODERN REALITYMother: 400 IU/day Supplement
Baby: 300 IU/day Supplement
2014 Ivor Cummins BE(Chem) CEng MIEI
Why is Breast Milk now D Deficient?MIMIC EVOLUTIONARY SUN
Mother: 6400 IU/dayBaby: Only Breast Milk
MODERN REALITYMother: 400 IU/day Supplement
Baby: 300 IU/day Supplement
2014 Ivor Cummins BE(Chem) CEng MIEI
V5=~620
V5=~70
Why is Breast Milk now D Deficient?MIMIC EVOLUTIONARY SUN
Mother: 6400 IU/dayBaby: Only Breast Milk
MODERN REALITYMother: 400 IU/day Supplement
Baby: 300 IU/day Supplement
Thus with Mediocre Nutrition in Northern Latitudes, we needed to rapidly devolvePigmentation to enhance D3 synthesis for Infant Needs
2014 Ivor Cummins BE(Chem) CEng MIEI
V5=~620
V5=~70
Evolution…….Matters.
2014 Ivor Cummins BE(Chem) CEng MIEI
Bone Mineral Density (g/cm2)
Fracture (RR)
Colon Cancer (RR)
8’ Walk Time (s)
Attachment Loss (mm)
Median 25(OH)D Concentration (ng/ml)
1612 20 24 3228 36 40 44
Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes1–3. Am J Clin Nutr 2006;84:18 –28. Printed in USA. © 2006 American Society for Nutrition.
Adapted from :
And: Nutrients, Endpoints, and the Problem of Proof – Prof. Robert P. Heaney - 2008
Another Evolutionary View…
2014 Ivor Cummins BE(Chem) CEng MIEI
Bone Mineral Density (g/cm2)
Fracture (RR)
Colon Cancer (RR)
8’ Walk Time (s)
Attachment Loss (mm)
Median 25(OH)D Concentration (ng/ml)
1612 20 24 3228 36 40 44
Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes1–3. Am J Clin Nutr 2006;84:18 –28. Printed in USA. © 2006 American Society for Nutrition.
Adapted from :
And: Nutrients, Endpoints, and the Problem of Proof – Prof. Robert P. Heaney - 2008
Another Evolutionary View…
2014 Ivor Cummins BE(Chem) CEng MIEI
Bone Mineral Density (g/cm2)
Fracture (RR)
Colon Cancer (RR)
8’ Walk Time (s)
Attachment Loss (mm)
Median 25(OH)D Concentration (ng/ml)
1612 20 24 3228 36 40 44
Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes1–3. Am J Clin Nutr 2006;84:18 –28. Printed in USA. © 2006 American Society for Nutrition.
Adapted from :
And: Nutrients, Endpoints, and the Problem of Proof – Prof. Robert P. Heaney - 2008
Prelude
1. The Centrality of the Sun
2. 25(OH)D – The Creation3. 25(OH)D – The Power4. 25(OH)D – The Human Cost5. Anatomy of a Debacle6. The Solution
Epilogue
Q&A
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
2014 Ivor Cummins BE(Chem) CEng MIEI
How This Most Critical Hormone is Made
7 DeHydroxyCholesterol Primary Source is Sun UVB
(Sunscreen Prevents Synthesis)
2014 Ivor Cummins BE(Chem) CEng MIEI
How This Most Critical Hormone is Made
7 DeHydroxyCholesterolCholecalciferol(“Vitamin” D3)
Primary Source is Sun UVB
Catalyzes “Cholesterol” to D3
(Sunscreen Prevents Synthesis)
2014 Ivor Cummins BE(Chem) CEng MIEI
How This Most Critical Hormone is Made
7 DeHydroxyCholesterol
D3/D2Supplements
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
How This Most Critical Hormone is Made
7 DeHydroxyCholesterol
D3/D2Supplements
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)
21st Century Science:In-Cell Local 1,25 D
Production on Demand
2014 Ivor Cummins BE(Chem) CEng MIEI
25(OH)D !
How This Most Critical Hormone is Made
7 DeHydroxyCholesterol
D3/D2Supplements
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)
21st Century Science:In-Cell Local 1,25 D
Production on Demand
2014 Ivor Cummins BE(Chem) CEng MIEI
How This Most Critical Hormone is Made
7 DeHydroxyCholesterol
D3/D2Supplements
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 Dihydroxy Vitamin D
Primary Source is Sun UVB
Catalyzes “Cholesterol” to D3
(Sunscreen Prevents Synthesis)
21st Century Science:In-Cell Local 1,25 D
Production on Demand
2014 Ivor Cummins BE(Chem) CEng MIEI
How This Most Critical Hormone is Made
7 DeHydroxyCholesterol
D3/D2Supplements
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 Dihydroxy Vitamin D
Primary Source is Sun UVB
Catalyzes “Cholesterol” to D3
(Sunscreen Prevents Synthesis)
21st Century Science:In-Cell Local 1,25 D
Production on Demand
2014 Ivor Cummins BE(Chem) CEng MIEI
How This Most Critical Hormone is Made
7 DeHydroxyCholesterol
D3/D2Supplements
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 Dihydroxy Vitamin D
Primary Source is Sun UVB
Catalyzes “Cholesterol” to D3
(Sunscreen Prevents Synthesis)
21st Century Science:In-Cell Local 1,25 D
Production on Demand
20th CenturyScience: Mainly Ca Regulation
2014 Ivor Cummins BE(Chem) CEng MIEI
How This Most Critical Hormone is Made
7 DeHydroxyCholesterol
D3/D2Supplements
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 Dihydroxy Vitamin D
1,25 does far more than Ca++ regulation !!!
Primary Source is Sun UVB
Catalyzes “Cholesterol” to D3
(Sunscreen Prevents Synthesis)
21st Century Science:In-Cell Local 1,25 D
Production on Demand
20th CenturyScience: Mainly Ca Regulation
2014 Ivor Cummins BE(Chem) CEng MIEI
What the Most Critical Hormone Regulates
Valdivielso J M et al. Am J Physiol Renal Physiol 2009;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
What the Most Critical Hormone Regulates
Valdivielso J M et al. Am J Physiol Renal Physiol 2009;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
Prelude
1. The Centrality of the Sun2. 25(OH)D – The Creation
3. 25(OH)D – Control System Criticality 4. 25(OH)D – The Consequences5. Anatomy of a Debacle6. The Solution
Epilogue
Q&A
2014 Ivor Cummins BE(Chem) CEng MIEI
Central Control System of the Human MachineUNIQUE
DNACODE
2014 Ivor Cummins BE(Chem) CEng MIEI
Central Control System of the Human Machine
35TRILLION
CELLS
!
UNIQUEDNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
Central Control System of the Human Machine
35TRILLION
CELLS
!
UNIQUEDNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
Central Control System of the Human Machine
35TRILLION
CELLS
!
BLOODSERUM
25(OH)D25(OH)D
UNIQUEDNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
Central Control System of the Human Machine
35TRILLION
CELLS
!
BLOODSERUM
25(OH)D25(OH)D
1,25 D
UNIQUEDNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ONDEMAND
Central Control System of the Human Machine
35TRILLION
CELLS
!
VDRRXR
BLOODSERUM
25(OH)D25(OH)D
1,25 D
UNIQUEDNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ONDEMAND
Central Control System of the Human Machine
35TRILLION
CELLS
!
VDRRXR
BLOODSERUM
25(OH)D25(OH)D
1,25 D + SAFETYSWITCH
UNIQUEDNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ONDEMAND
Central Control System of the Human Machine
35TRILLION
CELLS
!
VDRRXR
BLOODSERUM
25(OH)D
1,25 D
VDRRXR
VDRE
25(OH)D
1,25 D + SAFETYSWITCH
UNIQUEDNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ONDEMAND
Central Control System of the Human Machine
35TRILLION
CELLS
!
VDRRXR
BLOODSERUM
25(OH)D
1,25 D
VDRRXR
VDRE
25(OH)D
1,25 D + SAFETYSWITCH
UNIQUEDNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ONDEMAND
Central Control System of the Human Machine
35TRILLION
CELLS
!
VDRRXR
BLOODSERUM
25(OH)D
Transcription!!
1,25 D
VDRRXR
VDRE
25(OH)D
1,25 D + SAFETYSWITCH
UNIQUEDNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ONDEMAND
Central Control System of the Human Machine
35TRILLION
CELLS
!
VDRRXR
BLOODSERUM
25(OH)D
Transcription!!
1,25 D
VDRRXR
VDRE
25(OH)D
1,25 D + SAFETYSWITCH
SAFETYSWITCH
UNIQUEDNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ONDEMAND
Central Control System of the Human Machine
35TRILLION
CELLS
!
VDRRXR
BLOODSERUM
25(OH)D
Transcription!!
1,25 D
VDRRXR
VDRE
25(OH)D
1,25 D + SAFETYSWITCH
SAFETYSWITCH
UNIQUEDNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ONDEMAND
Central Control System of the Human Machine
35TRILLION
CELLS
!
VDRRXR
BLOODSERUM
25(OH)D
Transcription!!
1,25 D
VDRRXR
VDRE
25(OH)D
1,25 D + SAFETYSWITCH
SAFETYSWITCH
UNIQUEDNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ONDEMAND
CRITICAL PROTEINSe.g. CATHELICIDIN
Central Control System of the Human Machine
35TRILLION
CELLS
!
VDRRXR
BLOODSERUM
25(OH)D
Transcription!!
1,25 D
VDRRXR
VDRE
25(OH)D
1,25 D + SAFETYSWITCH
SAFETYSWITCH
UNIQUEDNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ONDEMAND
CRITICAL PROTEINSe.g. CATHELICIDIN
Replication!!
Central Control System of the Human Machine
35TRILLION
CELLS
!
VDRRXR
BLOODSERUM
25(OH)D
Transcription!!
1,25 D
VDRRXR
VDRE
Blood Pressure
Cancer
Heart Disease
MS, TB, Flu
Asthma
T1 Diabetes
T2 Diabetes
Obesity
Met Syndrome
Alzheimers
25(OH)D
1,25 D + SAFETYSWITCH
SAFETYSWITCH
UNIQUEDNA
CODE
2014 Ivor Cummins BE(Chem) CEng MIEI
ONDEMAND
CRITICAL PROTEINSe.g. CATHELICIDIN
Replication!!
Central Control System of the Human Machine
2014 Ivor Cummins BE(Chem) CEng MIEI
Central Control System of the Human Machine
2014 Ivor Cummins BE(Chem) CEng MIEI
SAFETYSWITCH↑↑CATHELICIDIN
Central Control System of the Human Machine
2014 Ivor Cummins BE(Chem) CEng MIEI
Prelude
1. The Centrality of the Sun2. 25(OH)D – The Creation3. 25(OH)D – The Power
4. 25(OH)D – The Consequences5. Anatomy of a Debacle6. The Solution
Epilogue
Q&A
2014 Ivor Cummins BE(Chem) CEng MIEI
Survival Outcome for low 25(OH)D reminiscent of Smokers Vs Non-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, andJoseph B. Muhlestein, MDa,b, for the Intermountain Heart Collaborative (IHC) Study Group
(Am J Cardiol 2010;106:963–968)
Population 25(OH)D Levels
Adequate>30ng/ml
36.4% V. Low <16
16.7%
Low16-30 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
Vitamin D and Cardiovascular Disease Carl J. Lavie, MD, John H. Lee, MD, Richard V. Milani, MD (J Am Coll Cardiol 2011;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
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 ColonCancer Risk associated with 38ng/ml 25(OH)D
Od
ds
Rat
io o
f C
olo
rect
al C
ance
r P trend <0.0001
COLON CANCER INCIDENCE
10 20 4030
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 ColonCancer Risk associated with 38ng/ml 25(OH)DO
dd
s R
atio
of
Co
lore
ctal
Can
cer
P trend <0.0001
COLON CANCER INCIDENCECOLON CANCER MORTALITY
RR = 0.28
RR = 0.44
Rel
ativ
e ri
sk
10 20 4030
P trend =0.02
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,Edward L. 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 riskwith 48 ng/ml
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,Edward L. 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 riskwith 48 ng/ml
P trend <0.002
R2 = 0.94
50% lower riskwith 52 ng/ml
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 = 0.28P <0.05
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 Adv Neurol Disord(2013) 6(2) 81–116DOI: 10.1177/1756285612473513
Ireland53O N
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 Adv Neurol Disord(2013) 6(2) 81–116DOI: 10.1177/1756285612473513
NOMS
MS
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) vs 273 Matched Controls
Summary:
2014 Ivor Cummins BE(Chem) CEng MIEI
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) vs 273 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
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) vs 273 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
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) vs 273 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
Prelude
1. The Centrality of the Sun2. 25(OH)D – The Creation3. 25(OH)D – The Power
4. 25(OH)D – The Consequences5. Anatomy of a Debacle6. The Solution
Epilogue
Q&A
2014 Ivor Cummins BE(Chem) CEng MIEI
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) Ceng MIEI
Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial
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) Ceng MIEI
Clear impact on Cancer and Overall mortality, especially with 1st Year removed
TYPE 1 DIABETES
2014 Ivor Cummins BE(Chem) CEng MIEI
The most common serious chronic disease in children, esp. in Northern Latitude
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 1st year of life, follow-up to 1997
Summary:
2014 Ivor Cummins BE(Chem) CEng MIEI
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 1st year 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
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 1st year 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
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 1st year 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
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 1st year 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
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 1st year 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
2014 Ivor Cummins BE(Chem) CEng MIEI
FINLAND GUIDELINE VIT D vs Type1 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
Vit
D
2014 Ivor Cummins BE(Chem) CEng MIEI
FINLAND GUIDELINE VIT D vs Type1 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/D
ay V
itD
2014 Ivor Cummins BE(Chem) CEng MIEI
FINLAND GUIDELINE VIT D vs Type1 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-fortifiedDairy
TYPE 1 DIABETES - Supplementation History?IU
/Day
Vit
D
10
20
30
40
50
60
70
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
Engineering Style Summary:
2014 Ivor Cummins BE(Chem) CEng MIEI
FINLAND GUIDELINE VIT D vs Type1 Diabetes Incidence in <15 Year Olds
D-fortifiedDairy
TYPE 1 DIABETES - Supplementation History?IU
/Day
Vit
D
10
20
30
40
50
60
70
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
Engineering Style Summary:
2014 Ivor Cummins BE(Chem) CEng MIEI
Add in the earlier historical data from another source that had it…
FINLAND GUIDELINE VIT D vs Type1 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-fortifiedDairy
TYPE 1 DIABETES - Supplementation History?IU
/Day
Vit
D
10
20
30
40
50
60
70
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
Engineering Style 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 vs Type1 Diabetes Incidence in <15 Year Olds
Add in the earlier historical data from another source that had it…
D-fortifiedDairy
TYPE 1 DIABETES - Supplementation History?IU
/Day
Vit
D
10
20
30
40
50
60
70
Strong Hypothesis that Flu Outbreaks are mediated by 25(OH)D levels
Summary:
INFLUENZA – Seasonal Triggering
Hypponen E, Power C:
Hypovitaminosis D 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
Strong Hypothesis that Flu Outbreaks are mediated by 25(OH)D levels
Summary:
INFLUENZA – Seasonal Triggering
Hypponen E, Power C:
Hypovitaminosis D 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
INFLUENZA – Seasonal Triggering
2014 Ivor Cummins BE(Chem) CEng MIEI
16
20
24
28
32
25
(OH
)D n
g/m
l
0
5
10
15
20
% R
esp
irat
ory
Infe
ctio
n
MonthSeason
0
5
10
15
20
% R
esp
irat
ory
Infe
ctio
n
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 Nutr 106, 1433–1440
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
Aloia JF, Li-Ng M: Epidemic influenza and vitamin D. Epidemiol Infect 2007; 135: 1095–1096
Cannell et al. Virology Journal 2008 5:29 doi:10.1186/1743-422X-5-29.
2014 Ivor Cummins BE(Chem) CEng MIEI
Increased to 2000 IU/day in 3rd Year
208 randomised individuals to placebo or 800 IU/day of D3 over 2 years
Key Takeaways:
Re: epidemic Influenza and vitamin D
Aloia JF, Li-Ng M: Epidemic influenza and vitamin D. Epidemiol Infect 2007; 135: 1095–1096
Cannell et al. Virology Journal 2008 5:29 doi:10.1186/1743-422X-5-29.
2014 Ivor Cummins BE(Chem) CEng MIEI
Increased to 2000 IU/day in 3rd Year
INFLUENZA – Hospital Experiment
208 randomised individuals to placebo or 800 IU/day of D3 over 2 years
Key Takeaways:
Re: epidemic Influenza and vitamin D
Aloia JF, Li-Ng M: Epidemic influenza and vitamin D. Epidemiol Infect 2007; 135: 1095–1096
Cannell et al. Virology Journal 2008 5:29 doi:10.1186/1743-422X-5-29.
2014 Ivor Cummins BE(Chem) CEng MIEI
Increased to 2000 IU/day in 3rd Year
25(OH)D acts via multiple mechanisms as discussed
INFLUENZA – Hospital Experiment
208 randomised individuals to placebo or 800 IU/day of D3 over 2 years
Key Takeaways:
Re: epidemic Influenza and vitamin D
Aloia JF, Li-Ng M: Epidemic influenza and vitamin D. Epidemiol Infect 2007; 135: 1095–1096
Cannell et al. Virology Journal 2008 5:29 doi:10.1186/1743-422X-5-29.
2014 Ivor Cummins BE(Chem) CEng MIEI
Increased to 2000 IU/day in 3rd Year
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
2014 Ivor Cummins BE(Chem) CEng MIEI
The Bottom Line: “Mechanisms From pre-Cradle to Grave”
Prelude
1. The Centrality of the Sun2. 25(OH)D – The Creation3. 25(OH)D – The Power4. 25(OH)D – The Consequences
5. Anatomy of a Debacle6. The Solution
Epilogue
Q&A
2014 Ivor Cummins BE(Chem) CEng MIEI
Witness An Unfolding Catastrophe….
NHANES III (1988-1994)
SER
UM
25
(OH
)D:
% >
30
ng/
ml
10
20
30
40
50
NHANES (2001-2004)
The Literature is Exploding
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
Pin
eal
Ho
rmo
ne
Vit
amin
D
SKIN
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
Pin
eal
Ho
rmo
ne
Vit
amin
D
SKIN
2014 Ivor Cummins BE(Chem) CEng MIEI
USA25(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
Pin
eal
Ho
rmo
ne
Vit
amin
D
SKIN
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….. P
ine
al H
orm
on
e
Vit
amin
D
SKIN
The Skin Cancer / Melanoma Hysteria
J Am Acad Dermatol. 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)
The Skin Cancer / Melanoma Hysteria
J Am Acad Dermatol. 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)
The Skin Cancer / Melanoma Hysteria
J Am Acad Dermatol. 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)
The Skin Cancer / Melanoma Hysteria
J Am Acad Dermatol. 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
The Skin Cancer / Melanoma Hysteria
J Am Acad Dermatol. 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
The Skin Cancer / Melanoma Hysteria
J Am Acad Dermatol. 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
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 Melanoma Victim Study:
2014 Ivor Cummins BE(Chem) CEng MIEI
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 Melanoma Victim Study:
2014 Ivor Cummins BE(Chem) CEng MIEI
Healthy Sun Exposure, LOWER Risk
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 Melanoma Victim Study:
2014 Ivor Cummins BE(Chem) CEng MIEI
Healthy Sun Exposure, LOWER Risk
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 Melanoma Victim Study:
2014 Ivor Cummins BE(Chem) CEng MIEI
Healthy Sun Exposure, LOWER Risk
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 Melanoma Victim 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
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 Melanoma Victim 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
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 Melanoma Victim Study:
Healthy Sun Exposure, LOWER Risk
This Effect Applied to BOTH Skin Types
2014 Ivor Cummins BE(Chem) CEng MIEI
The Real Risk Factors?
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 Melanoma Victim 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
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 Melanoma Victim 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
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 H
R
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 H
R
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 H
R
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 OverExp Highlighted
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 H
R
SUNSCREENS: A Counter-Intuitive Twist
2014 Ivor Cummins BE(Chem) CEng MIEI H
R
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
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 Halved in UPPER Quartile of Sun Exposure
2014 Ivor Cummins BE(Chem) CEng MIEI
~2x Mortality Rate Throughout
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 Halved in 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
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 Halved in 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
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 Halved in 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
2014 Ivor Cummins BE(Chem) MIEI
Prelude
1. The Centrality of the Sun2. 25(OH)D – The Creation3. 25(OH)D – The Power4. 25(OH)D – The Consequences5. Anatomy of a Debacle
6. The SolutionEpilogue
Q&A
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 FatDiet
Low Calcium Diet
Racial factors & Genetics
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 FatDiet
Low Calcium Diet
HIGH25(OH)D
>60? ng/ml
Excess SUN Exposure LG
Excess D3Supplements
Racial factors & Genetics AND
/OR
Low
Vit K2
ExcessiveCalcification?
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 RatioLack of SUN Exposure
Low FatDiet
Low Calcium Diet
OPTIMUM25(OH)D
32-50 ng/ml
Fat-Nutrient Dense Diet
Oily Fish, Cod Liver, Pate, etc
Correct D3Supplements
HIGH25(OH)D
>60? ng/ml
Excess SUN Exposure LG
Excess D3Supplements
Racial factors & Genetics
AND
Adequate
Calcium
AND/OR
Adequate
Vit AAdequate
Vit K2
ExcessiveCalcification?
Low
Vit K2
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 FatDiet
Low Calcium Diet
OPTIMUM25(OH)D
32-50 ng/ml
Fat-Nutrient Dense Diet
Oily Fish, Cod Liver, Pate, etc
Correct D3Supplements
HIGH25(OH)D
>60? ng/ml
Excess SUN Exposure LG
Excess D3Supplements
Racial factors & Genetics
AND
Adequate
Calcium
AND/OR
Adequate
Vit AAdequate
Vit K2
Immune Function
Bone Strength
Disease Protection
Cancer Resistance
Vigour & Longevity
Healthy Sun Exposure
UVB/UVA Ratio
ExcessiveCalcification?
Low
Vit K2
2014 Ivor Cummins BE(Chem) MIEI
Prelude
1. The Centrality of the Sun2. 25(OH)D – The Creation3. 25(OH)D – The Power4. 25(OH)D – The Consequences5. Anatomy of a Debacle6. The Solution
EpilogueQ&A
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
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…
• Calcium is 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
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…
• Calcium is 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.
• Vitamin K2 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
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…
• Calcium is 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.
• Vitamin K2 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
• Vitamin A 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
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 Adjt Prof. Family and Preventative Medicine, Division of Epidemiology, University of San Diego. Internationally recognized expert on the disease implications of vitamin D.
Dr. Chris MasterjohnPhD in Nutritional Science and Assistant Professor of Health and Nutrition Sciences at Brooklyn College.
Dr. Stephanie SeneffSenior Research Scientist at MIT.BS (Biophysics), MS/EE and Ph.D in Electrical Engineering and Computer Science MIT.
Prof. Reinhold ViethProfessor 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 Grimesccccc.
BACKUP / OTHER MATERIAL
Backup / Other
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 Coll Cardiol 2011;58:1547–56)
Coronary Vascular Disease strongly linked to admission level 25(OH)D
Synergy with Blood Pressure, also mitigated by Sun Exposure
Summary:
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
Key Takeaways:
BREAST CANCER MORTALITY – A Null Result??
Calcium Plus Vitamin D Supplementation and the Risk of Breast Cancer
J Natl Cancer Inst 2007;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
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 Natl Cancer Inst 2007;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
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 Natl Cancer Inst 2007;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?
2014 Ivor Cummins BE(Chem) Ceng MIEI
BREAST CANCER MORTALITY – A Deeper Dive
How did the Intervention Affect Subgroups?
BorderlineSignificant
Estimated D Intake
Non-Supplement Users Subgroup with poor Vit D intake showed signal
2014 Ivor Cummins BE(Chem) Ceng MIEI
BREAST CANCER MORTALITY – A Deeper Dive
How did the Intervention Affect Subgroups?
StatisticallySignificant
Estimated D Intake
BorderlineSignificant
Estimated D Intake
Non-Supplement Users Subgroup with poor Vit D intake showed signal
Supplement Users Subgroup with poor Vit D Intake showed signal
2014 Ivor Cummins BE(Chem) Ceng MIEI
BREAST CANCER MORTALITY – A Deeper Dive
Non-Supplement Users Subgroup with poor Vit D intake showed signal
Supplement Users Subgroup with poor Ca Intake showed signal
Supplement Users Subgroup with poor Vit D Intake showed signal
StatisticallySignificant
StatisticallySignificant
Estimated D Intake Estimated Ca Intake
BorderlineSignificant
Estimated D Intake
How did the Intervention Affect Subgroups?
2014 Ivor Cummins BE(Chem) Ceng MIEI
BREAST CANCER MORTALITY – A Deeper Dive
Conclusion: Engineering Signal There, but study is otherwise Near-Worthless
StatisticallySignificant
StatisticallySignificant
Estimated D Intake Estimated Ca Intake
BorderlineSignificant
Estimated D Intake
Non-Supplement Users Subgroup with poor Vit D intake showed signal
Supplement Users Subgroup with poor Ca Intake showed signal
Supplement Users Subgroup with poor Vit D Intake showed signal
How did the Intervention Affect Subgroups?
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
Another Evolutionary View…
2014 Ivor Cummins BE(Chem) CEng MIEI
0
16
32
48
60
32
ng/
ml
Land Mass in Southern Hemisphere retains high UVB year-round.
Annual Adequacy of UVB for Synthesis?
2014 Ivor Cummins BE(Chem) CEng MIEI
What the Most Critical Hormone Regulates
Valdivielso J M et al. Am J Physiol Renal Physiol 2009;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
Central Control System of the Human Machine
2014 Ivor Cummins BE(Chem) CEng MIEI
↑↑CATHELICIDIN
The Centrality of the Sun
2014 Ivor Cummins BE(Chem) CEng MIEI
….A Profound Evolutionary Paradigm
HEALTHYSun Exposure
But NOBURNING!
The Centrality of the Sun
2014 Ivor Cummins BE(Chem) CEng MIEI
….A Profound Evolutionary Paradigm
HEALTHYSun Exposure
But NOBURNING!
DSynthesis
PlusCholesterol
The Centrality of the Sun
2014 Ivor Cummins BE(Chem) CEng MIEI
….A Profound Evolutionary Paradigm
HEALTHYSun Exposure
But NOBURNING!
DSynthesis
PlusCholesterol
CholesterolSulfate
PlusCholesterol
/ Sulfur
The Centrality of the Sun
2014 Ivor Cummins BE(Chem) CEng MIEI
….A Profound Evolutionary Paradigm
HEALTHYSun Exposure
But NOBURNING!
DSynthesis
PlusCholesterol
CholesterolSulfate
PlusCholesterol
/ Sulfur
Health+Longevity
The Centrality of the Sun
2014 Ivor Cummins BE(Chem) CEng MIEI
….A Profound Evolutionary Paradigm
HEALTHYSun Exposure
But NOBURNING!
DSynthesis
PlusCholesterol
CholesterolSulfate
PlusCholesterol
/ Sulfur
Health+Longevity
B.S. degree in Biophysics in 1968
M.S. and E.E. degrees in Electrical Engineering in 1980Ph.D degree in Electrical Engineering and Computer Science in 1985 (All from MIT)
MIT Senior Research Scientist who has spent 3 decadesat the intersection Of Biology and Computation
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, Takaaki Segawa, Minoru Okazaki, Mana Kurihara, Yasuyuki Wada, and Hiroyuki Ida Am J Clin Nutr 2010;91:1255–60.
2014 Ivor Cummins BE(Chem) CEng MIEI
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, Takaaki Segawa, Minoru Okazaki, Mana Kurihara, Yasuyuki Wada, 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%
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, Takaaki Segawa, Minoru Okazaki, Mana Kurihara, Yasuyuki Wada, 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%
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, Takaaki Segawa, Minoru Okazaki, Mana Kurihara, Yasuyuki Wada, 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)
2014 Ivor Cummins BE(Chem) Ceng MIEI
BREAST CANCER MORTALITY – A Deeper Dive
Summary:
Conclusion: Engineering Signal There, but study is otherwise Near-Worthless
Non-Supplement Users Subgroup with poor Vit D intake showed signal
Supplement Users Subgroup with poor Ca Intake showed signal
Supplement Users Subgroup with poor Vit D Intake showed signal
2014 Ivor Cummins BE(Chem) MIEI
A Wider View
Hollis B W , and Wagner C L CMAJ 2006;174:1287-1290
©2006 by Canadian Medical Association
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
• Calcitriol decreases Stage II Carcinogenesis in Vivo, not Stage I
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 ofUV radiation. Dashed and dotted line (blue) shows
spectrum of previtamin D3 formation obtained from plotting reciprocal of photoenergy
(1/w cm_2). Dashed line ( green) represents both action spectrum of induction
ofsquamous cell carcinoma in human beings mathematically derived from experimental
data obtained from murineskin, and wavelength dependence of induction of DNA
damage, in this case cyclobutane pyrimidine 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
Future “Biochemistry for Life” Topics:
• 25 Hydroxy Vitamin 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
cccc
Key Takeaways:
COLON CANCER – New Discovery in 2000’s ?
2014 Ivor Cummins BE(Chem) C(Eng) MIEI
BACKUP
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