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“D” is for Debacle The Crucial Story of 25(OH)D www.thefatemperor.com 2014 Ivor Cummins BE(Chem) CEng MIEI.

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Presentation on theme: "“D” is for Debacle The Crucial Story of 25(OH)D www.thefatemperor.com 2014 Ivor Cummins BE(Chem) CEng MIEI."— Presentation transcript:

1 “D” is for Debacle The Crucial Story of 25(OH)D Ivor Cummins BE(Chem) CEng MIEI

2 A Thank-You to Some Experts: Prof. Michael Holick Endocrinologist 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 Gorham Associate 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 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 foetus and the implications for infections, diabetes, heart disease, liver disease and Crohn's disease.

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”ebacle Content: 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

5 The Literature is Exploding

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)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

8 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

9 Prelude – The Implications of Low… 2014 Ivor Cummins BE(Chem) C(Eng) MIEI

10 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 Yrs ago) 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 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…

17 Skin Pigmentation Hypotheses – to ~40kYrs ago Evolutionary Drivers 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 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 Yrs ago) 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 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 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 Yrs ago) 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 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 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 Yrs ago) 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 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 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 Yrs ago) 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 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 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 Yrs ago) Striding Bipedalism Sweat Gland System Whole Body Cooling Critical Brain Cooling ~1 million years…

22 Skin Pigmentation Hypotheses –~30-40k Yrs to present Evolutionary Drivers 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…

23 Evolutionary Drivers 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…

24 Evolutionary Drivers 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…

25 Evolutionary Drivers 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…

26 Evolutionary Drivers 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…

27 Evolutionary Drivers 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…

28 Evolutionary Drivers 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…

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

30 Luxwolda and Muskiet, Submitted Manuscript 60 MAASAI MEDIAN 25(OH)D = 42ng/ml MAASAIBANTU (OH)D ng/ml

31 Wyoming Woman Athletes 25(OH)D (OH)D (ng/ml) 120

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 Medocre 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

42 Evolution…….Matters Ivor Cummins BE(Chem) CEng MIEI Bone Mineral Density (g/cm 2 ) Fracture (RR) Colon Cancer (RR) 8’ Walk Time (s) Attachment Loss (mm) Median 25(OH)D Concentration (ng/ml) 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

43 Another Evolutionary View… 2014 Ivor Cummins BE(Chem) CEng MIEI Bone Mineral Density (g/cm 2 ) Fracture (RR) Colon Cancer (RR) 8’ Walk Time (s) Attachment Loss (mm) Median 25(OH)D Concentration (ng/ml) 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

44 Another Evolutionary View… 2014 Ivor Cummins BE(Chem) CEng MIEI Bone Mineral Density (g/cm 2 ) Fracture (RR) Colon Cancer (RR) 8’ Walk Time (s) Attachment Loss (mm) Median 25(OH)D Concentration (ng/ml) 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

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 D 3 (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 D 3 (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 D 3 (Sunscreen Prevents Synthesis) 21 st Century 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 D 3 (Sunscreen Prevents Synthesis) 21 st Century 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 Dihydroxy Vitamin D  Primary Source is Sun UVB  Catalyzes “Cholesterol” to D 3 (Sunscreen Prevents Synthesis) 21 st Century 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 Dihydroxy Vitamin D  Primary Source is Sun UVB  Catalyzes “Cholesterol” to D 3 (Sunscreen Prevents Synthesis) 21 st Century 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 Dihydroxy Vitamin D  Primary Source is Sun UVB  Catalyzes “Cholesterol” to D 3 (Sunscreen Prevents Synthesis) 21 st Century Science: In-Cell Local 1,25 D Production on Demand 20th Century Science: Mainly Ca Regulation 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 Dihydroxy Vitamin D  1,25 does far more than Ca++ regulation !!!  Primary Source is Sun UVB  Catalyzes “Cholesterol” to D 3 (Sunscreen Prevents Synthesis) 21 st Century Science: In-Cell Local 1,25 D Production on Demand 20th Century Science: Mainly Ca Regulation 2014 Ivor Cummins BE(Chem) CEng MIEI

55 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

56 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

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 mRNA 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)D Transcription!! 1,25 D VDR RXR VDRE mRNA 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)D Transcription!! 1,25 D VDR RXR VDRE mRNA 25(OH)D 1,25 D + SAFETYSWITCH SAFETYSWITCH 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)D Transcription!! 1,25 D VDR RXR VDRE mRNA 25(OH)D 1,25 D + SAFETYSWITCH SAFETYSWITCH 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)D Transcription!! 1,25 D VDR RXR VDRE mRNA 25(OH)D 1,25 D + SAFETYSWITCH SAFETYSWITCH 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)D Transcription!! 1,25 D VDR RXR VDRE mRNA 25(OH)D 1,25 D + SAFETYSWITCH SAFETYSWITCH UNIQUE DNA CODE 2014 Ivor Cummins BE(Chem) CEng MIEI ON DEMAND CRITICAL PROTEINS e.g. CATHELICIDIN Replication!!

72 Central Control System of the Human Machine 35 TRILLION CELLS ! VDR RXR BLOOD SERUM 25(OH)D Transcription!! 1,25 D VDR RXR VDRE mRNA 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 UNIQUE DNA CODE 2014 Ivor Cummins BE(Chem) CEng MIEI ON DEMAND CRITICAL PROTEINS e.g. CATHELICIDIN Replication!!

73 Central Control System of the Human Machine 2014 Ivor Cummins BE(Chem) CEng MIEI

74 Central Control System of the Human Machine 2014 Ivor Cummins BE(Chem) CEng MIEI SAFETYSWITCH ↑↑CATHELICIDIN

75 Central Control System of the Human Machine 2014 Ivor Cummins BE(Chem) CEng MIEI

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 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, MD a,b, *, Heidi T. May, PhD, MSPH a, Benjamin D. Horne, PhD, MPH a,c, Tami L. Bair, BS a, Nathaniel L. Hall, MD a,b, John F. Carlquist, PhD a,b, Donald L. Lappé, MD a, and Joseph B. Muhlestein, MD a,b, for the Intermountain Heart Collaborative (IHC) Study Group (Am J Cardiol 2010;106:963–968) Adequate >30ng/ml 36.4% V. Low < % Low ng/ml 46.4% 2014 Ivor Cummins BE(Chem) CEng MIEI  Majority Population Insufficient  Remember D is a proxy for Sun(!) > <16

78 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

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 < COLON CANCER INCIDENCE

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 < COLON CANCER INCIDENCE COLON CANCER MORTALITY RR = 0.28 RR = 0.44 Relative risk 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,Edward L. Giovannucci, Martin Lipkin, Harold Newmarke, Michael F. Holick, Frank C. Garland Journal of Steroid Biochemistry & Molecular Biology 103 (2007) 708– Ivor Cummins BE(Chem) C(Eng) MIEI P trend <0.001 R 2 = % 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,Edward L. Giovannucci, Martin Lipkin, Harold Newmarke, Michael F. Holick, Frank C. Garland Journal of Steroid Biochemistry & Molecular Biology 103 (2007) 708– Ivor Cummins BE(Chem) C(Eng) MIEI P trend <0.001 R 2 = % lower risk with 48 ng/ml P trend <0.002 R 2 = % 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 Adv Neurol Disord (2013) 6(2) 81–116 DOI: / Ireland 53 O 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 Adv Neurol Disord (2013) 6(2) 81–116 DOI: / NO MS

86 MULTIPLE SCLEROSIS Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study BMJ VOLUME AUGUST 2003 bmj.com  N=136 MS Cases (in their 30’s) vs 273 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 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 P<0.01 for trend

88 MULTIPLE SCLEROSIS Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study BMJ VOLUME 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  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 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  Consistent Dose-Response Benefit primarily for exposure age 6-10 and 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 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

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 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 1 st Year 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 1 st year 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 1 st 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

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 1 st 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

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 1 st 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

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 1 st 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

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 1 st 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

100 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

101 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? IU/Day Vit D

102 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-fortified Dairy TYPE 1 DIABETES - Supplementation History? IU/Day Vit D

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 Engineering Style Summary: 2014 Ivor Cummins BE(Chem) CEng MIEI FINLAND GUIDELINE VIT D vs Type1 Diabetes Incidence in <15 Year Olds D-fortified Dairy TYPE 1 DIABETES - Supplementation History? IU/Day Vit D

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 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 The Rise of Childhood Type 1 Diabetes in the 20th Century D-fortified Dairy TYPE 1 DIABETES - Supplementation History? IU/Day Vit D

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 Engineering Style Summary: 2014 Ivor Cummins BE(Chem) CEng MIEI  Conclusion: - go figure. Diabetes December 2002 vol. 51 no 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-fortified Dairy TYPE 1 DIABETES - Supplementation History? IU/Day Vit D

106  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– 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: 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

108 INFLUENZA – Seasonal Triggering 2014 Ivor Cummins BE(Chem) CEng MIEI (OH)D ng/ml % Respiratory Infection Month Season % 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 Nutr 106, 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 Aloia JF, Li-Ng M: Epidemic influenza and vitamin D. Epidemiol Infect 2007; 135: 1095–1096 Cannell et al. Virology Journal :29 doi: / X Ivor Cummins BE(Chem) CEng MIEI  Increased to 2000 IU/day in 3 rd Year

110  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 :29 doi: / X Ivor Cummins BE(Chem) CEng MIEI  Increased to 2000 IU/day in 3 rd Year 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 Aloia JF, Li-Ng M: Epidemic influenza and vitamin D. Epidemiol Infect 2007; 135: 1095–1096 Cannell et al. Virology Journal :29 doi: / X Ivor Cummins BE(Chem) CEng MIEI  Increased to 2000 IU/day in 3 rd Year  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 Aloia JF, Li-Ng M: Epidemic influenza and vitamin D. Epidemiol Infect 2007; 135: 1095–1096 Cannell et al. Virology Journal :29 doi: / X Ivor Cummins BE(Chem) CEng MIEI  Increased to 2000 IU/day in 3 rd 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

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 ( ) SERUM 25(OH)D: % >30ng/ml NHANES ( )

116 The Literature is Exploding

117 2014 Ivor Cummins BE(Chem) CEng MIEI European Journal of Clinical Nutrition (2012) doi: /ejcn 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: /ejcn 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: /ejcn 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: /ejcn Recall Where We Are Now….. Pineal Hormone Vitamin D SKIN

121 The Skin Cancer / Melanoma Hysteria J Am Acad Dermatol Feb;54(2): Ivor Cummins BE(Chem) CEng MIEI  Blue is UV-B zone that enables Vitamin D Synthesis (and Cholesterol Sulphate)

122 The Skin Cancer / Melanoma Hysteria J Am Acad Dermatol Feb;54(2): Ivor Cummins BE(Chem) CEng MIEI  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 Acad Dermatol Feb;54(2): Ivor Cummins BE(Chem) CEng MIEI  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 Acad Dermatol Feb;54(2): Ivor Cummins BE(Chem) CEng MIEI  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 Acad Dermatol Feb;54(2): Ivor Cummins BE(Chem) CEng MIEI  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 Acad Dermatol Feb;54(2): Ivor Cummins BE(Chem) CEng MIEI  So who’s the idiot? (a) Evolution Itself, or (b) how humans have interpreted it??  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 EffectiveMost 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 Melanoma Victim 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 Melanoma Victim 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 Melanoma Victim 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 Melanoma Victim 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 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

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 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

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 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?

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 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

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 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

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 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 HR

140 SUNSCREENS: A Counter-Intuitive Twist 2014 Ivor Cummins BE(Chem) CEng MIEI HR

141 The Bottom Line: All Cause Mortality Journal of Internal Medicine: doi: /joim “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: /joim “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

143 The Bottom Line: All Cause Mortality Journal of Internal Medicine: doi: /joim “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

144 The Bottom Line: All Cause Mortality Journal of Internal Medicine: doi: /joim “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

145 The Bottom Line: All Cause Mortality Journal of Internal Medicine: doi: /joim “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

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 LOW 25(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 LOW 25(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 HIGH 25(OH)D >60? ng/ml Excess SUN Exposure LG Excess D3 Supplements Racial factors & Genetics AND /OR Low Vit K2 Excessive Calcification?

149 Optimising 25(OH)D – Synergy and Interaction LOW 25(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 OPTIMUM 25(OH)D ng/ml Fat-Nutrient Dense Diet Oily Fish, Cod Liver, Pate, etc Correct D3 Supplements HIGH 25(OH)D >60? ng/ml Excess SUN Exposure LG Excess D3 Supplements Racial factors & Genetics AND Adequate Calcium AND /OR Adequate Vit A Adequate Vit K2 Excessive Calcification? Low Vit K2

150 Optimising 25(OH)D – Synergy and Interaction LOW 25(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 OPTIMUM 25(OH)D ng/ml Fat-Nutrient Dense Diet Oily Fish, Cod Liver, Pate, etc Correct D3 Supplements HIGH 25(OH)D >60? ng/ml Excess SUN Exposure LG Excess D3 Supplements Racial factors & Genetics AND Adequate Calcium AND /OR Adequate Vit A Adequate Vit K2 Immune Function Bone Strength Disease Protection Cancer Resistance Vigour & Longevity Healthy Sun Exposure UVB/UVA Ratio Excessive Calcification? Low Vit K2

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… 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

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… 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

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… 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

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157 A Thank-You to some Experts: Prof. Michael Holick Endocrinologist 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 Gorham Associate 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 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.D in 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. Dr Grimes ccccc.

158 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

159  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

160  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?

161 2014 Ivor Cummins BE(Chem) Ceng MIEI BREAST CANCER MORTALITY – A Deeper Dive How did the Intervention Affect Subgroups? Borderline Significant Estimated D Intake  Non-Supplement Users Subgroup with poor Vit D intake showed signal

162 2014 Ivor Cummins BE(Chem) Ceng MIEI 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 Vit D intake showed signal  Supplement Users Subgroup with poor Vit D Intake showed signal

163 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 Statistically Significant Statistically Significant Estimated D Intake Estimated Ca Intake Borderline Significant Estimated D Intake How did the Intervention Affect Subgroups?

164 2014 Ivor Cummins BE(Chem) Ceng MIEI BREAST CANCER MORTALITY – A Deeper Dive  Conclusion: Engineering Signal There, but study is otherwise Near-Worthless Statistically Significant Statistically Significant Estimated D Intake Estimated Ca Intake Borderline Significant 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?

165 Backup / Other

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168 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:

169  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

170 Sunlight UVB is the Primary Source of Human 25(OH)D ….and a lot more, as recent understanding grows Ivor Cummins BE(Chem) CEng MIEI

171 Another Evolutionary View… 2014 Ivor Cummins BE(Chem) CEng MIEI ng/ml

172  Land Mass in Southern Hemisphere retains high UVB year-round. Annual Adequacy of UVB for Synthesis? 2014 Ivor Cummins BE(Chem) CEng MIEI

173 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

174 Central Control System of the Human Machine 2014 Ivor Cummins BE(Chem) CEng MIEI ↑↑CATHELICIDIN

175 The Centrality of the Sun 2014 Ivor Cummins BE(Chem) CEng MIEI ….A Profound Evolutionary Paradigm HEALTHY Sun Exposure But NO BURNING!

176 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

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 Sulfate Plus Cholesterol / Sulfur

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 Sulfate Plus Cholesterol / Sulfur Health + Longevity

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 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.D degree 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

180  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– Ivor Cummins BE(Chem) CEng MIEI

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, Takaaki Segawa, Minoru Okazaki, Mana Kurihara, Yasuyuki Wada, and Hiroyuki Ida Am J Clin Nutr 2010;91:1255– Ivor Cummins BE(Chem) CEng MIEI  In a (rare) experiment, D3 supplements reduced Influenza A by >40%

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, Takaaki Segawa, Minoru Okazaki, Mana Kurihara, Yasuyuki Wada, and Hiroyuki Ida Am J Clin Nutr 2010;91:1255– 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%

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, Takaaki Segawa, Minoru Okazaki, Mana Kurihara, Yasuyuki Wada, and Hiroyuki Ida Am J Clin Nutr 2010;91:1255– 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)

184 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

185 2014 Ivor Cummins BE(Chem) MIEI A Wider View

186 Hollis B W, and Wagner C L CMAJ 2006;174: ©2006 by Canadian Medical Association

187 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

188 Making D and burning / Cancer Q J Am Acad Dermatol Feb;54(2):  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 D 3 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 ( nm) (dashed gray lines). (FromWolpowicz & Gilchrest, The vitamin D questions: how much do you need and how should you get it? J Am AcadDermatol Feb;54(2): With permission) Ivor Cummins BE(Chem) C(Eng) MIEI

189 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

190  cccc Key Takeaways: COLON CANCER – New Discovery in 2000’s ? 2014 Ivor Cummins BE(Chem) C(Eng) MIEI

191 BACKUP


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