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Micellized Vitamin D3 Micellized Vitamin D3 A paradigm A paradigm

shift for all shift for all healthcare providers.healthcare providers.

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Diseases of Civilization Diseases of Civilization

Associated with vitamin D deficiencyAssociated with vitamin D deficiency: : Prostate cancer, colon cancer, breast Prostate cancer, colon cancer, breast cancer, 12 other cancers, heart disease, cancer, 12 other cancers, heart disease, type-2 diabetes, metabolic syndrome, type-2 diabetes, metabolic syndrome, hypertension, stroke, osteoarthritis, hypertension, stroke, osteoarthritis, rheumatoid arthritis, depression, rheumatoid arthritis, depression, dementia, multiple sclerosis, chronic pain, dementia, multiple sclerosis, chronic pain, obesity, periodontal disease, Parkinson's obesity, periodontal disease, Parkinson's disease, autoimmune disease, and, disease, autoimmune disease, and, osteoporosisosteoporosis

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Vitamin D DeficiencyVitamin D Deficiency

Most whites are deficientMost whites are deficient

Virtually all African Americans are deficientVirtually all African Americans are deficient

Most vitamin D comes from the sunMost vitamin D comes from the sun

Vitamin D is a prehormone, not a vitaminVitamin D is a prehormone, not a vitamin

If you avoid the sun, and do not take adequate If you avoid the sun, and do not take adequate doses of cholecalciferol, you are deficientdoses of cholecalciferol, you are deficient

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Vitamin D Deficiency

Dickey, who is immediate past president of the American Academy of Clinical Endocrinologists, also points out research is pointing to more and more cases of vitamin D deficiency in the U.S. and Northern Europe.

"We now have an epidemic of vitamin D deficiency in our elderly and possibly our younger people." Vitamin D deficiency in the young can also coincide with the peak time in bone formation as well.

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Calcitriol is perhaps the most potent Calcitriol is perhaps the most potent anti-cancer agent known to mananti-cancer agent known to man

It promotes normal cell death (apoptosis), It promotes normal cell death (apoptosis), cell specialization (differentiation), cell specialization (differentiation), prevents vascularization prevents vascularization (neoangiogenesis), and inhibits (neoangiogenesis), and inhibits metastasismetastasis

Vieth showed it lowers PSA in prostate Vieth showed it lowers PSA in prostate cancercancer

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The current adult recommendations for vitamin D, 200-600 IU/d, are very inadequate when one considers that a 10-15 min whole-body exposure to peak summer sun will generate and release up to 20,000 IU vitamin D-3 into the circulation.

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A person standing in the summer sun for an hour at noontime in a Southern latitude (Arizona, Florida) in swim trunks would naturally produce about 10,000 IU (250 micrograms) of vitamin D through skin exposure. Sun poisoning from vitamin D overdose has never been reported. [Am J Clinical Nutrition 73 (2): 288-94, Feb 2001; Am J Clinical

How much Vitamin D should you How much Vitamin D should you take? take?

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Old-World Primates Humans with UV Canadian Winter Canadian + 25 ug/d Canadian + 100 ug/d0

40

80

120

160

Ser

um

25(

OH

)D

nm

ol/

L

Vitamin D Nutritional Status Vitamin D Nutritional Status

Primates Humans Americans 1000 IU 4000 IU

in sun in winter supplement supplement

60 55

1525

40

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Vitamin D levels in serum “M. Holick”

25 (OH) D Level ng/ml nMol/L

Deficient less than 8 less than 14 Insufficient 8-30 12.5-50 Optimal 30-90 (60) 50-150 High 90-150 150-250 Toxic greater than 150 greater than 250

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The winter mean winter concentration was 24.9 +/- 8.7 ng/ml in men and 22.4 +/- 8.2 ng/ml in women and the summer the mean concentration was 31+/-11ng/ml in men and 25 +/- 9.4 ng/ml in women.

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J Clin Endocrinol Metab. 2007;92:2130-2135. ide without sunscreen and 28.9 hours per week outside with and without sunscreen, the authors report.This translates to a mean of 11.1 hours per week of total body skin exposure with no sunscreen used, the results indicate.Despite this abundant sun exposure, 51% of the subjects had serum 25-hydroxyvitamin D concentrations below 30 ng/mL, defined as "low vitamin D status," the researchers report. The highest observed level was 62 ng/mL."This implies that the common clinical recommendation to allow sun exposure to the hands and face for 15 minutes may not ensure vitamin D sufficiency," the investigators say.Overall, vitamin D level did not correlate with age, skin color, or sun exposure, the report indicates. However, participants in the lowest vitamin D quartile compared to the rest of the participants had higher parathyroid hormone levels and lower sun exposure scores."Clinicians should not assume that individuals with abundant sun exposure have adequate vitamin D status," the authors conclude.They recommend that in treating vitamin D deficiency with vitamin D supplementation, "it seems prudent" to aim for a serum 25-hydroxyvitamin D concentration no greater than the maximum produced by natural UV exposure; i.e., approximately 60 ng/mL.Reuters Health Information 2007. © 2007 Reuters Ltd.

Inadequate sun exposure is blamed for the high prevalence of low vitamin D. (But is this true?)

In Hawaii despite abundant sun exposure without sunscreen 51% had low Vit D status below 30ng/ml.

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1,25(OH)(2)D(3) functions as a potent negative endocrine regulator of renin gene expression provides some insights into The concept of vitamin D regulation of blood pressure through the Renin-angiotensin System

Modulation of Blood pressure regulation with Vit D

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**Cardiovascular disease is more Cardiovascular disease is more common in the winter, more common in the winter, more common at higher latitudes and common at higher latitudes and more common at lower more common at lower altitudes altitudes People with 25(OH)D levels People with 25(OH)D levels above 35 ng/ml were half as above 35 ng/ml were half as likely to have a heart attack likely to have a heart attack than those whose level was than those whose level was less than 35 ng/ml less than 35 ng/ml John Connell MDJohn Connell MD

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The women, 1,179 healthy, postmenopausal women who were all 55 years or older and free of known cancers for at least 10 years prior to entering the study, were randomly assigned to take daily dosages of 1,400-1,500 mg supplemental calcium, 1,400-1,500 mg supplemental calcium plus 1,100 IU of vitamin D3, or placebos.

Over the four-year trial, women in the calcium/vitamin D3 group experienced a 60 per cent decrease in their cancer risk compared to the group taking placebos.

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**In an eight-year prospective In an eight-year prospective study of 25,000 subjects, study of 25,000 subjects, colon colon cancer was reduced by 80%cancer was reduced by 80% in in those with serum 25(OH)D levels those with serum 25(OH)D levels above 33 ng/ml above 33 ng/ml A recent English study showed A recent English study showed breast cancer was five times breast cancer was five times more commonmore common in those with the in those with the lowest 25(OH)D levelslowest 25(OH)D levels

Sato reported that two years of treatment Sato reported that two years of treatment with 1,000 IU of vitamin D per day with 1,000 IU of vitamin D per day

significantly increased muscle strengthsignificantly increased muscle strength,, doubled the mean diameter, and tripled the doubled the mean diameter, and tripled the percentage of fast-twitch muscle fibers, in percentage of fast-twitch muscle fibers, in the functional limbs of 48 severely vitamin the functional limbs of 48 severely vitamin

D deficient elderly stroke patients. The D deficient elderly stroke patients. The placebo control group suffered declines in placebo control group suffered declines in

muscle strength, and in the size and muscle strength, and in the size and percentage of fast-twitch muscle fibers.percentage of fast-twitch muscle fibers.

Sato Y, Iwamoto J, Kanoko T, Satoh K. Low-Dose Vitamin D Prevents Muscular Sato Y, Iwamoto J, Kanoko T, Satoh K. Low-Dose Vitamin D Prevents Muscular Atrophy and Reduces Falls and Hip Fractures in Women after Stroke: A Randomized Atrophy and Reduces Falls and Hip Fractures in Women after Stroke: A Randomized Controlled Trial. Cerebrovasc Dis. 2005 Jul 27;20(3):187-192 [Epub ahead of print]Controlled Trial. Cerebrovasc Dis. 2005 Jul 27;20(3):187-192 [Epub ahead of print]

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Immunity and Auto-ImmunityImmunity and Auto-Immunity

• Multiple SclerosisMultiple Sclerosis• Inflammatory bowl diseaseInflammatory bowl disease• Diabetes Mellitus -type 1- auto-Diabetes Mellitus -type 1- auto-

immunity and insulin productionimmunity and insulin production• Rheumatoid ArthritisRheumatoid Arthritis• PsoriasisPsoriasis• Promotes wound healing and Promotes wound healing and

immune supportimmune support

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.  The association was strong (P<.005) among their 120 women with polycystic ovarian disease.  However, like dozens of other studies, the authors also found a strong inverse correlation between obesity and vitamin D levels - the higher the vitamin D levels the thinner the patients - and this may explain the association with HDL cholesterol.  Unfortunately, the authors did not look further at their data to see if the association with HDL held after correction for body weight.Hahn S, et al. Low Serum 25-Hydroxyvitamin D Concentrations are Associated with Insulin Resistance and Obesity in Women with Polycystic Ovary Syndrome. Exp Clin Endocrinol Diabetes. 2006 Nov;114(10):577-83.

Vitamin D improves Vitamin D improves low back painlow back pain..Initial assessment involved Initial assessment involved 360 patients 360 patients (90% (90% women and 10%men) who had experience low women and 10%men) who had experience low back pain that had no obvious cause for more back pain that had no obvious cause for more

than 6 months.than 6 months.Finding 83% n=299 had an abnormally low level Finding 83% n=299 had an abnormally low level

of vitamin D of vitamin D . After treatment with Vit. D . After treatment with Vit. D clinical improvement in symptoms was seen clinical improvement in symptoms was seen

in 95% of all the patients n=341in 95% of all the patients n=341Spine 2003 Jan 15;(2);177-9Spine 2003 Jan 15;(2);177-9

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Osteoporosis and Osteoporosis and ArthritisArthritis

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CONCLUSIONS: In ambulatory adults on antiepileptic drugs, high-dose vitamin D 4,000 IU/day therapy substantially increased bone mineral density at several skeletal sites.

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•Framingham data showed osteoarthritis of the knee progressed more rapidly in those with 25(OH)D levels lower than 36 ng/ml

•Another study found that osteoarthritis of the hip progressed more rapidly in those with 25(OH)D levels lower than 30 ng/ml

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Cold and Flu Cold and Flu SeasonSeason

Flu Shots?Flu Shots?

A recent study published in the October issue of A recent study published in the October issue of the the Archives of Pediatric & Adolescent MedicineArchives of Pediatric & Adolescent Medicine found that vaccinating young children against the found that vaccinating young children against the flu appeared to have flu appeared to have no impact no impact on flu-related on flu-related hospitalizations or doctor visits during two recent hospitalizations or doctor visits during two recent flu seasons.flu seasons.

The researchers concluded that "The researchers concluded that "significant significant influenza vaccine effectiveness could not be influenza vaccine effectiveness could not be demonstrated for any season, age, or demonstrated for any season, age, or settingsetting" examined." examined.

Additionally, a Group Health study found that flu Additionally, a Group Health study found that flu shots do shots do not not protect elderly people against protect elderly people against developing pneumonia -- the primary cause of developing pneumonia -- the primary cause of death resulting as a complication of the flu.death resulting as a complication of the flu.

One credible hypothesis that explains the One credible hypothesis that explains the seasonal nature of flu is that influenza is a seasonal nature of flu is that influenza is a vitamin D deficiency disease. vitamin D deficiency disease.

Vitamin D levels in your blood fall to their Vitamin D levels in your blood fall to their lowest point during flu seasons. Unable to lowest point during flu seasons. Unable to be protected by the body’s own antibiotics be protected by the body’s own antibiotics (antimicrobial peptides) that are released (antimicrobial peptides) that are released by vitamin D, a person with a low vitamin by vitamin D, a person with a low vitamin D blood level is more vulnerable to D blood level is more vulnerable to contracting colds, influenza, and other contracting colds, influenza, and other respiratory infections respiratory infections

In 1981, a British general practitioner named R. In 1981, a British general practitioner named R. Edgar Hope-Simpson published the first paper Edgar Hope-Simpson published the first paper documenting a link between influenza epidemics documenting a link between influenza epidemics in the northern hemisphere and the winter in the northern hemisphere and the winter solstice. The solstice - which arrives on Dec. 21 solstice. The solstice - which arrives on Dec. 21 this year - is commonly identified with the start of this year - is commonly identified with the start of winter and is the shortest day of the year.  Hope-winter and is the shortest day of the year.  Hope-Simpson, who had no formal training in Simpson, who had no formal training in epidemiology, realized that epidemiology, realized that influenza infections influenza infections tended to jump just before and after the tended to jump just before and after the solstice. solstice. Solar radiation, he surmised, triggered Solar radiation, he surmised, triggered some sort of "seasonal stimulus" that affected the some sort of "seasonal stimulus" that affected the flu virus, its human host or both.flu virus, its human host or both.

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Honk Kong Pandemic in BritainHonk Kong Pandemic in Britain

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25(OH)D levels and flu season25(OH)D levels and flu season

In their forthcoming paper in Epidemiology and In their forthcoming paper in Epidemiology and Infection, John Cannell PhD and colleagues from Infection, John Cannell PhD and colleagues from Harvard University, the National Institutes of Harvard University, the National Institutes of Health and Boston University propose that Hope-Health and Boston University propose that Hope-Simpson's seasonal stimulus could be vitamin D. Simpson's seasonal stimulus could be vitamin D. The tip-off, says Cannell, came in April 2005, The tip-off, says Cannell, came in April 2005, when an outbreak of influenza swept through when an outbreak of influenza swept through Atascadero, a maximum-security facility for the Atascadero, a maximum-security facility for the criminally insane 200 miles south of San criminally insane 200 miles south of San Francisco. Francisco. "The ward below me got it, then the ward to my "The ward below me got it, then the ward to my right, to my left and the one across the hall," he right, to my left and the one across the hall," he recalls. Cannell's 32 patients, however, were recalls. Cannell's 32 patients, however, were spared. As far as he could tell, there was only one spared. As far as he could tell, there was only one glaring difference between his patients and those glaring difference between his patients and those who came down with flu: Cannell's patients were who came down with flu: Cannell's patients were taking high daily doses of vitamin D.taking high daily doses of vitamin D.

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Information SourcesInformation Sources

““The UV Advantage” Michael Holick The UV Advantage” Michael Holick and Mark Jenkins and Mark Jenkins

www.VitaminDCouncil.comwww.VitaminDCouncil.com

www. healthresearchforum.org.ukwww. healthresearchforum.org.uk

www.sunlightandvitamind.comwww.sunlightandvitamind.com

D3D3

Absorption Absorption IssuesIssues

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At the junction of membrane surface and body At the junction of membrane surface and body fluid, there is a double layer formation. This fluid, there is a double layer formation. This double layer is aqueous in nature. For a drug to double layer is aqueous in nature. For a drug to cross the membrane and arrive at its site of cross the membrane and arrive at its site of action, it must cross this double layer before action, it must cross this double layer before getting into the membranes. Absorption, getting into the membranes. Absorption, regardless of the site, is dependent upon drug regardless of the site, is dependent upon drug solubility in the double layer. The higher the solubility in the double layer. The higher the solubility, the higher the absorption, therefore solubility, the higher the absorption, therefore the higher the bioavailability. the higher the bioavailability.

Unstirred water Layer

Unstirred water Layer

Unstirred water Layer

Unstirred water Layer

How Well Does It Work?How Well Does It Work?

How Well Does It Work?How Well Does It Work?

Before

After

VITAMIN E - FIVE TIMES GREATER ABSORPTION

Platelets play an important role in thrombus formation in arterial vascular walls which may lead to vascular disease. It has been suggested in the scientific literature that vitamin E exhibits anti-platelet activity. 5 However, the plasma

level of vitamin E in oil form is found to be very low. The absorption of Vitamin E in oil form is lower than 25% in normal humans. 6

Dosage of 500 IU of d-alpha-tocopheryl acetate were administered to the 12 subjects and the plasma levels were measured as an increase over baseline levels (19.8 micromoles/liter) at 4 and 24 hours. Figure 3 shows the results of

the comparative absorption increases of vitamin E plasma levels of the oil, emulsified and EMUSOL® form at 4 and 24 hours.

VITAMIN AVITAMIN A - - FIVE TIMES GREATER ABSORPTIONFIVE TIMES GREATER ABSORPTION

Human subjects were given 50,000 IU vitamin A Human subjects were given 50,000 IU vitamin A palmitate in either an oil, emulsified or EMUSOL® form. palmitate in either an oil, emulsified or EMUSOL® form. The blood plasma levels were measured as an increase The blood plasma levels were measured as an increase over baseline levels (2.675 micromoles/ liter) at 4 and 8 over baseline levels (2.675 micromoles/ liter) at 4 and 8 hours. Figure 5 illustrates results while Table 3 provides hours. Figure 5 illustrates results while Table 3 provides a summary of the relative increases. a summary of the relative increases.

References:References: Goodman and Gilman’s “The Pharmacological Basis of Therapeutics”, Eighth Edition, pp 1-83, McGraw-Hill, Goodman and Gilman’s “The Pharmacological Basis of Therapeutics”, Eighth Edition, pp 1-83, McGraw-Hill, 1990 1990

Thomas M Devlin “Biochemistry with Clinical Correlations” Third Edition, pp 1059-1091, Wiley-Liss, 1993 Thomas M Devlin “Biochemistry with Clinical Correlations” Third Edition, pp 1059-1091, Wiley-Liss, 1993

– Lewis JM, Bodansky O, Birmingham J, Cohan SQ. Comparative absorption, excretion and storage of oily and aqueous Lewis JM, Bodansky O, Birmingham J, Cohan SQ. Comparative absorption, excretion and storage of oily and aqueous preparations of vitamin A. J Paediatr 31, 496-508 (1947); preparations of vitamin A. J Paediatr 31, 496-508 (1947);

– Kelleher J, Davies T, Smith CL, et al. The absorption of alpha tocopherol in the rat: the effect of different carriers and different Kelleher J, Davies T, Smith CL, et al. The absorption of alpha tocopherol in the rat: the effect of different carriers and different dose levels. Int J Vit Nutr Res 42, 394-411 (1972); dose levels. Int J Vit Nutr Res 42, 394-411 (1972);

– Gross S, Melhorn DK. Vitamin E dependent anaemia in the premature infant III. J Paediatr 85, 753-759 (1974); Gross S, Melhorn DK. Vitamin E dependent anaemia in the premature infant III. J Paediatr 85, 753-759 (1974); – Jansson L, Londrota M, Tyopponen J. Intestinal absorption of vitamin E in low birth weight infants. Acta Paediatr Scand 73, Jansson L, Londrota M, Tyopponen J. Intestinal absorption of vitamin E in low birth weight infants. Acta Paediatr Scand 73,

329-332 (1984); 329-332 (1984); – Bateman NE, Uccellini DA. Effect of formulation on the bio-availability of retinol, alpha-d-tocopherol and riboflavin. J Pharm Bateman NE, Uccellini DA. Effect of formulation on the bio-availability of retinol, alpha-d-tocopherol and riboflavin. J Pharm

Pharmacol 36, 461-464 (1984); Pharmacol 36, 461-464 (1984); – Hittner HM, Speer ME, Rudolph AJ, et al. Retrolental fibroplasia and vitamin E in the preterm infant - comparison of oral Hittner HM, Speer ME, Rudolph AJ, et al. Retrolental fibroplasia and vitamin E in the preterm infant - comparison of oral

versus intramuscular administration. Paediatrics 73, 238-249 (1984); versus intramuscular administration. Paediatrics 73, 238-249 (1984); – Traber MF, Kayden HJ, et al. Absorption of water-miscible forms of vitamin E in a pationt with cholestasis and in thoracic duct-Traber MF, Kayden HJ, et al. Absorption of water-miscible forms of vitamin E in a pationt with cholestasis and in thoracic duct-

cannulated rats. Am J Clin Nutr 44, 914-23 (1986); cannulated rats. Am J Clin Nutr 44, 914-23 (1986); – Sokol RJ, Heubi JE, Butler-Simon N, et al. Treatment of vitamin E deficiency during chronic childhood cholestasis with oral d-Sokol RJ, Heubi JE, Butler-Simon N, et al. Treatment of vitamin E deficiency during chronic childhood cholestasis with oral d-

alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS). Intestinal absorption, efficacy and safety. Gastroenterology 93, alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS). Intestinal absorption, efficacy and safety. Gastroenterology 93, 975-985 (1987); 975-985 (1987);

– Traber MG, Thellman CA, Rindler MJ, Kayden HJ. Uptake of intact TPGS, a water-soluble form of vitamin E by human cells in Traber MG, Thellman CA, Rindler MJ, Kayden HJ. Uptake of intact TPGS, a water-soluble form of vitamin E by human cells in vitro. Am J Clin Nutr 48, 605-611 (1988) vitro. Am J Clin Nutr 48, 605-611 (1988)

Bhargava HN, Narurkar A, Lieb LM. Using microemusions for drug delivery. Pharm Tech 12(3), 46-54 (1987) Bhargava HN, Narurkar A, Lieb LM. Using microemusions for drug delivery. Pharm Tech 12(3), 46-54 (1987)

– Machlin LJ, Filipski R, Willis AL, et al. Influence of Vitamin E on platelet aggregation and thrombocythemia in the rat. Machlin LJ, Filipski R, Willis AL, et al. Influence of Vitamin E on platelet aggregation and thrombocythemia in the rat. ProcSocExp Biol Med 149, 275-277 (1975); ProcSocExp Biol Med 149, 275-277 (1975);

– Steiner M, Anastasi J. Vitamin E: an inhibitor of the platelet release reaction. J Clin Invest 57, 732-737 (1976); Steiner M, Anastasi J. Vitamin E: an inhibitor of the platelet release reaction. J Clin Invest 57, 732-737 (1976); – Cox AC, Rao GHR, Gerrard JM, White JG. The influence of vitamin E quinone on platelet structure, function and biochemistry. Cox AC, Rao GHR, Gerrard JM, White JG. The influence of vitamin E quinone on platelet structure, function and biochemistry.

Blood 55, 07-912 (1980); Blood 55, 07-912 (1980); – Tangey CC, Diskoll JA. Effects of vitamin E deficiency on the relative incorporation of 14 c-arachidonate into platelet lipids of Tangey CC, Diskoll JA. Effects of vitamin E deficiency on the relative incorporation of 14 c-arachidonate into platelet lipids of

rabbits. J Nutr III, 1839-1845 (1981); rabbits. J Nutr III, 1839-1845 (1981); – Steiner M. Effects of alpha-tocopherol administration on platelet function in man. Thromb Haemotas 49(2), 3-77 (1983); Steiner M. Effects of alpha-tocopherol administration on platelet function in man. Thromb Haemotas 49(2), 3-77 (1983); – Kuo P, Wilson, Godstein R. Effect of long-term vitamin E and linoleate supplementation on platelet aggregation in man. J Am Kuo P, Wilson, Godstein R. Effect of long-term vitamin E and linoleate supplementation on platelet aggregation in man. J Am

Col N 3, 244-249 (1984) Col N 3, 244-249 (1984)

Klaskin G, Molander DW. The chemical determination of tocopherols in faeces and faecal excretion of vitamin Klaskin G, Molander DW. The chemical determination of tocopherols in faeces and faecal excretion of vitamin E in man. J Lab Clin Med 39, 802-807 (1952) E in man. J Lab Clin Med 39, 802-807 (1952)