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Vitamin D

I Saved you 40 HOURS in Research AND summarized the 30 min you need to treat patients RIGHT NOW. Your Welcome :) By: Christian Carroll

"Information Without Purpose is Useless"


One Goal: 1. Understand what the latest evidenced-based research in Vitamin D means for your patient's health. 2. Implement an effective strategy to reach optimum serum levels.

What Is The 80/20 Principle?


This is a research based guide to clinical dosages and maintenance dosages in a 80/20 style format

Included: 37 Published Papers = .0006% of the total vitamin D research

The Next Miracle Drug?

1,25(OH)Vitamin D = Active Vitamin D


Search "Vitamin D" in PUBMED Results: 53680!
*as of 12/30/11

What is Everyone so Amazed about?

Hybrid Vitamin D Seminar

Vitamin D Supplement

Image credit: Nature Reviews Cancer

Vitamin D Works. Period.


Musculoskeletal pain Chronic Low Back Pain Type 2 Diabetes Osteoporosis Osteoarthritis Hypertension CV Disease Syndrome X MS PCOS Depression Epilepsy Prevention of Cancer
Vasquez A, Manso G, Cannell J. The clinical importance of vitamin D (cholecalciferol): a paradigm shift with implications for all healthcare providers. Altern Ther Health Med. 2004 Sep-Oct;10(5):28-36; quiz 37, 94.

There is now extensive literature on adverse health outcomes in patients with vitamin D deficiency reporting increased mortality, cardiovascular events and impaired function of the immune and musculoskeletal systems (1,2)

1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266 281. doi: 10.1056/NEJMra070553. [PubMed] [Cross Ref] 2. Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, Kinkeldei J, Boehm BO, Weihrauch G, Maerz W. Independent association of low serum 25-hydroxyvitamin d and 1,25dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med. pp. 13401349.[PubMed] [Cross Ref]

BENEFITS >>> COSTS

Vitamin D Deficiency Rates

Gordon et al. (1) = Harkness and Cromer (3) =

found a 42% prevalence of vitamin D deficiency (<20 ng/ml). observed a 54% deficiency

1. Gordon CM, DePeter KC, Feldman HA, Grace E, Emans SJ. Prevalence of vitamin D deficiency among healthy adolescents. Archives of Pediatrics and Adolescent Medicine. 2004; 158: 531-537. 2. Saintonge S, Bang H, Gerber LM. Implications of a new definition of vitamin D deficiency in a multiracial US adolescent population: the national health and nutrition examination survey III. Pediatrics. 2009; 123: 797-803. 3. Harkness LS, Cromer BA. Vitamin D deficiency in adolescent females. J Adolesc Health. 2005; 37 (1):75

HypoVitaminosis D vs. Vitamin D Deficiency


MASSIVE STUDY OUT OF AUSTRALIA
11,247 Australian adults. RESULTS: prevalence of vitamin D deficiency

<20ng/ml =

31% (22% men; 39% women); <30ng/ml =

73%

Daly RM, Clin Endocrinol (Oxf). 2011 Dec 15. doi: 10.1111/j.1365-2265.2011.04320.x. Prevalence of vitamin D deficiency and its determinants in Australian adults aged 25 years and older: A national, population-based study.

Dr. John Cannell MD


"95% of Americans are deficient in Vitamin D -- that's how big the problem is."

Am I Vitamin D Deficient?
Do You Get Enough= SUN EXPOSURE or Vitamin D Supplementation? - It's a GUESS Until You TEST!

- Vitamin D Tests: Calcidiol = s25(OH)D

How Do I Get Tested? 1) Doctor or 2) Home Test of Vitamin D


http://www.zrtlab.com/vitamindcouncil

"I Get Enough Vitamin D in My Diet...I Don't have to Worry." I call BS!
1. 2009 American Journal of Clinical Nutrition: Vegetarians vs. partial vegetarians vs. non vegetarians. - Dietary Vitamin D = Mostly animal sources. - Mean Dietary Intakes of ~150 IU/daily = <41% of adequate dietary intake of Vitamin D (400IU) - Only 50% of white subjects had above 'sufficient' vitamin d levels = >30ng/ml. - Only 15% of black subjects had above 'sufficient' vitamin d levels = >30ng/ml.
- 80/20 = "s25(OH)D concentrations were not associated with vegetarian status. Other

factors, such as vitamin D supplementation, degree of skin pigmentation, and amount and intensity of sun exposure have greater influence on s25(OH)D than does diet."
1. Chan J., Jaceldo-Siegl K., Fraser G.E. Serum 25-hydroxyvitamin D status of vegetarians, partial vegetarians, and nonvegetarians: the Adventist Health Study-2. Am J Clin Nutr. 2009 May; 89 (5): 1686S-1692S.

-------------------------------------------------------------------------------2. 2007 European Journal of Clinical Nutrition - 65 Finnish men. Vitamin D levels raised 20%(avg) yoy from introduction of vitamin D fortified milk. -"19 men (29.2%) had vitamin D deficiency (8ng/ml) and 48 men (73.8%) had hypovitaminosis D (15ng/ml)" -

"Vitamin D fortification of milk products slightly but insufficiently improved the poor vitamin D status of young Finnish men during winter. Further

supplementation is warranted in order to normalize vitamin D levels and to support achievement of maximum peak bone mass."

= 80/20 - fortified foods doesn't improve vitamin D status to levels appropriate for maximizing disease prevention. Need Vitamin D3 Supplements to Achieve Healthy Levels.
Vlimki VV, Lyttyniemi E, Vlimki MJ Vitamin D fortification of milk products does not resolve hypovitaminosis D in young Finnish men. Eur J Clin Nutr. 2007 Apr; 61 (4): 493-7.

TO GET 1000 IU of VITAMIN D


You would need to eat....

40 EGGS 10 Cups of MILK 3 Salmon Steaks 7.3 lbs Cooked Liver

TO GET 5000 IU of VITAMIN D


You would need to eat....

200 EGGS 50 Cups of MILK 15 Salmon Steaks 36.5 lbs Cooked Liver

Or.....1 Capsule of 5000 IU vitamin D3. (11 cents)

"Well I Get Enough Sun Exposure...So I Can't Be Deficient." ...again, read the research!
2007, Cohort Study out of U of Wisc 93 Hawaiian Young Adults. Avg 29h/wk in sun. Results of Serum25(OH)vitamin D Found 51% - < 30ng/ml 67% - < 35ng/ml 79% - <40ng/ml 95% - <50ngml
Binkley et al. 92 (6): 2130 http://jcem.endojournals.org/content/92/6/2130.full.pdf+html

Sunlight and Supplementation: Fun Facts of the Day


1) 1 MED (sunburn threshold) in a bathing suit = estimated at 10,000 25,000 IU (1) 2) Studies in the U.S. and England found that serum 25(OH)D levels increase by about 10-15 ng/mL (25-37 nmol/L) in summer for younger people (2,3). 3) A good rule of thumb is: If your shadow is longer than you are tall (an indicator of the oblique angle of the Sun), you are not making vitamin D. 4) In Boston (42.2 degrees N), sun rays produced NO pre vitamin D from November - February. (4) 5) It takes about 5 min of sun exposure. 25% skin showing. to synthesize the equivalent of 400 IU 6) SPF 8 can block 95% of vitamin d production. SPF 30 blocks 100%. Glass Blocks all UVB rays as well.
1.Holick M.F., Chen T.C., Lu Z., Sauter E. Vitamin D and skin physiology: a D-lightful story. J Bone Miner Res. 2007 Dec; 22 (Suppl 2): V28-33. 2. Harris, S. S. Dawson-Hughes, B. Seasonal changes in plasma 25-hydroxyvitamin D concentrations of young American black and white women. Am J Clin Nutr. 1998 Jun; 67 (6): 1232-6. 3. 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 Mar; 85 (3): 860-8.1. 4. Webb A.R., Kline L., Holick M.F. Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endo Met. 1988; 67 (2): 373-378. 5. Terushkin V., Bender A., Psaty E.L., Engelsen O., Wang S.Q., Halpern A.C.Estimated equivalency of vitamin D production from natural sun exposure versus oral vitamin D supplementation across seasons at two US latitudes. J Am Acad Dermatol. 2010 June; 62 (6): 929.e1-9.

"Vitamin D Winter" = You Need Vitamin D Supplements

Vitamin D Levels
Rickets & Osteomalacia = Deficiency * = Insufficient = Sufficient = Upper Limit = Toxicity = <16ng/ml < 20ng/ml 20-30ng/ml >32ng/ml 100ng/ml >200-250ng/ml

Note that 1.0 nmol/L = 0.4 ng/mL for this compound

The Top Vitamin D Researchers = 45-60ng/ml

US Gov't: Food and Nutrition Board


Adequate Intake Levels established around maintaining bone health and calcium metabolism. Children to 70 yo adults = 600 IU/daily Adults 70 and Older = 800 IU/daily

Optimal Human Physiology can use 3000-5000 IU daily*


Bone & Calcium

Chronic Disease Prevention

What Clinical Signs To Test for Vitamin D Levels?


If Patient Has/or History of : Chronic Pains Cardiovascular Disease Depression ('winter blues') Autoimmune Frequent Colds (Low Immunity) Bone Diseases (Osteoporosis) Cancer TEST THEIR VITAMIN D LEVELS! At WORST put them on 5000IU/daily

So...What Do I Do If Myself or a Patient is Deficient?

Normalizing Patient Vitamin D Levels

80/20 & Vitamin D Dosages


1. 3000-5000IU Daily Dosages RECOMMENDED. 2. Mega Loading Dosages (100,000-300,000IU) appears efficient in quickly resolving deficiency (25ng/ml --> 50ng/ml) without producing side effects or toxicity (>200ng/ml). 3. <1000 IU/daily has been proven not to be able to maintain blood levels above 30ng/ml.

Great Research. Horrible Reporting.

Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Am J Clin Nutr. 2003 Jan;77(1):204-10. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol.

AJCN. 67 men. In Omaha. During Winter.


80/20= 1. "Healthy men seem to use 30005000 IU cholecalciferol/d"
2. 5,000 IU/daily = sweet spot daily dose.

100 ng/ml 80 60 40 28 20 10,000IU/d 5,000IU/d 1000 IU/d 0 IU/d

Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Am J Clin Nutr. 2003 Jan;77(1):204-10. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol.

Normalizing Patient Vitamin D Levels

Vitamin D Intake Needed for Desired Serum Levels


2008 American Journal Clinical Nutrition

DESIGN: was a 6-mo, prospective, randomized, double-blinded, double-dummy,


placebo-controlled study of vitamin D(3) supplementation.

RESULTS:
"..suggests a dose of 95 microg/d (3800 IU) for those above a 25(OH)D threshold of 55 nmol/L and a dose of 125 microg/d (5000 IU) for those below that threshold." "....an optimal daily dose of 115 microg/d (4600 IU). No hypercalcemia or hypercalciuria was observed."

Aloia JF, Am J Clin Nutr. 2008 Jun;87(6):1952-8.

Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration.

More Research Supporting 5000 IU/daily


Benefit-Risk Study of 20+ RCT's of over 40,000 people.

Found 3500 IU - 7000 IU oral Vitamin D needed to achieve the clinically beneficial serum D levels of 40-60ng/ml. At those levels there was no added risks.

Osteoporos Int. 2010 Jul;21(7):1121-32. Epub 2009 Dec 3. Benefit-risk assessment of vitamin D supplementation. Bischoff-Ferrari HA, Shao A, Dawson-Hughes B, Hathcock J, Giovannucci E, Willett WC.

10 Day High Dose vs. 3 Month Low Dose


59 vitamin D deficient inpatients (serum 25(OH)D < or = 20ng/ml) were enrolled in a prospective, randomised, open-label
trial. Participants were randomly assigned to

1) high-dose regimen of cholecalciferol 50,000 IU daily for 10 days 2) 3-month, continuous low-dose cholecalciferol regimen of 3000 IU daily for 30 days, followed by 1000 IU daily for 60 days.
*Both groups received calcium citrate 500 mg daily.

RESULTS:Started at Mean 10.4ng/ml -> 90% of both groups rose above the 20 ng/ml mark and 60% of patients above the 32ng/ml mark. 80/20 - Doesn't Seem to Matter. I wish they did the 10 day high dose followed by 1000 daily. Pick one your more likely to follow.
Med J Aust. 2010 Jun 21;192(12):6869 http://www.mja.com.au/public/issues/192_12_210610/hac11145_fm.html

Normalizing Patient Vitamin D Levels

At This Point: Rest. Deep Breath. Recall.


ESTABLISHED: 5000 IU/day = achieve desired levels NEXT: Mega Dosing.

Mega Dose Vitamin D

In Cohort study of over 3600 people:

- "40,000 IU intake daily UNLIKELY to Produce Toxicity"


- "The supplemental dose ensuring that 97.5% of this population achieved a serum 25(OH)D of at least 40 ng/ml was 9,600 IU/d."

Garland CF, et al, Anticancer Res. 2011 Feb;31(2):607-11. University of California, San Diego http://www.ncbi.nlm.nih.gov/m/pubmed/21378345/?i=7&from=300,000%20iu%20vitamin%20d

Semi Annual Megadosing


2011, European Journal of Clinical Nutrition -22 Vitamin D Deficient People in Australia (= 5ng/ml - 20ng/ml). -Randomized 3 Groups (received at t=0 and t=6 months) 1) 300,000 IU (1,643 IU/daily*) 2) 150,000 IU (822 IU/daily*) 3) Placebo -End of Study NO side effects. High Compliance. - At t=12 months levels were 25.2ng/ml,16.44ng/ml,14.32 ng/ml. (raised, but not enough). THE 80/20 = Mega 1 time Dosing in the 100,000 - 300,000 IU range seems to produce no side effects and is effective in raising serum 25(OH)D levels but does not sustain them in beneficial ranges for 6 months given the results (<32ng/ml)
Source: Eur J Clin Nutr. 2011 Dec 21. doi: 10.1038/ejcn.2011.204 http://www.ncbi.nlm.nih.gov/pubmed/22190133

Normalizing Patient Vitamin D Levels

Ultra-Mega Dose Vitamin D


-25 ICU patients in Austria with Vitamin D deficiency (25(OH)D) 20 ng/ml) -Randomized, Double-blind, placebo controlled -Randomly received either 540,000 IU or placebo -RESULTS: The mean serum 25(OH)D increase in the intervention group was 25 ng/ml (range 1-47 ng/ml). Highest reaching 64ng/ml.

- Important Finding: No hypercalcemia or hypercalciuria. No side effects for the 7 days they were monitored in ICU. - 80/20 = Mega dosing one time is effective at quickly raising vitamin D levels without risk of toxicity levels or symptoms (200ng/ml)
Crit Care. 2011;15(2):R104. Epub 2011 Mar 28 http://www.ncbi.nlm.nih.gov/pubmed/21443793

Pause & Reflect on Mega Dosing


- 100,000-300,000 IU delivered no toxic effects or serum levels of toxicity. Effective in for a quick 'boost' in serum levels. No hypercalcemia or hypercalciuria

Matter of Philosophy:
Example. Your Patient has 22ng/ml. Option A: 200,000 IU. 5000 IU daily maintenance thereafter Option B: 10,000 IU/daily for 4-5 weeks. 5000IU after. Option C: 50,000 IU 4-7 days, 5000 IU after. Option D: 5000 IU for 7 weeks.

Vitamin D Cofactors
List of Co-Factors Vitamin D Needs to Work Properly
Magnesium: Metabolism of Vitamin D Zinc: The base of the fingers of the Vitamin D Receptor each contains a zinc molecule Vitamin K2 (Vitamin K helps direct Vitamin D to calcify the proper organs and prevents calcification of improper organs), Boron (boron is involved in the rapid, non-genomic action of Vitamin D on the cell wall), Vitamin A.

The 80/20 - Eat Leafy Greens, grass-fed butter, and Seeds/Nuts. Reduce Grains.
Source: Dr. John Cannell http://www.vitamindcouncil.org/news-archive/2009/magnesium-and-vitamin-ds-co-factors/

TOXICITY IS ALMOST IMPOSSIBLE: The Merck Manual


**Reports 50,000 iu/daily for SEVERAL MONTHS can cause vitamin D toxicity...but that is ALOT! (= 4.5 MILLION IU's) Based on the research 1 loading dose of 100,000 - 300,000 IU dose and then a maintenance dose (4,000 - 10,000 IU/daily) is all that is required to be around 50ng/ml. (= 650,000 IU..just 14% of that)

NOWHERE NEAR THE TOXICITY LEVEL OF 200 ng/ml


source: http://www.merckmanuals.com/professional/nutritional_disorders/vitamin_deficiency_dependency_and_toxicity/vitamin_d.html?qt=&sc=&alt=

Vitamin D Toxicity: 80/20


Symptoms: Toxicity and OverdoseSigns of vitamin D toxicity are
high urine and blood calcium.
The first sign of vitamin D toxicity is hypercalcuria (excess calciumin the urine) followed by hypercalcemia (high blood calcium). The following symptoms may present:

nausea vomiting poor appetite constipation (possibly alternating with diarrhea) weakness weight loss tingling sensations in the mouth confusion heart rhythm abnormalities

The immediate symptoms of vitamin D overdose are: abdominal cramps nausea vomiting

100 ng/ml = upper limit 200-250ng/ml = toxicity threshold


(1,2,3,4,5)

1. Jones, G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr. 2008 Aug; 88 (2): 582S-586S. 2. Heaney, R. P. Vitamin D: criteria for safety and efficacy. Nutr Rev. 2008 Oct; 66 (10 Suppl 2): S178-81. 3. Vieth, R. Vitamin D toxicity, policy, and science. J Bone Miner Res. 2007 Dec; 22 Suppl 2V64-8. 4. Vieth, R. Critique of the considerations for establishing the tolerable upper intake level for vitamin D: critical need for revision upwards. J Nutr. 2006 Apr; 136 (4): 1117-22. 5. NIH Office of Dietary Supplements Dietary Supplement Fact Sheet: Vitamin D. 2009/11/13;

Vaccines vs. Vitamin D: A Cheaper Flu Shot?


Dosages of only 1200 iu/daily this study reduced Influenza A in a randomized, placebo controlled, double blind study by just under

50%!
Note: Half of the recommended dose for children! Doesn't account for actually normalizing levels.

Am J Clin Nutr. 2010 May;91(5):1255-60. Epub 2010 Mar 10

Cancer Prevention And Vitamin D: 60% Reduction?


4 year study, Nebraska, double blind, placebo controlled The unadjusted Relative Risk of (1500 mg Ca + 1100 IU D) vs. placebo = 0.402 (P = 0.01) If you take out cancers diagnosed in the first 12 months... the RR goes down to = 0.232 (CI: 0.09, 0.60; P < 0.005)
I Emailed Dr. Lappe, University of Creighton, to Clarify

http://www.ncbi.nlm.nih.gov/pubmed/17556697
Am J Clin Nutr. 2007 Jun;85(6):1586-91. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP.

Chronic Low Back Pain Is Not D-lightful


- 360 Patients of diverse ages over a 6 year period - Study

Vitamin D's effect with idiopathic low back pain

- Found 'Unusually Low' levels of vitamin D in 83% (n=299) - After Treatment = ALL the 'Low D level' Patient group's symptoms improved clinically. 95% of everyone else. - Study Concluded "Vitamin D deficiency is a major contributor to chronic low back pain in areas where vitamin D deficiency is endemic. Screening for vitamin D deficiency and treatment with supplements should be mandatory in this setting."
Al Faraj S, Al Mutairi K. Vitamin D deficiency and chronic low back pain in Saudi Arabia. Spine (Phila Pa 1976). 2003 Jan 15;28(2):177-9.

Pain Modulation, Inflammation and Vitamin D


Anti-inflammatory - Inhibits cyclooxygenase-2 (COX-2) = Non-Specific NSAIDS (Advil) - Study Found Inverse Relationship of COX-2 & PGE2 with VDR - Lowers CRP and IL-6, two measures of inflammation in the body
Anticancer Res. 2010 May;30(5):1673-9. Prostaglandin metabolising enzymes and PGE2 are inversely correlated with vitamin D receptor and 25(OH)2D3 in breast cancer

80/20 Take Home


- "95% of Americans are Deficient in Vitamin D - That's How Big the Problem is." - Dr. John Cannell, MD (Heads the Vitamin D Council)
- The Body Uses 3000-5000IU/daily = great maintenance dosage - Vitamin D Winter = Above Alabama = Taking Vitamin D Supplements - A loading dose appears to be a safe and effective way at rapidly increasing serum vitamin D levels. (100,000-300,000IU) - Top 5 Benefits: Bone, Immune, (Heart/Cancer/Diabetes), Autoimmune, Pain - About $60 to get a test done. Do it!

Want More Research and Information?


Dr. John Cannell and The Vitamin D Council Vitamin D Wiki Wikipedia - "Search Vitamin D" Vitamin d association or the good ole' fashioned 'PubMed.gov'

Thanks :)