Vitamin of the Decade

Friday April 17 2015

Vitamin of the Decade by Tara Loseth, R.Ph.

This is an in-depth article, containing both information and opinion. 

For basic advice on how much Vitamin D to take, go to http://www.pharmasaveladner.com/articles/vitamin-d

 

If the vitamin industry were to pick a poster boy for the 2010s it would definitely be Vitamin D.  There has been a lot of media attention on Vitamin D for the prevention of cancer and osteoporosis, as well as other stuff like S.A.D.  Doses seem to have soared over the past few years.  I’ve even received prescriptions for 40,000IU/day!  Everyone seems to be on the D bandwagon.  BUT… are we going overboard?  That is a tough question to answer.  Here are some questions that are easier to address:  What is the recommended dose?  What is the safe maximum dose?  What evidence is there for the various claims about Vitamin D?  The answers seem to be constantly changing.  This article will give an overview of Vitamin D, and the most current evidence and guidelines for its use.

 

The Basics

Vitamin D is a fat-soluble hormone.  It’s essential for many processes in the body, two of which are building bone and maintaining a healthy immune system.  When our skin is exposed to sunlight, precursors are converted into active Vitamin D.  If I wasn’t such a hater of superfluous quotation marks, I would call it “Vitamin” D.  It doesn’t fit the basic criteria to be a Vitamin since we are not fully dependent on ingestion in order to acquire it.  Many people can manufacture enough D from 10-30 minutes of sun exposure a few times a week; however, production varies a lot person-to-person.  Latitude and colour of skin make a big difference.  We have no evidence that allows us to recommend a certain amount of sun exposure that will both:  a) give a person enough D, and b) not increase their skin cancer risk.  For this reason, dietary supplementation is the current solution.

 

Deficiency

Low levels of D have been associated with increased CV mortality, colon cancer mortality and breast cancer risk and have been tentatively linked to skin cancer, metabolic disease, hypertension and obesity1.  People with inadequate vitamin D are more susceptible to upper respiratory tract infections and other microbe-borne infections2.  Vitamin D deficiency is associated with rickets in children, and osteoporosis in adults3.  Vitamin D is required in order for Calcium to do its job in the bones.

 

Overdose 

Too much Vitamin D causes hypercalcemia.  The main symptoms of Vitamin D overdose are those of hypercalcemia:  anorexia, nausea, and vomiting can occur, frequently followed by polyuria, polydipsia, weakness, insomnia, nervousness, pruritus and, ultimately, renal failure.  Proteinuria, urinary casts, azotemia, and metastatic calcification may develop.4  Maternal hypercalcemia during pregnancy may lead to mental retardation and facial deformities.5,6  Pregnant or breastfeeding women should consult a doctor before taking a Vitamin D supplement.6  Exposure to sunlight for extended periods of time does not normally cause Vitamin D toxicity.5  Within about 20 minutes of UV exposure in light-skinned people (3-6 X longer for pigmented skin), the concentrations of Vitamin D precursors produced in the skin reach an equilibrium, and any new D produced is degraded.8

 

So how much is too much? 

In healthy adults, sustained intake of more than 1250mcg/day (50,000 IU) can produce overt toxicity after several months4.  Toxicity has been produced in infants taking 40,000IU/day within one month.4  This year, after being commissioned by the Canadian and American governments, the Institute of Medicine and Health Canada have increased the tolerable upper limits.7  (see chart)

 

Daily Recommended Intake 

Health Canada stuck to their old recommendations for quite a while, despite higher doses becoming popular for specific conditions.  In 2007 they stated that more information was required on the safety of higher doses before they would change their recommendation.9  Just this year, Health Canada did come out with new recommendations (see chart).10

 

D Doses for other purposes

D is proven to prevent osteomalacia and rickets, but evidence for other health effects in the general population is inconsistent.23

 

Cancer:  Since June, 2007, the Canadian Cancer Society has recommendations that adults living in Canada take Vitamin D 1000IU/day, during fall and winter months (year round for those with high risk), to help reduce risk for colorectal, breast and prostate cancers.    They are sticking to this recommendation, despite the fact that they don’t match up with Health Canada’s recommendations.  Considering that 1000IU/day is well within the tolerable upper limit, risk is low.  However, level of evidence for cancer prevention is also low.  Evidence is insufficient to say for sure whether it prevents cancer (or causes other types of cancer!), and it appears not to help with prostate cancer.13

 

Osteoporosis:  Osteoporosis Canada goes even higher than the Canadian Cancer Society. The following is an excerpt from their guidelines, first published in 2010.

To most consistently improve clinical outcomes such as fracture risk, an optimal serum level of 25-hydroxyvitamin D is probably above 75 nmol/L; for most Canadians, supplementation is needed to achieve this level. 

The recommended vitamin D intake is 10–25 μg (400–1000 IU) daily for low-risk adults under 50 years of age and 20–50 μg (800–2000 IU) for high-risk and older adults, with potential for consideration of higher doses.  Doses up to 50 μg (2000 IU) are safe and do not require monitoring, but if higher doses are sometimes needed, monitoring is appropriate.13

 

I talked to a dietitian who was involved in Osteoporosis trials in the early 2000s and now works at the B.C. Dietitian Hotline.  She says several trials found benefit with 10,000IU/day dosing.  However, I don’t think they addressed long-term safety of this dose.

 

Other:  Vitamin D is being touted for many other conditions.  Of note is a trial that began in 2011 to see if it helps prevent MS.  There is theoretical reason to suspect it does, but proof is pending.20,21

The U.S. Endocrine Society states that “evidence that treatment prevents cardiovascular disease, lowers mortality, or generally improves quality of life is lacking.”13

If you wish to learn about other possible benefits of Vitamin D, I highly recommend checking out www.rxfiles.ca (subscription is required).   Look at the “Vitamin D Trial Summary Chart” and also page 2 of “Vitamin D Overview Q&A”.   It’s from 2010 (so some new trials are missing, and the daily dose recommendations on page 1 are out of date) but the rest is still good info. 

 

Weekly dosing of D3?

I called the B.C. Dietitian hotline in 2010 to discuss safety and efficacy of once-weekly, 10,000IU D3 dosing.  There exists good evidence that high doses of D2 at less frequent intervals still raises serum D levels.  Although the evidence is lacking for D3, if it works for D2 it should work for D3.  I was at least able to establish the safety of weekly dosing, if not its efficacy.

 

Types of D supplements:

Vitamin D3 (cholecalciferol), is the most common form of supplementation, and is the same form our body makes.

Vitamin D2 (ergocalciferol - eg.Osto-D2®) is made by phytoplankton, invertebrates, yeasts, and some fungi including mushrooms.  D2 should have the same conversion in the human body as D3.22  However, I have read that some controversy exists over whether or not D2 can fully substitute for D3 in the human diet.11 

Another Vitamin D analogue you will be familiar with is One-Alpha® (alfacalcidol).  It has a longer half-life and does not need to be converted in the kidneys like D2 or D3 do.  It is indicated for the management of hypocalcemia, 20 hyperparathyroidism, and osteodystrophy in patients with chronic renal failure.12 

Rocaltrol® (calcitriol) is another analogue.  It does not require conversion by the kidneys or by the liver, and thus can be used in some patients who would not get benefit from the other forms of D.  Rocaltrol® has a similar list of indications to that of One-AlphaR, with a few additions.12

 

Does this all seem a little familiar?  Taras perspective: learning from the history of Vitamin E

Some of you (older) pharmacists may recall the Vitamin E rage in the late ‘90s and early ‘00s.  Some of you (really old) pharmacists may recall that vitamin E deficiency used to be a cause of haemolytic anemia in infants.  Since the ‘60s, infant formula has contained Vitamin E which solved this.16

The medical community was not satisfied with merely preventing deficiency however.  Vitamin E was looked at for cancer prevention and a bunch of other stuff.  I recall a time when patients, especially those

with cardiovascular risk factors, were encouraged to take thousands of units per day. 

It made so much theoretical sense!  Consider:  blood vessel plaques are formed because high blood pressure forces cholesterol into the side wall of the blood vessel, where it is attacked by macrophages, resulting in a big, foamy oxidized mess.  These blobs of plaque encourage blood clots, leading to strokes and heart attacks.  Sooo… giving vitamin E made sense right?  Reducing oxidation should reduce clots… right?  Why wait for studies to be done if the benefit was so obvious?  So we thought. 

After years of encouraging higher doses, it was discovered that any more than 400IU/day of Vitamin E probably increases cardiovascular mortality.  Participants in the HOPE study were 13% more likely to experience, and 21% more likely to be hospitalized for, heart failure, a statistically significant and unexpected finding not previously reported.16  Vitamin E does not decrease mortality in adults, even at large doses17, and may slightly increase it.18,19   

Huh.  How ‘bout that.  What we now are guessing is that Vitamin E is reducing the amount of oxidized LDL in the bloodstream, but that this is actually down-regulating the expression of beneficial scavenger genes.

This is a great example of why evidence is so important.  It’s human nature to get excited about the possibilities.  Maybe we can prevent cancer, or cure disease!  This enthusiasm has led to many medical breakthroughs.  It’s also human nature to forget that we are still (often) wrong.  This is where careful study comes in, which requires diligence and patience.  Unfortunately, these days the Media distributes new ideas widely and quickly, before long-trials can be completed. 

 

Conclusion

Vitamin D dose recommendations have increased over the past few years.  Health Canada has upped the recommended intake and the tolerable upper limit; however, these numbers are still low when compared with recommendations from other sources for specific conditions.  While some evidence exists for high doses of Vitamin D for some conditions - for example Osteoporosis - in most cases more study is required in order to be sure.  Long-term safety data of high doses is also lacking.  Could D supplementation prevent certain cancers, or boost the immune system, or prevent MS?  Quite possibly.  Could D supplementation cause some types of cancer, or cause other problems, as yet unknown, in the long run?  Quite possibly.  Perhaps we should learn from our past mistakes with Vitamin E, and exercise a bit of caution when recommending giant doses.

 

References

1. Zittermann A, Gummert, JF, Börgermann, J (Nov 2009). "Vitamin D deficiency and mortality". Current opinion in clinical nutrition and metabolic care 12 (6): 634–9. DOI:10.1097/MCO.0b013e3283310767. PMID 19710612

2.Ginde 2009

3.Papandreou 2012

4.Merck Manual of Diagnosis and Therapy, Professional Edition.

5.(PDF) Tolerable Upper Intake Limits for Vitamins And Minerals. European Food Safety Authority. December 2006. ISBN 92-9199-014-0.

6.Vieth R (May 1999). "Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety". The American Journal of Clinical Nutrition 69 (5): 842–56. PMID 10232622.

7.Ross, AC; Manson, JE; Abrams, SA; Aloia ,JF; Brannon, PM; Clinton, SK; Durazo-Arvizu, RA; Gallagher, JC; Gallo, RL; Jones, G; Kovacs, CS; Mayne, ST; Rosen, CJ; Shapses, SA (January 2011). “The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know”.  Journal of Clinical Endocrinology & Metabolism 96 (1): 53-8. DOI:10.1210/jc.2010-2704.

8.Holick, MF (March 1995). “Environmental factors that influence the cutaneous production of vitamin D” The American Journal of Clinical Nutrition 61 (3 Suppl): 638S-645S. PMID 7879731 http://www.acgn.org/content/61/3/638S.full.pdf

9.June 2007 www.pharmacyconnects.com

10.Health Canada website: Vitamin D and Calcium: Updated Dietary Reference Intakes. http://www.hc-sc.gc.ca/fn-an/nutrition/vitamin/vita-d-eng.php

11.Houghton LA; Vieth R (October 2006).”The case against ergocalciferol (vitamin D2) as a vitamin supplement” The American Journal of Clinical Nutrition 84 (4): 694-7. PMID 17023693.

12.e-CPS 2012.

13.http://www.ecmaj.ca/content/182/12/E610.short  CMAJ September 7, 2010 vol. 182 no. 12 First published July 12, 2010, doi: 10.1503/cmaj.080663

14.Journal Watch General Medicine June 23, 2011.  Hollick MF et al. Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline.  J Clin Endocrinol Metab 2011 June 6; [Medline Abstract]

15.bell, EF (1987). “History of vitamin E in infant nutrition”. American Journal of Clinical Nutrition 46 (1 Suppl): 183-186. PMID 3300257

16.Lonn E, Bosch J, Yusuf S, Sheridan P, pogue J, Arnold JM, et al.; HOPE and HOPE_TOO Trial Investigators.  Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial.  JAMA 2005; 293:1338-47. [PubMed abstract]

17.Abner, EL; Schmitt, FA, Mendiondo, MS, Marcum, JL, Kryscio, RJ (July 2011). “Vitamin E and all-cause mortality: a meta-analysis”.  Current aging science 4 (2): 158-70. PMID 21235492.

18.Miller, Er, 3.; Pastor-Barriuso, R.; Dalal, D.; Riemersma, R.A.; Appel, L.J.; Guallar, E. (2005). “Meta-analysis: High-dosage vitamin E supplementation may increase all-cause mortality”. Annals of internal medicine 142 (1): 37-46.

19.Bjelakovic, G; Nikolova, D; Gluud, LL; Simonetti, RG; Gluud, c (16 April 2008).  Bjelakovic, Goran. ed. “Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases”.  Cochrane database of systematic reviews (Online) (2): CD007176.  DOI:10.1002/14651858.CD007176. PMID 18425980

20.ClinicalTrials.gov NCT01440062 Efficacy of Vitamin D Supplementation in Multiple Sclerosis (EVIDIMS)

21.Dorr J; Ohlraun S; Skarabis H; Paul F (2012) “Efficacy of vitamin D supplementation in multiple sclerosis (EVIDIMS Trial): study protocol for a randomized controlled trial”.  Trials 13 (1): 15. DOI:10.1186/1745-6215-13-15. PMC 3298796. PMID 22316314. Htt;://www.trialsjournal.com/content/13/1/15

22.Holick, MF; Biancuzzo, RM; Chen, TC; Klein, EK; Young, A; Bibuld, D; Reitz, R; Salameh, W; Ameri, A; Tannenbaum, AD (2007).”Vitamin D2 is as Effective as Vitamin D3 in Maintaining Circulating Concentrations of 25-Hydroxyvitamin D”. Journal of clinical Endocrinology & Metabolism 93 (3):677-681. DOI:10.1210/jc.2007-2308. PMC 2266966. PMID 18089691.

23. Pittas AG, Chung, M, Trikalinos, T, Mitri, J, Brendel, M, Patel, K, Lichtenstein, AH, Lau, J, Balk, EM (Mar 2010). "Vitamin D and Cardiometabolic Outcomes: A Systematic Review". Annals of internal medicine 152 (5): 307–14. DOI:10.1059/0003-4819-152-5-201003020-00009. PMC 3211092. PMID 20194237.



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