Monday, June 21, 2010

Vitamin D myths and management-Robert Carlson,MD

THE MANY VITAMIN D MYTHS

Patient EB is a 50-year-old female with a family history of colon cancer and breast cancer as well as a history of arthritis with probable autoimmune etiology. She takes a daily multivitamin which includes 10,000 units of Vitamin A as well as a separate 1000 IU of Vitamin D3 and her 25-(OH) Vitamin D3 level is 36 ng/mL (reference range 33-100 ng/mL). Should EB increase her dose of Vitamin D3? Should she continue her multi-vitamin?
There are so many myths surrounding Vitamin D. First and foremost, is the myth that Vitamin D is
a Vitamin. Vitamin D is not a Vitamin, it is actually a steroid hormone. Vitamin D is produced in one part of the body (the skin), and then travels to a remote site, where it exerts an endocrine effect. Thus, it fulfills the definition of a hormone. Another Vitamin D myth is that its only function is calcium regulation. That idea has been well and truly debunked in recent years. Then there is the idea that 1000 IUs a day is more than enough, which is simply not true. Also many believe that taking over 2000 units a day might cause toxicities. I hear this from numerous health professionals and even from pharmacists who should know better. The literature is very clear…..evidence from clinical trials shows that a prolonged intake of 10,000 units of Vitamin D per day poses no risk of adverse effects for adults 1 ……therefore one can take 10,000 units a day and have no risk for toxicity.

Other myths of interest include:
1) Most people living in the US get adequate amounts of Vitamin D – not true (see below).
2) Extreme care must be taken to avoid toxicity – not true! There have been numerous
studies on Vitamin D toxicity and no toxicity has been seen in doses lower than 30,000
IU/day (200 ng/mL). An excess of Vitamin D causes hypercalcemia, however all known
cases of Vitamin D toxicity with hypercalcemia have involved intakes of 40,000 IU or more
per day.2
3) Spending 15 minutes in the sun each day enables the body to produce ample amounts of
Vitamin D – that may be true if you are sitting on a beach in Hawaii at noon wearing
nothing but a bikini, but for the vast majority of us that is a myth. Unfortunately, once sunscreen is applied the Vitamin D production drops to nothing. If you live above 35 degrees latitude, the body is unable to produce adequate amounts of Vitamin D from the winter sun. In fact the only adequate amount of sunshine in Boston occurs, between May and Sept, otherwise there is inadequate sunlight for Vitamin D metabolism.
4) Eating a balanced diet will provide adequate amounts of Vitamin D – not true! Vitamin D is present, in small amounts, in only a handful of foods – oily fish, eggs, and fortified
foods. Vitamin D fortified Milk and Orange Juice only contain 50 Units of Vitamin D2, not Vitamin D3. Thus it is very unlikely that adequate amounts could be obtained from the diet.
• Vitamin D does not prevent cancer – it does , in fact one study showed the reduction in all cancers by 77 % over a four year period in a well designed study.(see below).
• Vitamin D does not prevent autoimmune disease – it does , reducing Systemic Lupus ,Rheumatoid Arthritis and Childhood onset diabetes(see below).
• Vitamin D does not prevent acute MI and heart disease – it does (see below).
As mentioned above, the notion that most people living in the US get adequate amounts of
Vitamin D is far from true. Research has shown that Vitamin D deficiency is present among all age groups of US citizens from children to the elderly, and especially in African-Americans.3 Studies have shown that the prevalence of low 25-(OH) D levels (<20 ng/mL) is approximately 36% in young adults aged 18-294 ,42% of African-American women aged 15-495 ,41% of outpatients aged 49-83,6 and 57% of inpatients.7
In Europe, it is believed that between 28 and 100% of healthy adults and 70-100% of hospitalized adults have low 25-(OH) D levels (<20 ng/mL).8,9,10
A study we completed examining women age 35-65 in Tampa, Florida in December, demonstrated that 92 % of the women had 25-(OH) D levels less than the low normal range of 32. Can you imagine what the Vitamin D levels are in the same group of women in Minneapolis, Minnesota in December?
Research has shown that the incidence of many diseases could be dramatically reduced by
increasing serum 25-(OH) D levels, and by looking at the list below, it is easy to see why Vitamin D has become a very hot topic in recent years:
1) Increasing serum 25-(OH) D levels to 35 ng/mL could prevent 30% of MI in men11 and
reduce the risk of fracture in elderly people by 50%.12
2) Increasing serum 25-(OH) D levels to approximately 40 ng/mL could reduce the risk of
cancer in postmenopausal women by 35%13 and reduce the risk of falls in elderly people
by 50%. 14
3) Increasing serum 25-(OH) D levels to 50 ng/mL could reduce the incidence of breast
cancer by as much as 80%,15 multiple sclerosis by as much as 60%,16 and type I
diabetes by up to 50%.17
Why is Vitamin D so beneficial? There is no clear answer at present. However, anything that has
such wide-ranging benefits has to possess the ability to modulate inflammation. Indeed, studies have shown that Vitamin D inhibits nuclear factor-κβ (NF-κβ) 18 – a protein that plays a key role in the inflammatory response and in the proliferation of cancer cells. It has also been shown to lower levels of the inflammatory marker CRP.19 Thus, it is vital that we ensure our patients are getting plenty of Vitamin D.
What about Patient EB, does she need to increase her daily dose of Vitamin D3? Yes. The
reference range for 25-(OH) D is 32-100 ng/mL Given the evidence published in the medical literature over the last few years, it is advisable to try and keep patients at the top end of the reference range – so, we should be aiming for 75-100 ng/mL The optimal dose for an average person is 5000-15,000 IU/day; however this should be lowered for people who get a lot of sun exposure. Ideally check Vitamin D leveIs and regularly check serum calcium in patients who take supplementary Vitamin D, just to ensure there is no risk of hypercalcemia.
So what about her multi-Vitamin choice? Some multi-Vitamins may be doing more harm than good. I recommend avoiding excessive amount of pre-formed Vitamin A in the retinol form, as opposed to the beta-carotene form that converts to Vitamin A in your body. The presence of excessive pre-formed actually will neutralize all the amazing benefits of Vitamin D3.20 Unfortunately, multi-vitamins often continue a lot of Vitamin A(average 4400 units) as retinol and very low levels of D3( average 400). Vitamin A and Vitamin D receptors are very close to each other and excess Vitamin A will block the beneficial effects of Vitamin D. Women who took the highest intake of pre-formed Vitamin A actually had twice as many hip fractures. 21 So keep the non- beta carotene Vitamin A supplements to less than 1000 units, and this will allow all the amazing benefits of Vitamin D3.

CONCLUDING REMARKS
There are many myths surrounding hormone replacement therapies, however from the evidence
presented above, we can see that not one of them is true. Hormone optimization provides us with an extremely powerful anti-aging tool to maximize quality of life.
REFERENCES
1. Vieth R. Vitamin D and Cancer Mini-Symposium: the risk of additional Vitamin D. Ann Epidemiol. 2009; 19(7):441-5.
2. Vieth R. Vitamin D supplementation, 25-hydroxyVitamin D concentration, and safety. Am J Clin Nutr. 1999;69:842-56.
3. Holick MF. High prevalence of Vitamin D inadequacy and implications for health. Mayo Clin Proc.
2006;81:353-373.
4. Tangpricha V, Pearce EN, Chen TC, Holick MF. Vitamin D insufficiency among free-living healthy young
adults. Am J Med. 2002;112:659-662.
5. Nesby-O'Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis BW, Looker AC, Allen C, Doughertly C,
Gunter EW, Bowman BA. HypoVitaminosis D prevalence and determinants among African American and
336 white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994. Am
J Clin Nutr. 2002;76:187-192.
6. Malabanan A, Veronikis IE, Holick MF. Redefining Vitamin D insufficiency [letter]. Lancet. 1998;351:805-
806.
7. Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM,
Prince RL, Finkelstein JS. HypoVitaminosis D in medical inpatients. N Engl J Med. 1998;338:777-783.
8 . McKenna MJ. Differences in Vitamin D status between countries in young adults and the elderly. Am J
Med. 1992;93:69-77.
9. Isaia G, Giorgino R, Rini GB, Bevilacqua M, Maugeri D, Adami S. Prevalence of hypoVitaminosis D in
elderly women in Italy: clinical consequences and risk factors. Osteoporos Int. 2003;14:577-582.
10. Passeri G, Pini G, Troiano L, Vescovini R, Sansoni P, Passeri M, Gueresi P, Delsignore R, Pedrazzoni M,
Franceschi C. Low Vitamin D status, high bone turnover, and bone fractures in centenarians. J Clin
Endocrinol Metab. 2003;88:5109-5115.
11. Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-hydroxyVitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med. 2008;168:1174-80.
12. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture
prevention with Vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA.
2005;293:2257-2264.
13. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium
supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007;85:1586-1591.
14. Broe KE, Chen TC, Weinberg J, Bischoff-Ferrari HA, Holick MF, Kiel DP. A higher dose of Vitamin d
reduces the risk of falls in nursing home residents: a randomized, multiple-dose study. J Am Geriatr Soc.
2007;55:234-239.
15. Garland CF, Gorham ED, Mohr SB, Grant WB, Garland FC. Breast cancer risk according to serum s5-
hydroxyVitamin D: Meta-analysis of dose-response. Presented at: American Association for Cancer
Research Annual Meeting; April 12-16, 2008; San Diego, California.

16. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyVitamin D levels and risk of
multiple sclerosis. JAMA. 2006;296:2832-2838.
17. Hyppönen E, Läärä E, Reunanen A, Järvelin MR, Virtanen SM. Intake of Vitamin D and risk of type 1
diabetes: a birth-cohort study. Lancet. 2001;358:1500-1503.
18. Szeto FL, Sun J, Kong J, Duan Y, Liao A, Madara JL, Li YC. Involvement of the Vitamin D receptor in the
regulation of NF-kappaB activity in fibroblasts. J Steroid Biochem Mol Biol. 2007;103:563-566.
19. Boxer RS, Dauser DA, Walsh SJ, Hager WD, Kenny AM. The association between Vitamin D and
inflammation with the 6-minute walk and frailty in patients with heart failure. J Am Geriatr Soc.
2008;56:454-461.
20. Melhus H, Michaëlsson K, Kindmark A, Bergström R,. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Annals of Internal Medicine, 1998;129(10):770-8.
21. Johansson S, Melhus H. Vitamin A antagonizes calcium response to vitamin D in man. J Bone Mineral Res. 2001;16(10):1899-905.




Robert G Carlson, MD, FACS

Prostate Cancer and Men Robert G Carlson, MD

Prostate Cancer Myth:
Testosterone therapy causes prostate cancer
Absolutely not, in fact lower testosterone levels are associated with an increased incidence of Prostate cancer.
For over 60 years there has been an overwhelming fear that testosterone therapy for low testosterone levels will cause new cancers or hidden ones to grow. There is very little scientific data to support that philosophy but even in the face of numerous recent studies saying there is NO association, doctors are still telling their patients that testosterone therapy causes prostate cancer. Instead the opposite is true. Low blood levels of testosterone don’t protect against prostate cancer, but in fact lower testosterone levels are associated with increased incidence of prostate cancer.
A Journal of National Cancer Institute article in 2008, pooled 18 separate studies looking at the effect of testosterone therapy and prostate cancer. In over 9000 men studied, there was no relationship between testosterone therapy and Prostate cancer. NONE. The authors pleaded with the medical community to move past the long-believed, but unsupported view that testosterone therapy causes prostate cancer. IT DOES NOT CAUSE PROSTATE CANCER.
To summarize:
1) Low testosterone levels do not protect against prostate cancer, and in fact are associated with a higher incidence of prostate cancer.
2) High testosterone levels in men are not associated with an increased incidence of prostate cancer.
3) Treatment with testosterone therapy does not increase the incidence of prostate cancer, even in the men who are presumably at a higher risk.
4) If a man has metastatic prostate cancer (spread all over) and has been aggressively treated to lower testosterone levels, then careful management with testosterone therapy is recommended.
5) By restoring Testosterone levels to healthy levels, aging men should expect higher energy levels, memory improvement, improvement of depression, reduction of osteoporosis, and improvement in erectile dysfunction.
Robert G Carlson, MD, FACS