Advisory regarding the risk of Zika and other diseases in Rio de Janeiro and means of protection, for August and September 2016. Alan Roth, Ph.D. July 15, 2016

Aedes aegypti/CDC

SOME ADVISORIES HAVE MISINFORMED THE PUBLIC

The World Health Organization (WHO), on June 14, 2016, observed that “the Games will take place during Brazil’s wintertime, when there are fewer active mosquitoes and the risk of being bitten is lower.”1 While this is true in general, during some winters the real numbers show that the risk can be higher.

Brazil’s new Health Minister, Ricardo Barros said, “there’s practically “zero” risk of any of the 350,000-500,000 expected foreign visitors contracting Zika.” Barros said mosquito populations drop significantly in

August, a winter month in the Southern Hemisphere, and cited data showing that infections of dengue — another virus spread by the same mosquito — tend to spike in the hot summer month and taper off in the winter.2

The Mayor of the City of Rio de Janeiro (Rio), Eduardo Paes, was quoted, "At this time of the year, in August, when the Olympics are going on, there are no cases of dengue or Zika because of the weather…" Yet, the government says there will be more ambulances, extra health professionals and at least 3,000 people working on anti-Zika campaigns in the city.3 Why do this if there are no cases?

The U.S. Centers for Disease Control and Prevention (CDC) has been silent regarding the risk level of Zika and dengue in Rio specifically for the period of August and September 2016 although they have several web pages devoted to travel to Rio for the Games. They state, “The presence of mosquitoes may change seasonally, with increasing temperatures or rainfall, and may change over time.” This may lead people to more readily believe the statements of Paes and the WHO. At least the CDC is saying, “The Zika outbreak in Brazil is dynamic. CDC will continue to monitor the situation and will adjust these recommendations as needed.”4 It’s now less than 3 weeks until the Games start.

Real Weather Data

The weather in Rio 2+ weeks before the Games is very warm with a high of 91o.5 The highs cool down to the low 70os the following week and then rise to the high 70os the week after. The long range forecast for early August is showing the average daily highs and lows for that period (78o and 66o). The average rainfall for the month of August is 2 inches. In September, for the Paralympic Games, the daily temperature averages are 77o and 67o with rainfall for the month averaging 3.4 inches.6 During periods of drought similar to the drought of 2015, the people store more water in open water tanks which provide more breeding opportunity for mosquitoes.7

Well, how bad could it be? Infections of dengue have been more numerous in August in some years than during the normally peak months of March, April and May. In 2014, the August peak of dengue infections was greater than March, April and May combined! Weather conditions vary. It could be cool and dry in August but Rio de Janeiro is closer to the equator than Miami and historical data show that rainfall and warm weather are common that month. Last year there were numerous August days when the high temperature was in the 90os while most days were in the high

1 WHO Statement, May 12, 2016, “Zika virus and the Olympic and Paralympic Games Rio 2016,” http://www.who.int/mediacentre/news/statements/2016/zika-olympics/en 2 Associated Press, “Brazil health minister says Zika not a worry for Olympics,” June 10, 2016 http://bigstory.ap.org/article/be13502a40c342709289d1f193bfb476/brazil-health-minister-says-zika-not-worry-olympics 3 Davies, Wyre, “Rio Olympics Zika: The trouble with Aedes Aegypti,” BBC, 14 June 2016, http://www.bbc.com/news/world-latin-america-36516209 4 Centers for Disease Control and Prevention, “CDC issues advice for travel to the 2016 Summer Olympic Games,” February 26, 2016 http://www.cdc.gov/media/releases/2016/s0226-summer-olympic-games.html 5 Temperature is given in Fahrenheit. 6 Weather.com, “Rio de Janeiro, Brazil Weather,” 10 Day Forecast, https://weather.com/weather/tenday/l/BRXX0201:1:BR 7 Berdjis, Noushin, “Dengue Epidemic in Brazil”, The Disease Daily, May 13, 2015 http://www.healthmap.org/site/diseasedaily/article/dengue-epidemic-brazil-51315

CONTENTS

SOME ADVISORIES HAVE MISINFORMED THE PUBLIC

Real Weather Data

Zika Symptoms

Chikungunya, Yellow Fever and Malaria

Dengue Fever is a Major Threat in Rio

VARIOUS MEANS OF PROTECTION

Steps to Prevent Mosquito Bites

An Option for Further Protection

A Focus on Vitamin D

The Risk of Taking Too Much

Vitamin D in Athletics

Sources of Vitamin D

80os. A small number of nights were in the 50os with most in the low 60os.8 For the Paralympic Games in September, the risk of mosquito bites, and therefore Zika, can still be high. This year, Zika may not be of epidemic proportion in August and September but it is better to prepare for the worst and hope for the best.

Zika Symptoms

Aside from pregnancy issues with Zika that have received a lot of media attention, there are a number of other risks that cause concern. The Centers for Disease Control and Prevention in Atlanta warn, “the most common symptoms of Zika are fever, rash, joint pain, and conjunctivitis (red eyes).” The illness is usually mild with symptoms lasting for several days to a week.9 Athletes contracting the disease could be unable to compete during the most severe days of sickness, depending on the specific symptoms. Once bitten, a person may go more than a week before symptoms are felt.

Also, Zika appears to trigger Guillain-Barré Syndrome (GBS) although this is rare. The CDC is studying the link between Zika and GBS. The common symptoms of GBS are muscle weakness, and sometimes, paralysis which can last from a few weeks to several months. It can occur days to weeks after the victim’s Zika sickness has ended.10

Chikungunya, Yellow Fever and Malaria

The Chikungunya virus has only been present in Brazil for a couple of years. It is carried by the same Aedes species mosquitoes as Zika and Dengue. It is very unlikely that it will be present in most of Brazil including the State of Rio de Janeiro in August.11 12

Yellow Fever virus, carried by the same Aedes species of mosquitoes, is common in most of Brazil but not in a narrow strip of territory along the Atlantic coast that includes the State of Rio de Janeiro. For those planning inland travel, a vaccination is advised. Malaria is not found anywhere near Rio de Janeiro. It is mostly in the watershed of the Amazon River. The federal capital city Brazilia and its surrounding State are also clear of malaria.13

Dengue Fever is a Major Threat in Rio

According to the CDC, Dengue “is a leading cause of illness and death in the tropics and subtropics. As many as 400 million people are infected yearly.” Like Zika, there are no vaccines for it even though its presence in many countries started to be encountered as long ago as the 1950’s.14

The CDC explains, “the principal symptoms of dengue fever are high fever, severe headache, severe pain behind the eyes, joint pain, muscle and bone pain, rash, and mild bleeding (e.g., nose or gums bleed, easy bruising).”15 Visitors to Rio de Janeiro should also be concerned about dengue due to these very severe symptoms and the prevalence of this disease.

People who have had dengue may be more vulnerable to enhanced Zika infection. Laboratory tests have shown the Zika virus can be enhanced by as much as one-hundred fold when there are dengue antibodies present. That this could happen in a human body has not yet been shown but people who have had dengue should be more cautious about being infected by the Zika virus.16

Various Means of Protection

The State of Rio de Janeiro (RJ) will be working to keep the mosquito population to a minimum. However, the Olympic and Paralympic Games extend over many weeks and use many venues, complicating the task, while RJ has been struggling to provide necessary support. The BFG at the end of June has given RJ, which is managing the Games, $850 million of additional funding to help cover the extra cost of services.

8 Weatherspark.com “Historical Weather For The Last Twelve Months in Rio de Janeiro, Brazil,” https://weatherspark.com/history/33372/2016/Rio-de-Janeiro-Brazil 9 CDC, “About Zika,” http://www.cdc.gov/zika/about 10 CDC, “Zika and Guillain-Barré Syndrome,” http://www.cdc.gov/zika/about/gbs-qa.html 11 Faria, Nuno Rodrigues, José Lourenço, et al, “Epidemiology of Chikungunya Virus in Bahia, Brazil, 2014-2015,” PLOS, CURRENT OUTBREAKS, February 1, 2016, http://currents.plos.org/outbreaks/article/epidemiology-of-chikungunya-virus-in-bahia-brazil-2014-2015. 12 Chow, Catherine, Serena Fuller, et al, “CDC Responds to the Spread of Chikungunya in the Americas, CDC, Updates from the Field, Spring 2014, Issue 14, p. 3. http://www.cdc.gov/globalhealth/healthprotection/fieldupdates/pdf/dghp-field-updates-2014-spring.pdf#page=7 13 Gershman, Mark D., Emily S. Jentes, et al, “Yellow Fever & Malaria Information, by Country,” CDC, Travelers' Health, Chapter 3, Infectious Diseases Related to Travel, accessed July 13, 2016, https://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/yellow-fever-malaria-information-by-country/brazil 14 CDC, Dengue, accessed July 13, 2016, http://www.cdc.gov/dengue 15 CDC, Dengue, Frequently Asked Questions, “What is dengue?”, http://www.cdc.gov/dengue/faqfacts/index.html 16 Racaniello, Vincent, “Antibodies to dengue virus enhance infection by Zika virus,” virology blog, http://www.virology.ws/2016/04/27/antibodies-to-dengue-virus-enhance-infection-by-zika-virus

Steps to Prevent Mosquito Bites (from the CDC17)

“When in areas with Zika and other diseases spread by mosquitoes, take the following steps [PDF - 2 pages]:

Wear long-sleeved shirts and long pants.

Stay in places with air conditioning and window and door screens to keep mosquitoes outside.

Take steps to control mosquitoes inside and outside your home.

Sleep under a mosquito bed net if you are overseas or outside and are not able to protect yourself from mosquito bites.

Use Environmental Protection Agency (EPA)-registered insect repellents with one of the following active ingredients: DEET, picaridin, IR3535, oil of lemon eucalyptus, or para-menthane-diol. Choosing an EPA-registered repellent ensures the EPA has evaluated the product for effectiveness. When used as directed, EPA-registered insect repellents are proven safe and effective, even for pregnant and breast-feeding women.

o Always follow the product label instructions. o Reapply insect repellent as directed. o Do not spray repellent on the skin under clothing. o If you are also using sunscreen, apply sunscreen before applying insect repellent.

Treat clothing and gear with permethrin or purchase permethrin-treated items. o Treated clothing remains protective after multiple washings. See product information to learn how

long the protection will last. o If treating items yourself, follow the product instructions carefully. o Do NOT use permethrin products directly on skin. They are intended to treat clothing.”

(Note: The CDC has more about Zika protection on their website (listed above)

An Option for Further Protection

Both the U.S. and Brazilian federal governments, along with WHO, are silent about other means of protection which may be found in the complementary and alternative medical marketplace. One important reason for this is that most products in this marketplace have not been approved by the Federal Drug Administration as drugs so they cannot be sold for healing or protective benefit and cannot be promoted as such for sales. Many of these are considered by the FDA to be natural, micro-nutrients with limited application.

A Focus on Vitamin D

The focus here will be on vitamin D which has a recommended daily intake (RDI) issued in November, 2010 by the Institute of Medicine (now and since July 1, 2016 known as the Health and Medicine Division of the National Academies of Sciences, Engineering, and Medicine) of 600 IU per day for people of ages 1 to 70 specifically for bone health.18 Vitamin D has a long history and has been extensively studied and reported on in many peer-reviewed medical journals. Paragraphs below contain technical language that may be difficult for some readers to understand. You are urged to share this advisory with your doctor.

Thousands of epidemiological studies have long shown that people who are deficient in vitamin D suffer from more diseases than those who are sufficient. While this might be enough to encourage people to raise their vitamin D levels sufficiently, doctors are generally conservative and want to see a cause and effect relationship that is obtained by randomized controlled trials (RCTs). These are difficult and expensive to do but slowly more and more are being done on vitamin D.19

There have now been enough RCTs related to vitamin D and viruses to show that vitamin D has a role to play in protecting people from some viruses. A lot of work has also been done to understand the minutiae of how vitamin D works at the cellular level to attack viruses. It is not the vitamin D itself that does the work but rather metabolites that the body produces using vitamin D as the raw material. Larger studies are needed and more viruses need to be studied.20

While Zika is too new of a threat to have had any significant studies done, case studies and laboratory work have shown that vitamin D can be at least partially effective against the dengue virus. Both Zika and dengue are of the

17 http://www.cdc.gov/zika/prevention/index.html 18 Health and Medicine Division, The National Academies of Sciences, Engineering, Medicine, Dietary “Reference Intakes for Calcium and Vitamin D,” November 30, 2010, http://nationalacademies.org/hmd/reports/2010/dietary-reference-intakes-for-calcium-and-vitamin-d.aspx 19 PubMed.gov, Vitamin D Search results, http://www.ncbi.nlm.nih.gov/pubmed/?term=vitamin+d, accessed July 13, 2016. 20 [Ibid]

Flavivirus genus of viruses. (see “Vitamin D-Regulated Micro-RNAs: Are They Protective Factors against Dengue Virus Infection”21

The Risk of Taking Too Much

Whether someone would risk ingesting vitamin D to protect against Zika and dengue is problematic as it might not work for any one individual and enough needs to be taken for it to work. However, the cost is only a few dollars and there is very little risk of taking too much. While there is always a risk of ingesting almost any substance as people can have rare allergies and sensitivities, the major problem with vitamin D is that too much can cause hypercalcemia meaning that the vitamin D would push up calcium in the blood to a level that would cause harm in numerous ways. However, the risk of hypercalcemia has been greatly overplayed and it continues to get media attention without serious scientific evidence. The reality is just the opposite with studies showing very low risk.

For example, recently, the Mayo Clinic conducted a study using 20,308 tests that had values for both vitamin D (in the form of 25hydroxyvitaminD3) and calcium, collected over a ten-year period. Of the 20,308 tests, 4 of them, using blood serum taken from 4 different patients that showed an unhealthy level of calcium that could be attributed to high vitamin D. Of those, 3 showed levels of both vitamin D and calcium just slightly above the normal range. Those patients had no symptoms of hypercalcemia. The 4th test had vitamin D and calcium at very high levels. The female patient, who had been taking 50,000 IU of vitamin D3 and 3,000 mg of calcium at least once daily for more than 3 months, had hypercalcemic symptoms and it took some months to get her back to a normal level by stopping her intake of the two substances. Her very high intake of calcium made it an unusual case. Her blood serum level of vitamin D was 364 ng/mL and calcium was 17.5 while normal calcium is in the 9-10 range. Those 3 other high calcium values mentioned above were 10.2, 10.4 and 10.8.22 The report identifies this one test as an “outlier” because of the very high calcium intake that biases the result.

The IOM Committee’s RDI of 600 IU would most often produce a blood serum level of vitamin D of about 20 ng/mL which many vitamin D experts say is too low. The Endocrine Society recommends 40 ng/mL and the Vitamin D Council recommends 50 ng/mL. The Endocrine Society suggests a daily dose of 4,000 IU while the Council suggests 5,000 IU.

The Mayo Clinic study had 1,714 tests that were above 50 ng/mL while 123 had concentrations of 80 ng/mL and above and 23 were 100 ng/mL and above. The full range was 51 ng/mL to 218 ng/nL with a median of 57 ng/mL. The 3 with moderately high calcium had vitamin D values of 74, 90 and 100 ng/mL. Note that the test with the 218 ng/mL value had a normal calcium value. Some people can tolerate higher vitamin D intake than others. This author has been comfortably taking 20,000 IU to 30,000 IU daily for 4 ½ years.

The Mayo Clinic study showed that it takes months of using very high doses of vitamin D before adverse effects can occur. It’s very common for doctors to prescribe 50,000 IU at least once to quickly overcome deficiency. Doses of 100,000 IU to 300,000 IU were often given in one dose to patients at the start of RCTs. These high single doses were reported to have no adverse effects. If an individual is deficient in vitamin D and is being medically challenged, it is reasonable to take 100,000 IU or more in one dose and then take less in subsequent doses. 10,000 IU to 20,000 IU daily for a few weeks or a month or two, depending on the medical challenge, is also reasonable as can be seen in the Mayo Clinic study. Doctors often prescribe 50,000 IU per week. A recent study found that one dose of vitamin D3 has only a 24-hour half-life while the 25hydroxyvitaminD3 metabolite has a 3-week half-life but the benefit from that metabolite is limited to bone health. For all other uses of vitamin D3, daily dosing is recommended.23

While individuals might find it beneficial to use vitamin D for help in protecting against Zika and dengue, it’s important to know that vitamin D does not directly treat, cure or prevent any disease. It is a raw material that gets converted in the body into a powerful yet very safe secosteroid hormone called “Calcitriol” that then does the work. It is not an anabolic steroid. It does its work by triggering the expression of genes that need the Calcitriol to do their intended tasks. This explains why vitamin D deficiency results in the body not performing adequately.24

More about Vitamin D and Its Use in Athletics

21 Arboleda, John F. and Silvio Urcuqui-Inchima, “Vitamin D-Regulated MicroRNAs: Are They Protective Factors against Dengue Virus Infection?,” Advances in Virology, vol. 2016, Article ID 1016840, 14 pages, 2016. doi:10.1155/2016/1016840, http://www.hindawi.com/journals/av/2016/1016840 22 Dudenkov, Daniel V. et al., “Changing Incidence of Serum 25-Hydroxyvitamin D Values Above 50 ng/mL: A 10-Year Population-Based Study,” Mayo Clinic Proceedings , May 2015, Volume 90 , Issue 5 , 577 – 586 http://www.mayoclinicproceedings.org/article/S0025-6196(15)00185-8/abstract 23 Hollis BW, Wagner CL. The Role of the Parent Compound Vitamin D with Respect to Metabolism and Function: Why Clinical

Dose Intervals Can Affect Clinical Outcomes. The Journal of Clinical Endocrinology and Metabolism. 2013;98(12):4619-4628. doi:10.1210/jc.2013-2653. 24 Hossein-nezhad A, Spira A, Holick MF. Influence of Vitamin D Status and Vitamin D3 Supplementation on Genome Wide Expression of White Blood Cells: A Randomized Double-Blind Clinical Trial. Campbell M, ed. PLoS ONE. 2013;8(3):e58725. doi:10.1371/journal.pone.0058725. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3604145

Vitamin D is not a banned substance in sports and unlikely ever to be as an individual can get a high dose from the sun just by spending sufficient time outdoors during the right season at the right times. It would be inconceivable that track and field regulations would change to ban athletes from spending time in the sun.

Humans have vitamin D receptors in all of their cells and tissues and naturally that includes the heart and muscles. One must assume that they are there to serve a purpose. Controlled trials have shown that supplementing with vitamin D or getting it from the sun or even sunlamps can result in better athletic performance. Besides stronger muscles, it helps to reduce injuries and inflammation.25 You can read about this in an article by this author that has the title “Vitamin D: An Opportunity for Improving Athletic Performance.” It was published in the peer-reviewed medical journal of the American Medical Athletic Association in the Spring of 201426. Note that in Recommendations on the last page of the AMAA article, “5,000 ng/mL” is a typo and should be changed to “50 ng/mL”. This current advisory includes new information that wasn’t available when writing the AMAA article.

The reduction of injuries using vitamin D has become of interest to college and professional sports teams.27 What became most apparent is that vitamin D deficiency was correlated with those players who suffered more injuries.28 29 30

Sources of Vitamin D

The best source of vitamin D is the sun. When its UVB rays reach your skin there is a chemical process that produces vitamin D3. You can also get vitamin D3 from fortified foods, fatty fish and supplements.31. There are two vitamin D substances: D3 is natural and is what you get from the sun while D2 is synthetic and is often what doctors prescribe because that’s what most pharmacies carry. Many studies have shown that D3 is far superior to D2 and most doctors don’t know that.32 There will be 5 hours each day in Rio during the Games during which UVB rays from the sun will be available. The sun’s UVB schedule is 9:30 am to 2:30 pm. The sun needs to be above 45 degrees in the sky for the UVB rays to penetrate through the atmosphere. Once it exceeds 45 degrees, your shadow will be shorter than your height. This can be used as a guide anywhere on earth.

If you wish to use the sun for your vitamin D, it’s important not to get sunburned. How much sun you can get will depend on your skin. People with dark skin can take much more sun but they need much more time in the sun to obtain the vitamin D. Some people with very light skin may have trouble getting any sun without getting burned. For people in between, it’s best to start with only getting a light pink color (which may take only ten to fifteen minutes) and then build up slowly over days and weeks to a tan color. More time can be spent in the sun without skin protection as the skin gets darker. Some people have fear of getting sun exposure on bare skin. Studies have shown that people who spend their lives working outdoors have less skin cancer than people who work indoors. Sun exposure is not a major cause of melanoma.33

There are online vendors that sell vitamin D3 in sizes of 5,000 IU and 10,000 IU. Those gelcaps are very small as 10,000 IU equals only 250 micrograms. 50,000 IU gelcaps are also available online through amazon.com.

Contact information for Alan Roth: alan@alanroth.net, 301 928-6314

Dr. Roth was a USATF Board of Directors member for ten years and was Chair of both the Associations Committee and the General Competition Division. He led the USATF medical study on pre-run stretching http://www.usatf.org/stretchstudy, and the USATF advisory on hydration that was issued in April, 2004. https://www.usatf.org/news/showRelease.asp?article=/news/releases/2003-04-19-2.xml

25 Yin K, Agrawal DK. Vitamin D and inflammatory diseases. Journal of Inflammation Research. 2014;7:69-87.

doi:10.2147/JIR.S63898. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070857 26 Roth, Alan, Vitamin D: An Opportunity for Improving Athletic Performance,” AMAA Journal, Winter/Spring 2014. http://www.amaasportsmed.org/Assets/American+Medical+Athletic+Assoc+Digital+Assets/AMAA+Journal/vitamind.pdf 27 The Wall Street Journal, “Elite athletes try a new training tactic: More vitamin D,” January 26, 2016, http://www.foxnews.com/health/2016/01/26/elite-athletes-try-new-training-tactic-more-vitamin-d.html 28 Life Extension Magazine, “Vitamin D insufficiency associated with football injuries,” July 15, 2011, http://www.lifeextension.com/newsletter/2011/7/Vitamin-D-Insufficiency-Associated-with-Football-Injuries/page-01?source=eNewsLetter2011Wk28-2&key=Article&l=0#article 29 Angeline, ME, Gee AO, et al, “The effects of Vitamin D in Athletes,” Am J Sports Med, February 2013vol. 41 no. 2 461-464, http://www.ncbi.nlm.nih.gov/pubmed/23371942 30 Melville, Nancy, “’Alarming' Vitamin D Deficiencies in NFL Football Players,” Medscape Medical News, July 13, 2011, http://www.medscape.com/viewarticle/746310 31 Wacker, Matthias, and Michael F. Holick. “Sunlight and Vitamin D: A Global Perspective for Health.” Dermato-endocrinology 5.1 (2013): 51–108. PMC. Web. 13 July 2016, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897598 32 Tripkovic L, Lambert H, Hart K, et al. “Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. ”The American Journal of Clinical Nutrition. 2012;95(6):1357-1364. doi:10.3945/ajcn.111.031070. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349454 33 Vuong K, McGeechan K, Armstrong BK, AMFS Investigators, GEM Investigators, Cust AE. Occupational sun exposure and risk of melanoma according to anatomical site. International journal of cancer Journal international du cancer. 2014;134(11):2735-2741. doi:10.1002/ijc.28603.

Note: This advisory has no official connection to USATF.