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A Cure for Multiple Sclerosis?

needleA research study published June 2016 in the prestigious journal, The Lancet, details a very risky but effective cure for patients with aggressive multiple sclerosis (1). In multiple sclerosis (MS), the immune system attacks its own insulating material called myelin which usually covers nerve cells in the brain and spinal cord. There is currently no cure, but symptoms may be managed through the use of medications that manage inflammation and inhibit the immune system to dampen further demyelinating damage. Symptoms vary among individuals but can include numbness, weakness in the limbs, loss of balance, fatigue, and blurred vision. More severe cases can involve paralysis. The medical procedure described in The Lancet relies on the harvesting of a patient’s own hematopoietic stem cells to be used as grafts after almost completely destroying the patient’s existing immune system. This autologous hematopoietic stem-cell harvest, which selects for CD34+ progenitor cells, is taken from the patient after stimulation (mobilization) to increase the numbers of circulating myeloid stem cells (2). This is done with the chemotherapy drug, cyclophosphamide, and filgrastim, a granulocyte colony-stimulating factor analog which promotes the rapid increase and differentiation of a type of white blood cell called granulocytes. A cure to MS is possible through the ablation of the current faulty immune system of MS, and the subsequent replacement with hematopoietic stem cells that can then become healthy immune blood cells.

The study began in 2000, and the paper describes Phase 2 of the study at three hospitals in Canada. Twenty-four patients participated, and one has died during the study due to liver complications. The treatment is initially quite toxic, and strong chemotherapy drugs are given to destroy the immune cells. After immune cells are rendered null through the use of busulfan, cyclophosphamide, and rabbit anti-thymocyte globulin, the patient is left vulnerable to infection. The chemotherapy is toxic to sperm or eggs, and women enter early menopause. Hair and fingernails fall off. Yet, MS patients desperately searching for a cure have chosen this option and experienced not only a cessation of symptoms, but also some recovery from previous MS-induced damage. Patients were followed up for up to thirteen years after autologous hematopoietic stem-cell transplantation, and even though they were not on any medications, they were found to be free of relapses and without any new brain lesions in MRI scans.

Interestingly, this process of “resetting” the immune system was found to be effective for MS quite accidentally. Initially, people with both leukaemia and MS were being treated for leukaemia, a cancer of the white blood immune cells. This cancer starts in the bone marrow, so autologous blood stem cells from the bone marrow are first collected and rid of any cancerous cells. The cells are then reintroduced into the body as a graft to elicit new, healthy immune cells after the existing, cancer-ridden immune system is destroyed by toxic chemotherapy. The results were found to be effective not only for leukaemia, but for MS as well. It is hoped that a similar approach can be used to cure other autoimmune diseases such as Crohn’s disease, scleroderma, and lupus. The risk associated with deleting a person’s entire immune system is great, but by adjusting the balance between toxicity and maximal therapeutic results, a safer medical intervention can be found. Larger trials can be conducted to determine the best dosage and effectiveness so that hopes can be high for people suffering from MS and other debilitating autoimmune diseases.

 

Sierra Delarosa

 

References

  1. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30169-6/abstract
  2. http://www.ncbi.nlm.nih.gov/pubmed/12592344

Hepatitis A From Frozen Berries

berriesOn April 15, 2016, the Canadian Food Inspection Agency (CFIA) announced a food recall warning regarding the possible contamination with Hepatitis A, a viral liver disease, of the frozen fruit product, “Nature’s Touch Organic Berry Cherry Blend”. Canadians have been advised that the food recall is in effect in the provinces of Ontario, Quebec, New Brunswick, Nova Scotia, and Newfoundland and Labrador, where the product has been sold. As of April 22, 2016, there are eleven related Hepatitis A cases in three provinces (1): Ontario (8 cases), Quebec (2 cases), and Newfoundland and Labrador (1 case). 

While it is frightening to know that Hepatitis A can be contracted by eating frozen berries, a product that is supposed to be healthy, coming into contact with hepatitis A can be quite easy. Hepatitis A is usually linked with the lack of potable water and inadequate sanitation,  and the virus is spread mainly by the faecal-oral route. It can be acquired from any food and drinks prepared by a person who is infected, as an  infected person can carry, due to improper hygiene, traces of their faeces when preparing refreshments. Shellfish derived from waters containing sewage can also carry hepatitis A. The frozen berries sold at Costco in Canada were at some point contaminated with hepatitis A from at least one infected worker (during harvest, manufacturing or processing) who was handling the berries, and who did not take preventative hygienic measures such as frequent hand-washing with soap and water, and the use of gloves. After infection with hepatitis A, symptoms usually reveal themselves two to seven weeks after viral infection. Fever, loss of appetite, abdominal pain, jaundice, dark urine, vomiting, and fatigue are all symptoms. Although cases usually last one to two weeks, a few severe cases can last several months before recovery, and some people can die from liver failure. People with pre-existing liver conditions are at a greater risk of severe illness. Older people tend to get sicker than younger people after infection.The disease is not chronic (there is usually no permanent liver damage), and lifetime immunity is acquired either from recovery after infection, or through immunization with the hepatitis A vaccine.

 

The hepatitis A virus, a picornavirus, is of an icosahedral shape and does not contain an envelope. It possesses a single-stranded RNA packaged in a protein capsid. There are three different numbered human genotypes of the virus, but type IA is the most commonly occurring. Genetic sequencing of the virus can reveal which molecular subtype of the virus is associated with a particular outbreak (2), thus narrowing down unassociated cases of infection. To determine whether infection has occurred, a blood test to look for IgM anti-hepatitis A antibodies, a particular immune response, can detect the virus as early as two weeks after the initial infection.

 

Known as a “traveller’s disease”, hepatitis A is usually associated with countries that are less developed, but it does and can occur in Canada. In industrialized countries, outbreaks of hepatitis A are often linked to contaminated produce (3). During March 2012, there was a small outbreak of hepatitis A in British Columbia, Canada that was traced to pomegranate seeds in a frozen fruit product (4). April 2013 saw more than 70 cases of hepatitis A infection in four Nordic countries (5,6). In the United States, there were 165 confirmed cases of hepatitis A infection found across 10 states, in 2013 (7). This outbreak was traced to pomegranate arils found in a frozen berry product sold at Costco, and 44% of the infected patients were hospitalized. Frozen fruit can last for up to a year in the store, and hepatitis A can incubate for up to 50 days, so a hepatitis A outbreak is often detected only after many people have been infected (8). Case-control studies, where patients with (case) and without (control) a disease, such as hepatitis A, are compared retrospectively for frequency of exposure to a risk factor (such as the contaminated frozen fruit), and through this study method the source of the outbreak can be unraveled.

 

Costco is publicly offering free vaccination clinics to affected individuals of this recent 2016 outbreak, as vaccination can prevent the disease symptoms from occurring if given within two weeks of exposure (9). There are two options for post-exposure prophylaxis of hepatitis A. The first is the vaccine injection, which is an inactivated version of the virus. The second is immunoglobulin (IG), which is injected and consists of antibodies which fight the virus to prevent infection. It is a blood product produced from paid donors. An exposed individual who may be allergic to the vaccine may opt for the IG. A study comparing the two options found that immunoglobulin was slightly more effective than the vaccine (10). However, the vaccine offers a lifetime immunity, whereas the response of immunoglobulin against hepatitis A is only for three months after the IG administration-subsequent exposure to hepatitis A can still result in an infection. Individuals can get a pre-exposure prophylaxis vaccination, which renders permanent immunity before any exposure, and travellers to countries where hepatitis A is endemic are required to receive the vaccination before leaving to their destination.

 

The recent 2016 hepatitis A outbreak in Canada from frozen fruit is only one of several similar outbreaks that have occurred in the past in different industrialized countries. Hepatitis A is spread through the faecal-oral route, and although it is more common in less developed nations where poor sanitation conditions are prevalent, improper hygiene during food handling can cause an outbreak.  Identifying the specific molecular subtype of hepatitis A can help trace which cases are associated with a particular outbreak. It is recommended that anyone handling food take proper precautions in food safety in order to prevent further hepatitis A outbreaks. If worried, one should obtain a pre-exposure vaccination to acquire permanent immunity to the virus.

 

Sierra Delarosa

 

References

 

 

1)    Public Health Notice: Outbreak of Hepatitis A infections; consumers advised not to eat Nature’s Touch Organic Berry Cherry Blend frozen fruit. (2016, April 22). Retrieved April 26, 2016, from http://www.phac-aspc.gc.ca/phn-asp/2016/hepatitisa-eng.php

2)    Chironna, M., Lopalco, P., Prato, R., Germinario, C., Barbuti, S., & Quarto, M. (2004). Outbreak of Infection with Hepatitis A Virus (HAV) Associated with a Foodhandler and Confirmed by Sequence Analysis Reveals a New HAV Genotype IB Variant. Journal of Clinical Microbiology, 42(6), 2825-2828. doi: 0.1128/JCM.42.6.2825-2828.2004

3)    Swinkels, H. M., Kuo, M., Embree, G., F., Andronov, A., Henry, B., & Buxton, J. A. (2014). Hepatitis A Outbreak in British Columbia, Canada: The Roles of Established Surveillance, Consumer Loyalty Cards AND Collaboration, February to May2012. Endosurveillance, 19(18), 4th ser. http://dx.doi.org/10.2807/1560-7917.ES2014.19.18.20792

4)    Hutin YJ, Pool V, Cramer EH, Nainan OV, Weth J, Williams IT, et al (1999). A multistate outbreak of hepatitis A. National hepatitis A investigation team. N Engl J Med, 340(8), 595-602.
http://dx.doi.org/10.1056/NEJM199902253400802

5)    Gillesberg Lassen S, Soborg B, Midgley SE, Steens A, Vold L, Stene-Johansen K, et al (2013). Ongoing multi-strain food-borne hepatitis A outbreak with frozen berries as suspected vehicle: four Nordic countries affected, October 2012 to April 2013. Euro Surveill.18(17):pii=20467.

6)    Nordic outbreak investigation team. Joint analysis by the Nordic countries of a hepatitis A outbreak, October 2012 to June 2013: frozen strawberries suspected (2013). Euro Surveill. 18(27):pii=20520.

7)    Multistate outbreak of hepatitis A virus infections linked to pomegranate seeds from Turkey (Final Update). (2013, October 28). Retrieved April 26, 2016, from http://www.cdc.gov/hepatitis/Outbreaks/2013/A1b-03-31/

8)    Heymann, D. L. (2008). Control of Communicable Diseases Manual (19th ed.). Washington, DC: American Public Health Association.

9)     Patil, A. (2016, April 18). Costco to provide free Hepatitis A vaccination clinics after frozen berry recall. CBC News. Retrieved April 26, 2016, from http://www.cbc.ca/news/canada/nova-scotia/costco-hepatitis-a-vaccination-clinics-1.3541908

10)   Victoria, J. C., PhD, Monto, A. S., MD, Surdina, T. Y., MD, Suleimenova, S. Z., MD, Vaughan, G., PhD, Nainan, O. V., PhD, .Favorov, M.O., MD, Margolis, H.S., MD, Bell, B. P., MD. (2007). Hepatitis A Vaccine versus Immune Globulin for Postexposure Prophylaxis. The New England Journal of Medicine, 357, 1685-1694. doi:10.1056/NEJMoa070546

The Zika Crisis

mosquitoIn 2015, the Zika virus outbreak began in the northeast region of Brazil. According to the World Health Organization, there has been 3174 suspected cases of microcephaly in Brazil since January 2, 2016, including 38 deaths (1). The northeastern region of Brazil continues to be the area most affected, with the highest number of suspected cases. On April 13, 2016, the US Centers for Disease Control and Prevention (CDC) published a paper in The New England Journal of Medicine which concluded that there is a direct causal relationship between prenatal exposure to Zika virus and the outcome of microcephaly and brain abnormalities in the exposed infants (2). While the common symptoms of Zika infection are fever, rash, joint pain, and conjunctivitis lasting from several days to a week after exposure from an infected mosquito’s bite, a recent study recounts two cases of patients who had contracted the Zika virus and later succumbed to acute disseminated encephalitis (ADEM) (3).  This is a condition in which the immune system attacks the body, producing swelling in the brain and spinal cord and damaging the myelin which serves to protectively encase nerve fibers. The same study also describes four patients who had Zika and then developed Guillain-Barré syndrome, a condition where the immune system attacks the body’s peripheral myelin.

Zika virus is quickly spread through the bite of the female Aedes aegypti mosquito, a mosquito that is usually associated with warmer climates. This species of mosquito bites during the day. The Pan American Health Organization (PAHO) sent out a warning of the first confirmed Zika virus infection in Brazil on May 2015, and on February 2016, the World Health Organization (WHO) declared Zika virus a public health emergency of international concern (PHEIC). The PAHO lists the following areas where local transmission of Zika virus is active (4): Aruba, Barbados, Belize, Bonaire, Brazil, Colombia, Costa Rica, Cuba, Curacao, Dominica, Dominican Republic, Ecuador, El Salvador, French Guiana, Guadeloupe, Guatemala, Guyana, Haiti, Hondruas, Jamaica, Martinique, Mexico, Nicaragua, Panama, Paraguay, Peurto Rico, Saint Vincent and the Grenadines, Saint Lucia, Saint Martin, Sint Maarten, Suriname, Trinidad and Tobago, US Virgin Islands, and Venezuela. Locally transmitted cases of Zika have been reported in the Commonwealth of Puerto Rico, the US Virgin Islands, and American Samoa. There is potential for Zika virus to continue to spread to other countries due to the expanding range of the Aedes aegypti mosquito. A population of this species not carrying Zika was found in Capitol Hill, Washington, DC. Genetic analysis revealed that this particular mosquito population survived five winters in the area (5). Although theAedes aegypti is the species most responsible for spreading the Zika virus, other mosquito species in the Aedes genus can also transmit it to humans. Once the virus enters the bloodstream of a human through the bite of a female mosquito (the male mosquitoes do not bite), another female mosquito can acquire Zika by feeding upon the same host, which can then go on to infect another human. In an area with many Aedes mosquitoes, the process will repeat itself exponentially, leading to widespread viral transmission. A possible solution can be to use genetically modified mosquitoes that are male which reproduce with local female mosquitoes to yield offspring which do not live past the pupae stage. Oxitec (6), a British biotechnology company, developed such a mosquito which has already been released and tested successfully in the Cayman Islands in 2010, leading to a drastic 80 percent reduction in population of Aedes aegypti. Release of the same strain of GMO mosquitoes in the suburb of Juazeiro, Brazil in 2011 resulted in a 81-95 percent reduction of Aedes aegypti in the test region. It is also possible to breed mosquitoes to be genetically resistant to diseases such as dengue, malaria, yellow fever and Zika. Gamma radiation is being used in Brazil to sterilize male mosquitoes. Moscamed, a non-profit organization based in Brazil, took to breeding 12 million male mosquitoes per week, sterilizing them with the cobalt-60 irradiator, and then releasing them into select high-risk areas (7). The released sterile males mosquitoes then meet wild female mosquitoes, but no offspring can be produced. As there is no vaccine available right now, the current method of battling Zika virus is to reduce the population of Aedes mosquitoes.

It has been found that the Zika virus can also be transmitted sexually from an infected human male to his sexual partners via vaginal or anal sex (8), and that the virus can remain for a longer duration in semen than in blood. As of now, it is not known whether a woman can sexually spread Zika virus, or if it can be transmitted through saliva or vaginal fluids. Couples who are pregnant, or men who have travelled to areas affected by Zika are advised by the CDC to abstain from sex or use condoms.

The Zika virus is in the Flavivirus genus of viruses, which also include the West Nile virus, dengue virus, tick-borne encephalitis virus, and yellow fever virus. As a flavivirus, the Zika virus is enveloped, has a capsid of icosahedral symmetry, and contains a single-stranded positive-sense RNA genome. The Zika genome is about 10.8 kilobase pairs long. The positive-sense RNA is significant because once the virus enters the host cell, this RNA viral genome can be directly translated into a viral polypeptide, which is then cleaved into structural proteins and proteins to aid in the replication process. The envelope (E) glycoprotein protruding from the membrane of the virus is used for attachment and entrance into human cells.  For the development of a potential vaccine for Zika virus, a segment of the E glycoprotein unique to the Zika virus can be used in the vaccine to mount an antibody-mediated immune response, possibly conferring immunity from future attacks of the virus.

The expanding range of travel of both humans and mosquitoes have allowed for rapidly widespread transmission of the Zika virus. The head and brain abnormalities caused by prenatal exposure from an infected mother are detrimental, and a direct casual link between the virus and microcephaly/brain defects has been determined by the CDC. For instance, the Zika virus genome was found in the brain of an aborted, infected infant (9) that had microcephaly, and Zika virus antigens were found in the brain of one newborn with microcephaly (10). Autopsies found the presence of Zika virus in the brains of infants with severe microcephaly who died. Pregnant women infected with Zika virus have consistently given birth to infants with microcephaly and other brain abnormalities (11). The CDC further found that women who deliver infants with microcephaly were infected with Zika virus during the first and second trimester of gestation, when the brain starts to form and develop (12). There are two hypotheses directed at explaining how the Zika virus causes birth defects such as microcephaly (13). The first hypothesis posits that the placenta transfers the virus directly from mother to the fetus. The second hypothesis refers to the possible reaction of the placenta in response to Zika, which may contribute to or result in birth defects. Pregnant women are advised not to travel to areas where Zika virus is occurring.

Sierra Delarosa

 

   References

 1) Microcephaly-Brazil. (2016, January 8). Retrieved April 15, 2016, from http://www.who.int/csr/don/8-january-2016-brazil-microcephaly/en/

2) Rasmussen, S. A., M.D., Jamieson, D. J., M.D., Honein, M. A., PhD, & Petersen, L. R., M.D. (n.d.). Zika Virus and Birth Defects — Reviewing the Evidence for Causality. The New England Journal of Medicine. doi:10.1056/NEJMsr1604338

3) American Academy of Neurology. (2016, April 11). Zika virus may now be tied to another brain disease. ScienceDaily. Retrieved April 16, 2016 from www.sciencedaily.com/releases/2016/04/160411082335.htm

4) Countries and territories with autochthonous transmission in the Americas reported in 2015-2016. (n.d.). Retrieved April 15, 2016, fromhttp://www.paho.org/hq/index.php?option=com_content&view=article&id=11603:countries-territories-zika-autochthonous-transmission-americas&catid=8424:contents&Itemid=41696&lang=en

5) Gustin, G. (2016, February 26). Zika Virus Mosquitos Have Been Found…on Capitol Hill. Retrieved April 15, 2016, fromhttp://www.washingtonian.com/2016/02/26/zika-virus-mosquitos-capitol-hill-aedes-aegypti/

6) More on the science: How does oxitec make genetically modified mosquitoes? (n.d.). Retrieved April 15, 2016, fromhttp://www.oxitec.com/oxitec-video/more-on-the-science-how-does-oxitec-make-genetically-modified-mosquitoes/

7) Boadle, A. (2016, February 22). Brazil to fight Zika by sterilizing mosquitoes with gamma rays. Reuters. Retrieved April 15, 2016, from http://www.reuters.com/article/us-health-zika-radiation-idUSKCN0VV2JK

8) Zika and Sexual Transmission. (2016, February 21). Retrieved April 15, 2016, from http://www.cdc.gov/zika/transmission/sexual-transmission.html

9) Mlakar, J., M.D. et al (March 10, 2016). Zika Virus Associated with Microcephaly. The New England Journal of Medicine, 374, 951-958. DOI: 10.1056/NEJMoa1600651

10) Martines RB, Bhatnagar J, Keating MK, et al. Notes from the Field: Evidence of Zika Virus Infection in Brain and Placental Tissues from Two Congenitally Infected Newborns and Two Fetal Losses — Brazil, 2015. MMWR Morb Mortal Wkly Rep 2016;65, 159–160. DOI:http://dx.doi.org/10.15585/mmwr.mm6506e1

11) Rasmussen, S. A., M.D., Jamieson, D. J., M.D., Honein, M. A., PhD, & Petersen, L. R., M.D. (n.d.). Zika Virus and Birth Defects — Reviewing the Evidence for Causality. The New England Journal of Medicine. doi:10.1056/NEJMsr1604338

12) Rasmussen, S. A., M.D., Jamieson, D. J., M.D., Honein, M. A., PhD, & Petersen, L. R., M.D. (n.d.). Zika Virus and Birth Defects — Reviewing the Evidence for Causality. The New England Journal of Medicine. doi:10.1056/NEJMsr1604338

13) Adibi, J. J., ScD. Et al (2016). Teratogenic effects of the Zika virus and the role of the placenta. The Lancet. http://dx.doi.org/10.1016/S0140-6736(16)00650-4

Chickens, toads, and gluten sensitivity

Keratosis pilarisBy: Laurie Laforest
Keratosis pilaris is one of the many symptoms attributed to non-celiac gluten sensitivity in alternative medicine circles.  Keratosis pilaris – or “chicken skin” – is a benign skin condition reminiscent of permanent goose bumps.  I first heard the term keratosis pilaris on a episode of The Dr. Oz Show about gluten sensitivity [1], the premise being that keratosis pilaris results from fat malabsorption caused by gluten-induced intestinal damage.  Since my family and I have little patches of this on our elbows and knees, I was eager to learn what was really behind it.
It turns out that the link between “chicken skin” and gluten sensitivity is one of mistaken identity.  Keratosis pilaris is a type of follicular hyperkeratosis where excess keratin – a key protein in our outer layer of skin and in our hair and nails – plugs the hair follicule, sometimes trapping a small hair inside. [2]  Enlargement of the follicule and the presence of the hard keratin plug produces the characteristic rough and bumpy appearance; reddening may also occur.  Keratosis pilaris is quite common – it affects around 50% adolescents (80% of females) and 40% of adults – and seems to have a strong hereditary component. [3]
Phrynoderma – or “toad skin” – is another type of follicular hyperkeratosis that is typically related to malnutrition in developing nations.  Phrynoderma is what alternative medicine folks are actually thinking of (or they should be) when they speak about a diet-related bumpy skin problem.  The exact nutrient deficiency behind phrynoderma is not known, but the condition can be reversed by supplementation with essential fatty acids, vitamin A, vitamin E, or B-complex vitamins; different people seem to respond to different nutrients. [4-7]
So “chicken skin” (keratosis pilaris) is common and benign, while “toad skin” (phrynoderma) is uncommon in the developed world and a sign of a serious problem.  But could it still be possible that gluten sensitivity is at the heart of these conditions?  Most likely not.  Keratosis pilaris is not related to diet, although it does seem to occur more often in people with a high body mass index. [8,9]  Hormones could also play a role, since keratosis pilaris is more common during adolescence.  Still, keratosis pilaris can come and go throughout adulthood and may worsen during the drier winter months.
Even for phrynoderma, the gluten connection doesn’t pan out.  Let’s first consider celiac disease, an autoimmune reaction triggered by gluten that damages the small intestine.  Celiac disease is the worst-case scenario when it comes to gluten sensitivity – fat malabsorption is a classic symptom of untreated celiac disease, and there is a risk that celiac sufferers could be deficient in fat-soluble vitamins like A, D, and E.  But even though it might seem like celiac disease could produce the kind of malnutrition that leads to phrynoderma, phrynoderma is not one of the skin conditions seen alongside celiac disease [10], and fat-soluble vitamin deficiencies are also not found in newly-diagnosed celiac patients as often as one is led to believe on TV [11-13].  Now consider that non-celiac gluten sensitivity is not supposed to involve the characteristic intestinal damage (and, hence, the potential vitamin deficiencies) found in celiac disease [14,15], and you have no reason for the average person to suspect that their rough skin is related to gluten.
If you do have “chicken skin” or other roughening or reddening of the skin, it is best to talk to a dermatologist to properly identify your skin condition or to your doctor if you do suspect that you have celiac disease.  Most people with keratosis pilaris don’t even realize that they have it, but others may be plagued by large, unsightly patches of skin.  Mild cases can be improved by over-the-counter moisturizers; more severe cases can be treated by medicated creams that soften keratin and help remove the outer layer of skin.  Even though there is an abundance of advice on treating keratosis pilaris on the Internet, ask a doctor or pharmacist to direct you to the right products to use.
<a rel=”author” href=”https://plus.google.com/108035110292301860932″>Laurie Laforest</a> – <a href=”http://foodconnections.org/”>foodconnections.org</a>
References
1. The 5 Hidden Signs You Have a Gluten Allergy [Internet]. The Dr. Oz Show. 2014 [cited 2014 Nov 14]. Available from: http://www.doctoroz.com/episode/5-hidden-signs-you-have-gluten-allergy
2. Hwang S, Schwartz RA. Keratosis pilaris: A common follicular hyperkeratosis. Cutis. 2008;82(3):177–80.
3. Alai AN, Elston DM. Keratosis Pilaris Treatment & Management [Internet]. Medscape. [cited 2014 Jun 12]. Available from: http://emedicine.medscape.com/article/1070651-overview
4. Ragunatha S, Kumar VJ, Murugesh SB. A Clinical Study of 125 Patients with Phrynoderma. Indian J Dermatol. 2011;56(4):389–92.
5. Bagchi K, Halder K, Chowdhury SR. The etiology of phrynoderma; histologic evidence. Am J Clin Nutr. 1959 Jun;7(3):251–8.
6. Nadiger HA. Role of vitamin E in the aetiology of phrynoderma (follicular hyperkeratosis) and its interrelationship with B-complex vitamins. Br J Nutr. 1980 Nov;44(3):211–4.
7. Therapeutic Response of Vitamin A, Vitamin B Complex, Essential Fatty Acids and Vitamin E in the Treatment of Phrynoderma: A Randomized Controlled Study. Journal of Clinical and Diagnostic Research. 2014;8(1):116–8.
8. Yosipovitch G, Mevorah B, Mashiach J, Chan YH, David M. High body mass index, dry scaly leg skin and atopic conditions are highly associated with keratosis pilaris. Dermatology (Basel). 2000;201(1):34–6.
9. Yosipovitch G, Hodak E, Vardi P, Shraga I, Karp M, Sprecher E, et al. The prevalence of cutaneous manifestations in IDDM patients and their association with diabetes risk factors and microvascular complications. Diabetes care. 1998;21(4):506–9.
10. Caproni M, Bonciolini V, D’Errico A, Antiga E, Fabbri P. Celiac Disease and Dermatologic Manifestations: Many Skin Clue to Unfold Gluten-Sensitive Enteropathy. Gastroenterology Research and Practice. 2012;2012:1–12.
11. Imam MH, Ghazzawi Y, Murray JA, Absah I. Is it Necessary to Assess for Fat Soluble Vitamin Deficiencies in Pediatric Patients With Newly Diagnosed Celiac Disease?: Journal of Pediatric Gastroenterology and Nutrition. 2014 Mar;1.
12. Villanueva J, Maranda L, Nwosu BU. Is vitamin D deficiency a feature of pediatric celiac disease? J Pediatr Endocrinol Metab. 2012;25(5-6):607–10.
13. Wierdsma NJ, van Bokhorst-de van der Schueren MAE, Berkenpas M, Mulder CJJ, van Bodegraven AA. Vitamin and Mineral Deficiencies Are Highly Prevalent in Newly Diagnosed Celiac Disease Patients. Nutrients. 2013 Sep 30;5(10):3975–92.
14. Sapone A, Bai JC, Ciacci C, Dolinsek J, Green PH, Hadjivassiliou M, et al. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC medicine. 2012;10(1):13.
15. Sapone A, Lammers KM, Casolaro V, Cammarota M, Giuliano MT, De Rosa M, et al. Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity. BMC Med. 2011 Mar 9;9:23.

Opioid peptides: the heroin within?

Screen Shot 2014-11-07 at 10.36.51 PMBy: Emily Brown PhD

If you were to hear the words ‘opioid peptides’, they might not trigger much within your brain, other than that the former sounds a bit like opium and together they sound quite scientific. Opium (also known as poppy tears) is a dried substance or latex that originates, as the alternative name suggests, from the opium poppy. Beautifully intricate pipes of bamboo, ivory, silver, jade and porcelain have been carved over the centuries and used to vaporise and inhale the latex traditionally obtained by scratching immature poppy seed pods by hand. Numerous Empires including the Egyptian, Greek, Roman, Persian and Arab made widespread use of the drug, which was then the most potent form of pain relief available. This analgesic property is conferred by morphine, which constitutes approximately twelve per cent of opium and is chemically processed to produce heroin. Commonly known by the street names H, smack, horse and brown, among others, the effects of heroin will be well known by any ‘Trainspotting’ fans. What writer Irvine Welsh did not reveal, however, is that opiates such as heroin mimic the effects of naturally occurring molecules that can be generated inside our own bodies.

Opioid peptides are small molecules that are produced in the central nervous system (the brain and spinal cord) and in various glands throughout the body such as the pituitary and adrenal glands. These peptides can be divided into three categories (enkephalins, endorphins, and dynorphins), depending on the type of larger precursor molecule from which they are derived. Opioid peptides function both as hormones and as neuromodulators; the former are secreted in the blood system by glands and are delivered to a variety of target tissues where they induce a response, while the later are produced and secreted by nerve cells (or neurons) and act in the central nervous system to modulate the actions of other neurotransmitters.

Neurons are electrically excitable cells that process and transmit information through electrical and chemical signals that travel via synapses, specialised connections with other cells. These signals are transmitted across a synapse from one neuron to another by neurotransmitters. By altering the electrical properties of their target neurons and making them difficult to excite, opioid peptides can influence the release of various neurotransmitters.

Through these two different mechanisms, opioid peptides can produce many effects including pain relief, euphoria and altered behaviour such as food and alcohol consumption. The apparent connection between exercise and happiness has been explained at least somewhat by the release of endorphins, for example. Exercise is commonly recommended as a strategy for stress-relief and mood improvement, but less widely accepted forms of therapy might also be connected to opioid peptides. Evidence suggests that pain relief induced by acupuncture results from stimulation of opioid peptides – these peptides act through receptors on their target neurons, and chemicals that inhibit opioid receptor function have been found to reverse acupuncture-induced analgesia. Painful, stressful or traumatic events or stimuli can induce the release of opioid peptides, with the resulting euphoria and pain relief making the sufferer less sensitive to noxious events. Opioid peptides have been reported to affect the release of specific neurotransmitters such as dopamine and serotonin, but the response of the neurons that receive opioid-peptide stimulation depends on their excitatory versus inhibitory nature, making the outcome difficult to predict.

The words ‘opioid peptides’ may not have left a dazzling feeling of recognition within your memory upon first encounter, but these peptides act within the brain and wider body to influence a number of important functions. Although it is not easy to predict the effect of neuromodulators that alter the release of other neurotransmitters, there is little question that opioid systems play a critical role in modulating a large number of sensory, motivational, emotional and cognitive functions. Alterations in opioid peptide systems may contribute to a variety of clinical conditions, including alcoholism, obesity, depression, diabetes and epilepsy. Many questions still remain, particularly those concerning the exact role of opioid peptides produced within the body in relation to addictive and emotional behaviour and psychiatric disorders. Since these disorders are typically of a complex nature, seeking the answers to these questions is not a simple feat. Advances in genetics and genomics research that aim to explain function by studying our DNA are helping to pave the way. But perhaps if there is one thing that can help motivate our talented scientists to reach their challenging goals, a healthy dose of opioid peptide might be just the thing.

Emily Brown PhD

An Apple a Day!

appleAn apple a day may keep the doctor away and is a good idea title for a book, but it’s probably a bad premise for a scientific study. The other day, a friend of mine drew my attention to a headline in the UK Telegraph “Eating an apple a day improves women’s sex lives, study shows.” Bad grammar not withstanding, I defied my better judgment and decided to read the article. The Telegraph doesn’t have the best track record of health reporting. Recently they wildly misreported a study about edible flowers and true to form they botched this one as well.

The article makes a number of claims. It says that that apples have “been show to be an aphrodisiac,” that “an apple a day can improve the sex lives of women” and that they “boost sexual pleasure in healthy women.” These are impressive attributes for a simple fruit, so I decided to read the actual study this report was based on.

The study was published in the Archives of Gynecology and Obstetrics. Essentially researchers took 731 women and asked them how many apples they ate every day and then asked them to fill out a questionnaire about their sex lives in areas such as desire, arousal, satisfaction, pain, etc. Researchers found an improvement in lubrication and consequently in the total score, but not in any other area of the questionnaire. Here is an actual quote from the study, “No significant differences between the two study groups were observed concerning desire, sexual arousal, satisfaction, pain and orgasm.” (Interestingly, the group that ate less apples had a slightly higher satisfaction score 4.5 vs. 4.3). This strikes me as fairly convincing that apples are don’t affect the quality of women’s sex lives at least in terms of the metrics that actually matter. Having read this study, I cannot for the life of me figure out how the Telegraph could have generated their headline. I can only assume they didn’t actually read it and just parroted the press release.

Even if you accepted their one single positive finding, the study has a lot wrong with it. First off, it is not a randomized clinical trial. Even though the newspaper story seemed to imply that it was, here researchers simply asked women how many apples they ate and did not actually conduct an experiment. It is easy to image why women who ate apples on a daily basis would be different than women who did not. They were likely more health conscious, probably exercised more, and probably had a better diet overall. Those who ate more apples probably ate more bananas, more oranges, more pears and more fruits in general. Researchers did not ask about other fruits and they likely could have just as easily shown an association with kiwis or pomegranates. So why apples? I guess the link to the biblical story of Adam and Eve was too good to pass up. Of course, the fruit of the tree of knowledge wasn’t actually an apple but why quibble on details.

The newspaper article also then makes a number of claims that the benefits of apples are due to phloridizin and polyphenols.  This is pure speculation. This study, as I mentioned, did not measure any hormone levels or perform any tests on the apples themselves. It was purely the analysis of questionnaire sent out to women.  Clearly, throwing in a few “sciency” terms (and adding the requisite photo of an alluring women biting into an apple) made the article more appealing to the newspaper editors.

Apples are unlikely to improve your sex life and, while we’re at it, neither will oysters, chocolate, or ginseng. An overall healthy lifestyle with regular exercise and a balanced diet is probably your best bet (but admittedly this would make for a lousy headline). So what can we conclude overall about eating an apple day? No effect on sexual desire or satisfaction, great title for a book, and (from my point of view) it’s bad for business.

Christopher Labos

MD CM FRCPC

e-mail: Christopher.labos@mail.mcgill.ca

twitter: @drlabos

Beware of the new contrarian embrace of dietary fat

dietBy: Christopher Labos MD CM FRCPC

 Some of you may have heard about a new book called The Big Fat Surprise. The basic premise of the book is that fat is not bad for you and that you should eat more of it. When I first heard about this book and recovered from my apoplectic fit, I marvelled at how many times we can keep having the same discussion. Most diets can be lumped into two broad categories of either low-fat or low-carbohydrate diets.

 The notion that fat is associated with cholesterol and heart disease goes back several decades with research programs like the Framingham Heart Study and the MRFIT study, and initially led physicians to recommend low-fat diets as a way to stave off heart disease. The problem with this strategy was two-fold. First, as people sought out low-fat alternatives to their favourite junk food, companies simply took out the fat and added more sugar.

 Thus they were able to preserve the taste while still being able to label their food fat-free. As you might imagine, this did not translate into health benefits. As a result, most studies of a low-fat diet have been negative, and this fact is proudly proclaimed in the book.

The second problem with the low-fat diet is more subtle. Our understanding of fat and cholesterol has evolved considerably since those early studies. Now we speak of LDL and HDL (bad and good) cholesterol, rather than total cholesterol, as we once did. Also, instead of talking about total fat, we now talk about good fats (mono and polyunsaturated fats) that we get from fish and vegetable oils and bad fats (trans fats) that are present in fried foods. So a problem with the low-fat diet is that people reduced their intake of both good and bad fat, which essentially cancelled out the effects of each.

 Admittedly, the evidence for different fat sources is not rock solid. Although it is incontrovertible that smoking causes lung cancer, and that high blood pressure leads to a stroke, trying to prove that good fats are protective while bad fats are harmful is very difficult. There are a number of reasons why nutrition-based research is hard to do, but the main difficulty is that people’s diets fluctuate over time and rarely stay consistent.

The book I mentioned starts by poking holes in the evidence for good and bad fats, which is fair enough because, like I said, it is not perfect. It then goes on to state that sugar and carbs are the real enemy. For those of you who realized that this is essentially the Atkins diet repackaged, congratulate yourselves on an astute observation. Finally, it makes the rather bold claims that we should eat more fat and butter in our diet. This strikes me as a very bad idea.

 Although we can say that the evidence on trans fats is not as good as we would like it to be, no reasonable researcher out there is going to claim that they are protective. That is just ridiculous, and eating more trans fats is not going to make you healthier.

Of course we need some fat in our diet, just as we need some carbs and proteins for everything to work properly. I’ve always suggested people should get their fat from fish and vegetable oils rather than fried foods, that they should get their carbs from whole grains rather than sugary treats and baked goods, and they should top it all off with a little bit of protein (either from lean meats, fish, lentils or nuts). I thought about writing a book and calling it the Labos diet, but then somebody told me that it already has a name. It’s called common sense.


Chris Labos MD

Raw Milk Is For Calves

calvesBy: Christopher Labos MD CM FRCPC

While I was down in the US recently, I discovered that one of the great debates going on that country is whether producers can sell unpasteurized milk. Raw milk has become the fad du jour with advocates claiming that it is safe and good for you. Sadly, neither point is true.

To understand the debate we have to go back to the beginning of pasteurization and to one of the greatest scientists of modern times, Louis Pasteur. Interestingly, Pasteur’s initial work had nothing to do with milk but with wine. He was commissioned to figure out why wine spoiled and turned to vinegar. He discovered that tiny microscopic organisms were present in the wine and caused it to spoil. It was the birth of the germ theory and the founding of a new field of medicine, microbiology.

To be fair, Pasteur didn’t actually invent the idea of heating a substance to kill the bacteria inside, that honour belongs to Nicolas Appert. However, heating a liquid to boiling would frequently change the taste of the wine and give it a more acidic flavour. Pasteur determined the optimal temperature and time required to kill the bacterial contaminants without affecting the taste. So French wine was saved, and the process became known as pasteurization in his honour.

It was Franz von Soxhlet, a German chemist, who first suggested in 1886 that pasteurization could be applied to milk. At the time, and into the early 20th century, milk was a common source of food borne illness, particularly tuberculosis and brucellosis. As a result of pasteurization and a policy to slaughter TB infected cattle, bovine tuberculosis fell drastically. While prior to 1917 it accounted for somewhere between 20-30% of TB cases, it now accounts for about 1%.

The main theme of the raw-milk lobby is that raw milk is safe, and that the bacteria in raw milk are the “good” bacteria. In fact, pasteurization was applied to milk specifically because it wasn’t safe and often transmitted disease. The raw milk literature often makes semi-scientific claims like “Staphylococci, Streptococci, Lactobacillis and Ent. faecalis in raw human milk inhibit pathogenic Staph aureus.” Clearly there is a lack of understanding here as Staph, Strep, and Enterococcus infections are very common and can be very dangerous if left untreated. If they had seen what I’ve seen, namely someone developing meningitis from a listeria infection they would sing a different tune.

The second major claim of the raw milk people is that pasteurization damages the milk and removes the health benefits. Well first off, you don’t really need milk to be healthy and milk consumption is rare in large parts of Asia and Africa. I drink milk daily because my mother made me drink a glass of milk with breakfast every morning and I fear that I am too old to break that habit now. Milk is a good source of calcium (and in Canada of Vitamin A and D because it is added to milk by the government to prevent deficiency). However, these vitamins and minerals aren’t going to be affected by temperature changes and so pasteurizing the milk will have no effect. Most expert organizations agree that apart from a change in the flavour, there is little nutritional difference between raw and pasteurized milk.  Raw milk enthusiasts make a number of other claims that raw milk will boost your immune system. Believe me when I say that if there were a way to “boost your immune system” we would be giving it to chemotherapy patients and those with HIV rather than wasting our time with this debate. The argument centers on the fact that raw milk contains leucocytes and other immune components that will help your immune system. Leucocytes, a.k.a. white blood cells, are the cells that fight off infection. Unfortunately, any leucocytes in milk came from the cow, and a cow’s leucocytes won’t do you any good. In fact they could theoretically do some harm because a cow’s leucocytes see your cells as foreign and would attack them (a concept in medicine we see in transplant patients called graft-versus-host disease). However, in the concentrations observed, they are unlikely to do much any good or harm.

It is possible to drink raw milk and not die in the same way that you can eat raw meat (steak tartar) and not die. But steak tartar is meticulously handled and carefully prepared to minimize the risk of bacterial contamination. However, the risk of infection is not zero and is not recommended for pregnant women or those with compromised immune systems. Sushi is also made of raw fish, but it too is carefully prepared and (in Canada at least) must be flash frozen prior to serving to kill off any bacteria. However, all this preparation incurs some cost which is why these products are somewhat more expensive and only served at fairly high end restaurants. Ordering cheap steak tartar at a local diner, much like buying sushi from a gas station, is no deal in the long run.

Raw milk is managed in the same way. The cows are well treated, fed only the best grain, allowed to roam free and generally treated better than we treat most humans. Importantly, they test their cows and milk for tuberculosis, listeria, and other bacteria and throw away anything contaminated. This is of course incredibly wasteful and costly. It also leads to the destruction of perfectly good food that would be fit for consumption if pasteurized. I know we have been blessed with an abundant food supply here in North America but wilfully destroying food seems wasteful to me when you consider how many people have to do without it.

Clearly, the people advocating raw milk will try to capitalize on the growing “natural is better” delusion that grips our society. It’s important to ask anyone that extols the virtue of raw milk if they have any financial interest in its sale, which of course they always do. So when it comes to raw milk, remember why we started pasteurizing it in the first place because if we forget our history we will be doomed to repeat it.

 

Chris Labos MD

 

Please don’t eat the daisies

daisiesBy: Christopher Labos MD CM FRCPC

Like most people I get most of my news by scanning the headlines and picking a few choice articles to read in depth. In general, political scandals get a pass and world events get a second look. But one day I awoke to find this headline in my Twitter feed: Eating flowers ‘could help reduce cancer risk.’

I really couldn’t let this slide.

I had to read this article if only to find out why “could help reduce cancer risk” was in quotation marks.

The article was published in the British newspaper The Telegraph and opened with this paragraph: “Eating flowers grown in British gardens could help to reduce the risk of heart disease and cancer, according to a new study.”

It made me wonder whether the chipmunks that harass my garden all summer might be on to something.

The article itself was sparse on details, so I went back to the original study, which was published in the Journal of Food Science. This is hardly a high-end medical journal, with an impact factor (how we measure the quality of medical journals) of 1.775, which is pretty underwhelming.

Already skeptical, I read on. Essentially a group of researchers measured the levels of phenols in various species of flowers and reported their antioxidant effects using a variety of chemical tests. Nowhere did the report mention cancer or heart disease, nor did they do any tests on human subjects. Clearly, the Telegraph reporter decided to editorialize a bit.

The big leap was that antioxidants must be good for you because everyone is talking about them. In fact, the clinical evidence for antioxidants is very poor.

It is true that antioxidants can neutralize free radicals. It also true that free radicals have been implicated in a number of diseases, including heart disease and cancer. But clinical trials of antioxidants have come back negative.

Vitamin A, vitamin C, vitamin E and carotenoids (all antioxidants) have been studied in large trials like the Physician’s Health study and the Women’s Health Initiative and have been found to have no benefit in preventing heart disease or cancer.

A recent Cochrane Review came to the same conclusion. Certain supplements like beta carotene have actually been seen to increase cancer risk in certain subgroups like smokers. Will phenols, the latest class of antioxidants to gain popularity, have better outcomes? We shall see; but so far the track record for antioxidants is not stellar.

Clearly, the conclusions of the newspaper account went beyond what the scientific study had reported. The danger of these types of stories is that, firstly, the public becomes misinformed. Although some flowers are edible and can be part of very appetizing dishes, some can be poisonous when ingested. Lilies, azaleas and poinsettias can cause health problems if eaten, although serious health consequences are fairly rare.

What happened here is that a study with very limited clinical applicability was given undue prominence by a British newspaper that capped it off with an eye-catching title that had little evidence to back it up.

Fortunately, most North American media outlets didn’t pick up the flower story and the National Health Service in Britain did a fairly good job of exposing the flimsy evidence behind the headline.

Although I recognize that most people are not going to start reading obscure medical journals, it is worthwhile to go beyond the headlines and read news reports all the way to the bottom. It is especially important to do so if the headline contains the word “miracle cure” or “breakthrough,” because by the end of the article you will probably realize that it is neither.

So my advice to you is not to go eat the flowers in your garden, not to go buy something simply because it has the name antioxidant on the label, and always read health related articles all the way to the bottom. For those of you who made it to the end of this article: well done.

 

Christopher Labos MD CM FRCPC

Division of Epidemiology, Biostatistics and Occupational Health

McGill University

Playing chess with pigeons

pigeons and chessBy: Christopher Labos MD CM FRCPC

I get a surprisingly large amount of hate mail when I advocate for such “radical” things like vaccinations, water fluoridation, and suntan lotion (yes even suntan lotion).  Some people just flat out insult me but some try to re-educate me with their version of the “evidence.”

A similar thing happened this week with the release of a document from an organization called Action on Smoking and Health, which has as its main goal to lobby for tighter restrictions on cigarette sales. Their report focused on the growing use of electronic cigarettes in the UK, which has tripled from 700,000 to about 2 million in the past 2 years. It has shown that electronic cigarettes are a very popular product in the UK and that most people are trying them as a means to quit smoking.

I had several problems with these assertions. Firstly, the sheer popularity of a product doesn’t make it a good idea.  There was of course a time when combustible cigarettes were very popular too. So I got on Twitter and pointed out that this report doesn’t actually provide any new evidence on the long term safety or effectiveness of this product from a medical standpoint.

What happened next was quite amazing. A flurry of e-cig supporters descended upon my post and started offering up “evidence” that e-cigs will “millions of lives” and that I was in the pocket of the big tobacco companies and wanted people to keep smoking. I calmly pointed out that the two biggest manufacturers of e-cigarettes, blu and Vuse, are owned by Lorillard and Reynolds, two of the biggest tobacco companies. Consequently the biggest promoter of e-cigarettes is the tobacco industry (note that Jenny McCarthy, the great luminary of our generation, has become the spokesperson of blu). This sparked apoplectic rage on Twitter where many claimed that what I said wasn’t true and that they were “fighting 4 lives now & future.”

I was then presented with a reference that the Royal College has stated “E-cigarettes will save lives, and we should support their use.” I looked up the reference and pointed out that it was actually an editorial written by a single person not a professional endorsement from the medical community. I was told in response, “What ever you wish to call it, the meaning is plain, Huge Health dividends can be had with Ecigs.” At this point I realized that I was wasting my time and that logic can seldom overcome this degree of idolatrous zealotry.

I remembered a quote that I heard a while back. It is attributed to Scott Weitzenhoffer in a review on Amazon of Eugenie Scott’s book “Evolution vs. Creationism: an introduction.” The quote was “Debating creationists on the topic of evolution is rather like trying to play chess with a pigeon — it knocks the pieces over, craps on the board, and flies back to its flock to claim victory.” Numerous versions of the quote now exist and is often applied to Internet trolls and most other groups who can never change their minds despite evidence to the contrary.

The astute reader will realize that I’ve never actually said what I think about e-cigarettes. I am reserving final judgment on the products, but I have some concerns. First, the widespread marketing so clearly aimed at children (why else would you make the product in cotton candy and bubble gum flavour) is unsettling. Second, while everyone is talking about these products as smoking cessation one company states “blu eCigs® electronic cigarettes are not a smoking cessation product … nor are they intended to treat, prevent or cure any disease or condition.”   The companies have to state this in order to be able to market and sell their product without restrictions or governmental oversight. They let Twitter make the health claims for them.

Sadly, it may take over 10 years before we have enough data to see if e-cigarettes actually do make people quit smoking, reduce cancer incidence, or have any health benefits. Until then I will remain cautiously skeptical, as all good scientists should.

Although I suspect my new found friends on Twitter, (who are seldom right but never in doubt, as Joseph Dobrian put it) will not be so circumspect in their assumptions and continue to claim that their product is the greatest thing since sliced bread. So as they fly back to their flock to claim victory and I pick up the dropping covered chess pieces lying on the floor, I have learned a valuable lesson about arguing with people on the Internet: you can’t win against someone who doesn’t understand the rules.

 

Christopher Labos MD CM FRCPC

Division of Epidemiology, Biostatistics and Occupational Health

McGill University

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