10 Questions and Answers about Vitamin D3 Toxicity

10 Questions and Answers about Vitamin D3 Toxicity --which you are likely to get wrong! By John Jacob Cannell, M.D. Executive director of The Vitamin D Council 1. If an otherwise healthy adult tried to kill himself by taking an entire bottle (250 capsules) of 1,000 iu cholecalciferol, which of the following would happen? a) The person would die within 24 hours from severe hypercalcemia and widespread calcinosis. b) If the person received intensive treatment for hypercalcemia he may survive. c) Hypercalcemia would be severe but require only supportive treatment. d) Such doses are called "Stoss" therapy and are occasionally used therapeutically although they do not replicate normal physiology. As most Americans are vitamin D deficient, such a one-time dose would probably be a health benefit for the majority of Americans. The correct answer is d. One of the most recent examples is the use of stoss therapy to reduce fracture rates in the elderly (100,000 IU of oral cholecalciferol every four months for five years) by Dr. Trivedi and colleagues (University of Cambridge School of Clinical Medicine) published in the British Medical Journal. How high do you think average 25-hydroxyvitamin D levels were in the subjects after they received 100,000 IU of cholecalciferol every four months for five years? Answer: about 29 ng/ml, still mildly deficient! ( Source) 2. Acute poisoning leading to rapid death from ingestion of vitamin d capsules (successful suicide attempt), a) Has frequently been reported in the literature. b) Has occasionally been reported in the literature c) Has never been reported in the literature. The answer is C, as far as we know. If you know of a report of a successful suicide attempt, accidental death or murder from overdosing on vitamin D supplements, let us know. We do know of one interesting case that demonstrates the relative safety of vitamin D. Industrial strength crystalline vitamin D was added to table sugar, either by accident or on purpose. The two men poisoned were getting about 1,700,000 IU of cholecalciferol every day for seven months. Again, they were getting at least, 1,700,000 units [440 times the Institute of Medicine's toxicity warning (LOAEL)] every day for seven months! Both got very sick but recovered. ( Source) 3. True of false: water has a higher (safer) therapeutic index (the median lethal dose divided by the median effective dose) than cholecalciferol? a) True b) False c) About the same The answer is b. Although exact human studies have never been done for obvious ethical reasons, water intoxication leading to hyponatremia, cerebral edema and occasional death is common in psychiatric populations and may become evident if one drank 80 glasses of water a day, instead of eight. Heaney, et al, recently showed healthy humans utilize about 4,000 IU of cholecalciferol a day, if they can get it. 40,000 IU a day is certainly not acutely toxic. In fact, some research reported that young white humans get up to 50,000 IU from one full body summer sun exposure. ( Source) 4. If a person totally avoided the sun and regularly took two standard multivitamins a day for several years, each containing 400 iu of ergocalciferol, as his sole source of vitamin d, he would, a) Rapidly become vitamin D toxic and require medical attention for symptoms of hypercalcemia. b) Slowly become vitamin D toxic and eventually become symptomatic. c) Slowly develop hypervitaminosis D but remain asymptomatic. d) Obtain a healthful vitamin D blood level. e) Inexorably become vitamin D deficient. The answer is e. Two standard multivitamins contain 800 IU of ergocalciferol, equivalent to about 500 IU of cholecalciferol. If you totally avoided the sun, as many dermatologists routinely recommend with impunity (so far), one would have enough vitamin D to prevent rickets and osteomalacia but would still have a suboptimal 25-hydroxyvitamin D and thus be at risk to develop numerous other chronic inflammatory diseases, not just osteoporosis. For a review of such illnesses, see Zittermann. ( Source) The key is "totally avoided the sun." Remember, most people get 90 percent of their vitamin D requirement from very casual sun exposure, like the sunlight that strikes the uncovered and unsunblocked face, arms and hands when you walk to your car. Vitamin D production in the skin is that fast. Of course, some people follow their doctor's advice and take obsessive steps to prevent sunlight from ever striking their unprotected skin. A host of chronic inflammatory diseases may await the patients who follow such advice, just as trial lawyers may await the doctors that give it. 5. Of the three medications listed below, which is the safest in overdose? a) Vitamin D (250 of the 1,000 IU capsules) b) Aspirin (250 of the 325 mg tablets) c) Tylenol (250 of the 500 mg tablets) The answer is a. In fact 250,000 IU of vitamin D at one time is used as "stoss" therapy, especially in Europe. For a review of many such studies and the doses needed to achieve toxic 25-hydroxyvitamin D levels, see Vieth. ( Source) 6. Which drug has the highest (safest) therapeutic index? a) Depakote b) Lithium c) Coumadin d) Dilantin e) Synthroid f) Theophylline g) Cholecalciferol The answer is g. All of the medication listed except cholecalciferol have narrow therapeutic indices and can easily cause death in overdose. Such is not true for vitamin D and, because of the huge number of capsules needed, is not likely unless one has the industrial strength compound. See below for a sample calculation. 7. In 1997, adams and lee wrote a widely publicized paper about vitamin d toxicity in the annals of internal medicine. The adams and lee paper was accompanied by a stern editorial warning of the dangers of vitamin d written by marriott of the national institute of health. The three authors, a) Correctly diagnosed all five of the patients b) Were thanked by nationally acclaimed vitamin D scientists for their contributions to understanding vitamin D toxicity. c) Showed frightening ignorance about vitamin D toxicity and appeared not to know the difference between the two standard deviation upper limit of a Gaussian distribution and levels known to reflect vitamin D toxicity. The Adams and Lee paper and the editorial by Dr. Marriott are a continued embarrassment to the usually stellar Annals of Internal Medicine. However, the papers are instructive in that they remind us that otherwise educated and intelligent research physicians can confuse the two standard deviation upper limits of a Gaussian distribution with toxicity. For a more detailed critique, as well as several other problematic articles about vitamin D, see this link. 8. By sunbathing for a few minutes in the noonday summer sun, one can easily obtain five times the vitamin d toxicity warning (lowest observed adverse effects level or loael) of the institute of medicine's food and nutrition board. a) True b) False The answer is a, at least for young whites. The IOM lists the Lowest Observed Adverse Effects Level (LOAEL) as 3800 IU for vitamin D. Studies show young whites can make between 10,000 to 25,000 IU in a single, relatively brief, sun exposure. Numerous factors affect the body's ability to make such high amounts of cholecalciferol, with age, race, latitude, clothing, season and sunblock being the main factors. ( Source) 9. If humans are twice as sensitive as the most sensitive mammal tested (male rats), then a 110-pound human would have to injest 88,000 capsules (352 bottles containing 250 of the 1,000 iu capsules) of cholecalciferol in order to have a 50 percent chance of dying (ld50) from an acute overdose. a) True b) False False, about 168 bottles would do it. The LD50 for male rats (the most sensitive mammal tested) is 42 mg/kg. If humans were twice as sensitive that would be an LD50 of 21mg/kg or 21,000 ug/kg or 1,050,000 ug for a 50 kg human which is 42,000,000 units or 42,000 capsules or 168 bottles of the 250 capsules of 1,000 IU cholecalciferol. [Dorman DC (1990) Toxicology of selected pesticides, drugs, and chemicals. Anticoagulant, cholecalciferol, and bromethalin-based rodenticides. Vet Clin North Am Small Anim Pract 20(2):339-352]. 10) As most american blacks suffer from vitamin d deficiency, some black activists feel unwarranted fear and scare techniques about vitamin d toxicity may be racially motivated. That is, racists may be intentionally repeating and promulgating vitamin d toxicity scares in order to prevent relevant government agencies from dealing with the problem of widespread vitamin d deficiency in the black community. a) True b) False True. The recent NIH conference on vitamin D was most interesting in this regard. Very few Blacks were attendees but several were helping with registration. As the conference progressed into the second day, Blacks helping with registration began to listen to the lectures and became increasingly angry as speaker after speaker pointed out how vitamin D deficiency adversely impacts the black community. One young black man told a sad story of how his infant son was recently diagnosed with rickets. Although the 1997 Food and Nutrition Board was an all-white board, most of the Blacks were angry that nothing is being done currently. Certainly, it is true that one of the most effective ways to paralyze the government into continued inaction on the pandemic of vitamin D deficiency would be to raise false and frightening toxicity fears. However, remember that it is easy to suspect vast conspiracies, but in the end it is usually simple incompetence. That is certainly true of the mistakes I've made in my life. 11. In the most recent case of vitamin d toxicity described in the literature, a man recovered uneventfully after taking a health supplement every day for two years that contained 156,000 iu of cholecalciferol. a) True b) False True. Actually, it is likely he took more than that. An industrial manufacturing error was implicated. Such reports help confirm what is known from animal data and that is that it takes a lot of vitamin D to hurt you, but it can be done. ( Source) 12. One of the world's foremost authorities on vitamin d metabolism and physiology recently said, "worrying about vitamin d toxicity is like worrying about drowning when you are dying of thirst." a) True b) False True. The quote is from one of the vitamin D scientists listed below. One of the problems is that there are so few vitamin D scientists in the world, that misconceptions, especially about toxicity, are the rule rather than the exception, even among medical researchers. In 1999, Dr. Reinhold Vieth, perhaps the world's leading expert on vitamin D toxicity and metabolism, wrote a systematic and scholarly review of the world's literature debunking the hysteria surrounding fears of vitamin D toxicity. ( Source) Later, Vieth demonstrated the safety of daily dosing with 4,000 IU of cholecalciferol, a dose that exceeded the current toxicity warnings of the IOM's FNB. ( Source) Two years later, Heaney, et al, demonstrated the safety of doses up to 10,000 IU a day while also demonstrating for the first time that healthy humans utilize 3,000 to 5,000 IU of cholecalciferol a day (10 times the Institute of Medicine Food and Nutrition Board's current recommended Adequate Intake). What the human body does with such high amounts of cholecalciferol remains unknown, but we suspect Nature has a plan. ( Source) In a reply to critics of his paper, Vieth challenged anyone in the scientific community to present even a single case of vitamin D toxicity in adults from ingestion of up to 1,000 ug (40,000 IU) a day of cholecalciferol saying, "I welcome any discussion of evidence of harm with vitamin D3 (not D2) in adults at doses <1,000 ug/d." Vieth's challenge remains unanswered and his work remains unrefuted. ( Source)

More than one-third of Division I college athletes may have low vitamin D levels

A new study presented today at the 2015 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS) found that more than one-third of elite, Division I college athletes may have low levels of vitamin D, which is critical in helping the body to absorb calcium needed to maintain bone mass, and to minimize musculoskeletal pain and injury risk.

Up to 1 billion people globally have insufficient or deficient vitamin D levels. Vitamin D is found in fish, regularly added to milk and dairy products in the U.S., and available as a supplement. Vitamin D also is produced in the body through sun exposure.

"Although multiple studies have demonstrated a high prevalence of vitamin D insufficiency across various populations, there is a paucity of data regarding elite level athletes," said orthopaedic surgeon and lead study author Diego Villacis, MD, administrative chief resident physician at the University of Southern California. "Recent studies also have demonstrated that vitamin D levels have a direct relationship with muscle power, force, velocity and optimal bone mass."

In this study, which appeared in the February 2014 online issue of Sports Health, researchers measured the serum 25-hydroxyvitamin D (serum 25) levels of 223 National Collegiate Athletic Association (NCAA) athletes (121 men and 102 women) between June 2012 and August 2012. The mean serum 25 level for the athletes, enrolled in a broad range of indoor and outdoor sports, was 40.1 ±14.9 ng/mL (?32 ng/mL is considered normal; 20 to <32 ng/mL, insufficient; and <20 ng/mL, deficient). Overall, 66.4 percent of participants had sufficient vitamin D levels and 33.6 percent, insufficient or deficient levels.

Men were 2.8 times more likely to have an abnormal vitamin D level, according to the results, and athletes with darker skin tones also faced a "much higher risk" for insufficient vitamin D. Black athletes were 19.1 times more likely to have abnormal vitamin D levels compared to white athletes, and Hispanics, 6.1 times more likely.

"Our study demonstrated abnormal vitamin D levels in nearly one out of three elite NCAA Division I athletes tested," said Dr. Villacis. "Although there is much more work to be done, our results open the possibility for improved performance and most importantly decreased risk of injury with correction of vitamin D levels. This may potentially be achieved simply and safely through modification of diet, sunlight exposure, and vitamin D supplementation."

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Low Vaccination Rates Fuel the 2015 Measles Outbreak

Inadequate vaccine coverage is likely a driving force behind the ongoing Disneyland measles outbreak, according to calculations by a research team at Boston Children's Hospital. Their report, based on epidemiological data and published online by JAMA Pediatrics, indicates that vaccine coverage among the exposed populations is far below that necessary to keep the virus in check, and is the first to positively link measles vaccination rates and the ongoing outbreak.

By examining case numbers reported by the California Department of Public Health and current and historical case data captured by the HealthMap disease surveillance system, the researchers--led by Maimuna Majumder, MPH, and John Brownstein, PhD, of Boston Children's Informatics Program--estimate that the measles vaccination rate among the case clusters in California, Arizona and Illinois is between 50 and 86 percent, far below the 96 to 99 percent necessary to create a herd immunity effect.

Measles is highly contagious. It's estimated that an infected individual in a population fully susceptible to measles will spread the virus to between 11 and 18 additional people. This number is called the virus's basic reproduction rate, or R0. In a population where at least some individuals are immune to measles, the virus spreads from person to person more slowly. The rate of spread in an immune population is called the virus's effective reproduction rate, or RE.

Using case data, R0 and measles' serial interval (the length of time for each successive wave of transmission to follow the one before), Majumder and Brownstein calculated that the virus's RE in the Disneyland outbreak is between 3.2 and 5.8. From there, the pair calculated their vaccination estimate.

The researchers are quick to note that their estimate does not reflect vaccination across the United States, the state of California or even among the population of Disneyland visitors at the outbreak's start. Rather, it reflects the vaccination rate among the exposed populations in each cluster of cases linked to the outbreak so far.

"It's as though you took everyone exposed to measles in the areas with case clusters, put them in a room and measured the level of vaccine coverage in that aggregate population," says Majumder.

Using the same data sources, the HealthMap team has separately released an interactive model illustrating how differing rates of vaccine coverage could affect the growth of a measles outbreak over time. The model, available at healthmap.org/measlesoutbreak, puts the effects of vaccination into stark relief. If a population is fully vaccinated against the virus, the model predicts that one case of measles will give rise to only two additional cases over 70 days. By contrast, if only 60 percent of a population is vaccinated, more than 2,800 cases will occur over the same time period.

"Our data tell us a very straightforward story--that the way to stop this and future measles outbreaks is through vaccination," says Brownstein, a digital epidemiologist and co-founder of HealthMap and VaccineFinder, an online service that allows users to search for locations offering a variety of vaccinations, including the MMR vaccine that protects against measles. "The fundamental reason why we're seeing the number of cases we are is inadequate vaccine coverage among the exposed.

"We hope these data encourage families to ensure they and their loved ones are vaccinated," he continues, "and help local public health officials in their efforts to control this outbreak."

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Folic Acid Supplementation Among Adults with Hypertension Reduces Risk of Stroke

In a study that included more than 20,000 adults in China with high blood pressure but without a history of stroke or heart attack, the combined use of the hypertension medication enalapril and folic acid, compared with enalapril alone, significantly reduced the risk of first stroke, according to a study appearing in JAMA. The study is being released to coincide with its presentation at the American College of Cardiology Annual Scientific Session.

Stroke is the leading cause of death in China and second leading cause of death in the world. Primary prevention (prevention prior to a first episode) is particularly important because about 77 percent of strokes are first events. Uncertainty remains regarding the efficacy of folic acid therapy for primary prevention of stroke because of limited and inconsistent data, according to background information in the article.

Yong Huo, M.D., of Peking University First Hospital, Beijing, China, and colleagues had 20,702 adults with hypertension without history of stroke or heart attack randomly assigned to receive daily treatment with a single-pill combination containing enalapril (10 mg) and folic acid (0.8 mg; n = 10,348), or a tablet containing enalapril alone (10 mg; n = 10,354). The trial was conducted from May 2008 to August 2013 in 32 communities in Jiangsu and Anhui provinces in China. Participants were tested for variations in the MTHFR C677T gene (CC, CT, and TT genotypes) that may affect folate levels.

During a median treatment duration of 4.5 years, first stroke occurred in 282 participants (2.7 percent) in the enalapril-folic acid group compared with 355 participants (3.4 percent) in the enalapril group, representing an absolute risk reduction of 0.7 percent and a relative risk reduction of 21 percent. Analyses also showed significant reductions among participants in the enalapril-folic acid group in the risk of ischemic stroke (2.2 percent vs 2.8 percent) and composite cardiovascular events (cardiovascular death, heart attack and stroke) (3.1 percent vs 3.9 percent).

There was no significant difference between groups in the risk of hemorrhagic stroke, heart attack, or all-cause death, or in the frequencies of adverse events.

The authors write that this trial (China Stroke Primary Prevention Trial; CSPPT), with data on individual baseline folate levels and MTHFR genotypes, has provided convincing evidence that baseline folate level is an important determinant of efficacy of folic acid therapy in stroke prevention. "The CSPPT is the first large-scale randomized trial to test the hypothesis using individual measures of baseline folate levels. In this population without folic acid fortification, we observed considerable individual variation in plasma folate levels and clearly showed that the beneficial effect appeared to be more pronounced in participants with lower folate levels."

"We speculate that even in countries with folic acid fortification and widespread use of folic acid supplements such as in the United States and Canada, there may still be room to further reduce stroke incidence using more targeted folic acid therapy -- in particular, among those with the TT genotype and low or moderate folate levels."

Editorial: Folate Supplements for Stroke Prevention

"The trial by Huo et al has important implications for stroke prevention worldwide," write Meir Stampfer, M.D., Dr.P.H., and Walter Willett, M.D., Dr.P.H., of the Harvard T. H. Chan School of Public Health and Channing Division of Network Medicine, Boston, in an accompanying editorial.

"Although the trial participants all had hypertension, there is little reason to doubt that the results would apply to normotensive persons, although the absolute effect would be smaller. It is possible to debate the ethics of whether a replication trial should be performed, especially because folic acid supplementation (or fortification) is safe and inexpensive, and carries other benefits. Large segments of the world's population, potentially billions of people, including those living in northern China, Bangladesh, and Scandinavia, have low levels of folate."

"Individuals with the TT genotype might particularly benefit, although it seems unlikely that genotyping for that purpose would be cost-effective. Also, some persons in the United States on the low end of the distribution of folate intake may benefit; effects in this subgroup would not have been detected in previous trials. Ideally, adequate folate levels would be achieved from food sources such as vegetables (especially dark green leafy vegetables), fruits and fruit juices, nuts, beans, and peas. However, for many populations, achieving adequate levels from diet alone is difficult because of expense or availability. This study seems to support fortification programs where feasible, and supplementation should be considered where fortification will take more time to implement."



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A breakfast of champions for diabetics

A breakfast of champions for diabetics

Our modern epidemic of obesity has led to an alarming rise in the incidence of diabetes. More than 382 million people on the planet suffer from diabetes, predominantly type-2 diabetes. For these people, blood sugar surges -- glucose spikes after meals -- can be life threatening, leading to cardiovascular complications.

A new Tel Aviv University study published in Diabetologia proposes a new way to suppress deadly glucose surges throughout the day -- eating a high-caloric breakfast and a more modest dinner. According to TAU's Prof. Daniela Jakubowicz and Dr. Julio Wainstein of the Wolfson Medical Center's Diabetes Unit, Prof. Oren Froy of the Hebrew University of Jerusalem, and Prof. Bo Ahrén of Lund University in Sweden, the combined consumption of a high-energy breakfast and a low-energy dinner decreases overall daily hyperglycaemia in type-2 diabetics.

"We found that by eating more calories at breakfast, when the glucose response to food is lowest, and consuming fewer calories at dinner, glucose peaks after meals and glucose levels throughout the day were significantly reduced," said Prof. Jakubowicz.

All in the timing

The new study was conducted on eight men and 10 women aged 30-70 with type-2 diabetes. Patients were randomized and assigned either a "B diet" or "D diet" for one week. The B diet featured a 2946 kilojoule (kj) breakfast, 2523 kj lunch, and 858kj dinner, and the D diet featured a 858 kj breakfast, 2523 kj lunch, and 2946 kj dinner. Both diets contained the same total energy measured in kilojoules, a food energy measurement similar to a calorie, but were consumed at different times through the day, with the larger meal taking place during breakfast in the B diet. The larger meal included two slices of bread, milk, tuna, a granola bar, scrambled egg, yoghurt and cereal; the smaller meal contained sliced turkey breast, mozzarella, salad and coffee.

Patients consumed their diets at home for six days before the day of testing. On the seventh day, each group consumed their assigned meal plan at the clinic, and blood samples were collected just before breakfast and at regular intervals after the meal. Blood sampling was repeated at the same intervals after lunch and dinner. Post-meal glucose levels were measured in each participant, as well as levels of insulin, c-peptide (a component of insulin), and glucagon-like-peptide 1 hormone (GLP-1, also known as incretin: an indicator of glucose metabolism that stimulates insulin release). Two weeks later, patients switched to the alternate diet plan, and the tests were repeated.

The results of the study showed that post-meal glucose elevations were 20% lower and levels of insulin, C-peptide, and GLP-1 were 20% higher in participants on the B diet compared with those on the D diet.

What -- and when -- to eat

Despite the fact that both diets contained the same calories, blood glucose levels rose 23 percent less after the lunch preceded by a large breakfast.

"By demonstrating that a diet of high-energy breakfasts and more modest dinners is more effective in lowering overall daily post-meal glucose surges, we suggest that such a regimen is a powerful therapeutic approach for improving glycemic control and may potentially reduce cardiovascular complications in type- 2 diabetics," said Prof. Jakubowicz. "It is not enough to tell the diabetic patient what he or she should or should not eat. It is more important to emphasize that a more advantageous meal schedule should be followed."

The researchers are currently engaged in an extended study of the benefits of high-energy breakfast and reduced-calorie dinners over time.


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Journal Reference:

Daniela Jakubowicz, Julio Wainstein, Bo Ahrén, Yosefa Bar-Dayan, Zohar Landau, Hadas R. Rabinovitz, Oren Froy. High-energy breakfast with low-energy dinner decreases overall daily hyperglycaemia in type 2 diabetic patients: a randomised clinical trial. Diabetologia, 2015; DOI: 10.1007/s00125-015-3524-9
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ACL injuries in female athletes traced to genes

Dr. William Landis, G. Stafford Whitby Chair in Polymer Science at The University of Akron, and his UA research associate Robin Jacquet discovered, with fellow collaborators, that a high occurrence in ACL injuries among female athletes may be traced to genes.
Credit: Lauren Collins

[Click to enlarge image]

Female athletes endure two to eight times more anterior cruciate ligament, or ACL, injuries than their male counterparts. Genes are likely a major factor, according to Dr. William Landis, G. Stafford Whitby Chair in Polymer Science at The University of Akron, and Dr. Kerwyn Jones, Chair of Pediatric Orthopedics for Akron Children's Hospital. The findings could change the way women athletes receive sports training and treatment for their injuries and could possibly lead to genetic counseling regarding athletic participation.

Jones and Landis have been probing the significant gap in ACL injury occurrence among young women and men athletes for years, exploring other potential attributes such as hormones and the gait or stance of women as compared to men.

"We wondered about the influence of genes and how they might affect the structure or integrity of these ligaments," Landis says, explaining that he and Jones examined 14 fresh surgical samples of ruptured ligament tissue taken from both female and male athletes who suffered non-contact injuries of the tissues. "After some very detailed and extensive analysis through gene microarray techniques, we discovered 32 genes that were expressed to much different degrees in the female injured ligaments compared with those of males."

Of the 32 expressed genes, the researchers closely examined three that gave rise to specific proteins related to ligament structure and integrity. They discovered that all three genes regulated ligament tissue in a much different manner in female compared to male tissue.

"The differences clearly may account for weaker anterior cruciate ligaments in the females compared to the males," Landis says.

Published in the Journal of Bone & Joint Surgery , the finding has significant implications in sports medicine and training, orthopedics and clinical practice. The discovery could open discussions about recommended genetic counseling for young women interested in participating in sports, with results either clearing them for participation or signaling a need for specialized training.

"We can't change genes," Jones says, "but we can help girls strengthen their core and improve their technique. Several exercises and prevention programs have been proven to reduce the number of ACL injuries and we can and should introduce them to all girl athletes starting in middle school."

Clinical treatment and training in sports for females and males would now likely need to be modified so that the anterior cruciate ligaments could be strengthened appropriately in order to reduce or avoid injuries to this tissue most common in females, Landis adds.

"It's also possible that genetic counseling may be used to guide personal decisions about taking part in athletics. The study presents an entirely new, unanticipated and extremely important perspective about anterior cruciate ligament injuries observed so often in female athletes compared to males," Landis says.

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Journal Reference:
J. S. Johnson, M. A. Morscher, K. C. Jones, S. M. Moen, C. J. Klonk, R. Jacquet, W. J. Landis. Gene Expression Differences Between Ruptured Anterior Cruciate Ligaments in Young Male and Female Subjects. The Journal of Bone & Joint Surgery, 2015; 97 (1): 71 DOI: 10.2106/JBJS.N.00246


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Infant gut bacteria and food sensitization: Associations in the first year of life

<<Being too clean is not healthy.  Perhaps we are caught in a negative feedback loop.>>

A new study from Canadian researchers at the University of Alberta and University of Manitoba is shedding new light on changes in intestinal bacteria of infants that can predict future development of food allergies or asthma.

The research, published in the February edition of the journal Clinical & Experimental Allergy and highlighted as the publication's "Editor's Choice," reveals that infants with a fewer number of different bacteria in their gut at three months of age are more likely to become sensitized to foods such as milk, egg or peanut by the time they are one year old. Infants who developed food sensitization also had altered levels of two specific types of bacteria, Enterobacteriaceae and Bacteroidaceae, compared to infants who didn't.

"Using DNA techniques to classify bacteria in the Scott and Guttman laboratories at the University of Toronto, we obtained information on the different types of 'good' bacteria present in infant stool collected at three months of age and then at one year of age," says Anita Kozyrskyj, professor in the Department of Pediatrics at the University of Alberta and senior author of the study. "We were able to then see which bacteria present at three months predicted the development of food sensitization at one year, as measured by a skin reaction test to the food."

"We are continuing to study this process," says Meghan Azad, assistant professor in the Department of Pediatrics & Child Health at the University of Manitoba and lead author of the study. "Ultimately, we hope to develop new ways of preventing or treating allergies, possibly by modifying the gut microbiota."

The study, funded by the Canadian Institutes of Health Research and AllerGen NCE, looked at data from 166 infants enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. This landmark study involves more than 3,500 families and their newborn infants across Canada, including 1,000 in Manitoba and 750 in Edmonton, who are being closely monitored to determine the genetic and home environment factors that contribute to future allergies and asthma.

Researchers say the data on gut bacterial patterns during infancy can serve as a biomarker for future disease.

"It is something that one can measure that indicates increased risk of food sensitization by one year of age," says Kozyrskyj.

Both Kozyrskyj and Azad, who is also a research scientist at the Children's Hospital Research Institute of Manitoba, caution that the results don't necessarily mean the children will progress to full-blown food allergies in later life. The researchers will soon be expanding their sample size as data comes in from other children at CHILD Study sites in Edmonton, Winnipeg, Vancouver and Toronto. The hope is to eventually have data from as many as 2,500 children from across Canada. The researchers plan to follow them as they grow, examining results again at the ages of three and five.

"At the end of the day, we want to know if infants who show changes to normal gut bacteria composition will go on to develop food or other allergies, or even asthma," says Kozyrskyj.

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