Vanguard Neurologist

A gluten-free, casein-free diet may lead to improvements in behavior and physiological symptoms in some children diagnosed with an autism spectrum disorder (ASD), according to researchers at Penn State. The research is the first to use survey data from parents to document the effectiveness of a gluten-free, casein-free diet on children with ASD. “Research has shown that children with ASD commonly have GI [gastrointestinal] symptoms,” said Christine Pennesi, medical student at Penn State College of Medicine. “Notably, a greater proportion of our study population reported GI and allergy symptoms than what is seen in the general pediatric population. Some experts have suggested that gluten- and casein-derived peptides cause an immune response in children with ASD, and others have proposed that the peptides could trigger GI symptoms and behavioral problems.” The team – which included Laura Cousino Klein, associate professor of biobehavioral health and human development and family studies – asked 387 parents or primary caregivers of children with ASD to complete a 90-item online survey about their children’s GI symptoms, food allergy diagnoses, and suspected food sensitivities, as well as their children’s degree of adherence to a gluten-free, casein-free diet. The team’s results appeared online this month in the journal Nutritional Neuroscience. Pennesi and Klein and their team found that a gluten-free, casein-free diet was more effective in improving ASD behaviors, physiological symptoms and social behaviors for those children with GI symptoms and with allergy symptoms compared to those without these symptoms. Specifically, parents noted improved GI symptoms in their children as well as increases in their children’s social behaviors, such as language production, eye contact, engagement, attention span, requesting behavior and social responsiveness, when they strictly followed a gluten-free, casein-free diet. According to Klein, autism may be more than a neurological disease – it may involve the GI tract and the immune system. “There are strong connections between the immune system and the brain, which are mediated through multiple physiological symptoms,” Klein said. “A majority of the pain receptors in the body are located in the gut, so by adhering to a gluten-free, casein-free diet, you’re reducing inflammation and discomfort that may alter brain processing, making the body more receptive to ASD therapies.” The team found that parents who eliminated all gluten and casein from their children’s diets reported that a greater number of their children’s ASD behaviors, physiological symptoms and social behaviors improved after starting the diet compared to children whose parents did not eliminate all gluten and casein. The team also found that parents who implemented the diet for six months or less reported that the diet was less effective in reducing their child’s ASD behaviors. According to the researchers, some of the parents who filled out the surveys had eliminated only gluten or only casein from their children’s diets, but survey results suggested that parents who completely eliminated both gluten and casein from their child’s diet reported the most benefit. “While more rigorous research is needed, our findings suggest that a gluten-free, casein-free diet might be beneficial for some children on the autism spectrum,” Pennesi said. “It is also possible that there are other proteins, such as soy, that are problematic for these children.” The reason Klein and Pennesi examined gluten and casein is because they are two of the most common “diet offenders.” “Gluten and casein seem to be the most immunoreactive,” Klein said. “A child’s skin and blood tests for gluten and casein allergies can be negative, but the child still can have a localized immune response in the gut that can lead to behavioral and psychological symptoms. When you add that in with autism you can get an exacerbation of effects.” Klein’s advice to parents of children with ASD? “If parents are going to try a gluten-free, casein-free diet with their children, they really need to stick to it in order to receive the possible benefits,” she said. “It might give parents an opportunity to talk with their physicians about starting a gluten-free, casein-free diet with their children with ASD.”

From  “It’s a Miracle, I am a New Person” by Akiva Novick and Sarit Rosenblum

Charedi rabbis don’t usually show up on the cover of Yediot Achronot, Israel’s #1 secular newspaper, but the unprecedented miracle that happened this month to Mir Rosh Yeshiva Rabbi Rafoel Shmuelevitz landed him on the cover of Yediot this morning. Rabbi Shmuelevitz is the first ALS patient in history to be cured from this previously non-treatable and devastating illness.

The following post is a translated excerpt from the Yediot Achronot article “It’s a Miracle, I am a New Person” by Akiva Novick and Sarit Rosenblum

What took place this past month at Hadassah Hospital’s Department of Neurology was not expected even by the most senior neurologists.

An ALS patient- a chronic disease with no known cure that causes a slow and painful process of muscular dystrophy- who was wheelchair-bound and had difficulty speaking and breathing, underwent an complete turnaround. From being handicapped and dependent on others for his most basic daily needs, suddenly Rabbi Rafoel Shmuelevitz stood on his feet, and returned to teaching at the flagship Mir Yeshiva, which he heads.

The treatment that is responsible, it appears, for the dramatic improvement in his condition was developed by the Israeli biotechnology company Brainstorm, and is based on stem cells. This is the first time that someone who has been treated with stem cells has regained abilities which were previously lost. Despite the great caution that is guiding the doctors as they discuss the rabbi’s condition, it is difficult to ignore the excitement which surrounds even the most stern of staff members when they talk about the turnaround that the rabbi has experienced…

Rabbi Rafoel Shmuelevitz recalls, “I couldn’t talk. It was difficult for me to breathe, and my lack of balance made it impossible to get up from my wheelchair. Even when they supported me I was able to walk only with difficulty. My students couldn’t understand me when I spoke.”…

In 2010, after a series of tests at Minnesota’s Mayo Clinic, his doctors told him the difficult news, Rabbi Shmuelevitz had ALS [also known as Lou Gehrig's Disease], which is considered the most severe known neuromuscular disease. ALS patients gradually lose all of their motor abilities, until they eventually lose their ability to breathe and die from suffocation. The vast majority of patients die within three to five years following diagnosis. A small number of patients, for example physicist Stephen Hawking, manage to survive for years, but are almost unable to function.

“The American doctors and the Israeli doctor who treats me, Professor Menachem Sade of Wolfson Hospital, agreed that the only possible way to improve my condition would be to receive stem cell treatment at Hadassah,” explains the rabbi. “That was my final hope.”

Last May, the Ministry of Health granted approval to the Israeli biotechnology company Brainstorm, specializing in the development of technologies and medications based on stem cells, and the Hadassit company associated with Hadassah Medical Center, to begin a clinical trial of a new treatment based on cell therapy, which is meant to delay or stop the degeneration of nerve cells in ALS patients…This is the first treatment of its kind in history.

Because of the severity of his condition, and the fact that he was suffering from 2 different muscular diseases, the rabbi was not allowed to participate in the clinical trial…However he was given the treatment as a “compassionate treatment,” intended for patients who have no other hope.

A month ago, the rabbi was given the treatment for the first time, and the effect on him was incredible. “A few days after the treatment, my whole life began to change,” he says with a smiling face. “My speech began to improve, it became easier to breathe and I began to walk unassisted. I am even able to climb stairs. My students understand every word I say. It’s truly a miracle from Heaven. I am a new person as a result of the treatment I received.”

“It’s hard to describe the excitement that took hold of us as a result of the amazing results of this treatment,” says Brainstorm president Chaim Leibovitch…

Also the doctors could not remain apathetic to the amazing effect of the treatment on the rabbi’s condition. “The change that occurred in him was huge, and also the objective improvement in his functioning was extremely impressive,” explains one of the hospital’s doctors with excitement. “From being handicapped, a person who couldn’t walk and couldn’t talk, a significant amount of his abilities have returned…There is no doubt that a great drama is taking place here. We need to remember that we are talking about a single isolated case. On the other hand, even isolated reports like this can also signal a medical breakthrough.”

Encouraging results, even if they are on a smaller scale, have also been witnessed among some of the 12 patients participating in the clinical trial…

As is the way of the world, the rabbi and his students see things a little differently [from the doctors]. His students talk about “Mass prayer rallies” and “A miracle.” At the same time that top medical minds were laboring to rehabilitate the rabbi’s systems at the hospital, at the Mir Yeshiva the top minds were constantly reading Psalms for his recovery, and learning pages of gemara in order to “tip the scale” in the upper worlds in favor of the 74-year-old rabbi, who has stood for close to 30 years at the head of one of the largest yeshivot in the world (with over 7000 students).

“The rabbi’s family decided when they started treatment to turn to all of the yeshivot in the world to request assistance,” says the rabbi’s assistant. An emotional plea went out in the name of important rabbis to pray for the rabbi’s recovery, and his full name was released for special “Mee Sheberach” prayers worldwide. When the rabbi was lying on the treatment table at the hospital, thousands of students gathered to read Psalms at the Lakewood Yeshiva in New Jersey, at the Ponevitch Yeshiva in Bnei Brak, and at Jerusalem’s Mir Yeshiva.

“The rabbi saw the announcement that went out with his name and broke out into tears,” his assistant says. “During the two or three days that he was at the hospital, the prayers didn’t stop. After that we returned home, and an extreme improvement began in his condition. He got up and started walking, even without support…Everyone who saw him said that this was a revealed miracle, that this is simply a new human being.”

At this stage, of course, it is still difficult to state whether we are talking about a miracle or just a historic medical breakthrough, which will grant hope to patients suffering from one of the most difficult and cruel diseases that exists. But about one thing nobody is arguing: such a dramatic improvement in such a nearly hopeless situation, has very rarely ever been witnessed in the natural world.

From Medical News Today:

A gluten-free, casein-free diet may lead to improvements in behavior and physiological symptoms in some children diagnosed with an autism spectrum disorder (ASD), according to researchers at Penn State. The research is the first to use survey data from parents to document the effectiveness of a gluten-free, casein-free diet on children with ASD.

“Research has shown that children with ASD commonly have GI [gastrointestinal] symptoms,” said Christine Pennesi, medical student at Penn State College of Medicine. “Notably, a greater proportion of our study population reported GI and allergy symptoms than what is seen in the general pediatric population. Some experts have suggested that gluten- and casein-derived peptides cause an immune response in children with ASD, and others have proposed that the peptides could trigger GI symptoms and behavioral problems.”

The team – which included Laura Cousino Klein, associate professor of biobehavioral health and human development and family studies – asked 387 parents or primary caregivers of children with ASD to complete a 90-item online survey about their children’s GI symptoms, food allergy diagnoses, and suspected food sensitivities, as well as their children’s degree of adherence to a gluten-free, casein-free diet. The team’s results appeared online this month in the journal Nutritional Neuroscience.

Pennesi and Klein and their team found that a gluten-free, casein-free diet was more effective in improving ASD behaviors, physiological symptoms and social behaviors for those children with GI symptoms and with allergy symptoms compared to those without these symptoms. Specifically, parents noted improved GI symptoms in their children as well as increases in their children’s social behaviors, such as language production, eye contact, engagement, attention span, requesting behavior and social responsiveness, when they strictly followed a gluten-free, casein-free diet.

According to Klein, autism may be more than a neurological disease – it may involve the GI tract and the immune system.

“There are strong connections between the immune system and the brain, which are mediated through multiple physiological symptoms,” Klein said. “A majority of the pain receptors in the body are located in the gut, so by adhering to a gluten-free, casein-free diet, you’re reducing inflammation and discomfort that may alter brain processing, making the body more receptive to ASD therapies.”

The team found that parents who eliminated all gluten and casein from their children’s diets reported that a greater number of their children’s ASD behaviors, physiological symptoms and social behaviors improved after starting the diet compared to children whose parents did not eliminate all gluten and casein. The team also found that parents who implemented the diet for six months or less reported that the diet was less effective in reducing their child’s ASD behaviors.

According to the researchers, some of the parents who filled out the surveys had eliminated only gluten or only casein from their children’s diets, but survey results suggested that parents who completely eliminated both gluten and casein from their child’s diet reported the most benefit.

“While more rigorous research is needed, our findings suggest that a gluten-free, casein-free diet might be beneficial for some children on the autism spectrum,” Pennesi said. “It is also possible that there are other proteins, such as soy, that are problematic for these children.”

The reason Klein and Pennesi examined gluten and casein is because they are two of the most common “diet offenders.”

“Gluten and casein seem to be the most immunoreactive,” Klein said. “A child’s skin and blood tests for gluten and casein allergies can be negative, but the child still can have a localized immune response in the gut that can lead to behavioral and psychological symptoms. When you add that in with autism you can get an exacerbation of effects.”

Klein’s advice to parents of children with ASD?

“If parents are going to try a gluten-free, casein-free diet with their children, they really need to stick to it in order to receive the possible benefits,” she said.

“It might give parents an opportunity to talk with their physicians about starting a gluten-free, casein-free diet with their children with ASD.”

• From: Holistic Primary Care – Summer 2012, Ciel Patenaude

Gut and vaginal microflora are probably not the first things you think about when working with a couple struggling to conceive a child, but perhaps they should be.

Jean-Jacques Dugua, ND, a naturopathic physician from Toronto who specializes in fertility and hormonal balance, has found that presence or absence of particular strains of beneficial bacteria in the female digestive and reproductive tracts have a much greater influence on fertility than most clinicians realize.

Strategies aimed at balancing the GI and vaginal microbiome hold huge promise for optimizing fertility—both with and without in vitro fertilization (IVF) interventions—while simultaneously influencing the health of mother and child in a positive manner.

In order to understand how the microenvironment influences fertility, Dr. Dugua believes it is essential to recognize the human body as a symbiotic organism, a system that is reliant upon the presence and proper activity of other species for optimal functioning.

The Symbiotic Human

Distinctly human cells are outnumbered 10 to 1 by microbial cells representing thousands of different strains of commensal bacteria. Flora in the GI tract are responsible for many essential metabolic and physiologic processes including: proper digestion of food, bioavailability of many types of vitamins, sleep cycle and immune system regulation, and primary defense against incoming pathogens.

Though research in this field is still in its infancy, there is an increasing body of evidence that suggests that bacterial populations play an important role in the perpetuation of our species.

Researchers exploring the potential of probiotic organisms to positively influence human fertility have looked at this issue from three main angles: improving IVF outcomes and fertility through management of pathogenic bacterial infections; use of probiotics to minimize pregnancy complications, reduce systemic inflammation and decrease pre-term births; and supporting the future health of the child and mother through optimal states of health during pregnancy.

Infections and Infertility

Infections within any organ system can be extremely detrimental to fertility and pregnancy; reproductive system infections are an obvious threat. Several studies have shown that Bacterial Vaginosis (BV) increases the risk of spontaneous preterm delivery of a low birth-weight infant, decreases the possibility of successful implantation through IVF, and greatly raises the risk of other adverse pregnancy outcomes and complications (Hillier SL, et al. N Engl J Med. 1995; 333: 1737–1742).

A vaginal infection related to imbalances in vaginal pH, BV is characterized by a lack of Lactobacilli—a genus normally found in high numbers in the vaginal tract—and increased numbers of facultative or anaerobic organisms that decrease the normal acidity of the vagina.

Researchers at Ghent University in Belgium, reported that presence of BV is a strong and negative factor in overall fecundity. They point to the large percentage of IVF patients who test positive for BV (Verstraelen H, Senok AC. Reprod Biomed. 2005 Dec; 11(6): 674–675).

The mechanism linking BV with preterm birth is unknown, though Dr. Dugua hypothesizes that it relates to stimulation of the fetal adrenal system, a process normally activated only when gestation is complete. In response to an environmental stressor such as the presence of infection, it is possible that the fetal endocrine system initiates the birthing process in order to escape a potential threat. Dr. Dugua acknowledged that this explanation is entirely hypothetical at this point, but it is plausible. He anticipates future research outlining the precise physiological correlation between infections and preterm delivery.

Along with BV, there are countless other infections that may potentially affect fertility and pregnancy, all of which are related to the presence or absence of beneficial bacterial populations.

Probiotic organisms in the gut produce lactic acid as well as their own endogenous antibiotic (called bacteriocin) which can counter pathogenic organisms (Isolauri E, et al. Am J Clin Nutr. 2001 Feb; 73(2 Suppl): 444S–450S). They also act as a physical barrier to shield the GI mucosa from pathogens, literally “taking up all the space” so that colonization is not possible.

Without adequate numbers of these bacterial populations, a woman’s overall immune system is compromised, making her far more susceptible to viruses, parasites, and other invading pathogens that can be detrimental to fertility and pregnancy

Follicular Foci

Previously thought to be entirely sterile, the follicular fluid surrounding the developing fetus can harbor pathogenic species of bacteria in large numbers of women undergoing IVF treatment. In an Australian study, women who tested positive for follicular bacteria had only a 25% IVF success rate, as compared to the standard success rate of 47–50%.

The bacterial presence was hypothesized at first to be a side effect of transvaginal oocyte retrieval (TVOR), the process by which eggs are retrieved for fertilization. This procedure allows for the possibility of cross-contamination between the vaginal tract and the follicular fluid. However, in a third of the women tested, the species of bacteria found were unlike anything present in the lower vaginal tract!

Further research is necessary in order to fully understand how these follicular bacterial infections arise, where the organisms originate, and how they affect the course of pregnancy. One can assume that the presence of infection so close to a developing fetus cannot be beneficial.

Inflammation & Infertility

Infertility correlates with increased systemic inflammation (as seen in patients with endometriosis and other gynecologic disease), as do pregnancy complications such as preeclampsia and preterm birth (Weiss G, et al. Reproductive Sciences. 2009; 16: 216–229). Several studies have shown that probiotic supplementation can attenuate inflammatory biomarkers. It is plausible to suppose that use of probiotics to down-regulate nonspecific chronic inflammation could potentially enhance fertility.

Investigators in Helsinki found that serum hsCRP levels were significantly reduced in people given a milk-drink containing one of the following probiotic species: Lactobacillus rhamnosus GG, Bifidobacterium animalis subsp. Lactis, or Propionibacterium freudenreichii subsp. Shermanii.

It is interesting that Interleukin-2 (IL-2) was also significantly reduced through the consumption of particular strains, suggesting that bacterial populations have a direct effect on systemic inflammatory cascades (Kekkonen RA, et al. World J Gastroenterol. 2008 Apr 7; 14(13): 2029–2036).

Bifidobacterium lactis has been found to reduce TNF-a and systemic cytokines all of which are important biomarkers in inflammation expression and treatment (Matsumoto M, Benno Y. Biosci Biotechnol Biochem. 2006 Jun; 70(6): 1287–1292).

Probiotics may also have a role in the modification of placental trophoblast inflammation., This has clinical relevance in the context of preeclampsia. A recent cohort study of over 33,000 women in Norway found a significant correlation between consumption of probiotic dairy products and reduced likelihood of pregnancy complications such as a preeclampsia, increased the potential for fullterm births and reduced chance of birth defects and miscarriage.

Clinical Implications

There are many reasons to consider probiotics in the management of infertility, but Dr. Dugua cautioned against simplistic approaches and exaggerated expectations. Probiotic supplementation does not always succeed in rectifying imbalances in commensal flora, and may not translate directly into improved fertility.

Research on this subject is fairly limited, and hardly conclusive. Investigators at Tel Aviv University looked at intravaginal supplementation with Lactobacillus species, and found that it had no effect on IVF outcomes in women with BV.

That said, if probiotics are used judiciously in the context of an overall lifestyle intervention aimed at improving a woman’s total health status, they can sometimes make a difference. Dr. Dugua said that in order to approach imbalances in the female reproductive system, one must look at the functioning of her whole body. Merely supplementing with species that seem to be lacking will not address the underlying causes for why those bacterial populations were diminished in the first place.

“Antibiotics, stress, poor eating habits— these throw our bacterial species out of balance”, he affirms. Effective fertility treatment— with or without IVF—requires a whole-person approach. The state of the GI and vaginal flora is, in effect, a biomarker for the overall health of the whole body.

While probiotics are in no way a “cure” for infertility, Dr. Dugua does have several recommendations for women attempting to get pregnant or maintain a pregnancy. He has found that supplementation with Lactobacillus rhamnosus GG, Bifidobacterium bifidum, Lactococcus lactis, and Bifido breve have been found to be beneficial in optimizing fertility and preventing complications of pregnancy. He recommends that women take the probiotics throughout pregnancy.

If BV infection is present, he prescribes probiotics to be administered vaginally as a suppository, as it appears that oral probiotic intake doesn’t always lead to significant increases in the vaginal bacterial population. In all other cases, he suggests that patients take oral probiotics—preferably a blend of several recommended bacterial species.

Since probiotics are living organisms that interact with one another, and with the biological “environment” into which they’re placed, probiotic supplementation is by nature an inexact science. Dr. Dugua emphasized that, “You’ll never really know how each species behaves in an individual until they try it” (see related article, Strategies for Establishing a Healthy Gut Microbriome, p. 1).

A Challenge and Opportunity

The causes of infertility are not always obvious, and in many cases, the picture is complicated. One thing, however, is very clear: the problem is common. According to the Center for Disease Control, over 7 million Americans—nearly 12% of the reproductive age population—experience difficulty conceiving.

In the absence of obvious reasons for infertility, or when those reasons are insurmountable, many couples are opting for Assisted Reproductive Technology (ART). IVF is the most common approach, and considered to be the most effective.

However, even among 20–29 year olds—the most fertile age for women— the success rate of IVF (which does not always reflect live birth rate, but rather the maintenance of a transplanted fetus) is only 47%. Success decreases significantly with age, moving to a low of 11% for women aged 40–44. The procedure is also physically and emotionally stressful, time-consuming, and expensive.

Clearly, we need a wider spectrum of options to help enhance fertility. Diet and lifestyle factors may be the keys to increasing fertility and successful complication- free pregnancy.

In the search for future fertility treatments, we may find that the answer doesn’t even lie within our own cells, but within those of the commensal organisms that continually support our existence. Research on the microbiome’s influence on human reproduction is still in very early stages, yet the discoveries to date are promising.

It makes sense to at least consider probiotic supplementation as part of a broader lifestyle intervention aimed at improving fertility; the potential for side effects is nearly nonexistent, and there are reasons to think that it could be helpful.