Is Wheat Making You Wait For Babies? The Gluten Infertility Link
Written By: Dr. Kelly Brogan, M.D.
There are few anxiety triggers as provocative as the primal desire to conceive. To experience that drive, and to be thwarted by seemingly uncontrollable and unidentifiable factors is maddening. Many patients end up in my office because they feel they need help managing these feelings. Instead of medicating their anxiety, I help them to learn relaxation and mindfulness in the midst of stress, and then I help them get pregnant. How?
I have many tools in my kit, but the most powerful one is a grain, sugar, and dairy free diet. In traditional cultures, the preconception couple is offered prime access to nutrient dense foods such as egg yolks, fish eggs, and organ meats, high in fats, fat-soluble vitamins, B vitamins, and choline. Perhaps they appreciated the recently discovered importance of nutrients on both the egg and the sperm.
A woman's body needs to sense that it is an optimal time to conceive and a low fat, high carb diet is a sure way to hang up the "closed for business" sign. Babies, after all, are made of fat and protein like adults, with very little 'starch' to speak of (beyond glycogen and the pinch or two of sugar in the bloodstream). Loren Cordain, in his seminal paper entitled Cereal Grains: Humanity's Double Edged Sword, posits compelling evidence that our genome may not yet have fully adapted successfully, over the past 10,000 years, to meet the challenges of grain consumption. These challenges include the in-built defense mechanisms of these grasses (so-called anti-nutrients and 'invisible thorns' called lectins) that protect them against us, ensuring their survival, including the promotion of local inflammation in the gut, mineral binding, digestive impairments, and changes to gut permeability, recently elucidated by Dr Alessio Fasano.
There is a growing body of evidence to support the efficacy of an approach which controls for glycemic instability and associated polycystic ovarian syndrome, a major cause of infertility, but it is worth focusing on one particularly baby unfriendly "food": gluten.
Gluten is found in wheat and is a member of the prolamine class of proteins; prolamines are predominantly found in the seeds of cereal grass (aka grains) such as barley (horedin), oats (avenin), rye (secalin), rice (Orzenin) and corn (zein). Wheat gluten contains an alcohol soluble class of proteins known as alpha-gliadins, whose proteins trigger autoimmune celiac disease in approximately 1% of the population, and are now understood to trigger inflammatory changes in even non-Celiac immune response in a fraction of the population that may include up to 80%. Up to 87.5% of those with celiac disease do not have any gastrointestinal symptoms leading to a "silent" pathology that often causes decades of malaise before diagnosis. Celiac disease has been associated with non-gut pathology like diabetes, osteoporosis, thyroid dysfunction, and malignancy, and I discuss the relationship, in up to 17% of these patients, between gluten and brain-based symptoms here. For a condemning list of its body polluting effects, a review by Shah and Leffler had this to say:
The spectrum of systemic manifestations associated with CD is broad and encompasses iron deficiency anemia, hyposplenism, reduction in BMD, liver function abnormalities, neuropathy, psychological disturbances, fatigue, myalgias, arthralgias, asthma, weight loss, bloating, abdominal pain, bowel changes, alopecia, headaches, menstrual irregularities, infertility and adverse pregnancy outcomes.
Also, for a list of over 200 adverse health effects linked to gluten across both celiac and non-celiac populations you can view the biomedical abstracts on the Greenmedinfo database: wheat health effects.
Does Gluten Cause Infertility?
According to a recent prospective analysis, the answer may be that, in a subset of women with unexplained infertility (15% of the 7.4-14% of women struggling with infertility are "unexplained"), gluten exposure may be a primary contributor to a distressing and expensive chapter in their lives. Only the second to be done in the US, this study looked at 188 infertility patients and found that 5.9% of those with unexplained infertility turned out to have celiac disease as diagnosed by antibodies and biopsy. All of these patients were Caucasian. They all went on to conceive within a year of dietary change.
A number of European studies (reviewed here) have demonstrated that women with infertility, even those who have failed multiple rounds of IVF, once identified to have antibodies to gliadin and/or tissue transglutaminase (blood tests used in the diagnosis of celiac disease), can go on to conceive once they adopt a gluten free diet. On average, previous data suggests that 2.6-8% of those struggling with infertility have undiagnosed celiac disease. Sticking to dietary recommendations results in decreased secondary amenorrhea, delays in period onset, early menopause, and miscarriage according to a study that analyzed the health of Celiac patients who adhered to a gluten free diet, or who didn't. According to data that suggests a 2.25 fold increased risk of miscarriage, intrauterine growth restriction, low birth weight, and preterm birth, this dietary change may also protect the pregnancy once it does occur. To take related concerns one step further, according to a notable association between adult schizophrenia and gluten antibodies in the pregnant mom, we may be be positively guiding the future brain health of our offspring, epigenetically, by shunning these grains.
How It Messes With You
Notably, the majority of women diagnosed with celiac disease, and those represented in these studies, had no gastrointestinal complaints. That is because we now have a growing understanding of how much more far-reaching gluten's effects are than just the intestine. The effects of wheat on the body, and proposed ways that it interferes with a healthy conception and pregnancy include:
• Nutrient depletion: Zinc, selenium, iron, vitamin D, and calcium deficiency can result from associated changes to the small intestinal lining following exposure to gluten, which a 2007 study published in GUT indicates can occur in those with and without celiac disease, i.e. everyone. These nutrients are vital to proper hormonal signaling including LH and FSH production (ovulation managers), DNA production, and oxygenation. Notably, thyroid dysfunction and its association with celiac disease may be driven, in part, by selenium deficiency, and thyroid balance is critical for conception, miscarriage, and preterm birth prevention.
• Autoimmunity: Gluten typically activates the adaptive immune system by linking to tissues and organs containing an enzyme called transglutaminase, like the gut lining, skin and nervous system, stimulating immune response. This concept of molecular mimicry also accounts for antibodies to thyroid, synapsin, GAD (glutamic acid decarboxylase), and gangliodise, expanding the potential influence of these grains to impact hormonal neurological health. In the setting of pregnancy, placental tissue transglutaminase may be specifically targeted with altered recognition of the fetus by the maternal immune system. There is also evidence that wheat lectin (WGA) has direct, non-immune and genetic susceptibility-mediated adverse effects, and due to its ability to travel freely throughout the body (including the blood brain barrier and perhaps the placental barrier) it may do direct harm to the developing fetus.
• Inflammation: Directly related to triggering the immune system to misrecongnize the body as foreign is the production of inflammatory cytokines or messengers that let the hormonal systems of the body know it is in danger. These typically result after gluten has been "processed" by tissue transglutaminase in the small intestinal tissue and then presented to antibody forming cells as a dangerous trigger of destruction. When exposure to lectins in these grains and or to protein components such as glutenin and gliadin stimulates the innate immune system, we have inflammatory, but potentially non-antibody mediated destruction (meaning it may elude conventional testing).
There's more than the data shows
The kicker is that, even with all of the compelling data leading authors to unequivocally recommend that:
"Owing to the higher risk of CD in these populations, and the likelihood that the GFD improves pregnancy and fertility outcomes as detailed later, we argue that given the low cost of serological screening compared with the great medical expense associated with infertility and complications of pregnancy, CD testing should be strongly considered. We have reason to believe that our current methods of testing grossly underestimate how many women are being negatively impacted by gluten. This is secondary to limited testing for compounds in these grains and also for other foods that may be triggering a related response."
Most physicians who do a "celiac panel" are only testing for alpha gliadin, tissue transglutaminase 2, and endomesial antibody. In a grain consisting of 6 sets of chromosomes, capable of producing greater than 23,000 proteins, this testing may just be too small a window into a very complex space. Testing should optimally include response to all known gluten epitopes, lectins, glutenin, gluteomorphin, and cross-reactants such as dairy, corn, and millet as examined in this study.
Some degree of gluten reactivity is thought to occur in up to 80% of the population and is driven by shared and distinct immune response mechanisms. Response to gluten free diets in placebo-controlled trials and inflammation in the guts of non-celiac patients, even without gliadin antibodies (such as in this study of exposed non-celiac patients) argues for the universal effects of this food, and the individuality of our immune responses accounting the variations in severity and presentation.
The take-home to take-home your baby
One of the reasons I love working with infertility patients is because they are uniquely motivated to improve their health and wellness. My recommendation is to eliminate gluten, at a bare minimum, and to do it for 3-6 months. Find an enlightened practitioner who can help you with these changes and recommend other fertility promoting interventions. Data will continue to emerge around this connection, but if you've been in the infertility mill, or if you are just looking to promote a healthy pregnancy, don't wait. Just do it!