Gluten has become the villain of the diet world, most commonly associated with wheat intake. However, the question as to whether a gluten-free diet is always better for women’s health is one that deserves to be settled. A new study in the journal Nutrients explores existing evidence in this area.
Review: Gluten and Wheat in Women’s Health: Beyond the Gut. Image Credit: Galigrafiya / Shutterstock
Wheat is a cheap, shelf-stable, easy-to-use complex carbohydrate. Traditionally, it is used along with beans or legumes of various sorts, this combination presenting a complete amino acid profile. It contains gluten protein as well, which accounts for the flip side of this ubiquitous cereal.
Gluten is one of the main storage proteins of wheat but is also found in barley and rye. It contains large amounts of proline and glutamine, which give it its twisted form. When mixed with water, as in every wheat-based food, and especially when kneaded, gluten ‘develops’, that is, the chains form numerous inter-chain bonds to give wheat-based breads their characteristic rise and give.
The developed gluten is a film of elastic air-filled spaces that can expand to hold the gas incorporated during kneading, mixing, or formed during fermentation or chemical reactions. This film is stable enough when heated to hold the shape of the expanded bubbles even after the cooled air contracts.
Gluten yields three major forms of the soluble component called gliadins, which are rich in proline and glutamine and are not easily broken down by human gut proteases. Gliadins are chiefly responsible for celiac disease (CD) in genetically predisposed individuals.
Another condition associated with wheat protein is wheat allergy (WA), which is at present linked to a lipid transfer protein (LTP, Tri a 14), omega-5-gliadin (Tri a 19), and amylase trypsin inhibitor family (ATIs), all of which evoke an immunoglobulin-E (IgE)-mediated allergic response. A third category of wheat-linked disease is non-celiac gluten/wheat sensitivity (NCGWS). The exact component associated with this condition is unknown at present, though gluten, ATIs, and FODMAPs (fermentable oligo-, di-, and monosaccharide and polyol) have been investigated.
In all these conditions, increased gut permeability is a prime factor in disrupting normal immune tolerance to gut bacteria. Zonulin is a protein secreted in response to gluten or bacterial overgrowth and reduces the integrity of the gut epithelial barrier by disrupting the epithelial cell tight junctions.
This results in antigens moving more freely between the gut lumen and the underlying subepithelial barrier, the lamina propria. This ‘leaky gut’ is at the heart of multiple conditions caused by chronic inflammation.
When exposed to gluten in vitro, specifically gliadin, intestinal cells produce higher levels of zonulin, which then return to normal in half an hour. This response is excessive in CD patients, both in magnitude of rise and duration.
A GFD avoids all foods containing gluten, namely, the three cereals named above, plus spelt, kamut, and triticale. Instead, it includes gluten-free grains like rice, corn, buckwheat, quinoa, legumes, or processed gluten-free (GF) products. In Europe, GF products accounted for sales of USD 3.3 billion in 2023 and will probably rise to USD 5.4 billion over the next five years.
Interestingly, GF products may often be less healthy, with more saturated fat, sugar, and salt but less protein, fiber, and vitamins. Thus, GFDs may increase the risk of metabolic diseases like coronary artery disease and high blood sugar or high blood cholesterol, and micronutrient deficiency. Of course this is not so when the diet is part of a healthier lifestyle with little processed foods and more fruits and vegetables.
A GFD may also reduce bacterial diversity in the gut and alter the microbiota composition, more especially in healthy women. This could lead to the replacement of favorable probiotic species like Bifidobacteria by opportunistic pathogens like Enterobacteriaceae.
Healthy women choose to adopt a GFD despite these clear risks because of gluten-associated symptoms or because they think it will help them control their weight or is healthier. This motivated the current study.
What did the study show?
Celiac disease (CD) is an autoimmune disorder affecting about 1.5% of the population, especially in developed countries. Females are at double the risk. Many CD patients have other autoimmune conditions such as type 1 diabetes mellitus, Addison’s disease, or connective tissue disorders like Sjogren’s syndrome.
A GFD helps resolve symptoms and avoid complications in CD patients with any of these conditions. However, women with CD have a lower quality of life (QOL) than men due to lingering bowel symptoms, feeling different and therefore worried or depressed, and are more likely to accept it passively.
If untreated, CD may affect reproductive health and pregnancy outcomes. GFDs may help improve this area. GFDs may also increase bone mass density (BMD), which is typically lower since CD may increase the risk of osteoporosis via lower nutrient absorption.
Overall, about one in five CD patients continue to have symptoms even on a GFD, probably due to cross-contamination.
Non-Celiac Gluten/Wheat Sensitivity (NCGWS)
NCGWS is diagnosed if wheat triggers both gut-related and unrelated symptoms compared to placebo in a double-blind challenge. The difficulty of this criterion has left the prevalence of NCGWS unclear. Half of these patients have IgG antigliadin antibodies.
NCGWS patients, especially women, often go on a GFD. This increases the chances of lower BMD of the lower spine and femoral necks compared to those with irritable bowel syndrome (IBS), though not so low as CD patients. Especially with other food sensitivities, NCGWS patients have a significantly lower calcium intake, indicating that in addition to GFD, they may be avoiding other foods, including dairy, as well.
About a quarter of NCGWS patients, especially females or those diagnosed at older ages, have autoimmune disease (AID), higher than with IBS or in healthy individuals. Possibly prolonged gluten exposure causes sustained local inflammation and triggers more robust autoimmune responses. This results in increased gut permeability with later AID.
Notably, over 70% of patients with NCGWS have antinuclear antibodies (ANA), a known AID biomarker.
IBS patients usually react to the presence of FODMAPs rather than a single food component like gluten. Yet, the GFD helps relieve bloating and abdominal pain. In fact, IBS is closely associated with NCGWS, though without the non-gut-related symptoms.
A GFD also suppresses antigliadin antibodies in NCGWS patients.
GF diets also help some patients with fibromyalgia (FM). FM causes chronic pain, tiredness, sleep disruption, mood aberrations, and poor cognitive performance. Going gluten-free may also help women with chronic autoimmune thyroiditis (CAT) who have normal levels of thyroid function, preventing the onset of hypothyroidism.
It is important to look for the presence of NCGWS in these patients, indicating a subset who might benefit from the GFD.
Again, in endometriosis, which affects up to a tenth of women of reproductive age, most current treatments do not relieve symptoms adequately. About two-thirds, therefore, follow various diets, with 15% choosing a GFD. Some evidence indicates a potential for reduction in pain, better physical function, and improved social and mental health for such patients.
What are the implications?
“Only in the case of the coexistence of gluten-related disorders do we recommend gluten restriction, here proven to be beneficial.”
In most CD patients, a GFD demonstrably and reliably relieves symptoms and brings the gut epithelium back to its normal form. For NCGWS patients, the GFD may be temporary.
A GFD is not per se a healthier diet or a therapy for any disease. Like any diet that restricts certain food groups, care must be taken to keep it balanced and avoid deficits in calories or macro/micronutrients. It is significantly more expensive and affects social eating as well.
Further high-quality studies are mandatory before a GFD can be recommended for other conditions, including FM, CAT, or endometriosis, unless the presence of NCGWS is proven.