by Em Prof Fred Brouns, Maastricht University, Netherlands; Prof Peter Shewry, Rothamsted Research, Harpenden, UK and Prof Daisy Jonkers, Maastricht University, Medical Center, Netherlands
In recent years, it has been suggested in popular science books and the social media that the consumption of today’s bread causes weight gain and a range of other health problems which may result from changes in the content and type of gluten. These reports have led to increasing public concern about the health effects of not only wheat bread but also other gluten-containing foods. In response has been a strong promotion of the ‘gluten-free diet’ and the use of ‘ancient grains’ which have been suggested to contain less gluten and therefore be healthier.
The international “WellonWheat?” research consortium, led by Maastricht University in collaboration with Wageningen University & Research and other European research centres, aimed to address the concerns about the effects of modern bread types of wheat and bread making processes on health. Previous articles in this series have discussed aspects of wheat gluten content and composition in modern and older types of wheat and bread. Here we discuss the evidence for the frequently heard suggestion that ‘gluten makes you fat!’
Gluten causes obesity, gluten-free induces weight loss
Many of the messages communicated are based on perceived associations between gluten consumption and weight gain. However, an association is not proof of a causal effect. We will therefore discuss whether gluten present in cereal foods indeed may lead to weight gain.
Various explanations are given for how gluten consumption may lead to overweight and eating gluten-free may lead to losing weight. Three of these explanations are:
1) The digestion of gluten leads to the release of peptides, some of which are structurally similar to endorphins (peptide hormones) produced by our nervous system. Generally, endorphins block the perception of pain and increase feelings of wellbeing. Endorphins may also stimulate appetite and therefore increased eating. Gluten peptides which have a structural similarity with endorphins are called glutenexorphins (‘exo’ meaning from outside the body as opposed to ‘endo’ which means secreted by the body). It has been suggested that gluten-exorphins resulting from gluten digestion in our intestine will be absorbed and act as appetite stimulating hormones.
2) Gluten peptides slow down our resting metabolism, resulting in burning less calories and a positive energy balance, causing weight gain.
3) Eating gluten-free foods leads to weight loss: this is taken as evidence that gluten is a cause of weight gain.
Are gluten peptides absorbed?
It is important to note that the presence of gluten derived peptides in the intestine does not show that they are absorbed and have effects on the brain to stimulate appetite or on resting metabolism. In order to have such effects the peptides must not only be absorbed into the body but also in sufficient amounts. In addition, they must remain intact long enough after absorption into the blood to maintain biological activity.
It has been shown that such effects are indeed possible but only when a relatively high concentration is achieved by infusing chemically synthesised gluten-exorphins directly into the brain of rats. The question is whether such effects can also be achieved after gluten consumption in humans and, in particular, whether the uptake into the blood and subsequently transfer into the brain are sufficient. The latter requires passing the blood brain barrier, which in the rat experiments was circumvented by infusion directly into the brain.
It has been shown that extremely small amounts of peptides derived from food digestion may pass from the intestine into blood in specific circumstances, for example when the intestinal wall is inflamed or damaged (leaky) due to alcohol consumption or the use of anti-inflammatory drugs (such as ibuprofen). However, they are rapidly degraded after arriving in the blood (within a few minutes) resulting in loss of bioactivity. Similarly, rapid degradation occurs for all hormone peptides secreted in our body, such as insulin and appetite-regulating peptides. For this reason, a continuous secretion of insulin is required to maintain an effective concentration. Highly controlled studies addressing the quantitative absorption of bioactive peptides from the intestine into blood have shown that the amount absorbed is extremely small and that their enzymatic breakdown in the blood was so rapid that only one-thousandth of the required effective concentration was achieved.
In summary, available scientific data provides no evidence that dietary gluten peptides (gluten exorphins) are absorbed into the blood in sufficient quantities and remain intact for a sufficient time to have a measurable effect on appetite stimulation and food intake.
Does gluten lower resting energy expenditure?
A study in mice showed weight gain after adding gluten to the diet, compared to a gluten-free diet and it was suggested that this weight gain resulted from changes in resting metabolic rate. However, there was no evidence provided to support this suggestion. The question is whether there are comparable data from human studies?
In a recent study entitled ‘Inconsistent effects of gluten on obesity’ (Silva et al. 2020), 40 overweight women (in whom the presence of celiac disease had been excluded) were included in a dietary intervention study in which either gluten-free muffins or gluten-containing muffins (containing 24g gluten) were consumed daily for four weeks. In this study the consumption of gluten had no effect measurable effects on energy intake, body fat, fat-free mass and resting energy expenditure.
Other studies have shown inconsistent correlations between resting metabolic rate and obesity. It is therefore not valid to conclude that gluten peptides cause obesity by lowering resting metabolism.
What do observational studies in humans show?
If the consumption of gluten does have a causal effect on obesity, the incidence of obesity would be expected to be much higher in countries where the consumption of wheat/gluten is very high, compared to countries where consumption is low. However, this does not appear to be the case (see Figure 1).
A study in which all dietary protein intake was exchanged for wheat gluten as the sole protein source also showed no effect on body weight (see Figure 2). Although the study was of relative short duration (50 days exclusively wheat protein consumption) and did not tar get changes in body weight as primary outcome, it did show that a > 5-fold increase in daily wheat protein intake (of which 70-80% is gluten) for 50 days did not result in increased body weight. Furthermore, although the analysis of data from the UK Biobank showed a weak positive association between gluten intake and body weight in women, the opposite (a negative association) was found in men. The authors called these ‘contradictory findings’ and concluded that ‘all observed metabolic associations between gluten and health were weak and clinically irrelevant’. Consequently, although some observational studies have reported associations between estimated gluten intake and body weight, it is likely that other factors play a decisive role.
Finally, in contrast to suggestions that gluten-free eating is associated with a lower body weight, controlled ‘gluten-free studies’ generally show an increase in body weight (Peleg 2024 (4)) which may be explained by an the unfavourable composition of gluten-free foods/meals (which often contain more fat, sugar and starch and less fibre).
Despite containing gluten whole grain foods are beneficial for health and weight
Maki et al. (2019) reported that studies extending between five and 20 years generally showed an inverse association between the consumption of whole grain foods and weight change (Figure 3). Other available data also consistently show that long-term consumption of whole grains is associated with lower risk of developing type two diabetes, cardiovascular disease and colon cancer. Consequently, food authorities worldwide recommend consuming whole grain products (many of which contain gluten) in the daily diet, in addition to vegetables and fruit, in order to reduce the risks of chronic diseases.
It can be concluded based on published scientific studies that extremely small amounts of peptides, released by the digestion of gluten and other food proteins, can enter the blood if the intestinal barrier function is disturbed. However, these peptides are broken down very quickly after appearing in the blood, resulting in loss of biological activity and there is no evidence that peptides from food remain intact into the blood in physiologically relevant amounts for a sufficient period of time to produce measurable effects. Observational studies of gluten intake in large groups of people show that gluten consumption is not related to daily energy intake and body weight. In fact, the consumption of whole grain foods, which usually contain significant amounts of gluten, is widely recommended by national and international health authorities to improve the quality of the diet and reduce the incidence of diet-related chronic diseases. Although gluten and other grain components can trigger celiac disease, allergy and intolerance in genetically-sensitive individuals, about 95 percent of the population may consume gluten and wheat without any problem and there is no reason to label gluten/wheat-free as a healthier dietary lifestyle.
Published in the September 2024 issue of Milling and Grain.
