Effects of hypocaloric wholegrain rye vs refined wheat diets on weight loss, cardiometabolic risk factors and gut microbiota: A 12-week randomized controlled trial

Journal article, 2026

Background and aims: Wholegrain rye foods have shown promising effects on metabolic regulation and weight-loss, which may be mediated via gut microbiota and derived metabolites. This study aimed to investigate effects of hypocaloric diets with wholegrain rye versus commonly consumed refined wheat on body weight, fat mass, metabolic risk markers and gut microbiota. The study also explored determinants of diet-induced weight loss.
Methods: Participants with overweight or obesity were randomized (1:1) to 12-week hypocaloric diets, substituting habitual cereals with wholegrain rye or refined wheat foods. Body weight and composition were measured and fecal- and blood samples were collected at baseline, after 6 weeks and 12 weeks.
Results: Of 255 participants, 229 completed the study. Weight loss was 3.2 kg in the rye-group and 2.9 kg in the wheat-group, with no significant difference between groups (p = 0.32). Plasma acetate and butyrate were higher after 12 weeks in the rye-group versus wheat-group (p = 0.003) and microbial taxa, previously associated with negative health outcomes were reduced in the rye-group. Reductions in CRP by 17 % (p = 0.03) were observed in the rye-group, while both CRP (r = 0.17, p = 0.001) and HOMAIR (r = 0.13, p = 0.02) at baseline were associated with fat mass change in the wheat-group. Additionally, acetate at baseline was inversely associated with body weight change across groups (r = -0.25, p < 0.001). Baseline gut microbiota was not associated with weight loss after 12 weeks.
Conclusions: Wholegrain rye versus refined wheat foods as part of a hypocaloric diet did not result in larger weight loss. However, wholegrain rye reduced CRP and induced changes in gut microbiota and short-chain fatty acids which may have positive implications for cardiometabolic health. Notably, baseline HOMA-IR and CRP correlated with weight and fat mass reductions, suggesting that individuals with elevated inflammation and insulin resistance may benefit more from wholegrain rye foods. Gut microbiota at baseline was not associated with intervention-induced weight loss. Trial Registration: ClinicalTrials.gov ID: NCT04203758. https://classic.clinicaltrials.gov/ct2/show/ NCT04203758?term=Rye&cond=Overweight+and+Obesity&cntry=SE& city=Gothenburg&draw=2&rank=3. (c) 2026 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).