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Validity of food additive maltodextrin as placebo and effects on human gut physiology: systematic review of placebo-controlled clinical trials

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A Correction to this article was published on 26 June 2023

This article has been updated

Abstract

Purpose

Maltodextrin (MDX) is a polysaccharide food additive commonly used as oral placebo/control to investigate treatments/interventions in humans. The aims of this study were to appraise the MDX effects on human physiology/gut microbiota, and to assess the validity of MDX as a placebo-control.

Methods

We performed a systematic review of randomized-placebo-controlled clinical trials (RCTs) where MDX was used as an orally consumed placebo. Data were extracted from study results where effects (physiological/microbial) were attributed (or not) to MDX, and from study participant outcomes data, before-and-after MDX consumption, for post-publication ‘re-analysis’ using paired-data statistics.

Results

Of two hundred-sixteen studies on ‘MDX/microbiome’, seventy RCTs (n = 70) were selected for analysis. Supporting concerns regarding the validity of MDX as a placebo, the majority of RCTs (60%, CI 95% = 0.48–0.76; n = 42/70; Fisher-exact p = 0.001, expected < 5/70) reported MDX-induced physiological (38.1%, n = 16/42; p = 0.005), microbial metabolite (19%, n = 8/42; p = 0.013), or microbiome (50%, n = 21/42; p = 0.0001) effects. MDX-induced alterations on gut microbiome included changes in the Firmicutes and/or Bacteroidetes phyla, and Lactobacillus and/or Bifidobacterium species. Effects on various immunological, inflammatory markers, and gut function/permeability were also documented in 25.6% of the studies (n = 10/42). Notably, there was considerable variability in the direction of effects (decrease/increase), MDX dose, form (powder/pill), duration, and disease/populations studied. Overall, only 20% (n = 14/70; p = 0.026) of studies cross-referenced MDX as a justifiable/innocuous placebo, while 2.9% of studies (n = 2/70) acknowledged their data the opposite.

Conclusion

Orally-consumed MDX often (63.9% of RCTs) induces effects on human physiology/gut microbiota. Such effects question the validity of MDX as a placebo-control in human clinical trials.

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Funding

Research was supported by the NIH grant DK055812, DK091222 and DK097948 (to FC), F32DK117585 and K01DK127008-01 (to AB), and P01DK091222 Germ-free and Gut Microbiome Core and R21DK118373 (to ARP).

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  1. Rawan Almutairi and Abigail Raffner Basson have equally contributed to this work.

  2. Fabio Cominelli is a Senior Medical Scientist.

Authors and Affiliations

  1. Department of Pathology, Case Western Reserve University, 2109 Adelbert Road, Cleveland, OH, 44106, USA

    Rawan Almutairi & Pamela Wearsh

  2. Department of Medicine and Division of Gastroenterology & Liver Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Abigail Raffner Basson, Fabio Cominelli & Alexander Rodriguez-Palacios

  3. Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA

    Abigail Raffner Basson, Fabio Cominelli & Alexander Rodriguez-Palacios

  4. Germ-Free and Gut Microbiome Core, Cleveland Digestive Diseases Research Core Center, Case Western Reserve University, 2109 Adelbert Road, Cleveland, OH, USA

    Alexander Rodriguez-Palacios

  5. University Hospitals Research and Education Institute, University Hospital Cleveland Medical Center, Cleveland, OH, USA

    Fabio Cominelli & Alexander Rodriguez-Palacios

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  1. Rawan Almutairi
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AR-P, ARB: Conceptualization; ARB, RA: Literature search and data analysis; RA, ARB, AR-P: Writing- original draft preparation; AR-P, ARB, PW, FC: Writing—review and editing; AR-P, ARB, FC: Funding acquisition; AR-P, FC, PW: Resources; AR-P, ARB, PW: Supervision.

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Correspondence to Alexander Rodriguez-Palacios.

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Almutairi, R., Basson, A.R., Wearsh, P. et al. Validity of food additive maltodextrin as placebo and effects on human gut physiology: systematic review of placebo-controlled clinical trials. Eur J Nutr 61, 2853–2871 (2022). https://doi.org/10.1007/s00394-022-02802-5

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