Caloric Restriction Mimetics in Nutrition and Clinical Trials
Open accessAbstract
The human diet and dietary patterns are closely linked to the health status. High-calorie Western-style diets have increasingly come under scrutiny as their caloric load and composition contribute to the development of non-communicable diseases, such as diabetes, cancer, obesity, and cardiovascular disorders. On the other hand, calorie-reduced and health-promoting diets have shown promising results in maintaining health and reducing disease burden throughout aging. More recently, pharmacological Caloric Restriction Mimetics (CRMs) have gained interest of the public and scientific community as promising candidates that mimic some of the myriad of effects induced by caloric restriction. Importantly, many of the CRM candidates activate autophagy, prolong life- and healthspan in model organisms and ameliorate diverse disease symptoms without the need to cut calories. Among others, glycolytic inhibitors (e.g., D-allulose, D-glucosamine), hydroxycitric acid, NAD+ precursors, polyamines (e.g., spermidine), polyphenols (e.g., resveratrol, dimethoxychalcones, curcumin, EGCG, quercetin) and salicylic acid qualify as CRM candidates, which are naturally available via foods and beverages. However, it is yet unclear how these bioactive substances contribute to the benefits of healthy diets. In this review, we thus discuss dietary sources, availability and intake levels of dietary CRMs. Finally, since translational research on CRMs has entered the clinical stage, we provide a summary of their effects in clinical trials.
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Pharmacological compounds mimicking calorie restriction became widely used in the medication of metabolic diseases as a substitute for decreased calorie intake.
“Pharmacological compounds mimicking calorie restriction (CRM) became widely used in the medication of metabolic diseases as a substitute for decreased calorie intake [88].”
From Molecular Targets of 20-Hydroxyecdysone in Mammals, Mechanism of Action: Is It a Calorie Restriction Mimetic and Anti-Aging Compound? (2025) · cites this paper as [88]
The Introduction (page unavailable) says experimental CRM candidates are rare in clinical research and hold promise for medical use, contrary to the claim that they have become widely used as medication. The Abstract says candidates may mimic some effects of calorie restriction without cutting calories, but does not describe established treatment of metabolic diseases. (LLM, conf=0.88)
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Experimental — accuracy not yet measuredCalorie restriction mimetics typically achieve weight loss, change metabolic rates, prevent accumulation of reactive oxygen species, and influence pathways that are also activated in calorie restriction.
“these typically achieve weight loss, change metabolic rates, prevent accumulation of reactive oxygen species, and influence pathways that are also activated in calorie restriction.”
From Molecular Targets of 20-Hydroxyecdysone in Mammals, Mechanism of Action: Is It a Calorie Restriction Mimetic and Anti-Aging Compound? (2025) · cites this paper as [88]
The Introduction (page not given) says caloric restriction mimetics can mimic metabolic alterations induced by calorie restriction and activate related pathways. It does not establish that they typically change metabolic rates or prevent reactive oxygen species from accumulating. The Hydroxycitric Acid clinical-studies section (page not given) reports only small, short-term weight-loss effects for one candidate and says its effects in humans remain controversial, so it does not support typical weight loss across mimetics. (LLM, conf=0.88)
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Flagged first, then by citations
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The significance of caloric restriction mimetics as anti-aging drugs
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- Authors
- Hofer, S. J., Davinelli, S., Bergmann, M., Scapagnini, G., & Madeo, F.
- Affiliations
- University of Graz (AT)
- University of Molise (IT)
- Corresponding author
- Hofer, Sebastian J.
- Venue
- Frontiers in Nutrition
- Publisher
- Frontiers Media SA
- Published
- 2021-09-06
- Volume
- 8
- Pages
- 717343-717343
- ISSN
- 2296-861X (ISSN-L)
- PMC
- PMC8450594
- OpenAlex
- W3197727205
- Cited by
- 109
- References
- 304
- Citations by year
- 2026: 12 · 2025: 26 · 2024: 17 · 2023: 30 · 2022: 21 · 2021: 3
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Nutrition (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Archivio Istituzionale della Ricerca - Università degli Studi del Molise (submittedVersion)
- Funders
- Austrian Science Fund (F3007, F3012, P27893, P29203, P29262, P31727, W1226)
- Bundesministerium für Bildung, Wissenschaft und Forschung (Fast4Health, flysleep, Unkonventionelle Forschung-InterFast)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- caloric restriction mimetics, caloric restriction, autophagy, healthspan, lifespan extension, non-communicable diseases, Western diet, dietary polyphenols, resveratrol, curcumin, epigallocatechin gallate, quercetin, NAD+ precursors, polyamines, glycolysis inhibitors, hydroxycitric acid, D-glucosamine, D-allulose, salicylic acid, dietary bioactive compounds, clinical trials
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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