From caffeine to trigonelline, coffee has surprising links to muscle biology

From NAD+ metabolism and glucose uptake to muscle mass and frailty, researchers mapped how coffee and its compounds interact with the biological processes that shape skeletal muscle health.

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In a recent study published in the journal Food & Function, researchers reviewed evidence on the effects of coffee and its bioactive compounds on skeletal muscle (SM) health.

Coffee is a widely consumed beverage valued for its stimulating effects, organoleptic properties, and potential health benefits. It is a major source of bioactive compounds, such as caffeine, hydroxycinnamic acids, trigonelline, and diterpenes, some of which exhibit anti-inflammatory and antioxidant properties.

Habitual coffee intake is linked to a lower risk of certain cancers, cardiovascular disease, type 2 diabetes, and neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases. However, the relationship between coffee (and its bioactive compounds) and SM health is poorly understood.

The study and findings

In the present study, researchers reviewed evidence on the effects of coffee and its bioactive compounds on SM health. First, a systematic literature search was conducted across multiple databases to identify human, animal, and in vitro studies evaluating the effects of coffee, coffee extracts, or major bioactive compounds in coffee. Studies published from 2014 to 2025 were included.

Human studies were restricted to the general population, with studies primarily focused on sports performance or ergogenic effects excluded. Reviews, conference abstracts, meta-analyses, protocols, book chapters, and letters to editors were excluded. Retrieved records underwent abstract/title screening and full-text assessment. Relevant data, such as study characteristics, exposure, measures, and findings, were extracted from studies, and a narrative synthesis was performed.

Of the 21,000+ records identified through database searches, 54 studies were selected for inclusion. These included 21 in vitro studies, 19 animal studies, 13 human studies, and one study with all three models. In vitro studies predominantly used murine SM cell lines, with only two studies on human SM cells or myotubes. Ferulic acid was the most-studied phenolic compound in in vitro studies.

Ferulic acid increased the expression of myosin heavy chain isoforms I (MyHC I) and IIa (MyHC IIa) while reducing MyHC IIb expression in murine myotubes, suggesting a shift in myogenic programming toward an oxidative fiber-type profile. Another study reported that ferulic acid enhanced myoblast proliferation and differentiation in a dose- and time-dependent manner, potentially through increased osteogenic gene expression.

Several in vitro studies indicated that caffeine could reduce myotube diameter and protein synthesis and promote cell death, although many used concentrations considerably higher than those typically achieved in humans after coffee consumption. The only in vitro study on trigonelline showed that it increased nicotinamide adenine dinucleotide (NAD+) levels in differentiated human SM myotubes and primary myotubes from aged mice. Likewise, the only in vitro study on cafestol, a diterpene, found that it enhanced insulin-stimulated glucose uptake in differentiated human SM cells, which was comparable to an anti-diabetic drug (rosiglitazone).

Animal studies showed substantial variation in exposure time, route of administration, animal models, and dose. In one study, coffee supplementation increased the weight of several muscles, including the gastrocnemius, extensor digitorum longus, quadriceps, and tibialis anterior, in male mice. In the triceps, it also reduced the expression of transforming growth factor (TGF)-β and myostatin proteins, which are negative regulators of muscle growth.

Another study showed that coffee administration increased SM weight and grip strength in a murine model of aging. Furthermore, coffee administration decreased fasting blood glucose but did not improve muscle diameter or body weight in diabetic rats compared with controls. Separately, coffee consumption increased glucose oxidation and promoted muscle glycogen accumulation in rats fed a control diet, but these effects were not observed in rats fed a high-fat diet.

Human studies were limited and predominantly observational, with only two clinical trials. One trial reported reduced body fat and increased BIA-estimated SM mass after daily intake of three cups of coffee for 12 weeks. The other trial reported that supplementation with a standardized decaffeinated green coffee bean extract rich in chlorogenic acids led to favorable changes in body composition compared with placebo, although the higher lean mass-to-fat mass ratio appeared to be driven mainly by fat loss rather than a clear increase in lean mass.

One observational study showed that higher coffee intake, total caffeine intake, or caffeinated coffee alone was positively associated with appendicular skeletal muscle mass adjusted for body mass index (ASMBMI) in a middle-aged United States (US) population. A separate analysis identified a non-linear association between caffeine intake and ASMI. Other observational studies conducted in Asian populations reported that coffee intake was positively associated with SM mass or inversely associated with low muscle mass or sarcopenia-related outcomes.

Inverse associations between coffee intake and functional impairment or frailty have also been reported in older adults. For example, habitual coffee intake was associated with a reduced risk of frailty compared with low coffee consumption among European adults aged over 55 years. In a prospective study of older adults (aged ≥ 60 years), consuming at least 2 cups of coffee daily was associated with a lower hazard of impaired mobility compared with no consumption.

Concluding remarks

Collectively, coffee and some of its bioactive compounds may modulate biological pathways pertinent to SM metabolism. However, available evidence remains insufficient to make causal inferences. Most human evidence is observational, while many preclinical studies use isolated compounds, extracts, or doses that may not reflect habitual coffee consumption.

Additionally, long-term intervention studies are needed, with well-defined exposures and validated SM measures, to determine whether coffee and its bioactive compounds have clinically meaningful effects on SM health in humans.

Journal reference:

• Fernández-Cardero Á, Esteves-Mesquita V, Sarriá B, Bravo L (2026). Coffee and coffee-derived bioactive compounds in skeletal muscle health: a scoping review of mechanistic pathways, preclinical evidence and human outcomes. Food & Function. DOI: 10.1039/d6fo02600a, https://pubs.rsc.org/fo/article/doi/10.1039/d6fo02600a/