Microcrystalline and modified cellulose
Also known as: Microcrystalline Cellulose, MCC, Modified cellulose, powdered cellulose, cellulose powder, cellulose ethers, cellulose esters, methylcellulose, carboxymethyl cellulose, hydroxypropyl cellulose
Overview
Microcrystalline Cellulose (MCC) is a purified, partially depolymerized cellulose derived primarily from wood pulp or cotton linters. It is classified as an insoluble dietary fiber and a widely used pharmaceutical excipient. Modified celluloses are chemically or physically altered cellulose derivatives, such as methylcellulose and carboxymethyl cellulose, designed to enhance specific functional properties like solubility or viscosity. While MCC is primarily used as a bulking agent, binder, and anti-caking agent in supplements and pharmaceuticals due to its insolubility, high surface area, and thermal stability, modified celluloses serve as emulsifiers, stabilizers, and thickening agents. Both forms are considered dietary fibers. Research on MCC and modified celluloses is extensive, particularly regarding their safety as excipients and food additives, with a strong foundation of safety data. While human clinical data on their specific physiological benefits are limited, animal studies provide insights into their potential gut health effects.
Benefits
Microcrystalline Cellulose (MCC) and modified celluloses primarily act as insoluble dietary fibers, offering several potential benefits, particularly for gut health. In animal models, MCC has been shown to significantly improve gut barrier integrity and modulate gut microbiota. Specifically, in mouse models of colitis, MCC reduced inflammation markers such as TNF-α and IL-1β, improved colon length, and enhanced the expression of tight junction proteins, indicating a stronger intestinal barrier. These effects suggest a potential role in mitigating inflammatory bowel conditions, though human clinical evidence is currently lacking. Furthermore, the fermentation of cellulose by gut microbiota promotes beneficial bacteria like *Alistipes finegoldii*, which in turn induces anti-inflammatory cytokines (IL-22) and antimicrobial peptides (Reg3γ), contributing to reduced colitis severity in animal studies. The observed effects in animal models, such as significant reductions in inflammatory cytokines and disease activity indices, highlight the potential of MCC to support gut health, with benefits typically observed within 21 days of dietary supplementation in these models. However, the strength of evidence for these benefits in humans is limited, primarily relying on mechanistic and animal studies.
How it works
Microcrystalline Cellulose (MCC) and modified celluloses function primarily as insoluble fibers within the gastrointestinal tract, as they are not absorbed into the bloodstream. Their main mechanism involves physically reinforcing gut barrier integrity and modulating the composition of the gut microbiota. They achieve this by reducing the expression of pro-inflammatory cytokines, such as TNF-α and IL-1β, and promoting the expression of tight junction proteins like claudins, occludin, and ZO-2, which are crucial for maintaining the epithelial barrier function. Additionally, these fibers influence the gut immune system through microbiota-mediated processes. The fermentation of cellulose by specific gut bacteria, such as *Alistipes finegoldii*, leads to the production of anti-inflammatory mediators like IL-22 and antimicrobial peptides (Reg3γ). MCC has also been shown to downregulate Toll-like receptor 4 (TLR4) signaling, further contributing to its anti-inflammatory effects. All these actions occur locally within the gut lumen.
Side effects
Microcrystalline Cellulose (MCC) and modified celluloses are generally recognized as safe (GRAS) by regulatory agencies, with a very high safety profile. Extensive toxicology studies, including those reviewed by EFSA, have found no evidence of carcinogenicity or reproductive toxicity. Side effects are minimal and typically mild. The most common adverse effects, occurring in a small percentage of individuals, may include mild gastrointestinal discomfort or bloating, particularly at higher doses. Rare reports suggest mild laxative effects in some sensitive individuals. Hypersensitivity reactions are extremely rare. There are no significant drug interactions reported with MCC or modified celluloses. Contraindications are not specifically identified, and these compounds are considered safe for the general population, including children and the elderly. However, caution is advised in individuals with severe gastrointestinal disorders, as with any dietary fiber. Overall, the risk of adverse effects is very low, making them widely used and well-tolerated ingredients in supplements and pharmaceuticals.
Dosage
While specific human dosage recommendations for Microcrystalline Cellulose (MCC) as a standalone dietary fiber supplement are not well-established, typical dietary fiber supplementation ranges from 5-15 grams per day for general health benefits. In animal studies, effective doses were approximately 2.5 g/kg body weight, but human equivalent doses are not clearly defined. As an excipient in supplements and pharmaceuticals, MCC doses vary widely depending on the formulation and desired effect. There is no established maximum safe dose for MCC; high doses are generally well tolerated, but excessive intake may lead to gastrointestinal symptoms such as bloating or discomfort due to its bulking properties. MCC can be taken with or without food, as its timing of intake is not critical given its local action in the gut. It is available in various forms, including powder, tablets, and capsules, and is often combined with other fibers or excipients. Since MCC is not absorbed, its action is entirely local within the gastrointestinal tract, and no specific cofactors are required for its efficacy.
FAQs
Is MCC safe as a dietary fiber supplement?
Yes, Microcrystalline Cellulose (MCC) is widely used and considered safe by regulatory agencies, with minimal side effects reported even at high doses. It is generally well-tolerated.
Does MCC have direct anti-inflammatory effects?
Evidence from animal models suggests MCC can reduce gut inflammation by modulating pro-inflammatory cytokines and influencing the gut microbiota, leading to beneficial immune responses.
Can MCC replace soluble fibers?
MCC is an insoluble fiber and does not ferment as extensively as soluble fibers. It complements, but does not replace, the distinct benefits offered by soluble fibers.
How quickly do benefits appear?
Animal studies have shown effects within approximately three weeks of consistent supplementation. However, human data on the time course of benefits are currently lacking.
Is MCC absorbed or metabolized?
No, Microcrystalline Cellulose is not absorbed or metabolized by the human body. It remains in the gut lumen and acts locally as a dietary fiber.
Research Sources
- https://pubs.acs.org/doi/10.1021/acsomega.1c06552 – This animal study investigated the effects of Microcrystalline Cellulose (MCC) in a mouse model of colitis. It found that MCC improved gut barrier function, reduced pro-inflammatory cytokines (TNF-α, IL-1β), and modulated gut microbiota composition, leading to an amelioration of colitis symptoms. The study highlights MCC's potential anti-inflammatory properties in the gut.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC7583510/ – This mechanistic animal study explored how dietary cellulose influences gut microbiota and immune responses in gnotobiotic mice. It demonstrated that cellulose fermentation by gut microbiota promoted the growth of *Alistipes finegoldii*, which in turn induced anti-inflammatory cytokines (IL-22) and antimicrobial peptides (Reg3γ), contributing to reduced colitis severity. The research provides insights into the microbiota-mediated benefits of cellulose.
- https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2018.5047 – This systematic safety review by EFSA evaluated the safety of Microcrystalline Cellulose and modified celluloses as food additives. Based on multiple toxicology studies, the review concluded that these compounds show no evidence of carcinogenicity or reproductive toxicity and are considered safe for consumption. This authoritative assessment focuses on the safety profile rather than efficacy.