Is Trehalose Toxic? The Comprehensive Safety Profile
Trehalose is a naturally occurring disaccharide, or double sugar, made of two glucose molecules. It is found in a wide range of natural sources, including mushrooms, yeast, and insects. Commercially, trehalose is produced from starch via an enzymatic process and is used as a food ingredient for its stabilizing, moisture-retaining, and sweetness-providing properties. Its safety has been the subject of several evaluations by leading food safety authorities around the world.
Regulatory Approval and Toxicology Studies
Trehalose has undergone extensive toxicological testing to determine its safety for use in food. These studies have consistently shown no significant adverse effects at standard intake levels.
- U.S. Food and Drug Administration (FDA): In 2000, the FDA issued a “No questions” letter regarding trehalose's Generally Recognized As Safe (GRAS) status, indicating no safety concerns for its intended use.
- European Union (EU): The Scientific Committee on Food (SCF) evaluated trehalose and authorized it to be marketed as a novel food ingredient, declaring it safe.
- Joint FAO/WHO Expert Committee on Food Additives (JECFA): This international committee allocated an Acceptable Daily Intake (ADI) of “not specified” for trehalose in 2000, signifying that it has a very low toxicity and does not pose a health risk at levels used in food.
- Animal Toxicology: Comprehensive studies on mice, rats, and dogs examining acute, short-term, and reproductive toxicity at high doses showed no treatment-related adverse effects.
- Genotoxicity and Carcinogenicity: Trehalose has been tested for its ability to cause genetic mutations or cancer, with all tests showing negative results.
The Trehalose and C. difficile Controversy
In 2018, a study published in the journal Nature sparked widespread media reports suggesting a causal link between trehalose consumption and the rise of two particularly virulent strains of Clostridioides difficile, RT027 and RT078. The study found that these strains, which emerged around the same time as the wider use of trehalose in the food supply, have acquired genetic mutations that allow them to metabolize very low concentrations of trehalose efficiently.
However, this initial media sensationalism was largely overblown and based on a misunderstanding of the epidemiological evidence. Subsequent, more robust studies, including reviews published in EBioMedicine and Gut Microbes, have refuted this direct link.
Key findings from later research include:
- Epidemiological evidence shows the rise of these C. difficile strains predated the significant increase in trehalose usage in the food supply.
- Genetic analysis revealed that the trehalose-metabolizing variants were already common long before the epidemic rise of the virulent strains.
- Studies using a human gut model found that trehalose supplementation did not cause C. difficile infection. Instead, it remodeled the microbiota in a way that prevented simulated C. difficile infections.
- Further research even showed trehalose intake led to a reduction in the detection of the C. difficile toxin to undetectable levels in a human gut model.
Potential Side Effects and Considerations
While generally safe, trehalose is not completely free of potential side effects, though they are mild and typically related to dosage.
- Gastrointestinal Discomfort: Consuming large quantities of trehalose at one time, much like with sugar alcohols or lactose for intolerant individuals, can lead to osmotic diarrhea, bloating, and borborygmus (stomach rumbling). For a 60 kg person, a laxative effect is typically seen at intakes over 39g.
- Trehalase Deficiency: A very small percentage of the population has a congenital or acquired deficiency of the intestinal enzyme trehalase, which breaks down trehalose. These individuals may experience gastrointestinal symptoms after consuming even small amounts of trehalose. While rare, one study noted a higher prevalence in parts of Greenland.
Trehalose vs. Sucrose: A Comparison
| Feature | Trehalose | Sucrose (Table Sugar) |
|---|---|---|
| Sweetness | Approximately 45% as sweet as sucrose. | 100% (Standard for comparison). |
| Glycemic Index (GI) | Low (GI of 38), causing a much slower and lower rise in blood glucose and insulin levels. | High, causing a rapid spike in blood glucose and insulin levels. |
| Digestion | Slowly digested by the enzyme trehalase in the small intestine. | Rapidly digested by the enzyme sucrase into glucose and fructose. |
| Cellular Benefits | Known for cellular protection against stress, neuroprotective, and antioxidant properties. | Lacks specific protective cellular functions associated with trehalose. |
| Dental Health | Non-cariogenic, meaning it is not readily fermented by oral bacteria that cause tooth decay. | Highly cariogenic, a primary contributor to tooth decay. |
For those interested in the detailed human studies confirming the lack of toxicity, further information is available on the Inchem website for trehalose safety evaluations.
Conclusion
Based on comprehensive research and evaluations by international food safety authorities, trehalose is not considered toxic for the vast majority of people. The previous concerns linking trehalose to the emergence of virulent C. difficile strains were largely dismissed by subsequent scientific studies. For most individuals, any adverse effects are limited to mild gastrointestinal discomfort resulting from high intake, a physiological response similar to other poorly absorbed sugars. Its unique properties, such as a low glycemic index and potential cellular protective benefits, have positioned it as a valuable ingredient in the food, cosmetic, and pharmaceutical industries.
However, people with a rare trehalase deficiency should limit consumption. As with any sugar, balanced consumption is key, especially for diabetics who need to monitor their carbohydrate intake. Ultimately, the scientific consensus strongly supports trehalose as a safe food ingredient when used in moderation.
