The Clostridioides difficile Controversy
In early 2018, a study published in the journal Nature suggested a possible link between the increased use of trehalose in the food supply and the rise of particularly virulent strains of Clostridioides difficile (C. difficile). The study was based on laboratory experiments with mice and in vitro tests, finding that certain virulent strains of C. difficile could more effectively metabolize lower concentrations of trehalose. This led to media sensationalism and public concern that the sugar additive was fueling a dangerous epidemic.
The evidence refuting causation
Following the initial publication, a significant body of research emerged to challenge the simple cause-and-effect conclusion drawn from the animal studies. Critics pointed out that association does not prove causation, and several epidemiological and human gut model studies provided contradictory evidence.
- Timing discrepancy: Analyses of trehalose imports in countries like Canada showed that the widespread use of the sweetener postdated the epidemic outbreaks of C. difficile by several years, making a direct causal link unlikely.
- Human models: Unlike the mouse studies, research using human gut models demonstrated that trehalose supplementation did not promote C. difficile growth. In some instances, it even helped reduce the detection of C. difficile toxins to undetectable levels.
- Genetic prevalence: Further studies found that the genetic ability to metabolize trehalose is common across many C. difficile strains, not just the epidemic ones, and the presence of this mutation was not associated with increased disease severity in patients.
The overwhelming consensus among subsequent research indicates that dietary trehalose is not a significant risk factor for contracting or worsening C. difficile infections in humans.
Potential Digestive Issues
For the vast majority of people, trehalose is well-tolerated. The enzyme trehalase in the small intestine breaks trehalose down into two glucose molecules, which are then absorbed. However, some individuals may experience digestive discomfort, especially with excessive consumption.
Trehalase deficiency
A small portion of the population, including a notable percentage of individuals in Greenland, has a genetic deficiency of the trehalase enzyme. For these individuals, consuming trehalose can lead to symptoms similar to lactose intolerance. When undigested trehalose reaches the large intestine, gut bacteria ferment it, which can cause:
- Bloating
- Abdominal pain
- Diarrhea
- Excess gas
Excessive intake
Even in people with normal trehalase activity, very high intakes of trehalose can overwhelm the digestive system and lead to temporary gastrointestinal side effects. This is a general risk associated with excessive consumption of many sugar substitutes and carbohydrates, not a unique danger posed by trehalose.
Regulatory Approvals and Toxicological Findings
Trehalose's safety as a food additive has been reviewed and approved by multiple international bodies. The U.S. Food and Drug Administration (FDA) issued a "no questions" letter for trehalose's Generally Recognized As Safe (GRAS) status. Similarly, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) allocated an Acceptable Daily Intake (ADI) of "not specified," indicating it has very low or no toxicity.
Regulatory acceptance around the globe
Trehalose is approved in dozens of countries, reflecting a broad scientific consensus on its safety. Key approvals include:
- European Union (EU): Authorized as a novel food ingredient.
- Australia/New Zealand (FSANZ): Approved as a novel food.
- Canada (Health Canada): Notified that there is no objection to its use.
- Japan: Used safely for decades as a food ingredient.
Benefits and Considerations for Specific Health Conditions
Beyond safety, trehalose offers several potential benefits and requires consideration for certain groups.
Table: Trehalose vs. Other Common Sugars
| Feature | Trehalose | Sucrose (Table Sugar) | High-Fructose Corn Syrup (HFCS) |
|---|---|---|---|
| Relative Sweetness | ~45% of sucrose | 100% | Often sweeter than sucrose |
| Glycemic Index (GI) | Low (approx. 38) | High (approx. 65) | High |
| Digestion Speed | Slow, gradual release | Fast, rapid absorption | Fast absorption of glucose and fructose |
| Insulin Response | Milder, stable response | Significant spike | Significant spike |
| Digestive Risks | GI issues with high dose/deficiency | None (most people) | Can cause issues with high intake |
Considerations for Diabetics
Because trehalose releases glucose more slowly and has a lower glycemic index than sucrose, it offers a more stable energy source and does not cause a rapid spike in blood sugar or insulin. This makes it a potentially better alternative for diabetics. However, it still contains calories and is broken down into glucose, so diabetics must factor it into their total carbohydrate intake and consult with a healthcare provider.
Ophthalmic use
Trehalose is also used in eye drops to treat dry eye syndrome due to its moisture-retaining properties. While generally safe, some individuals may experience side effects such as eye irritation, temporary burning, or blurred vision. Allergic reactions are rare but possible.
Conclusion: The Verdict on Trehalose's Safety
Based on decades of use and numerous scientific studies, trehalose is generally considered safe for human consumption as a food additive. The highly publicized concerns linking trehalose to the rise of virulent C. difficile strains have been largely discredited by subsequent human and epidemiological research, which showed the animal studies were not applicable to humans and the timelines did not match. The primary health risk is the potential for gastrointestinal distress in individuals with trehalase deficiency or from excessive intake, similar to other non-absorbable carbohydrates. For most people, and especially in the small quantities added to many processed foods, trehalose poses minimal health risks. Individuals with diabetes or those considering eye drops should consult a healthcare professional. For more in-depth information on regulatory findings, sources like the NIH provide extensive reviews.
Key Takeaways
- C. difficile link is largely disproven: The sensationalized link between dietary trehalose and epidemic C. difficile strains, based on animal studies, has been contradicted by later human and epidemiological research.
- Digestive discomfort is possible: Excessive intake or a rare genetic trehalase deficiency can cause bloating, gas, and diarrhea, similar to lactose intolerance.
- Approved by regulatory bodies: Trehalose has been deemed safe by major global authorities, including the FDA, JECFA, and Health Canada, for use as a food additive.
- Good for controlled energy: As a sugar with a low glycemic index, trehalose provides a slower, more stable energy release compared to sucrose, making it a better option for blood sugar management.
- Consult health experts for specific conditions: Diabetics and individuals with trehalase deficiency should seek professional advice on appropriate trehalose intake.
FAQs
Question: Is trehalose definitively safe? Answer: Trehalose is considered safe for human consumption by major regulatory bodies, including the FDA, with an "ADI not specified," meaning it has very low toxicity. Potential side effects are generally limited to digestive issues from very high intake or a specific genetic deficiency.
Question: Did trehalose cause the C. difficile epidemic? Answer: No, the causal link suggested by a 2018 animal study has been widely debunked. Later human and epidemiological studies showed that the increase in trehalose consumption occurred after the epidemic outbreaks began and that the sugar does not stimulate C. difficile growth in human gut models.
Question: Can trehalose cause stomach problems? Answer: Yes, consuming excessive amounts of trehalose can lead to digestive discomfort such as bloating, gas, and diarrhea, particularly in individuals with trehalase deficiency.
Question: What is trehalase deficiency? Answer: Trehalase deficiency is a rare genetic condition where the body lacks the enzyme needed to break down trehalose. This leads to digestive issues when trehalose is consumed, and is more common in certain populations like those in Greenland.
Question: Is trehalose bad for diabetics? Answer: Trehalose has a low glycemic index and provides a slower, more stable glucose release compared to other sugars like sucrose. However, it is still a sugar and contains calories, so diabetics should monitor their intake and consult a doctor.
Question: Where is trehalose found naturally? Answer: Trehalose occurs naturally in small amounts in various foods, including mushrooms, honey, and some seafood. It is also present in foods prepared with brewer's or baker's yeast, such as bread and wine.
Question: Are there any side effects from trehalose eye drops? Answer: While generally safe for ophthalmic use, trehalose eye drops can cause side effects such as temporary eye irritation, burning, or blurred vision in some users. Allergic reactions are possible but rare.
Question: Why was trehalose linked to C. difficile in the first place? Answer: A single 2018 study in Nature involving mouse models suggested that certain C. difficile strains could thrive on low concentrations of trehalose. However, the conclusions were later found to be inapplicable to human health and were sensationalized by the media.
