Fermented Food Clinical Trial Services: Gastrointestinal Health and Tolerability

Fermented foods are foods or beverages made through fermentation by microorganisms, such as yogurt, kefir, kimchi, kombucha, tempeh and fermented plant-based beverages. Besides microorganisms that may still be alive in the product, fermented foods contain substances formed during fermentation, which give them properties that differ from those of the starting ingredients (Marco et al., 2017). A fermented food clinical trial is a study in volunteers who consume the actual product, to measure its effects on gastrointestinal symptoms and function and to assess whether the target consumers tolerate it well.

Fermented foods are becoming more popular as functional foods associated with gastrointestinal health, both in Thailand and worldwide. Brand owners who want to state on a label or in marketing materials that a product “supports digestive health” or “contains beneficial microorganisms” need scientific evidence to support that statement, and food advertising must comply with the Food Act B.E. 2522 (1979), including advertising approval where the law requires it.

What makes fermented foods particularly complex is the diversity of live microorganisms in the product and the need to show that the target consumers tolerate the product well. VISBIO Co., Ltd. provides study design, project management and project coordination for clinical studies dedicated to fermented food products, in collaboration with a network of partner clinical research sites and hospitals. The service covers both gastrointestinal health outcomes and tolerability assessment under Good Clinical Practice (GCP), from protocol planning to the final report, for sponsors in Thailand and abroad.

Fermented food products sold in Thailand are regulated by the Thai Food and Drug Administration (Thai FDA) under the Food Act B.E. 2522 (1979). Authorization of food products is based mainly on safety and quality; it does not confirm that health statements on the label are supported by evidence.

If a brand says that a fermented food product “helps support digestive health” or “helps balance the gut microbiota” without supporting evidence, the statement may be considered exaggerated advertising, which is against the law.

Some fermented foods, such as those made with ingredients or processes that have no history of consumption as food, may be classed as novel foods, which must pass a safety assessment under the Thai FDA’s criteria before they go on sale. Tolerability data from volunteers are supplementary information that shows acceptance by the target consumers, but they do not replace the safety assessment required by law. For novel foods that are not yet authorized, the sponsor, the research site and VISBIO check the relevant Thai FDA requirements and plan together before the study starts.

Clinical study data are therefore both evidence to support health statements and a way to build confidence among consumers, importers and sales channels in Thailand and abroad.

Marco et al. (2017) reviewed the evidence on the health benefits of fermented foods and concluded that, besides live microorganisms, some of which are genetically similar to strains used as probiotics, fermented foods have nutritional and functional properties that differ from those of the starting ingredients, as a result of the transformation of substrates and the formation of bioactive compounds during fermentation. These may affect the gut microbiota and the immune system. The health effects of fermented foods therefore do not come from the microorganisms alone. The authors also noted that clinical studies of fermented foods are still limited in number, so clinical study design must take these complex components into account.

Wastyk et al. (2021) conducted a 17-week randomized study in healthy adults that compared a diet high in fermented foods with a diet high in fiber. The group eating more fermented foods showed a steady increase in gut microbiome diversity and a decrease in several inflammatory markers. This shows that consuming fermented foods can change the human gut microbiota and immune markers, which is a reason to measure a product’s effects in a study in volunteers.

A challenge in designing clinical studies for fermented foods is keeping the quality and quantity of microorganisms in the product constant throughout the study period. VISBIO therefore designs the protocol together with the investigators of the partner research site with these variables in mind, from specifying how the study product is stored and quality-controlled to choosing endpoints that cover both gastrointestinal (GI) symptom outcomes and tolerability.

Every study follows GCP and takes into account the particular characteristics of fermented food products, which require strict quality control of the product during the study and a protocol suited to both gastrointestinal health outcomes and tolerability. VISBIO designs the study and manages it from planning to delivery of the report, while volunteers are recruited and cared for by the physicians and investigators of the research site responsible for the study.

Step 1: Consultation and protocol design

Together with the investigators of a partner research site, VISBIO reviews the characteristics of the fermented food product, the effects the sponsor wants to claim and the purpose of the product, in order to define a suitable study plan, including the choice of a primary endpoint for gastrointestinal health and tolerability. This step covers setting inclusion and exclusion criteria that fit the claim, and estimating a sample size with adequate statistical power.

Step 2: Approval from the human research ethics committee

Before any data are collected, the protocol and the informed consent documents must in every case be approved by a human research ethics committee (Institutional Review Board: IRB). VISBIO coordinates document preparation with the site’s investigators and follows up on revisions requested by the committee until approval is granted.

Step 3: Volunteer recruitment and screening

Once approval is granted, the research site responsible for the study recruits and screens volunteers according to the protocol. The site’s physicians and investigators make sure that every volunteer receives complete information, gives written consent and passes a health screening before joining the study. VISBIO coordinates schedules and study readiness between the sponsor and the research site.

Step 4: Study conduct and data collection

Volunteers receive the product, and data are collected at the time points set in the protocol, using standard assessment tools accepted in international clinical research, such as the Gastrointestinal Symptom Rating Scale (GSRS) (Svedlund et al., 1988), the Bristol Stool Form Scale (BSFS), which can reflect changes in intestinal transit time (Lewis & Heaton, 1997), and a tolerability diary, together with recording of adverse events throughout the study. The site’s investigators assess the volunteers and look after their safety, while VISBIO, as project manager, monitors progress and the completeness of the data.

Step 5: Data analysis and reporting

All data are analyzed statistically according to a statistical analysis plan (SAP) set in advance and summarized in a complete scientific report in an internationally used format. VISBIO coordinates the analysis and delivers the report to the sponsor. The report supports product development and evidence-based communication.

This service is designed for fermented food products that aim to communicate about gastrointestinal health or tolerability. Examples of suitable product types are shown below.

Evidence from a clinical study is not just a regulatory document. It is a strategic asset that owners of fermented food brands can use to create value in several ways.

Credible health statements for functional foods

Fermented food products with clinical study data can communicate their health benefits with supporting evidence. In a market where consumers are increasingly interested in scientific evidence, GSRS or BSFS data measured in the group that received the product, compared with a control group, give the product’s value proposition a data foundation that sets it apart from competitors. Wording on labels and in advertising must still comply with food law.

Access to modern trade and health food channels

Many modern trade buyers and health food stores ask for supporting scientific documents for functional food products. A clinical study report prepared under GCP makes negotiations and product listing in these channels smoother.

Export support

Export markets for functional fermented foods in Asia, Europe and North America are placing more weight on evidence that supports health statements. A study designed and reported to international practice is part of preparing to enter these markets, although each country has its own requirements.

Lower legal risk in advertising

Clinical study data give health communication supporting evidence and reduce the risk of complaints. Advertising use, however, requires proper advertising approval from the Thai FDA before publication, as required by law.

1. Fermented food products already authorized by the Thai FDA can start a study through the normal process. For formulas that are not yet authorized, the sponsor, the research site and VISBIO check the relevant Thai FDA requirements and plan together before the study starts. For products of sponsors from abroad, VISBIO assesses the legal conditions together with the research site on a project-by-project basis.
2. VISBIO and the research site design the study plan specifically for each product and its claim.
3. Every study must be approved by a human research ethics committee before it starts, without exception.

For brands that want evidence at every level, VISBIO supports work from activity testing at the cellular level (In Vitro) and ex vivo models through to clinical studies in volunteers. GCP applies to studies in humans, while laboratory work follows the test method for each assay. This page focuses on products consumed as fermented foods. For probiotic or postbiotic dietary supplements in capsule or powder form, and for functional drinks for gut health, VISBIO offers separate clinical trial services by product type.

What are fermented foods?

Fermented foods are foods or beverages made through fermentation by microorganisms, such as yogurt, kefir, kimchi, kombucha and tempeh. Besides microorganisms that may still be alive, fermented foods contain substances formed during fermentation, so their health effects do not come from the microorganisms alone.

What does tolerability mean?

Tolerability means that the target consumers can consume the product without troublesome adverse symptoms. In these studies it is assessed with a tolerability diary and by recording adverse events throughout the study.

Which tools are used to measure outcomes?

Standard assessment tools accepted in clinical research, such as the Gastrointestinal Symptom Rating Scale (GSRS), the Bristol Stool Form Scale (BSFS) and a tolerability diary, together with recording of adverse events throughout the study.

Why does product quality need to be controlled during the study?

Fermented foods contain many kinds of microorganisms that may still be alive, so the quality and quantity of microorganisms must stay constant throughout the study period. The protocol therefore specifies how the study product is stored and quality-controlled, so that the measured outcomes reflect the same product throughout the project.

What is VISBIO’s role, and who looks after the volunteers?

VISBIO designs the study and provides project management and coordination in collaboration with a network of partner clinical research sites and hospitals. Volunteers are recruited and cared for by the physicians and investigators of the research site responsible for the study.

Do study results guarantee advertising approval?

No. Study results support product development and evidence-based communication. Use on labels or in advertising must comply with the law, with approval from the relevant authorities where the law requires it. VISBIO does not guarantee study outcomes or regulatory decisions.

If you are interested in a clinical trial for your fermented food product, contact VISBIO for a free initial consultation through any of these channels:

• Contact form: https://visbio.co.th/en/contact-us/
• LINE Official Account: @visbio
• Email: service@visbio.co.th
• Phone: 098-635-4197
• Timeline: please ask our team directly.

See all clinical trial services on VISBIO’s clinical trial service page.

• VISBIO’s role: VISBIO designs studies and provides project management and project coordination in collaboration with a network of partner clinical research sites and hospitals, for sponsors in Thailand and abroad. Volunteers are recruited and cared for by the physicians and investigators of the research site responsible for the study.
• Research ethics: Every study in humans starts only after approval by a human research ethics committee and is conducted under Good Clinical Practice (GCP). Every volunteer signs an informed consent form after receiving complete information.
• Drugs and herbal medicines: Studies must follow the Thai FDA requirements that apply to the product. The sponsor, the research site and VISBIO plan these steps together from the start of the project.
• Use of results: Study results support product development and evidence-based communication. Use on labels or in advertising must comply with the law for each product type, with approval from the relevant authorities where the law requires it. VISBIO does not guarantee study outcomes or regulatory decisions.
• Foods and dietary supplements: Study results are not a claim that a product diagnoses, treats, cures, mitigates or prevents any disease.
• Timeline: This depends on the study design and the approval process. Please ask our team directly.

References:

1. Lewis, S. J., & Heaton, K. W. (1997). Stool form scale as a useful guide to intestinal transit time. Scandinavian Journal of Gastroenterology, 32(9), 920–924. https://doi.org/10.3109/00365529709011203
2. Marco, M. L., Heeney, D., Binda, S., Cifelli, C. J., Cotter, P. D., Foligné, B., Gänzle, M., Kort, R., Pasin, G., Pihlanto, A., Smid, E. J., & Hutkins, R. (2017). Health benefits of fermented foods: Microbiota and beyond. Current Opinion in Biotechnology, 44, 94–102. https://doi.org/10.1016/j.copbio.2016.11.010
3. Svedlund, J., Sjödin, I., & Dotevall, G. (1988). GSRS — A clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Digestive Diseases and Sciences, 33(2), 129–134. https://doi.org/10.1007/BF01535722
4. Wastyk, H. C., Fragiadakis, G. K., Perelman, D., Dahan, D., Merrill, B. D., Yu, F. B., Topf, M., Gonzalez, C. G., Van Treuren, W., Han, S., Robinson, J. L., Elias, J. E., Sonnenburg, E. D., Gardner, C. D., & Sonnenburg, J. L. (2021). Gut-microbiota-targeted diets modulate human immune status. Cell, 184(16), 4137–4153.e14. https://doi.org/10.1016/j.cell.2021.06.019