Humans discovered long ago that food promotes health, and as the relationship between food composition and health has become better understood, functional foods have gradually become a focus of research. Strictly speaking, all foods are functional, i.e. they provide the energy and nutrients needed for survival. However, the term “functional food” refers to foods that provide health benefits beyond those required for survival.

The science of food and nutrition has evolved from identifying and correcting nutritional deficiencies to designing functional foods to promote optimal health and reduce the risk of disease.

The development of functional foods must follow certain scientific steps. To address this issue, the Institute of Food Science (IFT) has organized a group of functional food research experts from around the world to summarize the scientific steps for the development of functional foods.

Determine the relationship between food composition and
Health Benefits

Determining the relationship between food composition and health benefits must be based on scientific theory. There is a large body of scientific literature documenting the potential relationship between food composition and health benefits. Once a researcher has determined the relationship between the two, he or she must select appropriate test materials and conduct comparative experiments to study the relationship in detail.

For example, to investigate the health benefits of plant phenols, researchers conducted a variety of epidemiological and clinical comparative trials, which revealed that plant phenols have a variety of potential health benefits, including reduced risk of hypertension, reduced risk of cardiovascular disease and scavenging of free radicals in the body by antioxidant components.

To demonstrate the efficacy of food components
and determining the necessary intake to achieve the desired effects

The first step is to characterize the structure of the active ingredient in the functional food and to determine the method for quantifying the ingredient. When the structure of an active ingredient (e.g., terpenoids or alkaloids) cannot be completely determined, the “fingerprint” of the active substance is used to identify it. When the researcher has little or no knowledge of the chemical identification of an active ingredient, an alternative compound is often chosen for efficacy assessment.

Secondly, the stability and bioavailability of active ingredients in the whole functional food formulation are evaluated. The stability and bioavailability of an active ingredient depends on the physicochemical state of the ingredient, the influence of other ingredients in the food formulation, food processing and environmental factors.

Finally, efficacy tests are conducted. Efficacy tests must be evaluated by appropriate biological endpoints and biomarkers. In some cases, researchers are able to measure biological endpoints and biological effects directly, however, in many cases, appropriate biomarkers must be selected to evaluate efficacy indirectly.

Criteria for evaluating efficacy, the methodology proposed by Hill 1971 is used. The main elements of this criterion include:

• Strength of the correlation (how does statistical significance demonstrate that the data support a relationship between the biological effect and the intake of the efficacy ingredient?) .;
• Consistency of the observed correlation (how well do data from different sources, different fields and different types of trials support the correlation?). ;
• Specificity of the correlation (how well do the data support the relationship between the active ingredient and the efficacy?). .;
• Casual associations in the observed correlation (does the observed efficacy occur immediately after ingestion of the active substance?). ;
• Quantitative efficacy relationships (do the data demonstrate an increase in efficacy with increasing intake of the active substance?). ;
• Biological plausibility (is there a plausible mechanism to explain the efficacy of the active ingredient?). ;
• Consistency of trial evidence (when considered as a whole, can the relationship between the active ingredient and efficacy help to explain the data obtained from the trial?). (i);

In addition, the IFT Expert Panel considered that consideration should be given to: the quantity and type of trial evidence; the quality of the trial evidence; the evidence from the trials as a whole; and the relevance of the evidence to the particular efficacy claim.

Demonstration of the safety of an active ingredient in humans at the essential intake level
Safety in humans

Safety assessments must be flexible to take into account multiple factors related to consumer response to an ingredient, including genetics, age, gender, nutritional status and lifestyle. The nature of the ingredient and the sensitivity of the population to the ingredient should also be considered. For example, functional foods designed for pregnant women should be evaluated for reproductive function.
Guidelines for safety assessment:

• Retrace the history of the ingredient’s use (if not a novel compound);
• Estimate the intake of the potent ingredient in the population;
• Toxicological / safety evaluation of the essential intake;
• Bioavailability and possible mode of action in the body;
• Estimation of half-life of the efficacious ingredient in vivo;
• Estimation of the quantitative relationship within the dose range of the efficacy;
• Figuring out pharmacological / toxicological effects;
• Evidence of allergic reactions;

Toxicity and safety evaluation (in vivo in humans, in vivo in experimental animals and in vitro systems such as microorganisms and cultured cells).
When the active ingredient of a functional food is unknown, epidemiologic information demonstrating the safety of the functional food will be an important part of the safety assessment.

Development of suitable food carriers for active ingredients

It is important to develop suitable food carriers. At present, most of the domestic functional food products are in the form of drugs, such as capsules, tablets and oral liquids. Foreign countries have begun to pay attention to the food properties of their products. We should learn more from the advanced ideas of foreign countries and make many traditional Chinese foods into functional food carriers to make Chinese functional foods unique in the world.

The selection of food carriers depends on their acceptability, stability, bioavailability of active substances in the carriers, and the consumption and living habits of the target group. The efficacy of functional food is a combination of its own efficacy and consumer compliance. “Efficacy” refers to the extent to which the active ingredient achieves its desired effect, and “compliance” refers to the extent to which the target consumer adheres to the recommended consumption method. Consumer compliance is the key to the success of functional foods.

There are many challenges to using active ingredients in food vehicles: active ingredients often have unpleasant sensory and physicochemical properties, such as the unpleasant odor of n-3 fatty acids and the sour taste of cranberries. However, these problems are gradually being solved by advances in food processing technology, such as microencapsulation, which has enabled the successful incorporation of n-3 fatty acids into cereals and dairy products.
The food carrier should provide a stable environment in which the active ingredient can maintain the desired bioavailability. The selection of food carriers must also take into account the characteristics of the target consumers. For example, people with high cholesterol levels are the target population for functional foods that lower blood cholesterol levels, so foods that are regularly consumed by the target population must be selected as carriers.

Argue that the efficacy and safety evaluation of
Test evidence is sufficiently scientific

To ensure that the experimental evidence for efficacy and safety evaluation is sufficiently scientific, it should be evaluated by an independent panel of experts with certain specialized skills.

The establishment of an independent panel of experts to conduct GRAE will increase public confidence and save government expenditure.

The multidisciplinary nature of the panel would provide a wide range of data to ensure that the conclusions are scientifically sound and relevant to consumer habits.

The panel will use the Hill guidelines to assess whether the available evidence supports the health claims of the active ingredients. The independence of the panel must be guaranteed and its composition must be publicly available.

Expert panels can be convened by professional firms, private consulting firms, or companies developing functional foods.

Communicating product efficacy to consumers

If consumers are not aware of the benefits of functional foods, few will buy and benefit from them and the food industry will have no incentive to develop new functional foods.

To communicate product efficacy to consumers, it is important to establish a relationship between functional food properties and the health outcomes of consuming these foods.

Research on consumer understanding and perception of functional food efficacy is important. The efficacy of functional foods must be fully, clearly and promptly communicated to consumers.

Health claims on food labels are an excellent vehicle for educating consumers about the health benefits of dietary ingredients.

The media plays an important role in communicating research advances in the discipline and in developing consumer awareness of new functional food ingredients.

To guide the communication of product efficacy, the International Food Information Council (IFIC), in conjunction with the IFT and other organizations, has published Guidelines for the Communication of Knowledge on the Health Benefits of Dietary Ingredients. Key elements of the guidelines include:

• Enhancing public awareness of foods, food ingredients, dietary supplements and their role in promoting healthy lifestyles;
• Clearly communicating the differences between new research findings and most people’s traditional beliefs;
• Communicating information accurately and in a balanced manner;
• Placing new research findings in the context of the background knowledge consumers need to make dietary decisions;
• Revealing all key details of a specific study;
• Consideration of peer review;
• Assessing the objectivity of a particular study.

Post-market surveillance of products to
further determine efficacy and safety

“Post-market surveillance (IMS) is the process of collecting information on the actual efficacy of a functional food after it has been introduced to the market.IMS monitors actual product consumption patterns and the impact of the functional ingredients on consumer dietary patterns and determines whether there are any negative health effects that were not detected prior to the product’s introduction to the market.

The optimal IMS program should be determined on a case-by-case basis. An IMS program can be active or passive. In an active IMS program, the sponsor (usually the food manufacturer) employs a team of experts to conduct a systematic survey of consumers’ actual intake patterns of functional foods. A passive IMS program involves the collection of information, documentation, and evaluation of consumer complaints about the product (e.g., sensory factors, possible contamination); it may also include the reporting of adverse health effect events.

IMS program objectives include two important tasks: monitoring the intake achieved and evaluating the actual efficacy of the active ingredient. If the amount of the active ingredient present in the diet is known, then assay tests can assess how well the ingredient is absorbed and utilized. If the presence of the ingredient or its metabolites in blood and other body fluids can be quantified, then determining the level of consumer intake and bioavailability of the ingredient can effectively assess consumer exposure to the ingredient. Once intake is determined, researchers can evaluate the efficacy produced by adding an active ingredient to the diet.

Determining the baseline exposure level of the population to the active ingredient in a functional food when it is first introduced, and then determining the exposure level and efficacy of the functional food after it has been consumed, will provide a grasp of the efficacy of the functional food. These tests require the use of large databases or clinical trials, which are difficult, time-consuming, and costly, and although they are useful, the practical difficulties of conducting such long-term tests often make them nearly impossible to accomplish.

Next, Mr. Pan Suhua from Nanjing University of Traditional Chinese Medicine shared his thoughts and methods of writing a product development report as an example to illustrate the development of functional foods.