EFSA Provides Guidance on Antioxidant, Cardio Health Claims

The European Food Safety Authority (EFSA; Parma, Italy) has published draft guidance on scientific substantiation for health claims related to antioxidant, oxidative damage, and cardiovascular health. For cardiovascular health claims, EFSA’s NDA Panel seemed to embrace most of the generally accepted biomarkers. For antioxidant claims, EFSA stressed that physiological effects should be demonstrated in vivo.

Antioxidants

• EFSA noted that the antioxidant properties or content of foods demonstrated in vitro do not necessarily translate to physiological benefits in humans. Even in vivo, EFSA says that changes in the overall antioxidant capacity of human plasma, as measure by methods such as TRAP, TEAC, FRAP, ORAC, or FOX assays, do not necessarily demonstrate a physiological effect in humans.

• Moreover, EFSA specified that when it comes to antioxidant enzymes such as superoxide dismutase or glutathione peroxidase, it “is considered a beneficial physiological effect only if such changes provide (additional) protection of cells and molecules from oxidative damage, which should be demonstrated in vivo in humans. Therefore, induction of antioxidant enzymes cannot be used alone as evidence for claims related to the ‘antioxidant defence system’ for non-essential food constituents.”

• Regarding claims of “protection of cells from premature aging” or “healthy aging,” EFSA stated that these terms have not been well defined and are therefore are considered to be too general and nonspecific.

• For claims related to protecting cells and molecules from oxidative damage, including UV-induced damage, EFSA indicated that a case-by-case approach can be taken. While acknowledging that there may be a beneficial physiological effect, EFSA stated: “In this specific context, an appropriate method of assessment should be able to determine accurately and specifically the oxidative modification of the target molecule in vivo. The scientific substantiation of health claims on the protection of molecules from oxidative damage requires at least one appropriate marker of oxidative modification of the target molecule assessed in human studies, preferably in combination with other marker(s) as defined in sections 4.1.1 to 4.1.3. However, these other markers of oxidative damage to molecules cannot be used alone for substantiation as they have some limitations, either because they represent a result of two processes (oxidative damage and repair), or because they suffer from technical limitations (interferences from other unrelated processes or substances), or both. A marker cannot be accepted for substantiation when these limitations are considered to be severe.”

• Moreover, it underlined again, “The antioxidant properties of foods (measured in vitro), and changes in the overall antioxidant capacity of plasma (measured in vivo as, for example, TRAP, TEAC, FRAP, ORAC, or FOX), do not predict a role of the food/constituent in the protection of body cells and molecules such as DNA, proteins, and lipids from oxidative damage in vivo, and therefore are not suitable outcome measures for the scientific substantiation of the claimed effect.

Cardiovascular Health
EFSA addressed the biomarkers it considers generally acceptable in scientific substantiation for cardiovascular health claims, including LDL and HDL cholesterol, triglycerides, and blood pressure.

LDL Cholesterol
For foods stating that the absence or reduced content of a constituent is beneficial on LDL cholesterol, EFSA stated: “Substantiation may be based on evidence for an independent role of the food constituent in increasing LDL-cholesterol concentration. For example, for claims on a reduced content of saturated fatty acids (SFAs) in relation to blood LDL-cholesterol concentration, SFAs in mixed diets have been shown to increase blood LDL-cholesterol concentration when compared to carbohydrates which have a neutral effect on LDL-cholesterol concentration, and therefore SFAs in mixed diets have an independent role in increasing LDL-cholesterol concentration.”

For food stating that a replacement of a constituent is beneficial, EFSA stated: “Substantiation may be based on evidence for an independent role of the replaced food constituent in increasing LDL-cholesterol concentration, together with evidence for the lack of an effect or a reduced effect of the food constituent which is used for replacement (e.g. claims for unsaturated fats and reduced LDL-cholesterol concentration when replacing saturated fats).”

HDL Cholesterol
EFSA stated: “Maintenance of normal HDL-cholesterol concentration is a beneficial physiological effect as long as LDL-cholesterol concentration is not increased.”

Triglycerides
EFSA stated that maintaining normal blood concentrations of triglycerides or a reduction in fasting triglyceride concentration within the normal range may be considered beneficial.

EFSA also addressed the study population: “With respect to the study population, results from studies conducted in hypertriglyceridaemic treated with lifestyle measures only (e.g. diet) could be used for the scientific substantiation claims. However, the rationale for extrapolation of results obtained in hypertriglyceridaemic under treatment with ‘triglyceride-lowering’ medications (e.g. fibrates) to the target the claim should be provided, and will be considered on a case-by-case basis (e.g. evidence of interaction between the food and the medications used on the claimed effect).”

Blood Pressure
EFSA stated that maintenance of normal blood pressure or reductions in blood pressure within the normal range is considered beneficial.

Regarding study population, it added: “With respect to the study population, results from studies conducted in hypertensive subjects treated with lifestyle measures only (e.g. diet) could be used for the scientific substantiation of these claims. However, the rationale for extrapolation of results obtained with blood pressure-lowering medications (e.g. ACE-inhibitors, calcium channel blockers and diuretics) to the target population will be considered on a case-by-case basis (e.g. evidence and the medications used on the claimed effect).”

Endothelial Function, Platelet Aggregation, Homocysteine
EFSA stated that an improvement in certain endothelial functions (e.g., endothelium-dependent vasodilation), decreasing platelet aggregation, and maintenance of normal homocysteine metabolism may be beneficial.

As per its usual disclaimer, EFSA noted: “It is not intended that the [guidance] document should include an exhaustive list of beneficial effects and studies/outcome measures which are acceptable. Rather, it presents examples drawn from evaluations already carried out in order to illustrate the approach of the NDA Panel, as well as some examples which are currently under consideration within ongoing evaluations.”

The agency is also currently working on or has released guidance on the following topics:

• Postprandial blood glucose responses/blood glucose control

• Weight management, energy intake, and satiety

• Bone, joints, and oral health

• Neurological and physchological functions

• Physical performance

Guidance is meant to provide companies submitting applications for health claims with more information on the type of scientific substantiation that EFSA in general is seeking.