Scientific Documents

Regulat® and “the immune system” - Scientific substantiation of a health claim related to Regulat® and “enhancement/modulation/improvement/regulation of the activity of the immune system” pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [1]

Summary (109 KB)

Opinion (162 KB)

Summary

Following an application from Dr. Niedermaier Pharma GmbH submitted pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Germany, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim related to Regulat^® and “enhancement/modulation/improvement/regulation of the activity of the immune system”.

The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence and including a request for the protection of proprietary data.

The food/constituent that is the subject of the claim is Regulat^®, a liquid concentrate derived from a stepwise fermentation of 17 vegetable and fruit species by five different fermentation steps involving five different strains of Lactobacillus, which are inactivated by heat and removed after the fermentation process. The bacterial cultures used are not clearly identified and characterised. The types of bacteria may have an impact on the fermentation outcome and the metabolites present in the final product. The Panel considers that Regulat® has not been sufficiently characterised.

The claimed effect is “enhances the activity of the immune system by immune-stimulation, antioxidative and enzyme regulating effects and modulates the innate unspecific immune system improving the immune-cell function and immune system performance. Moreover, it down regulates cell adhesion molecules stabilising cell/cell contacts and interactions”. The target population is the general population. The Panel notes that the applicant has not provided any evidence that the measured changes in the biomarkers of the activity of the immune system represent beneficial physiological effects.

One human intervention study was provided, claimed as proprietary and reported as pertinent by the applicant. The study was a randomised double-blind placebo-controlled design of 4-weeks intervention investigating the effect of Regulat® in 24 healthy human male volunteers aged from 20 to 48 years.

With regard to immune parameters, no significant changes were reported in TNF-alpha response (Tumour Necrosis Factor-alpha), concentrations of prostaglandin metabolites, and natural killer (NK) cell activity. Following stimulation with Interleukin 2 (IL-2), the NK cell activity was significantly increased in the Regulat® group when volunteers with no increase in lytic activity after IL-2 activation had been excluded for this statistical evaluation. Glutathione values in lymphocytes and monocytes increased significantly in the Regulat® group while the increase in the placebo group was not significant. Levels of  reduced glutathione in NK cells increased significantly in both groups, but when excluding the subjects with high TNF-alpha values the increase was no longer significant in the placebo group while remaining significant in the Regulat^® group. A significant reduction of total oxidation status was reported for the Regulat® group, while no change could be observed in the total antioxidative status of subjects in both groups. Levels of soluble VCAM (Vascular cell adhesion molecule-1) and ICAM (intercellular adhesion molecule-1) were significantly reduced in the Regulat® group after the intervention. The Panel notes that upregulation of VCAM may occur in reaction to a high TNF-alpha response, and that the subjects excluded for this reason earlier were not excluded from this analysis.

The Panel notes the weaknesses of the study which include the small sample size, absence of power calculations and inconsistent exclusions of subjects for the statistical analyses. Moreover, frequent symptoms of cold and/or influenza were common among the subjects of both groups (with about 50% reporting such symptoms during the trial) which is considered to limit the significance of the results in a study measuring immune parameters.

The Panel considers that studies provided on potential antioxidant and immune stimulating properties of Regulat® using in vitro and ex vivo models provide little evidence to support the claimed effect.

In weighing the evidence the Panel took into account the lack of information to sufficiently characterise Regulat®, the lack of evidence that the measured changes in the biomarkers of the activity of the immune system represent beneficial physiological effects, the weaknesses of the human intervention study, and the limited evidence provided by the in vitro and ex vivo studies to support the claimed effect.

The Panel concludes that a cause and effect relationship has not been established between the consumption of Regulat® and the claimed effect, relating to enhancement/modulation/improvement/regulation of the activity of the immune system.