The design of probiotic studies to substantiate health claims

The EC Regulation No. 1924/2006 on Nutrition and Health claims made on foods has generated considerable debate and concern among scientists and industry. At the time of writing, the European Food Safety Authority (EFSA) has not approved any probiotic claims despite numerous human trials and meta-analyses showing evidence of beneficial effects. On 29th and 30th September 2010, ten independent, academic scientists with a documented record in probiotic research, met to discuss designs for future probiotic studies to demonstrate health benefits for gut and immune function. The expert panel recommended the following: (i) always formulate a precise and concrete hypothesis, and appropriate goals and parameters before starting a trial; (ii) ensure trials have sufficient sample size, such that they are adequately powered to reach statistically significant conclusions, either supporting or rejecting the a priori hypothesis, taking into account adjustment for multiple testing (this might necessitate more than one recruitment site); (iii) ensure trials are of appropriate duration; (iv) focus on a single, primary objective and only evaluate multiple parameters when they are hypothesis-driven. The panel agreed that there was an urgent need to better define which biomarkers are considered valuable for substantiation of a health claim. As a first step, the panel welcomed the publication on the day of the meeting of EFSA's draft guidance document on immune and gut health, although it came too late for study designs and dossiers to be adjusted accordingly. New validated biomarkers need to be identified in order to properly determine the range of physiological functions influenced by probiotics. In addition, validated biomarkers reflecting risk factors for disease, are required for article 14 claims (EC Regulation No. 1924/2006). Finally, the panel concluded that consensus among scientists is needed to decide appropriate clinical endpoints for trials.

Food health claims – What consumers understand

Issues pertaining to consumer understanding of food health claims are complex and difficult to disentangle because there is a surprising lack of multidisciplinary research aimed at evaluating how consumers are influenced by factors impacting on the evaluation process. In the EU, current legislation is designed to protect consumers from misleading and false claims but there is much debate about the concept of the ‘average consumer’ referred to in the legislation. This review provides an overview of the current legislative framework, discusses the concept of the ‘average consumer’ and brings together findings on consumer understanding from an international perspective. It examines factors related to the personal characteristics of individuals such as socio-demographic status, knowledge, and attitudes, and factors pertaining to food and food supplement products such as the wording of claims and the communication of the strength and consistency of the scientific evidence. As well as providing insights for future research, the conclusions highlight the importance of enhancing the communication of scientific evidence to improve consumer understanding of food health claims.

Authorised EU health claims for polyphenols in olive oil

There is evidence that various phenolic compounds (such as oleuropein, tyrosol and hydroxytyrosol) found in virgin olive oil may be responsible for the beneficial effects on cardiovascular disease. In the EU there is an authorized health claim that‘olive oil polyphenols contribute to the protection of blood lipids from oxidative stress’ on the basis of human studies showing significantly reduced levels of oxidized LDL in plasma after virgin olive oil consumption. The claim may be used only for olive oil that contains at least 5 mg of hydroxytyrosol and its derivatives per 20 g of olive oil. Other claims proposed (including maintenance of normal blood pressure and HDL cholesterol concentration, and anti-inflammatory properties) were rejected.

Weight of evidence needed to substantiate a health effect for probiotics and prebiotics: regulatory considerations in Canada, EU, and US

Successful and responsible introduction of probiotic and prebiotic products into the worldwide marketplace requires labelling for health benefits that meets consumer needs, adheres to regulatory standards and does not overextend scientific evidence. Regulations differ among countries, but underlying all is an emphasis on scientific credibility of any statements of health benefits. This paper considers the value of different types of evidence offered in substantiation of efficacy and reviews different regulatory approaches to labelling for health claims. Limitations of in vitro, animal and different types of human studies used for efficacy substantiation for probiotics and prebiotics are discussed.

PASSCLAIM - gut health and immunity

Background The gut and immune system form a complex integrated structure that has evolved to provide effective digestion and defence against ingested toxins and pathogenic bacteria. However, great variation exists in what is considered normal healthy gut and immune function. Thus, whilst it is possible to measure many aspects of digestion and immunity, it is more difficult to interpret the benefits to individuals of variation within what is considered to be a normal range. Nevertheless, it is important to set standards for optimal function for use both by the consumer, industry and those concerned with the public health. The digestive tract is most frequently the object of functional and health claims and a large market already exists for gut-functional foods worldwide. Aim To define normal function of the gut and immune system and describe available methods of measuring it. Results We have defined normal bowel habit and transit time, identified their role as risk factors for disease and how they may be measured. Similarly, we have tried to define what is a healthy gut flora in terms of the dominant genera and their metabolism and listed the many, varied and novel methods for determining these parameters. It has proved less easy to provide boundaries for what constitutes optimal or improved gastric emptying, gut motility, nutrient and water absorption and the function of organs such as the liver, gallbladder and pancreas. The many tests of these functions are described. We have discussed gastrointestinal well being. Sensations arising from the gut can be both pleasant and unpleasant. However, the characteristics of well being are ill defined and merge imperceptibly from acceptable to unacceptable, a state that is subjective. Nevertheless, we feel this is an important area for future work and method development. The immune system is even more difficult to make quantitative judgements about. When it is defective, then clinical problems ensure, but this is an uncommon state. The innate and adaptive immune systems work synergistically together and comprise many cellular and humoral factors. The adaptive system is extremely sophisticated and between the two arms of immunity there is great redundancy, which provides robust defences. New aspects of immune function are discovered regularly. It is not clear whether immune function can be "improved". Measuring aspects of immune function is possible but there is no one test that will define either the status or functional capacity of the immune system. Human studies are often limited by the ability to sample only blood or secretions such as saliva but it should be remembered that only 2% of lymphocytes circulate at any given time, which limits interpretation of data. We recommend assessing the functional capacity of the immune system by: measuring specific cell functions ex vivo, measuring in vivo responses to challenge, e. g. change in antibody in blood or response to antigens, determining the incidence and severity of infection in target populations during naturally occurring episodes or in response to attenuated pathogens.

Low-grade inflammation, diet composition and health: current research evidence and its translation

The importance of chronic low-grade inflammation in the pathology of numerous age-related chronic conditions is now clear. An unresolved inflammatory response is likely to be involved from the early stages of disease development. The present position paper is the most recent in a series produced by the International Life Sciences Institute's European Branch (ILSI Europe). It is co-authored by the speakers from a 2013 workshop led by the Obesity and Diabetes Task Force entitled ‘Low-grade inflammation, a high-grade challenge: biomarkers and modulation by dietary strategies’. The latest research in the areas of acute and chronic inflammation and cardiometabolic, gut and cognitive health is presented along with the cellular and molecular mechanisms underlying inflammation–health/disease associations. The evidence relating diet composition and early-life nutrition to inflammatory status is reviewed. Human epidemiological and intervention data are thus far heavily reliant on the measurement of inflammatory markers in the circulation, and in particular cytokines in the fasting state, which are recognised as an insensitive and highly variable index of tissue inflammation. Potential novel kinetic and integrated approaches to capture inflammatory status in humans are discussed. Such approaches are likely to provide a more discriminating means of quantifying inflammation–health/disease associations, and the ability of diet to positively modulate inflammation and provide the much needed evidence to develop research portfolios that will inform new product development and associated health claims.

Diet, immunity and functional foods

Functional foods (specific nutrient and/or food components) should beneficially affect one or more target functions in the body. The use of functional foods as a form of preventive medicine has been the subject of much research over the last two decades. It is well known that nutrition plays a vital role in chronic diseases, but it is only recently that data relating to the effects of specific nutrients or foods on the immune system have become available. This chapter aims to summarize the effects of some functional foods (e.g., prebiotics and micronutrients) on the immune system. It should be noted, however, that studies into the role of functional foods with regard to the human immune system are still in their infancy and a great deal of controversy surrounds the health claims attributed to some functional foods. Consequently, thorough studies are required in human and animal systems if we are to move towards developing a functional diet that provides maximal health benefits.

Novel probiotics and prebiotics : road to the market

Novel probiotics and prebiotics designed to manipulate the gut microbiota for improving health outcomes are in demand as the importance of the gut microbiota in human health is revealed. The regulations governing introduction of novel probiotics and prebiotics vary by geographical region. Novel foods and foods with health claims fall under specific regulations in several countries. The paper reviews the main requirements of the regulations in the EU, USA, Canada and Japan. We propose a number of areas that need to be addressed in any safety assessment of novel probiotics and prebiotics. These include publication of the genomic sequence, antibiotic resistance profiling, selection of appropriate in vivo model, toxicological studies (including toxin production) and definition of target population.

Conjugated linoleic acid and human health: a critical evaluation of the evidence

Purpose of review: This review critically evaluates studies investigating the effects of conjugated linoleic acid on human health, including effects on body composition, blood lipids, liver metabolism, insulin sensitivity and immune function. It focuses mainly on human intervention studies, but includes some reference to animal and cellular studies which provide insight into potential molecular mechanisms of action of conjugated linoleic acid. Recent findings: Human studies continue to report inconsistent effects of conjugated linoleic acid on human health. Some of these reports are based on overinterpretation of marginal effects of supplementation. Recent data suggest that the effects of the substance may be isomer dependent and that cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acids have opposing effects on blood lipids and on metabolism in adipocytes and hepatic cells. Summary: Claims that conjugated linoleic acid is beneficial for health remain as yet unconvincing. Human studies investigating the effects of conjugated linoleic acid supplements have tended to use mixtures of isomers and have been inconsistent. More recent studies have attempted to use relatively pure preparations of single isomers and these studies suggest that the effects of conjugated linoleic acid may be isomer-specific. These recent data suggest a relative detrimental effect of trans-10, cis-12 conjugated linoleic acid on blood lipids. There appears to be little effect of conjugated linoleic acid on immune function and the effects on insulin sensitivity remain unclear.

Probiotics: their potential to impact human health

Probiotics—live microorganisms that when administered in adequate amounts confer a health benefit on the host—have been studied for both human and animal applications, and worldwide research on this topic has accelerated in recent years. This paper reviews the literature on probiotics, describes how probiotics work in human ecosystems, and outlines the impact of probiotics on human health and disease. The paper also addresses safety issues of probiotic use, suggests future developments in the field of probiotics, and provides research and policy recommendations. Product considerations and potential future developments regarding probiotics also are discussed. The authors conclude that controlled human studies have revealed a diverse range of health benefits from consumption of probiotics, due largely to their impact on immune function or on microbes colonizing the body. Additional, well-designed and properly controlled human and mechanistic studies with probiotics will advance the essential understanding of active principles, mechanisms of action, and degree of effects that can be realized by specific consumer groups. Recommendations include establishment of a standard of identity for the term “probiotic,” adoption of third-party verification of label claims, use of probiotics selectively in clinical conditions, and use of science-based assessment of the benefits and risks of genetically engineered probiotic microbes.

Drug control, human rights, and the right to the highest attainable standard of health: a reply to Saul Takahashi

A recent article in this journal challenged claims that a human rights framework should be applied to drug control. This article questions the author’s assertions and reframes them in the context of socio-legal drug scholarship, aiming to build on the discourse concerning human rights and drug use. It is submitted that a rights-based approach is a necessary, indeed obligatory, ethical and legal framework through which to address drug use and that international human rights law provides the proper scope for determining where interferences with individual human rights might be justified on certain, limited grounds.