25 August 2015 Research
Alternatives address safety concerns about surfactant-based emulsifiers
Compounds normally thought of as medicines are being added to food. Elinor Hughes looks at the scientific and regulatory challenges facing these nutraceuticals.
‘Health-promoting compounds added to foods are usually termed “nutraceuticals”,’ says Yoav Livney, associate professor at the biotechnology and food engineering department, Technion, Israel Institute of Technology, in Haifa, Israel. The word itself is a combination of nutrition and pharmaceutical, but there’s ‘no real consensus about what a nutraceutical is’, says Amanda Wright, director of the Human Nutraceutical Research Unit at the University of Guelph in Canada. ‘What I tell my students is that it’s a product isolated from a food that is sold in medicinal form and has some benefit physiologically beyond basic nutritional requirements.’ She adds that a nutraceutical could also be added back to the food, making a so-called functional food. ‘This would look like a food, behave like a food, but it would have some constituent that provides an additional benefit,’ says Wright.
Fortifying food with extra nutrients is nothing new. We are used to seeing cereals labelled as ‘fortified with vitamins and iron’, for example. And in the US and Canada, flour is enriched with folic acid, a compound that pregnant women are advised to take to prevent neural tube birth defects such as spina bifida. You may also have noticed the rise of margarines that contain plant sterols that promise to lower low density lipoprotein (or ‘bad’) cholesterol. These are just a couple of examples of additives in foods that have been specially introduced to tackle serious health problems with very little change to our lifestyles. Now, there is an increase in research into adding nutrients to food to prevent or cure diseases.
‘People are looking more at lifestyle factors to prevent and manage disease and, of course, diet is a huge part of that,’ says Wright. So what do scientists want to put into food to confer health benefits? ‘There’s a huge spectrum of ingredients, of medicinal compounds,’ says Wright. Some of the interest is in finding dietary-based constituents, especially those that have similar effects to actual drugs. For example, polyunsaturated fatty acids and fish oils may have blood-thinning activity similar to warfarin. They are also seen as being more ‘natural, whatever that means’, she says, with potentially fewer side effects.
Wright’s own interest lies in delivering carotenoids into the body. Carotenoids are a class of lipids and include molecules like beta-carotene and lutein. Beta-carotene is found in carrots and has provitamin A activity, which means that it is converted to vitamin A in the body. A lack of vitamin A can lead to blindness. Lutein, found in green leafy vegetables, prevents age-related macular degeneration. ‘As people age, you could have a dietary strategy including foods or nutraceuticals containing lutein that might actually prevent age-related macular degeneration,’ says Wright. Gut health is another large research area, she points out, and researchers are working on ways to ensure that probiotics can reach the lower intestine where they are believed to have a beneficial effect. To do this requires them being packaged into capsules, tablets or added into food formulations in which they can survive processing in the stomach.
Packaging up nutraceuticals to deliver their health benefits seems to be an increasingly important area of research. But, as Wright admits, there is no magic bullet. ‘No one structure seems to be appropriate for all situations. If a nutraceutical is going to be put into a tablet, that’s going to be different to what can be added to a beverage for example.’ And that’s not all. Researchers have to consider the food to which the nutraceutical is added, to ensure that the food itself does not break down the capsule. ‘You could have an acidic matrix or there may be pro-oxidants present. Things like that are going to drive the nature of the encapsulate structure that may be required,’ she says. They also have to consider the high temperature manufacturing involved in food production and the shelf life of the product. Another target is bioavailability – the nutraceutical has to be able to be absorbed and reach systemic circulation so that it can exert its health benefit. To this end, research has focused on making the nutraceutical stable in the stomach but able to be absorbed in the small intestine.
Nanoparticles made from the protein casein and sugar maltodextrin can be used to encase vitamins
Another consideration is how the additives are going to affect the look, smell, taste and texture of the food. In another project, Livney’s team showed that heat-treated beta lactoglobulin (another milk protein) can entrap and protect green tea epigallocatechin gallate (EGCG, linked to the prevention of neurodegenerative and cardiovascular diseases, as well as cancer) from degradation in clear drinks. The capsule can also suppress EGCG’s bitterness and astringency, which limit its addition to beverages. ‘Currently, we are studying the interaction of these nanodelivery systems with the human digestive tract, to facilitate high bioavailability and protection of the bioactive compounds during digestion,’ says Livney.
‘One must be careful when designing and utilising food-grade nanoparticles to ensure that they do not have any adverse effects on human health,’ warns Julian McClements from the department of food science at the University of Massachusetts, US. He adds that there are a number of potential problems that need to be addressed. If the bioavailability of an encapsulated component is increased so that it is much higher than in conventional products, the component could be over-consumed, and for some compounds, there is an upper limit for safety. Nanoparticles may be digested and absorbed in a different way to conventional food components in the human body, altering their bio-distribution and potential toxicity. The nanoparticles could interfere with the normal function of other components in the gastrointestinal tract, for example digestive enzymes. ‘Different types of nanoparticles will behave differently, and more research is needed to establish their potential effects,’ says McClements.
Despite drawbacks in some areas of research, some successful delivery mechanisms have already been commercialised. These include nanosized self-assembled structured liquids, developed by NutraLease, a company in Israel that develops carriers for nutraceuticals to be incorporated in food systems. Within these liquid structures, they were able to solubilise hydrophobic nutraceuticals such as coenzyme Q-10, vitamins A, D and E as well as omega-3 acids. These fatty acids have also been formulated into nanoparticle systems by US drug delivery company BioDelivery Sciences International and German liquid formula company Aquanova.
Wright points out that, in terms of regulating nutraceuticals, demonstrating efficacy for a product in the long term is a challenge. ‘I think the regulatory environment makes it challenging, maybe not so much from a research perspective, because I can still investigate the questions that are interesting to me on a scientific level, but the adoption of some of these technologies are going to be challenging,’ she says. ‘You’re not looking at an acute effect, you’re looking at the idea that, over a relatively long period of time, these molecules could have some health benefits, most likely in terms of preventing a disease. Quantifying that is difficult because you’re looking at such a long time period.’
In Europe, nutraceuticals are covered by a novel foods regulation that has been in place since 1997. ‘Essentially it means that any new ingredient or new process that might be applied to food needs to be evaluated, assessed and approved before it can be used in Europe,’ says Sandy Lawrie, head of the novel food unit at the Food Standards Agency (FSA) in the UK. In Canada and Australia, the regulations are similar, while in the US, new ingredients are evaluated to show that they’re generally regarded as safe. Each new nanomaterial that will be added to food must be treated as a new entity, even if it is a familiar substance, and it is important to know whether the nanomaterial is still present in that form in the final product. ‘What we’re interested in is not what we put into food, but what people actually consume,’ he says.
‘Any new ingredient that might be applied to food needs to be evaluated, assessed and approved before it can be used’There are three criteria that the FSA judges novel foods against. ‘An applicant needs to show that the product is safe, that it has appropriate nutritional qualities and also that consumers are not going to be misled,’ explains Lawrie. Then, an FSA panel of independent experts called the Advisory Committee on Novel Foods and Processes (ACNFP) evaluates the product. ‘They look at the composition of the ingredient, the way it’s manufactured (which could impact its safety), its nutritional quality and its biological effect – whether it might harm some people, or everyone, at particular doses.’ The ACNFP prepares a report, which gets sent to the other 26 European member states. Ultimately, there would be a vote at a European level before the product could be authorised. The same rules apply whether a food has been manufactured in the UK or imported.
‘We get a lot of enquiries about what you might class as functional foods,’ says Lawrie. ‘We have regular contact with the Medicines and Healthcare products Regulatory Agency (MHRA) about whether a product falls on one side or another. There is a clear definition of what a medicinal product is and it’s the MHRA’s job to enforce those regulations.’ But how are those cholesterol-lowering margarines classed? ‘They’re regarded as food,’ says Lawrie. ‘It’s a question of judgement sometimes as to which side of the boundary a product falls. Sometimes it’s to do with the dose of the product, sometimes it’s to do with the way it’s presented. For example, a high dose of a vitamin you might add into a vitamin supplement could be regarded as a medicine if it’s there to treat a particular disease.’
Wright acknowledges that there are differences between giving medicine through food rather than in prescribed pill form. ‘You can’t control dosage in the same way. You don’t know how much people are going to eat,’ says Wright. ‘The risk with dosage would be, not necessarily overdosing, but underdosing because the nutraceutical may not be as efficacious when it’s consumed in a different format.’ Consumers also need to have confidence in the products that are coming out or, overall, the market will falter, she says.
So, what will we see in the future? ‘I think we’re going to see all types of foods being affected,’ says Wright. ‘It would be much more effective to enrich staple foods and popular drinks with nutraceuticals, so as to reach the largest numbers of people, without them having to make dramatic changes to their eating habits,’ says Livney. However, he cautions that ‘it would not be advisable to enrich foods that are basically unhealthy, for example high in fat (particularly saturated or trans fat), high in sugar, high in sodium, so as not to promote their increased consumption by making them seem healthy’.
In the short term, Livney says, a lot can be done to improve people’s diets without them making significant changes to their eating habits, using effective enrichment technologies. In the long term, though, it is important that public awareness of healthy eating is increased, as enrichment alone cannot address the problems that come with an unbalanced diet. ‘No diet can lead to good health without physical exercise and avoiding exposure to health-risks, such as smoking,’ he says.
And you can listen to an interview with Amanda Wright in the October Chemistry World podcast.
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