Plant sterols have long been known to lower low-density lipoprotein cholesterol (LDL-C) levels, whereas high intakes of the omega-3 fish fatty acids EPA and DHA are known to lower triglyceride levels. It was speculated that consuming a combination of plant sterols and EPA+DHA could address these two blood lipid risk factors simultaneously. High circulating levels of triglycerides and LDL-C have both been linked to a greater risk of heart disease and stroke although, for triglycerides, this link is less established. People with elevated cholesterol levels are advised to do what they can to reduce them (by managing their weight, exercising and moderating their diet).
To test the theory that consuming a low-fat spread enriched with plant sterols and EPA+DHA from fish oil lowers both LDL-cholesterol and triglycerides, researchers conducted a gold-standard nutrition study: a randomised, placebo-controlled, double-blind trial in which 85 men and 247 women with elevated blood cholesterol levels consumed daily one of five low-fat experimental spreads. As hypothesised, the study concluded that the consumption of a low-fat spread enriched with plant sterols and different low doses (<2g/d) of omega-3 fatty acids from fish oil decreases triglyceride concentrations in a dose-dependent manner while also decreasing LDL-C concentrations.
The combination effect
'The study was done as part of our overall blood lipids research programme,' notes Dr Trautwein, 'and this particular study aimed to investigate the dual blood lipid effect of combining plant sterols and fish oil. Plant sterols are well known for their cholesterol lowering benefits and fish oil has been recognised as having triglyceride reducing benefits.
We were interested in the dual lipid benefit of the combination and therefore incorporated these ingredients in a low-fat spread
'We were interested in the dual lipid benefit of the combination and therefore incorporated these ingredients in a low-fat spread. Formulating these types of fats into a margarine is quite challenging, so our study was designed to investigate low doses of EPA+DHA, together with plant sterols, to get a better idea of the triglyceride lowering effect we could achieve, in addition to the established LDL-cholesterol reducing effect of the plant sterols, in a low-fat spread.'
Regarding application areas and end-user outcomes, Dr Ras commented: 'The pro.activ margarine that we currently have in the market is targeted at people that have elevated blood cholesterol concentrations. We wanted to look at an additional triglyceride lowering benefit, as this is a frequently occurring condition that also needs to be addressed; it affects 30–40% of adults. This research provided an opportunity to work further in this area and perhaps address conditions such as individuals with metabolic syndrome and type 2 diabetes.'
| About the study |
| The study was designed as a randomized, double-blind, placebo-controlled, parallel study. After a 4-week run-in period, 332 subjects were randomized to receive either a control spread (no plant sterols, no EPA+DHA) or one out of four intervention spreads containing a fixed amount of plant sterols (2.5g/d) and varying amounts of EPA+DHA (0.0, 0.9, 1.3 and 1.8g/d) for four weeks. Blood samples were collected at the beginning and end of the study. Results showed reductions in triglycerides ranging dose-dependently from 9.3% to 16.2% in the various EPA+DHA groups compared with the control. LDL-cholesterol was significantly decreased in all groups consuming plant sterols (~13%) compared with the control. |
Looking at the trial results and what they mean for the study population, she added: 'The cholesterol lowering effect of the plant sterols was an expected result, the same as when you investigate plant sterols individually. We investigated the dose-response relationship of the fish oil and saw a very clear, highly correlated effect on triglyceride levels. We also saw a small reduction in triglyceride levels with the plant sterol only group, and there is some evidence to suggest that plant sterols can also modify triglyceride levels, but we’re assuming that that overall effect is mainly due to the fish oil.'
'Basically, the study has shown that one product, a low-fat spread, which contains two active ingredients, fish oil and plant sterols, can play a role in providing a dual blood lipid benefit,' added Dr Trautwein. 'The study has helped us to understand what dose of fish oil would be needed to obtain a significant triglyceride lowering effect — which was the main purpose of the study — and to get a better understanding of how much fish oil to add to the low-fat spread, which is quite a formulation challenge.'
Goods news for omega-3s
It is important to note that fish oil has many beneficial effects: the triglyceride lowering effect is just one of many
Given that marine omega-3s have had quite a rough ride in the media recently, Dr Ras believes that this study has shown that, alongside its many other benefits, fish oil also has a triglyceride lowering benefit, which can be achieved with EPA+DHA doses of approximately 1g per day. 'As you might know,' she says, 'there are EFSA opinions about the triglyceride lowering effect of fish oil; there, they talk about doses in the range of 2–4g/day of EPA+DHA, which requires quite a lot of fish oil and it would be very difficult to incorporate that much into a low-fat margarine. Our study shows that low doses, about 1g, induce a substantial triglyceride lowering effect.'
'Often, the discussion about omega-3 fatty acids is related to their cardiovascular disease risk reduction benefits and there I think it is important to note that fish oil has many beneficial effects: the triglyceride lowering effect is just one of many. They all contribute towards disease reduction, but that was not the focus of our study. We really concentrated on triglycerides, which is an emerging risk factor for cardiovascular disease,' she added.
Helping the nutraceutical industry
Asked whether their research would benefit the greater nutraceutical industry, Dr Trautwein said: 'For the functional food or nutraceutical industry, it is essential that whatever we make in terms of health claims is supported by substantiated scientific evidence. That’s a very important aspect and, here in Unilever, it’s very high on our research agenda. Every health claim that we make is backed by scientific evidence. In this respect, you have to validate the science itself, and the best way to do this is by conducting human intervention studies. Ultimately, you have to demonstrate that the end-result or benefit that you want to claim can be seen in humans and, ideally, in the population for whom the product is intended.'
Consumers better understand the message if they hear consistent stories and understand how all the elements fit together
Dr Ras agreed, saying 'It’s always important, when writing about the results of studies such as this, that we put it into perspective. We have to communicate the benefits to the end-user. Consumers better understand the message if they hear consistent stories and understand how all the elements fit together. If they’re bombarded with different messages from different studies — that have actually done different things — it can detract from the good news that is being delivered, which reduces its impact and leads to a poor level or perception.'
When questioned about Big Pharma casting a beady eye on the nutraceutical industry and the need to conduct gold standard trials to establish credibility with evidence-based research, Dr Trautwein stated: 'We don’t want to compare ourselves to the pharmaceutical industry. Big Pharma focuses on treating diseases and treating patients, whereas we focus on prevention. For that reason, we talk about cardiovascular health, as opposed to cardiovascular disease reduction and we want to focus on keeping people healthier for longer if they take action earlier in life.
'There is plenty of evidence to show that if you control the risk factors for cardiovascular disease early, it’s the best way to prevent the disease happening later in life. In that sense, I think we have completely different entry points; our focus is on primary prevention, healthy people and a dietary and lifestyle approach, whereas pharmaceutical companies treating patients, often providing secondary prevention for people who have already survived a cardiovascular event, and that’s a completely different population. So, we don’t really see a great degree of overlap between the two industries.'
Dr Ras agrees, though, that running an intervention study such as this can only add to the credibility and overall perception of products containing nutraceuticals. 'For sure,' she said, 'I think it’s an absolute prerequisite. If you look at our pro.activ business, Unilever has demonstrated that plant sterols have an LDL-cholesterol reducing benefit by initiating more than 45 human intervention studies. If you look at all the evidence that’s been collected, which has been nicely summarised in meta-analyses, we have contributed with quite a large number of trials around the world, with different population groups from a variety of ethnic backgrounds, so I think that’s pretty significant. And if you want to get a health claim approved by the authorities, that’s the level of evidence that you have to provide and demonstrate.'
| Quick-fire Q&A | |
| NBR: | Could the fish oil be replaced with EPA+DHA from other sources? |
| RR: | I think so, the actual triglyceride lowering active in the fish oil is EPA+DHA so it could be obtained from non-marine sources, for example. But that does lead me on to make some comments about the dose: the doses we’re talking about are those relating to EPA+DHA and not the fish oil. Fish oil comprises about one third EPA+DHA, but also contains other (saturated) fats that are known to increase LDL-cholesterol levels. The combination of fish oil and plant sterols actually serves a dual benefit. |
| NBR: | If the benefits of these actives have been known for some time, why is it that significant studies are being done now to provide the supporting scientific data? |
| ET: | We know that plant sterols have been recognized since the 1950s for their cholesterol lowering properties. In the mid-90s, though, it started to become clear that you could incorporate them into foods. Subsequent research into these food matrixes, such as dairy products, spreads and margarines, confirmed a cholesterol lowering benefit in human intervention studies for claim substantiation. Getting a health claim has been a key driver. |
| NBR: | Could different solid/liquid dosage forms or delivery platforms be used? |
| ET: | Of course, you can always look into other formats but we at Unilever are primarily interested in spreads; it’s a valuable food format because it delivers essential fatty acids, vitamins, etc. in an everyday product that’s used by a large number of consumers. |
Now and the future
In conclusion, Dr Ras noted: 'The use of low-fat spreads enriched with both plant sterols and fish oil may offer an interesting opportunity for a combined blood lipid benefit that would fit in with manageable diet and lifestyle changes to improve blood lipid profiles.' Looking ahead, without giving too much away, Dr Trautwein added: 'We are exploring levels of consumer acceptance: most end-users are aware of cholesterol; they know what it is and that it shouldn’t be too high. We need to investigate how well educated they are about triglycerides. Comparatively, this is still an emerging field. Ideally, we’ll explore further studies to substantiate the results of this study in target populations that have both high cholesterol and high triglyceride levels, in diabetics and/or those with metabolic syndrome.'