How can we know if food additives are safe?
The food authorities tell us that the additives in our food are harmless. Yet, an additive was recently banned after a long period of use. How can that be?
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Recently, a Norwegian popular TV programme called Folkeopplysningen - Public information - asked a thousand people which harmful substances and chemicals they were most worried about. At the top of the list was the slightly woolly term ‘E numbers’.
E numbers are additives approved for use within the EU. The ‘E’ refers to Europe, and then all additives are given a number. An E number.
In the programme, viewers were assured that the additives hiding behind E numbers are not dangerous.
E numbers have been extensively studied and there is little cause for concern, Trine Husøy said in the programme (link in Norwegian). She is a senior researcher at the Norwegian Institute of Public Health, and is head of the expert group for food additives in the Scientific Committee for Food Safety.
But what does that really mean? How sure are we that the additives are safe? And how can a substance that was previously permitted suddenly become prohibited?
Thorough testing
“Before a substance is approved, thorough documentation must be provided that it does not have harmful effects,” Husøy tells sciencenorway.no.
Those applying to have the additive approved must submit documentation to the European Food Safety Authority (EFSA).
Groups of independent experts assess the risks of each individual food additive. This risk assessment becomes an important part of the European Commission’s reasonings for whether an additive should be approved or not.
The studies required for approval are mainly carried out on animals, but also on cell cultures – i.e., cells in a dish in a laboratory.
These tests are intended to document how the substance is metabolised and how it works in the body. Any harmful effects must also be uncovered. Can the additive, for example, increase the risk of cancer or affect fetal development?
Also long-term effects
The researchers look for signs that the substance is acutely toxic, but also for long-term effects.
“We test the effect over a lifetime in mice or rats. This is a measure of the long-term effects of additives,” Husøy says.
Such animal experiments can thus capture chronic effects that will only appear after a long time.
Studies also have to show how the substance works in different doses, so that the EFSA can assess what limits they should set for safe use.
“It is a long-term process. It can take up to ten years before an additive is approved,” Husøy says.
Of little concern compared to other additives
“It is absolutely certain that the additives have been well studied,” says Husøy.
“Also, they are generally not very toxic, and we often ingest them in much lower quantities than what has been tested in animal experiments.”
Husøy believes that the additives pose little danger, especially if you compare them to other substances we are exposed to. For example, heavy metals, which the participants in the TV programme's survey ranked third among substances they feared.
“Heavy metals can cause serious health effects and some can accumulate in the body. Food additives should not have been on the list of substances to worry about, although there is genuine cause for concern when it comes to heavy metals,” she says.
But wait a minute.
If the additives are so unproblematic, how is it that titanium dioxide (E171) was recently banned after being allowed for several years?
And what about the controversial substance carrageenan (E407) (link in Norwegian)?
This is where we get to the complicated part.
Always uncertainty
The body is an extremely complex system and getting a complete overview of all the potential effects of a substance is practically impossible.
“Serious health effects will always be studied thoroughly, but nothing can be 100 per cent certain,” says Husøy.
She believes this is important, but often difficult to convey. Even though we know a lot, there will always be new studies that can change the assessments of certain additives. In both directions.
Some substances may be safe in even higher amounts than we thought. Other substances may prove to be harmful in lower amounts.
Titanium dioxide
It was precisely a new assessment of research that led to the recent banning of titanium dioxide.
The EFSA uncovered gaps in the knowledge about the substance and called for more data. Based on the data gathered, the European Commission therefore decided that the substance should be banned in food.
“It could not be ruled out that titanium dioxide could cause damage to the DNA. Studies did not provide clear answers, but this is a very serious health effect,” Husøy says.
The studies did not claim that the additive caused harm, but they could not rule out the possibility either. And since DNA damage is a serious health threat, they wanted to be on the safe side.
But when titanium dioxide went under the radar for years, isn’t it possible that other E numbers could also have adverse health consequences?
All E numbers are being reassessed
Although most of the substances are completely unproblematic, we cannot rule out that certain additives have negative effects in the body.
Many of the additives were approved a long time ago. The studies that formed the reasoning behind these approvals were not always up to today's standards.
“The requirements for the studies and for their reporting were different before. Some of the older studies are worse than what would be expected today, while others are of good quality,” Husøy says.
“This is one of the reasons why all the substances are now being examined and reassessed by the EFSA,” she says.
The EFSA has launched a program to review the existing documentation on the additives. It is a long process, since there are many hundreds of E numbers. The focus is currently on sweeteners.
Intestinal flora can convert cyclamate into harmful substances
The sweeteners in particular illustrate how earlier assessments can change in line with progress in research.
In recent years, researchers have had much greater opportunity and interest in investigating how the substances around us affect our intestinal bacteria.
Studies have shown that bacteria in the intestinal flora can break down the substance cyclamate into compounds that are harmful to us. And new studies concluded that more people than expected have an intestinal flora that creates toxic substances in this way.
“This led to the limit values for what is considered a safe intake of cyclamate being adjusted down,” Husøy says.
But this does not mean that all sweeteners are problematic. Again, the picture is complicated.
Aspartame works completely differently
Cyclamate and aspartame are both synthetic substances with a sweet taste. But chemically speaking, they are completely different and are converted in different ways in the body.
“Aspartame breaks down quickly in the intestine and turns into two amino acids and a little methanol. This also happens when we ingest ordinary foods,” Husøy says.
It therefore makes sense – purely chemically – that we are able to tolerate aspartame in fairly large quantities.
Certain studies (link in Norwegian) have shown that aspartame is also linked to changes in the intestinal flora. But change in itself does not necessarily have to be negative.
Studies have shown that the bacterial community in the intestinal flora often changes when we alter our diet, and that the composition of bacteria varies greatly from person to person. But we don't know much about how all the different variants impact our health.
“It is difficult to know which changes in intestinal flora are outside the normal range and can cause serious health effects,” Husøy says.
Synthetic and natural have the same effect
It is also important to remember that there is no clear distinction between synthetic and natural.
Husøy emphasises that a substance with a chemically similar structure acts in the same way in the body, regardless of whether it is synthetically produced or found naturally in a food product.
“Benzoic acid is treated the same in the body, regardless of whether it comes from lingonberries or soft drinks,” she says.
In some cases, manufacturers actually replace E numbers with natural ingredients that contain the same substance.
Studies have linked preservatives with nitrate and nitrite to an increased risk of cancer, and the substances are only permitted in small amounts. However, celery contains a lot of nitrate and powdered celery is therefore used in some meat products.
The manufacturers can then advertise that the product has no added nitrate or nitrite, even though it contains nitrate from the celery powder.
Although it may seem as if these products are safer than conventional options, we don’t have evidence to support that, the American Institute for Cancer Research wrote in 2017.
Controversy about carrageenan
In a way, we can view the regulation of food additives as an eternal project, where new knowledge can over time change the rules around some of the substances.
Such updates contribute to us being able to trust that E numbers are generally safe.
But in the specific cases where new research raises questions about previous assessments, temporary uncertainty and disagreements can arise both among researchers and the general public.
An example is the discussion around the substances carrageenan (E407), carboxymethyl cellulose (E466) and polysorbate 80 (E433).
Several studies in recent years have shown that these substances cause changes in the intestinal flora and can lead to intestinal inflammation, obesity, metabolic syndrome and cancer in animals. They even seem to affect the animal's psyche via the intestinal flora.
Recently, a study also showed that the intestinal flora in humans was altered by such substances.
Call for caution
Following a new assessment, the EFSA called for more data, but would not change its recommendations in the meantime.
Two Norwegian experts questioned this in an article in the Journal of the Norwegian Medical Association in 2019 (link in Norwegian).
Nutritional biologist Marit Kolby at Oslo New University College and nutritionist Inge Lindseth at Balderklinikken wrote that it was a paradox that animal studies are enough to get a substance approved, but not to intervene when harmful effects are documented.
“The best solution would be to avoid products that contain agents that have shown harmful effects in lab animals,” they wrote.
In 2020, the National Association against Digestive Diseases came out with a petition in which they demanded that the Norwegian Food Safety Authority urge caution until we have documentation that the substances are safe.
Husøy says that animal studies of intestinal flora are not always very relevant to humans.
“The intestinal flora of mice and rats is different from that of humans, and this makes it difficult to use animals to study effects in humans,” she says.
Risk is not the only factor
There is not always agreement among researchers on how the data should be interpreted and used.
Another factor that can make certain cases complicated is that the risk assessments are not the only considerations that are taken into account when the European Commission makes its decisions.
In the case of titanium dioxide, for example, the substance is only prohibited in food. It is still allowed in medicines in tablet form.
The reason is that tablets contain smaller amounts of titanium dioxide than foodstuffs, but also that the industry has no good alternatives to this substance, Sigurd Hortemo in the Norwegian Medicines Agency told Norwegian national broadcaster NRK earlier this year (link in Norwegian).
Attempting to change this would be be costly and time-consuming, and hasty decisions can in the worst case lead to medication shortages, which can be a bigger health problem than small amounts of titanium dioxide.
“In Norway alone, we have 684 approved medicines that contain titanium dioxide,” Steinar Madsen from the Norwegian Medicines Agency told the journal Dagens Medisin in 2021 (link in Norwegian).
Not always of great benefit to the consumer
A final question is, of course, whether we really need to use as many additives as we currently are.
Many E numbers are completely harmless, and some are very important for our food to be safe. But others are mostly used because they make the food prettier, easier to produce or better in terms of consistency.
Carrageenan in chocolate milk is a good example. Here, the substance is used to distribute the chocolate particles in the liquid, so that they do not sink to the bottom of the carton.
But this problem can also be solved by shaking the carton before use.
When the benefits are so modest for the consumer, while there is a possibility that the substance is harmful, it is perhaps not so surprising that many consumers have wanted the substance to be removed from chocolate milk.
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Translated by Alette Bjordal Gjellesvik.
Read the Norwegian version of this article on forskning.no
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