No proof of health benefit claims, no evidence of food safety. Report: Claire Robinson

Recently NPR ran a story reporting that the GM purple tomato, genetically engineered with genes from snapdragons to contain high levels of the antioxidant anthocyanin, is now on sale to home gardeners in the US. But there are lingering doubts about whether it's safe to eat – and that even applies to the intended change of high antioxidant levels, let alone the GM process-induced unintended changes. And dubious claims about the tomato’s supposed “cancer-fighting” ability have resurfaced.

The GM tomato was developed by scientists at Norfolk Plant Sciences in the UK, a spinout company from the John Innes Centre and the Sainsbury Laboratory. The company was established by the John Innes Centre's Professors Cathie Martin and Jonathan Jones.

The NPR article mentions the claimed anti-cancer benefits of anthocyanins, albeit the "cancer-fighting tomato" message is toned down from the earlier hype around this GM product. For example, back in 2008, the Daily Express headlined its story about the GM tomato's development, "Purple tomato can beat cancer". The article added that it could also keep you slim, ward off diabetes, and safeguard your eyesight.

The Express and other media following the same line were slapped down by the UK's National Health Service (NHS) and Cancer Research UK (CRUK), which both expressed strong reservations about the claims. According to an article in NHS Choices, reporting the views of the NHS Knowledge Service: “These claims are not actually based on benefits seen in humans, but rather from a small-scale study of mice that were given an extract of genetically modified tomatoes.” The NHS Knowledge Service also noted: “The small sample sizes used mean the results may have occurred by chance. Also until the tomato is tested in humans we cannot be sure that it will offer the same benefits, or that there will not be any unexpected harms.” It concluded that without further research the claims that these GM tomatoes "can beat cancer" cannot be supported.

Cancer Research UK wrote on its Science Update blog that "cancer is a complex disease that has lots of 'causes'... The problem with a lot of the coverage of the super-tomato story is that it misses out on this complexity... There's also a big – and in our opinion unwarranted – assumption in some of the coverage. And that's the simple equation that antioxidants = good. There's a fair amount of evidence that some antioxidants in our foods can help prevent some kinds of cancer in some people. But the complexity of this evidence often gets translated in the media and in advertising to 'antioxidants prevent disease'. And that's not what the science says."

Dubious claims

The dubious claims about purple tomatoes and cancer and the simplistic claims about antioxidants were not made up by the press, but originated with the media work of the John Innes Centre ("Purple tomatoes may keep cancer at bay") in 2008. In their 2023 press release about the tomato, Norfolk Plant Sciences seems to have learned lessons about making unsubstantiated claims about cancer, yet it repeatedly uses the word "healthy" to describe the GMO tomato. Indeed, the company has even named its US subsidiary "Norfolk Healthy Produce".

What’s more, some people within the GMO industry lobby are still upholding the deceptive "cancer-fighting" narrative. Maddie Hall, CEO of Living Carbon, which promotes GM trees "to soak up more carbon and cool the climate", greeted the USDA's deregulation of the GM purple tomato on Twitter/X with the tweet: "Yesterday was a historic day in plant biotech: A purple tomato engineered with high antioxidants was approved by USDA. BigPurpleTomato helps prevent cardiovascular disease and fight cancer in humans. This approval under new regulation ushers in a new era for plant synbio!" But Wayne Riekhof, an associate professor of biology at the University of Nebraska-Lincoln, replied: "As someone who has been enmeshed in plant biotech AND cancer biology AND lipid metabolism in both plants and animals for a quarter century, this makes EVEN ME cringe at the unsubstantiated claims and overselling of the promise of plant biotechnology."

No evidence of food safety

The GM purple tomato was deregulated in the US by the USDA in 2022. It received a "no questions" letter from the FDA in 2023 – which, in line with the standard FDA practice, simply confirmed that the developer that stands to profit from the tomato believes it to be safe to eat and that the FDA has no further questions.

However, molecular geneticist Prof Michael Antoniou warns that as the GM tomato has been genetically engineered to change biochemical pathways in order to produce high amounts of anthocyanin, it will in all likelihood lead to unintended alterations in the tomato's composition: "Biochemical pathways are interlinked, so introducing a new core pathway could lead to biochemical changes resulting in the production of novel toxins or allergens.

“And this is the risk from just the intended change. We must also bear in mind that the GM transformation process (plant tissue culture and plant cells transformation) will inevitably give rise to hundreds if not thousands of sites of unintended DNA damage (mutations). These wide scale mutations can change patterns of gene function and alter biochemistry and composition, with unknown downstream health consequences.

“There's no evidence that the developers of the GM purple tomato have carried out the kind of molecular analyses (proteomics and metabolomics) that could help establish whether they only got the change they want, with no unintended changes. As a result, we don't know if these tomatoes are safe to eat."

As for the "pilot" feeding study on cancer-prone mice conducted by Cathie Martin and colleagues, which found that the mice fed the GM tomato lived longer than those fed non-GM red tomatoes, GMWatch agrees with Cancer Research UK that this study is too weak to provide evidence of food safety or of cancer-fighting ability in humans. It is not a properly designed toxicological study, which would look at various health endpoints. There is not enough detail in the published paper to provide evidence of the full range of health effects.

Conventional breeding outstrips GM

Tellingly, the NPR article hailing the GM tomato's availability to home gardeners, after indulging in the predictable pro-GMO hype, goes on to feature the "Indigo" family of conventionally bred purple tomatoes. These were developed by Jim Myers, a plant breeder and professor at Oregon State University, by crossing genes from wild tomatoes with modern varieties.

In addition, there are also heirloom varieties of purple tomato available to growers, such as the Black Zebra, Black Beauty, and Black Krim.

According to the NPR piece, it took Martin and her colleagues at Norfolk Plant Sciences no less than 20 years to successfully genetically engineer the GM tomato. As is generally the case with desirable plant traits, conventional breeding has far outstripped GM in producing anthocyanin-rich purple tomatoes. Myers' non-GM Indigo Rose purple tomato was released in 2011. Now there are reportedly more than 50 cultivars of the Indigos being grown and bred throughout the world. As Myers says, "There's just all this diversity in the Indigo market class that has come about through conventional breeding. With the GMO tomato, it's taken them all this time and more to get one variety out there."

This is yet another illustration of the falsity of claims that genetic engineering is much quicker and more efficient than conventional breeding – a narrative relied upon by advocates of GMO deregulation (removal of regulatory safety checks) on the claimed basis that GM is needed to enable us to meet the challenges of the climate and biodiversity crises.

Patents

Given the wide availability of non-GM purple tomatoes, why bother with GM? As usual, and in spite of the “humanitarian” spin given to the GM purple tomato, it’s all about patents. Cathie Martin and her Norfolk Plant Sciences colleague Jonathan Jones hold active and pending patents on methods to genetically engineer plants with higher antioxidant compounds, as well as on the plants made with those methods.

How much is too much? Dangers of overdosing on antioxidants

Pro-GMO advocates have told GMWatch that the GM tomato is purple all the way through, so the high anthocyanin content also goes all through the fruit, whereas the conventionally bred ones mostly concentrate the purple anthocyanin in their skins. Hence they believe that the GM tomatoes are superior.

However, the high anthocyanin content may present risks. As former US EPA scientist Dr Ray Seidler pointed out in 2022:

"When consumed in moderation, anti-inflammatory compounds like anthocyanins can have health benefits. But too much of a good thing may not be good. It has been demonstrated that over-consumption of anthocyanins (e.g. when taken as pill supplements) may cause kidney, liver, and thyroid hormone health effects. Anthocyanins are part of a group of compounds called polyphenols, which may also limit or interfere with iron absorption.      

"The average American consumes around 12.5 milligrams of these antioxidants [anthocyanins] per day. The anthocyanin content from the GM tomato averages about 500mg per 100g of fresh fruit, some 40 times more than the daily average consumption.  One hundred grams of tomato is less than half a cup. Other naturally purple and red coloured fruits (sweet cherries, blackberries, strawberries, red raspberries, black grapes) contain anthocyanins in the range of 3-143mg/100g, up to 160-fold less than the GM purple tomato."

Dr Seidler cites a mini-review from Harvard University and University of Melbourne scientists, which stresses the need for increased regulation and guidelines for polyphenol consumption and supplementation in order to ensure that consumers remain safe and informed about polyphenols (like anthocyanins). The scientists point out that when taken in pill form it may be easily possible to exceed safe levels, potentially causing serious ailments, such as stroke or increased risk of death.

Dr Seidler gives an example of a certain commercial pill formulation made from sour cherries. The manufacturer recommends two pills per day, with a resulting daily dose of 40mg of anthocyanins. Dr Seidler says that this 40mg per day "represents only 8% of the 500mg level found in 0.4 cups of the fresh GM tomato".

In an article for CBC News on the general topic that doesn't relate specifically to GM tomatoes, Venket Rao, professor emeritus in the nutritional sciences department at the University of Toronto, has also warned of the dangers of overdosing on antioxidants.

Prof Rao said studies in Canada, the US, Australia, Italy, Finland and elsewhere have shown that giving megadoses of antioxidants to people with lung cancer and cardiovascular diseases actually promotes oxidative stress instead of countering it. "That's the paradox," Prof Rao said. "We have evidence that antioxidants are good for you, but we also have well-controlled clinical studies showing that at megadoses they could be harmful to you. So what do you believe in?"

Prof Jim Kehrer of the pharmacy department at the University of Alberta in Edmonton is another scientist who has cautioned against taking high doses of certain antioxidants. For example, he said high levels of vitamin A can cause severe liver damage. He suggested that people need a better grasp of good nutritional intake and not try to overdo selected chemicals.

Prof Antoniou explained the double-edged role of antioxidants, which, it seems, can benefit or impair health, depending on the individual person and the circumstances:

“The health claims around ingesting high levels of antioxidants such as anthocyanins are based on their ability to neutralise reactive oxygen species (ROS, e.g.  superoxide anion, hydrogen peroxide, hydroxyl radicals). All organisms produce ROS as part of natural oxygen-based respiration.

“Although ROS can damage molecules (including DNA) and cells, leading to diseases such as cardiovascular disease and cancer, they also perform vital health-promoting functions. ROS are produced by certain classes of immune system cells to destroy invading pathogenic bacteria, fungi, and yeasts, and thus counteract their infectivity.

“In addition, ROS act as signalling molecules, activating core biochemical pathways and the function of protein factors involved in the regulation of gene expression. The key to good cell and organ function is maintaining a balance between producing enough ROS to appropriately modulate vital functions but not so much as to bring about damage and disease. The body achieves this healthy balance by producing its own ROS-destroying enzymes (e.g. superoxide dismutase) and antioxidants (e.g. glutathione).

“I’m concerned that ingesting megadoses of antioxidants, such as anthocyanins from even a modest portion of the GM purple tomatoes, could interfere with the delicate balance between too much and too little ROS, leading to negative health outcomes. Over-consumption of antioxidants could lead to too little ROS, which is just as bad as having too much. Indeed, it is not beyond the realms of possibility that some of the health issues (e.g. liver and kidney dysfunction) observed from the over-consumption of antioxidants could be resulting from such an imbalance in ROS levels – with too little ROS leading to cellular and organ dysfunction.”             

Given all the above, it is not surprising that a review of randomised trials on antioxidants published by the Cochrane Library concluded that "Antioxidant supplements need to be considered medicinal products and should undergo sufficient evaluation before marketing."

This has not happened with the GM purple tomato. Instead, assumptions have been made about its safety and the wild claims made for its supposed anti-cancer properties are not based on solid evidence.