“This is the first time that specific fruit has been demonstrated to reduce human C-reactive protein (CRP) and that transgenic over-expression of specific flavonoids results in a further reduction of this important cardiovascular risk marker,” wrote lead author Dietrich Rein from BASF Plant Science Holding GmbH.
A number of genetically modified plants and crops are coming to light with enhanced nutritional content considered to offer human health benefits, including zeaxanthin to potato tubers, and the omega-3 fatty acid, eicosapentaeoic acid (EPA), to soybeans, brassica, and stearidonic acid (SDA) in canola crops.
However, no GM crops with potentially enhanced health benefits have been approved for human consumption, and consumer acceptance continues to be one of the biggest challenges for these crops.
Potential human benefits studied
By feeding the peel of transgenic tomatoes to mice genetically engineered to express human CRP, the researchers report that this enables them to putatively study the potential human health effects of these flavonoid-enriched tomatoes (flTom).
CRP is produced in the liver and is a known marker for inflammation. Increased levels of CRP are a good predictor for the onset of both type-2 diabetes and cardiovascular disease.
Rein and his associates, writing in the September issue of the Journal of Nutrition (Vol. 136, pp. 2331-2337), report that feeding the CRP mice with a diet supplemented with 4g per kilogram of flTom peel, wild-type tomato (wtTom) or a control. The amount of tomato fed to the mice is equivalent to a human daily intake of 2,3g of peel or about 230g of fresh tomato.
This, said the researchers, “constitutes a portion that is achievable in the human diet”.
After seven weeks of feeding the respective diets, Rein and his co-workers measured levels of general health and cardiovascular risk, such as plasma CRP, and cholesterol levels.
It was found that consumption of tomato peels was associated with a significant decrease in levels of human CRP, with flTom “significantly exceeding” the effect of wtTom (56 versus 43 percent reductions, respectively).
Levels of HDL-cholesterol, so-called ‘good’ cholesterol, were also up in both tomato groups.
The levels of CRP in the flTom-fed mice were found to have increased back to baseline levels after a two-week washout period.
“To our knowledge, results from this study demonstrate for the first time that a genetically engineered fruit with enhanced flavonoid levels can have anti-inflammatory effects that exceed the effects of its wild-type counterpart,” wrote the researchers.
Increasing the flavonoid content
To increase the flavonoid content in the tomato, the Dutch and German researchers inserted Petunia chalcone isomerase (CHI) and Gerbera hybrida flavone synthase (FNS) genes into tomato plants to obtain the final transgenic plant, Lycopersicon esculentum cv. Moneymaker.
Since the skin of the tomatoes contain more than 95 percent of the flavonoids, the researchers used the peel of this flavonoid-enriched tomato (flTom) to feed to mice that express human CRP.
The flTom contained significantly higher concentrations of the flavonoles, quercitin and kampferol, and their respective glucosides and rutinosides, and the flavone, luteolin (aglycon and glucoside derivatives) than the normal wild-type tomato (wtTom).
The mechanism behind the benefits
It is the effect of these flavonoids, propose the researchers, on the signalling of the so-called nuclear factor-kappa B(NF-kB), a pro-inflammatory protein that is also said to activate a variety of human cancers, that could be behind the benefits.
“Flavanols and flavones exert anti-inflammatory activities on NF-kB-regulated genes,” they said. Despite such positive results in the mouse model with human CRP, Rein wrote that it remained unclear whether similar results would be obtained in humans as a consequence of eating flavonoid-enriched tomatoes.
However, “genetic enhancement of valuable dietary components in plant foods, such as specific flavonoids in tomatoes, may allow us to reduce the burden of cardiovascular disease,” he concluded. - (Decision News Media, August 2006)