Individuals with Down syndrome often have certain facial features. New research has suggested that green tea supplements could reduce the likelihood of this characteristic appearance when taken by children with Down syndrome throughout their first three years of life if taken in the right dose. When scientists made this observation, they confirmed it in a mouse model of Down syndrome. However, the dose was extremely critical; high doses of these same green tea supplements can cause problems with facial and bone development. The authors of a new study on these findings in Scientific Reports note that more work will be needed to understand the effects of green tea supplements so they should be used with caution and medical guidance.
Down syndrome is also known as trisomy 21, which refers to the cause of the disorder: a third copy of chromosome 21. The extra chromosome causes cells to overexpress some genes chromosome 21 carries, including DYRK1A, which is partly to blame for disruptions in brain and bone development in those with Down syndrome. It's known that a compound in green tea called EGCG (epigallocatechin-3-gallate) can inhibit DYRK1A activity, and research has suggested that it could improve cognition in young people with Down syndrome. The compound has also been studied for its potential as an anti-inflammatory or anti-cancer molecule.
In this work, the researchers exposed a mouse model to different doses of EGCG. It was given to moms carrying pups as they developed, who did well on a low dose but had negative effects at a high dose.
"The low dose treatment had a positive effect on mice that are a model of Down syndrome. Sixty percent of them showed a facial shape similar to the control group. The high dose treatment, however, generated very mixed results, and even disrupted normal facial development in some cases, causing additional dysmorphology. This occurred in all mice, in the model of Down syndrome as well as in the control group," revealed co-study author Professor Greetje Vande Velde of KU Leuven.
The research team also investigated the effects of EGCG supplements in people. The Spanish study recruited 287 children between birth and 18 years of age. This group included thirteen children with Down syndrome that received EGCG supplements and 63 who did not. Those receiving the supplements were self-medicated. The researchers were able to collect data on the facial morphology of the study volunteers. In this small sample size, the timing of the supplements seemed to be very important; the facial dysmorphology seen in Down syndrome was reduced in infants and toddlers that were treated.
"All participants were photographed from various angles to create a 3D model of their faces," explained co-lead study author Neus Martínez-Abadías, a professor at the University of Barcelona. "We use 21 facial landmarks and the distances between them to compare the faces of the participants. In the youngest group between zero and three years, we observed that 57 percent of the linear distances are significantly different when you compare the faces of children with Down syndrome that never received the treatment to those of children that do not have Down syndrome. For babies and toddlers who did receive EGCG treatment, this difference was much smaller, only 25 percent. After green tea supplementation, the facial dysmorphology decreases and the children with or without Down syndrome look more alike."
"We didn't identify a similar effect in the adolescent group. Even when treated with green tea extracts, children with Down syndrome still show a difference of more than 50 percent compared to the control group. These findings suggest that the green tea supplements only affect facial development when they are administered in the early stages of life when the face and skull are rapidly growing."
The researchers cautioned that while these results are encouraging, the data has to be applied very carefully. More research will be needed before we know exactly how and when ECGC should be used as a treatment.
"Despite the potential benefits we observed, we must handle these findings with caution considering they are preliminary and based on an observational study," noted Professor Vande Velde. "Much more research is necessary to evaluate the effects of EGCG-containing supplements, the appropriate dose, and their therapeutic potential in general. We also need to take into...account [the] possible effects on other organs and systems, not just on the development of the face. This requires first more basic research in the lab with mice, and then clinical studies with more participants and controlled use of these supplements."
"Our findings suggest that effects of EGCG strongly depend on the dose," Professor Martínez-Abadías concluded. "EGCG products are commercially available and they are used regularly as...general health-promoting compounds. However, it's important to follow the European Food Safety Authority recommendations regarding the maximal intake and to always consult a physician before taking the supplements. Our research shows potential beneficial effects of facial development at low doses, but at very high doses they can produce unpredictable effects in mice. More research is needed in humans to determine the optimal dose at each age that maximizes the potential benefits."
Sources: AAAS/Eurekalert! via KU Leuven, Nature Scientific Reports
