Gene-Edited Vitamin D Tomato Soup Trial Seeks Volunteers

Researchers from the John Innes Centre and Quadram Institute are launching one of the first human trials of gene edited food, to understand whether biofortifying tomatoes in this way leads to higher levels of vitamin D in the blood after people have eaten them.

The ViTaL-D Study (Link quadram.ac.uk/vital-d) will enrol 76 participants with low vitamin D.

levels, aged over 18 and living within 40 miles of Norwich, who will consume a portion of tomato soup daily for three weeks, to see if this leads to an increase in their blood of the active form of vitamin D that helps us stay healthy.

If successful, this would be a step towards using these biofortified gene edited tomatoes,

which were developed at the John Innes Centre, to address a growing global problem of vitamin D deficiency. This step forward is likely to benefit people who follow a vegan or vegetarian diet because vegan sources of vitamin D are nearly non-existent.

Sufficient levels of Vitamin D are essential for optimum health. It helps the body absorb calcium and phosphorus to keep our bones, teeth and muscles strong. It boosts the immune system to fight off infections and low vitamin D levels have been linked to depression, dementia and a higher risk of internal cancers.

Vitamin D is produced naturally in the skin when it's exposed to sunlight. This gives it the nickname the "sunshine vitamin", but in autumn and winter when there's less daylight and people are more covered up, vitamin D is sourced from the diet.

Vitamin D rich foods are limited; oily fish, red meat and egg yolks are good sources, but plants lack this essential vitamin. The combination of limited dietary sources and sunny days has led

to vitamin D deficiency becoming a significant problem; an estimated 1 in 5 people in the UK are deficient during winter and spring and worldwide almost one billion lack enough vitamin D. The prevalence isn't uniform; people with darker skin, the elderly, pregnant and breastfeeding people, and people who are confined indoors are more likely to be deficient. Vitamin D

supplementation in winter is now advised for all, and especially those in at risk groups.

The world-leading plant scientists from the John Innes Centre have provided an innovative and sustainable solution that could boost vitamin D in foods.

Some plants, including tomato, make a precursor of vitamin D, called pro-vitamin D3 as an intermediary, which is then converted to compounds the plant uses for defence. Using gene editing, Professor Cathie Martin FRS and her team in the John Innes Centre have precisely

tailored the genes in tomato plants so they accumulate very high levels of pro-vitamin D3 in the fruit and leaves. Exposure to sunlight or shining UVB light on the plants converts it into vitamin D3, which is the more stable form that's useful for humans.

This change in the genetic makeup does not affect the appearance or growth of the plants, or

their yield. But it means the gene edited tomatoes accumulate vitamin D at levels that could be used to supplement diets; each tomato has as much vitamin D as two eggs or 28g of tuna - two recommended sources.

Extended exposure of the ripe fruit to UVB light, during the process of sun-drying for example, can increase the vitamin D levels even more.

Now the tomatoes will be tested to check that the body takes up this vitamin D and converts it to higher active levels in the blood. Each participant will consume one of four different soups - one made from the biofortified (gene edited) tomatoes, one made from the same tomatoes exposed to UV light, one made from tomatoes that haven't been biofortified (gene edited), and one made with tomatoes that haven't been biofortified (gene edited), but have been

supplemented with another form of vitamin D. Participants won't know which soup they are given, and the study team won't know until after the study has ended.

The participants will wear a UV monitor throughout the study to see what level of sunlight they have been exposed to.

During the study, participants will make five short visits to the Quadram Institute Clinical

Research Facility, which is managed by the Norfolk and Norwich University Hospital. Here they will be provided with a daily portion of tomato soup and donate a sample of blood for testing as well as providing information on their diet and exposure to sunlight.

Participants also can provide optional urine and saliva samples, but this is not essential to being a part of the study.

"Vitamin D plays a critical role in maintaining overall health, yet deficiency rates continue to rise globally. This study seeks to better understand the growing need for accessible and reliable sources of vitamin D, especially in populations at risk for deficiency" said Professor Martin Warren, Chief Investigator on the ViTaL-D Study and Chief Scientific Officer at the Quadram Institute".

"Our goal is to identify whether these biofortified tomatoes meet this nutritional need and help address the wide range of health problems associated with vitamin D deficiency, including weakened immune systems and bone disorders."

Professor Cathie Martin FRS, group leader at the John Innes Centre, said: "Food is health care - diet has a huge impact on the health of us all and vitamin D deficiency is a widespread problem both here in the UK and the rest of the world."

"It has been exciting to use cutting-edge science to enrich a food such as tomato with extra vitamin D3. In this first-of-its-kind trial we are exploring the impact this produce might have on our diets and health here in Norwich, using tomatoes grown in our glasshouses at the John Innes Centre."

"People often take vitamin supplements, but new breeding techniques mean that in the future this already healthy, fresh food that lots of people eat could be fortified with micronutrients from day one, with the potential to help boost the health of all of us."

"We're really excited to be setting up and delivering this first gene edited food trial" said Dr Antonietta Hayhoe from Quadram's Human Studies Team. "With the help of the participants who volunteer we can provide the best evidence that these innovative biofortified tomatoes can deliver their benefits and reduce vitamin D deficiency."

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