Investigating the Impact of Vitamin D Biofortified Tomatoes on Serum Levels of 25(OH)D

The ViTaL-D study is a 21-day randomized, double-blind, placebo-controlled four-arm parallel pilot study conducted at the NIHR (National Institute for Health and Care Research) Norfolk Clinical Research Facility (CRF) in the Quadram Institute in Norwich. Researchers are seeking adult (at least 18 years and older) men and women who have serum 25-hydroxyvitamin D (25[OH]D) levels between 25-40 nmol/L to determine whether soups made with precision bred, biofortified vitamin D tomatoes will increase vitamin D levels. There are a total of 6 study visits (1 consent visit, 1 screening visit, and 4 short visits). At these visits, anthropometric measurements and vital signs will be collected. Participants will be asked to complete questionnaires (food frequency, international physical activity, and sensory evaluation). They will record their daily consumption of soup as well as their daily sun exposure and wear a UV tracker when they are outdoors.

Researchers will measure fasting blood samples for serum 25[OH]D, serum electrolytes, calcium, phosphorous, parathyroid hormone, cholesterol, triglycerides, plasma lycopene, plasma beta carotene, and bone turnover biomarkers. Participants will be given the choice to donate optional samples of saliva and/or 24 hour urine collection. For these optional samples, researchers will quantify vitamin D metabolites (7-DHC, 1,25(OH)2D, 24,25(OH)2D, and C-3 epi 25(OH)D) in saliva and urine as well as vitamin D binding protein in saliva.

Participants will consume one of four soups everyday for 21-days. The four soups are described as such:

• Soup with precision bred tomatoes biofortified with provitamin D (7-dehydrocholesterol-rich, No UV-Treatment). This soup is made with precision bred tomatoes. Tomatoes have been engineered to accumulate 7-dehydrocholesterol (7-DHC, also called provitamin D, a precursor of vitamin D3). The bioefficacy of the provitamin D in the diet is largely unknown.
• Soup with precision bred tomatoes (Vitamin D-rich, UV-Treated) This soup is made with the same precision bred tomatoes, but in this case, the tomatoes have been treated with ultraviolet (UV) light to convert the accumulated 7-DHC into vitamin D3. UV exposure mimics the natural process by which human skin synthesizes vitamin D3 from sunlight.
• Soup with store bought tomatoes (placebo). In this soup, store bought conventional tomatoes contain negligible amounts of 7-DHC and no vitamin D3. This soup is the placebo soup.
• Soup with store bought tomatoes supplemented with Vitamin D3. In this soup, same store-bought tomatoes will be supplemented with vitamin D (from lanolin).

Inclusion criteria

• Be willing to eat a tomato soup daily for 21 days.
• Have access to a smartphone or tablet device and internet access.
• Be at least 18 years old
• Be able to understand the study and provide informed consent
• Have serum 25-hydroxyvitamin D (25[OH]D) levels between 25-40 nmol/L
• Body Mass Index 18.5 to 35 kg/m2
• Live within 40 miles of the Quadram Institute.

Exclusion criteria

• Have a known allergy or intolerance to tomatoes or to any of the soup components (tomatoes, milk, wheat, lanolin are the major allergens, but a detailed list is in Annex 16) of the test soups.
• Currently undergoing treatment or on medications for hypo/hypercalcaemia, hypo/hyperparathyroidism, kidney stones, or bone diseases.
• Have anaemia, immunocompromised or viral infections that may compromise immunity. This will be assessed on a case-by-case basis by QI medical advisor.
• Have any acute or chronic illnesses that affects the outcome of the study such as a gastrointestinal disorder. This will be assessed on a case-by-case basis by Quadram Institute medical advisor.
• Have just started taking or changed dose of vitamin D supplement in the month prior to the start of the intervention or at any point during the intervention, or are regularly taking more than 400 International Units (IU) of vitamin D.
• Are on a routine regimen of vitamin D supplementation over 400 IU who have begun supplementation or had changes in their dose a month prior or have changes during the course of the study.
• Are on any medication regimen that may alter vitamin D absorption they are as follow but not limited to; bile acid sequestrants, hormone replacement therapy, thiazides, calcium channel blockers, isoniazid, anti-seizure medications, and antacids.
• Any dietary restriction that prevents the consumption of the study soups or follow a diet programme which requires fasting for multiple days (soups are not suitable for vegans).
• Have abnormally low or high blood pressure (i.e. ≤90/60, ≥160/100).
• Plan to become pregnant during the study duration, pregnant or breastfeeding.
• Are currently taking part in an intervention study.
• Are a registered blood donor and have donated a large quantity of blood within the last 6 weeks. Registered blood donors should abstain from blood donations for the duration of the study.
• Are unable to give written or verbal informed consent
• Unable to provide your GP contact details.
• Fall under the line management structure or live in the same household with any of the research team, or the QIB Human Studies Team