Effect of Lettuce With Different Nitrate Contents on Blood Pressure

NCT02701959 | Completed Phase 1 DMC

• 1 other identifier: 15-QAD-15
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Leafy vegetables are a natural source of dietary nitrate, which may reduce systolic blood pressure (BP). However, the evidence has been obtained from studies using nitrate solutions (i.e., potassium or sodium nitrate) or beetroot juice supplementation which have a suitable placebo for the design of double-blind clinical trials. However, the design of food-based nutritional interventions is complicated by the fact that an appropriate placebo treatment is not available and, therefore, it is not possible to meet the criteria for proper double-blind randomised placebo-controlled intervention trials. In addition, the biological effects of processed products such as beetroot juice or solutions with a pharmacological grade may be different from that of fresh vegetables, e.g. due to conversion of nitrate to nitrite in the mouth during chewing. Objectives: to investigate whether two sets of lettuce specifically grown with different nitrate content but otherwise similar composition show different effects on nitrate uptake and bioavailability in humans. Additionally, the investigators also aim to design human intervention studies to investigate the effect of intake of lettuce with different nitrate content on vascular health. These objectives will be tested by growing lettuce with different fertiliser compositions resulting in high and low nitrate content and then investigating the bioavailability and short-term effect on BP in healthy young volunteers in a double-blind cross-over design. Eligible subjects will consume one meal each of either low or high nitrate lettuce. Urine, blood and saliva samples will be collected at baseline, for 6 hours after the ingestion and then again after 24hr. Blood Pressure BP will be measured continuously for 24 hours starting at baseline. The volunteers will repeat the intervention with the second treatment.

Conditions

Dietary Modification; Blood Pressure

Keywords

Nitric oxide; Dietary intervention trail

Outcome Measures

Primary Outcomes (1)

• Change in 24-hour Ambulatory Blood Pressure (AMBP)

  Change in Systolic and Diastolic Blood Pressure at baseline and every 30 minutes at day time and every hour at night time for 24 hours.

  Baseline and 24 hours

Secondary Outcomes (5)

• Change in bio-availability of nitrate and nitrite in plasma

  24 hours

• Change in Cyclic Guanosine Monophosphate (cGMP) in plasma samples

  24 hours

• Change in bio-availability of nitrate and nitrite in urine samples

  24 hours

• Change in bio-availability of nitrate and nitrite in saliva samples

  24 hours

• Change in Antioxidant capacity of Ferric Reducing Antioxidant Power (FRAP) and Trolox Equivalent Antioxidant Capacity (TEAC) in plasma samples.

  24 hours

Study Arms (2)

Low nitrate lettuce

PLACEBO COMPARATOR

50g of low nitrate lettuce (placebo) on single occasions

Dietary Supplement: Low Nitrate Lettuce

High nitrate lettuce

ACTIVE COMPARATOR

50g of high nitrate lettuce (intervention) on single occasions

Dietary Supplement: High Nitrate Lettuce

Interventions

High Nitrate Lettuce DIETARY_SUPPLEMENT

The lettuce has been grown with high concentration of nitrogen fertilizer (150ppm) to produce the high of nitrate content in the lettuce, the nitrate content of 50 grams of high nitrate lettuce was (\~530 mg nitrate derived).

High nitrate lettuce

Low Nitrate Lettuce DIETARY_SUPPLEMENT

The lettuce has been grown with low concentration of nitrogen fertilizer (25ppm) to produce the low amount of nitrate in the lettuce, the nitrate content of 50 grams of high nitrate lettuce was (\~3 mg nitrate derived).

Low nitrate lettuce

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The investigators aim to recruit 20 healthy young volunteers, non-smoking, male and female aged 18-35 years with a body mass index (BMI) in the range of 20 to 25 kg/m2.

You may not qualify if:

• Current participation in other clinical investigations.
• Mouthwash users.
• Vegetarianism (likely to have very high nitrate intake)
• Dislike to lettuce consumption or inability to comply with the study diet (lack of compliance)
• Use of antihypertensive or cholesterol lowering medication.
• History of any major illness such as cancer; or cholesterol lowering medication; history of cardiovascular or peripheral vascular disease;
• History of any major illness such as cancer; a psychiatric illness; recent history of asthma, renal, liver or gastrointestinal disease.
• Use of antibiotics within previous 2 months; current or recent (within previous 6 months) significant weight loss or gain (\>6% of body weight); --woman who were pregnant, lactating or wishing to become pregnant during the study.
• Previous diagnosis of type 1 or type-2 diabetes treated with insulin (modification of regulation of intermediate metabolism).
• Major surgical operations interfering with the study outcomes (systemic effects on study outcomes).
• Alcohol intake \>21 units/week for men and \>14 units/week women
• Non English speakers or volunteers requiring translators or interpreters (since these services are not available for this study).

Sponsors & Collaborators

• Newcastle University: lead

Study Sites (1)

School of Agriculture, Food and Rural Development

Newcastle upon Tyne, England, NE1, United Kingdom

Location

Related Publications (1)

• Qadir OK, Seal CJ, Ashor AW, Tassotti M, Mena P, Del Rio D, Siervo M, Brandt K. Double-blind controlled dietary cross-over intervention with differentially fertilised intact lettuce leaves shows acute reduction in blood pressure in young adults, associated with faster uptake of nitrate than of phenolics. Eur J Nutr. 2022 Dec;61(8):4191-4203. doi: 10.1007/s00394-022-02961-5. Epub 2022 Jul 23.

  PMID: 35871120 DERIVED

Study Officials

• AFRD School

  School of Agriculture, Food and Rural development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2016
• First Posted: March 8, 2016
• Study Start: April 1, 2015
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: May 23, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)