Is dietary nitrate effective in breast cancer
Research type
Research Study
Full title
Is dietary nitrate effective in reducing aerobic glycolysis (AG) in breast cancer? – A longitudinal study using specialist magnetic resonance (MR) methods
IRAS ID
255238
Contact name
Jiabao He
Contact email
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 5 months, 30 days
Research summary
Summary of Research
Breast cancer is the most prevalent cancer affecting women, with 1 in 8 women in the UK developing breast cancer in their life time. Chemotherapy drugs, currently used for locally advanced breast cancers, are associated with side effects while dietary supplements have complex effects with a relatively small effect size.
Breast tumours have different metabolism compared to healthy tissue, including elevated lactate production by aerobic glycolysis (AG), an underpinning feature of metabolism in breast cancer cells. Dietary nitrate, contained in leafy green vegetables and beetroot, has been shown to improve energy efficiency in exercising skeletal muscle, positioning itself as a disruptor of AG.
The purpose of this study is to examine if dietary nitrate can disrupt AG and as a result to halt or even reverse tumour progression and survival. This study will look at scans of breast tumours using magnetic resonance imaging (MRI). Changes to tumour related biochemical substances including lactate will be measured by advanced magnetic resonance spectroscopy.
In this study, 16 patients undergoing surgery will be recruited for two MRI scans following a 5 day intervention programme. Magnetic resonance measurements of lactate concentration will be compared before and after intervention.
Summary of Results
1. Project overview
Breast cancer is associated with tissue hypoxia and increased lactate production due to the upregulation of lactate dehydrogenase (LDH), known as aerobic glycolysis (AG). It has been proposed that AG is associated with stronger cancer cell survival advantage and invasiveness or metastatic risk. Disrupting AG has the potential to half or even reverse tumour progression. Dietary nitrate, contained in leafy green vegetables, has been shown to improve energy efficiency in the exercising muscle, positioning itself as a possible disruptor of AG.
We hypothesise that dietary nitrate disrupts AG in breast cancer, and this disruption is the result of the suppression of lactate production, leading to reduced proliferative activity. We propose to examine the role of dietary nitrate on AG in breast cancer through a longitudinal study in 16 patients with advanced invasive ductal carcinoma undergoing wide local excision or mastectomy. Each patient will be asked to follow a 5-day dietary nitrate intervention programme. Lactate concentration will be measured from the tumour using specialist magnetic resonance (MR) method, before and after the dietary nitrate intervention.
2. Achievement of the project’s objectives
We were unable to recruit sufficient number of patients into the study, and could not meet our primary objective as outlined in the protocol. We were unable to recruit any patient before COVID-19 in a 6-month period (up to February 2020), and the study was suspended for one and a half years during COVID-19. We recruited one patient in a 12-month period after COVID-19 (restarted November 2021). After careful discussion involving all the investigators of the study team, the study was terminated prematurely.
3. Results
We were unable to report clinical relevant results due to early termination of the study.
4. Discussion and learning
There were several factors that might have contributed to the low enrolment rate of the study. A significant number of patients turned down the invitation due to personal distaste of dietary nitrate in the form of concentrated beetroot juice and demand for patient commitment. Subsequent to COVID-19, there were increased logistical challenges to conduct an interventional study in the waiting window prior to patient surgery and chemotherapy. There were also frequent study contraindications, including medications, metal implants and radiofrequency identification marker coils.
REC name
North of Scotland Research Ethics Committee 2
REC reference
19/NS/0021
Date of REC Opinion
20 Mar 2019
REC opinion
Further Information Favourable Opinion