The Impact of Almond Nut Consumption on Markers of CVD & Metabolic Health

Cardiovascular Disease Clinical Trial

— Almonds  

Official title:

A Randomised, Controlled Parallel Dietary Intervention to Investigate the Effect of Almond Snack Consumption on Cardio-metabolic Disease Risk Markers Compared With Isocaloric Snacks, in Adults at Moderate Risk of Cardiovascular Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02907684
• Other study ID #: ABC RFP-DHW001
• Status: Completed
• Phase: N/A
• Start date: March 29, 2017
• Est. completion date: October 30, 2019

Study information

• Verified date: February 2019
• Source: King's College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the cardio-metabolic health effects of consuming almond nuts in place of habitual (usual) snack products in adults at moderate risk of developing cardiovascular disease

Description:

Tree nuts are recommended in the prevention and management of cardiovascular disease (CVD) largely based on their LDL (low density lipoprotein) lowering effects, but the CVD risk reduction observed with tree nut consumption is greater than that predicted by their hypocholesterolemic effects alone. Other health benefits have also been noted by our group, such as moderation of postprandial lipemia , as well as by others such as modified postprandial glycemia , decreased blood pressure (BP) , improvement in oxidant status and weight loss. Robust evidence for the protective cardio-metabolic effects of nuts from the PREDIMED study has highlighted the association between nut consumption and decreased risk of cardiovascular events, obesity, metabolic syndrome and type 2 diabetes (T2DM). However, there is a paucity of evidence on the effects of almonds on vascular function in humans (BP and endothelium-dependent vasodilation (EDV)), although there is evidence that almonds promote nitric oxide (NO) release in animals consuming high-fat diets. Fundamental to vascular health is a well-functioning liver and there is increasing evidence to demonstrate that the accumulation of liver fat is a causative factor in the development of cardio-metabolic disorders. Non-alcoholic fatty liver disease (NAFLD) is now considered the hepatic manifestation of the metabolic syndrome (MetS); recent data has shown that it is linked to increased CVD risk via direct effects on vascular function (and EDV) independently of obesity and MetS . NAFLD is thought to affect 30% of the population in developed countries, and up to two-thirds of people with obesity and 50% of people with hyperlipidemia. Development of fatty liver, mainly attributable to obesity and elevated postprandial lipemia, is associated with increased inflammation, oxidative stress, insulin resistance, dyslipidemia and impaired EDV, and predicts risk of CVD and T2DM .

Therefore, the long-term goal of this research is to understand the mechanisms underpinning how dietary change can drive favourable modification of CVD disease risk and to identify patterns in population food choices, specifically almond consumption, that tend to correlate with reduced CVD disease risk. The primary aim of this proposal is to investigate, in a randomised controlled, parallel arm, 6-wk dietary intervention (n=100) whether replacing snacks based on refined carbohydrates and poor in micronutrients/non-nutrient bioactives (NNB) with nutrient/NNB-dense, whole almond snacks can influence liver fat content (a key metabolic driver of insulin resistance and vascular dysfunction, and a hallmark of metabolic syndrome) and EDV (brachial FMD being an independent predictor of CVD events, in addition to related biomarkers of cardio-metabolic disease risk. The snacks products provide participants with 20% of their energy requirements via either whole almonds or as muffins/crackers that have been designed to mimic the average UK snack.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: October 30, 2019
• Est. primary completion date: May 13, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 70 Years

Eligibility

Inclusion Criteria:

Subjects will be male or female, aged between 30-70 years who regularly consume =2 snack products a day. A principal aim is to identify and recruit subjects with increased risk of CVD, in order to increase the sensitivity of the study subjects to dietary change. Subjects who are at above average risk for developing CVD (relative risk >1.5) will be selected using a metabolic scoring system (scoring =2 points), adapted from the Framingham risk score system, as used previously by Chong et al. 2012. Subjects will give their own written informed consent.

Exclusion Criteria:

1. Non-snack consumers (assessed as subjects consuming <2 snack products per day by a specific FFQ (food frequency questionnaire) at screening, adapted from the short Health Survey for England (2007) Eating Habits Questionnaire).

2. A reported history of myocardial infarction or cancer.

3. Being fitted with a heart pacemaker.

4. Presence of metal inside the body (implants, devices, shrapnel, metal particles in eyes from welding etc.). History of black-outs/epilepsy.

5. Diabetes mellitus (fasting plasma glucose >7 mmol/L).

6. Chronic coronary, renal or bowel disease or history of cholestatic liver disease or pancreatitis.

7. Presence of gastrointestinal disorder or use of a drug, which is likely to alter gastrointestinal motility or nutrient absorption.

8. History of substance abuse or alcoholism (past history of alcohol intake >60 units/men or 50 units/women).

9. Currently pregnant, planning pregnancy, breastfeeding or having had a baby in the last 12 months.

10. Allergy or intolerance to nuts.

11. Unwilling to follow the protocol and/or give informed consent.

12. Weight change of > 3 kg in preceding 2 months. BMI <18 kg/m2 (underweight) or >40 kg/m2 (morbidly obese due to potential technical difficulties making FMD and ambulatory blood pressure (ABP) measurements).

13. Current smokers or individuals who quit smoking within the last 6 months.

14. Participation in other research trials involving dietary or drug intervention and/ or blood collection in the past 3 months.

15. Unable or unwilling to comply with study protocol.

16. The above criteria will be measured using the screening questionnaires and from physical (blood pressure, weight, height) and biochemical measurements (full lipid count, liver function test, full blood count, glucose and insulin) made during the screening visit. Participant eligibility will be assessed against the inclusion/exclusion criteria and 'fitness' to participate will be assessed and signed off by a clinician.

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases

Intervention

Dietary Supplement:
• Almonds
Participants to consume almonds as snacks to contribute to 20% of their energy requirements daily for 4 weeks
• Muffins/Crackers
Participants to consume muffins/crackers as snacks to contribute to 20% of their energy requirements daily for 4 weeks NB all participants will have a run in period for 2 weeks whereby muffins are consumed, this is prior to randomisation.

Locations

Country	Name	City	State
United Kingdom	King's College London, Diabetes and Nutritional Sciences Division	London

Sponsors (2)

Lead Sponsor	Collaborator
King's College London	Almond Board of California

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse events		Through study completion, average of 1.5 years.
Other	Snack product acceptability	Questionnaire for participants to rate acceptability including self-rated enjoyment, sensory aspects, gastrointestinal effects, palatability, and appetite sensations, and likelihood that they will continue to consume the almonds/muffins as a snack after the study has ended	Week 6
Other	4 day food diaries		4 days at screening
Other	4 day food diaries		4 days at week 0 'Baseline'
Other	4 day food diaries		4 days at week 6
Primary	Endothelium-dependent vasodilation	Measured via flow mediated dilation (FMD)	Baseline (week 2)
Primary	Endothelium-dependent vasodilation	Measured via flow mediated dilation (FMD)	Week 8 (after 2 week run in)
Primary	Liver fat %	Via MRI and magnetic resonance spectroscopy (MRS) analysis. Only a subset of 48 participants with aim of 20 per each arm to complete	Baseline (week 2)
Primary	Liver fat %	Via MRI and MRS analysis. Only a subset of 48 participants with aim of 20 per each arm to complete	Week 8 (after 2 week run in)
Secondary	Pancreatic fat	Via body MRI. Only a subset of 48 participants with aim of 20 per each arm to complete.	Baseline (week 2)
Secondary	Abdominal fat	Via body MRI. Only a subset of 48 participants with aim of 20 per each arm to complete.	Baseline (week 2)
Secondary	Muscle fat	Single measurement via body MRI. Only a subset of 48 participants with aim of 20 per each arm to complete.Muscle fat will be measured in the soleus muscle in the lower calf.	Baseline (week 2)
Secondary	Pancreatic fat	Single measurement via body MRI. Only a subset of 48 participants with aim of 20 per each arm to complete.	Week 8 (after 2 week run in)
Secondary	Abdominal fat	Single measurement via body MRI. Only a subset of 48 participants with aim of 20 per each arm to complete.	Week 8 (after 2 week run in)
Secondary	Muscle fat	Single measurement via body MRI. Only a subset of 48 participants with aim of 20 per each arm to complete. Muscle fat will be measured in the soleus muscle in the lower calf.	Week 8 (after 2 week run in)
Secondary	Body composition: body weight	Using Tanita scales	Week 0, prior to 2 week run in
Secondary	Body composition: body weight	Using Tanita scales	Week 2 'Baseline'
Secondary	Body composition: body weight	Using Tanita scales	Week 4
Secondary	Body composition: body weight	Using Tanita scales	Week 6
Secondary	Body composition: body weight	Using Tanita scales	Week 8
Secondary	Body composition: body mass index		Week 0, prior to 2 week run in
Secondary	Body composition: body mass index		Week 2 'baseline'
Secondary	Body composition: body mass index		Week 4
Secondary	Body composition: body mass index		Week 6
Secondary	Body composition: body mass index		Week 8
Secondary	Body composition: Waist circumference		Week 0, prior to 2 week run in
Secondary	Body composition: Waist circumference		Week 2 'baseline'
Secondary	Body composition: Waist circumference		Week 4
Secondary	Body composition: Waist circumference		Week 6
Secondary	Body composition: Waist circumference		Week 8
Secondary	Body composition: Hip circumference		Week 0 (prior to 2 week run in)
Secondary	Body composition: Hip circumference		Week 2 'baseline'
Secondary	Body composition: Hip circumference		Week 4
Secondary	Body composition: Hip circumference		Week 6
Secondary	Body composition: Hip circumference		Week 8
Secondary	Blood pressure		Week 0 (prior to 2 week run in)
Secondary	Blood pressure		Week 2 'baseline'
Secondary	Blood pressure		Week 4
Secondary	Blood pressure		Week 6
Secondary	Blood pressure		Week 8
Secondary	24 hour ambulatory blood pressure		Week 2 'Baseline
Secondary	24 hour ambulatory blood pressure		Week 8
Secondary	24 hour heart rate variability		Week 2 'baseline'
Secondary	24 hour heart rate variability		Week 8
Secondary	Fecal short chain fatty acids	Subset of participants, n=30	Week 2 'baseline
Secondary	Fecal short chain fatty acids	Subset of participants, n=30	Week 8
Secondary	Gut microbiota	Subset of participants, n=30	Week 2 'baseline'
Secondary	Gut microbiota	Subset of participants, n=30	Week 8
Secondary	Fasting insulin		week 2 'baseline'
Secondary	Fasting insulin		week 8
Secondary	Fasting glucose		Week 2 'baseline'
Secondary	Fasting glucose		Week 8
Secondary	Fasting non esterified fatty acids (NEFA)		Week 2 'baseline'
Secondary	Fasting non esterified fatty acids (NEFA)		Week 8
Secondary	Plasma Total cholesterol	Fasting	Week 2 'baseline
Secondary	Plasma Total cholesterol	Fasting	Week 8
Secondary	Plasma LDL cholesterol	Fasting	Week 2 'Baseline'
Secondary	Plasma LDL cholesterol	Fasting	Week 8
Secondary	Plasma HDL cholesterol	Fasting	Week 2 'Baseline'
Secondary	Plasma HDL cholesterol	Fasting	Week 8
Secondary	Plasma HDL:LDL ratio	Fasting	Week 2 'Baseline'
Secondary	Plasma HDL:LDL ratio	Fasting	Week 8
Secondary	Plasma triglyceride concentration	Fasting	Week 2 'baseline'
Secondary	Plasma triglyceride concentration	Fasting	Week 8
Secondary	Homeostasis model assessment estimated insulin resistance (HOMA-IR)	Fasting (calculated from insulin and glucose)	Week 2 'Baseline'
Secondary	Homeostasis model assessment estimated insulin resistance (HOMA-IR)	Fasting (calculated from insulin and glucose)	Week 8
Secondary	Plasma adiponectin		Week 2 'Baseline'
Secondary	Plasma adiponectin		Week 8
Secondary	Plasma resistin		Week 2 'baseline'
Secondary	Plasma resistin		Week 8
Secondary	Plasma leptin		Week 2 'baseline'
Secondary	Plasma leptin		Week 8