Investigating the Dose Response of an Almond-enriched Diet on Optimizing HDL-C in a Population With Hypercholesterolemia

Hypercholesterolemia Clinical Trial

Official title: A Randomized, Comparator-controlled Parallel Study to Investigate the Dose Response of an Almond-enriched Diet on Optimizing HDL-C in a Population With Hypercholesterolemia

Status Completed

Clinical Trial Summary

This study will determine the quantity of almonds (1.5 oz or 2.5 oz) consumed as a snack that will provide optimal increases in HDL-C levels.

Clinical Trial Description

Elevated lipid levels are a major modifiable risk factor for cardiovascular disease (CVD), which is the leading cause of death worldwide, accounting for over 17.8 million deaths globally, equating to approximately 71 million Americans with the total annual cost associated with CVD approximating $351.3 billion USD. The National Cholesterol Education Program (NCEP) ATP III Guidelines and supporting literature recommend diet and lifestyle approaches for patients with elevated lipid levels prior to lipid lowering medication, as changing lifestyle and diet cost less than medications and does not lead to polypharmacy or unwanted side effects. Low nut and seed consumption has been identified as the leading dietary risk factor attributed to ischemic heart disease. Indeed, studies have demonstrated that almond consumption reduces total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels compared to no almond controls or substitutions. Additionally, emerging and predictive CVD risk factors such as abdominal obesity and concentrations of Apolipoprotein (ApoB), for which a dose-response effect may also be present, are also improved by almond consumption.

While the benefits of an almond-rich diet on TC, TG, and LDL-C are clear, the effects of almonds on high-density lipoprotein cholesterol (HDL-C) levels is less clear. In populations with hyperlipidemia, almond consumption appears to improve HDL-C, among other lipid markers. Yet, a recent systematic-review and meta-analysis reported a significant decrease in HDL-C compared to control across 12 studies. It is possible that a dose-response relationship exists for almond consumption and HDL-C levels. Almond consumption of ≤42.5 g/day significantly decreased LDL-C/HDL-C, TC/HDL-C and ApoB compared to control, however, significant reductions in TC, BP and body weight were only observed with >42.5 g of almonds/day. Sabate et al., found that the NCEP Step I Diet as well as a low almond diet (10% from calories) significantly reduced HDL-C by 3% and 4%, respectively. However, a high almond-diet (20% from calories) maintained HDL-C levels, while having favorable changes on LDL-C, LDL-C/HDL-C and ApoB/ApoA . Daily almond consumption between 37-73 g/day (~1.3-2.5 oz/day) resulted in significantly higher HDL-C levels compared to a muffin control, with the higher dose of almonds (73 g/day) resulting in a greater increase in HDL-C compared to a lower dose (37 g/day). Additionally, the majority of studies are of limited length and often less than 12 weeks long. A previous study on the long term effects of almonds and other lipid-modulating foods found the greatest reductions on LDL-C and TC/HDL-C were not observed until 12 weeks, and then maintained. Further, it has been suggested that other outcomes such as BP, body weight and abdominal obesity may require longer term consumption of almonds to show beneficial changes. Therefore, it is likely heterogeneity in the effect of HDL-C levels with almond consumption is due to inadequate study duration, background diet, population, control used or too low quantity of almonds.

The existing FDA health claim for almonds states: "scientific evidence suggests, but does not prove, that eating 1.5 ounces per day of most nuts, such as almonds, as part of a diet low in saturated fat and cholesterol may reduce the risk of heart disease". Despite the benefits of almonds on cardiometabolic health, clinical trials designed to determine the optimal dose of almonds on the improvement of lipid profile in a population at greater risk of CVD have not been conducted. This study will address this research gap and establish the optimal dose of almonds for improving HDL-C and other CVD markers and ultimately lowering risk in a population at increased risk of disease development. The specific aim of this study is to demonstrate the efficacy of consuming increasing quantities of almonds on blood lipid levels in adults with hypercholesterolemia. Two doses of almonds will be used, 1.5 oz and 2.5 oz, referred to the Almond-enriched Diet Dose 1 (AD1) and Almond-enriched Diet Dose 2 (AD2), respectively, compared to a Nut-Free Diet (NFD). This study will determine the optimal quantity of almonds consumed as a snack that will provide the most clinically relevant increase of HDL-C levels. Further, this study will investigate the dose-response of almonds on other lipid profile markers, blood pressure (BP), weight, and markers of abdominal obesity in a population with hypercholesterolemia. The hypothesis is that there will be an improvement in HDL-C in a dose-dependent manner with increased consumption of almonds for 16 weeks.

Participants in this study represent a target population that aligns with the goals of healthcare to provide lifestyle management prior to the introduction of prescription medication plans. The study is to be conducted in a population at risk of developing heart disease, who have hypercholesterolemia based on the NCEP definition (LDL-C levels >4.1 mmol/L (>160 mg/dL)). Currently, approximately 53% of the North American population is considered to have elevated LDL-C levels, yet less than half receive treatment. Participants aged 30 to 65 years will be considered for enrolment to avoid complications related to advanced age and a body mass index (BMI) of and up to 34.9 kg/m2 will eliminate confounders related to advanced obesity. Significant metabolic or physiological conditions that may affect lipid levels will be excluded and any participants on prescribed lipid lowering medication will be excluded to limit confounders. Current use of supplements known to affect blood lipid levels, vitamin E status or tree nuts that may impact study outcomes will be excluded unless participants undergo an appropriate washout period prior to enrollment. As well, an extensive list of exclusions in place will ensure that eligibility is based on establishing health and each participants' eligibility will be overseen by the Qualified Investigator (QI). ;

Related Conditions & MeSH terms

• Hypercholesterolemia

• NCT number: NCT05174663
• Study type: Interventional
• Source: Almond Board of California
• Status: Completed
• Phase: N/A
• Start date: January 10, 2022
• Completion date: November 18, 2023