Investigating the Dose Response of an Almond-enriched Diet on Optimizing HDL-C in a Population With Hypercholesterolemia
Condition: HDL-C; Hypercholesterolemia
MeSH terms: Hypercholesterolemia
Study type: Interventional

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.
    

Detailed 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).
    

Intervention name(s): Almond-enriched diet - 1.5 oz; Almond-enriched diet - 2.5 oz; Control snack
Intervention type(s): Other; Other; Other
Intervention description(s): Participants will receive 1.5 oz of almonds consumed as a snack daily for 16 weeks.; Participants will receive 2.5 oz of almonds consumed as a snack daily for 16 weeks.; Participants will receive a control snack daily for 16 weeks.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Hypercholesterolemia; HDL-C; Almond-enriched diet