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

A

Almond Board of California

Status

Completed

Conditions

Hypercholesterolemia
HDL-C

Treatments

Other: Almond-enriched diet - 1.5 oz
Other: Control snack
Other: Almond-enriched diet - 2.5 oz

Study type

Interventional

Funder types

Other
Industry

Identifiers

NCT05174663
21ABCFA01

Details and patient eligibility

About

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.

Full 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).

Enrollment

75 patients

Sex

All

Ages

30 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  1. Males and Females between 30-65 years of age, inclusive

  2. BMI between 25.0 - 34.9 kg/m2, inclusive

  3. Individual is not of child-bearing potential, defined as those who have undergone a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy, bilateral tubal ligation, complete endometrial ablation) or have been post-menopausal for at least 1 year prior to screening

    Or,

    Individuals of child-bearing potential must have a negative baseline urine pregnancy test and agree to use a medically approved method of birth control for the duration of the study. All hormonal birth control must have been in use for a minimum of three months. Acceptable methods of birth control include:

    • Hormonal contraceptives including oral contraceptives, hormone birth control patch (Ortho Evra), vaginal contraceptive ring (NuvaRing), injectable contraceptives (Depo-Provera, Lunelle), or hormone implant (Norplant System)
    • Double-barrier method
    • Intrauterine devices
    • Non-heterosexual lifestyle or agrees to use contraception if planning on changing to heterosexual partner(s)
    • Vasectomy of partner at least 6 months prior to screening
  4. Individuals with hypercholesterolemia based on the NCEP definition (LDL-C levels >4.1 mmol/L (>160 mg/dL))

  5. Motivated to comply with dietary guidelines as assessed by a motivation questionnaire at screening

  6. Self-reported stable body weight for the past 3 months defined as not having gained or lost more than 5 kg of body weight throughout the 3 months prior to baseline

  7. Agrees to adhere to dietary guidelines and to maintain current lifestyle habits as much as possible throughout the study depending on the participants' ability to maintain the following: medications, supplements, exercise, and sleep and avoid taking new supplements

  8. Provided voluntary, written, informed consent to participate in the study

  9. Healthy as determined by medical history, and laboratory results exam as assessed by Qualified Investigator (QI)

Exclusion criteria

  1. Individuals who are pregnant, breast feeding, or planning to become pregnant during the study
  2. Allergy, sensitivity, or intolerance to the investigational product/control snack ingredients
  3. Current regular consumption of nuts >2 times per week, unless willing to washout prior to baseline
  4. Current use of prescribed lipid lowering medications as assessed by QI (see Section 7.3.1)
  5. Current use of over-the-counter medications or supplements known to affect blood lipid levels (i.e. omega-3) or vitamin E status
  6. Unstable metabolic disease or chronic diseases as assessed by the QI
  7. Current or history of any significant diseases of the gastrointestinal tract as assessed by QI
  8. Type I or Type II diabetes
  9. Unstable hypertension. Treatment on a stable dose of medication for at least 3 months will be considered by the QI
  10. Significant cardiovascular event in the past 6 months. Participants with no significant cardiovascular event on stable medication may be included after assessment by the QI on a case-by-case basis
  11. Major surgery in the past 3 months or individuals who have planned surgery during the course of the study. Participants with minor surgery will be considered on a case-by-case basis by the QI
  12. Self-reported confirmation of current or pre-existing thyroid condition. Treatment on a stable dose of medication for at least 3 months will be considered by the QI
  13. Individuals with an autoimmune disease or are immune compromised as assessed by QI
  14. Self-reported confirmation of a HIV-, Hepatitis B- and/or C-positive diagnosis
  15. Self-reported confirmation of blood/bleeding disorders as assessed by QI
  16. Use of tobacco products within 12 weeks of baseline and during the study period as assessed by QI
  17. Alcohol intake average of >2 standard drinks per day as assessed by the QI
  18. Alcohol or drug abuse within the last 12 months
  19. Clinically significant abnormal laboratory results at screening as assessed by the QI
  20. Individuals who are unable to give informed consent
  21. Any other condition or lifestyle factor, that, in the opinion of the QI, may adversely affect the participant's ability to complete the study or its measures or pose significant risk to the participant

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Single Blind

75 participants in 3 patient groups

Almond-enriched diet dose 1
Experimental group
Description:
Participants will be instructed to ingest 1.5 oz of almonds daily for 16 weeks. The 1.5 oz of almonds can be split into a morning and afternoon snack. Participants will be advised not to exceed 2 doses of almonds daily. If a dose is missed, participants should take the missed dose as soon as the participants remember.
Treatment:
Other: Almond-enriched diet - 1.5 oz
Almond-enriched diet dose 2
Experimental group
Description:
Participants will be instructed to ingest 2.5 oz of almonds daily for 16 weeks. The 2.5 oz of almonds can be split into a morning and afternoon snack. Participants will be advised not to exceed 2 doses of almonds daily. If a dose is missed, participants should take the missed dose as soon as the participants remember.
Treatment:
Other: Almond-enriched diet - 2.5 oz
Nut-free diet
Other group
Description:
Participants will be instructed to ingest the control snack (Iso-caloric \[to 1.5 oz of almonds\] control snack of chocolate chip cookies or Oreo cookies) daily for 16 weeks. The control snack can be split into a morning and afternoon snack. Participants will be advised not to exceed 2 doses of snack daily. If a dose is missed, participants should take the missed dose as soon as the participants remember.
Treatment:
Other: Control snack

Trial contacts and locations

1

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Central trial contact

Mal Evans, PhD

Data sourced from clinicaltrials.gov

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