Almond Dose Response Study.
Condition: Hyperlipidemia; Diet Therapy; Cardiovascular Disease
MeSH terms: Cardiovascular Diseases; Hyperlipidemias; Hyperlipoproteinemias
Study type: Interventional
Phase: Phase 2

Summary: 
      To assess the effects of almonds on coronary heart disease (CHD) risk factors (serum lipids,
      measurements of oxidative stress and nitric oxide production) when added to the diets of
      subjects with high cholesterol. Also, to assess whether the amount of almonds consumed (i.e.
      almond dose) decreases CHD risk factors in a dose dependent manner. We hypothesize that since
      almonds have been shown to reduce serum lipids, we believe they will also increase nitric
      oxide levels related to their high levels of arginine and reduce markers of oxidative stress
      related to their content of bioactive phenolics. We anticipate that a dose-dependent
      relationship will be observed resulting in greater reductions in risk factors for coronary
      heart disease when greater doses of almonds are consumed.
    

Detailed description: 
      Previous studies have shown that nuts, specifically almonds, result in an improved coronary
      heart disease (CHD) lipid risk profile. Part of the reason has been ascribed to their high
      content of monounsaturated fat. However in a previous study we have done, the almond
      supplement, in comparison with an olive oil and dairy protein based supplement, still showed
      a significant reduction in total cholesterol (total-C) and low density lipoprotein
      cholesterol (LDL-C). We wish to use this paradigm to confirm the lipid lowering effect of
      almonds, to establish a similar relationship for the apolipoproteins and so add further
      support for the cardiovascular risk reduction associated with an almond diet. In addition, in
      view of the relatively high arginine content of almonds, we believe higher levels of nitric
      oxide (NO) will be produced, as indicated by increased NO in expired air from perfused
      olfactory mucosa. With this technique, we have found higher levels of NO in preliminary
      studies of subjects on soy diets. These data would further add to interest in nuts in
      relation to cardiovascular disease risk reduction. Furthermore, phenolics are present in high
      concentrations in oil seeds and nuts, and are known to have antioxidant activity. As yet,
      they do not appear to have been emphasized in relation to almonds. We will therefore
      determine the effect of feeding almonds on measures of oxidative stress, including oxidized
      LDL-C, considered to be of direct relevance to CHD; and oxidized DNA, of potential importance
      to neoplastic transformation and carcinogenesis.

      These studies could lead to assessment of postprandial effects of almonds to determine a
      mechanism, and to studies of cardiovascular effects of almonds including exercise stress
      tests and measures of vascular reactivity (e.g. forearm blood flow) in conjunction with NO
      measurements.

      Protocol: All subjects underwent three 4-week treatments in a randomized crossover trial.

      Background Diet: Subjects were instructed to follow the National Cholesterol Education
      Program (NCEP) Step 2 dietary guidelines. Nuts, soy and dietary supplements (vitamins,
      minerals or herbal remedies) were excluded in the background diet during all phases of the
      study.

      Treatments: The three phases were all weight maintaining, self-selected diets: control, full
      almond and half almond. Almond: Raw almonds were added as supplements to the subject's usual
      diet. Subjects with calorie needs of 2,400 kcal or greater, assessed by LRC tables, received
      the full almond supplement (100 g/d, approximately 600 kcal). Subjects requiring between
      1,600-2,400 kcal daily received 75% of the full supplement (75 g/d, approximately 450 kcal).
      Subjects requiring less than 1,600 kcal daily received 50% of the full supplement (50 g/d,
      approximately 300 kcal). Control: The full control supplement was four 150 kcal muffins.
      Control supplements was matched with the energy content of the nut supplements; i.e. either
      600 kcal/d (4 muffins); 450 kcal/d (3 muffins) or 300 kcal/d (2 muffins). The macronutrient
      composition of the muffins conformed to an NCEP Step 2 diet with 25% total fat, <7% saturated
      fat (by use of corn oil as the oil commonly used in healthy baked goods), with 18% protein
      (the average for our subject population using added skim milk powder), and zero cholesterol.
      Muffins were made with wheat flour. Half Portion: The Half Portion was matched with the
      energy content of the other two treatment periods. However on this treatment, half of the
      energy was derived from almonds and half from the control muffins.

      Design: Randomized crossover design.

      Duration: The study consisted of three months subject recruitment and selection; three 4-week
      treatment periods where supplements are provided, and at least two-week washout periods
      between supplements. (Total duration: approximately 7.5 months per subject).

      Study Details: Subjects came after a 12h overnight fast to the Risk Factor Modification
      Center at St. Michael's Hospital (Toronto) immediately prior to commencement of each study
      and at weekly intervals during the course of each study period. Prior to the start of the
      study, subjects were instructed on details of the study diet protocol. They were also asked
      to maintain a constant level of physical activity throughout the course of the study. At all
      visits, body weight (in kg) was obtained in indoor clothing, without shoes.

      Measurements: Bloods were taken at baseline and at weeks 2 and 4 of each phase. Pulmonary air
      was collected at baseline and at week 4 of each phase. Diet histories were recorded during
      the last week of each phase.

      Compliance:Compliance was assessed from completed one-week diet records where supplement
      intake is recorded. Diet records were reviewed by the dietitian with the subject at the end
      of the week. In addition, uneaten supplements were returned, weighed and noted on the menu
      plans by the dietitian.
    

Intervention name(s): Full dose almonds; Half dose almonds+half dose muffin; Full dose whole wheat muffin
Intervention type(s): Procedure; Procedure; Procedure
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single
Primary purpose: Treatment
Keywords: RCT; Almonds; Hyperlipidemia; Blood Lipids