Nutritional Therapy for Autonomic Dysfunction in Elderly Heart Failure Patients
Condition: Heart Failure
MeSH terms: Heart Failure
Study type: Interventional

Summary: 
      Recent studies suggest that patients with heart failure (HF) may have a reduced ability to
      control the tone of their blood vessels, heart rate or blood pressure in response to stress.
      This study will test whether 16 weeks of protein supplements can improve control of blood
      pressure and heart rate in HF patients.
    

Detailed description: 
      Heart Failure is defined as "a complex clinical syndrome that can result from any structural
      or functional cardiac disorder that impairs the ability of the ventricle to fill or eject
      blood." The New York Heart Association classifies heart failure four functional classes: NYHA
      1-4, with Class 1 as minimal and Class 4 as the most advanced stage.

      As a clinical syndrome, HF can be associated with significant limitations in functional
      capacity which can be very debilitating in the elderly population. It is a major cause of
      morbidity and mortality and is the leading cause of hospitalization among older individuals
      in the United States (1-15), particularly among those aged ≥65 years (16, 18). Nearly 1
      million hospitalizations for HF occur each year with rates of hospitalization continuing to
      rise. Prevalence of heart failure was estimated to be more than 5.8 million in the United
      States and HF was singled out as an emerging epidemic (17).

      Heart failure is associated with autonomic and endothelial dysfunction. Recent studies
      suggest that patients with HF maybe more prone to having impaired vasomotor and autonomic
      response to stress (19-29). A reduced ability to increase blood flow or heart rate
      appropriately in response to demand could limit the functional capacity of these subjects and
      would contribute to orthostasis (drop in blood pressure on standing). Another factor
      contributing to orthostasis in these individuals is poor muscle tone in the lower extremities
      reducing venous flow.

      Endothelial dysfunction in HF on the other hand is attributed to decreased production of NO
      and increased oxidative stress due to neurohumoral activation, release of inflammatory
      messengers from the myocardium, altered local shear force and resultant atherogenesis (30,
      31). The endothelial dysfunction itself causes an increase in the production of cytokines,
      uncoupling of eNOS and further increases the oxidative stress (32-35). The endothelium helps
      in regulating the vascular tone by balancing the production of vasodilators and
      vasoconstrictors in response to various stimuli (36) and its dysfunction would also impair
      baroreceptor function which in turn would affect cardiac autonomic activity and blood flow.

      In our research we hope to improve both autonomic and endothelial function by supplementing
      protein and carnitine in diet. Studies have shown that when protein is metabolized to the
      amino acids L-arginine and citrulline, there is increased synthesis of NO (37). L-arginine, a
      semi-essential basic amino acid, is a precursor in the formation of nitric oxide by the
      enzyme nitric oxide synthase and directly increases the formation of NO (38). The
      administration of arginine and/or citrulline in patients in HF has been reported to improve
      endothelial function. Systolic and diastolic arterial pressures as well as pulmonary arterial
      systolic pressure have been shown to decrease significantly after administration of arginine
      or citrulline administration, which in turn improves right ventricular diastolic diameter
      (37, 39). One clinical study reported improvement in pulmonary artery pressure and right
      ventricular ejection fraction after two months of oral supplementation with L-arginine or
      citrulline in patients with HF and right ventricular dysfunction (39). It is hoped that
      protein supplementation will improve autonomic function by having a positive impact on
      physiological and biochemical parameters, including nitric oxide synthesis which is expect
      will improve baroreceptor blood flow, autonomic BP and HR in response to tilt.

      Carnitine supplementation of 1g/d for 12 wk in hemodialysis patients significantly reduced
      systemic inflammation, as reflected by decreases in CRP, IL-1β, and IL-6 (40). In obesity,
      the mitochondrial abnormalities of reduced fatty acid oxidation, incomplete β-oxidation, and
      impaired substrate switching from fatty acid to pyruvate were reversed after 8wks of oral
      supplementation with the same dosage of carnitine (41). It is anticipated the same beneficial
      effects of carnitine in individuals with HF.

      The purpose of this study is to evaluate the effects of 16 weeks of protein supplementation
      on measures of autonomic regulation of blood pressure and heart rate, as well as physical
      strength and function in elderly subjects with mild to moderate heart failure (NYHA 1, 2, or
      3). Each participant will be randomized to one of two groups (whey protein + L-carnitine or
      placebos). Study endpoints will be measured at baseline and after 4 months of treatment.
    

Intervention name(s): Whey protein powder and L-carnitine; Maltodextrin placebo powder and Psyllium Husk capsules
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Dietary supplement intervention for 16 weeks; Maltodextrin placebo powder and Psyllium Husk capsules
Other intervention name(s): Dymatize Elite Whey, Europa Sports Products
Intervention MeSH terms: Psyllium; Calcium polycarbophil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science