Amino Acids

All Drugs and Chemicals

Arginine

Nicolaas Deutz, M.D., Ph.D.

Muscle catabolism is a major problem in cancer patients undergoing surgery as it negatively affects post-operative recovery. Recent evidence exists that protein metabolic changes are already apparent in cancer before muscle wasting is being present. In line, patients with breast cancer, generally characterized by a normal nutritional status, were recently found to be arginine deficient. Arginine deficiency in cancer can be explained by: 1) Reduced arginine availability, due to exhaustion of endogenous (muscle) sources of arginine 2) Enhanced arginine catabolism, due to conversion of arginine by arginase, which is abundant in tumors. Protein is the most important endogenous source of arginine. Arginine deficiency will lead to a negative feedback loop in cachexia by promoting protein breakdown in an attempt to restore plasma arginine levels. We hypothesize that pre-operative arginine supplementation in breast cancer patients diminishes the occurrence of muscle wasting after surgery by 1) normalizing arginine availability pre-operatively, resulting in conservation of protein, 2) diminishing the catabolic effects of surgery by supplying exogenous arginine for the post-operative response, 3) enhancing the anabolic capacity to feeding through supplying substrate for protein synthesis.

In the present proposal, the effects of surgery and cancer will be examined by comparing subjects undergoing breast surgery because of malignancy vs. prophylactic reasons (aim 1). Furthermore, the effects of one-week pre-operative protein feeding with or without enrichment with arginine on post-operative protein metabolism (aim 2) will be investigated in the cancer group. Variables of interest are: 1. Whole-body and skeletal muscle protein metabolism, whole body arginine turnover and de-novo arginine production rate, and the anabolic capacity to feeding(assessed by stable isotope methodology). 2. Body weight, muscle mass and functional status, score for well-being (assessed by Profile of Mood State and Mini Mental State).

In the present study, we propose that a nutritional supplement that is high in protein content and enhanced in arginine will be more effective than a typical commercial nutritional supplement in diminishing the catabolic effects of surgery in subjects with cancer, thereby optimizing their quality of life. If this is found to be the case, this would provide the basis for reformulating the nutritional composition in accord with the effects of cancer and surgery on protein metabolism.

Arginine Feeding: a Novel Strategy to Improve Protein Metabolism in Cancer and the Response to Surgery

Texas A&M University

Symptoms and General Pathology

All Conditions

Nutritional and Metabolic Diseases

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Syndrome

Overweight

Obesity

Polycystic Ovary Syndrome

Insulin Resistance

Overnutrition

Nutrition Disorders

Body Weight

Hyperinsulinism

Metabolic Diseases

Glucose Metabolism Disorders

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Endocrine System Diseases

Hypoglycemic Agents

Central Nervous System Depressants

Other Dietary Supplements

Insulin

Insulin, Globin Zinc

Benzocaine

Tannic Acid

Participants will be randomized to an exercise training program or sedentary control group. The sedentary will not perform any structured physical activity or exercise. Participants will be encouraged to maintain their sedentary lifestyle and will be monitored by an accelerometer to track physical activity.

Participants will perform 12-weeks of aerobic exercise training

A progressive increase in duration, frequency and intensity so the last 8 weeks of exercise are performed for 60 min, 5 days per week and at 80% of aerobic capacity. The duration includes a 5 minute warm up and 5 minute cool down. All exercise will be performed on a stationary bicycle (i.e., cycle ergometer).

Aerobic Exercise Training

A goal of this study is to use a novel methodology to determine whether insulin resistance in women with polycystic ovary syndrome (PCOS) is related to the accumulation of proteins with modifications. This could lead to future research to determine if these modifications interfere with their proper function. Additionally, the investigators will determine how protein quality is affected by exercise training. Aerobic exercise enhances the endogenous oxidant buffering systems which may minimize oxidative damage to proteins. The investigators propose that aerobic exercise minimizes the accrual of modified proteins by increasing the synthesis of new proteins, but also by increasing the degradation and removal of old and damaged proteins. Based on our previous studies the investigators observed that insulin affects plasma protein synthesis and aerobic exercise improves insulin sensitivity not only in muscle but also in liver. The investigators therefore propose that aerobic exercise and related increase in insulin sensitivity (and decline in insulin levels) will reduce accumulation of old and modified skeletal muscle and plasma proteins leading to improved function.

Potential Impact of Polycystic Ovarian Syndrome on Protein Modifications and Accumulation

To determine the effect of 12 weeks of aerobic exercise training or sedentary behavior on insulin sensitivity measured by a 3 hour hyperinsulinemic-euglycemic clamp and response to a mixed-meal.

Alterations in protein modifications and accumulation will be measured by a novel methodology developed within our laboratory. Infusion of stable amino acid isotopes will be used to measure the accumulation of proteins before and after 12 weeks of aerobic exercise training or sedentary behavior. Plasma and muscle will be resolved using a two dimensional gel electrophoresis which will allow the identification of protein modifications and age.

Mayo Clinic

Principal Investigator

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Arginine Feeding: a Novel Strategy to Improve Protein Metabolism in Cancer and the Response to Surgery	NCT00497380	Protein Metabol...	Arginine	30 Years -	Texas A&M University
Potential Impact of Polycystic Ovarian Syndrome on Protein Modifications and Accumulation	NCT02105428	Polycystic Ovar... Insulin Resista... Overweight Obese	Aerobic Exercis...	18 Years - 50 Years	Mayo Clinic
Arginine Feeding: a Novel Strategy to Improve Protein Metabolism in Cancer and the Response to Surgery	NCT00497380	Protein Metabol...	Arginine	30 Years -	Texas A&M University

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