LycoRed 40051 Product as a Countermeasure to Exercise Stress

STUDY DESIGN

• Randomized-crossover, double-blind, placebo-controlled study, with N=20 endurance runners. (May start with up to 26 subjects to ensure that 20 subjects complete all study requirements). Subjects will ingest the supplement for 4 weeks prior to running 2 hours at high intensity, washout for 2 weeks, crossover and ingest the supplement for 4 weeks prior to running 2 hours at high intensity.
• 2 arms: LycoRed (code 40051) product and placebo.
• During the 3-day period prior to each running session, subjects will taper exercise training and ingest a moderate-carbohydrate diet using a food list restricting high fat foods and visible fats. Subjects will record all food and beverage intake during the 3-day period, with macro- and micro-nutrient intake assessed using the Food Processor dietary analysis software system (ESHA Research, Salem, OR).
• Exercise protocol: Subjects (overnight fasted) will run on laboratory treadmills at 70% VO2max (~marathon race pace) for 1.5 hours followed by 30 minutes of downhill running (10%) at the same intensity. The downhill running portion will induce delayed onset of muscle soreness (DOMS). The run sessions will occur at 7:00-9:00 am.
• Blood samples will be collected pre- and post-4 weeks supplementation, and immediately post-, 1-h post-, and 24-h post-exercise. DOMS will be measured using a 10-point Likert scale at each blood sampling time point.

STUDY PERFORMANCE

• Male and female endurance runners in the Kannapolis/Charlotte, NC metropolitan area will be recruited through mass advertising and direct email messages. Runners will also be recruited during the Expo event the day before the Charlotte Marathon.
• Study duration is 10 weeks, with 6 visits to the ASU-NCRC Human Performance Lab, two exercise sessions, and 10 blood samples.
• Visit 1: 0-week, pre-study, baseline testing and orientation, early morning; provide blood sample (overnight fasted). Subjects will sign the consent form, fill in the ACSM/AHA screening questionnaire, and complete a training history questionnaire. Subjects will be tested for VO2max (treadmill graded exercise test with metabolic measurement), and body composition (BodPod). Subjects will be given instructions for taking the supplements, and initiate supplementation (4-weeks) (with capsules contained in supplement trays to improve compliance). Subjects will be asked to maintain their normal training schedules, and will record weekly training distances in a log.
• Visit 2: 4-weeks, ~7:00 am, overnight fasted; provide blood pre- and post-running for 2 h (70% VO2max), and 1-h post run.
• Visit 3: ~7:00 am, overnight fasted, 24-h post-run: provide blood sample. Start 2-week washout period.
• Visit 4: 6-weeks, provide blood sample (~7:00 am, overnight fasted), crossover to opposite study arm, and start 4-week supplementation.
• Visit 5: 10-weeks, (~7:00 am, overnight fasted), provide blood pre- and post-running for 2 h (70% VO2max), and 1-h post run.
• Visit 6: 24-h post-run (~7:00 am, overnight fasted), provide final blood sample.

INVESTIGATIONAL PRODUCTS

• LycoRed (code 40051) product with mixture of selected carotenoids and phytochemicals in medium chain triglycerides (MCT).
• Placebo: Each softgel will be identical looking, containing the vehicle of MCT oil with all active ingredients removed.
• One serving (1 capsule) of the supplement will be consumed daily during the morning meal.

PRIMARY ENDPOINT

• Oxidative stress biomarkers

SECONDARY ENDPOINTS

• Inflammation biomarkers
• Muscle damage biomarkers
• Plasma lycopene, phytofluene, and phytoene
• Oxidative capacity

Inclusion criteria

• Male or female endurance runner (ages 18 to 45).
• Compete in long distance road races and are capable of running on a treadmill at marathon race pace for two hours (including 30 min of downhill running). Note: Preference will be given to runners who have completed a half-marathon or greater distance race in the previous year.
• At "low risk" status for cardiovascular disease (as determined with the screening questionnaire).
• Agree to train normally, stay weight stable, and avoid the use of large-dose vitamin/mineral supplements (above 100% of recommended dietary allowances), herbs, and all medications during the project.
• Agree to taper exercise prior to each of the two lab running sessions as if preparing for a long distance race.

Exclusion criteria

• Inability to comply with study requirements.
• Any other concurrent condition which, in the opinion of the primary investigator (PI), would preclude participation in this study or interfere with compliance.
• Weigh less than 110 pounds.
• Current, active history of coronary heart disease, stroke, cancer, diabetes, rheumatoid arthritis, high blood pressure, kidney disease, liver disease, blood disease, hormonal disease, or metabolic disease.
• History of cancer in the 5 years prior to the screening visit (except skin or cervical cancer that was successfully treated).
• Current use of any type of medication (or unwillingness to stop use of over-the-counter medications two weeks before the start of the study).
• Use of any 'recreational substance' whether legal or illegal, by prescription or over the counter.
• Pregnant or nursing, or planning to be pregnant or nursing during the study.
• Use of vitamin/antioxidant supplements within 4 weeks prior to starting the study. For subjects using vitamin/antioxidant supplements, a 4-week wash out will be required prior to starting the study.
• Unwilling to follow dietary guidelines from the screening visit through the final visit as follows:
• no more than an average of 2 servings*/week of lycopene-rich foods (e.g. tomatoes and tomato products, including all sauces containing tomatoes that are contained in pizza, soups, etc., ketchup, vegetable juice with tomato, French salad dressing, mango, guava, watermelon, papaya, red grapefruit).
• no more than an average of 5 servings*/day of vegetables and fruit
• avoidance of antioxidant vitamin, mineral or herbal supplements including, but not limited to vitamin C, vitamin E, flavonoids, carotenoids, selenium, etc.
• Consumption of more than an average of 2 units of alcohol daily.**
• Known allergy to tomatoes or citrus fruits.
• Following any special diet including, but not limited to liquid, high or low protein, raw food, vegetarian or vegan, etc. (Subjects should normally consume mixed diets).
• Current use of muscle enhancing supplements such as HMB, ATP and other similar muscle building agents.
• Current use of use of sodium bicarbonate or medications containing sodium bicarbonate such as Alka-Seltzer.
• Recent history of musculoskeletal trauma (fracture, strain, sprain, etc.) that has not fully healed prior to baseline testing.
• Planning to have surgery during the study.

• For the purpose of this study one serving of vegetables or fruit is defined as: Vegetables
• 1 c raw leafy vegetable; ½ c cut-up raw or cooked vegetable; ½ c vegetable juice Fruit
• 1 med fruit; ¼ c dried fruit; ½ c fresh, frozen, or canned fruit; ½ c fruit juice

• For the purpose of this study, one unit of alcohol is defined as 12 oz (400 ml) of beer, 6 oz (200 ml) of wine or 1.5 oz (50 ml) of hard spirits.