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Choline and Exercise Chang-Woock Lee Human Countermeasures Laboratory Department of Health and Kinesiology Texas A&M University
Choline: What is it? Physiological roles How much is needed? Choline & Exercise Future study plan
Choline: what is it? Quaternary ammonium cation(N,N,N-trimethylethanolammonium)
Choline: what is it? * Membrane Phospholipids: Phosphatidylcholine, Sphingomyelin
Choline: what is it? * Precursor to Acetylcholine (neurotransmitter) Choline + Acetyl-CoA Acetylcholine(ACh) choline acetyltransferase (ACh choline + acetate) ACh esterase
Choline: what is it? * Precursor to Betaine (trimethylglycine) Choline Betaine aldehyde Betaine choline dehydrogenase betaine aldehyde dehydrogenase * Two sources: - Endogenous de novo synthesis: Phosphatidylethanolamine PEMT Phosphatidylcholine - Exogenous: from diet (PEMT: phosphatidylethanolamineN-Methyltransferase)
Choline: what does it do? Folate Intertwined w/ folate, Vit B12, & betaine metabolism SAM: S-adenosylmethionine
Choline: what does it do? Intertwined w/ folate, Vit B6, B12, & betaine metabolism
Choline: what does it do? Intertwined w/ folate, Vit B6, B12, & betaine metabolism
Choline: what does it do? Choline is an essential nutrient: - Phosphatidylcholine (lecithin), Sphingomyelin: cell membrane integrity/function/signaling - Betaine: methylation of homocysteine to form Met - Lipid transport in liver (VLDL/LDL) - Neurotransmitter (Acetylcholine) synthesis in cholinergic neurons - Fetal development - Endogenous synthesis is not sufficient to support the physiological demand Choline deficiency causes: - Hepatosteatosis (fatty liver) - Muscle damage / liver damage (apoptosis) / renal dysfunction - CVD - Cognitive dysfunction - Birth defects / growth retardation -
How much is needed? * 7.5mg/kg/day in general: the intakes needed to prevent liver dysfunction (Zeisel, 2006)
How much is needed? Gender difference in choline requirement (Fischer et al, 2007) - 26 men, 16 premenopausal women, & 15 postmenopausal women - Normal diet (550mg choline/70kg/d) for 10days, followed by choline deficient diet (<50mg/70kg/d)
How much is needed? Gender difference in choline requirement (Fischer et al, 2007) - 77% of men, 80% of postmenopausal women, & 44% of premenopausal women developed fatty liver or muscle damage - Estrogen increases PEMT activity (de novo choline synthesis), thus may have affected the results - 6 of 26 men showed deficiency signs even with normal diet: Current AI may not be adequate for some people
How much is needed? Effects of estrogen and genetic variation in choline requirement (Fischer et al, 2010) - 27 premenopausal women & 22 postmenopausal women - Normal diet (550mg choline/70kg/d) for 10days, followed by choline deficient diet (<50mg/70kg/d) - Postmenopausal women : randomly assigned to estrogen supplement group and placebo group.
How much is needed? Effects of estrogen and genetic variation in choline requirement (Fischer et al, 2010) - The subjects were genotyped for single nucleotide polymorphism (SNP) in the PEMT gene - 75% of NC population has one variant allele - 80%, 43%, & 13% of premenopausal women with 2, 1, or 0 alleles, respectively, developed organ dysfunction - 73% of placebo group & 18% of estrogen group showed organ dysfunction
How much is needed? Suboptimal choline intake is prevalent: - 95th percentile in Nurses’ Health Study: 411mg/d - NHANES 2003-2004 data: ≤ 10% had adequate choline intakes What about the effect of/on physical activities? - Effect of choline on exercise - Effect of exercise on choline level
The role of interest Motor Unit Brooks et al.
The role of interest Neuromuscular Junction Brooks et al.
The role of interest Neuromuscular Junction Ferguson and Blakely, 2004
Choline and Exercise Mixed results from previous studies on relationship between choline and exercise: - Acetylcholine release was reduced in rat phrenic nerve-diaphragm muscle preparation perfused w/ low choline concentration (Bierkamper et al., 1980) - 26 km marathon resulted in 40% decrease in plasma choline level (Conlay et al., 1992) - No change in plasma choline levels after 120 min cycling (Burns et al., 1988) - No decrease in plasma choline after treadmill tests (Warber et al., 2000)
Exercise effects on choline Mixed results from previous studies on relationship between choline and exercise: (Conlay et al., 1992)
Choline and Exercise Mixed results from previous studies on relationship between choline and exercise: - Lecithin supplementation before a marathon maintained normal plasma choline levels with no effects on performance (Buchman et al, 2000)
Choline and Exercise Mixed results from previous studies on relationship between choline and exercise: (Spector et al., 1995)
Choline & Exercise Summary of previous choline/exercise studies: - Limited dietary information - Mostly looked at blood choline level changes w/ endurance type exercise: only strenuous and prolonged exercises such as marathon seem to decrease blood choline levels - Phosphatidylcholine supplementation increased/maintained blood choline levels and resulted in improved recovery, but did not enhance endurance exercise performances - Few studies on resistance exercise: Response may be different (different nerve firing pattern, effect may be local at NMJ)
Study #1 Purpose: To examine the effect of dietary choline consumption on muscle responses to resistance exercise training (RET)
Study #1 36 generally healthy (14 male & 22 female) volunteers completed the study - 50~69 years old, non-smoking, disease-free - Mean age: 59.8±5 years - Blood pressure: <160/100mmHg - Post-menopausal >2 years - Not resistance trained
Study #1 Nutrition - Diet/Nutrition education by an RD - 2 weeks of pre-study diet standardization - 50% CHO, 30% fat, 20% protein - <10% of saturated fat - <200mg/d cholesterol - At least 4 daily food logs / week - Post-exercise protein supplement (egg/milk based protein)
Study #1 RET - 8 exercises (Keiser Equipment: Chest press, Lat pull down, Leg press, Leg extension, Leg curl, Calf raise, Biceps curl, Triceps pushdown) - 3 times/week for 12 weeks - 3 sets of 8~12 repetitions @ 70% of max strength/exercise Testing/Measurement: Pre & Post Training - Body composition w/ DEXA - Basic caloric needs: RMR - Maximum strength (1RM) - Blood draws
Study #1 Diet data - ≥12 days (week 3, week 6, & week 9) - Analyzed w/ Nutribase 7 software & USDA database Low cholinegroup (<350mg/d, Mean: 210±20mg/d) vs. Adequate choline group (>350mg/d, Mean: 462±19mg/d)
Study #1 No difference between two groups: - Energy & macro-nutrient intakes - B6, B12, B5, Folate intakes - Liver damage markers (AST, ALT, GGT) - Change in body fat %, weight, & BMI - Change in RMR - Peak power (force x velocity) - Betaine intake ?
Effect of Dietary Choline and RET on Strength Gain % Gender Male Female Adequate Low Study #1 60 50 40 30 20 10
Study #2 (plan) The effect of choline intake and acute RE on force/power production 50~60 year old, healthy, untrained males & females (postmenopausal: >2yr) Pre-study diet standardization for 1 week (slightly lower than current AI value(7.5mg/kg/d)) - maybe 5mg? Choline (2 different dosage) or Placebo Supplementation during 2 weeks of study period - Low Choline (slightly deficient): 5mg+0mg=5mg/kg? - Adequate Choline (AI): 5mg+2.5mg = 7.5mg/kg? - High Choline (Higher than AI): 5mg+5mg= 10mg/kg?
Study #2 (plan) 1RM tests before/after study (Leg Press, Leg Extension) Acute (4) bouts of high intensity leg RE will be performed w/ Surface EMG on rectus femoris muscle throughout the study Isometric/Isokinetic force/power assessment on knee extension exercise using Kin-Com dynamometer Plasma choline, muscle/liver damage markers, homocysteine levels will be measured
Study #3 (plan) To elucidate the potential mechanisms of choline effect on muscle responses 36 male, 5~6 month old, Sprague-Dawley rats Operant conditioning to perform ‘squat-like’ exercises Random assignment of 6 groups (sedentary low choline, sedentary adequate choline, sedentary high choline, exercise low choline, exercise adequate choline, & exercise high choline) Exercise training w/ flywheel device (3x/week, 2sets, ~25reps/set)for 4 weeks Force production for each rep will be measured using a load cell
Study #3 (plan) (Fluckey et al., 2002)
Study #3 (plan) Body composition & blood choline level before/after training Acute exercise testing (in situ) 2 days after the last training session - Electric stimulation mimicking resistance exercise (~100Hz) on tibial nerve of one leg (the other leg: control) - Force production in soleus and gastrocnemius will be measured during the stimulation - Neuromuscular junction of tibial nerve in soleus/gastrocnemius of both legs will be harvested and assayed for ACh content, choline transporter,ACh esterase, & choline acetyltransferase - Blood markers of muscle/liver damage
Another possibility? Betaine(trimethylglycine) methylatesGuanidinoacetate to creatine? • Trimethylglycine→ dimethylglycine? • or • viaMet → SAM?