2/11 - Caffeine & Such 

Early Research Hypothesis

  • Caffeine is widely studied as a performance-enhancing supplement 

  • Endurance exercise research focus on caffeine effects on fat metabolism, glycogen sparing + central nervous system (CNS) activation 

  • 78% of studies show ergogenic effects of caffeine on endurance performance 

    • Increases free fatty acids release from adipose tissue 

    • Spares muscle glycogen prolonging endurance 

Conflicting Evidence on Fuel Utilization 

  • No metabolic shift after caffeine ingestion 

Current Understanding - CNS activation 

  • Primary ergogenic mechanism = CNS stimulation NOT fuel utilization 

  • Adenosine receptor blockade leads to: 

    • Reduced perception of fatigue 

    • Increased alertness + endurance performance   

  • Majority of studies support caffeine’s ergogenic benefits in endurance exercise 

  • CNS activation = key mechanism behind caffeine performance-enhancing effects 

  • Recommended dose 3-6 mg/kg for endurance benefits

Death do we part? 

  • FDA recommends limit of 400 mg or 0.4 g 

    • 4-5 cups of coffee

    • Estimate of dangerous effects w consumption around 1,200 mg of caffeine

  • Average caffeine intake for a American = 165-230 mg

  • Caffeine sound in energy drinks ranges - 40-250 mg per 8 fl oz. 

Caffeine Mechanisms of Action - Adenosine Receptor Blockade 

  • Rapidly Absorbed + 99% bioavailable within 45 min 

  • Peak plasma concentration = 15-120 min (post ingestion) 

  • Caffeine binds to adenosine receptors prevents adenosine from inducing fatigue   

  • Results = increased levels

    • Norepinephrine 

    • Dopamine 

    • Acetylcholine 

    • Serotonin 

    • Glutamate 

    • Leads to enhanced alertness + cog function 

Absorption + Metabolism

  • No hepatic first pass effect  - directly enters circulation 

  • Metabolized mainly in the liver into paraxanthine (70-80%) 

  • Factors that affect metabolism

    • Pregnancy 

    • Obesity 

    • Smoking 

    • Altitude 

    • Oral contraceptives

Effects on Lipid Metabolism 

  • Mechanisms = increases lipolysis via beta adrenergic stimulation 

  • Mobilizes free fatty acid for energy 

  • Increased cAMP - stimulates neurotransmitter + hormone release 

  • Inhibits phosphodiesterase - prevents cAMP breakdown 

Research 

  • Previous studies suggest >300 mg of caffeine may induce acute diuresis 

    • In contrast - excessive + impractical doses of caffeine 6 mg/kg or >500 mg may facilitate acute diuresis

Popular Trend - Delaying Morning Caffeine 

  • Tik tok suggests waiting 90-120 min after waking to drink coffee 

  • Claims 

    • Prevents prologing morning cortisol peak 

    • Avoids an afternoon energy crash 

Cortisol Natural Circadian Rhythm 

  • Cortisol peaks within 1 hr of waking + declines throughout the day 

  • Additional to small peaks occur around meals 

  • Key - caffeine does not disrupt the natural rhythm 

Caffeine + Cortisol Response 

  • Caffeine increases cortisol + ACTH secretion 

  • Effects occurs regardless of when caffeine is consumed 

  • Conclusion = delaying caffeine does not prevent cortisol related effects 

Adenosine + Sleep-Wake Cycle 

  • LOOK AR SLIDE

Afternoon Crash 

  • No evidence links to morning caffeine intake to an afternoon energy crash 

  • Possible causes of fatigue 

    • Poor sleep 

    • Blood sugar fluctuation 

    • Natural circadian rhythm dips 

  • Solution - small afternoon caffeine does - not delayed morning intake 

Benefits to Delaying Caffeine 

  • Effectiveness - no cortical or adenosine decline should guide timing 

Pregnant Women Avoid Caffeine - Risks 

  • Caffeine freely crosses the placenta - 

    • Fetus or placenta can metabolize it 

  • May accumulate in oviducts + uterine fluids - can affect embryonic development 

    • Can contribute adult onset disease 

  • Around 80% pregnant ladies consume caffeine daily 

  • Research - suggest caffeine intake during pregnancy = linked to adverse gestational outcomes 

    • Increase risks 

      • Intrauterine growth retardation/ low birth weight 

      • Subfertility + spontaneous abortion 

      • Fetal growth restrictions + cognitive impairments 

      • Obesity + metabolic rates 

      • Potential epigenetic changes across generations 

Individual Variability + Caffeine Metabolism 

  • Effects vary -

    • Adenosine receptor activity 

    • CYP1A2 enzyme activity - responsible for caffeine metabolism

  • Some women can be more vulnerable to adverse effects than others 

Conclusions + Rec 

  • Maternal caffeine consumption linked to neg pregnancy outcomes 

  • Rec = pregnant women or those considering - should limit or abstain from caffeine 

  • More research needed 

Supplements 

  • Nutritional weight loss supplements = purported to work by increasing energy expenditure, modulating carbs or fat metabolism, increasing satiety or blocking fat or carb absorption 

2/13

  • Ephedrine = the primary active ingredient of herbal ephedra - has been studied both alone or in combo with caffeine 

    • Placebo controlled studies have demonstrated the ephedrine w caff

DNP - Dinitrophenol 

  • Chemical compound historically used in explosives, dyes + pesticides 

  • Later marketed as a weight loss aid

  • Extremely dangerous with severe side effects + high fatality risk

Mechanism of Action

  •  increases basal metabolic rate (BMR) - rapid fat + carb burning 

  • Thermogenic effect - body temperature rises dangerously

  • Average metabolic rate increase = 11 % per 100 mg dose 

  • Loss up to 1.5 kg per week reported 

Uncoupling of Oxidative Phosphorylation 

  • With DNP: ATP synthase func = disrupted 

  • ATP production = stopped 

  • Energy dissipates as a heat instead of being stored 

  • DNP Mechanism of Action

    • Prevents ATP formation by blocking inorganic phosphate uptake 

    • Increases oxygen consumption

    • Causes proton (H+) leakage across mitochondrial membrane

Risk

  • Carb consumption markedly increase - allows for rapid weight loss with small doses

  • Pyruvic acid is aerobically metabolised to H2O and CO2 

    • Results in production of lactic acids when metabolized anaerobically 

  • Discrepancy between stimulation of glycolysis + inhibition of oxidative phosphorylation = rapid production of pyruvic acid - leading to increase production of lactic acid 

  • Failure of Thermoregulation 

    • Excess proton leakage = heat generation 

    • Increased metabolic rate - uncontrolled cal burings 

  • Hyperthermia 

  • Rapid heart rate, sweating, shortness of breath 

  • Death 

Capsaicin 

  • Important compound in chili peppers 

  • Animal studies - can reduce prevalence of obesity by suppressing inflammatory responses + enhancing fatty acid oxidation in adipose tissue + liver

  • Human studies - controversial 

  • Some research - can help control body weight (BW) + reduce risk of developing obesity 

Perception of Spicy Foods 

  • Eating spicy food - increases appetite but reduces appetite + increases satiety 

    • Mechanism = unclear

  • Acute lunches containing capsaicin = shown to increase + decrease auxin-releasing peptide - can affect hunger 

  • Release of catecholamines caused by capsaicin affects appetite

Results of Capsaicin 

  • Potential intake to reduce BMI, BW, and WC but no effect on WHR 

  • Potential to promote lipid oxidation reduce appetite + accelerate energy metabolism - impacts weight loss 

  • Mechanism of increasing liquid oxidation + energy consumption due to the activation of transient receptor potential vanilloid subtype 1 

Large Scale Chinese Study Findings 

  • The increase in body size may be linked to these added ingredients rather than capsaicin

 Thermogenic 

  • Caffeine 

    • Proposed mechanism- CNS stimulation, lipolysis 

    • Dosage - 100-400 mg 

  • Green Tea 

    • Proposed mechanism - norepinephrine enhancement 

    • Dosage - 250-500 mg 

  • Capsaicin 

    • Proposed mechanism - TRPV1 receptor activation

    • Dosage - 2-10 mg/day

  • Yohimbine 

    • Proposed mechanism - Alpha-2 receptor blockade 

    • Dosage - 5-20 mg 

  • Synephrine 

    • Proposed mechanisms - beta adrenergic agonist

    • Dosage - 10-50 mg

  • L-Carnitine 

    • Proposed mechanism - fatty acid transport 

    • Dosage -1-3 g 

  • 5-HTP 

    • Proposed mechanism - serotonin increase (appetite control) 

    • Dosage - 100-300 mg 

  • Forskolin 

    • Proposed mechanism - cAMP activation (fat breakdown) 

    • Dosage - 25-50 mg 

  • Raspberry Ketones 

    • Proposed mechanism - norepinephrine induced lipolysis 

    • Dosage - 100-200 mg

  • CLA

    • Fat metabolism alteration 

    • Dosage - 3-6 g