Optimize & Control Your Brain Chemistry to Improve Health & Performance

Study: The Importance of Sleep States for Metabolism and Performance

• A recent study published in Cell Reports explored how different sleep states affect human metabolism.
• The study found that sleep states regulate more than 50% of all metabolite features detected in human breath.
• Researchers measured close to 2000 metabolites in breath every 10 seconds across an entire night’s sleep.
• They discovered that different sleep states, such as slow-​​wave sleep and rapid eye movement (REM) sleep, regulate individual metabolic pathways.
• The switch from sleep to wakefulness reduces fatty acid oxidation, while the transition from REM sleep to other sleep states affects the tricarboxylic acid (TCA) cycle.
• This study emphasizes the importance of experiencing different sleep states for optimizing metabolic circuits for human performance and health.
• Not getting sufficient sleep duration prevents the body and brain from transitioning through all the different aspects of fuel utilization, which can impact emotional stability and glucose metabolism during wakefulness.
• Ensuring enough sleep and experiencing all sleep states is particularly important for “night owls” who tend to go to bed late and wake up late.

• The findings underscore the need for sufficient sleep quality and duration to optimize mental and physical health and performance.
  Chronotypes and Sleep Schedules

• People may select sleep schedules based on social activities or personal preferences

• Unclear if there are real genetic propensities for being a night owl or early bird
• Important for people to have control over their sleep schedule and get sufficient REM sleep and slow wave sleep

Study: Resetting Night Owls’ Sleep Schedule

• Published in Sleep Medicine in 2019
• Randomized control trial with male and female participants
• Used nonpharmacological interventions in a real-​​world setting 
  • Targeted light exposure
  • Consistent sleep-​​wake times
  • Fixed meal times
  • Caffeine intake
  • Exercise
• Results showed significant improvements in mood, cognitive performance, and physical grip strength

Interventions for Shifting Sleep Schedule

1. Wake up 2–3 hours before typical wake-​​up time
2. Maximize outdoor light exposure during mornings
3. Keep sleep-​​wake times fixed between workdays and weekends
4. Go to sleep 2–3 hours before habitual bedtime
5. Limit light exposure during evenings
6. Keep a regular schedule for daily meals
7. Don’t drink caffeine after 3 PM
8. Don’t take naps after 4 PM or nap for more than 90 minutes
9. Exercise during the morning, ideally before noon

Benefits of Shifting Sleep Schedule

• Improved cognitive performance
• Improved mood
• Improved physical performance (grip strength)
• Applicable to night owls, early birds, and people with typical sleep schedules

• Useful for adjusting to new schedules, traveling, or matching sleep times with a partner
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Neural Communication

• Nervous system made of nerve cells called neurons
• Neurons communicate through chemicals and electricity
• Synapses: small gaps between neurons where chemicals are released
• Neural circuits: chains of neurons creating different states of mind and behaviors

Neuromodulators

• Chemicals that influence the activity of neural circuits
• Four key neuromodulators: dopamine, epinephrine (adrenaline), serotonin, and acetylcholine

• Can be controlled through behavioral tools and supplementation to achieve desired brain and body states
  Neuromodulators: Fast and Baseline Features

• Neuromodulators: dopamine, serotonin, epinephrine, and acetylcholine

• Fast actions: occur on the order of seconds, minutes, or up to an hour
• Baseline actions: occur on the order of hours, days, or even weeks

Phases of the Day

• Phase 1 (0–9 hours after waking): dopamine and epinephrine dominate
• Phase 2 (9–16 hours after waking): serotonin levels increase
• Phase 3 (17–24 hours after waking): chaotic levels of neuromodulators during sleep

Hormones and Neuromodulators

• Hormones have fast and slow effects on the brain and body
• Steroid hormones (e.g., estrogen, testosterone, corticosterones) can control gene expression

• Understanding the backdrop of neuromodulators and hormones is essential for leveraging tools to optimize brain chemistry
  Hormones and Neuromodulators

• Hormones can change the identity of cells, genes, and proteins

  • Example: Puberty — testosterone and estrogen are released, transforming the body and brain
• Hormones can have slow, long-​​lasting actions or fast actions 
  • Example: Adrenaline (epinephrine) — fast action, increases heart rate, changes blood flow, and alters vision
• Hormones can impact neuromodulators (dopamine, serotonin, epinephrine, and acetylcholine) 
  • Testosterone generally increases dopamine
  • Corticosterones (like cortisol) generally increase epinephrine
  • Oxytocin and prolactin generally increase serotonin
  • Acetylcholine doesn’t have a clear link to hormone systems

Effects of Hormones on Neuromodulators

• Testosterone and dopamine tend to collaborate in the same direction
• Cortisol and epinephrine tend to collaborate in the same direction
• Oxytocin, prolactin, and serotonin tend to collaborate in the same direction
• Acetylcholine has potent effects on its own

Neuromodulator Functions

• Dopamine: Increases motivation, drive, and focus 
  • Misconception: Dopamine is about pleasure, but it’s actually about motivation and pursuit of goals
• Epinephrine and norepinephrine: Generate energy and baseline level of activity 
  • High levels: Feel agitated, want to move, can’t shut down thinking
  • Low levels: Less physical and mental energy
  • Epinephrine is manufactured from dopamine

Understanding these neuromodulators and their interactions with hormones can help create a toolkit for managing mental and physical health. This can include behavioral, supplementation, and prescription drug-​​based approaches.
Neuromodulators

• Epinephrine (Adrenaline)
  • Increases energy and state of readiness
  • Activates the immune system
  • Released during stress
• Serotonin
  • Creates states of contentment, happiness, relaxation, and relief from pain
  • Associated with satiety and feeling of having enough
  • High levels can lead to sedation and lack of motivation
  • Low levels can lead to agitation and stress
• Acetylcholine
  • Associated with focus, learning, and encoding new information (neuroplasticity)
  • Not directly controlled by major hormone systems
  • Can be released during calm states, such as when focusing on a newborn child

Increasing Dopamine for Motivation

• Natural behavioral tools for increasing dopamine:

  • Sunlight exposure in the early part of the day (within the first 3 hours of waking) 
    • Maximizes sunlight exposure to eyes and skin (without causing harm)
    • Sets in motion biological cascades that trigger dopamine release and increase dopamine receptors
  • Increase the number or efficacy of dopamine receptors (D2 and D3 receptors) 
    • Allows circulating dopamine to have a greater effect on motivation, mood, and feelings of pursuit
      Caffeine and Dopamine

• Regular ingestion of caffeine (100–250mg) increases the number of D2 and D3 dopamine receptors

  • Immediate effects: increased adrenaline and epinephrine, decreased adenosine (feeling less sleepy)
  • Long-​​term effects: increased number and efficacy of dopamine receptors
• Recommended caffeine intake varies from person to person 
  • Limit caffeine intake to early in the day (not past 2–4pm) to avoid disrupting sleep architecture

Tyrosine-​​rich Foods and Dopamine

• Tyrosine is a precursor to dopamine and can be found in certain foods 
  • Examples: meats, Parmesan cheese, some vegetables
• Eating Tyrosine-​​rich foods can increase dopamine synthesis 
  • Be cautious if taking drugs that manipulate dopamine pathways (e.g., for Parkinson’s or depression)

Supplements to Increase Dopamine

• Mucuna pruriens: contains L‑DOPA, a potent dopamine increaser, but may cause a substantial crash afterward
• L‑Tyrosine: can be taken as a supplement, increases dopamine within 15–45 minutes and lasts for 30 minutes to 2 hours 
  • Dosage varies from person to person (500mg-​​1000mg)
• Phenylethylamine: fast-​​acting and potent, increases dopamine and related metabolites 
  • Dosage: 300–600mg

Behavioral Tools to Increase Dopamine

• Deliberate cold exposure: a potent behavioral tool for increasing dopamine in a sustained way

  • Reduces inflammation, improves resilience, and increases adrenaline
  • Study: Sramik et al. (2000) — “Human physiological responses to immersion into water of different temperatures”
    Cold Water Exposure and Dopamine

• Cold water exposure can increase dopamine and epinephrine levels

  • Study showed 60-​​degree Fahrenheit water for up to 2 hours increased dopamine transmission
  • Colder water (45–55 degrees Fahrenheit) for shorter durations (30 seconds to 1 minute) can also increase dopamine
• Cold showers or cold water immersion can be used to increase dopamine 
  • Duration can vary from 1 to 10 minutes depending on individual’s cold adaptation
  • Can be used as a tool to maintain dopamine levels when coming off drugs that increase dopamine

B Vitamins and Dopamine

• B vitamins, particularly B6, can reduce prolactin levels, which can help maintain dopamine levels 
  • Be cautious about taking excessive levels of B6, as it can cause peripheral neuropathy
• Ensure sufficient intake of B vitamins to keep prolactin levels in check

Avoiding Bright Light Exposure at Night

• Avoid bright light exposure to eyes between 10:00 PM and 4:00 AM (or 17–24 hours after waking up) 
  • Bright light exposure during this time can reduce dopamine levels by activating the habenula
  • Keep lights dim or off during this time to maintain dopamine levels

Epinephrine (Adrenaline)

• Released in both the brain and body 
  • Brain: locus ceruleus, a collection of neurons that increase excitability of neural networks
  • Body: adrenal glands
• Increases energy, alertness, and the desire to move
• Pupil dilation and wide-​​open eyes are signs of high epinephrine levels 
  • Stimulant drugs can cause large pupils and wide-​​open eyes
  • Sedatives have the opposite effect

Using Tools to Adjust Dopamine and Epinephrine Levels

• Use the provided tools and information to adjust dopamine and epinephrine levels according to individual goals
• Consider using tools individually rather than all at once

• Adjust tools based on personal circumstances (e.g., travel, diet, sleep)
  Increasing Epinephrine for Energy

• Epinephrine (adrenaline) associated with stress, but can be beneficial for energy and alertness

• Physical activity increases epinephrine levels 
  • Exercise early in the day for more energy throughout the day
• Caffeine increases epinephrine 
  • Best to consume 90–120 minutes after waking to avoid afternoon crash
• Cyclic hyperventilation (e.g., Wim Hof breathing, Tummo breathing, Kundalini breathing) 
  • Increases epinephrine and alertness
  • Can be done through deep inhales and exhales, repeated 25 times, followed by a brief breath hold with lungs empty
• Cold water exposure increases dopamine and epinephrine

Acetylcholine and Focus

• Acetylcholine associated with states of focus and attention
• Released from two major sites in the brain: nucleus basalis (forebrain) and an area in the back of the brain
• Increasing acetylcholine levels during learning can improve focus and retention

• Nutrition and supplementation important for maintaining healthy baseline levels of acetylcholine

  • Foods high in choline (e.g., beef liver) can help support acetylcholine synthesis
    Increasing Acetylcholine for Focus

• Choline-​​rich foods: beef liver, eggs, beef, soybeans, chicken, fish, mushrooms, kidney beans, and other vegetables

• Supplements for increasing acetylcholine: 
  • Nicotine (not recommended due to addiction and health risks)
  • Alpha GPC: 300mg before workouts or cognitive work, 3–4 times a week 
    • Note: Long-​​term, high-​​dose use may increase stroke risk and TMAO levels
    • To counteract TMAO increase, take 600mg of garlic (contains allicin)
  • Huperzine: works on the enzymatic pathway, adjusting acetylcholine breakdown
• Behavioral tools for enhancing focus: 
  • Deliberate visual focus exercises
  • Staring at a visual target at the same distance as your work for 30–60 seconds before starting

Serotonin for Well-Being

• Prescription drugs for increasing serotonin should be managed by a licensed physician

• Behavioral tools for increasing serotonin:

  • Physical contact with loved ones (e.g., holding hands, hugs, cuddling)
  • Gratitude
    • Receiving gratitude has a more potent effect on serotonin than giving gratitude
    • Observing others giving and receiving gratitude also increases serotonin levels in the observer
      Increasing Serotonin in the Brain and Body

• Receiving and observing gratitude can increase serotonin levels

• Long-​​lasting effects and no known side effects

Nutritional Approaches to Increasing Serotonin

• Tryptophan: amino acid precursor to serotonin synthesis
• Foods high in tryptophan:
• White meat turkey
• Milk (whole milk)
• Canned tuna
• Oats
• Cheese (e.g., cheddar)
• Nuts and seeds
• Breads
• Chocolate
• Fruits (e.g., bananas, apples)

Supplements to Increase Serotonin

• Cissus quadrangularis
• Dosages of 300–600 mg can increase serotonin levels by 30–39%
• May need to be cycled (e.g., two weeks on, two weeks off)
• 5‑HTP (5‑Hydroxytryptophan)
• Dosages of 300–500 mg
• Can increase circulating serotonin
• May have varying effects on individuals (e.g., sleep, appetite, libido)
• Myo-​​inositol
• Dosages of 900 mg
• Can increase serotonin and other neurochemicals
• Has been explored for treating anxiety, bipolar disorder, migraines, ADHD, etc.
• Can improve sleep quality and depth

Safety and Considerations

• Always consult with a physician before adding or removing supplements from your regimen
• Be aware of potential side effects, such as changes in appetite or libido

• Consider individual responses to supplements and adjust accordingly
  Neuromodulators: Dopamine, Epinephrine, Acetylcholine, and Serotonin

• Neuromodulators: potent molecules that control mental states and physical well-being

• Four main neuromodulators: dopamine, epinephrine, acetylcholine, and serotonin
• No simple test to measure levels of these neuromodulators

Dopamine

• Related to motivation, focus, and energy
• Can be influenced by diet, behaviors, supplementation, and prescription drugs

Epinephrine

• Also known as adrenaline
• Involved in alertness and energy
• Can be influenced by caffeine intake

Acetylcholine

• Important for learning and plasticity
• Can be influenced by supplementation and prescription drugs

Serotonin

• Related to relaxation and sleep
• Can be influenced by diet (e.g., tryptophan in turkey) and supplementation

Using Neuromodulators for Desired Effects

• Experiment with different protocols to find what works best for each individual
• Consider natural fluctuations in neuromodulator levels throughout the day
• Use a combination of tools (e.g., supplements, prescription drugs, behavioral protocols) to achieve desired mental and physical states