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  3. Supplement Series: Tier 2 | Episode 23

Supplement Series: Tier 2 | Episode 23

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The Dr. Layne Norton Podcast is back with Part 2 of the highly anticipated Supplement Series! In Episode 23, Layne dives deep into his Tier 2 supplements — the ones with solid (but not quite elite) evidence for supporting strength, power, endurance, recovery, body composition, stress management, sleep, and overall training performance.

Building on the Tier 1 foundations from Episode 22 (creatine, whey protein, and caffeine), Layne breaks down the science, mechanisms, optimal dosing, timing, safety profiles, and real-world takeaways for these promising options. No hype, just evidence-based insights to help you decide what’s worth adding to your stack.

In this episode, Layne covers:

  • Ashwagandha — Boosts strength, lean mass, testosterone, recovery, sleep, and stress management as a powerful adaptogen.
  • Betaine (Trimethylglycine) — Potential improvements in body composition, strength, power output, and recovery.
  • Rhodiola Rosea — Enhances resistance training performance, endurance, VO2 max, fatigue resistance, recovery, and cognition.
  • Citrulline (including Citrulline Malate) — Increases muscular endurance, reps to failure, nitric oxide production, and reduces fatigue.
  • Beta-Alanine — Buffers acidity for better performance in high-intensity efforts (1–10 minutes), more reps in resistance training.
  • Tart Cherry Extract — Reduces DOMS, speeds strength/power recovery, and lowers inflammation/oxidative stress markers.
  • Melatonin — Improves sleep quality (with indirect benefits for body composition and recovery via better rest).
  • Taurine — Supports endurance, acute power/strength, and recovery from muscle damage/DOMS.
  • Carnitine — Aids recovery, reduces soreness, boosts power/volume, and may enhance high-intensity performance.
  • Magnesium — Benefits exercise performance, recovery, and sleep — especially if you’re deficient.

Layne references key studies, meta-analyses, practical dosing protocols, side effects to watch for, and who might benefit most.

Whether you’re chasing PRs, better recovery, or optimized health, this episode cuts through the supplement noise with Layne’s no-BS, science-first approach.


I. Ashwaghanda

A. Effects

  • Increased strength and lean mass. 1 2 3 4 5 6
  • Increased speed and power.
  • Improved VO2 Max and blood hemoglobin. 2 3
  • Increased testosterone and decreased cortisol. 2
  • Improved recovery, decreased soreness, reduced fatigue, better stress management, reduced inflammation and improved sleep. 2 3 5
  • May have favorable effects on blood lipids. 7

B. Mechanisms of action

  • Ashwaghanda is termed an ‘adaptogen’ which helps the body resist stressors and restore homeostasis. Training exerts a (good) stressor on the body but there is evidence Ashwaghanda has a synergistic effect with training to improve adaptations
  • Improved global recovery through stress reduction
    • Reduction in perceived stress
    • Reduction in stress hormones (cortisol)
    • Improved sleep
    • Reduced inflammation
    • Decreased soreness
  • None of these changes appear to explain the beneficial effects on muscle mass, strength, and performance in isolation. There is likely either an unknown mechanism that is yet to be identified that is at least partially responsible for these outcomes OR it is the combination of the effects listed previously.

C. How to take and dosing

  • Best evidence for improving strength and lean mass is 300-600mg/day standardized to 5% withanolides. This can be consumed in 1-2 doses of 300mg/day
  • Timing appears to be unimportant

D. Safety and side effects

  • Appears to be well tolerated in human RCTs for 2-3 months.
  • Some people report GI distress or headaches but these side effects do not appear to occur at a greater rate than those receiving placebo in studies.
  • Some case reports of liver injury and hepatotoxicity have been reported but these have not been observed in controlled studies. May be worth exercising caution for those with pre-existing liver conditions or taking medications that can cause liver issues.
    • Could be a contamination issue
    • Genetic susceptibility
    • Possible mechanisms exist but isolated to in vitro or animal high dose studies.

II. Betaine (aka Trimethyglycine)

A. Effects

  • May improve body composition and strength. 10 11 12
  • Increase power output and vertical jump. 10 13

B. Mechanisms of action

  • Osmolyte increasing cell volume and a methyl donar. 14
  • Improved training performance may indirectly lead to better body composition as a secondary effect
  • May decrease inflammation and improve recovery. 15
  • Disagreement between studies likely due to small, indirect effects as well as differences in baseline betaine dietary intake

C. How to take and dosing

  • 2.5g per day is most common dosing, sometimes split into 2 doses but likely not necessary unless GI effects noted. 10
  • Typically taken peri-workout but likely less important or not important at all relative to consistent daily intake as the effect is likely chronic rather than acute. 10

D. Safety and side effects

  • Very well tolerated in most studies
  • Some reported GI side effects and may effect blood lipids (slight increase in LDL cholesterol in obese but not healthy subjects) at higher doses (>4g/day). 16

III. Rhodiola Rosea

A. Effects

  • May improve strength and resistance training performance (volume and reps to fatigue). 17
  • Improved VO2 Max, time to fatigue, perception of fatigue, and endurance performance. 18 19
  • Improved recovery and decreased soreness. 20
  • Improved cognitive function. 21

B. Mechanisms of action

  • It is an adaptogen that modulates stress and CNS fatigue. 18
  • Anti-oxidant. 18
  • Anti-inflammatory. 18
  • Reduces muscle damage and creatine kinase. 18

C. How to take and dosing

  • 200-400mg/day at a standardization of 3% rosavins and 1% salidrosides
  • Has small acute effects on fatigue but most benefits are due to sustained use over time

D. Safety and side effects

  • Some reported GI irritation as well as some people report jitters. 18
  • Overall it is well tolerated

IV. Citrulline

A. Effects

  • May enhance muscular endurance, allow for more reps before reaching failure, and reduce fatigue. 22 23 24
  • May improve strength and power performance during high intensity exercise but the effect is small. 25
  • Increases nitric oxide production. 25

B. Mechanisms of action

  • Increases NO production which may help improve blood flow and muscle oxygenation. 26
  • May improve ammonia clearance during exercise which may possibly reduce lactate accumulation and fatigue. 27 28

C. How to take and dosing

  • Citrulline Malate is most common form and dosing is typically 6-8g 30-60 minutes before a workout (when citrulline:malate ratio is 2:1)
  • Pure citrulline is likely just as good in which case 4-6g would be an efficacious dose

D. Safety and side effects

  • Well tolerated and the most commonly reported side effect is mild GI distress at higher doses. 29

V. Beta-Alanine

A. Effects

  • Improved performance in high intensity or maximal exercise lasting 1-10 minutes. 30 31
  • Increase number of repetitions performed before hitting failure during resistance training with moderate loads (60-70% of 1RM). 32 33

B. Mechanisms of action

  • Increases muscle carnosine concentrations by 40-80%. 34
  • Carnosine buffers hydrogen ions and Beta-alanine supplementation can decrease acidosis which may reduce fatigue during high intensity exercise. 35
  • Carnosine acts as a Calcium channel regulator and may improve the sensitivity of muscle fibers to calcium release, improving contractability. 36

C. How to take and dosing

  • 3.2-6.4g per day, typically pre-workout but timing is less important than consistent dosing to increase muscle carnosine concentrations. 30

D. Safety and side effects

  • Well tolerated but most common side effects are paresthesia (skin tingling), flushing, and mild GI distress. 30

VI. Tart Cherry Extract

A. Effects

  • Reduces delayed onset muscle soreness. 37
  • Improves objective recovery markers like time to strength recovery, power recovery, jump height recovery, and recovery of sprint time. 37

B. Mechanisms of action

  • Anti-oxidant and anti-inflammatory effects may help improve time to recovery post exercise.
  • Reduces inflammatory markers like CRP, IL-6, and IL-8.  38 39
  • Reduces markers of oxidative stress like protein carbonyl content. 40
  • Reduces markers of muscle damage like creatine kinase. 40

C. How to take and dosing

  • Typically Montmorency Tart Cherries powdered form (can also be administered in a liquid juice form).
  • Most common dosing is 480mg per day of Montmorency Tart Cherry Extract. 41
  • Effects are more likely due to chronic use rather than acute consumption.

D. Safety and side effects

  • Well tolerated. Most common reported side effect is mild GI distress.

VII. Melatonin

A. Effects

  • My improve body composition (increased lean mass, decreased fat mass), likely indirectly via better sleep. 42
  • Improves exercise recovery. 43
  • Improves many metrics of sleep: latency, duration, quality, etc. 44

B. Mechanisms of action

  • Not a sedative, but rather a chronobiotic signaling night and helping to regulate circadian rhythms. 45 46
  • Acts as an anti-oxidant. 47 48
  • Anti-inflammatory, decreasing IL-1, IL-8, and TNF-ɑ. 49

C. How to take and dosing

  • 0.1-10mg/day about 1-2 hours before bed most common dosing. 50

D. Safety and side effects

  • Grogginess (day after). 51
  • Vivid dreams. 51
  • Headache. 51

VIII. Taurine

A. Effects

  • Improves endurance performance. 52
  • May improve strength and power even at an acute dose. 53
  • Improves recovery by decreasing DOMS and muscle damage. 54 55

B. Mechanisms of action

  • Osmolyte that draws water into the cell. 56
  • Improved calcium handling, increasing calcium available to the myofibrils, which improves contractability of muscle fibers. 57
  • Anti-oxidant and anti-inflammatory effects. 58 59

C. How to take and dosing

  • Typical dose is 1-6g per day consumed around 1-2 hours before training. 60

D. Safety and side effects

  • Most common side effect is GI distress and there have been some reported seizures when consumed at high doses as part of energy drinks in adolescents. 61

IX. Carnitine (From various forms)

A. Effects

  • Improves recovery and reduces delayed onset muscle soreness. 62
  • May increase power output and lifting volume output. 63
  • Improves high-intensity exercise performance and reduces the rate of perceived exertion. 64
  • May improve cognitive function, but most evidence is in those with deficits. 65

B. Mechanisms of action

  • Reduces muscle damage and markers of inflammation and oxidative stress. 66 67
  • Enhanced cholinergenic activity, improved mitochondrial energy production, and better synaptic functioning may explain cognitive benefits. 68
  • May increase androgen receptor density in skeletal muscle. 69

C. How to take and dosing

  • 2g L-Carnitine L-Tartrate per day appears best for exercise recovery. 63 69
  • 2g of Acetyl-L-Carnitine per day appears best for cognitive function 65
  • 2-4.5g of Propionyl-L-Carnitine per day appears best for endothelial function and improved blood flow, which may also enhance exercise performance. 70 71

D. Safety and side effects

  • GI distress at high doses and may cause a fishy odor in high doses. 72
  • Some concern over carntine increasing TMAO levels, which may contribute to heart disease but studies directly assessing carnitine intake have found either neutral or positive effects on mortality or heart disease. 73 74

X. Magnesium

A. Effects

  • May improve exercise performance and recovery in those who are low in magnesium status. 75 76
  • People replete in magnesium status don’t appear to see benefits. 77
  • May help with sleep. 78

B. Mechanisms of action

  • Mg is a co-factor in reactions involving ATP, important for neuromuscular function, and deficiency can impair performance, sleep, and recovery. 76

C. How to take and dosing

  • 200-400mg/day of magnesium glycinate, malate, or threonate

D. Safety and side effects

  • Mostly GI related, especially for magnesium citrate and magnesium oxide which are used as laxatives. 75 76

References

  1. Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial
  2. Effects of Ashwagandha (Withania somnifera) on Physical Performance: Systematic Review and Bayesian Meta-Analysis
  3. The effect of Ashwagandha (Withania somnifera) on sports performance: a systematic review and meta-analysis
  4. The effect of Ashwagandha (Withania somnifera) on sports performance: a systematic review and meta-analysis
  5. Evaluation of Withania somnifera (L.) Dunal (Ashwagandha) on Physical Performance, Biomarkers of Inflammation, and Muscle Status in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Study
  6. Effects of Ashwagandha ( Withania somnifera) standardized root extract on physical endurance and VO 2max in healthy adults performing resistance training: An eight-week, prospective, randomized, double-blind, placebo-controlled study
  7. Impact of ashwagandha (Withania somnifera L.) supplementation on serum lipid concentrations and anthropometric parameters in adults with overweight and obesity: a double-blind, placebo-controlled pilot study
  8. Safety of Ashwagandha Root Extract: A Randomized, Placebo-Controlled, study in Healthy Volunteers
  9. Ashwagandha-induced liver injury: A case series from Iceland and the US Drug-Induced Liver Injury Network
  10. Effects of chronic betaine supplementation on exercise performance: Systematic review and meta-analysis
  11. Decoding Betaine: A Critical Analysis of Therapeutic Potential Compared with Marketing Hype—A Narrative Review
  12. Effect of Betaine on Reducing Body Fat—A Systematic Review and Meta-Analysis of Randomized Controlled Trials
  13. Ergogenic effects of betaine supplementation on strength and power performance
  14. The clinical significance of betaine, an osmolyte with a key role in methyl group metabolism
  15. Betaine Inhibits Interleukin-1β Production and Release: Potential Mechanisms
  16. Safety of betaine as a novel food pursuant to Regulation (EC) No 258/97
  17. Dose–Response Effects of Short-Term Rhodiola rosea (Golden Root Extract) Supplementation on Anaerobic Exercise Performance and Cognitive Function in Resistance-Trained Athletes: A Randomized, Crossover, Double-Blind, and Placebo-Controlled Study
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  21. Rhodiola rosea L. Improves Learning and Memory Function: Preclinical Evidence and Possible Mechanisms
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