Episode 06: Shawn Wells – All About Supplements & Mitochondrial Health| The Joe Cohen Show

Check out the Joe Cohen Show episode page

Key Takeaways

  • Sourcing high-quality supplements is critical – don’t just choose what’s cheapest, a lot of companies have dubious practices, and their supplements are contaminated with heavy metals
  • We put too much weight on cholesterol – lp(a) is really what we should be focusing
  • Protecting mitochondria is a powerful way to keep cellular energy and not get into deficient cellular states – consider supplementing with mitochondrial enhancers: NMN, niacin, nicotinic acid, apigenin, fisetin, spermidine, ergothioneine
  • Up to 59% of people are slow metabolizers of caffeine – if you fall into this group, you get the side effects of caffeine but with minimal benefit (fast metabolizers also get little benefit because their tolerance is high)
    • Paraxanthine is the main helpful compound in caffeine that gives us neurological benefits, focus, and adenosine inhibition – it may be worth supplementing
  • Stack and experiment with supplements one at a time (and best IF the supplements are single ingredient) – what works for one person might not be best for you


Shawn Wells, MPH, LDN, RD, CISSN, FISSN, (@ingredientology) is the world’s leading nutrition biochemist and an expert on health optimization. He’s formulated over 700 supplements, foods, and beverages, and is the author of The Energy Formula.

In this episode of The Joe Cohen Show, Joe Cohen and Shawn Wells take a deep dive into the world of taking supplements – addressing topics like whether supplements improve health, the problem with certain supplement companies, the importance of optimal mitochondrial function, and much more.

Host: Joe Cohen (@mrbiohacker)

Dosing Supplement Intake

  • Play with supplements: rotate through supplements in and out, try intuitive supplementing based on how you’re feeling, etc.
  • Should you take supplements every day? You probably don’t need nutrients or substrates like DHA and creatine every day; when it comes to herbs or compounds similar to pharmaceutical counterparts, you may want to cycle and have a reset
  • There’s an erroneous perception that taking supplements will damage or stress your liver – this is false unless it’s a pro-hormone or anything with heavy metals
    • The liver is resilient and a great detoxifier
    • Only cinnamon has stressed Joe’s liver and he takes 70 supplements per day
  • Mega dosing: some supplements can have tremendous effects at larger doses

Sourcing Supplements

  • Supplements are not just creating expensive pee – supplements work, the question is who they work for and what are they for
  • Supplements come from animals, foods, nature, plants, etc. whose ingredients are used for medicinal purposes
    • But be wary of companies cashing in on using cheaper ingredients such as ginseng but selling the plant sans root which doesn’t have the same effect
  • Sourcing high-quality supplements is critical – don’t just choose what’s cheapest, a lot of companies have dubious practices
  • A good supplement company (Thorne, Xymogen, Doctor’s Best) will test for heavy metals with raw ingredients and after formulation
    • If you want full transparency in ingredients, stay away from “proprietary blends”

Mitochondrial Enhancers

  • “Mitochondrial health is at the core of biological versus chronological aging, it’s at the core of 99% of diseases because they’re metabolic in nature.” – Shawn Wells
  • 87% of Americans are metabolically dysfunctional
  • Ergothioneine is a trace amino acid that naturally occurs in some beans, mushrooms, and organ meats
    • The body has a unique transport and storage system for it in the body
    • It’s not just a cellular antioxidant but also a mitochondrial antioxidant
    • There may be a benefit for loading but take 5-20mg per day
    • It’s a potent mitochondrial antioxidant, shown to be anti-aging in nature, reduce mitochondrial dysfunction, and promote mitochondrial biogenesis (may want to stack with NMN and/or niacin 500mg 2x per day but be mindful of side effects and maybe taper up)
  • Remember, as we age we make less NAD and break it down faster – this is important to counter because NAD promotes the production of ATP and mitochondrial health
  • Ultimate mitochondrial stack: NMN (250-500mg), niacin (few hundred mg), nicotinic acid, apigenin, fisetin, spermidine, ergothioneine
    • Nicotinic acid reduces lp(a), increases NAD, and is generally good for aspects of health but doesn’t seem to reduce all-cause mortality
  • Areas of the body that require the most energy are where you’ll notice improvements like brain health, vascular system, immune system
  • Sleep is important for mitochondrial health: when you get less sleep, there’s a shortfall of energy created versus energy needed there’s inflammation, insulin resistance, brain fog
    • Taking mitochondrial enhancers will make you more resilient and antifragile
  • Spermidine: works on cellular autophagy and cleans out mitochondria (mitophagy)
  • Lipoic acid: not stable and dosing is confusing
  • Dihydro-berberine: at least as effective as metformin and strong role in anti-aging and repairing
    • The problem is metformin is it depletes B12, and can cause GI distress, it’s by prescription only; berberine is more bioavailable and over the counter
    • Dihydro-berberine (versus berberine) is potentially effective against TMAO
  • Carnitine and TMAO: it’s not clear that there’s a causal link between TMAO when taking carnitine or eating red meats – the preferred form is acetyl-carnitine
  • Astaxanthin: marine carotenoid; take 3mg with omega


  • Up to 59% of people are not ideal metabolizers of caffeine
  • Caffeine metabolism: it can take up to 10.5 hours for the half-life of caffeine
  • Caffeine itself has very little benefit and has some degree of toxicity
  • Paraxanthine: the main helpful compound in caffeine that gives us neurological benefit, focus, and adenosine inhibition (check out MuscleTech, Drink Update)

Testing & Tracking

  • Check out Self Decode for robust biomarker and genetic testing
  • It’s essential to know your baseline to understand where to tinker
  • Wearables like oura ring are useful in helping dial in lifestyle

Managing Mood

  • When you’re feeling low, try a natural SSRI: zembrin kanna extract to re-establish serotonin
    • Stack with 5-HTP and saffron extract, vitamin D3
  • If you’re exhausted from mental work, you depleted acetylcholine – try alpha-gpc, curcumin, or huperzine (but don’t stay on this, use it as a one-off)
The Joe Cohen Show : , , , ,
Notes By Maryann

More Notes on these topics

Top Insights and Tactics From

31 Best Podcasts of All Time

FREE when you join over 35,000 subscribers to the
Podcast Notes newsletter

No Thanks