Supplements That Can WRECK Your Health Because of Genetics
This video features a deep conversation between the host and Dr. Tyler Panzner about how your unique genetic makeup determines whether popular supplements will help or harm you. From caffeine and creatine to vitamin D and omega-3s, they explore why one-size-fits-all health advice often fails, and how understanding your genes can transform your health approach.
1. Introduction: Why Bio-Individuality Matters in Health
The conversation kicks off with a powerful statement that sets the tone for everything to come:
"I think anyone that's barking that like this is good or bad for every human, they clearly don't know what they're talking about because we are all very different."
The host introduces Dr. Tyler Panzner, noting that he covers something often overlooked in health information – bio-individuality and how your genes affect your response to different foods and supplements. While many people vaguely know this already, the health space tends to push one-size-fits-all solutions when reality is much more nuanced and complex.
Dr. Tyler points out that there's an overabundance of people on social media who simply regurgitate information from supplement labels. But the real question is: what else is that supplement doing in your body? Every supplement or nutrient has many mechanisms, and we need to make sure those mechanisms serve us without causing deleterious or negative effects on our physiology.
2. How Tyler Got Into Genetics: A Personal Health Journey
Dr. Tyler shares his fascinating backstory. As a kid, he wanted to be the next Crocodile Hunter – Steve Irwin was his idol. 🐊 His love for biology eventually shifted from "macro-biology" (animals) to the microscopic world when he took an 11th-grade biology class.
"It's like we have a whole city or a world inside of each one of our cells – all these organelles, all these proteins doing these things."
He pursued molecular and cellular biology at the University of South Florida, where he got deep into supplements and biohacking. He was literally making his own pre-workout in his dorm room and selling it at the school gym! This hands-on experimentation taught him how different compounds affected his body – more anxious with certain stimulants, calmer with others.
A professor suggested pharmacology, and suddenly everything clicked. Looking at his coffee one day, he realized:
"It doesn't magically wake me up – there's a molecule that blocks a receptor which blocks the tired signal. So that's why I'm awake."
He went straight into a PhD in pharmacology, eventually working on breast cancer research. But during a period of poor health – dealing with anxiety, brain fog, and sleep issues – he got his 23andMe test done about seven or eight years ago.
The results were disappointing initially – mostly trivial stuff like whether cilantro tastes like soap or if asparagus makes your pee smell weird. So he dug into the raw genetic data himself, figured out his mutations, and did targeted supplementation. Doctors wanted to put him on medications, but he changed his life within days or a couple of weeks through this personalized approach.
"That's when I decided I want to be in personalized medicine."
After working at an oncology company doing next-generation sequencing, he started his own business. Over two years, he's worked with over 700 people one-on-one, bridging the gap between conventional and holistic medicine.
3. How Genes Affect Caffeine Metabolism ☕
When discussing caffeine, Dr. Tyler explains there are multiple layers to how it affects you – it's not just about the famous "slow metabolizer" gene.
The Adrenaline Connection
Beyond caffeine metabolism speed, there's how quickly you metabolize the adrenaline and neurotransmitters that caffeine makes you release. Mutations in the COMT gene or MAO gene affect how quickly you break down dopamine and adrenaline.
"I have a double slow COMT mutation – that was actually the first gene I figured out for myself years ago. And it made a lot of sense why I'm very go-go-go, extroverted, Type A, prone to stress – because I'm just sensitive."
The Adenosine Receptor
There's also the adenosine receptor itself. Some people have mutations where caffeine binds more strongly to this receptor, making them more prone to anxiety – even if their serum caffeine levels and metabolism are normal.
"So there's how much of the molecule is floating around for how long, and there's how tightly it binds to the adenosine receptor."
Caffeine Alternatives
For sensitive people, there are alternatives to traditional caffeine:
- Dynamine – shorter-acting, often used in pre-workouts
- Theacrine – longer-acting, more mild, naturally plant-based from the same family as caffeine
- Paraxanthine – another option that some find smoother
People with adenosine receptor mutations often respond really well to theacrine, saying:
"This is what caffeine should feel like – I feel peppy but not my heart's beating out of my chest."
Hidden Adrenaline Boosters 🚨
Dr. Tyler warns about ingredients people don't realize boost adrenaline:
- L-tyrosine and L-DOPA – give your body more ingredients to make adrenaline
- Rhodiola rosea and astragalus root – inhibit COMT/MAO genes (like plugging the drain in your adrenaline bathtub)
- Yohimbe – mimics adrenaline
- Methylene blue – can make sensitive people overstimulated and anxious
"People will take a thyroid supplement that has tyrosine, astragalus root, licorice root, and they wonder why they're losing their marbles because they're jacking up this adrenaline."
Many natural supplements for brain health, joint health, or gut health contain these stimulatory ingredients without caffeine – so combining them with your morning coffee can leave you overstimulated without understanding why.
4. Creatine and Genetics: The Most Well-Studied Supplement
Dr. Tyler considers creatine the most well-studied supplement we have, with benefits beyond muscle strength – including sleep deprivation recovery, topical skin health, and potentially neurodegenerative disorders. It helps you make ATP, and he views it as very safe for most people to try.
Potential Issues
The most common problem is GI upset, which a micronized creatine might help. Studies show it doesn't really affect the kidneys. But there's an interesting twist:
"One interesting thing is that creatine is also a methyl donor."
The Methylation Connection
For people sensitive to methylation, creatine's methyl groups can be problematic. While these methyl groups can help with mental health by supporting neurotransmitter production and cellular energy, they also help convert norepinephrine into epinephrine (adrenaline).
"For people that are sensitive to adrenaline like me, it can make people feel overstimulated or anxious."
If you're already taking too much methylfolate or methyl B12 (which many people are overdoing nowadays with all the MTHFR hype), adding creatine might push you over the edge.
The DHT and Hair Loss Question 💇
There's ongoing debate about creatine and hair loss through DHT (dihydrotestosterone). Dr. Tyler notes there was one study showing creatine can raise DHT, but:
"I haven't seen any studies actually conclusively linking it to that DHT leading to that hair loss."
The host adds important context: in that study, participants did a loading phase of 20 grams for five days, then 5 grams for two weeks. Their baseline DHT was already lower, so while there was a percentage increase, it didn't reach supraphysiological levels.
Dr. Tyler's perspective from clinical experience:
"I've seen it firsthand – creatine cause hair loss in certain individuals. But guess what? Those individuals had mutations for higher DHT. They were already starting out in that area."
This highlights a fundamental problem with how we study supplements:
"The way we study these things is kind of flawed in certain ways because you can't just get a bunch of people with all different levels of baseline DHT and then see if creatine does that."
For those with high DHT who want to keep their hair, combining creatine with DHT-lowering compounds like saw palmetto or reishi mushroom might let you enjoy the benefits while mitigating the risk.
5. Citrulline, Arginine, and Nitric Oxide Boosters
When it comes to pump-increasing supplements like citrulline and arginine, genetics play a significant role. Dr. Tyler reveals that his citrulline report analyzes 11,245 SNPs (genetic variants) – it's far deeper than just one gene.
Personal Experience with NOS3 Mutations
Dr. Tyler has several mutations in the NOS3 gene (the gene that synthesizes nitric oxide). After 15+ years of bodybuilding, he only discovered this a few years ago:
"I switched from arginine to agmatine and I noticed massive differences... Bro, I had to stop working out – my arms are going to explode! I've never – now I understood what a pump really was."
Agmatine is a metabolite of arginine, and if the enzyme that creates agmatine doesn't work well, switching directly to agmatine can make a huge difference.
Cardiovascular Connections
These same NOS3 mutations affect much more than gym pumps:
- Erectile dysfunction
- Blood pressure
- Neurotransmission and brain health
- Preeclampsia
- Cardiovascular risk
"The same thing that helps with erectile dysfunction can help you get a better pump at the gym, can lower your blood pressure, can help with histamine."
6. Glycine: A Favorite Longevity Molecule
Both Dr. Tyler and the host love glycine as a longevity molecule. The host takes about 10 grams daily plus 3 grams from collagen (13 grams total), while Dr. Tyler hovers around 7-8 grams.
"It's an added bonus – it tastes so delicious! I love mixing that at night... literally tastes like sugar."
Why Some People React Badly
Despite glycine being well-tolerated in studies (even at 90 grams/day!), some people report headaches, insomnia, or nausea at low doses. Dr. Tyler explains:
Glycine is a co-agonist at the NMDA receptor – a receptor crucial for neurotransmission. Glutamate (an excitatory neurotransmitter) needs glycine or serine to activate this receptor. Magnesium blocks it (which is why it's calming), and ketamine blocks it (which is why it's essentially a tranquilizer).
"For some people, they have mutations in that NMDA receptor... they might be extra sensitive, more overactive."
If you're more sensitive to glutamate or have excess glutamate floating around, glycine can worsen symptoms like headaches, anxiety, and insomnia. Adequate magnesium can help – people who are magnesium deficient often find their glycine sensitivity improves with supplementation.
The Problem with Getting Glycine from Food
Most people don't eat enough glycine-rich foods:
"When's the last time someone ate a bone or a tendon or a sinew? Unless you're doing a lot of bone broth or nose-to-tail carnivore, you're going to be missing out on a lot of that glycine."
The host notes that 100 grams of pork rinds contains about 20 grams of glycine – but that's a lot of pork rinds with extra calories and saturated fat!
7. Histamine, Fermented Foods, and Bone Broth 🍖
The Hidden Histamine Problem
Dr. Tyler can't tolerate bone broth – he gets headaches, feels anxious, and doesn't sleep well. Why? Bone broth is high in glutamate and very high in histamine. The roasting process converts histidine into histamine.
"A lot of people I work with – they think they're doing the right thing having bone broth. Well, it can help with a lot of things, but what else does it do? If you're very sensitive to histamine or glutamate, it may be a no-go for you."
How Easy It Is to Overload on Histamine
Dr. Tyler paints a common scenario:
"A lot of people I work with, their morning routine – they wake up fasting, have black coffee (freshly roasted = high in histamine), have apple cider vinegar (high in histamine), then go to the gym (exercise stimulates histamine release). They feel horrible after the gym, off the whole day because you just overloaded so much histamine into your body."
Genetic Variations in Histamine Processing
Interestingly, many East Asian populations have better genetics for gut histamine breakdown – possibly an evolutionary adaptation since their cultures consume many fermented foods. They're genetically better equipped to enjoy the benefits without absorbing excessive histamine.
Dr. Tyler's Travel Kit
When traveling, Dr. Tyler always brings:
- DAO enzymes – digestive enzymes for histamine
- Molybdenum – digestive support for sulfur
"If they're serving something with pickles or onions or garlic, if I don't have that, I'll just get the brain fog or feel a little socially awkward."
8. Food Sensitivities and Plant Chemicals 🌱
The conversation turns to plant defense chemicals, oxalates, and the debate about whether all plants are harmful.
Oxalate Sensitivity Report
Dr. Tyler's oxalate sensitivity analysis includes over 87,000 SNPs. When this report shows high sensitivity, he asks about kidney stone history – about 80% of the time, there's a family history.
The Balanced Diet Perspective
"I think anyone that's barking that this is good or bad for every human, they clearly don't know what they're talking about because we are all very different."
Dr. Tyler believes a balanced diet works for most people most of the time:
- Lean animal proteins
- Fruits and vegetables
- Low-GI carbs
More extreme diets (deep keto, carnivore, pro-metabolic, vegan) should be short to mid-term tools to reset, not lifelong commitments.
"The longer you do these more extreme diets, I do think down the road you'll run into some complications and issues."
Eating Ancestrally Means Different Things
"When we say eat ancestrally, that means different for different people. If you're from Russia, you're going to be eating a lot of animal fat and meat – not a lot of foliage there. Versus someone in the Caribbean."
He cautions against making any diet your identity:
"The same exact thing that healed you is rarely what keeps you healthy."
9. Methylation and Homocysteine
The host shares a personal experience with methylation supplements. His homocysteine was around 11 (ideally below 10, closer to 5). He added 4 grams of TMG (trimethylglycine) plus a B complex, but his levels only dropped to 9.
The game-changer? Hyperbaric oxygen therapy (HBOT) – after about 15-20 sessions over two months, his homocysteine dropped dramatically to 5.5. His wife had similar results for her mold illness recovery.
Dr. Tyler notes this could be because the BHMT gene (which uses betaine/TMG) might not have been the bottleneck. Other methyl donors include:
- Phosphatidylcholine
- Creatine
Different people respond to different methyl donors based on their specific genetic variants.
10. Microplastics and Detoxification Strategies 🧪
The conversation shifts to emerging biohacking modalities. The host mentions recent concerning research about microplastics, including a study finding them in the brains of dementia patients.
Potential Detox Methods
- Blood donation – shown to reduce "forever chemicals"
- Plasma exchange/donation
- EBOO (Extracorporeal Blood Ozone Oxygenation) – blood is removed, filtered, ozonated, exposed to UV light, then returned. Used medically for autoimmune and inflammatory conditions, potentially filtering microplastic particles. Cost is around $2,000.
More Accessible Options
- Chlorella – studies show it removes plastics from aquatic environments. No human data yet, but:
"It's not evidence-based, I like to say I'm evidence-guided, science-based... Chlorella – how many benefits are there anyways?"
- Certain mushrooms – used environmentally to degrade plastics
- Melatonin – a powerful antioxidant with potential to degrade BPA
11. Melatonin: The Wrongly Demonized Supplement 😴
Dr. Tyler considers melatonin one of the most wrongly demonized supplements, alongside vitamin D.
Addressing the "It's a Hormone" Concern
The host explains why melatonin is different from other hormones:
"It doesn't work like testosterone... Your body makes melatonin in response to the absence of light primarily."
Unlike testosterone (always present in blood with diurnal variation), melatonin production is mediated by gut hormones and light cues through circadian rhythm signals.
Genetic Factors in Melatonin Response
Dr. Tyler has mutations in:
- Clock gene – affects how cells tell time
- Melatonin receptors 1A and 1B
Interestingly, the same gene that metabolizes caffeine (CYP1A2) also metabolizes melatonin. He needs more melatonin but breaks it down slowly, so he takes only about 0.5-1 milligram nightly.
A useful indicator for melatonin receptor mutations:
"If you're very sensitive to light when you sleep – like if there's that tiny little blue light you got to cover up across the room – that's a good indicator you have these melatonin receptor mutations."
Melatonin Beyond Sleep
Dr. Tyler prefers to classify melatonin as a detox antioxidant more than a sleep aid. At high doses (200-500mg) for conditions like long COVID, some people actually get more energized and take it in the morning.
His wife is an ultra-fast metabolizer who can take triple or quadruple his dose and still bounce out of bed, while he gets groggy over 1 milligram.
The Hypocrisy of Melatonin Critics
"It's really interesting that the same practitioners that say don't take vitamin D or don't take melatonin – they're hormones – they'll also prescribe testosterone, estrogen, and progesterone. It's kind of hypocritical."
12. Vitamin D: Conversion Issues Most People Don't Know About ☀️
Dr. Tyler shares his vitamin D journey. He loves the beach, was going frequently, yet his levels stayed low. On 10,000 IU of supplemental vitamin D, his levels only went up by 10-11 nanograms per milliliter – not much at all.
The Genetic Bottlenecks
-
DHCR7 gene – converts UVB radiation + cholesterol into pre-vitamin D. Mutations here mean you can't make vitamin D well from sunlight.
-
CYP2R1 gene – hydroxylates vitamin D to its active form. Dr. Tyler has five mutations in this gene.
"The vitamin D I'm taking – that calciferol – 99.9% of people that take vitamin D need to convert it. If your vitamin D levels don't go up on blood work with supplementation, they try to give you an injection, that still doesn't go up – it's not an absorption issue, it's a conversion issue."
The Solution: Pre-Activated Vitamin D
He found an over-the-counter brand of pre-activated vitamin D (calcifediol):
"I took it – within two days I felt so much better, and within three weeks my levels were actually too high. I had to back off on the dosing."
Vitamer-D is the brand he recommends, which ships globally. It's the exact form your body needs to circulate and work.
⚠️ Caution: Levels can go up very quickly with this form – start with one tablet.
Target Ranges and Receptor Mutations
For most people, Dr. Tyler likes levels around 50-70 nanograms per milliliter. But for those with vitamin D receptor mutations, levels might need to reach 100 ng/mL before they feel effects, since their cells can't detect vitamin D properly at normal ranges.
"People that say no one should take vitamin D – we make it from sunlight – not everyone makes it from sunlight the same."
13. Omega-3s and the Histamine Connection 🐟
Omega-3s are well-researched, but there's debate about increased atrial fibrillation risk. Dr. Tyler offers a unique perspective:
Fish and Biogenic Amines
Fish are very high in biogenic amines (histamine is an amine). For histamine-sensitive people, these amines can trigger mast cell degranulation, dumping more histamine and causing:
- AFib
- Heart palpitations
- Headaches
Scombroid Fish Poisoning
"Certain big fish, if they're not stored properly, certain bacteria can convert those amines into histamine. People will eat that, get covered head to toe bright red like eczema rashes, crazy heart palpitations – they go to the ER, they just give them Benadryl to block the histamine."
The Solution: Algae-Based Omega-3s
"For certain people that are more histamine-sensitive... I like to opt for a good algae, vegan-sourced one. It has the same omega-3 structure – same molecule – just lacking all the amines from the fish."
Dr. Tyler personally takes around 2 grams EPA/DHA daily from algae-based omegas (Nordic Naturals and Metagenics have good options). Anything over 1.5-2 grams of fish-based omega-3s makes him feel a little revved up.
Important clarification: this isn't about oxidation or quality. Even the purest fish oil will have amines. If you're sensitive, you may need to either:
- Use algae-based omega-3s
- Lower histamine elsewhere in your diet
- Support histamine clearance with DAO enzymes
- Clean up gut health or address infections that raise histamine
14. Where to Start Understanding Your Genetics 🧬
For those wanting to dive deeper, Dr. Tyler offers several resources:
Free Educational Content
- Genetics 101 course – basics of understanding these concepts
- Cell signaling pathway courses – including a histamine primer
- Content on why thinking in terms of pathways (histamine, glutamate, etc.) simplifies everything
The Missing Piece in Genetic Testing
"A big missing piece of genetics – a lot of people know what the mutations mean. How do you know the pharmacology of what nutrients to use to help those genes?"
He sees reports where people are put on supplements that help one thing but hurt others. The interpretation matters more than the test itself – the same DNA sent to three different companies can yield different recommendations.
One-on-One Genetic Work
Dr. Tyler offers personalized genetic analysis with a special discount code "SIIM" for viewers – either a free DNA kit ($150 value) or $150 off package offerings for those who already have genetic data.
15. Food Allergy Testing: Dr. Tyler's Life-Changing Discovery
When asked for one piece of advice he wishes he'd adopted sooner, Dr. Tyler's answer is immediate: food allergy testing.
"Turns out a lot of my histamine brain fog issues – I was eating peas and almonds every day for lunch. I was allergic. And I was working with mice pretty much every day – and I'm allergic to mice!"
He had to visit five allergists before one would test him. The first four refused because he didn't have classic symptoms (sneezing, runny nose).
"Headaches, brain fog – these are signs of allergies, high histamine. Thank God the fifth one tested me."
IGE vs. IGG Testing
- IGG (G as in George) – food sensitivity tests; more transient, gut-centralized
- IGE (E as in Eric) – true allergic reaction; body-wide immune response
The standard skin prick test or IGE blood test can reveal allergies that aren't life-threatening but are definitely life-impacting.
"The minor things can add up."
Final Thoughts
This conversation powerfully demonstrates that health optimization isn't about finding the "best" supplements – it's about finding your best supplements. From caffeine alternatives for adrenaline-sensitive individuals to pre-activated vitamin D for those with conversion issues, the message is clear: genetics matter.
Dr. Tyler's approach isn't about fear-mongering or telling everyone to avoid certain supplements. As he repeatedly emphasizes, nothing is universally good or bad – it depends on the individual. The goal is to understand your unique biology so you can make informed decisions rather than blindly following one-size-fits-all health advice.
"We should be excited to have these types of conversations... I love being proved wrong because you're getting closer to the truth."
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