252. What Is Bioavailability and Why It Matters for Your Supplements - The Ultimate Human with Gary Brecka

Podcast Summary: The Ultimate Human with Gary Brecka Episode 252: What Is Bioavailability and Why It Matters for Your Supplements
Date: March 12, 2026
Host: Gary Brecka

Episode Overview

In this episode, Gary Brecka dives deep into the concept of bioavailability—the critical but often overlooked factor that determines whether the supplements you take actually benefit your health. Brecka explains how the form of a nutrient, your genetics, and the overall practices of the supplement industry all play major roles in how effective supplements really are. By understanding bioavailability, listeners can avoid wasting money on ineffective products and give their bodies nutrients in forms they can actually use.

Key Discussion Points & Insights

1. Bioavailability Defined

Bioavailability is the percentage of a substance that enters your bloodstream and is available for your body to use.
- "[Bioavailability] is the percentage of a substance that enters your bloodstream and becomes available for your body to use." (01:40)
Taking a supplement does not guarantee your body absorbs or benefits from the entire dose.

2. The Supplement Industry’s Problem

Industry often prioritizes cost and shelf stability over what actually works in the human body.
Most supplements use cheap, synthetic, or poorly-absorbed forms of nutrients.
Marketing claims usually ignore the critical detail of ingredient form.
“The supplement industry has prioritized cost and shelf stability over what actually works in the human body.” (02:45)

3. Forms Matter: Nutrient Case Studies

Every supplement example Brecka gives highlights the pivotal role of form in effectiveness.

a. Creatine

Creatine Monohydrate is the most common form but isn’t very water-soluble.
- Needs large amounts of water to dissolve (500ml per serving).
- Undissolved creatine can cause bloating and has low absorbability.
Creatine Hydrochloride (HCl):
- 41 times more water-soluble than monohydrate.
- More intestinally permeable and thus more bioavailable.
- “Creatine hydrochloride gave them the performance benefits without the extra water weight. And that’s bioavailability at work. Same nutrient, completely different outcome based on the form.” (06:15)
Study cited: Only the HCl group showed significant improvements in body composition.

b. B Vitamins: Folate and B12

Most multi-vitamins contain folic acid (synthetic, shelf-stable), which the body must convert into active methylfolate.
MTHFR Gene
- 46% of people have an MTHFR mutation, impairing their ability to convert folic acid.
- Supplementing with methylfolate bypasses this issue.
“If you have this mutation, your ability to convert folic acid is significantly impaired or sometimes completely blocked.” (08:30)
Vitamin B12
- Most supplements use cyanocobalamin (synthetic). Body must convert this to methylcobalamin, the usable form.
- Individuals with MTR/MTRR gene variations may be unable to convert, resulting in functional deficiency—even if blood B12 levels appear high.
- “You could be taking B12 every single day and still be functionally deficient.” (12:35)
- Studies that compare methylcobalamin to cyanocobalamin only measure blood (serum) B12, not cellular availability.

c. Magnesium

Magnesium Oxide: Cheapest and most common, but only 4% is absorbed.
Primarily acts as a laxative.
Magnesium Glycinate (Bisglycinate): Bound to glycine, promoting both relaxation and absorption. Does not cause digestive upset and is highly bioavailable.
- “Magnesium glycinate...won’t cause digestive upset and it’s more bioavailable.” (15:40)
Best to support sleep, relaxation, and muscle recovery compared to oxide form.

4. Genetic Variability

What works for one person may completely fail for another due to genetic and gut microbiome differences.
Brecka emphasizes personalized supplementation based on genetics and individual biology.
“What works for one person might fail completely for another, because your genetics are different. Your gut health is different.” (21:20)

5. Actionable Takeaways

Check supplement labels for the actual form of key nutrients.
Folic Acid → Switch to methylfolate
Cyanocobalamin (B12) → Switch to methylcobalamin
Magnesium oxide → Switch to magnesium glycinate
Creatine monohydrate (if bloating) → Try creatine HCl
Bioavailability is a scientific not a marketing concept.
Making these swaps will produce a measurable difference in health and well-being.

Notable Quotes & Memorable Moments

On wasted supplements:
"Maybe you've heard that supplements are only good for making expensive pee. And honestly, the critics aren't entirely wrong." (00:01)
On ingredient form:
"If a supplement isn't structured in a way that fits those mechanisms, it doesn't matter how much you take, you're holding a key that's the wrong shape for the lock." (03:35)
On B vitamins and genetics:
"It's estimated that roughly 46% of the population has this gene mutation. If you have this mutation, your ability to convert folic acid is significantly impaired or sometimes completely blocked." (08:15)
On B12 tests:
"Serum B12 doesn’t tell you what’s happening at a cellular level. It doesn’t measure whether or not that B12 is being converted into the active form that your mitochondria need for energy production." (13:20)
On magnesium absorption:
"Magnesium oxide is the worst offender—cheap, but its bioavailability is terrible. Only 4% gets absorbed. The rest sits in your intestine and acts as a laxative." (15:25)
On individualized supplementation:
"When you understand [bioavailability], you stop wasting money on supplements that don't work, and you start giving your body what it actually needs in the form it can use." (20:45)

Timestamps for Key Segments

Definition & Significance of Bioavailability — 01:40
Creatine Forms: Monohydrate vs. Hydrochloride — 04:45
B Vitamins: Folic Acid, Methylfolate, and Genomics — 07:35
Vitamin B12 and the Role of Genetics — 11:55
Magnesium Supplement Forms — 15:20
Personalized Supplementation & Final Takeaways — 19:55

Final Thoughts

Gary Brecka systematically breaks down why how you supplement is often more important than what you supplement with. He urges listeners to become supplement-skeptical, seek out science-backed forms, and remember that individual differences—including genetics—matter. The main message: bioavailability is real, measurable, and crucial for becoming the ultimate human.

Recommended Next Steps:

Audit your supplement labels using the tips provided by Gary Brecka to ensure you’re taking the most bioavailable forms.
Consider individual genetic testing to further personalize your nutrient strategy.

For deeper learning and additional resources, Gary invites listeners to join his Ultimate Human VIP community (details omitted as per instructions to skip promotional sections).

Transcript

A (0:00)

Maybe you've heard that supplements are only good for making expensive pee. And honestly, the critics aren't entirely wrong. Walk into any pharmacy or health food store and you'll find shelves packed with supplements that your body can't even use. Today, we're talking about bioavailability. It's the percentage of a substance that enters your bloodstream and becomes available for your body to use. The supplement industry has prioritized cost and shelf stability over what actually works in the human body. And most people have no idea they're taking supplements based on marketing claims without understanding the form of the ingredient determines humans whether it will do anything at all. Bioavailability isn't a marketing term. It's absolutely real, and it's rooted in biochemistry and genetics. When you understand it, you stop wasting money on supplements that don't work, and you start giving your body what it actually needs in the form it can use. This is actually fixable when the nutrient is. Ultimate human. Maybe you've heard that supplements are only good for making expensive pee. And honestly, the critics aren't entirely wrong. Walk into any pharmacy or health food store and you'll find shelves packed with supplements that your body can't even use, which means you're spending money on tablets and capsules, and most of it is passing right through you unchanged. But the problem isn't supplementation itself. The issue is that most supplements are formulated with the cheapest possible ingredients in forms your body was never designed to absorb. I'm biohacker and human biologist Gary Brecke, and you're listening to the Ultimate Human Podcast. Today we're talking about bioavailability. I'm going to walk you through why the form of a nutrient matters just as much as the nutrient itself, and why the supplement industry has been getting this wrong for decades. Let's start with the basics. What does bioavailability mean? It's the percentage of a substance that enters your bloodstream and becomes available for your body to use. That means you could take a pill with 100 milligrams of a nutrient, but only 10% of that is bioavailable. Your body is only getting 10 milligrams, but what happens to the other 90 milligrams? That's the expensive urine we're talking about. This is actually fixable when the nutrient is in a form your body can actually recognize and utilize. Your cells have specific receptors and transport mechanisms designed to pull nutrients across the cell membrane. If a supplement isn't structured in a way that fits those mechanisms, it doesn't matter how much you take, you're holding a key that's the wrong shape for the lock. Let me give you a perfect example of this. Creatine. It's one of the most researched supplements in sports nutrition and it works. But there's a problem. There are so many different forms of it. One of the most commonly taken is creatine monohydrate. But it's not too highly soluble. You need about 500 milliliters of water just to dissolve a single serving. If you've ever mixed it, you know exactly what I'm talking about. That gritty residue at the bottom of your shaker bottle. Because it doesn't dissolve well, a significant amount of that creatine monohydrate never gets absorbed. It sits in your intestines, draws in water and causes bloating. If you've been feeling the creatine bloat for a long time now check your bottle and see if it says creatine monohydrate. Now compare that to creatine hydrochloride or creatine HCl. This form is 41 times more water soluble than creatine monohydrate. Because the solubility is so much higher, it has significantly better intestinal permeability. This means more of it actually gets absorbed into your bloodstream or is more bioavailable. There was a study published in the Food and Nutrition Sciences that compared these two forms head to head in recreational weightlifters only the creatine HCL group saw significant improvements in body composition. They reduced body fat percentage and increased fat free mass. The creatine monohydrate group didn't see those changes because the monohydrate form causes water retention and potentially weight gain. You're holding extra water because of the large amount of liquid needed to dissolve it. Creatine hydrochloride gave them the performance benefits without the extra water weight. And that's bioavailability at work. Same nutrient, completely different outcome based on the form. Now let's talk about B vitamins, specifically folate and B12. This is where bioavailability extends beyond absorption and into whether or not your genetics even allow you to use what you're taking. Most multivitamins contain folic acid, which is cheap, stable on the shelf and has been added to fortified foods for decades. You've heard me harp on this for years. But there's a problem. Folic acid is synthetic and your body doesn't use this form directly. For folic acid to work, your body actually has to convert it into the active form called methylfolate or or 5 mthf. And this is where genetics come in. There's a gene called MTHFR that stands for methylene tetrahydrofolate reductase. This gene controls the enzyme that converts folic acid into the usable folate. And genetic variants in MTHFR are way more common than you think. It's estimated that roughly 46% of the population has this gene mutation. If you have this mutation, your ability to convert folic acid is significantly impaired or sometimes completely blocked. So while you're taking a supplement with folic acid, you think you're getting folate, but actually folic acid is just building up in your body. This comes with its own issues. It can mask B12 deficiency. It can interfere with methylation pathways that are critical for everything from detoxification to neurotransmitter production. So now if you take methylfolate instead, you bypass this problem. Methylfolate is already in the active form, the one that your body can use, the one that is more bioavailable. The same principle applies to vitamin B12. Most supplements use a form called cyanocobalamin. But cyanocobalamin is also synthetic, and your body has to convert it into the active form called methylcobalamin. You can actually take already active methylcobalamin so that you aren't having to process and convert the cyanocobalamin. If you have genetic variants in the MTR or MTRR genes, your ability to convert cyanocobalamin is very compromised. You could be taking B12 every single day and still be functionally deficient. This might be why your B12 levels are so high in your blood, because they are so low in your cells. And remember, when our cells use it as fuel, the levels drop in our blood. Some studies will tell you that cyanocobalamin works just fine. There was a study that compared methylcobalamin and cyanocobalamin supplementation and found similar results in raising serum B12 levels. And. And that's true if you're only measuring serum B12. But serum B12 doesn't tell you what's happening at a cellular level. It doesn't measure whether or not that B12 is being converted into the active form that your mitochondria need for energy production. It doesn't account for genetic polymorphisms that affect conversion efficiency. It means that you can be taking cyanocobalamin and have high serum B12, meaning high B12 in your blood, and still be functionally deficient in B12 methylcobalamin skips the conversion step entirely. You're giving your body exactly what it needs in the form your body likes. So let's talk about one more example. Magnesium magnesium deficiency is incredibly common, and a lot of people try to supplement with magnesium oxide or magnesium citrate. Magnesium oxide is the worst offender cheap. But its bioavailability is terrible. Only 4% gets absorbed. The rest sits in your intestine and acts as a laxative. That's why magnesium oxide is often used for constipation. It works, but that's not the kind of absorption we're looking for when we're trying to support sleep relaxation or muscle recovery. Magnesium glycinate, also called bisglycinate, is a completely different story. It's bound to glycine, which is an amino acid that naturally promotes relaxation and enhances absorption in the small intestine. It won't cause digestive upset and it's more bioavailable. So when you take magnesium glycinate, especially before bed, your body can actually absorb it and use it to support the parasympathetic nervous system, reduce muscle tension and improve your sleep quality. Here's what all of these examples have in common. The supplement industry has prioritized cost and shelf stability over what actually works in the human body. And most people have no idea they're taking supplements based on marketing claims without understanding the form of the ingredient determines what whether it will do anything at all. If you're taking supplements right now, look at the label, check the forms of the ingredients. If it says folic acid, switch to methylfolate. If it says cyanocobalamin, switch to methylcobalamin. If it says magnesium oxide, switch to magnesium glycinate. If you're taking creatine monohydrate and dealing with bloating, try creatine HCl. These changes will make a measurable difference in how you feel and how your body responds. If you've enjoyed learning more about bioavailability today and you're ready to go deeper, I want to tell you about my VIP community. When you join, you get access to tons of perks like monthly live Q&As, exclusive private podcast episodes specifically for my VIP members and my brand new course called Becoming the Ultimate Human. This course is a seventeen hundred dollar value and I give it away to my VIPs for free. It includes modules on sleep, stress, nutrition and mindset. Everything you need to become the ultimate human version of yourself. As we close out today, don't forget that bioavailability isn't a marketing term. It's absolutely real, and it's rooted in biochemistry and genetics. When you understand it, you stop wasting money on supplements that don't work, and you start giving your body what it actually needs in the form it can use. What works for one person might fail completely for another, because your genetics are different. Your gut health is different. You and your enzyme activity is different. So the next time someone tells you that supplements just make expensive pee, you can tell them they're only half right. Bad supplements do exactly that. But the right supplements in the right forms, based on your individual biology, change everything, and that's just science.