The Ultimate Human with Gary Brecka
252. What Is Bioavailability and Why It Matters for Your Supplements
12 Mar 2026
Chapter 1: What is the main topic discussed in this episode?
Maybe you've heard that supplements are only good for making expensive pee.
Chapter 2: What is bioavailability and why is it important?
And honestly, the critics aren't entirely wrong.
Chapter 3: What are the differences between creatine monohydrate and creatine HCl?
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.
Chapter 4: How do folic acid and methylfolate differ in 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 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
Chapter 5: What are the risks of magnesium deficiency and how can it be addressed?
Maybe you've heard that supplements are only good for making expensive pee. And honestly, the critics aren't entirely wrong.
Chapter 6: Why do some supplements fail to deliver results?
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 and forms your body was never designed to absorb. I'm biohacker and human biologist Gary Brekka, 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.
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Chapter 7: How does the MTHFR gene affect folate absorption?
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 and supports nutrition, and it works, but there's a problem. There's 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.
Chapter 8: What are the implications of using cyanocobalamin versus methylcobalamin?
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 the large amount of liquid needed to dissolve it. Creatine hydrochloric 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 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. This 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.
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