In discussions about nutrition, health and nutritional supplements, we often encounter terms that are used as synonyms, even though they actually describe very different things. Bioactivity and bioavailability are among the most commonly confused. In my opinion, this misconception is one of the main reasons why many “good” substances do not work as we would expect in practice.
Bioactivity describes the ability of a substance to induce a biological response – for example, to influence an enzyme, receptor or inflammatory process. This is a property of the molecule itself, often demonstrated in laboratory conditions. Bioavailability, on the other hand, refers to whether and in what quantity this substance can enter the human body in its active form. In other words, bioactivity answers the question of what a substance can do, while bioavailability answers the question of whether it will ever have the opportunity to prove it.
I believe that the problem arises when bioactivity is automatically considered proof of efficacy. Between potential and reality stands the entire human body – with its barriers, metabolism and regulatory mechanisms. And it is here that the decision is made as to whether the promise from the laboratory will be transformed into a real biological effect.
Most of the promising effects of substances come from in vitro studies – from test tubes, Petri dishes or cell cultures. This is a reduced model of reality in which the researcher has absolute control over the environment. The substance reaches the cell directly, in a precisely defined concentration, without having to undergo digestion, absorption or metabolic changes.
This approach has its merits. It allows us to identify the biological potential of a molecule and understand its mechanism of action. However, I believe that the problem arises when this potential is presented as a proven effect on human health.
The human body is not a laboratory model. It is a complex biological system with regulatory mechanisms, barriers and protective filters. A substance that works at a certain concentration in a test tube often never reaches the body at that concentration – and sometimes does not reach it at all¹.
Bioavailability determines how much of the ingested substance actually enters the bloodstream in its active form, and this is where it is decided whether bioactivity will remain a theoretical concept or be transformed into a real effect.
One of the best-studied examples of this contradiction is curcumin. It is a substance with significant bioactivity – in vitro studies show anti-inflammatory, antioxidant and antiproliferative effects². These results have been published repeatedly and the mechanisms of action are relatively well studied.
However, when curcumin is administered orally to humans, the picture changes dramatically. Pharmacokinetic studies published in Molecular Pharmaceutics³ and Clinical Cancer Research⁴ show that curcumin has very low water solubility, minimal intestinal absorption, and is rapidly metabolised in the liver. It appears in the systemic circulation only in trace concentrations, often well below the level at which biological effects have been observed in laboratory conditions.
Interestingly, science has been aware of this problem for decades. This has led to the development of combinations of curcumin with piperine, lipid forms and nanoformulations. This is not because curcumin “does not work”, but because without interfering with its bioavailability, it has no chance of working in the body as promised by cell experiments³.
Even if the substance is absorbed, its story does not end there. Metabolism acts as a silent but extremely influential player that determines what actually happens to the molecule in the body. The liver and other metabolic organs have a single goal: to protect the body from foreign substances.
Many bioactive compounds are therefore chemically modified very quickly. The result is a metabolite that may no longer have its original biological activity⁵. In some cases, the effect is weaker, in others negligible.
I note that this aspect is systematically underestimated in popular communication about substances. There is often talk of the effect of a molecule that practically does not exist in the body in its original form.
Curcumin is now almost a textbook example of a substance that demonstrates the difference between laboratory potential and actual effect in the body. As I mentioned above, its problem is not bioactivity, but bioavailability – and that is precisely why it has become the impetus for the development of various technological solutions.
However, this principle does not apply only to curcumin. Many substances that show convincing effects in vitro encounter the same biological limitations in the body. Low solubility, poor absorption, rapid metabolic conversion and rapid excretion create a set of barriers that can significantly weaken or completely eliminate the potential effect.
It is at this point that I believe it makes sense to talk about the form of the supplement. Not as a detail, but as a tool that can — in some cases — determine whether bioactivity comes into play at all. Lipid forms, emulsified preparations, or nanoformulations were not created as trendy forms of supplements, but to reduce biological losses that occur between administration and the site of action.
It makes sense to address the form, especially for substances that we know have low natural availability — for example, fat-soluble vitamins (A, D, E, K), coenzyme Q10, or certain plant polyphenols. In these cases, the form does not guarantee the effect, but it increases the likelihood that the substance will enter the circulation in an amount that is biologically significant.
I believe that the technological “advancedness” of a supplement is only valuable if it solves a specific physiological problem. If no such problem exists, the form becomes more of an aesthetic element than a real benefit.
For people who want to make informed decisions, it is important to change their perspective. Instead of asking, “Is this substance bioactive?”, the question should be: Does it enter the body in an effective form and quantity? When choosing a dietary supplement, it makes sense to focus primarily on clinical studies in humans, pharmacokinetic data and information about the formulation. These are more informative than cell experiments alone. Not because laboratory science is misleading, but because it only describes the first phase of the story.
Bioactivity represents potential. Bioavailability determines whether this potential is ever realised. I believe that confusing the two is one of the main reasons why many “good” substances are overrated. The effect does not occur in a test tube, but in the body – and these are two very different worlds.
Dr. Mária Zajičková,
organic chemist, science populariser
1. Manach, C., et al. (2005). Bioavailability and bioefficacy of polyphenols in humans. American Journal of Clinical Nutrition, 81(1), 230S–242S.
2. Aggarwal, B. B., & Harikumar, K. B. (2009). Potential therapeutic effects of curcumin. International Journal of Biochemistry & Cell Biology, 41(1), 40–59.
3. Anand, P., Kunnumakkara, A. B., Newman, R. A., & Aggarwal, B. B. (2007). Bioavailability of curcumin: Problems and promises. Molecular Pharmaceutics, 4(6), 807–818.
4. Cheng, A. L., et al. (2001). Phase I clinical trial of curcumin. Clinical Cancer Research, 7(7), 1894–1900.
5. Williamson, G. (2017). The role of polyphenol metabolism in human health. American Journal of Clinical Nutrition, 105(1), 10–17.
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