Bioavailability

Absolute and Relative Bioavailability

In pharmacology and nutraceuticals, there are two measures of Bioavailability:

• Absolute Bioavailability — the ratio of the amount of a substance that reaches the systemic circulation after oral administration to the amount that reaches it after intravenous administration (reference value: 100%). Rarely determined for nutraceuticals, but relevant for efficacy estimates.
• Relative Bioavailability — a comparison between two different forms of the same substance, or between two different administration matrices. It is the most commonly used parameter in the selection of ingredients for formulation: selenomethionine vs. sodium selenite; zinc gluconate vs. zinc oxide; omega-3 in triglyceride form vs. ethyl ester.

Factors Affecting Bioavailability

The oral bioavailability of an active ingredient is determined by a series of steps that begins in the mouth and ends when the active ingredient reaches its site of action. The main factors are:

• Solubility — a substance must dissolve in gastrointestinal fluids in order to be absorbed. Ingredients that are poorly soluble in water—such as vitamin D, CoQ10, and many polyphenols—require specific formulations (emulsions, nanoparticles, liposomal forms) to achieve adequate bioavailability.
• Chemical Form of the Ingredient — The molecular structure determines how the substance interacts with intestinal transporters. Chelated amino acids such as zinc gluconate (zinc + gluconic acid) and selenomethionine (selenium + methionine) utilize amino acid transporters for more efficient absorption than inorganic forms.
• Food Matrix — The presence of food in the stomach can increase or decrease bioavailability, depending on the ingredient. Fat-soluble vitamin D is better absorbed when taken with a meal containing fat; non-heme iron is better absorbed on an empty stomach or when taken with vitamin C.
• Gastrointestinal pH — The highly acidic pH of the stomach can break down certain active ingredients (e.g., probiotics, enzymes) before they reach the intestine. Gastro-resistant capsules or enteric-coated formulations circumvent this problem.
• First-pass Hepatic Metabolism — a portion of the substance absorbed in the intestine is metabolized by the liver before reaching the systemic circulation, thereby reducing the biologically active fraction.
• Interactions with Other Nutrients — Calcium, iron, and zinc compete for the same intestinal transporters: when consumed together, they reduce each other’s bioavailability. The tannins in tea reduce the absorption of non-heme iron. Phytic acid in whole grains binds to minerals, forming insoluble phytates.

Practical Examples in Nutraceutical Formulation

Selenium: Selenomethionine has an oral bioavailability of approximately 90%, which is higher than that of sodium selenite (~50%) and selenate (~60%). This difference can be explained by the absorption mechanism: selenomethionine utilizes amino acid transporters rather than ionic transporters.

Zinc: Organic forms — gluconate, bisglycinate, and picolinate—have higher bioavailability than zinc oxide, which requires gastric acidity to dissolve and is less effective in individuals with reduced acid secretion.

Magnesium: Magnesium bisglycinate and magnesium glycerophosphate have higher bioavailability than magnesium oxide; the latter, while inexpensive, has very low relative bioavailability and primarily exerts an osmotic effect in the intestine.

Omega-3: The fatty acids EPA and DHA in reconstituted triglyceride (rTG) form have higher bioavailability than the ethyl ester (EE) form, which requires intestinal transesterification before absorption. Taking them with a high-fat meal increases bioavailability in both forms.

Marine Collagen: Hydrolyzed collagen in the form of low-molecular-weight peptides (under 3,000 Da) passes through the small intestine in a partially intact form, entering the bloodstream as bioactive dipeptides and tripeptides — a mechanism that does not occur with intact, non-hydrolyzed collagen.

Bioavailability and Formulation Choices

Bioavailability is one of the primary criteria in selecting ingredients for a supplement: a form with higher bioavailability allows the desired biological effect to be achieved with lower doses, improving tolerability and optimizing the formulation’s cost-effectiveness. It is not the only criterion — product stability, ingredient compatibility, packaging format, and consumer preferences (vegan, allergies) all contribute to the final decision —but it is the foundation upon which the scientific soundness of a formula is built.

Always remember that it is important to consult a health care professional before starting any new supplement or treatment.