Bioavailability of food supplements: what it really depends on

Bioavailability is the portion of a nutrient that, after being released from the product and absorbed, reaches the bloodstream in a usable form. No label declares it.

What the label always declares is the chemical form of the active ingredient, the form the product comes in, and when it should be taken. These are the three things on which bioavailability depends, and knowing how to read them allows you to compare two products that show the same number of milligrams on the front of the packaging.

What is the bioavailability of a supplement: definition and three stages

1. 1. Releasethe active ingredient leaves the dosage form
2. 2. Absorptionit crosses the intestinal wall
3. 3. First passthe mucosa and liver transform part of it

In pharmacology, bioavailability is the fraction of the administered dose that reaches the systemic circulation in an active form. Between the capsule you swallow and that fraction, there are three distinct stages.

Bioaccessibility is the first: the active ingredient must be released from the form that contains it and pass into solution in the fluids of the digestive tract. A capsule must open and a tablet must disintegrate; a salt, to be effective, must dissolve. As long as the molecule remains trapped in its matrix, for the body, it is as if it is not there.

Then comes absorption, when the dissolved molecule crosses the intestinal epithelium. Some pass through by diffusion, others need specific transporters, and the transporters are finite in number — as we will see later.

The third stage is the least intuitive. Before reaching general circulation, what has been absorbed passes through the intestinal wall and the liver, where a portion is transformed: this is the first-pass metabolism. This is why a molecule can be absorbed very well and appear in the blood in only a modest amount.

The milligrams printed on the label describe what enters your mouth. The three stages decide how much of those milligrams becomes available to the body. Each one depends on formulation choices that the label makes visible.

First factor: the chemical form of the active ingredient

• Chemical formcitrate, chelate, oxide — solubility changes
• Product formcapsule, gastro-resistant capsule, softgel, sublingual
• Timingwith a meal or between meals

A mineral, in a supplement, is always bound to something else to form a salt. The same mineral can be bound to an organic acid (citrate, gluconate), to an amino acid (chelates, such as bisglycinate), or to an inorganic anion (oxide, carbonate). The choice changes two things at once: how much mineral there is per gram of the compound and how easily that compound dissolves.

The two parameters go in opposite directions, and this is where the decision is made. Magnesium oxide is a textbook case: it has a very high mineral density, about 60 grams of magnesium per 100 grams of the compound, much more than any organic form. But it dissolves very poorly in water, and solubility is the prerequisite for the first stage, bioaccessibility.

The practical result is seen in the intestine: a significant portion of that magnesium passes through it without being absorbed and remains in the lumen, drawing in water. Hence the historical use of magnesium oxide as an osmotic laxative.

In this respect, the poorly soluble inorganic forms lose out, and the data show it. Citrate and bisglycinate carry less mineral per gram, so they require larger tablets or more numerous doses. In return, they dissolve better and are more tolerable at the gastrointestinal level.

Magnesium is the most studied example of this difference: citrate and bisglycinate are two forms of magnesium used in supplements.

The same question also arises outside of minerals. Coenzyme Q10 exists in two forms, ubiquinone and ubiquinol, and the comparison between the two has been measured directly in humans. A study on twelve healthy volunteers compared four weeks at 200 mg per day for each form, with the same excipients in the softgel: total plasma coenzyme Q10 increased to a greater extent with the reduced form [1]. This is the form used in our Ubiquinol with Kaneka QH®. The complete comparison, study by study, is in Ubiquinol or ubiquinone: which coenzyme Q10 to choose.

The general principle applies to any active ingredient: the declared quantity matters as much as the form in which it is bound. A very dense but poorly soluble form makes less available than the number on the label might suggest.

The same logic leads to the methylcobalamin in our Sublingual Vitamin B12, and explains why our Glucosamine + Chondroitin + MSM fully declares the salt used, glucosamine sulphate 2KCl, instead of just writing "glucosamine". We explain why the form and route of administration matter so much for B12 in Vitamin B12: what it is for and when it is lacking.

The wording "of which" on the label: how many mg of nutrient are there really

Potassium citrate 2000 mg↓of which potassium 730 mg

• The first number is the weight of the compound.
• The second is the nutrient it provides.

There is a very simple way to check all this on any package, and it lies in two words: of which. In a table of amounts, the compound and the nutrient occupy two different lines, and the second is the one that matters.

On the label of our Potassium Citrate, the daily dose of 4 tablets declares 2,000 mg of potassium citrate, of which 730 mg is potassium, equal to 36.5% of the nutrient reference value. The two numbers measure different things: the first is the weight of the salt, the second is the actual mineral intake.

Anyone who compares two products by looking only at the large number is comparing the weight of the salts, which depends on the chosen form more than on the nutrient content.

The same principle governs plant extracts, with a different vocabulary. Our 5-HTP declares 500 mg of dry extract of griffonia seeds of which 100 mg is 5-hydroxytryptophan, because the extract is standardised to 20%. Here too, the useful number is the second one, and we have written a dedicated guide on how standardisation and extraction ratios work.

The "of which" line is therefore the quickest check you can do with the jar in your hand: it takes three seconds, and it tells you how much nutrient you are actually taking. The complete process of reading a label is explained in how to read a supplement label.

Second factor: the pharmaceutical form of the product

The pharmaceutical form governs the first of the three stages, i.e. the time and place where the active ingredient is released. Three examples are enough to understand the mechanism.

The gastro-resistant capsule keeps the casing closed in the acidic environment of the stomach and opens it further on, where the pH approaches neutrality. It is for active ingredients that gastric acidity would degrade before absorption: in our catalogue, this is the case for Bromelain 5000 GDU and Nattokinase, both of which are enzymes.

With the softgel and the oil-based capsule, the active ingredient arrives already dissolved in a lipid base, and for molecules that do not dissolve in water, the problem of solubility is effectively bypassed. Ubiquinol with Kaneka QH® is a softgel, our Organic Astaxanthin Oil is a capsule with the active ingredient dispersed in olive oil.

The sublingual tablet takes a different route: it dissolves in the mouth and absorption begins through the oral mucosa, as with our Sublingual Melatonin and the aforementioned Vitamin B12.

How to choose between these forms, and what ensures that a tablet actually disintegrates, is the subject of gastro-resistant capsules or tablets: which form for which supplement.

Third factor: when to take it and what is in the stomach

The third factor is the only one that depends on the person taking the product, and it is also the easiest to follow: just follow the label.

A fat-soluble active ingredient enters the bloodstream better when the meal contains fats: fats are the vehicle in which that molecule dissolves. The labels for Ubiquinol and Astaxanthin Oil do indeed state to take them with a meal.

There is a solid human study on the principle of the lipid vehicle. Odeberg and colleagues, in 2003, administered a single 40 mg dose of astaxanthin to healthy volunteers, comparing three lipid formulations with a reference one: the measured bioavailability was found to be 1.7 to 3.7 times higher [2]. The formulations tested contained polysorbate 80 and are different from ours; that study documents the general principle of the lipid vehicle.

Gastro-resistant enzymes follow the opposite logic and carry the instruction "away from meals" on their label. The full topic — which products when, and why — is covered in when to take supplements.

When absorption has a ceiling: saturation kinetics

For some nutrients, absorption increases in proportion to the dose up to a certain point, then it plateaus: the intestinal transporters that allow them to pass through are finite in number and become saturated. Beyond that threshold, increasing the amount per single intake primarily increases the amount that is eliminated.

Vitamin C is the nutrient for which this curve has been best described. The reference study remains that of Levine and colleagues from 1996, conducted on seven volunteers who were hospitalised for months on a diet with controlled content. The resulting plasma kinetics have a sigmoid shape: complete absorption at the lowest single doses, and an absorbed fraction that decreases as the single intake increases [3].

The practical consequence is that many labels split the daily intake instead of concentrating it into a single dose. Our Vitamin C + Bioflavonoids provides 1,000 mg per day with one tablet twice a day, during or after meals. For any nutrient with saturation kinetics, two separate intakes work better than a single double dose.

Liposomal, phytosomal, micellar: how to evaluate a delivery technology

Liposomes, phytosomes and micelles are legitimate and, in many cases, documented approaches, and they all serve the same purpose: to bring a molecule that does not dissolve in water into solution, by enclosing it in or binding it to phospholipids so that it can more easily cross the aqueous environment of the intestine.

Faced with any of these terms, there is only one question to ask: was the cited study conducted on the raw material or on the finished product? A technology documented for a raw material does not automatically transfer its results to the product that contains it, which has its own dose, its own matrix and its own excipients.

For the same reason, on none of our products do we declare an absorption percentage: the pharmacokinetic studies concern the raw materials and general principles, not our finished products. We declare precisely what is inside and in what form, and we let that be the basis for comparison.

Bioavailability factors in a table: where to find them on the label

Frequently asked questions

What is the bioavailability of a supplement?

It is the fraction of a nutrient that, after being released from the product and absorbed in the intestine, reaches the bloodstream in a usable form. It depends on the chemical form of the active ingredient, the product form, and the time of intake. No label declares it as a number, because it varies with the conditions under which the product is taken.

What is the difference between bioaccessibility and bioavailability?

Bioaccessibility is the amount of the active ingredient that is released from the form that contains it and goes into solution in the digestive tract: it is the prerequisite for everything else. Bioavailability is the amount that, after absorption and first-pass metabolism, reaches the circulation. An active ingredient can be fully bioaccessible and still have a modest bioavailability.

How can you tell from the label how much nutrient you are really taking in?

Look for the words "of which" in the table of amounts per daily dose. The first line indicates the weight of the compound, the second the nutrient content: 2,000 mg of potassium citrate of which 730 mg of potassium. For plant extracts, the same role is played by titration, which indicates how much of the marker compound the declared extract contains.

Are organic forms absorbed better than inorganic ones?

In general, organic salts and chelates dissolve more easily, and solubility is the prerequisite for absorption: in this comparison, poorly soluble inorganic forms, such as magnesium oxide, are at a disadvantage. However, inorganic forms have a higher mineral density per gram of compound, which is why they are used.

Why should some supplements be taken with meals and others away from meals?

Fat-soluble active ingredients reach the circulation better if the meal contains fats, which are the vehicle in which they dissolve: this is the case for oil-based products and softgels. Enzymes in gastro-resistant capsules have the opposite indication, because their form protects them from the gastric environment and transit on an empty stomach is faster.

Does taking a higher dose mean absorbing more?

Up to a point. For nutrients whose passage depends on intestinal transporters, beyond a certain amount per single intake the transporters become saturated and the amount absorbed stops increasing proportionally. This is why many labels split the daily intake into two separate doses.

Are liposomal supplements more effective?

Liposomal formulations have a documented rationale for active ingredients with solubility problems. The question to ask when faced with any delivery technology is what the cited study was conducted on: a result obtained on the raw material does not automatically transfer to the finished product, which has its own dose, matrix and excipients.

Further reading

• Ubiquinol or ubiquinone: which coenzyme Q10 to choose
• Vitamin B12: what it is for and when it is lacking
• How to read a supplement label: a practical six-step guide
• What "titrated extract" means: titration and extraction ratio
• Gastro-resistant capsules or tablets: which form for which supplement

References

Studies

1. Langsjoen P.H., Langsjoen A.M., Comparison study of plasma coenzyme Q10 levels in healthy subjects supplemented with ubiquinol versus ubiquinone, Clin Pharmacol Drug Dev 2013;3(1):13-7. PMID 27128225 — doi:10.1002/cpdd.73
2. Mercke Odeberg J. et al., Oral bioavailability of the antioxidant astaxanthin in humans is enhanced by incorporation of lipid based formulations, Eur J Pharm Sci 2003;19(4):299-304. PMID 12885395 — doi:10.1016/s0928-0987(03)00135-0
3. Levine M. et al., Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance, PNAS 1996;93(8):3704-9. PMID 8623000 — doi:10.1073/pnas.93.8.3704

Regulatory references

1. Legislative Decree 21 May 2004, no. 169 — Implementation of Directive 2002/46/EC on food supplements.
2. Regulation (EU) No 1169/2011 — Food information to consumers: declaration of ingredients and substances.