NutriStack
Oxide, citrate, glycinate: what the form changes.
“More absorbable” is a comparative claim, and a comparative claim with no comparator is not a claim at all. What a form genuinely changes is how much mineral is in each gram, how readily it dissolves, and by what route it crosses the gut wall. Those are chemistry, and they are knowable.
Definition
What bioavailability measures.
The pharmacological definition is narrow and useful: the fraction of an administered amount that reaches systemic circulation unchanged, and the rate at which it gets there.
How it is actually measured
- AUC, the area under the plasma concentration-versus-time curve, is the standard measure of extent. Cmax and Tmax describe the peak and when it arrives.
- Absolute bioavailability compares an oral form against intravenous administration. Relative bioavailability compares one oral form against another, and almost every marketing claim is the relative kind.
- Plasma concentration is not tissue concentration. Magnesium is the standard illustration: most of the body’s magnesium is intracellular and in bone, so serum magnesium is a poor reflection of total body status and a poor endpoint for comparing forms.
- Some nutrients are measured by urinary excretion, some by red cell content, some by a downstream biomarker. These are not interchangeable, and a claim is only as good as the endpoint it was measured on.
- Absorption differences do not automatically become outcome differences. That requires an outcome study, which is a separate and much rarer thing.
Counter-ions
What the second half of the name does.
A mineral supplement is a salt or a chelate. The mineral is the cation; whatever follows it in the name is the counter-ion or the ligand. It changes three things.
The three things a pairing changes
- Stoichiometry. How much mineral rides in each gram of compound. A heavy organic ligand means less mineral per gram, which is why the elemental figure on the panel matters more than the compound name.
- Solubility. Oxides and carbonates are poorly soluble and depend on gastric acid to dissociate. Organic salts such as citrate, malate and gluconate dissolve more readily and are less dependent on stomach acidity.
- Route. Amino acid chelates such as bisglycinate pair the mineral with an amino acid ligand, which is proposed to allow uptake by peptide and amino acid transport routes rather than purely by the mineral’s own pathway. The strength of the evidence for that varies by mineral.
Solubility is necessary but not sufficient. A dissolved mineral still has to cross the intestinal epithelium, and uptake of iron and zinc in particular is regulated by the body according to status, not simply driven by how much arrives.
The laxative effect is chemistry, not a defect
Poorly absorbed magnesium salts remain in the intestinal lumen and are osmotically active, drawing water in. That is the mechanism behind the laxative behaviour of magnesium oxide, magnesium citrate and magnesium sulfate, and it is the same mechanism these compounds are used for deliberately in other contexts.
It follows directly from low fractional absorption. It is a property of the compound rather than a sign of a badly made product, and forms with higher fractional absorption show it less.
Minerals
The common forms, side by side.
Elemental fraction is arithmetic. Everything in the third column is a description of the chemistry and of what comparative studies have measured, not a recommendation.
Mineral forms
| Form | Elemental share | Chemistry and what has been measured |
|---|---|---|
| Magnesium oxide | about 60% | Poorly soluble; requires gastric acid to dissociate. Highest mineral density per gram and the lowest fractional absorption of the common forms, with a correspondingly strong osmotic effect. |
| Magnesium citrate | about 16% | Soluble organic salt. Comparative studies generally report higher fractional absorption than the oxide. Retains an osmotic effect at larger amounts. |
| Magnesium bisglycinate | about 14% | Magnesium chelated to two glycine molecules. Low mineral density per gram, and the form most often reported as better tolerated in the gut. |
| Magnesium malate, taurate, L-threonate | varies | Organic salts and chelates differing in ligand. L-threonate is the form with the most specific published claims about tissue distribution, and correspondingly the smallest body of independent comparative data. |
| Calcium carbonate | about 40% | Requires an acidic environment to dissolve, so its absorption is more dependent on gastric conditions than calcium citrate’s. |
| Calcium citrate | about 21% | Soluble and less dependent on gastric acidity. Lower calcium per gram, so more material is needed for the same elemental amount. |
| Ferrous sulfate | about 20% | The reference iron salt in most comparative trials. Ferrous (Fe²⁺) iron is far better absorbed than ferric (Fe³⁺). Gastric irritation is common and is why the “with food” instruction appears despite food reducing absorption. |
| Ferrous fumarate, gluconate | about 33%, about 12% | Other ferrous salts, differing mainly in elemental density and tolerability rather than in absorption route. |
| Iron bisglycinate | varies | Amino acid chelate; studied as less affected by phytate and polyphenol inhibition than ferrous sulfate, with generally milder gastrointestinal effects. |
| Zinc oxide | about 80% | Poorly soluble; the densest zinc form per gram and generally the least well absorbed. |
| Zinc gluconate, picolinate, citrate | about 14%, about 21%, about 31% | Soluble zinc salts. Comparative absorption data between them is limited and inconsistent, and zinc uptake is homeostatically regulated by status, which complicates single-dose comparisons. |
Elemental shares are calculated from molar masses for the stated hydration state; a differently hydrated salt gives a different number.
Vitamins
Where the form genuinely differs.
For most vitamins the form is a detail. For these, it is a real chemical difference with measurable consequences.
Forms that are not interchangeable
- D2 versus D3. Ergocalciferol (D2) is produced by yeast and fungi; cholecalciferol (D3) comes from lanolin or from lichen. Both raise circulating 25-hydroxyvitamin D, and comparative trials generally find D3 raises and sustains it more efficiently per unit.
- K1 versus K2. Phylloquinone (K1) is the leafy-green form. The menaquinones (K2) differ from each other pharmacokinetically: MK-4 has a half-life measured in hours, MK-7 in days. That is a genuine difference in behaviour, not a marketing distinction.
- Folic acid versus L-5-MTHF. Folic acid is the synthetic, fully oxidised form and must be reduced enzymatically before use. L-5-methyltetrahydrofolate is the circulating form and bypasses that step, which is the basis of the discussion around MTHFR variants.
- B12 forms. Cyanocobalamin is stable and inexpensive and releases a trace cyanide moiety on conversion. Methylcobalamin and adenosylcobalamin are the two coenzyme forms. Hydroxocobalamin is used clinically and is retained longer in the body.
- Vitamin E. Natural d-alpha-tocopherol is a single stereoisomer; synthetic dl-alpha-tocopherol is a mixture of eight, and the liver’s alpha-tocopherol transfer protein preferentially retains some of them. This is why the two carry different potency conversion factors.
- Niacin. Nicotinic acid causes prostaglandin-mediated cutaneous flushing; nicotinamide does not. They are different molecules that share a vitamin name.
Solubility problems
Compounds that need help getting in.
A handful of popular compounds absorb so poorly in their raw state that the entire formulation industry around them exists to address it.
The formulation approaches
- Curcumin has very low aqueous solubility and is rapidly conjugated in the gut wall and liver. Formulations attack that differently: piperine co-administration slows glucuronidation, phospholipid complexes and micellar or nanoparticle dispersions improve solubilisation, and cyclodextrin inclusion complexes do the same by another route. Each has its own pharmacokinetic data against its own comparator.
- CoQ10 exists as ubiquinone (oxidised) and ubiquinol (reduced), and the body interconverts them. For absorption, whether the compound is delivered in a solubilised or oil-suspended matrix generally matters more than which redox form is on the label.
- Fat-soluble compounds in general, including vitamins A, D, E and K, carotenoids, curcumin and CoQ10, depend on bile and micelle formation, which is the mechanism behind the “with food” instruction on their labels.
- “Liposomal” describes a genuine delivery technology and is also one of the most loosely used words in the category. The question that separates the two is whether pharmacokinetic data exists for that exact formulation rather than for the concept.
Reading claims
How to judge a bioavailability number.
Five questions, in order. Most marketing claims fail on the first one.
The five questions
- Compared to what? A multiple is meaningless without its comparator. Against unformulated curcumin powder, which absorbs very poorly, almost any number is achievable, which is exactly why published multiples for curcumin formulations range across two orders of magnitude.
- Measured how? Plasma AUC, urinary excretion, red cell content and a downstream biomarker answer different questions and cannot be compared with each other.
- In whom? Human or animal, single dose or steady state, fasted or fed, healthy or depleted. Each changes the result.
- Is the tested material the material in the bottle? A study on a branded, characterised extract does not transfer to a generic version of the same plant.
- Does more absorption mean more benefit? Only an outcome study answers that, and absorption data is not a substitute for one.
This page describes chemistry and measurement. Which form is appropriate for a particular person, in what amount, alongside what else, is a clinical question and belongs with a clinician or pharmacist who can see the whole picture.
Questions
Common questions.
Short answers, and an explicit stop where the honest answer is “that depends on you and belongs with a clinician”.
Frequently asked
What does “more bioavailable” actually claim?
That a larger fraction of the administered amount reached systemic circulation than from some comparator, usually measured as area under the plasma concentration-time curve. Without naming the comparator, the endpoint, and the population, the phrase carries no information. Most consumer claims are relative comparisons against a deliberately poor reference.
Why does magnesium oxide have a laxative effect?
Because a large share of it is not absorbed. What stays in the intestinal lumen is osmotically active and draws water in, which is the same mechanism magnesium salts are used for deliberately elsewhere. Forms with higher fractional absorption leave less behind and show the effect less.
Is magnesium glycinate different from magnesium citrate?
Chemically, yes. Bisglycinate is magnesium chelated to two glycine molecules and carries about 14% elemental magnesium; citrate is an organic salt at about 16%. Comparative studies generally report better gastrointestinal tolerability for the chelate and higher absorption for both compared to the oxide. Which of those properties matters depends on the person, which makes it a clinical question rather than a chemical one.
Is ubiquinol worth more than ubiquinone?
The body interconverts the two, so the redox form on the label is not the main determinant of how much gets in. The delivery matrix, whether the compound is solubilised or suspended in oil and taken with fat, generally accounts for more of the difference between products than the ubiquinone-versus-ubiquinol distinction does.
Is vitamin D3 better than D2?
Both raise circulating 25-hydroxyvitamin D. Head-to-head trials generally find cholecalciferol (D3) raises and maintains that level more efficiently per unit than ergocalciferol (D2). D3 from lichen is available for anyone avoiding the lanolin-derived version.
Keep reading
The rest of the reference set.
Four more pages on the parts of a supplement routine that are factual rather than clinical.
In the app
Record the form, not just the name.
“Magnesium” is not a routine entry. NutriStack keeps the specific form and amount, so what you are tracking matches what you own.