Swallowing is not absorbing, and almost everything that surprises people about a supplement lives in the gap between the two.
~12 min read
A label states what went into the capsule. Your body deals in what crossed the wall of your gut, and those two figures are rarely the same. Bioavailability is the name for the distance between them.
Two bottles carrying the same number on the panel can behave differently, and a nutrient can be plentiful in a food and largely unavailable from it. None of it is mysterious once you follow the substance through. Three ideas do the work. Whether a molecule is polar or non-polar decides which door it can use, whether it carries a charge decides whether it needs a carrier, and enzymes decide what it has become by the time it arrives.
Dose administered
What you swallowed — the only figure a label can state, and the one most people read as though it were the last.
Absorption
The fraction that crosses the intestinal wall: a physical event at a surface, specific to the molecule and the meal around it.
Bioavailability
The fraction reaching the circulation intact and usable — absorption, minus whatever was taken apart on the way.
Digestion gets drawn as one long tube doing one job. It is a sequence of rooms with different chemistry in each, and most nutrients have one room where they are taken up and no other.
Mouth
Amylase starts on starch, lingual lipase on fat, and almost nothing is absorbed. One exception: the lining under the tongue is thin and drains into veins that bypass the liver — the reason a sublingual form exists.
Stomach
An acid room, pH about 1.5 to 3.5. Little crosses the wall but much is prepared — a mineral salt dissolves into free ions, protein unfolds so protease can reach it, and the carrier protein B12 must bind to is released. Weak acid slows all three.
Duodenum — the first 25 centimetres
Bile and pancreatic enzymes arrive, the acid is neutralised, and iron and most calcium are taken up here and not much beyond.
Jejunum — about two and a half metres
Where the bulk happens: sugars, amino acids, fats, most water-soluble vitamins.
Ileum — about three and a half metres
Specialised, not general. B12 is taken up at a receptor found nowhere else, and around 95 per cent of the bile salts are reclaimed here.
The small intestine is six to seven metres of tube about two and a half centimetres wide — as a plain cylinder, well under a square metre of surface. It is not a plain cylinder. The wall is thrown into circular folds, the folds are covered in villi under two millimetres tall, and every villus cell carries thousands of microvilli about a micrometre long. Each layer multiplies the one beneath, and the measured surface comes out near thirty square metres.
Diagram to come
Four panels left to right, each a magnification of the last, with the multiplication stated beneath each. Panel one: a plain smooth cylinder cut open, captioned with its area. Panel two: the same cylinder with circular folds running around the inside, roughly tripling the area. Panel three: one fold magnified, its surface covered in finger-shaped villi — draw a capillary loop and a single central lymph vessel inside one villus, because that pair is reused in the next diagram. Panel four: one enterocyte at the tip of a villus, its upper surface a dense palisade of microvilli. A running total of surface area beneath the row, ending at the final figure. The reader must be able to see that the gain is multiplicative, not additive.
Nothing is absorbed by the intestine as such, but by the cells lining it — enterocytes, replaced every three to five days. A molecule has to pass through a cell, not between two.
At the brush border a molecule meets a membrane, and that membrane is a double layer of fat. What happens next is settled by the question the bonding lesson left you holding.
The question to bring to every nutrient
Is it polar, or is it not? A polar molecule is at home in the watery contents of the gut and then cannot get through a fatty membrane. A non-polar one passes through that membrane unaided and cannot reach it, because it will not dissolve in the water on the way. Each has the other’s problem, and vitamins as molecules sorted the thirteen by it.
A water-soluble nutrient — the B group, vitamin C, a mineral ion, an amino acid — dissolves in the intestinal contents and reaches the brush border easily. Its trouble is the last few nanometres, which it crosses on a carrier protein. Out of the far side of the cell it enters a capillary draining into the portal vein, which runs straight to the liver. Everything water-soluble meets the liver before the rest of the body sees any of it.
A fat-soluble nutrient — A, D, E, K, a carotenoid, a long omega-3 chain — has the opposite difficulty. It will not dissolve in the water it must cross, so it arrives as a droplet far too large for a cell to take up. Bile solves that. A bile salt is amphipathic: a flat uncharged steroid face on one side, hydroxyls and an ionised group on the other. Dozens of them surround a scrap of fat, non-polar faces inward, making a mixed micelle three to eight nanometres across — fat inside, water-friendly shell out — which ferries its cargo to the membrane.
Which is why the fat in a meal decides the outcome for four of the thirteen. Fat arriving in the duodenum is the signal for the gallbladder to release bile. No fat, little bile; little bile, few micelles; and much of the A, D, E and K travels on and leaves. The daily foundation makes that a habit.
Inside the enterocyte the paths part for good. Fat-soluble material is repackaged into a chylomicron, too large for a capillary, so it goes into the lacteal at the centre of the villus, up the thoracic duct, and joins the bloodstream at the base of the neck — reaching the body without meeting the liver. Which is part of why it can accumulate where a water-soluble nutrient cannot.
Diagram to come
One villus drawn large in cross-section, gut lumen to the left, the two vessels inside it — a capillary loop and a central lymph vessel — clearly distinct in colour. Two journeys traced across it as separate paths a reader can follow end to end with a finger. Path one, water-soluble: a small polar molecule in the lumen, through a carrier protein in the brush-border membrane, across the cell, out into the capillary, then one arrow leaving the frame to a small liver symbol. Path two, fat-soluble: a droplet of fat in the lumen, wrapped by bile salts into a micelle drawn with its polar shell facing outward, delivered to the membrane where the vitamin alone passes through and the micelle stays behind, then repackaged inside the cell into a large coated chylomicron, exported into the lymph vessel, and an arrow leaving the frame marked as bypassing the liver. The bile salts must visibly not enter the cell, and the two destinations must be unmistakably different.
The whole pool of bile salts is two to four grams — nothing against the fat in a day’s eating — and it works because it is reused. A transporter in the ileum reclaims around 95 per cent and hands it back to the liver, six to eight times a day, so a two-gram pool does the work of thirty.
Then the layer nobody draws. Clinging to the brush border is a stagnant film of water and mucus a few hundred micrometres thick, which the churning of the gut does not stir. To a polar molecule it is nothing. To a non-polar one it is the real barrier — the membrane beyond easy, the water in front impassable. The micelle exists to cross that film, and that is why uptake tracks emulsification rather than amount.
Reaching the membrane is one problem. Getting through it is another, and there are three general answers — plus one exception, for cargo too large for any of them.
Passive diffusion
Down a gradient, straight through the membrane, no protein and no energy spent. Open only to small non-polar molecules — fats, the fat-soluble vitamins once a micelle has delivered them, and almost every constituent of an oil.
Facilitated transport
Through a specific carrier protein, still down a gradient and still free, but depending on a finite number of proteins. Fructose and much of vitamin C cross this way.
Active transport
Against a gradient, at a cost in ATP. Glucose and amino acids ride in coupled to sodium; the divalent metal transporter hauls in iron, zinc and manganese, which is why minerals of similar charge and size compete for one route.
Endocytosis
The cell swallows the package whole, for cargo too large for anything above. Cyanocobalamin weighs near 1,355 against limonene’s 136, and nothing that size travels unassisted.
The middle two saturate, and that explains more label behaviour than anything else here. A carrier is a protein and a cell has a fixed number of them: below a certain concentration more in the gut means more taken up, and above it every carrier is busy and the rate stops rising. Vitamin C is the standard illustration — something like 70 to 90 per cent absorbed at modest intakes, below half at gram quantities, and what does get in is cleared past a renal threshold and leaves in urine. The plateau on the dose-response curve, seen from the transporter’s side.
Diagram to come
Two linked figures in one frame. Left, a stretch of membrane drawn as a lipid bilayer with three crossings side by side: a small uncoloured molecule slipping straight between the lipid tails with no protein; the same size of molecule passing through a channel-shaped protein with a downward gradient arrow beside it; a charged ion pushed through a pump-shaped protein against an upward gradient arrow, with a small ATP symbol on the pump. Right, a graph sharing the frame: amount in the gut along the horizontal axis, amount absorbed up the vertical. Two curves — a straight diagonal for passive diffusion that never flattens, and a carrier curve that rises then levels off, its flat portion shaded. A dotted vertical line marks where the carriers fill. No numbers on the axes; the shape is the content.
Then the liver, which everything absorbed into the portal vein meets before anywhere else. Its enzymes convert and distribute a nutrient the body wants — and, for a plant compound the body reads as foreign, can remove most of what arrived before any circulates. This is first-pass metabolism, and why absorbed and bioavailable are two words.
Two phases. The first is mostly the cytochrome P450 family, oxidising — exposing a reactive group where there was none. The second conjugates: a glucuronide, a sulphate, a methyl group or glutathione, each bolting on a large polar group so that kidney or bile can dispose of the molecule. Together they are the body’s policy for anything it did not build itself.
Some of it happens before the liver gets a look: enterocytes carry their own P450 and conjugating enzymes, and a transporter that pushes certain molecules back into the gut having just taken them in — so a molecule can be absorbed twice and still not arrive. Which is why sublingual uptake, skin and the lymph route all behave differently.
A nutrient on a label is never the bare nutrient. It is a compound somebody chose, and the choice decides how much arrives.
| Nutrient | Two forms | What the form changes |
|---|---|---|
| Magnesium | Oxide against a glycinate or citrate | The oxide is barely soluble once the stomach acid is behind it, so much never becomes a free ion at the absorbing surface. A chelate holds the ion in solution as the pH changes. |
| Folate | Folic acid against methylfolate | Folic acid is synthetic and fully oxidised, so the body must reduce it through an enzyme of limited throughput. Methylfolate is already the circulating form. |
| Vitamin B12 | Cyanocobalamin against methylcobalamin | Neither moves without the stomach protein and the ileal receptor, which handle only a small quantity per meal. Past that, well under one per cent crosses passively. |
| Vitamin E | Natural against synthetic | The natural form is one stereoisomer; the synthetic is a mixture of eight, of which the liver’s transport protein accepts half. |
| Iron | With or without vitamin C alongside | The transporter accepts iron only in its doubly charged state; vitamin C holds it there by giving it an electron. |
The magnesium row is chelation doing what the minerals lesson described. The vitamin E row is a shape problem rather than a purity one: the transport protein recognises one three-dimensional arrangement out of eight.
Curcumin is the extreme case. It barely dissolves in water, and both the intestinal wall and the liver conjugate it heavily, so after a gram-scale oral amount the free compound in blood sits in the nanomolar range — vanishingly low against the concentrations used in laboratory work on cells in a dish, which is not the same as what happens in a person. That gap is why curcumin is formulated with fat, with phospholipids, or alongside compounds that slow conjugation. Which formulations you can buy differs by market.
The meal around a nutrient works both ways, and the mechanism is usually charge. Phytic acid — how a seed stores its phosphorus — carries six phosphate groups on one small ring, every one negative. A mineral ion passing by is gripped between two of them and locked into a complex no transporter recognises. Oxalate does the same to calcium, tea and coffee tannins to iron from plant foods; soaking, sprouting and fermenting help, because they give the seed’s own phytase time to cut those phosphates off. Pushing the other way, fat raises uptake of carotenoids.
Bioavailability is a comparison, not a property
A percentage alone means nothing. Absolute bioavailability compares an oral amount against the same amount put straight into a vein; relative bioavailability compares two oral forms, which is what nearly every figure you will read actually is. And what gets measured is concentration in blood, not arrival in the tissue that uses it — so give a single number the caution you would give a reading from a tube.
The large intestine holds a bacterial population that manufactures vitamins: the menaquinones — the K2 forms of vitamin K — are largely bacterial in origin, as are useful quantities of biotin, folate and B12.
Only some of it reaches you, and the reason is geography. Uptake across the colon wall is limited, and colonic B12 is a lost cause — the receptor that takes it up sits in the ileum, upstream of where the bacteria made it, so something produced downstream of its own door leaves in the stool. Where a transporter sits matters as much as whether the nutrient is there.
This lesson sits in the Science course rather than in the nutrition one for one reason, and it arrives here.
Almost every constituent of an essential oil is a small non-polar molecule. Limonene weighs 136, linalool 154, menthol 156 — tiny against cyanocobalamin at 1,355. Small, non-polar and with nothing charged on it anywhere is the precise description of a molecule needing neither a carrier nor a micelle: it dissolves into a membrane and passes through by passive diffusion.
That opens doors a nutrient does not have. The outer layer of skin is a barrier of dead cells packed with lipid and turns back very nearly everything — but not a small lipophilic molecule, which is why a diluted oil on skin reaches the capillaries of the dermis directly, with no gut and no first pass. The nose and the lung do the same and faster. A vitamin can use none of those doors: too polar, too large, or both.
The same property carries the other edge, because a molecule that dissolves into your membranes dissolves into other fats too. Hence the rules: an undiluted oil stays off skin and out of plastic; one to two drops in a teaspoon of fractionated coconut oil is an ordinary adult dilution, with more carrier for children and sensitive skin and noticeably heavier dilution for the warm oils — oregano, thyme, cinnamon bark, cassia, clove; skin treated with an expressed citrus oil stays out of direct sunlight and UV for up to twelve hours; and an oil is taken internally only if the label on your bottle says it is for internal use. Labelling differs across the sixty-five markets, so the bottle in your hand is the authority.
One boundary worth keeping clear. An oil is not a nutrient. Nothing in your body is built out of a terpene — it arrives, interacts with chemistry already running, and leaves. And the laboratory work behind the oil effect found that isolated constituents did not reproduce what the whole oil did on cells in a dish, which is not what happens in a person either way. The absorption of one molecule is never the whole account of a bottle; how to use oils holds the practical side.
Keep oils away from eyes and inner ears, and out of reach of children. Dilute before applying to skin, and dilute more heavily for children, for sensitive skin and for the warm oils named above. Only take an oil internally if the label on your bottle states that it is for internal use. These statements have not been evaluated by the Food and Drug Administration. If you are pregnant, nursing, under medical care or taking medication, speak to your healthcare practitioner before use. Nothing here is intended to diagnose, treat, cure or prevent any disease.
Bioavailability is not a quality a substance has. It is what happens when one molecule meets one surface under the conditions of one meal — polarity at the membrane, charge at the carrier, enzymes on the far side. Six lessons ago a nutrient was a word on a label; it is now a molecule with a shape, a charge and a route.
Lesson 18 of 18 · Science