Functional foods & nutraceuticals

A functional food is one to which a physiological benefit beyond basic nutrition is attributed. The category is defined by a claim rather than by a composition, which is why the useful question is not what a functional food is but what would have to be true for the claim to hold.

Four conditions have to be met in sequence. Each is a place where most candidates fail.

One: the compound must actually be in the product, in a stable form

Bioactive compounds are usually minor plant metabolites, and they degrade. Polyphenols oxidise, carotenoids isomerise and bleach, probiotic organisms die, omega-3 fatty acids go rancid. Content at manufacture is not content at consumption, and shelf-life data for the active — rather than for the product’s microbiological safety — is the relevant evidence. Where a product is heated, dried or stored warm, the active’s stability under those exact conditions is the question.

Two: the dose must be attainable

This is where in-vitro findings most often break down. A cell-culture experiment demonstrating an effect at, say, tens of micromolar concentration is describing an exposure that dietary intake cannot produce. Plasma concentrations of most dietary polyphenols after a normal portion are in the nanomolar to low micromolar range — often two or three orders of magnitude below the concentration used to show the mechanism.

An effect demonstrated at an unattainable concentration is not evidence about food. It is evidence about the molecule, and the two are routinely conflated.

Three: it must be absorbed, and survive metabolism

Bioavailability is the field’s central obstacle. Absorption depends on solubility, molecular size and transporters; fat-soluble compounds need dietary fat present, and their uptake varies severalfold with the meal.

Whatever is absorbed then meets first-pass metabolism. Phase II enzymes in the intestinal wall and liver conjugate polyphenols to glucuronides and sulfates within minutes, and these conjugates are chemically different from the parent compound — often much less active in the assays used to select it. A large share of ingested polyphenol is not absorbed at all in the small intestine and instead reaches the colon, where the microbiota degrades it into smaller phenolic acids.

That last point cuts both ways, and it is the field’s most interesting current question: some benefits attributed to a parent compound may be produced by microbial metabolites instead, and since microbiotas differ between people, so does the metabolite produced. The best-documented example is that only some individuals harbour bacteria able to convert soy daidzein to equol — which would make the response to a soy isoflavone intervention depend on who is taking it.

Four: the matrix matters

The same compound behaves differently in different foods. Fibre and phytate bind minerals; fat improves carotenoid uptake; protein binds polyphenols. Isolating a compound from its food and putting it in a capsule changes its bioavailability in both directions, so a supplement is not a concentrated version of the food and evidence for one is not evidence for the other.

What substantiation requires

Regulatory frameworks for health claims generally require a characterised substance, a defined and measurable physiological outcome, and human intervention evidence that the food as consumed produces that outcome — not a plausible mechanism. Most claims submitted under such frameworks are rejected, and the usual reason is precisely the chain above: the mechanism is real, and the effect in people is not demonstrated.