Lactoferrin, graded by the evidence.

Lactoferrin is a single-chain glycoprotein of roughly 80 kilodaltons, built from two similar lobes. Each lobe binds one ferric iron ion with a tenacity few biological molecules match, and holds it across a range of acidity that would strip most carriers. The protein occurs in milk, most abundantly in colostrum, and also in tears, saliva, nasal and intestinal secretions, and in the granules of neutrophils, where it is released at sites of inflammation. That last property is what turns the protein into a laboratory measurement: fecal lactoferrin tracks neutrophil traffic into the bowel, and pooled analyses put its specificity for inflammatory bowel disease against irritable bowel syndrome at 0.94 to 0.95. The published thresholds for that measurement are another matter: six validation studies of the lactoferrin test share no common unit, and only one of them reports a cutoff with its sensitivity and specificity attached. A fuller account of what lactoferrin is covers the crystal structure, the iron site and the measured concentrations by source.

Its best-characterized action follows directly from the iron binding. By sequestering free iron it denies an essential nutrient to bacteria that need it, which is where the antimicrobial reputation began. Subsequent work has described effects that do not depend on iron at all, including direct interaction with bacterial membranes and with host cell receptors.

What that means for a person taking a supplement is a separate question, and a much less settled one. The ledger below is this site's answer to it.

How this site works

Every claim gets graded on the best available evidence, not the most recent study and not the most favorable one. A grade of Laboratory only is a description rather than a criticism: a great deal of genuinely interesting lactoferrin research has been done in cells, and reporting it as though it were a clinical finding is the error, not the research itself.

Where the honest grade is Insufficient, the page still gets written. Recording that nobody has run an adequate trial is useful, and it is information that is otherwise hard to find.

Figures carry their units and their source. Lactoferrin concentrations vary by more than an order of magnitude between human colostrum, mature human milk and bovine milk, and quoting a single number without saying which one it describes is the most common error in writing on this subject. What pasteurization does to those figures is a separate measurement question, and the section on lactoferrin sources pairs each concentration with the method that measured it.

Units get the same treatment. Two of the validation studies behind the stool assay disagree on them: one reports micrograms per gram of stool, the other micrograms per milliliter of extract, and neither states a conversion, so their numbers cannot be placed on one axis. Lactoferrin reference data collects tables of this kind, every row carrying the assay behind it. That section is thin at present, and saying so is better than filling it with figures whose method nobody recorded.

The published record has gaps of its own. A 2013 analysis in the BMJ took 585 large randomized trials that were registered with ClinicalTrials.gov and completed before 2009, and found that 171 of them were never published, with no results posted to the registry for 133 of those. Nothing in that finding is specific to lactoferrin, and it is why a registration counts here as a question rather than an answer. Lactoferrin research records trials with their status, including the ones that recruited and then reported nothing.

More on sourcing and method on the about page.