Skip to content
Peptide Atlas
All peptides

Lactoferrin

Tier 1 · Human trials
Also known as Lactotransferrin · Bovine lactoferrin · Talactoferrin

The strongest evidence present is Tier 1: multiple human randomized/controlled trials are cited, including a Phase 1 intravenous hLF1-11 dose-escalation study in healthy volunteers and HSCT recipients4,10, a Phase 1/2 protocol2,5, a meta-analysis of 19 trials of oral bovine lactoferrin versus ferrous sulfate6, an RCT of a lactobacilli-plus-lactoferrin adjuvant in 48 women7, and a Phase II/III talactoferrin sepsis trial8. Much mechanistic, antimicrobial, anticancer and antiviral evidence, however, is in vitro14,16,18,19,26 or animal23, and recombinant human lactoferrin safety data comes from an unpublished medRxiv preprint1. Several use-case claims rest on single small studies reported by consumer-health sources28,29,30.

Half-life
Not recorded
Routes
Intravenous (hLF1-11 in trials) · Oral (tablets, capsules, supplements, infant formula) · Vaginal (topical/local, bLF pharmacokinetic study)
Goals
Iron deficiency / anemia support · Immune support · Antimicrobial / anti-infective · Gut health · Anti-inflammatory / antioxidant · Reproductive and vaginal health
Cost / mg
Not recorded

How it works

Investigators describe lactoferrin as a natural iron-binding defence protein found in milk, tears, saliva, other body fluids and neutrophils, with a broad range of reported functions: killing microbes, calming inflammation, acting as an antioxidant and helping regulate cell growth and the immune system3,4,10,24. Researchers report it works partly by sequestering the iron that many pathogens need to grow while sparing beneficial commensals such as lactobacilli and bifidobacteria, and partly through short positively charged sequences at its N-terminus that bind and disrupt microbial cell surfaces3,30. Reviewers note that ingested lactoferrin is also taken up by cells through a receptor-mediated pathway that can influence gene transcription and immune function. The peptide fragment hLF1-11 represents the first 11 amino acids of human lactoferrin, which investigators say carry much of its antimicrobial and anti-inflammatory activity6,17.

Overview

Overview

Lactoferrin (also called lactotransferrin; the bovine form is bovine lactoferrin, and talactoferrin/talactoferrin alfa is a recombinant human form) is described by investigators as a natural defence protein present in body fluids, secretions and neutrophils, with pleiotropic functions including broad-spectrum antimicrobial activity, antitumour activity, regulation of cell growth and differentiation, and modulation of inflammatory, humoral and cellular immune responses4,10. A review characterizes it as a versatile glycoprotein with antimicrobial, anti-inflammatory and antioxidant capabilities that limits microbial proliferation by sequestering iron and whose immunomodulatory properties help balance inflammation and accelerate tissue repair15.

Structurally, researchers describe bovine lactoferrin as a single-chain ~80 kDa glycoprotein of the transferrin family (689 amino acids) with two homologous lobes each binding one ferric ion29, while a trial registry describes human lactoferrin as a 692-amino-acid glycoprotein found in saliva, milk, tears and other body fluids6. A review notes bovine lactoferrin shares up to 70% similarity with human lactoferrin12. Human milk is reported to contain 5–7 mg/mL lactoferrin in colostrum and 1–3 mg/mL in mature milk1, and RxList states colostrum contains about seven times the lactoferrin of later milk28.

Peptide fragments

Several active fragments are described. Investigators state that hLF1-11 contains the N-terminal 11 amino acids of human lactoferrin, essential for antimicrobial and anti-inflammatory activity17, and animal experiments reported this first cationic domain was significantly more effective than full-length hLF at killing bacteria in vivo27. Reviewers describe lactoferricin as a potent antimicrobial peptide produced from lactoferrin by pepsin/acid-pepsin digestion, with bovine lactoferricin (LfcinB) comprising 25 residues14.

Reported clinical and preclinical findings

Iron status/anemia. A meta-analysis of 19 trials (published 2006–2022) reported that oral bovine lactoferrin produced a statistically significant increase in hemoglobin compared with ferrous sulfate (SMD -0.81, 95% CI -1.21 to -0.42, p < 0.0001, I² = 95.8%) in patients with low hemoglobin26; the review reports it was effective at 100–250 ng/day and can serve as an iron replacement for patients with adverse effects from iron8. A preprint cites a meta-analysis of 11 studies (1,262 participants) finding greater improvements in serum iron, ferritin and hemoglobin with daily oral lactoferrin versus ferrous sulfate, though fractional iron absorption was superior with ferrous sulfate. WebMD reports that taking 100 to 200 mg daily can increase iron levels in adults with low levels.

Antimicrobial/infection. The hLF1-11 registry states the fragment is being developed as an antibacterial and antifungal agent for infections during neutropenia in HSCT, with safety and tolerability established in HSCT recipients4; investigators note lactoferrin levels are decreased following HSCT15. Researchers describe lactoferrin as selectively bactericidal, sparing lactobacilli and bifidobacteria while killing pathogens30. An in vitro study of 112 isolates found lactoferrin-based supplements gave no inhibition in 24%, moderate in 31% and strong in 45%. RxList reports bovine lactoferrin improves the effectiveness of some H. pylori medications but is not effective alone even at high doses.

Reproductive/gut/infant health. An RCT in 48 women reported an oral lactobacilli-plus-bovine-lactoferrin adjuvant to topical clotrimazole significantly improved itching and discharge with markedly lower recurrence than placebo. A review reports enteral lactoferrin may reduce late-onset sepsis in very low-birth-weight preterm infants with a trend toward diminished necrotizing enterocolitis; however, WebMD reports that adding lactoferrin to formula does not reduce infection risk in very preterm infants — a point of disagreement between sources.

Other reported uses. Consumer and reference sources describe use for hepatitis C, H. pylori, ulcers, diarrhea, acne, COVID-19 and as an antioxidant, generally noting the underlying studies are small or laboratory-based28,29. In vitro and animal work is reported for antiviral activity, anticancer activity of LfcinB14, and bone effects in ovariectomized mice.

Regulatory/production context

A preprint notes bovine milk lactoferrin is generally recognized as safe (GRAS) in the US for use in term infant formula, sports foods, functional foods, chewing gum and as an antimicrobial agent. A review notes Morinaga Milk Industry has industrially produced bovine lactoferrin since 1989 and that Novel Food (EU) and GRAS (USA) specifications require more than 95% lactoferrin purity in protein.

What the research shows

258 findings extracted from the 30 sources cited below, strongest evidence first within each group. Every one links to the source it came from.

What human studies found

Based on 10 human trial findings, 21 human study findings, 11 animal findings, 11 in vitro findings and 3 expert opinion findings.

  • human trialLactoferrin showed a statistically significant increase in Hb concentration levels, compared to those in the iron group6

  • human trialOral bovine lactoferrin group showed a statistically significant increase in Hb levels compared to ferrous sulfate (SMD -0.81, 95% CI: -1.21, -0.42, p < 0.0001)6

  • human trialOral formulation containing Lactobacillus acidophilus GLA-14, Lactobacillus rhamnosus HN001 and bovine lactoferrin as adjuvant therapy to topical clotrimazole shows significant improvement of itching and discharge at 3 and 6 months in women with recurrent vulvovaginal candidiasis7

  • human trialWomen treated with probiotics and lactoferrin showed recurrence rates of 33.3% at 3 months and 29.2% at 6 months compared to placebo group with 91.7% at 3 months and 100% at 6 months7

  • human trialPhase II/III clinical trial compared talactoferrin with placebo in addition to standard of care in patients with severe sepsis8

  • human trialTwenty-eight-day mortality was higher in talactoferrin-treated patients although this difference was not statistically significant (24.8% vs 17.8% placebo)8

  • human trialIn-hospital mortality rates were significantly higher in talactoferrin-treated patients than placebo (28.1% vs 17.8%)8

  • human trialThree-month mortality rates were significantly higher in talactoferrin-treated patients than placebo (30.1% vs 20.4%)8

Show 48 more findings

  • human trialMortality difference was largely the result of differences in patients with shock (talactoferrin 31.4% vs placebo 20.2%); no mortality difference was seen in patients without shock (talactoferrin 10.4% vs placebo 12.5%)8

  • human trialClinical and preclinical studies underscore lactoferrin's contributions to gut health, immune enhancement, and oxidative stress mitigation15

  • human studyIn a meta-analysis of 11 studies with 1,262 participants, serum iron, serum ferritin, and hemoglobin showed greater improvements following daily supplementation with oral lactoferrin vs. oral ferrous sulfate1

  • human studyFractional iron absorption was superior with ferrous sulfate vs. lactoferrin1

  • human studyEight out of 13 studies in a systematic review and meta-analysis reported improvements in at least one biomarker of immune function following lactoferrin supplementation1

  • human studyLactoferrin given enterally may reduce the incidence of necrotizing enterocolitis in preterm infants9

  • human studyLactoferrin alleviates or prevents necrotizing enterocolitis in preterm infants9

  • human studyVery low-birth weight preterm infants given bovine lactoferrin had a significant reduction in late-onset sepsis9

  • human studyThere was a trend towards a diminished incidence of necrotizing enterocolitis in very low-birth weight preterm infants given bovine lactoferrin9

  • human studyLactoferrin has been shown to enhance iron status of infants and pregnant women, possibly also via the receptor-mediated pathway11

  • human studyLactoferrin has been shown to inhibit carcinogenesis11

  • human studyOral lactoferrin treatment may have an anti-inflammatory effect on pregnant women, reducing pregnancy complications11

  • human studyOral administration of lactoferrin or lactoferricin exerts a host-protective effect in various animals and in humans12

  • human studySome patients with hepatitis C seem to respond to lactoferrin taken from cows with doses of 1.8 or 3.6 grams/day of lactoferrin28

  • human studySome studies show bovine lactoferrin improves the effectiveness of some prescription medications for Helicobacter pylori infection28

  • human studyTreating Helicobacter pylori infection with bovine lactoferrin alone isn't effective, even at high doses28

  • human studyOne study with 63 participants found that lactoferrin increased interleukin-18 levels, a protein important in combating hepatitis C29

  • human studyPreliminary studies suggest lactoferrin may assist in managing asymptomatic and mild to moderate COVID-19 cases, but these studies were small, involving only 92 people29

  • human studyIn one study, participants consumed either fermented milk with 200 mg of lactoferrin or fermented milk alone every day for 12 weeks; those given lactoferrin-supplemented milk had fewer acne lesions and less sebum compared to placebo29

  • human studyA 2017 study in International Journal of Dermatology found that taking a supplement containing lactoferrin, vitamin E, and zinc two times daily for three months helped reduce acne lesions in those with mild to moderate acne vulgaris29

  • human studyTaking lactoferrin 100 to 200 milligrams daily can increase iron levels in adults who have low levels30

  • human studyResearch in very preterm infants shows that adding lactoferrin to formula does not reduce the risk of an infection30

  • human studyResearch in adults is mixed, with some studies showing small benefits and other studies showing no benefits for immune function30

  • animalPreclinical studies have shown promising antimicrobial activity even in the setting of immunodeficiency4

  • animalLactoferrin given orally before enteral infection with pathogenic Escherichia coli reduced bacteremia and mortality in neonatal rats9

  • animalPreclinical studies showed promising antimicrobial activity in the setting of immunodeficiency10

  • animalSystemic or intratumoral administration of LfcinB is able to inhibit in vivo growth and/or metastasis of several different tumor types in mice14

  • animalSubcutaneous administration of LfcinB inhibited blood vessel development in B16–BL6 melanoma tumors implanted in mice14

  • animalOrally administered lactoferrin displays immunomodulatory activity, with a direct effect on the development of the immune system in the newborn, together with a specific antinflammatory effects23

  • animalOrally administered lactoferrin displays anticancer activity23

  • animalSeveral animal studies have investigated lactoferrin's potential in treating fungal infections such as yeast infections or candida29

  • animalIn a study involving yeast-infected mice, those treated with lactoferrin experienced less severe infections compared to untreated mice29

  • animalIn lab and mouse studies, lactoferrin has been found to stimulate osteoblasts, the cells needed to build bones29

  • animalLactoferrin helped strengthen and preserve bones in mice whose ovaries had been removed29

  • in vitroLfcinB exhibits in vitro cytotoxic activity against many different types of mouse and human cancer cell lines, including leukemia cells, fibrosarcoma cells, various carcinomas, and neuroblastoma cells at concentrations that do not substantially affect the viability of normal fibroblasts, lymphocytes, epithelial cells, endothelial cells, or erythrocytes14

  • in vitroAt 1 mg/mL of bovine lactoferrin, cell proliferation was significantly suppressed in endometriotic stromal cells compared to controls16

  • in vitroBovine lactoferrin treatment remained unchanged in endometrial stromal cells16

  • in vitroLactoferrin-based food supplement showed no inhibition of growth on 24% of tested bacterial isolates18

  • in vitroLactoferrin-based food supplement showed moderate inhibition on 31% of tested bacterial isolates18

  • in vitroLactoferrin-based food supplement showed strong inhibition on 45% of tested bacterial isolates18

  • in vitroCommercially available lactoferrin-based food supplements and purified bovine lactoferrin showed strain- as well as product-specific growth inhibition18

  • in vitroViral titres were reduced by 1-1.1 log by lactoferrin treatment19

  • in vitroThe isolated antimicrobial domain has potent broad spectrum antimicrobial properties with lethal effect causing rapid loss of colony-forming capability26

  • in vitroIn one laboratory study, cow-derived lactoferrin inhibited H. pylori growth and enhanced the effectiveness of common medications for the infection (in vitro study)29

  • in vitroLaboratory studies have explored lactoferrin's potential to protect against viral infections like common cold, flu, herpes, and gastroenteritis29

  • expert opinionLF supplementation (currently bovine) supports the immune system and helps maintain iron homeostasis in adults17

  • expert opinionClinical trials are needed to evaluate further the safety, efficacy, and optimal dosing regimens of hLF in the treatment of various fungal infections27

  • expert opinionSome evidence indicates lactoferrin may support immune health, but most studies have been conducted in laboratory settings29

How it works

Based on 4 human trial findings, 8 human study findings, 9 animal findings, 30 in vitro findings, 40 expert opinion findings and 10 theoretical findings.

  • human trialPepsin-like aspartyl proteases are not responsible for vaginal proteolysis of bLF3

  • human trialHuman lactoferrin 1-11 is an antimicrobial peptide4

  • human trialLactoferrin is a globular glycoprotein of the transferrin family that has shown promising results in patients with a low hemoglobin profile6

  • human trialTalactoferrin alfa is a recombinant form of the human glycoprotein, lactoferrin, which has been shown to have a wide range of effects on the immune system8

  • human studyLactoferrin enhances intestinal absorption of iron and improves hemoglobin production1

  • human studyBovine lactoferrin (bLF) is a single chain, 80-kDa glycoprotein of the transferrin family consisting of 689 amino acids3

  • human studybLF consists of two homologous, 40 kDa N- and C-terminal lobes, each containing an iron binding site that binds one ferric (Fe3+) ion3

  • human studyLactoferrin is selectively bactericidal, contributing to the maintenance of healthy microbiomes in the gastrointestinal tract and vagina by sparing lactobacilli, bifidobacteria, and other commensal organisms, while killing pathogens3

Show 93 more findings

  • human studyLactoferrin's bacteriostatic and bactericidal effects result from its ability to bind iron and from short, polycationic sequences that bind directly to microbial cell surfaces3

  • human studyIngested lactoferrin has been suggested to exert antibacterial and antiviral activities in the intestine, in part through a direct effect on pathogens, but possibly also affecting mucosal immune function11

  • human studyLactoferrin is taken up by cells via a unique receptor-mediated pathway and affects gene transcription11

  • human studyLactoferrin can stimulate intestinal cell proliferation and differentiation, causing expansion of tissue mass and absorptive capacity11

  • animalPeptide representing the first cationic domain (hLF1-11) was significantly more effective than the full length hLF or the peptide representing the second cationic domain in killing a variety of bacteria in vivo2

  • animalThe results of in vitro and in vivo experiments suggest that the mechanism of action is predominantly through the intermediary of cells and/or components of the host as opposed to a direct interaction with the pathogen2

  • animalPeptide representing the first cationic domain (hLF1-11, first eleven residues of hLF) was significantly more effective than the full length hLF or the peptide representing the second cationic domain in killing a variety of bacteria in vivo5

  • animalResults of in vitro and in vivo experiments suggest that the mechanism of action is predominantly through the intermediary of cells and/or components of the host as opposed to a direct interaction with the pathogen5

  • animalMouse fibrosarcoma cells and human neuroblastoma cells exposed to LfcinB die primarily via necrosis caused by a cell membrane lytic effect14

  • animalLfcinB interferes with bFGF- and VEGF-induced angiogenesis in subcutaneous Matrigel plugs implanted in mice by competing with bFGF and VEGF for growth factor receptor-associated heparan sulfate proteoglycans on the endothelial cell surface14

  • animalOrally administered lactoferrin displays antimicrobial activity, which has been presumed due to iron deprivation, but more recently attributed also to a specific interaction with the bacterial cell wall and extended to viruses and parasites23

  • animalProtective activities of lactoferrin have been found, sometimes to a greater extent, also in peptides derived from limited proteolysis of lactoferrin that could be generated after lactoferrin ingestion23

  • animalLactoferrin has been found to alleviate osteoporosis symptoms, possibly through cell signaling in lab and mouse studies29

  • in vitroThe mechanism of action comprises a number of independent factors with the classical direct killing effect typically observed in vitro at relatively high concentrations2

  • in vitroAn aspartyl protease was at least partially responsible for bLF cleavage in ex vivo VF digests3

  • in vitroThe classical way to explain the efficacy is the direct killing effect, which typically is observed in vitro at relatively high concentrations5

  • in vitroLactoferricin is a potent antimicrobial peptide derived from lactoferrin molecule by pepsin digestion12

  • in vitroLactoferricin is a cationic AMP produced by acid-pepsin hydrolysis of mammalian lactoferrin14

  • in vitroBovine lactoferricin (LfcinB) isolated from cow's milk consists of 25 amino acid residues (FKCRRWQWRMKKLGAPSITCVRRAF), including two Cys residues that create a disulfide bond14

  • in vitroLfcinB assumes a twisted β-sheet configuration with the basic amino acid residues arranged on one face and most of the hydrophobic amino acid residues arranged on the other face in aqueous solution14

  • in vitroThe cytotoxic activity of LfcinB against cancer cells is dependent on the amphipathic structure and high net positive charge of the peptide14

  • in vitroLfcinB binds to cancer cell membranes, causing membrane integrity to be lost due to the formation of transmembrane pores that allow the peptide to enter the cytoplasmic compartment and co-localize with negatively-charged mitochondria14

  • in vitroLfcinB kills human leukemia and breast carcinoma cells by a process that involves the sequential generation of reactive oxygen species, loss of mitochondrial transmembrane potential, and activation of the caspase cascade culminating in cell death by apoptosis14

  • in vitroLfcinB suppresses both basic fibroblast growth factor (bFGF)- and VEGF-driven proliferation and migration of human endothelial cells in vitro14

  • in vitroThe antiangiogenic activity of LfcinB is dependent on the primary structure of the peptide14

  • in vitroBovine lactoferrin significantly increased the number of endometriotic stromal cells in the G0/G1 phase16

  • in vitroBovine lactoferrin significantly decreased endometriotic stromal cells in the S phase16

  • in vitroBovine lactoferrin suppressed the protein expression of phosphorylated-AKT, phosphorylated-mTOR, phosphorylated-S6K, and cyclin D116

  • in vitroBovine lactoferrin inhibits the transition from the G1 to the S phase by suppressing the PI3K/Akt/mTOR pathway and reducing the synthesis of cyclin D116

  • in vitroPeptides identified in digested hmLF samples strongly correlated with digested rhLF samples in the gastric phase (r between 0.86 and 0.92)17

  • in vitroPeptides identified in digested hmLF samples correlated with digested rhLF samples in the intestinal phase (r between 0.63 and 0.70)17

  • in vitroDigested bLF samples were significantly different from hmLF and rhLF17

  • in vitroLactoferrin is an iron-binding glycoprotein with a wide range of antibacterial effects18

  • in vitroHuman lactoferrin showed no inhibitory effects in comparison to bovine lactoferrin18

  • in vitroPurified lactoferrin and lactoferrin-based food supplements inhibit bacterial growth in a dose-, strain-, and product-dependent manner18

  • in vitroLactoferrin did not have a protective effect on cells, although it inhibited the replication of the virus during the adsorption and post-adsorption stages19

  • in vitroA decrease in the viral RNA level in cells by up to 75% was observed19

  • in vitroLactoferrin belongs to the group of glycoproteins and is modified with several different-glycans20

  • in vitroLactoferrin is an iron-binding protein present in large quantities in colostrum and in breast milk, in external secretions and in polymorphonuclear leukocytes23

  • in vitroLactoferrin contains an antimicrobial sequence near its N-terminus which functions by a mechanism distinct from iron chelation26

  • in vitroThe antimicrobial sequence consists mainly of a loop of 18 amino acid residues formed by a disulfide bond between cysteine residues 20 and 37 of human lactoferrin, or 19 and 36 of bovine lactoferrin26

  • in vitroThe identified domain contains a high proportion of basic residues, like various other antimicrobial peptides known to target microbial membranes26

  • in vitroThe antimicrobial domain is located on the surface of the folded protein allowing its interaction with surface components of microbial cells26

  • expert opinionHuman lactoferrin (hLF) is a glycoprotein containing 692 amino acids and found in the saliva, milk, tears, and other body fluids2

  • expert opinionHuman lactoferrin is a natural defence protein present in body fluids and secretions as well as neutrophils with pleiotropic functions including broad spectrum antimicrobial activity, antitumour activity, regulation of cell growth and differentiation, and modulation of inflammatory, humoral and cellular immune responses4

  • expert opinionhLF1-11 contains the N-terminal moiety of hLF, consisting of 11 amino acids, that is essential for the antimicrobial and anti-inflammatory activity4

  • expert opinionHuman lactoferrin (hLF) is a glycoprotein containing 692 amino acids and found in the saliva, milk, tears, and other body fluids5

  • expert opinionHuman lactoferrin is a natural defence protein present in body fluids and secretions and neutrophils with broad spectrum antimicrobial activity10

  • expert opinionhLF1-11 contains the N-terminal moiety of human lactoferrin consisting of 11 amino acids that is essential for antimicrobial and anti-inflammatory activity10

  • expert opinionLactoferricin is the functional domain of lactoferrin12

  • expert opinionEffects of oral lactoferrin are mediated by modulation of the immune system12

  • expert opinionLactoferrin is an iron-binding glycoprotein that plays a significant role in the innate immune system13

  • expert opinionLactoferrin-related peptides have antimicrobial activity13

  • expert opinionLactoferrin is a versatile glycoprotein renowned for its critical roles in immunity, iron regulation, and host defence15

  • expert opinionLactoferrin possesses antimicrobial, anti-inflammatory, and antioxidant capabilities15

  • expert opinionBy sequestering iron, lactoferrin limits microbial proliferation15

  • expert opinionLactoferrin's immunomodulatory properties help balance inflammation and accelerate tissue repair15

  • expert opinionBovine-specific glycosylation patterns may impact the heterogeneous effects of lactoferrin observed in humans20

  • expert opinionLactoferrin is an iron-binding glycoprotein and one of the most important bioactivators in milk and other external secretions21

  • expert opinionLactoferrin regulates iron absorption and modulates immune responses21

  • expert opinionLactoferrin has anti-microbial, anti-viral, antioxidant, anti-cancer, and anti-inflammatory activities21

  • expert opinionLactoferrin regulates the quantity of iron absorbed in the intestine via its role in iron transport and can chelate iron directly or indirectly21

  • expert opinionLactoferrin's main function is non-immune protection23

  • expert opinionLactoferrin is involved with immunoprotection and regulation of innate immunity24

  • expert opinionLactoferrin functions include iron transfer to cells and control of the level of free iron in blood and external secretions24

  • expert opinionLactoferrin interacts with DNA, RNA, heparin, and polysaccharides24

  • expert opinionLactoferrin possesses antimicrobial and antiviral activities24

  • expert opinionLactoferrin belongs to the class of hybrid proteins possessing both ordered domains and functionally important intrinsically disordered regions24

  • expert opinionLactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa consisting of two homologous domains known as N-terminal and C-terminal lobes24

  • expert opinionEach lobe of lactoferrin can bind a single ferric ion concomitantly with one bicarbonate anion24

  • expert opinionThe N-lobe of lactoferrin possesses the majority of antimicrobial activities24

  • expert opinionLactoferrin and its lobes possess anti-cancer, wound healing, anti-inflammatory, and immunomodulation activities24

  • expert opinionLactoferrin is a protein found in cow milk and human milk28

  • expert opinionLactoferrin is found in fluids in the eye, nose, respiratory tract, intestine, and elsewhere28

  • expert opinionLactoferrin helps regulate the absorption of iron in the intestine and delivery of iron to the cells28

  • expert opinionLactoferrin protects against bacterial infection, possibly by preventing the growth of bacteria by depriving them of essential nutrients or by killing bacteria by destroying their cell walls28

  • expert opinionLactoferrin seems to be active against infections caused by some viruses and fungi28

  • expert opinionLactoferrin seems to be involved with regulation of bone marrow function (myelopoiesis)28

  • expert opinionLactoferrin is believed to offer antioxidant, antiviral, and antibacterial benefits29

  • expert opinionLactoferrin is believed to have anti-fungal properties29

  • expert opinionIn infants, lactoferrin plays an important role in building a healthy gut and immune system30

  • expert opinionThroughout life, lactoferrin acts as part of the immune response to bacteria and viruses30

  • expert opinionLactoferrin naturally contains iron, a mineral that your body needs to function30

  • theoreticalThe mechanism of action of hLF1-11 comprises a number of independent factors5

  • theoreticalBovine LF shares a high degree of similarity (up to 70%), with human lactoferrin, which is found in body exocrine secretions (human milk, tears, and saliva) and in the secondary granules of neutrophils6

  • theoreticalLactoferrin is an iron-binding glycoprotein found in human milk that facilitates iron absorption and exhibits antimicrobial properties by inhibiting iron-dependent bacteria in the gastrointestinal tract14

  • theoreticalLactoferrin has roles in cell growth regulation, DNA binding, and various enzymatic activities14

  • theoreticalLactoferrin has cell proliferation-suppressing effects, reportedly in various malignant tumours16

  • theoreticalNearly all extracellular proteins undergo post-translational modification with sugar chains during their transit through the endoplasmic reticulum and the Golgi apparatus20

  • theoreticalPost-translational modifications of glycoproteins influence the activity of the carrier protein20

  • theoreticalGlycosylation modifications themselves often have bioactivity, independent of the carrier function20

  • theoreticalLactoferrin is thought to protect against bacteria by binding to iron, preventing bacteria from using iron to move through the body29

  • theoreticalLactoferrin is thought to protect against viral infections by preventing viruses from attaching to cells and multiplying29

Dosing

Based on 7 human trial findings, 1 human study finding and 1 in vitro finding.

  • human trialSingle dose of 5 mg of hLF1-11 was given to autologous haematopoietic stem cell transplant recipients2

  • human trialTablet formulations containing 300 mg of bLF progressed through three phases: Pre-Dissolution, Dissolution, and Washout, over a 30-h time course3

  • human trialSingle intravenous dose of hLF1-11 given in a volume of 20mL given over 20 minutes (1mL per minute)5

  • human trialLactoferrin is an effective intervention at doses of 100–250 ng/day, for patients with a low Hb concentration6

  • human trialDosing regimen: 2 capsules/day for 5 days followed by 1 capsule/day for additional 10 days as induction phase, then 1 capsule/day verum or placebo for 10 consecutive days each month for 6 months maintenance7

  • human trialTalactoferrin dose was 1.5 g (15 mL) three times a day orally or by enteral route for 28 days or until ICU discharge8

  • human trialA lower dose is recommended for forthcoming multiple dosing studies in HSCT patients10

  • human studyLower doses of bovine lactoferrin for hepatitis C don't seem to work28

Show 1 more finding

  • in vitroMinimal inhibitory concentrations against B. cereus and Bacillus thuringiensis strain-specifically ranged from 0.31 mg/mL to no impairment at all18

How the body handles it

Based on 5 human trial findings, 3 in vitro findings and 2 expert opinion findings.

  • human trialbLF was initially cleaved approximately in half between its N- and C-lobes, then degraded into sub-fragments and small peptides3

  • human trialThe extent of proteolysis was less than 10–20% across multiple subjects3

  • human trialConcentrations of intact 80 kDa bLF and smaller fragments decreased in VF with a similar time course suggesting washout not proteolysis was the main clearance mechanism3

  • human trialConcentrations of intact and/or nicked 80 kDa bLF peaked between 4 and 8 h after administration and remained above 5 mg/mL for approximately 24 h3

  • human trialThe 3.1 kDa antimicrobial peptide lactoferricin B was not detected in VF3

  • in vitroThe cytotoxic activity of LfcinB is reduced in the presence of high concentrations of serum14

  • in vitroIntact LF retention across digestion was similar across LF types17

  • in vitroThe highest iron-saturated hmLF had greater retention in the simulated gastric fluid than all other sample types17

Show 2 more findings

  • expert opinionLactoferrin's efficacy is often hindered by limited bioavailability due to gastrointestinal degradation during oral administration15

  • expert opinionAdvanced strategies including encapsulation, nano formulations, and enteric coatings have been developed to enhance stability and absorption of lactoferrin15

Safety and side effects

Based on 24 human trial findings, 4 human study findings, 1 animal finding, 1 in vitro finding, 17 expert opinion findings and 1 anecdotal finding.

  • human trialThe change from baseline to Day 56 in serum anti-bLF antibodies in the bLF group was greater than the changes in serum anti-hLF antibodies in the low-dose rhLF and high-dose rhLF groups1

  • human trialrhLF at doses up to 3.4 g/d was safe and well-tolerated in healthy adults1

  • human trialChanges in all safety outcomes including complete blood count, iron biomarkers, and metabolic panel were similar between groups and within normal ranges1

  • human trialSafety and tolerability of hLF1-11 was established in HSCT recipients at risk of developing infectious complications due to invasive fungal disease2

  • human trialSingle and multiple doses of hLF1-11 were tolerable up to 5 mg intravenously in healthy volunteers4

  • human trial5 mg single dose was tolerable in autologous HSCT recipients (patients)4

  • human trialElevations in transaminases possibly related to treatment were reversible and not serious4

  • human trialhLF1-11 is well tolerated in healthy volunteers with repeated daily doses up to 5 mg4

Show 40 more findings

  • human trialThe side-effect profile is very favourable for an antimicrobial4

  • human trialSingle and multiple doses of hLF1-11 were tolerable up to 5 mg intravenously in healthy volunteers4

  • human trial5 mg single dose was tolerable in autologous HSCT recipients4

  • human trialElevations in transaminases possibly related to treatment were reversible and not serious4

  • human trialhLF1-11 is well tolerated in healthy volunteers with repeated daily doses up to 5 mg4

  • human trialThe side-effect profile is very favourable for an antimicrobial4

  • human trialThe only undesirable effect being a possible elevation of transaminases4

  • human trialPrimary outcome is safety and tolerability by recording vital signs, clinical chemistry, local tolerability and adverse events during the study over 28 days5

  • human trialSecondary outcome is formation of antibodies anti-hLF1-11 during the study over 28 days5

  • human trialLactobacilli mixture in combination with lactoferrin represents a safe and effective adjuvant approach for reducing symptoms and recurrences of recurrent vulvovaginal candidiasis7

  • human trialThe occurrence of treatment-related adverse or serious adverse events was similar between groups8

  • human trialhLF1-11 was tolerable up to 5 mg intravenously in healthy volunteers with single and multiple doses10

  • human trial5 mg single dose of hLF1-11 was tolerable in autologous HSCT recipients10

  • human trialElevations in transaminases possibly related to hLF1-11 treatment were reversible and not serious10

  • human trialThe side-effect profile of hLF1-11 is very favourable for an antimicrobial10

  • human trialSafety of purified lactoferrin confirmed from clinical studies12

  • human studyOral iron supplementation, the most common method of treatment, is reported to have poor patient adherence, due to its unwanted side effects6

  • human studyOral iron supplementation usually causes unwanted gastrointestinal side effects in patients in 70% of cases6

  • human studyColostrum, a natural lactoferrin concentrate, given immediately after birth to extremely preterm infants appears well tolerated9

  • human studyFor some people, lactoferrin may cause fewer side effects than iron supplements30

  • animalSafety of purified lactoferrin confirmed from 13-week oral repeated-dose toxicity study in rats12

  • in vitroSafety of purified lactoferrin confirmed from reverse mutation test using bacteria12

  • expert opinionBovine milk lactoferrin is generally recognized as safe (GRAS) in the United States for use in term infant formula, sports foods, functional foods, chewing gum, and as an antimicrobial agent1

  • expert opinionGlobal standardization in the quality of bovine lactoferrin is progressing through Novel Food and GRAS in the EU and USA, respectively22

  • expert opinionNovel Food was applied or notified to seven lactoferrin manufacturers and GRAS was notified to three manufacturers by the end of 201722

  • expert opinionSpecifications of Novel Food and GRAS regulations include more than 95% lactoferrin purity in protein22

  • expert opinionAn industrial lactoferrin sample may contain LPS at a maximum LPS/lactoferrin molecule ratio of 1/1724, meaning 99.9% of the lactoferrin molecule is LPS-free22

  • expert opinionLPS is immunologically toxic when invading the body but is distributed normally in foods and the gut22

  • expert opinionQuality concerns for lactoferrin include contamination of lipopolysaccharide (LPS) and angiogenin, purity, and degradation of lactoferrin sample22

  • expert opinionLactoferrin can be produced relatively cheaply from bovine milk and has widely recognized tolerance after ingestion23

  • expert opinionLactoferrin is safe in amounts consumed in food28

  • expert opinionConsuming higher amounts of lactoferrin from cow's milk might also be safe for up to a year28

  • expert opinionHuman lactoferrin made from specially processed rice appears to be safe for up to 14 days28

  • expert opinionLactoferrin can cause diarrhea28

  • expert opinionLactoferrin is safe for pregnant and breast-feeding women in food amounts28

  • expert opinionTaking too much lactoferrin may result in stomach upset, skin rash, and loss of appetite29

  • expert opinionThere are few side effects associated with lactoferrin29

  • expert opinionLactoferrin seems to be well tolerated by most people30

  • expert opinionLactoferrin may cause serious allergic reactions including breathing problems, swelling of face/lips/mouth/tongue/throat, and skin reactions30

  • anecdotalIn very high doses, skin rash, loss of appetite, fatigue, chills, and constipation have been reported28

What people use it for

Based on 5 human trial findings, 2 human study findings, 2 in vitro findings, 12 expert opinion findings and 3 theoretical findings.

  • human trialhLF1-11 is being developed as an effective and safe antibacterial and antifungal for the treatment of fungal and bacterial infections that develop during the neutropenia that results from myeloablative therapy to prepare for a haematopoietic stem cell transplant2

  • human trialhLF1-11 is being developed as an effective and safe antibacterial and antifungal for the treatment of fungal and bacterial infections that develop during neutropenia resulting from myeloablative therapy in HSCT5

  • human trialLactoferrin can serve as an iron replacement treatment for patients who may be experiencing adverse side effects due to iron intake6

  • human trialAdministration of oral talactoferrin was not associated with reduced 28-day mortality in patients with severe sepsis and may even be harmful8

  • human trialLactoferrin has shown promise in anticancer applications, wound healing, reproductive health, and metabolic regulation15

  • human studyLevels of lactoferrin are decreased following HSCT, contributing to the overall immune deficiency4

  • human studyLactoferrin levels are decreased following HSCT, contributing to overall immune deficiency10

  • in vitroRecombinant human lactoferrin (rhLF) has potential for use as a food ingredient for human consumption17

Show 16 more findings

  • in vitroBovine lactoferrin ensures some degree of protection against infection by bovine enterovirus, particularly important for young animals that receive this protein in their mother's milk19

  • expert opinionRecombinant human lactoferrin (rhLF) is of commercial interest for support of the immune system and iron homeostasis1

  • expert opinionLactoferrin treatment may have beneficial preventive and therapeutic effects on infection, inflammation, and cancer as well as enhancing iron status and growth in vulnerable groups11

  • expert opinionLactoferrin allows for pregnancy and lactation during administration16

  • expert opinionBovine lactoferrin is often selected for the development of novel therapeutic approaches in humans20

  • expert opinionLactoferrin has been used as an adjuvant therapy for some intestinal diseases21

  • expert opinionLactoferrin is used in nutraceutical-supplemented infant formula and other food products21

  • expert opinionLactoferrin is used for treating stomach and intestinal ulcers, diarrhea, and hepatitis C28

  • expert opinionLactoferrin is used as an antioxidant and to protect against bacterial and viral infections28

  • expert opinionLactoferrin is a protein found in milk used in supplements for its potential to combat infections and inflammation29

  • expert opinionLactoferrin is often used to help manage and prevent low iron levels30

  • expert opinionLactoferrin may also be used to support the immune system and improve digestive health, but its benefits for these uses are not well defined30

  • expert opinionThere is very limited research on using lactoferrin supplements for digestive health30

  • theoreticalDepletion of iron from the vaginal environment with bLF will have beneficial effects on the vaginal microbiome since lactobacilli do not require iron for growth while bacteria common to vaginal infections, including bacterial vaginosis (BV), require iron3

  • theoreticalLactoferrin has been used in a wide variety of products since it was first added to infant formula in 198612

  • theoreticalActive peptides produced by enzymatic digestion of lactoferrin may contribute to the host defense against microbial disease26

Other findings

Based on 1 human trial finding, 1 human study finding, 1 in vitro finding, 6 expert opinion findings and 1 theoretical finding.

  • human trialNineteen trials published between 2006 and 2022 met the eligibility criteria6

  • human studyHuman milk contains 5-7 mg/mL lactoferrin in colostrum and 1-3 mg/mL in mature milk1

  • in vitroLactoferrin (LF) is a major component of human milk17

  • expert opinionLactoferrin is a whey protein and food-derived bioactive agent13

  • expert opinionLactoferrin is found abundantly in human and bovine milk, as well as in bodily fluids like saliva, tears, and mucosal secretions15

  • expert opinionMorinaga Milk Industry has been industrially producing bovine lactoferrin in Milei GmbH, Germany, since 198922

  • expert opinionLactoferrin is a multifunctional glycoprotein found in blood circulation, mucosal surfaces, neutrophils, and in various secretory fluids such as milk, bile, tears, nasal secretion, pancreatic juice, and saliva24

  • expert opinionColostrum contains high levels of lactoferrin, about seven times the amount found in milk produced later on28

Show 2 more findings

  • expert opinionLactoferrin is a protein found in cow's milk and human milk30

  • theoreticalBovine lactoferrin is produced on an industrial scale from cheese whey or skim milk12

Points of contention

Where the evidence is unsettled, thin, or says less than the popular claim — worth knowing before you draw conclusions.

Contested

Oral talactoferrin appeared harmful in severe sepsis, contrasting with lactoferrin's generally favourable safety profile

The Phase II/III sepsis RCT (Talactoferrin in Severe Sepsis: Results From the Phase II/III Oral tAlactoferrin in Severe sepsIS Trial.) found significantly higher in-hospital (28.1% vs 17.8%) and 3-month (30.1% vs 20.4%) mortality in talactoferrin-treated patients and concluded it may be harmful, whereas most other sources (A Randomized, Double-Blind, Controlled Trial to Assess the Effects of Lactoferrin at Two Doses vs. Active Control on Immunological and Safety Parameters in Healthy Adults | medRxiv, Lactoferrin: Health Benefits, Side Effects, Uses, Dose & Precautions, Bovine lactoferrin and lactoferricin derived from milk: production and applications., Lactoferrin from Milk: Nutraceutical and Pharmacological Properties.) describe lactoferrin as safe and well-tolerated.

Limited evidence

Much lactoferrin efficacy evidence is in vitro or animal, not human trials

Many antimicrobial, anticancer, antiviral and bone claims come from in vitro or animal studies (Lactoferricin - an overview | ScienceDirect Topics, Lactoferrin: Supplement Benefits and Side Effects, Strain-specific Antimicrobial Activity of Lactoferrin-based Food Supplements., Antiviral Effect of Bovine Lactoferrin against Enterovirus E., Antimicrobial peptides of lactoferrin., Bovine lactoferrin suppresses the proliferation of endometriotic stromal cells via the PI3K/Akt/mTOR pathway., Lactoferrin from Milk: Nutraceutical and Pharmacological Properties.); Lactoferrin: Supplement Benefits and Side Effects explicitly notes most studies were in laboratory settings, and Full article: Potential health benefits of lactoferrin and derived peptides states clinical trials are still needed for antifungal use.

Preprint

Recombinant human lactoferrin safety data comes from an unpublished preprint

The claim that rhLF up to 3.4 g/day is safe and well-tolerated (66 and 24 healthy adults) is from a medRxiv preprint (A Randomized, Double-Blind, Controlled Trial to Assess the Effects of Lactoferrin at Two Doses vs. Active Control on Immunological and Safety Parameters in Healthy Adults | medRxiv) that has not completed peer review.

Single source

COVID-19, hepatitis C IL-18, and acne findings each rest on small single studies

The COVID-19 benefit (92 people total), hepatitis C interleukin-18 increase (63 participants), and acne improvements (200 mg/12 weeks) are each reported by a single consumer-health source (Lactoferrin: Supplement Benefits and Side Effects) describing small preliminary studies.

Other

Human vs bovine lactoferrin may differ in activity and glycosylation

Strain-specific Antimicrobial Activity of Lactoferrin-based Food Supplements. found human lactoferrin showed no inhibitory effects compared to bovine lactoferrin in vitro, and The-glycans of lactoferrin: more than just a sweet decoration. notes bovine-specific glycosylation patterns may impact heterogeneous effects observed in humans, so results may not transfer between lactoferrin types.

Other

Oral lactoferrin bioavailability is limited by gastrointestinal degradation

Lactoferrin in health and disease: A review of its bioavailability and evidence-based benefits across study models notes lactoferrin's efficacy is often hindered by limited bioavailability due to GI degradation during oral administration, and Lactoferrin: Health Benefits, Side Effects, Uses, Dose & Precautions reports lower oral doses of bovine lactoferrin do not appear to work for hepatitis C or H. pylori alone.

Inconsistency

A widely cited meta-analysis lists an effective lactoferrin dose of 100–250 nanograms per day, but that is almost certainly a misprint for milligrams, since every other study uses…

A 2024 systematic review and meta-analysis in BMC Nutrition comparing oral bovine lactoferrin with ferrous sulfate concluded that lactoferrin was 'an effective intervention at doses of 100–250 ng/day' for people with low hemoglobin. A nanogram is a billionth of a gram, and no oral protein could raise hemoglobin at such a tiny dose; this reads as a printing error for milligrams. Consistent with that, other reference figures for the same use are in the milligram range — for example, WebMD cites 100–200 mg daily — so the intended figure is almost certainly 100–250 mg/day.

Using it with other compounds

Check a stack
  • PidotimodComplementary

    No documented conflict

    Pidotimod boosts adaptive and innate defences (dendritic-cell maturation, Th1, immunoglobulins) to reduce recurrent infections, while lactoferrin provides direct antimicrobial and iron-sequestering innate defence. Coming at infection resistance from adaptive-immune priming versus direct antimicrobial action, they are complementary rather than redundant.

    Tier 4Theoretical — not established

    Shares innate immune · anti inflammatory · antimicrobial

  • ThymulinComplementary

    No documented conflict

    Thymulin fine-tunes T-cell maturation and dampens excess pro-inflammatory cytokines, while lactoferrin acts on the innate/antimicrobial front. Their immune roles are distinct but converge on balanced immune function, making them a plausible complementary immune-support pairing.

    Tier 4Theoretical — not established

    Shares innate immune · anti inflammatory

  • VilonComplementary

    No documented conflict

    Lactoferrin adds direct antimicrobial and innate-immune defense plus anti-inflammatory activity, while Vilon works at the gene-expression level to support T-cell/thymic immunity. Different mechanisms both reinforcing host defense, making them a reasonable complementary immune pairing.

    Tier 4Theoretical — not established

    Shares innate immune · anti inflammatory

  • ThymalinComplementary

    No documented conflict

    Lactoferrin supports innate defense through direct antimicrobial/iron-sequestering and cytokine-calming actions, a different mechanism from Thymalin's thymic T-cell restoration. The two hit host defense from separate angles (mucosal/innate barrier vs. adaptive T-cell compartment) and both temper pro-inflammatory cytokines, so they can reasonably layer for broad immune support.

    Tier 4Theoretical — not established

    Shares innate immune · anti inflammatory

  • Thymosin Alpha-1Complementary

    No documented conflict

    Lactoferrin is an iron-sequestering defense protein with broad direct antimicrobial and immunomodulatory action, whereas Thymosin Alpha-1 restores and coordinates cellular immunity. These are distinct mechanisms (iron-based/direct microbial killing vs. T-cell/NK modulation) both supporting host defense, so they can be complementary.

    Tier 4Theoretical — not established

    Shares innate immune · anti inflammatory · antimicrobial

  • LL-37Complementary

    May be complementary

    Both are frontline innate-immune defence peptides but attack microbes by different routes: LL-37 is a cationic peptide that punches holes in bacterial membranes, while lactoferrin starves microbes of iron and also binds their surfaces. Because the mechanisms differ, they can broaden antimicrobial coverage and both help calm inflammation — a classic complementary innate-immunity pairing seen naturally in neutrophils and mucosal fluids.

    Tier 3Largely anecdotal — commonly discussed

    Shares antimicrobial · innate immune · anti inflammatory

  • KPVComplementary

    No documented conflict

    Lactoferrin provides direct antimicrobial defence and iron sequestration at mucosal surfaces, while KPV suppresses the inflammatory cytokine cascade. Both are oriented toward gut/mucosal health from different mechanisms, making them a plausible complementary pair for barrier and microbiome support.

    Tier 4Theoretical — not established

    Shares innate immune · anti inflammatory

  • ImunofanComplementary

    No documented conflict

    Lactoferrin adds broad-spectrum antimicrobial and iron-homeostasis activity plus immune/antioxidant modulation. Its mechanisms differ from imunofan's thymic pathway, so combining innate antimicrobial defense with imunofan's enhanced phagocytic and NK activity is a reasonable complementary immune-support pairing.

    Tier 4Theoretical — not established

    Shares innate immune · anti inflammatory · antimicrobial

  • Alpha-MSHComplementary

    Worth caution

    Lactoferrin defends against microbes largely by sequestering iron and binding microbial surfaces, and calms inflammation via immune modulation — a completely different route from alpha-MSH's melanocortin/NF-κB-based antimicrobial and anti-inflammatory action. The two converge on innate immune defense through non-overlapping mechanisms, which is the hallmark of a complementary combination.

    Tier 4Theoretical — not established

    Shares anti inflammatory · antimicrobial

  • ElafinComplementary

    May be complementary

    Lactoferrin defends by sequestering iron away from microbes and calming inflammation, while elafin blocks neutrophil serine proteases. They are two arms of innate mucosal immunity working through different mechanisms toward the same goal of infection control and reduced inflammatory tissue damage.

    Tier 3Largely anecdotal — commonly discussed

    Shares innate immune · antimicrobial · anti inflammatory

Safety and side effects

Safety and Side Effects

Intravenous hLF1-11 (Phase 1)

A Phase 1 trial reported that single and multiple intravenous doses of hLF1-11 were tolerable up to 5 mg in healthy volunteers, and a 5 mg single dose was tolerable in autologous HSCT recipients4,10. Investigators reported that elevations in transaminases possibly related to hLF1-11 were reversible and not serious, described this as the only undesirable effect, and judged the side-effect profile very favourable for an antimicrobial4,10. The trial authors nonetheless recommended a lower dose for forthcoming multiple-dosing studies in HSCT patients5.

Recombinant human lactoferrin (preprint)

A medRxiv preprint (not peer-reviewed) reported trials in 66 and 24 healthy adults using 28-day supplementation with washout and follow-up, in which recombinant human lactoferrin at doses up to 3.4 g/day was safe and well-tolerated, with CBC, iron biomarkers and metabolic panel similar between groups and within normal ranges. The preprint reported the rise in anti-bovine-LF antibodies in the bovine LF group exceeded the changes in anti-human-LF antibodies in the rhLF groups.

Talactoferrin in sepsis — a contested safety signal

Importantly, a Phase II/III trial in 305 patients (oral talactoferrin 1.5 g three times daily for up to 28 days) reported 28-day mortality of 24.8% vs 17.8% placebo (not significant, p = 0.117), but significantly higher in-hospital mortality (28.1% vs 17.8%, p = 0.037) and 3-month mortality (30.1% vs 20.4%, p = 0.036); the difference was largely in patients with shock. Treatment-related adverse events were similar between groups, and the investigators concluded oral talactoferrin was not associated with reduced 28-day mortality and may even be harmful. This contrasts with the generally favourable safety profile reported elsewhere.

Consumer/reference-source safety notes

A consumer website states clinical study doses ranged from 100 mg to 4,500 mg/day, that lactoferrin has few side effects, but that too much may cause stomach upset, skin rash and loss of appetite(vendor claim). WebMD states lactoferrin seems well tolerated and may cause fewer side effects than iron supplements for some people, but may cause serious allergic reactions including breathing problems and swelling of the face, lips, mouth, tongue or throat. RxList states lactoferrin is safe in food amounts, possibly safe from cow's milk for up to 1 year and from specially processed rice for up to 14 days, can cause diarrhea, and in very high doses has been associated with skin rash, loss of appetite, fatigue, chills and constipation. A review notes oral iron supplementation causes gastrointestinal side effects in about 70% of patients, providing context for lactoferrin as an alternative16.

Production/quality considerations

A study states bovine lactoferrin safety was confirmed by a bacterial reverse mutation test, a 13-week oral repeated-dose toxicity study in rats and clinical studies. A review lists LPS (endotoxin), angiogenin contamination, purity and degradation as quality concerns, and reports an industrial sample may contain LPS at a maximum LPS/lactoferrin ratio of 1/1724 (99.9% of molecules LPS-free).

Reconstitution and handling

Dosing

No universal dose has been established for lactoferrin as a research peptide, and no regulatory drug label sets a recommended dose for the figures below. Bovine milk lactoferrin is generally recognized as safe (GRAS) in the US for uses such as infant formula and functional foods, but the trial and reference figures below reflect what specific sources reported in specific settings — not general guidance.

Injectable hLF1-11 (clinical trial protocol)

The Phase 1 study administered ascending intravenous doses of 0.005 mg, 0.05 mg, 0.5 mg and 5 mg4,10. The registered protocol specifies a single intravenous 5 mg dose given in a 20 mL volume over 20 minutes (1 mL per minute), with 8 subjects, a 28-day follow-up, ages 18–80 and BMI < 302,5. Entry criteria included creatinine < 110 µmol/L (men)/< 90 µmol/L (women), ASAT < 40 U, ALAT < 45 U and bilirubin < 10 µmol/L, with primary outcomes of safety/tolerability and secondary outcome of anti-hLF1-11 antibody formation over 28 days2,5. The trial authors recommended a lower dose for subsequent multiple-dosing studies5.

Oral lactoferrin figures reported by sources

  • A review reports lactoferrin was effective at 100–250 ng/day for patients with low hemoglobin8.
  • WebMD reports 100 to 200 mg daily can increase iron levels in adults with low levels.
  • A consumer website states clinical study doses ranged from 100 mg to 4,500 mg/day(vendor claim).
  • RxList reports some hepatitis C patients respond to cow-derived lactoferrin at 1.8 or 3.6 g/day, while lower doses do not appear to work.
  • A preprint's healthy-adult trials used recombinant human lactoferrin at up to 3.4 g/day (versus a 0.34 g/day low dose and a 3.4 g/day bovine LF control); prior trials used bovine LF doses ranging from 32.4 mg/day to 3 g/day.
  • A vaginal-health RCT used an oral lactobacilli-plus-bovine-lactoferrin regimen: an induction of 2 capsules/day for 5 days then 1 capsule/day for 10 days, followed by 1 capsule/day for 10 consecutive days each month for 6 months.
  • The contested sepsis trial used oral talactoferrin 1.5 g (15 mL) three times daily for 28 days or until ICU discharge.
  • Acne studies reported by a consumer website used 200 mg lactoferrin daily in fermented milk for 12 weeks, or a lactoferrin/vitamin E/zinc supplement twice daily for three months.

Formulation and bioavailability

A review notes lactoferrin's efficacy is often hindered by limited oral bioavailability due to gastrointestinal degradation, and that encapsulation, nano-formulations and enteric coatings have been developed to enhance stability and absorption15,18. In a human study of 300 mg bovine lactoferrin tablets, intact/nicked 80 kDa bLF peaked in vaginal fluid between 4 and 8 hours and remained above 5 mg/mL for about 24 hours, with proteolysis kept below 10–20%7,28. Sources also caution that human and bovine lactoferrin may differ in activity and glycosylation, so results may not transfer between types18.

Sources

Ordered by evidence quality — the strongest first.

  1. A Randomized, Double-Blind, Controlled Trial to Assess the Effects of Lactoferrin at Two Doses vs. Active Control on Immunological and Safety Parameters in Healthy Adults | medRxiv(opens in a new tab)
    Tier 1Web · medrxiv.org
  2. Human lactoferrin peptide 1-11 in Bacterial Infections and Mycoses and Hematopoietic Stem Cell Transplantation - Clinical Trials Registry - ICH GCP(opens in a new tab)
    Tier 1Web · ichgcp.net
  3. Proteolysis of vaginally administered bovine lactoferrin: clearance, inter-subject variability, and implications for clinical dosing(opens in a new tab)
    Tier 1Web · pmc.ncbi.nlm.nih.gov
  4. Safety and tolerability of the antimicrobial peptide human ... - PMC(opens in a new tab)
    Tier 1Web · pmc.ncbi.nlm.nih.gov
  5. Safety of a Single Dose of 5 mg of hLF1-11 Given to Autologous Haematopoietic Stem Cell Transplant Recipients(opens in a new tab)
    Tier 1Web · clinicaltrials.gov
  6. The effectiveness of oral bovine lactoferrin compared to iron supplementation in patients with a low hemoglobin profile: A systematic review and meta-analysis of randomized clinical trials | BMC Nutrition | Springer Nature Link(opens in a new tab)
    Tier 1Web · link.springer.com · 2024
  7. Randomised clinical trial in women with Recurrent Vulvovaginal Candidiasis: Efficacy of probiotics and lactoferrin as maintenance treatment.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2019
  8. Talactoferrin in Severe Sepsis: Results From the Phase II/III Oral tAlactoferrin in Severe sepsIS Trial.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2015
  9. Lactoferrin and necrotizing enterocolitis.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2014
  10. Safety and tolerability of the antimicrobial peptide human lactoferrin 1-11 (hLF1-11) | BMC Medicine | Springer Nature Link(opens in a new tab)
    Tier 1Web · link.springer.com · 2009
  11. Nutritional roles of lactoferrin.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2009
  12. Bovine lactoferrin and lactoferricin derived from milk: production and applications.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2002
  13. Antimicrobial Activity of Lactoferrin-Related Peptides and Applications in Human and Veterinary Medicine(opens in a new tab)
    Tier 2Web · mdpi.com
  14. Lactoferricin - an overview | ScienceDirect Topics(opens in a new tab)
    Tier 2Web · sciencedirect.com
  15. Lactoferrin in health and disease: A review of its bioavailability and evidence-based benefits across study models(opens in a new tab)
    Tier 2Web · sciencedirect.com
  16. Bovine lactoferrin suppresses the proliferation of endometriotic stromal cells via the PI3K/Akt/mTOR pathway.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2025
  17. Digestive Profiles of Human Milk, Recombinant Human and Bovine Lactoferrin: Comparing the Retained Intact Protein and Peptide Release - PubMed(opens in a new tab)
    Tier 2Web · pubmed.ncbi.nlm.nih.gov · 2024
  18. Strain-specific Antimicrobial Activity of Lactoferrin-based Food Supplements.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2023
  19. Antiviral Effect of Bovine Lactoferrin against Enterovirus E.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2022
  20. The-glycans of lactoferrin: more than just a sweet decoration.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2021
  21. Lactoferrin: Major Physiological Functions and Applications.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2019
  22. Quality control of commercial bovine lactoferrin.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2018
  23. Lactoferrin from Milk: Nutraceutical and Pharmacological Properties.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2016
  24. Structural heterogeneity and multifunctionality of lactoferrin.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2014
  25. Bovine lactoferrin, human lactoferrin, and bioactivity.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2011
  26. Antimicrobial peptides of lactoferrin.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 1994
  27. Full article: Potential health benefits of lactoferrin and derived peptides(opens in a new tab)
    Tier 3Web · tandfonline.com
  28. Lactoferrin: Health Benefits, Side Effects, Uses, Dose & Precautions(opens in a new tab)
    Tier 3Web · rxlist.com
  29. Lactoferrin: Supplement Benefits and Side Effects(opens in a new tab)
    Tier 3Web · verywellhealth.com
  30. Lactoferrin: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD(opens in a new tab)
    Tier 3Web · webmd.com

See something wrong or out of date on this page? Report it.