Life Extension Magazine May 2014
Weight Loss Benefits of Lactoferrin
By Monica Mollica & Will Brink
Lactoferrin is well known for its immune-supportive properties.1-3 Surprising new research is uncovering an unexpected benefit—that lactoferrin might help humans shed body fat as well.
Lactoferrin’s ability to reduce body fat was first discovered at the cellular level. In these studies, researchers found that lactoferrin can help fight against obesity by inhibiting the accumulation of fat in fat cells and by inhibiting the formation of new fat cells (a process called adipogenesis ).3,4
A follow-up study investigating the molecular mechanism behind these results showed that lactoferrin works by inhibiting fat synthesis and stimulating liberation of stored body fat (a process called lipolysis).5 These are important findings with direct relevance for the well-documented expanding waist lines in Americans of all ages,6-8 and its ensuing detrimental health consequences.7,9-13
Lactoferrin For Fat Loss
The potential anti-obesity effect of lactoferrin was confirmed in obese mice, when researchers found that a lactoferrin-rich diet resulted in increased fat loss.14 Another study in mice found that a lactoferrin-rich whey protein isolate prevents obesity by inhibiting weight gain, and fights obesity by enhancing fat loss.15 During spontaneous feeding (when mice were not calorie restricted), the lactoferrin-rich whey protein isolate prevented weight gain and fatty liver formation. During a calorie-restricted diet, the lactoferrin-rich whey protein isolate enhanced fat loss.15
New research is showing that lactoferrin might help humans shed body fat as well. One indicator is that higher blood levels of lactoferrin are associated with lower BMI (body mass index, an indicator of obesity), lower waist-to-hip ratio, and lower fasting triglyceride (blood fat) and glucose concentrations.16,17
A number of studies confirm this finding as well. In one notable study, healthy men and women between 22 and 60 years old supplemented with 300 mg of lactoferrin tablets a day for 8 weeks.18 Subjects were told to maintain their regular food habits. Compared to the placebo group, the group taking the lactoferrin supplement experienced a significant 12.3% reduction in intra-abdominal (visceral) fat.18 The lactoferrin group also showed significant decreases in body weight (-3.3 lb), BMI (-0.6), hip circumference (-1 inch), and waist circumference (-1.7 inches). The placebo group, on the other hand, gained 2.2 pounds.
The researchers concluded that lactoferrin appears to be a promising supplement for counteracting the accumulation of belly fat.
Another Fat Fighting Target Of Lactoferrin
Another way lactoferrin can help in the fight against obesity and its associated metabolic and cardiovascular complications is by decreasing the risk of a condition called metabolic endotoxemia.
Metabolic endotoxemia is a condition characterized by two- to three-fold increases in blood lipopolysaccharide (LPS) levels.19,20 Lipopolysaccharide is an endotoxin, a toxin produced by certain bacteria.19
Unhealthy food habits (like the typical Western diet high in fat and processed foods, and low in fiber) increase the production, absorption, and blood levels of lipopolysaccharide (LPS), which in turn increase the risk of metabolic endotoxemia.19-21
This is important because elevated blood levels of lipopolysaccharide and metabolic endotoxemia can result in insulin resistance andobesity.19,22 In addition, metabolic endotoxemia produces low-grade inflammation that can damage many organs in the body.22-25
By binding to and sequestering lipopolysaccharide,26,27 lactoferrin and its metabolites help prevent the development of metabolic endotoxemia and can help relieve an already established metabolic endotoxemia condition.
Metabolic endotoxemia represents a molecular link between obesity and the diseases related to it.
Further evidence for the involvement of metabolic endotoxemia in the development of obesity is the finding that it directly stimulates the formation of new fat cells.28 Thus, lactoferrin might inhibit new fat cell formation via several different mechanisms.3,4
Lactoferrin’s Role As A Prebiotic
In addition to fighting obesity and protecting against metabolic endotoxemia, lactoferrin also has a number of actions that contribute to a healthy gut.
First, it inhibits the growth of bacteria that produce bacterial toxins, such as Listeria, Staphylococcus, Salmonella, Clostridium, and Escherichia coli.29-33 Research has shown that lactoferrin supplementation reduces both intestinal levels of toxins (such as lipopolysaccharide) produced by bacteria, protects against lipopolysaccharide-induced immune cell stress, and down-regulates production of harmful reactive nitrogen species.34,35
Lactoferrin stimulates the growth of several strains of good bacteria in the gut, such as various species of Bifidobacteria.36-38 A recent study found that digestion of lactoferrin in the stomach releases a peptide that has an even stronger bifidogenic (bifidobacteria growth promoting) effect than intact lactoferrin.39 Lactoferrin also stimulates the growth of Lactobacillus acidophilus .37 Since Lactobacilli and Bifidobacteria both promote a healthy gut flora, this might provide an even greater health benefit.40,41
Lactoferrin Helps Prevent Osteoporosis
There is a growing interest in the scientific community regarding the potential therapeutic use of lactoferrin in osteoporosis. In fact, a number of recent studies have found that lactoferrin supplementation improved bone mineral density and bone strength.42
Since osteoporosis primarily affects postmenopausal women, researchers investigated the effect of lactoferrin supplementation on bone parameters using rodents with surgically removed ovaries as a model for post-menopausal bone loss. The studies revealed that dietary lactoferrin promoted an increase in biomarkers of bone formation, decrease in biomarkers of bone resorption, and improvements in bone microarchitecture.43-45
Similar benefits have been found in humans as well. In a clinical study, 38 healthy postmenopausal women between 45 and 60 years old received a lactoferrin dietary supplement or placebo.46 The researchers monitored bone health status by assessing blood markers of bone breakdown (resorption) and of bone formation. They discovered that lactoferrin supplementation significantly reduced bone breakdown and increased bone formation, moving toward restoring the balance of bone turnover in just six months.46
This is the first demonstration in a clinical study that lactoferrin has a favorable effect on biomarkers of bone turnover in postmenopausal women, and confirms the findings previously seen in cell culture and rodent studies.
Recent evidence has shown that lactoferrin helps prevent osteoporosis by acting as an anabolic and anti-catabolic agent in bone tissue42,43,47 and by stimulating bone growth and healing.47 Studies have shown that lactoferrin potently induces the growth of bone forming cells called osteoblasts, while inhibiting the growth and activity of osteoclasts, another type of bone cell that breaks down bone tissue.42,47,48
Lactoferrin continues to demonstrate a wide range of potential benefits to humans. It has well-documented anti-infective, immune strengthening, anti-inflammatory, and anti-cancer effects.49
New research is showing that lactoferrin might be an effective weight-loss agent that also can help maintain a healthy gut flora. Lactoferrin is also a potent anabolic agent that stimulates bone growth and bone repair, and helps in prevention of osteoporosis.42,43,47,48
Lactoferrin is a natural component of both human breast milk and cow’s milk, which are ingested by infants. It is considered to be very safe and bovine lactoferrin has been granted GRAS (generally recognized as safe) status in the US.50
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
- Actor JK, Hwang SA, Kruzel ML. Lactoferrin as a natural immune modulator. Curr Pharm Des. 2009;15(17):1956-73.
- Legrand D, Elass E, Carpentier M, Mazurier J. Lactoferrin: a modulator of immune and inflammatory responses. Cell Mol Life Sci. 2005 Nov;62(22):2549-59.
- Moreno-Navarrete JM, Ortega FJ, Ricart W, Fernandez-Real JM. Lactoferrin increases (172Thr)AMPK phosphorylation and insulin-induced (p473Ser)AKT while impairing adipocyte differentiation. Int J Obes (Lond). 2009 Sep;33(9):991-1000.
- Yagi M, Suzuki N, Takayama T, et al. Lactoferrin suppress the adipogenic differentiation of MC3T3-G2/PA6 cells. J Oral Sci. 2008 Dec;50(4):419-25.
- Ono T, Fujisaki C, Ishihara Y, et al. Potent lipolytic activity of lactoferrin in mature adipocytes. Biosci Biotechnol Biochem. 2013;77(3):566-71.
- Conceicao-Machado ME, Silva LR, Santana ML, et al. Hypertriglyceridemic waist phenotype: association with metabolic abnormalities in adolescents. J Pediatr (Rio J). 2013 Jan-Feb;89(1):56-63.
- Carlsson AC, Riserus U, Arnlov J. Hypertriglyceridemic waist phenotype is associated with decreased insulin sensitivity and incident diabetes in elderly men. Obesity (Silver Spring). 2013 Mar 20.
- Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002 Jan 16;287(3):356-9.
- Alavian SM, Motlagh ME, Ardalan G, Motaghian M, Davarpanah AH, Kelishadi R. Hypertriglyceridemic waist phenotype and associated lifestyle factors in a national population of youths: CASPIAN Study. J Trop Pediatr. 2008 Jun;54(3):169-77.
- Polotsky HN, Polotsky AJ. Metabolic implications of menopause. Semin Reprod Med. 2010 Sep;28(5):426-34.
- Vieira DC, Tibana RA, Tajra V, et al. Decreased functional capacity and muscle strength in elderly women with metabolic syndrome. Clin Interv Aging. 2013;8:1377-86.
- Blackburn P, Lemieux I, Lamarche B, et al. Hypertriglyceridemic waist: a simple clinical phenotype associated with coronary artery disease in women. Metabolism. 2012 Jan;61(1):56-64.
- Blackburn P, Lemieux I, Alméras N, et al. The hypertriglyceridemic waist phenotype versus the National Cholesterol Education Program-Adult Treatment Panel III and International Diabetes Federation clinical criteria to identify high-risk men with an altered cardiometabolic risk profile. Metabolism. 2009 Aug;58(8):1123-30.
- Pilvi TK, Harala S, Korpela R, Mervaala EM. Effects of high-calcium diets with different whey proteins on weight loss and weight regain in high-fat-fed C57BL/6J mice. Br J Nutr. 2009 Aug;102(3):337-41.
- Shia J, Tauriainena E, Martonen E. Whey protein isolate protects against diet-induced obesity and fatty liver formation. Int Dairy J. 2011;21:513–22.
- Moreno-Navarrete JM, Ortega FJ, Bassols J, Castro A, Ricart W, Fernandez-Real JM. Association of circulating lactoferrin concentration and 2 nonsynonymous LTF gene polymorphisms with dyslipidemia in men depends on glucose-tolerance status. Clin Chem. 2008 Feb;54(2):301-9.
- Moreno-Navarrete JM, Ortega FJ, Bassols J, Ricart W, Fernandez-Real JM. Decreased circulating lactoferrin in insulin resistance and altered glucose tolerance as a possible marker of neutrophil dysfunction in type 2 diabetes. J Clin Endocrinol Metab. 2009 Oct;94(10):4036-44.
- Ono T, Murakoshi M, Suzuki N, et al. Potent anti-obesity effect of enteric-coated lactoferrin: decrease in visceral fat accumulation in Japanese men and women with abdominal obesity after 8-week administration of enteric-coated lactoferrin tablets. Br J Nutr. 2010 Dec;104(11):1688-95.
- Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007 Jul;56(7):1761-72.
- Neves AL, Coelho J, Couto L, Leite-Moreira A, Roncon-Albuquerque R, Jr. Metabolic endotoxemia: a molecular link between obesity and cardiovascular risk. J Mol Endocrinol. 2013;51(2):R51-64.
- Mani V, Hollis JH, Gabler NK. Dietary oil composition differentially modulates intestinal endotoxin transport and postprandial endotoxemia. Nutr Metab (Lond). 2013;10(1):6.
- Manco M, Putignani L, Bottazzo GF. Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk. Endocr Rev. 2010 Dec;31(6):817-44.
- Suganami T, Tanimoto-Koyama K, Nishida J, et al. Role of the Toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages. Arterioscler Thromb Vasc Biol. 2007 Jan;27(1):84-91.
- Puppa MJ, White JP, Sato S, Cairns M, Baynes JW, Carson JA. Gut barrier dysfunction in the Apc(Min/+) mouse model of colon cancer cachexia. Biochim Biophys Acta. 2011 Dec;1812(12):1601-6.
- Stoll LL, Denning GM, Weintraub NL. Potential role of endotoxin as a proinflammatory mediator of atherosclerosis. Arterioscler Thromb Vasc Biol. 2004 Dec;24(12):2227-36.
- Wakabayashi H, Takase M, Tomita M. Lactoferricin derived from milk protein lactoferrin. Curr Pharm Des. 2003;9(16):1277-87.
- Latorre D, Berlutti F, Valenti P, Gessani S, Puddu P. LF immunomodulatory strategies: mastering bacterial endotoxin. Biochem Cell Biol. 2012 Jun;90(3):269-78.
- Luche E, Cousin B, Garidou L, et al. Metabolic endotoxemia directly increases the proliferation of adipocyte precursors at the onset of metabolic diseases through a CD14-dependent mechanism. Mol Metab. 2013;2(3):281-91.
- Bullen JJ. Iron-binding proteins and other factors in milk responsible for resistance to Escherichia coli. Ciba Found Symp. 1976(42):149-69.
- Murdock CA, Cleveland J, Matthews KR, Chikindas ML. The synergistic effect of nisin and lactoferrin on the inhibition of Listeria monocytogenes and Escherichia coli O157:H7. Lett Appl Microbiol. 2007 Mar;44(3):255-61.
- Tian H, Maddox IS, Ferguson LR, Shu Q. Influence of bovine lactoferrin on selected probiotic bacteria and intestinal pathogens. Biometals. 2010 Jun;23(3):593-6.
- Tomita S, Shirasaki N, Hayashizaki H, Matsuyama J, Benno Y, Kiyosawa I. Binding characteristics of bovine lactoferrin to the cell surface of Clostridium species and identification of the lactoferrin-binding protein. Biosci Biotechnol Biochem. 1998 Aug;62(8):1476-82.
- Chen PW, Jheng TT, Shyu CL, Mao FC. Antimicrobial potential for the combination of bovine lactoferrin or its hydrolysate with lactoferrin-resistant probiotics against foodborne pathogens. J Dairy Sci. 2013 Mar;96(3):1438-46.
- Griffiths EA, Duffy LC, Schanbacher FL, et al. In vivo effects of bifidobacteria and lactoferrin on gut endotoxin concentration and mucosal immunity in Balb/c mice. Dig Dis Sci. 2004 Apr;49(4):579-89.
- Tian H, Maddox IS, Ferguson LR, Shu Q. Evaluation of the cytoprotective effects of bovine lactoferrin against intestinal toxins using cellular model systems. Biometals. 2010 Jun;23(3):589-92.
- Petschow BW, Talbott RD, Batema RP. Ability of lactoferrin to promote the growth of Bifidobacterium spp. in vitro is independent of receptor binding capacity and iron saturation level. J Med Microbiol. 1999 Jun;48(6):541-9.
- Kim WS, Ohashi M, Tanaka T, et al. Growth-promoting effects of lactoferrin on L. acidophilus and Bifidobacterium spp. Biometals. 2004 Jun;17(3):279-83.
- Rahman MM, Kim WS, Ito T, Kumura H, Shimazaki K. Growth promotion and cell binding ability of bovine lactoferrin to Bifidobacterium longum. Anaerobe. 2009 Aug;15(4):133-7.
- Oda H, Wakabayashi H, Yamauchi K, et al. Isolation of a bifidogenic peptide from the pepsin hydrolysate of bovine lactoferrin. Appl Environ Microbiol. 2013 Mar;79(6):1843-9.
- Boesten RJ, de Vos WM. Interactomics in the human intestine: Lactobacilli and Bifidobacteria make a difference. J Clin Gastroenterol. 2008 Sep;42 Suppl 3 Pt 2:S163-7.
- Kleerebezem M, Vaughan EE. Probiotic and gut lactobacilli and bifidobacteria: molecular approaches to study diversity and activity. Annu Rev Microbiol. 2009;63:269-90.
- Cornish J, Naot D. Lactoferrin as an effector molecule in the skeleton. Biometals. 2010 Jun;23(3):425-30.
- Blais A, Malet A, Mikogami T, Martin-Rouas C, Tome D. Oral bovine lactoferrin improves bone status of ovariectomized mice. Am J Physiol Endocrinol Metab. 2009 Jun;296(6):E1281-8.
- Malet A, Bournaud E, Lan A, Mikogami T, Tome D, Blais A. Bovine lactoferrin improves bone status of ovariectomized mice via immune function modulation. Bone. 2011 May 1;48(5):1028-35.
- Guo HY, Jiang L, Ibrahim SA, et al. Orally administered lactoferrin preserves bone mass and microarchitecture in ovariectomized rats. J Nutr. 2009 May;139(5):958-64.
- Bharadwaj S, Naidu AG, Betageri GV, Prasadarao NV, Naidu AS. Milk ribonuclease-enriched lactoferrin induces positive effects on bone turnover markers in postmenopausal women. Osteoporos Int. 2009 Sep;20(9):1603-11.
- Cornish J, Palmano K, Callon KE, et al. Lactoferrin and bone; structure-activity relationships. Biochem Cell Biol. 2006 Jun;84(3):297-302.
- Cornish J, Callon KE, Naot D, et al. Lactoferrin is a potent regulator of bone cell activity and increases bone formation in vivo. Endocrinology. 2004 Sep;145(9):4366-74.
- Available at: http://www.nrcresearchpress.com/doi/abs/10.1139/o06-054#.UufdcXko4dU. Accessed January 28, 2014.
- Available at: http://www.efsa.europa.eu/en/efsajournal/doc/2701.pdf. Accessed January 28, 2014.
- Leon-Sicairos N, Lopez-Soto F, Reyes-Lopez M, Godinez-Vargas D, Ordaz-Pichardo C, de la Garza M. Amoebicidal activity of milk, apo-lactoferrin, sIgA and lysozyme. Clin Med Res. 2006 Jun;4(2):106-13.
- Norrby K. Human apo-lactoferrin enhances angiogenesis mediated by vascular endothelial growth factor A in vivo. J Vasc Res. 2004 Jul-Aug;41(4):293-304.
- Yoo YC, Watanabe S, Watanabe R, Hata K, Shimazaki K, Azuma I. Bovine lactoferrin and lactoferricin inhibit tumor metastasis in mice. Adv Exp Med Biol. 1998;443:285-91.
- Superti F, Ammendolia MG, Valenti P, Seganti L. Antirotaviral activity of milk proteins: lactoferrin prevents rotavirus infection in the enterocyte-like cell line HT-29. Med Microbiol Immunol. 1997 Oct;186(2-3):83-91.