By Monica Mollica & Will Brink
As seen in The Life Extension Magazine May 2014 issue © 2014
Lactoferrin has been experiencing an increased interest by researchers and medical professionals, and rightly so: It’s shown an astounding array of potential benefits to human health and disease prevention. The wide range of potential health and disease fighting properties of lactoferrin are covered extensively in two prior articles “The Bioactive Peptide that Fights Disease” and a later update outlining recent research findings with additional research found . This article shows a recently discovered benefit of this unique peptide that were quite unexpected.
What Is Lactoferrin?
In a nut shell, Lactoferrin is a multi-functional peptide, derived from whey protein; in bovine milk it’s present at approximately 0.5-1.5% of total whey proteins 1, and 0.1 g/liter 2. In addition to its known anti-bacterial 3, anti-viral 4), immune strengthening 5, antioxidant 6, 7, anti-inflammatory 7 and cancer-preventive potential 8, recent studies have discovered novel targets of lactoferrin that can help with fat loss and improve insulin sensitivity and glucose control, which are also essential components to weight loss and overall health.
Lactoferrin for fat loss
A role for lactoferrin in reducing adiposity was first discovered in fat cell culture studies. It was found that lactoferrin specifically inhibits fat accumulation in fat cells, as well as formation of new fat cells (a process called adipogenesis) 9, 10.
The potential anti-obesity effect of lactoferrin has been shown in obese mice, where a lactoferrin rich diet resulted in increased fat loss 11. Another study on mice found that a lactoferrin rich whey protein isolate prevents obesity by dose- dependently preventing fat gain and fatty liver formation during spontaneous feeding, and enhancing fat los during a calorie restricted diet 12.
Research is showing that lactoferrin might help with fat loss in humans as well. Higher blood levels of lactoferrin are associated with lower BMI (an obesity indicator), waist-to-hip ratio and fasting triglyceride and glucose concentrations 13, 14. A notable study supplemented healthy men and women, aged 22–60 years, with 300 mg lactoferrin (enteric coated) tablets per day for 8 weeks 15. Subjects were told to maintain their regular food habits. It was found that the lactoferrin supplement, compared to placebo, resulted in a 12.4% significant reduction in intra-abdominal (visceral) fat 15. The lacroferrin group also showed significant decreases in body weight (-3.3 lb), BMI (-0.6) and hip circumference (-1 inch), while the placebo group instead gained 0.45 lb body weight. In addition, there was a 1.7 inch reduction in waist circumference in the lacroferrin group. It was concluded that lacroferrin appears to be a promising supplement for counteracting intra-abdominal fat accumulation.
Lactoferrin for improved insulin sensitivity and blood sugar control
There are also indications for a role for lactoferrin in the regulation of glucose control. In humans, higher blood levels of lactoferrin are associated with lower blood sugar levels and higher insulin sensitivity 14, and supplementing mice on high-fat diet with a lactoferrin rich whey protein isolate was found to improve glucose tolerance compared to the same diet supplemented with casein 12.
Metabolic endotoxemia – 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 binding to and inactivating an endotoxin called lipopolysaccharide 16. The gut houses a vast microbial community of diverse bacterial species 17, 18. Lipopolysaccharide is continuously produced by Gram-negative Intestinal bacteria, and absorbed in small quantities into the blood stream 19, 20. Unhealthy food habits, like the typical Western diet high in fat and processed foods, and low in fiber), can increase production, absorption and blood levels of lipopolysaccharide, and cause a condition called “metabolic endotoxemia” 19-21.
Metabolic endotoxemia is a condition characterized by two- to threefold increases in blood lipopolysaccharide levels 19, 20, and there are indications that it might initiate insulin resistance and obesity 19, 22. In addition, it elicits a chronic low-grade pro-inflammatory and pro-oxidative stress status that can damage organs in the body 23-25. Metabolic endotoxemia can thus represent a molecular link between obesity and its related diseases. This is supported by the recent finding that people with overweight, obesity, and metabolic syndrome (particularly, low HDL cholesterol levels) have higher lipopolysaccharide-binding protein levels 26. Lipopolysaccharide-binding protein might be a biomarker to indicate activation of the immune system in response to microbial compounds, particularly lipopolysaccharide 27-30. These findings are consistent with microbial exposure playing a role in these inflammatory, metabolic abnormalities 26.
Further evidence for the involvement metabolic endotoxemia in obesity development is the finding that it directly stimulates formation of new fat cells 31. Thus, lactoferrin might inhibit new fat cell formation via several different mechanisms 9, 10.
Lactoferrin continues to demonstrate a wide range of potential benefits to humans and now appears to be an effective weight loss agent. The precise dose of lactoferrin that’s optimal for fat loss in humans has yet to be fully studied, but 300-1000mg+ is good target dose until further studies are carried out, and the only side effect is likely to be improved health…
NOTE: It should be noted also that lactoferrin can come in two forms; called apo-lactoferrin (apo-LF) and halo-lactoferrin (halo-LF). One role of lactoferrin is to sequester and bind iron until it’s needed by the immune system to fight pathogens. Apo- lactoferrin is iron depleted. Halo-lactoferrin contains iron. Although studied suggest both forms are beneficial, Apo-LF appears to be the more potent of the two as it relates to a number of benefits seen with lactoferrin. The vast majority of companies that sell lactoferrin sell the Halo (iron saturated) from. The company I’d recommend for apo-LF form is the Life Extension Foundation but there may be others I’m not aware of.
1. Artym J, Zimecki M. Milk-derived proteins and peptides in clinical trials. Postepy Hig Med Dosw (Online). 2013;67:800-816.
2. Korhonen HJ. Bioactive milk proteins and peptides: from science to functional applications. Aust J Dairy Technol. 2009;64:16-21.
3. Tomita M, Bellamy W, Takase M, Yamauchi K, Wakabayashi H, Kawase K. Potent antibacterial peptides generated by pepsin digestion of bovine lactoferrin. J Dairy Sci. Dec 1991;74(12):4137-4142.
4. Harmsen MC, Swart PJ, de Bethune MP, et al. Antiviral effects of plasma and milk proteins: lactoferrin shows potent activity against both human immunodeficiency virus and human cytomegalovirus replication in vitro. J Infect Dis. Aug 1995;172(2):380-388.
5. Zimecki M, Wlaszczyk A, Cheneau P, et al. Immunoregulatory effects of a nutritional preparation containing bovine lactoferrin taken orally by healthy individuals. Arch Immunol Ther Exp (Warsz). 1998;46(4):231-240.
6. Shoji H, Oguchi S, Shinohara K, Shimizu T, Yamashiro Y. Effects of iron-unsaturated human lactoferrin on hydrogen peroxide-induced oxidative damage in intestinal epithelial cells. Pediatr Res. Jan 2007;61(1):89-92.
7. Fernandez-Real JM, Garcia-Fuentes E, Moreno-Navarrete JM, et al. Fat overload induces changes in circulating lactoferrin that are associated with postprandial lipemia and oxidative stress in severely obese subjects. Obesity (Silver Spring). Mar 2010;18(3):482-488.
8. Sekine K, Ushida Y, Kuhara T, et al. Inhibition of initiation and early stage development of aberrant crypt foci and enhanced natural killer activity in male rats administered bovine lactoferrin concomitantly with azoxymethane. Cancer Lett. Dec 23 1997;121(2):211-216.
9. 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). Sep 2009;33(9):991-1000.
10. Yagi M, Suzuki N, Takayama T, et al. Lactoferrin suppress the adipogenic differentiation of MC3T3-G2/PA6 cells. J Oral Sci. Dec 2008;50(4):419-425.
11. 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. Aug 2009;102(3):337-341.
12. Shia J, Tauriainena E, Martonen E. Whey protein isolate protects against diet-induced obesity and fatty liver formation. Int Dairy J. 2011;21:513–522.
13. 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. Feb 2008;54(2):301-309.
14. 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. Oct 2009;94(10):4036-4044.
15. 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. Dec 2010;104(11):1688-1695.
16. Wakabayashi H, Takase M, Tomita M. Lactoferricin derived from milk protein lactoferrin. Curr Pharm Des. 2003;9(16):1277-1287.
17. Sanz Y, Santacruz A, Gauffin P. Gut microbiota in obesity and metabolic disorders. Proc Nutr Soc. Aug 2010;69(3):434-441.
18. Jeffery IB, O’Toole PW. Diet-microbiota interactions and their implications for healthy living. Nutrients. Jan 2013;5(1):234-252.
19. Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. Jul 2007;56(7):1761-1772.
20. 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.
21. Mani V, Hollis JH, Gabler NK. Dietary oil composition differentially modulates intestinal endotoxin transport and postprandial endotoxemia. Nutr Metab (Lond). 2013;10(1):6.
22. Manco M, Putignani L, Bottazzo GF. Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk. Endocr Rev. Dec 2010;31(6):817-844.
23. 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. Jan 2007;27(1):84-91.
24. 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. Dec 2011;1812(12):1601-1606.
25. Stoll LL, Denning GM, Weintraub NL. Potential role of endotoxin as a proinflammatory mediator of atherosclerosis. Arterioscler Thromb Vasc Biol. Dec 2004;24(12):2227-2236.
26. Gonzalez-Quintela A, Alonso M, Campos J, Vizcaino L, Loidi L, Gude F. Determinants of serum concentrations of lipopolysaccharide-binding protein (LBP) in the adult population: the role of obesity. PLoS One. 2013;8(1):e54600.
27. Schumann RR. Old and new findings on lipopolysaccharide-binding protein: a soluble pattern-recognition molecule. Biochem Soc Trans. Aug 2011;39(4):989-993.
28. Hudgins LC, Parker TS, Levine DM, et al. A single intravenous dose of endotoxin rapidly alters serum lipoproteins and lipid transfer proteins in normal volunteers. J Lipid Res. Aug 2003;44(8):1489-1498.
29. Opal SM, Scannon PJ, Vincent JL, et al. Relationship between plasma levels of lipopolysaccharide (LPS) and LPS-binding protein in patients with severe sepsis and septic shock. J Infect Dis. Nov 1999;180(5):1584-1589.
30. Schumann RR, Latz E. Lipopolysaccharide-binding protein. Chem Immunol. 2000;74:42-60.
31. 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):281-291.