| Lactoferrin
Introduction
Lactoferrin is a fascinating biologically protein that is a key
component of human and bovine colostrum. It plays a critical role
in nourishing the newborn as well as protecting it from infection
via its immune enhancing and antimicrobial effects. Through modern
filtering technology, bovine lactoferrin can now be separated out
from cow’s milk. As a result there has been a virtual explosion
of research into this extremely valuable biological agent showing
a broad range of clinical applications.1,2
The name lactoferrin signifies that this compound is from milk
(lacto) and is able to bind iron (ferrin). Initially because of
its close resemblance to transferrin, research focused on lactoferrin’s
iron-binding properties and how that relates to its impact on iron
absorption, antimicrobial activity, and iron metabolism during inflammation.
For example, one of the ways in which lactoferrin inhibits the growth
of so many organisms is by making iron unavailable to these organisms.
However, recent research has shown lactoferrin to exert biological
activity via other means as well. Here are just some of the key
actions of lactoferrin:1,2
- Enhancement of immune function
- Antibacterial, antifungal, and antiviral properties
- Promotion of a healthy gut flora
- Regulation of iron metabolism
- Antioxidant effects
How does bovine lactoferrin compare
with human lactoferrin?
One of the first things that researchers discovered was that through
digestion in the human intestinal tract that bovine lactoferrin
is converted to compounds known as lactoferricins. These compounds
have been shown to be even more potent than human lactoferricins.3
Does lactoferrin affect iron metabolism?
Lactoferrin was first thought to play a role in iron absorption
in newborns, however, recent research seems to indicate that it
does not regulate iron metabolism in normal circumstances. Instead,
lactoferrin is able to enhance iron absorption and improve iron
status when iron stores are low as well as modulate iron metabolism
during infection and inflammation. In these latter situations iron
acts to add fuel to the fire, in the case of an infection iron stimulates
the growth of the infecting organism. In the case of inflammation,
free, unbound iron generates free radicals that damage body tissues.
By binding the iron, lactoferrin reduces the amount of free radicals
in the inflammatory environment. This action may turn out to be
particularly useful in sequestering free iron in the joints of people
with rheumatoid arthritis. Lactoferrin is definitely indicated in
people with elevated iron levels such as hemochromatosus.
What are lactoferrin’s antimicrobial
properties?
Lactoferrin exerts broad spectrum antimicrobial action as it has
been shown to be effective in inhibiting the growth of disease causing
protozoa, yeast, bacteria, and viruses. More important than actually
killing organisms, is the recent discovery that lactoferrin prevents
the attachment of disease causing organisms to cells that line the
mouth and entire gastrointestinal tract. At the same time, lactoferrin
is a powerful growth promoter of health promoting bacteria like
Bifidobacteria and Lactobacillus species. By preventing growth of
harmful bacteria while promoting the growth of beneficial bifidobacteria,
lactoferrin assists in the development of a proper intestinal flora.
In general, lactoferrin appears to be particularly important in
the health and function of the intestinal tract. Many clinicians
have found lactoferrin to greatly reduce intestinal inflammation
in such conditions as Crohn’s disease and ulcerative colitis.
Some research also suggests that lactoferrin is able to stimulate
intestinal cell growth and may lead to better digestive functions
in general.1,2
Are there any clinical studies showing
anti-infective actions?
Yes, research has focused on two areas; (1) the
treatment of peptic ulcers and digestive disturbances caused by
the bacteria Helicobacter pylori; and (2) chronic viral hepatitis.
H. pylori infection is very common in the United States: About 50
percent of people over 60 years have it. Although most infected
people do not develop ulcers, many may experience digestive disturbances
associated with H. pylori infection. H. pylori infection can lead
to a peptic ulcer because it weakens the protective mucous coating
of the stomach and duodenum. The standard medical treatment of H.
pylori infection is a 1- or 2-week course of treatment called triple
therapy. It involves taking two antibiotics to kill the bacteria
and an acid suppressor drug. Unfortunately, it does not resolve
digestive disturbances or heal ulcers in all patients and typically
involves taking as many as 20 pills a day. Also, mild side effects
such as nausea, vomiting, diarrhea, dark stools, metallic taste
in the mouth, dizziness, headache, and yeast infections are common.
Lactoferrin alone or in combination with triple
therapy may soon be the treatment of choice based upon the results
of recent clinical trials. In one study, 151 H. pylori positive
patients, suffering from indigestion symptoms were given either
triple therapy alone or with lactoferrin. H. pylori status assessed
8 weeks after the end of the treatment indicated a 95.9% eradication
rate for the group getting the lactoferrin while the other group
had only a 72.5% eradication rate.4
Is lactoferrin helpful in chronic
hepatitis?
Lactoferrin has shown direct antiviral effects
against hepatitis B and C virus. Preliminary clinical trials have
also shown beneficial effects in some people with patients with
chronic hepatitis C.5-8
The key is that it is most effective for people with lower viral
loads. People with moderate to high viral loads will need stronger
nutritional support like the Liver Health Formula and DetoxiTech
from Natural Factors.
Does lactoferrin exert immune
enhancing effects?
Yes, lactoferrin seems to exert a wide range of
effects on the immune system. Researches using various animals models
(i.e., rats, sheep, pigs and cats, as well as others) as well as
two human clinical trials on healthy subjects have found bovine
lactoferrin has direct effects on the regulation and modulation
of the immune system. While some of these effects may involve its
iron binding action, it has also shown effects unrelated to this
mechanism. In particular, lactoferrin has shown an ability to impact
of number of anticancer mechanism including regulating natural killer
cell activity; the expression of mediators of white blood cell function;
inhibit the formation of blood vessels to feed tumors; and enhancement
of cellular suicide of cancer cells.1,2,9,10
In perhaps the most significant human study, the
effect of oral administration of bovine lactoferrin vs. a placebo
was evaluated in patients after a surgery.11
Those taking the lactoferrin showed significant improvements in
a variety of parameters (e.g., the proliferative response of white
blood cells, the production of important immune system regulators,
and white blood cell counts). Perhaps the most interesting result
from the study was that the data presented revealed an increased
immune responsiveness in all patients treated with lactoferrin.
This result is significant as it suggests that lactoferrin can help
prevent the common occurrence of post-surgical infections.
What about antioxidant and anti-inflammatory
actions?
In addition to preventing iron-generated free radicals, there is
now a substantial amount of research lactoferrin directly regulates
the inflammatory response. One interesting mechanisms is lactoferrin’s
binding to bacterial endotoxins. These lipopolysaccharide components
of certain gut-derived bacteria are major stimulators of inflammation.
For example, the level of circulating endotoxins from the gut has
been shown to correlate with the severity of psoriasis and psoriatic
arthritis. These gut-derived toxins are among the major contributors
to the excessive cell replication in the skin and inflammation seen
throughout the body in people with psoriasis. By binding to these
compounds, lactoferrin may prove useful in conditions linked to
excessive absorption of endotoxins such as psoriasis, cirrhosis
of the liver, and symptoms of candida.12
Can lactoferrin be taken if people are
lactose sensitive or allergic to milk?
It depends upon the source of lactoferrin. If it is a highly purified
lactoferrin product like the one from Natural Factors, then it can
be taken with confidence by people with lactose-intolerance or milk
allergies.
Does lactoferrin contain iron?
Again, it depends upon the source of lactoferrin. The highly purified
lactoferrin product from Natural Factors is virtually free of iron
(less than 180 mcg per gram). This form of lactoferrin is referred
to as “apolactoferrin” as it is free of iron.
What is the proper dosage?
The dosage of lactoferrin varies from one manufacturer to another.
Most of the research on bovine lactoferrin has been on the highly
purified product. The dosage for this product is typically 250 to
500 mg one to three times per day. The dosage depends on an individual’s
size and indication. Lower dosages are for general health promotion,
children, and smaller individuals; higher dosages are for specific
indications and adults. For maximum absorption, lactoferrin should
be taken before meals or on an empty stomach.
Key References:
- Brock JH. The physiology of lactoferrin.
Biochem Cell Biol 2002;80(1):1-6.
- Lönnerdal B, Iyer S. Lactoferrin:
molecular structure and biological function. Annu Rev Nutr 1995;15,
93-110.
- Vorland LH, Ulvatne H, Andersen J,
et al. Lactoferricin of bovine origin is more active than lactoferricins
of human, murine and caprine origin. Scand J Infect Dis 1998;30(5):513-7.
- Di Mario F, Aragona G, Dal Bo N, et
al. Use of bovine lactoferrin for Helicobacter pylori eradication.
Dig Liver Dis 2003;35(10):706-10.
- Okada S, Tanaka K, Sato T, et al. Dose-response
trial of lactoferrin in patients with chronic hepatitis C. Jpn
J Cancer Res 2002;93(9):1063-9.
- Tanaka K, Ikeda M, Nozaki A, et al.
Lactoferrin inhibits hepatitis C virus viremia in patients with
chronic hepatitis C: a pilot study. Jpn J Cancer Res 1999;90(4):367-71.
- Hirashima N, Orito E, Ohba K, et al.
A randomized controlled trial of consensus interferon with or
without lactoferrin for chronic hepatitis C patients with genotype
1b and high viral load. Hepatol Res 2004;29(1):9-12.
- Ishii K, Takamura N, Shinohara M, et
al. Long-term follow-up of chronic hepatitis C patients treated
with oral lactoferrin for 12 months. Hepatol Res. 2003;25(3):226-233.
- Zimecki M, Wlaszczyk A, Cheneau P,
Brunel AS, et al. Immunoregulatory effects of a nutritional preparation
containing bovine lactoferrin taken orally by healthy individuals.
Arch Immunol Ther Exp 1998;46(4):231-40.
- Yamauchi K, Wakabayashi H, Hashimoto
S, et al. Effects of orally administered bovine lactoferrin on
the immune system of healthy volunteers. Adv Exp Med Biol 1998;443:261-5.
- Zimecki M, Wlaszczyk A, Wojciechowski
R, Dawiskiba J, Kruzel M. Lactoferrin regulates the immune responses
in post-surgical patients. Arch Immunol Ther Exp 2001;49(4):325-33.
- Zhang GH, Mann DM, Tsai CM. Neutralization
of endotoxin in vitro and in vivo by a human lactoferrin-derived
peptide. Infect Immun 1999;67(3):1353-8.
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