| |
Mother's Milk
Products from Nature have a long and
intriguing history of providing man with useful materials for his
daily life. None is more important than the medium-chain fats found
in mother's milk. Mention was made in Sanskrit medicine that freshly
expressed human milk was routinely used as an "antibiotic" after
eye surgery. Research in our laboratory discovered that the most
active lipid ingredient (monolaurin) was accountable for these antimicrobial
effects.
Early Role of Mother's Milk As A Nutriceutical
By definition, a nutriceutical is a functional food that has
nutritional/caloric value and pharmacological (drug) effects.
Hippocrates (Greek physician, circa 460-377 B.C.) recognized this truism
when he declared "Let thy food be your medicine and your medicine thy
food". Historically mother's milk must be considered the first nutriceutical. Mother's milk not only provides the infant with important
nutrients for growth and development but also it also contains
substances, which have antimicrobial, antiviral and other protective
properties.
This concept of human milk having sanitizing effects was recognized
early in human medicine. In the history of cataract surgery that extends
back at least 3000 years, the translation of Hindu manuscripts gives
detailed methods of the great surgeon Susruta. He described principles
of surgery based on anatomic dissection. He practiced asepsis (fumigated
the operating room with sweet vapors) and gave an excellent account of
his technique of couching (depression of the lens into the vitreous) as
well as an outline of postoperative care. After couching the milk of a
nursing mother would be distributed into the eyes conjunctiva much in
the way that antiseptics are used presently after an operation.
Unfortunately, this knowledge was buried with the rise of Buddhism and
the caste system of the Brahmins, who forbade dissection, and the
shedding of blood. The surgeon gave way to the priests and the brilliant
discoveries of the Hindus did not pass down to the Greeks or Egyptians.
The knowledge that mother's milk acted as an antiseptic agent was lost
until recently (Fieldsteel, 1974). He found that the cream but not the
skim milk was biologically active after heating. Kabara et al (circa
1968) evaluating the structure-function properties of lipids found that
certain fatty acids and more particularly their monoglycerides were
antimicrobial. Tri- and diglycerides were shown not to be active. It was
evident from these two studies that the non-protein portion of human
milk was also biologically active since of the formation of fatty acids
and monoglycerides from the lipolysis of milk fats (triglycerides). The
human baby however does not posses lipases at birth while the calf is
able at birth to have lipase activity on its own. Thus, human milk, in
contrast to bovine milk, needs accompanying lipases from the mother to
change by predigesting the inactive fat (triglycerides) into active
antimicrobial fatty acids and monoglycerides.
While protein macromolecules and humoral factors are all-important
antiinfecting properties of mother's milk, emphasis here will be the
discussion of the fat content of mothers milk. As will be shown in this
discussion the fat content in human milk, specifically the medium-chain
lipids ( monolaurin), is important to its' nutriceutical activity.
Fatty Acids and Monoglycerides as Antimicrobial Agents
Fatty acids have a long history of use as antimicrobial agents. Soaps
(i.e., salts of fatty acids) have been used as cleaning and disinfecting
agents for centuries. Before 1930, the lack of success in the search for
active antibacterial agents other than fatty acids resulted in pessimism
as to whether any other active agent would ever be found.
Two important discoveries, however, occurred around this time (circa
1930). First, was the serendipitous finding by Alexander Fleming. In
1928, Fleming observed the breakdown (Iysis) of Staphylococcus bacterial
colonies in an area surrounding the growth of Penicillium mold. From
this observation new biochemical structures, called antibiotics, were
added to the small arsenal of organic and inorganic compounds lethal to
microorganisms. Second, was the discovery of antimicrobial sulfonamides,
first observed by Trefouel, Nitti, and Boret in Fourneau's laboratory
(Pasteur Institute) in 1935. This gave new hope for finding new and more
effective synthetic biocidal agents. These two important discoveries in
less than a decade apart gave tremendous impetus to the search for new
antimicrobial agents.
The biocidal activity of the newly isolated antibiotics and
synthesized germicides was much greater than that of fatty acids. In
proportion to the speed with which new and more powerful antibiotics and
synthetic useful products were discovered, interest in fatty acids as
biocides waned. The use of these more powerful "magic bullets" was
accompanied by complications. First, antibiotics and synthetic
germicides are not without health risks in terms of toxicity and
irritation; second the cost of these newer agents precluded their use by
low income people and third and most important, the improper use of
these germicides caused resistant organisms to appear. Today the problem
has reached critical proportions.
Today because of these shortcomings, new approaches, even those based
on old technologies, need to be reexamined. This included fatty acids,
which even today play an important role in food preservation. Many fatty
acids more active than the old standbys such as vinegar (i.e. about 4%
acetic acid (C2:0) from ancient Egypt) have been discovered. Sorbic acid
(C 6: 2) isolated from rowanberry oil and reported in 1859 by Hoffman,
the aromatic benzoic acid discovered by Fleck, and propionic (C 3:0)
acid have been found to be useful in food preservation. Detailed studies
dealing with structure-antimicrobial effects of lipid derivatives, fatty
acids and their corresponding monoesters, have been published by Kabara
in an American Oil Chemists' Society monograph (The Pharmacological
Effects of Lipids, Volume I).
Much of the modern research on the germicidal activity of fatty acids
was concluded between 1920 to 1940. More up-to-date studies have been
reviewed (Kabara 1978,1984 and 1997). The term "antimicrobial" is also
intended to cover antibacterial, -yeast and -viral effects. It has will
be shown that enveloped viruses, as Herpes and others, can be
inactivated as other microorganisms by treatment with specific fatty
acids. Thus, the relationships found for chain length, degree and kind
of unsaturation (cis or trans) found for fatty acids against bacteria
were shown to be similar to activity later found for viruses.
The antimicrobial activity for fatty acids found in mother's milk
against some common microorganisms is given in Table 1. See also Welsch
et al, 1979, 1981; Clarke and May (2000).
Table 1 Minimal Inhibitory Concentrations(mM) of Fatty acids
found in mother's milk
| Fatty acid |
Staphylococcus
Aureus |
Streptococcus
Group A |
Candida
albicans |
| Capric (C10, 2.0%)* |
2.90 |
1.45 |
2.90 |
| Lauric (C12, 10%) |
2.49 |
0.12 |
2.49 |
| Mvristic (C14, 6.0%) |
4.37 |
0.55 |
4.37 |
| PaImitic (C16, 22%) |
Nl |
3.90 |
Nl |
| Stearic (C18, 8.0%) |
Nl |
Nl |
Nl |
| Oleic (C18:1, 32%) |
Nl |
1.77 |
Nl |
| Linoleic
(C18:2, 15%) |
Nl |
0.09 |
0.46 |
| Linolenic(C18:3, 0.1%) |
1.79 |
0.35 |
Nl |
* Approximate concentration in mother's milk Nl, not inhibitory at
the concentrations tested (1.0 mg/ml.)
Milk fatty acids also killed L. Monocytogenes in a dose?dependent
manner whereas much less killing of Salmonella (a gram-negative
organisms) was observed (Sprong et al, 1999). The antimicrobial effects
of individual fatty acids depended on concentration and chain length.
The rank order found for human milk fatty acids was
C 14: 0 <C 18: 2 <C
IO: O <C 18: 1 <C 12: 0
The long?chain saturated fatty acids C16: 0 and
C18: 0 as well as the shorter chain C4: 0, C6: 0, and C8: 0 were not
active under these same concentrations.
Monoglycerides As Antimicrobial
Agents
A fatty acid esterified with glycerin always increased its
antimicrobial activity. Kabara extensively published details of these
findings (Kabara, 1978). In all cases our conclusions of relating
chemical structure to antimicrobial activity were solidly based so that
later authors, many of whom never referred to our earlier papers,
confirmed these structure-function relationships.
Isaacs et al (1991) added lipids previously shown to have antiviral
and antibacterial activity by Kabara to human milk, bovine milk, and
infant formulas to determine whether increased protection from infection
could be provided to infants as part of their diet. Again fatty acids
and monoglycerides with chain lengths varying from 8 to 12 carbons were
found to be more strongly antiviral and antibacterial when added to milk
than long chain monoglycerides. Since both cow's milk and artificial
human milk are devoid of antimicrobial activity such studies suggest
that increased protection from infection may be provided to infants at
mucosal surfaces by the addition of antimicrobial medium chain
monoglycerides to an infant's diet. Fatty acids should not be used in
these instances since they are known to be irritating to mucosal tissue.
Antiviral Effects of Monoglycerides
The same structure-function relationships that were initially
discovered against various bacteria, yeast, and fungi were likewise
found for lipid-containing bacteriophages/viruses.
Hierholzer and Kabara (1982) reported on the antiviral aspects of
monolaurin (Lauricidin®). These studies involved selected virus
prototypes or recognized representative strains of human viruses. They
elucidated virucidal effects of monolaurin on enveloped RNA and DNA
viruses. Viruses that have a lipid membrane were especially vulnerable
to lauric acid and its derivative monolaurin. This work was done at the
Center for Disease Control of the U.S. Public Health Service.
Some of the viruses inactivated by these lipids are the measles
virus, herpes simplex virus-1 (HSV-1) and virus-2(HSV-2), herpes family
members (HIV, hepatitis C ...), vesicular stomatitis virus (VSV), visna
virus, and cytomegalovirus (CMV). Many of the pathogenic organisms
inactivated by monolaurin are those known to be responsible for
opportunistic infections in HIV-positive individuals. For example,
concurrent infection with cytomegalovirus is recognized as a serious
complication for HIV positive individuals. For a summary of the kind of
pathogens inactivated by monolaurin from mother's milk
(click here).
A number of fungi, yeast, and protozoa are inactivated or killed by
monolaurin. The fungi include several species of ringworm (Isaacs et al
1991). The yeast reported is Candida albicans (Isaacs et al 1991). The
protozoan parasite Giardia lamblia, responsible for diarrhea in babies,
is killed by monoglycerides from hydrolyzed human milk ( Reiner et al
1986, Crouch et al 1991, Isaacs et al 1991). Chlamydia trachomatis is
also inactivated by (Bergsson et al 1998), and hydrogels containing
monocaprin/monolaurin are potent in vitro inactivators of sexually
transmitted viruses such as HSV-2 and HIV-1 and bacteria such as
Neisseria gonorrhea.
Most important and different from drug antibiotics is the fact that
there appears to be very little development of resistance in organisms
to the bactericidal effects of these natural antimicrobial lipids
(Petschow et al 1996). In fact monolaurin has been shown to reduce or
prevent resistance of organisms to certain antibiotics.
The Role of Lipids on Microbial Resistance
Present data based on medium chain fatty acids (MCFA's) and medium
chain monoglycerides (MCM's) may ideally become part of the solution to
antibiotic resistance.
Using an antibiotic-resistant(R) and an antibiotic-sensitive (S)
strain of P. aeruginosa, Vadehra and Wahi(1985) found that the minimum
inhibitory concentration (MIC) for lauricidin® (a highly purified
monolaurin) was 165 and 75 ug/ml, respectively. The MlC values for
butylated hydroxyanisole (BHA) against the same organism was 210-and115
ug/ml, respectively. Testing R and S strains of S. aureus, the MIC value
were 20 and 10 µg/ml respectively, and 150 and 110 ug/ml for BHA. With
both test organisms there was more leakage of the intracellular contents
from S cells as compared to R cells. The involvement of the membrane as
the site of action was also confirmed by the extensive leakage of
hemoglobin from human and animal erythrocytes.
Flournoy (1985) found that over 100 Oxacillin-resistant Staphylococci
all had the same MIC and MBC values to Lauricidin®. This indicates that
antibiotic resistance can be over come by the use of this monolaurin.
Monolaurin inhibited the induction of vancomycin resistance in
Enterococcus faecalis. This non-toxic lipid was found to repress the
post-exponential phase activation of virulence factor production and the
induction of beta-lactamase in Staphylococcus aureus. It has been
suggested that signal transduction is the most probable target for
monolaurin action. Monolaurin suppresses growth of vancomycin-resistant
Enterococcus faecalis on plates with vancomycin and blocks the induction
of vancomycin resistance.
Conclusions
Thus, it would appear to be important to investigate the practical
aspects and the potential benefit of using Lauricidin® for nutritional
support for microbial infected individuals. Until now no one in the
mainstream nutrition community seems to have recognized the added
potential of antimicrobial lipids in the treatment of infected patients.
The lipid-coated (envelope) viruses, bacteria and other microorganisms
are dependent on host lipids for their lipid constituents. The
variability of fatty acids in the foods of individuals as well as the
variability from de novo synthesis accounts for the variability of fatty
acids in their membranes. Putting special lipids like monolaurin into
our diet may have adverse effects on parasitic organisms.
Most important monolaurin does not appear to have an adverse effect
on desirable gut bacteria, but rather on only potentially pathogenic
microorganisms. For example, Isaacs et al (1991) reported major
inactivation of Hemophilus influenza, Staphylococcus epidermidis and
Group B gram positive Streptococcus. by monolaurin. The other
potentially pathogenic bacteria inactivated by monolaurin include
Listeria monocytogenes, Staphylococcus aureus, Streptococcus agalactiae,
gram-positive organisms, and some gram-negative organisms (Vibrio
parahaemolyticus and Helicobacter pylori). Monolaurin rapidly inactivate
the latter organism which is thought to cause gastric ulcers (Petschow
et al,1996)
While there are many studies and examples for the use of monolaurin (Lauricidin®)
as a topical antimicrobial agent, its systemic use for human infections
is only now being vigorously investigated. Human studies underway today
suggest that many antimicrobial effects found for monolaurin (Lauricidin®)
in the laboratory setting are being replicated clinically when used as a
dietary supplement. Individuals with genital Herpes, Hepatitis C, fungal
infections, autism etc.. are being helped as witnessed by testimonials
that are receive. While it is difficult to conduct double-blind
experiments for dietary supplements in the real world, anecdotal
positive reports from thousands of users indicate that serious
consideration should be given to Lauricidin® as an important supplement
for optimal health.
|
|