Anti-Inflammatory Diet

All health care starts with diet. My recommendations for a healthy diet are here:
Anti-Inflammatory Diet and Lifestyle.
There are over 190 articles on diet, inflammation and disease on this blog
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more articles by Prof. Ayers on Suite101 .

Saturday, May 16, 2009

Lactoferrin: Natural Anti-Microbial Milk Protein

Nosocomial infections happen when the immune system is compromised through a medical procedure and common bacteria, such as Staphlococcus aureus, get introduced. From my perspective, that means that the walking bacterial reservoirs, i.e. gut flora of healthcare practitioners, provide an inoculum directly to the damaged tissue, or indirectly by contaminating the patients gut flora and then spreading the pathogens from the patient’s digestive tract to the damage site. This is what happens with ventilator-associated pneumonia and sepsis in critically ill patients.

The trick is to keep the patient’s gut flora healthy -- healthy as a breastfed baby’s. The typical medical approach is to kill off lurking pathogens with a dose of antibiotics. The problem with this approach is that it is both indiscriminant and selective, i.e. it kills both pathogens and beneficial bacteria, but it also provides a selective advantage for the antibiotic resistant hospital strains of opportunistic pathogens.

Humor break: Why do babies spit up half-digested breastmilk and then smile? Answer: Pepsin produces antimicrobial peptides from milk proteins. The baby smugly acknowledges that she knows that she has just protected her upper respiratory and digestive tracts against bacterial pathogens.

Pepsin hydrolyzes proteins next to aromatic amino acids and away from the basic amino acids, arginine and lysine. That means that heparin-binding domains, which consist of groups of basic amino acids in a hydrophobic environment, are clipped out intact from proteins by pepsin. Thus, babies sucking down milk make their own isolated peptides with heparin-binding domains.

Lactoferricin with basic amino acids in blue.


Many organisms, from fruit flies to frogs to humans, produce anti-microbial peptides. They also produce proteins with nucleic acid-binding domains and nuclear localization signals and heparin-binding domains and IP3-binding domains. If all of those binding domains are clipped out by pepsin and the peptides are compared to the anti-microbial defensive peptides, amazingly they are all the same. All have groups of basic amino acids among hydrophobic neighbors, and all are toxic to bacteria.

Lactoferrin is a major component of milk whey. It binds iron and heparin. It can be digested by pepsin into an an anti-microbial peptide, lactoferricin. Baby’s smile and spit-up on your shoes when you say lactoferrin.

Transgenic mice that produce porcine lactoferrin in their milk, transfer extra lactoferrin their little suckling mouse pups and that extra lactoferrin gives extra protection against bacterial and yeast pathogens. That is the experimental justification to suggest that treating patients at risk of nosocomial infections (I guess that would mean every patient in contact with a nurse or doctor) with oral lactoferrin should selectively eliminate the pathogens. Lactoferrin is prebiotic and supports the growth of probiotic gut flora.

ref:
Yen CC, Lin CY, Chong KY, Tsai TC, Shen CJ, Lin MF, Su CY, Chen HL, Chen CM. Lactoferrin as a natural regimen for selective decontamination of the digestive tract: recombinant porcine lactoferrin expressed in the milk of transgenic mice protects neonates from pathogenic challenge in the gastrointestinal tract .J Infect Dis. 2009 Feb 15;199(4):590-8.

14 comments:

Dr. B G said...

Dr. Ayers,

My babies even had projectile vomiting -- inadvertently protecting a large area besides shoes against microbes. *ha*

What are good sources of lactoferrin in addition to breastmilk? Casein-free (for those allergic)?

Never thought much about heparin until I started reading your wonderful blog.

Thank you,
G

Dr. Art Ayers said...

G,
I know nothing about using lactoferrin for medical applications, other than what I read, but it is available in capsule form as a food supplement. It is very cheap and relatively pure, because it is a major component of milk whey. I don't know how much contaminating casein is present.

When I used bovine lactoferrin as a model heparin-binding protein, I purchased it as a food supplement at $.25 per 250 mg capsule (with added rice powder as filler.) It was trivial to purify by heparin sepharose affinity chromatograpy. Compare that to the biochemical form at $1 per mg.

Sorry I can't be more helpful.

Thanks for reading.
Art

Daniel said...

Isn't raw egg whites a good source of lactoferrin as well.

Dr. B G said...

Hi,

I appreciate your reply!

Also, is lactoferrin affected by heat? I wonder b/c so many immunoprotective peptides are heat-labile (eg, taurine in grassfed meat/wild seafood).

-G

Adolfo David said...

Congratulations for this blog. I am journalist on health in Europe. I believe strongly in antiinflamatory medicine. I go on years ago antiinflamatory Zone Diet with 3 grams EPA-DHA, 1500 IU vitamin D, and a spectrum of polyphenol supplements daily among others. I like and use sometimes supplements like Zyflammend for example. Since I live in Spain I have many terrific mediterranean foods here.

I am going to see if you have any mention maybe to Sears work/theories.

A hug from Europe!

Dr. Art Ayers said...

Dr. B G,
The lactoferrin protein is probably sensitive to heat, but the digested peptide, lactoferricin is small. I would predict that most of the small antimicrobial peptides don't have a stable structure that is needed for activity. Most of the heparin-binding domains are said to be unstructured, because they don't participate in protein secondary structure, i.e. alpha helices or beta sheets. They only have a stable structure in complexes with heparin.

Dr. Art Ayers said...

Daniel,
Egg white has somewhat different functions than milk, although it does have antibacterial components that degrade bacterial walls (lysozyme), or sequester iron (transferrin) or biotin (avidin). But it doesn't have lactoferrin. Some of the egg white proteins bind to heparin and should make antimicrobial peptides in the stomach. I don't expect egg white to be as prebiotic as milk.

Dr. Art Ayers said...

Adolfo David,
I got a lot of my original thoughts about omega-3 oils form Sears and his various Zone diets. I found that his perspective combined with Michael Pollan's agricultural views, provide a good idea of how US health has been systematically undermined by the various food industries and a complacent medical community.

I envy your access to Spanish cuisine.
Art

Daniel said...

Well, ovotransferrin and lactoferrin has about 50% sequence homology implying that they would share the same overall structure. No wonder that ovotransferrin also have bacteriostatic and bactericidal properties.

Cristian Stremiz said...

A protein that plays a key role in tumor formation, oxygen metabolism and inflammation is involved in a pathway that extends lifespan by dietary restriction.

The finding, which appears in the May 22, 2009 edition of the on-line journal PLoS Genetics, provides a new understanding of how dietary restriction contributes to longevity and cancer prevention and gives scientists new targets for developing and testing drugs that could extend the healthy years of life.


http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000486

Dr. Art Ayers said...

Cristian,

So now you want to see the relationship between longevity (hypoxia, superoxide dismutatase, starvation, vitamin C), glucose metabolism (dietary restriction, cancer, mitochondria, apoptosis), lipid metabolism (LDL, fish oil, prostaglandins, snake venom), gut flora (glucosamine, probiotics), heparan metabolism (everything), immunity (presentation/tolerance, cytokines, complement), bone metabolism (vitamin D, osteoporosis), blood circulation (hypertension, clotting) and all things inflammatory? The hypoxia trigger is the cytoplasmic equivalent to the use of ER use of oxygen as the final acceptor of electrons from proline in the production of hydroxyproline, the interesting amino acid that permits collagens to coil into the triple helices. Vitamin C is needed to keep the enzyme involved in the correct oxidation state. Low vitamin C means low hydroxyproline/collagen = scurvy. Low oxygen in tissue stimulates capillary production, i.e. angiogenesis, a key process in tumor survival.

The hypoxia trigger/transcription factor is another big player in disease and longevity.

Alinus said...

Hi, Dr. Aerys.

Not expecting you to answer this , probably you are more busy than usual and probably there aree to manny comments on your blog those days.

I've found an interesting article regarding lactoferrin activity in IBD patients wich kind off suggests limitation of this protein in those situations.

It can be found here:
http://www.clinsci.org/cs/095/0637/0950637.pdf

Alinus said...

Hi, Dr. Aerys.

Not expecting you to answer this , probably you are more busy than usual and probably there aree to manny comments on your blog those days.

I've found an interesting article regarding lactoferrin activity in IBD patients wich kind off suggests limitation of this protein in those situations.

It can be found here:
http://www.clinsci.org/cs/095/0637/0950637.pdf

Mrs. Ed said...

I am so glad to learn about lactoferrin from your blog. When you first suggested a post to me that mentioned lactoferrin (it was about autism), it was great timing. My son was taking iron supplementation for anemia and it was making an already constipated child even worse. So I dug around in PubMed and found studies where it was used on preterm babies and pregnant women and it appeared quite safe, so we took him off the iron and tried the lactoferrin, and it worked.

We just saw his developmetal pediatrician last week and she said it might not be a bad idea to use it periodically for him. (It's always so nice to see her twice a year, its 3 hrs away in Lubbock but I can discuss things like this with her, here where I live it's a no-no to do anything outside the box).

There's so much interesting stuff on lactoferrin, and it appears to be safer than iron supplementation.