Google Answers Logo
View Question
 
Q: Dairy Proteins - Bovine (Cow) Lactoferrin ( Answered 5 out of 5 stars,   0 Comments )
Question  
Subject: Dairy Proteins - Bovine (Cow) Lactoferrin
Category: Health > Medicine
Asked by: prorag1-ga
List Price: $150.00
Posted: 04 Jan 2005 13:24 PST
Expires: 03 Feb 2005 13:24 PST
Question ID: 451855
I would like a summary (i.e. reference list so I can locate the actual
complete articles) of all clinical research data relating to the use
of Bovine Lactoferrin in human clinical trials.  The clinical trials
can be in any area but they must relate to actual trials on human
subjects.

Bovine Lactoferrin is a glycoprotein which is extracted from the whey
fraction of the dairy protein found in bovine (cows) milk.

If you require any addiotal information please ask.

Thanks.

Request for Question Clarification by librariankt-ga on 04 Jan 2005 19:19 PST
Hi Prorag1,

I have done a search of the MEDLINE database from 1956-current time of
published literature and found 12 articles reporting on human clinical
trials involving bovine lactoferrin.  I also checked the US Clinical
Trials database for ongoing studies but found none that are either in
process or closed.  Same for the ISRCTN
(http://controlled-trials.com/isrctn/search.asp).

Would the citations and abstracts for the 12 articles be a sufficient
answer to your question?  With questions valued as high as yours I
want to be especially sure that I'm giving you what you want.  Please
let me know what additional information I can provide, if any.

Librariankt

Request for Question Clarification by pafalafa-ga on 04 Jan 2005 20:18 PST
I spent a while looking into this question, and I must say, I agree
with librariankt-ga 100%.  There are only a handful of human clinical
trials involving bovine LF (I'm not even sure there are as many as a
dozen!).

Most of the experimental work has been carried out on animals or cell
cultures -- there are quite a number of these studies, and there are
numerous references to the >>desire<< to carry out human trials. 
There are also some trials involving non-bovine LF.

But very few actual human trials of bovine LF to speak of.

pafalafa-ga

Clarification of Question by prorag1-ga on 13 Jan 2005 15:21 PST
Hi Librariankt,

Thanks for your comments re my question on BLF.  I agree with both of
you that it is difficult to locate inforation on actual human clinical
trials.  We do have copies of a few but not 12.

I would be happy to pay USD100 for the list of 12 that you have found
and if I double up, so be it.

I am also happy to pay USD50 to Pafalfa if you have found any
additional information.

Please advise if this is possible.

Thanks & Best Regards,  Rudi

Request for Question Clarification by librariankt-ga on 15 Jan 2005 17:50 PST
Hi Prorag -
To my knowledge the only way to divide up a question's payment to two
researchers is to ask it twice, and have each answer the question
separately.  Also, remember that we split your payment with Google 75%
to us, 25% to Google.  I'm happy to answer this any way you'd like -
and Pafalafa can comment if he's got additional info to share, at
which time you'd be free to ask a separate question to elicit that
answer.  I am not sure I'm explaining this quite clearly enough.
- LKT

Clarification of Question by prorag1-ga on 15 Jan 2005 18:05 PST
Hi LKT,

Thanks for the reply.  Probably the first thing to confirm is if you
are cool about a USD100 fee for the 12 clinical articles you have
found.

I have not had any commenrts back from Proalfa as yet.

You were alsoi the first to reply to my quesitons.  

Please let me know ASAP as I would like to see the list in the next 1
- 2 days at the latest.

Thanks & Best Regards,  Rudi

Request for Question Clarification by librariankt-ga on 15 Jan 2005 18:12 PST
For 12 articles, I would be okay with the $100 fee (of which I'll see
$75).  If you'd like, I can also find direct links to some of the free
online articles, get you more info on the labs doing the recent
trials, etc. for these.  For that I'd want the whole fee... I'm not
sure how much extra Pafalafa has found/would find - we tend to look in
the same or very similar places for our answers on questions like
these.  But you should do things as you feel are best!  LKT

Clarification of Question by prorag1-ga on 15 Jan 2005 19:30 PST
Hi LKT,

No propblem with me re your offer.  You are welcome to take the USD150
fee for the 12 articles and additional information you have offered to
forward.  I'll sort the rest out.

Appreciate your help on this.  Hopefully you have found some additonal
information that I do not have.

Just out of curiousity are you located on the West Coast (USA)?  I am
based in Australia.

If possible can you please forward the information areas that you are
strong in; i.e. I will need a lot of this type of work done in the
future.

Thanks,  Rudi

Request for Question Clarification by librariankt-ga on 15 Jan 2005 19:40 PST
Hi Rudi -
I'll get to this tomorrow (Sunday) in the early afternoon my time -
I'm on the US East Coast so am (yawn) going to bed now!  In general I
answer medical/health questions, particularly ones asking for
citations to articles on topics - as I am (as my handle suggests) a
medical librarian.  Happy to help any time.
- Librariankt
Answer  
Subject: Re: Dairy Proteins - Bovine (Cow) Lactoferrin
Answered By: librariankt-ga on 16 Jan 2005 13:04 PST
Rated:5 out of 5 stars
 
Hi there!

Included below are the twelve articles from MEDLINE (www.pubmed.gov)
that deal with bovine lactoferrin in human clinical trials.  The
entries are in reverse chronological order, and include the citation
and abstract for the article, a link to full text when it was clearly
free, any information about the author that I could find, and a few
additional notes with information I gleaned from other sources.

I will caution that the twelve articles do not represent twelve
different trials.  There are ____ separate studies here (named
according to the disease/condition that BLF was being used against):
1: Helicobacter pylori (University of Parma, Italy, laboratory of
Frencesco Dimario) ? articles 1, 2; note that both articles have
comments on them (citation included).
2: Chronic hepatitis C (National Cancer Center Hospital, Japan, work
of S Okada et al) ? articles 3, 7
3: Group A streptococci (University of Naples, Italy, P Valenti lab) ? article 4
4: Gastric digestion in vivo (University of Maastricht, Netherlands,
FJ Troost) ? article 5
5: Tinea pedis (Morinaga Milk Industry Co., Japan) ? article 6
6: Metastatic carcinoma (Dalhousie University, Canada, RS Kennedy) ? article 8
7: Newborn fecal flora (Sorrento Maternity Hospital, UK; University of
California Davis, US) ? articles 9, 10, 11
8: Amoebiasis (unknown lab) ? article 12

The search strategy to get these twelve articles ended up looking like
this:  ?(("cattle"[TIAB] NOT Medline[SB]) OR "cattle"[MeSH Terms] OR
bovine[Text Word]) AND ("lactoferrin"[MeSH Terms] OR lactoferrin[Text
Word]) AND Clinical Trial[ptyp] AND "humans"[MeSH Terms]?.  This is an
automatic translation of my search ?bovine lactoferrin? with limits
placed for Human and Clinical Trials.  Note that I did NOT put a
language limit on these articles ? but they all happen to be in
English (even though most are from non-English countries).  Good luck
for you, I guess.  Yay for English as the de facto language of
medicine!  Note that this search separates out any article that isn?t
clearly marked as a clinical trial ? and only includes ones for which
?bovine? is present (or ?cattle?).  When I did a search for ?BLF? I
found an additional two articles, neither of which was relevant (one
is about blood pressure and anger, the other is ?That swimsuit becomes
you: sex differences in self-objectification, restrained eating, and
math performance?).

I have provided locations at time of publication for most of the
primary authors, as well as email address when I could locate them. 
In addition, for the first eight articles I looked in the ISI Citation
Indexes to see how many times each article has been cited since
publication ? that number is listed at the end of each abstract, with
some comments about what the citations were to (in one or two cases I
included a citation I thought might be of interest).  If you?d like to
see the complete list of citing articles for any of the below just let
me know in a clarification request and I?ll be happy to give you them.
 At the end are an additional two articles that I found by looking at
the really recent or otherwise not fully indexed articles for BLf in
PubMed MEDLINE.  I also checked the International Pharmaceutical
Abstracts to see if there were any other trials that I?d missed from
MEDLINE but found only human lactoferrin, not bovine.

I also looked in several online registries of clinical trials to see
if there are current studies underway of BLf.  I found none.  Here are
the places I looked: US Clinical Trials database
(www.clinicaltrials.gov), CenterWatch Clinical Trials directory
(www.centerwatch.com), the (UK) National Research Register
(http://www.update-software.com/National/search.htm ? note that this
one had lots on lactoferrin, but it?s all (so far as I can tell)
human), and the International Standard Registry of Clinical Trials
Numbers ? ISRCTN (http://controlled-trials.com/isrctn/search.asp).

Finally, I looked in several databases of drugs in development to see
if there was anything underway for which we could look for a trade
name (and found none): US National Cancer Institute Investigational
Drugs (http://dtp.nci.nih.gov/docs/idrugs/drugstatus.html) and PhRMA
New Medicines in Development
(http://www.phrma.org/newmedicines/newmedsdb/drugs.cfm).

Please let me know how else I can help you with this or any other
question.  On this one you can just request a clarification of the
answer and I?ll get an email prompting me to come back for another go
? on further answers if you want me to look at it just put my name
(librariankt) in the question and I?ll find it.

Yours,

Librariankt

1: Digestive and Liver Disease. 2003 Oct;35(10):706-10. 
A comment on this article appears in: Digestive and Liver Disease.
2003 Oct;35(10):691-3.
Use of bovine lactoferrin for Helicobacter pylori eradication.
Di Mario F, Aragona G, Dal Bo N, Cavestro GM, Cavallaro L, Iori V,
Comparato G, Leandro G, Pilotto A, Franze A.
University of Parma, Parma, Italy. francesco.dimario@unipr.it
BACKGROUND: One-week triple therapy is the most frequently recommended
treatment for Helicobacter pylori infection. Eradication rate is
satisfactory, nevertheless is advisable to look for more effective
therapies. AIM: To test the efficacy of a standard triple therapy plus
bovine lactoferrin in the eradication of H. pylori infection. PATIENTS
AND METHODS: One hundred and fifty consecutive H. pylori positive
patients, suffering from dyspeptic symptoms were recruited in a 7-day
triple therapy open randomised single centre study with rabeprazole,
clarithromycin, tinidazole, bovine lactoferrin (group A) or
rabeprazole, clarithromycin, tinidazole (group B), or a 10-day therapy
with rabeprazole, clarithromycin, tinidazole (group C). H. pylori
status was assessed 8 weeks after the end of the treatment by means of
a 13C-urea breath test or a H. pylori stool antigen-test. RESULTS:
Eradication rates (intention to treat/per protocol) were: group A
(92.2/95.9%), group B (71.2/72.5%) and group C (70.2/75%). The
efficacy of triple therapy added with lactoferrin was significantly
higher than other two regimens (p=0.01, intention to treat analysis;
p=0.005, per protocol analysis). CONCLUSION: These results suggest
that lactoferrin tested in the present study was effective in curing
H. pylori and could be a new agent to assist the antimicrobials in the
eradication of the bacterium.
Publication Types: Clinical Trial; Randomized Controlled Trial
This article was cited four times; all four articles deal with
helicobacter pylori eradication/therapy/treatment/etc.


2: Journal of Clinical Gastroenterology. 2003 May-Jun;36(5):396-8. 
A comment on this article appears in: Journal of Clinical
Gastroenterology. 2003 May-Jun;36(5):384-5.
Use of lactoferrin for Helicobacter pylori eradication. Preliminary results.
Di Mario F, Aragona G, Bo ND, Ingegnoli A, Cavestro GM, Moussa AM,
Iori V, Leandro G, Pilotto A, Franze A.
Section of Gastroenterology, University of Parma, Italy. francesco.dimario@unipr.it
BACKGROUND: One-week triple therapy is the most frequently recommended
treatment of Helicobacter pylori infection. The associated eradication
rate is satisfactory; nevertheless, it is advisable to look for more
effective therapies. Our aim was to test the efficacy of a standard
triple therapy plus bovine lactoferrin for the eradication of H.
pylori infection. STUDY: This open, randomized, single-center study
was designed to include 150 consecutive H. pylori-positive patients
with dyspeptic symptoms and gastritis who received triple therapy with
rabeprazole, clarithromycin, and tinidazole plus lactoferrin for 7
days (group A), rabeprazole, clarithromycin, and tinidazole for 7 days
(group B), or rabeprazole, clarithromycin, and tinidazole for 10 days
(group C). H. pylori status was assessed 8 weeks after the end of
treatment by means of the 13C-urea breath test or H. pylori stool
antigen test. RESULTS: The 7-day treatment including lactoferrin
(group A) was successful in 100% (24/24) of the patients. The
eradication rates in groups B and C were 76.9% (20/26 patients; 95%
CI, 61%-93%) and 70.8% (17/24 patients; 95% CI, 53%-89%),
respectively. A significant difference was found between group A and
group B (P = 0.023) and group A and group C (P = 0.022). No
differences were found between group B and group C (P = 1.00).
CONCLUSION: These results suggest that lactoferrin could be a new,
effective agent when added to antimicrobial therapy for the
eradication of H. pylori. This treatment schedule could be proposed
for larger trials of H. pylori eradication therapy, focusing on the
excellent preliminary cure rate, good compliance to the treatment
schedule, and relatively low price of lactoferrin for full treatment.
Publication Types: Clinical Trial; Randomized Controlled Trial
This article has been cited five times: four are the same as cited
article #1; the fifth is similar.


3: Japanese Journal of Cancer Research. 2002 Sep;93(9):1063-9. 
FREE ONLINE: http://www.jca.gr.jp/cs/93/9/1063.pdf
Dose-response trial of lactoferrin in patients with chronic hepatitis C.
Okada S, Tanaka K, Sato T, Ueno H, Saito S, Okusaka T, Sato K, Yamamoto S,
Kakizoe T.
Hepatobiliary and Pancreatic Oncology Division, National Cancer Center
Hospital, Chuo-ku, Tokyo 104-0045, Japan. sokada@ncc.go.jp
Hepatitis C virus (HCV) is one of the most common causes of chronic
hepatitis. Interferon is presently the only effective treatment for
chronic hepatitis C (CH-C), though its effectiveness is limited.
Lactoferrin (LF), which is an 80-kDa, iron-binding glycoprotein, has
several biological activities including anti-viral activity, and it
was recently reported to inhibit HCV infection in cultured human
hepatocytes. The present trial was designed to assess the relationship
between the dose of bovine LF (bLF) and the effect of bLF on serum
alanine aminotransaminase (ALT) and HCV RNA levels in patients with
CH-C. Forty-five patients entered at each of the three dose levels
(bLF of 1.8, 3.6, and 7.2 g/day) received orally an 8-week course of
bLF. There was no significant relation between the dose of bLF and the
effect of bLF on serum ALT or HCV RNA levels. Biochemical (a 50% or
greater decrease in the serum ALT level) and virological (a 50% or
greater decrease in HCV RNA level) responses were observed in two and
four patients, respectively, but all responders relapsed during the
follow-up period after bLF treatment. The bLF treatment was generally
well tolerated, and no patient had any serious adverse event. In
conclusion, the excellent tolerance and potential anti-HCV activity of
bLF shown in this trial suggest that further trials using a large
number of patients are mandatory. We are currently conducting a
double-blind randomized controlled trial comparing bLF with placebo to
clarify the anti-HCV activity of bLF in patients with CH-C.
Publication Types: Clinical Trial
This article was cited five times: most deal with either lactoferrin
(one is an article about recent clinical trials).  It is unclear to me
whether this one specifically human or bovine Lf:  Title: A randomized
controlled trial of consensus interferon with or without lactoferrin
for chronic hepatitis C patients with genotype 1b and high viral load
Author(s): Hirashima N, Orito E, Ohba K, Kondo H, Sakamoto T,
Matsunaga S, Kato A, Nukaya H, Sakakibara K, Ohno T, Kato H, Sugauchi
F, Kato T, Tanaka Y, Ueda R, Mizokami M  Source: HEPATOLOGY RESEARCH
29 (1): 9-12 MAY 2004



4: Biochemistry and Cell Biology. 2002;80(1):119-24. 
Anti-invasive activity of bovine lactoferrin towards group A streptococci.
Ajello M, Greco R, Giansanti F, Massucci MT, Antonini G, Valenti P.
Department of Experimental Medicine, II University of Naples, Napoli, Italy.
Contact: Piera Valenti, piera.valenti@uniroma1.it
Group A streptococci (GAS) are able to invade cultured epithelial and
endothelial cells without evidence of intracellular replication. GAS,
like other facultative intracellular bacterial pathogens, evolved such
ability to enter and to survive within host cells avoiding the host
defences, and bacterial intracellular survival could explain the
recurrence of infections. We report here that 1 mg bovine lactoferrin
(bLf)/mL significantly hindered the in vitro invasion of cultured
epithelial cells by GAS isolated from patients suffering from
pharyngitis and completely inhibited the invasiveness of GAS
pretreated with subinhibiting concentrations of erythromycin or
ampicillin. One milligram of bLf per millilitre was also able to
increase the number of epithelial cells undergoing apoptosis following
GAS invasion, although the number of intracellular GAS in the presence
of bLf decreased by about 10-fold. The ability of bLf to decrease GAS
invasion was confirmed by an in vivo trial carried out on 12 children
suffering from pharyngitis and already scheduled for tonsillectomy. In
tonsil specimens from children treated for 15 days before
tonsillectomy with both oral erythromycin (500 mg t.i.d. (three times
daily)) and bLf gargles (100 mg t.i.d.), a lower number of
intracellular GAS was found in comparison with that retrieved in
tonsil specimens from children treated with erythromycin alone (500 mg
t.i.d.).
Publication Types: Clinical Trial; Controlled Clinical Trial
This article has been cited 6 times, most of which are essays about
current research into  the antimicrobial nature of Lf, two are studies
against cultures.

5: Journal of Nutrition. 2001 Aug;131(8):2101-4. 
FREE ONLINE: http://www.nutrition.org/cgi/content/full/131/8/2101
Gastric digestion of bovine lactoferrin in vivo in adults.
Troost FJ, Steijns J, Saris WH, Brummer RJ.
Department of Human Biology, Nutrition and Toxicology Institute
Maastricht, Universiteitssingel, Maastricht, The Netherlands.
f.troost@hb.unimaas.nl
Lactoferrin (LF), an iron-binding glycoprotein present in milk and
other endocrine and exocrine secretions, may exert a number of
physiologic effects in the intestines. To study the effects of oral LF
supplementation in vivo in the gastrointestinal tract, information
about the gastric survival of LF in vivo is important. We tested 12
healthy volunteers (age 21 +/- 0.3 y) on 3 separated according to a
randomized, cross-over design. A test drink containing 4.5 g of bovine
LF (20% iron-saturated LF; apoLF) in the presence of a gastric pH
buffer (0.1 mol/L sodium citrate/citric acid; apoLFbuf), apoLF without
the buffer (apoLF) or iron-saturated LF (holoLF) was administered into
the stomach using nasogastric intubation. Gastric emptying rate,
determined by a marker dilution technique, did not differ among any of
these drinks. Gastric survival of LF, analyzed by gel permeation
chromatography under denaturing conditions, was 64%, 62% and 79% after
consumption of the apoLFbuf, apoLF and holoLF test drinks,
respectively. Addition of the gastric pH buffer initially lowered
intragastric pH because of its hydroxide buffering effect. However, it
did not elevate intragastric pH over a prolonged period and thereby
inhibit intragastric LF breakdown. We conclude that after oral
administration, substantial amounts of apoLF and holoLF survive
gastric transit.
Publication Types: Clinical Trial; Randomized Controlled Trial
This has been cited 7 times, mainly in animal studies.
The Troost lab appears to have moved onto clinical studies using human Lf.

6: Mycoses. 2000;43(5):197-202. 
Oral administration of bovine lactoferrin for treatment of tinea
pedis. A placebo-controlled, double-blind study.
Yamauchi K, Hiruma M, Yamazaki N, Wakabayashi H, Kuwata H, Teraguchi
S, Hayasawa H, Suegara N, Yamaguchi H.
Nutritional Science Laboratory, Morinaga Milk Industry Co., Ltd, Kanagawa, Japan.
A clinical study was conducted to evaluate the effectiveness of
lactoferrin, which is a protein component of cow's milk, in the
treatment of tinea pedis. Doses of either 600 mg or 2000 mg of
lactoferrin, or a placebo was orally administered daily for 8 weeks to
37 adults who were judged to have mild or moderate tinea pedis.
Dermatological improvement and antifungal efficacy were assessed. In
the analysis of all subjects, dermatological symptoms scores in all
groups decreased but the differences were not statistically
significant comparing the three groups. However, in the analysis
limited to subjects with moderate vesicular or interdigital tinea
pedis, dermatological symptoms scores in the lactoferrin-treated
groups decreased significantly in comparison with the placebo group (P
< 0.05). The organisms isolated were Trichophyton rubrum and
Trichophyton mentagrophytes. A mycological cure was not seen in any of
the subjects. In the 37 subjects there were no adverse events and no
subject withdrew from the study because of an adverse event. These
results suggest that orally administered lactoferrin can improve the
dermatological symptoms in some subjects. The potential usefulness of
lactoferrin as a functional food material for treating tinea pedis was
seen for the first time in this study.
Publication Types: Clinical Trial; Randomized Controlled Trial
This has been cited 13 times, mostly for animal studies of Lf on
various yeasts as well as other reports on therapeutic uses of Lf.
I believe this is the same Yamauchi as appears elsewhere on this list,
including in the very last article given (hepatitis C research).

7: Japanese Journal of Cancer Research. 1999 Apr;90(4):367-71. 
FREE ONLINE: http://www.jca.gr.jp/cs/90/4/367.pdf
Lactoferrin inhibits hepatitis C virus viremia in patients with
chronic hepatitis C: a pilot study.
Tanaka K, Ikeda M, Nozaki A, Kato N, Tsuda H, Saito S, Sekihara H.
Third Department of Internal Medicine, Yokohama City University School
of Medicine, Yokohama. tanaka97@med.yokohama-cu.ac.jp
Hepatitis C virus (HCV) is associated with the development of
cirrhosis and hepatocellular carcinoma. We recently found that bovine
lactoferrin, a milk protein belonging to the iron transporter family,
effectively prevented HCV infection in cultured human hepatocytes
(PH5CH8). We tested the hypothesis that lactoferrin inhibits HCV
viremia in patients with chronic hepatitis C. Eleven patients with
chronic hepatitis C received an 8-week course of bovine lactoferrin
(1.8 or 3.6 g/day). At the end of lactoferrin treatment, a decrease in
serum alanine transaminase and HCV RNA concentrations was apparent in
3 (75%) of 4 patients with low pretreatment serum concentrations of
HCV RNA. However, 7 patients with high pretreatment concentrations
showed no significant changes in these indices. This pilot study
suggests that lactoferrin is one potential candidate as an anti-HCV
reagent that may be effective for the treatment of patients with
chronic hepatitis.
Publication Types: Clinical Trial; Controlled Clinical Trial
This has been cited 34 times!
It looks like this paper has also been given at least once as a
conference report, see: HEPATOLOGY 34 (4): 424A-424A 1007 Part 2
Suppl. S, OCT 2001

8: Anticancer Research. 1995 Nov-Dec;15(6B):2643-9. 
The use of a whey protein concentrate in the treatment of patients
with metastatic carcinoma: a phase I-II clinical study.
Kennedy RS, Konok GP, Bounous G, Baruchel S, Lee TD.
Department of Surgery, Dalhousie University, Halifax, Nova Scotia, Canada.
Glutathione (GSH) concentration is high in most tumour cells and this
may be an important factor in resistance to chemotherapy. Previous
in-vitro and animal experiments have shown a differential response of
tumour versus normal cells to various cysteine delivery systems. More
specifically, an in-vitro assay showed that at concentrations that
induce GSH synthesis in normal human cells, a specially prepared whey
protein concentrate, Immunocal, caused GSH depletion and inhibition of
proliferation in human breast cancer cells. On the basis of this
information five patients with metastatic carcinoma of the breast, one
of the pancreas and one of the liver were fed 30 grams of this whey
protein concentrate daily for six months. In six patients the blood
lymphocyte GSH levels were substantially above normal at the outset,
reflecting high tumour GSH levels. Two patients (#1, #3) exhibited
signs of tumour regression, normalization of haemoglobin and
peripheral lymphocyte counts and a sustained drop of lymphocyte GSH
levels towards normal. Two patients (#2, #7) showed stabilisation of
the tumour, increased haemoglobin levels. In three patients (#4, #5,
#6,) the disease progressed with a trend toward higher lymphocyte GSH
levels. These results indicate that whey protein concentrate might
deplete tumour cells of GSH and render them more vulnerable to
chemotherapy.
Publication Types: Case Reports; Clinical Trial; Clinical Trial, Phase
I; Clinical Trial, Phase II
This has 13 citations.
GP Konok hasn?t published anything under that name since 1996.  RS
Kennedy appears to be a surgeon, possibly in oncology.

9: Acta Paediatrica Japonica. 1994 Oct;36(5):579-84. 
Sorrento studies of diet and fecal flora in the newborn.
Wharton BA, Balmer SE, Scott PH.
Sorrento Maternity Hospital, Department of Microbiology, Birmingham, UK.
The fecal flora of a breast-fed baby is very different from that of a
bottle-fed baby. This paper reviews five previous studies, performed
at this hospital concerning the effect of various dietary components
(whey proteins, casein, lactoferrin, iron, nucleotides) on the fecal
flora. The babies received either breast milk or one of the test
formulas from birth. Fecal samples were examined by quantitative
microbiological methods at 4 and 14 days and at various intervals
thereafter. By 14 days differences in the fecal flora were
established. Among breast-fed babies bifidobacteria, lactobacilli and
staphylococci were predominant organisms, whereas in the formula-fed
babies the predominant organisms were enterococci, coliforms, and
Bacteroides. A whey-based formula without bovine lactoferrin, iron or
nucleotides gave a flora a little closer to but still remote from the
breast-fed one. Despite extensive modification of cow's milk in the
manufacture of a modern infant formula, the fecal flora of bottle-fed
babies remains substantially different from that of breast-fed babies.
Publication Types: Clinical Trial; Controlled Clinical Trial


10: Acta Paediatrica. 1994 Apr;83(4):367-73. 
Iron, zinc, copper and selenium status of breast-fed infants and
infants fed trace element fortified milk-based infant formula.
Lonnerdal B, Hernell O.
Department of Nutrition, University of California, Davis.
Infants were fed cow's milk-based formulas containing 4 mg of iron/l
from 1.5 to 6 months of age and their hematological status was
compared to infants receiving the same formula but with 7 mg of iron/l
and with breast-fed infants. One formula with 4 mg of iron/l contained
iron as ferrous sulfate, in another, part of the iron was provided as
bovine lactoferrin. We also studied the effect of selenium (10
micrograms/l) and copper (0.4 mg/l) supplementation on selenium and
copper status. There were no significant differences in hematological
indices among the groups at 6 months of age; all infants had
satisfactory iron status. Serum transferrin receptor levels, a
potential novel indicator of iron status, were highest in breast-fed
infants, suggesting a cellular need for iron, and lowest in infants
receiving formula with 7 mg of iron/l. Selenium status, as assessed by
serum glutathione peroxidase activity, was similar at 6 months of age
in breast-fed infants and infants fed formula fortified with selenium
but lower in infants fed unfortified formula. The lowest levels of
glutathione peroxidase activity were found in infants fed the highest
concentration of iron (7 mg/l). Serum copper concentrations were
similar in all groups, but the lowest levels were found in infants fed
the highest concentration of iron. These results suggest that 4 mg of
iron/l is adequate for infants up to 6 months of age and that higher
levels may have some negative effects.
Publication Types: Clinical Trial; Randomized Controlled Trial


11: Archives of Disease in Childhood. 1989 Dec;64(12):1685-90. 
Diet and faecal flora in the newborn: lactoferrin.
Balmer SE, Scott PH, Wharton BA.
Sorrento Maternity Hospital, Birmingham.
The faecal flora of breast fed babies differs from that of bottle fed
babies. We have shown that the use of a whey predominant formula
rather than a casein predominant one induced a faecal flora generally
closer to that of breast fed babies but substantial differences
remained. The whey proteins of breast milk include much more
lactoferrin than is found in cows' milk. Observations both in animals
and in vitro suggest that lactoferrin could be responsible for some of
these differences between bottle and breast fed babies. This study was
designed to determine the effects on faecal flora of the addition of
bovine lactoferrin to the diet of bottle fed babies while holding
other qualities of their diet constant. As lactoferrin is an iron
binding protein three test formulas were used: (a) no added iron and
no added lactoferrin (basic), (b) no iron but added lactoferrin (L),
and (c) added iron and lactoferrin (LF). The addition of lactoferrin
had little effect upon the faecal microflora and did not move the
pattern of the faecal flora in the direction of the breast fed baby.
The addition of iron to the formula had more effect on the faecal
flora than did lactoferrin. At day 4 it encouraged Escherichia coli
and discouraged staphylococcal faecal colonisation. At day 14 the
addition of iron to the formula discouraged bifidobacteria. The
reasons why bovine lactoferrin was ineffective in vivo in this study
are discussed.
Publication Types: Clinical Trial; Controlled Clinical Trial


12: British Medical Journal. 1980 Jun 7;280(6228):1351-2. 
The salutary effect of milk on amoebiasis and its reversal by iron.
Murray MJ, Murray A, Murray CJ.
Observations among milk-drinking African nomads showed an unusual
freedom from infection with Entamoeba histolytica compared with
similar nomads taking a mixed diet. A controlled study among Maasai
pastoralists showed that the administration of iron to correct their
dietary iron deficiency sharply increased their susceptibility to
amoebiasis. Examination of the milk of their Zebu cattle showed that
it not only had a concentration of iron below the minimum necessary
for the growth of E histolytica but also contained partly saturated
lactoferrin and transferrin, which may actively compete with the
parasite in the colon for ambient iron. These observations suggest the
possibility of a long-standing ecological compromise between nomads,
their milk diet, and E histolytica.
Publication Types: Clinical Trial; Controlled Clinical Trial


In addition, the following two articles have not yet been fully
indexed by MEDLINE, so they do not have the ?clinical trials? label
attached (I found them by scanning through the 35 articles that deal
with BLf but aren?t in MEDLINE proper):

1: Biometals. 2004 Jun;17(3):245-8. 
Potential usefulness of bovine lactoferrrin for adjunctive immunotherapy for
mucosal Candida infections.
Yamaguchi H, Abe S, Takakura N.
Teikyo University Institute of Medical Mycology, Tokyo 192-0395, Japan.
Immunosuppressed children and adults have a higher prevalence of
oropharyngeal candidiasis. In this patient population, anti-fungal
therapy of this condition is often ineffective, and new approaches to
treatment are needed. The use of bovine lactoferrin is considered a
promising option in treating oropharyngeal candidiasis. Here we review
the results of in vitro and in vivo studies that have examined the
antimicrobial characteristics of bovine lactoferrin as an adjunctive
therapy for oropharyngeal candidiasis.


2: Hepatology Research. 2003 Mar;25(3):226-233. 
Long-term follow-up of chronic hepatitis C patients treated with oral
lactoferrin for 12 months.
Ishii K, Takamura N, Shinohara M, Wakui N, Shin H, Sumino Y, Ohmoto Y, Teraguchi
S, Yamauchi K.
Second Department of Internal Medicine, Toho University School of Medicine,
6-11-1, Omori-nishi, Ota-ku, 143, Tokyo, Japan
BACKGROUND/AIMS: Bovine lactoferrin (bLF) has been shown to prevent
the infection of cultured hepatocytes by hepatitis C virus (HCV). The
present study attempted to clarify the effects of long-term
administration of bLF on serum parameters, including immunomodulatory
cytokines, in patients with chronic hepatitis C (CHC). METHODS:
Sixty-three CHC patients were randomly assigned into 2 groups. At an
oral dose of 600 mg/day, bLF was administered for 12 months to 36
patients (bLF group), while no bLF was given to the remaining 27
patients (control group. Serum levels of alanine aminotransferase,
HCV-RNA, IL-10, and IL-18 were evaluated, as well as CD4-positive T
cell subsets in the peripheral blood. RESULTS: The serum IL-18 level
was increased by bLF administration, but not in the control group.
After 3 months of bLF treatment, it was significantly higher than
before bLF administration, but it decreased gradually thereafter. The
percentage of interferon (IFN)-gamma+ and IL-4- (Th1) cells in the
peripheral blood increased along with the serum IL-18 level, although
the change was not statistically significant. The other parameters did
not change significantly during the study period in both groups.
CONCLUSIONS: These results suggest that oral administration of bLF to
CHC patients for up to 3 months can produce a Th1-cytokine dominant
environment in the peripheral blood that favors the eradication of HCV
by IFN therapy.

Request for Answer Clarification by prorag1-ga on 16 Jan 2005 16:06 PST
Hi LKT (librariankt),

Have just had a quick read of your answer.  Thanks heaps.  Appreciate
your effort on this.  There is some new information in here that we do
not have.

You mentioned that you would be happy to forward the complete list of
citing articles.

Can yo uplease do this.  Also, did you by any chance come across any
clinical trials using any other forms of Lactoferrin, even human?

If you have this informaiton, can you please forward as well.

Thanks & Best Regards,  Rudi

Clarification of Answer by librariankt-ga on 16 Jan 2005 17:47 PST
Hi Rudi -
Glad you found the first response helpful!  As you have two requests
for further info, I'm addressing them as two responses.  First, citing
articles to the first set:

Because there are so many citations, I'm just including the citing
articles to the first six from the set I gave you above.  They are
listed according to article number from the first set, with the brief
citation included.  I conflated results for the first two articles as
they seem to be two parts of the same study.

1: Digestive and Liver Disease. 2003 Oct;35(10):706-10. 
2: Journal of Clinical Gastroenterology. 2003 May-Jun;36(5):396-8. 
Mueller, A; Merrell, DS; Grimm, J; et al.  Profiling of microdissected
gastric epithelial cells reveals a cell type-specific response to
Helicobacter pylori infection
GASTROENTEROLOGY, 127 (5): 1446-1462 NOV 2004

McLoughlin, R; Racz, I; Buckley, M; et al. Therapy of Helicobacter
pylori HELICOBACTER, 9: 42-48 Suppl. 1 2004

Zullo, A; Hassan, C; Campo, SMA; et al. Evolving therapy for
Helicobacter pylori infection EXPERT OPINION ON THERAPEUTIC PATENTS,
14 (10): 1453-1464 OCT 2004

Basset, C; Holton, J; Gatta, L; et al. Helicobacter pylori infection:
anything new should we know? ALIMENTARY PHARMACOLOGY & THERAPEUTICS,
20: 31-41 Suppl. 2 JUL 2004

Zullo, A; Hassan, C; Morini, S Quadruple therapy as a first-line
Helicobacter pylori treatment: past or future? DIGESTIVE AND LIVER
DISEASE, 36 (6): 377-379 JUN 2004

Borody, TJ; Ashman, O Lactoferrin: milking ulcers? DIGESTIVE AND LIVER
DISEASE, 35 (10): 691-693 OCT 2003

Meyer, JM Use of lactoferrin for Helicobacter pylori eradication
JOURNAL OF CLINICAL GASTROENTEROLOGY, 36 (5): 384-385 MAY-JUN 2003


3: Japanese Journal of Cancer Research. 2002 Sep;93(9):1063-9. 
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 HEPATOLOGY
RESEARCH, 29 (1): 9-12 MAY 2004

Wakabayashi, H; Kurokawa, M; Shin, K; et al. Oral lactoferrin prevents
body weight loss and increases cytokine responses during herpes
simplex virus type 1 infection of mice BIOSCIENCE BIOTECHNOLOGY AND
BIOCHEMISTRY, 68 (3): 537-544 MAR 2004

Bayes, M; Rabasseda, X; Prous, JR Gateways to clinical trials METHODS
AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY, 25 (10):
831-855 DEC 2003

De Waard, R; Van Belzen, N The anti-carcinogenic potential of
lactoferrin AGRO FOOD INDUSTRY HI-TECH, 14 (2): 35-39 MAR-APR 2003

Weinberg, ED The therapeutic potential of lactoferrin EXPERT OPINION
ON INVESTIGATIONAL DRUGS, 12 (5): 841-851 MAY 2003


4: Biochemistry and Cell Biology. 2002;80(1):119-24. 
Valenti P, Berlutti F, Conte MP, et al. Lactoferrin functions -
Current status and perspectives JOURNAL OF CLINICAL GASTROENTEROLOGY
38 (6): S127-S129 Suppl. S JUL 2004

Di Biase AM, Tinari A, Pietrantoni A, et al. Effect of bovine
lactoferricin on enteropathogenic Yersinia adhesion and invasion in
HEp-2 cells JOURNAL OF MEDICAL MICROBIOLOGY 53 (5): 407-412 MAY 2004

Orsi N The antimicrobial activity of lactoferrin: Current status and
perspectives  BIOMETALS 17 (3): 189-196 JUN 2004

Ward PP, Conneely OM Lactoferrin: Role in iron homeostasis and host
defense against microbial infection BIOMETALS 17 (3): 203-208 JUN 2004

Weinberg ED The therapeutic potential of lactoferrin EXPERT OPINION ON
INVESTIGATIONAL DRUGS 12 (5): 841-851 MAY 2003

Di Biase AM, Pietrantoni A, Tinari A, et al. Heparin-interacting sites
of bovine lactoferrin are involved in anti-adenovirus activity JOURNAL
OF MEDICAL VIROLOGY 69 (4): 495-502 APR 2003


5: Journal of Nutrition. 2001 Aug;131(8):2101-4. 
Norrby K Human apo-lactoferrin enhances angiogenesis mediated by
vascular endothelial growth factor A in vivo JOURNAL OF VASCULAR
RESEARCH 41 (4): 293-304 2004

Chen PW, Ho SP, Shyu CL, et al. Effects of bovine lactoferrin
hydrolysate on the in vitro antimicrobial susceptibility of
Escherichia coli strains isolated from baby pigs  AMERICAN JOURNAL OF
VETERINARY RESEARCH 65 (2): 131-137 FEB 2004

Troost FJ, Saris WHM, Brummer RJM Recombinant human lactoferrin
ingestion attenuates indomethacin-induced enteropathy in vivo in
healthy volunteers EUROPEAN JOURNAL OF CLINICAL NUTRITION 57 (12):
1579-1585 DEC 2003

Weinberg ED The therapeutic potential of lactoferrin  EXPERT OPINION
ON INVESTIGATIONAL DRUGS 12 (5): 841-851 MAY 2003

van Belzen N The role of lactoferrin in cancer prevention SCIENCES DES
ALIMENTS 22 (4): 461-468 2002

Troost FJ, Saris WHM, Brummer RJM  Orally ingested human lactoferrin
is digested and secreted in the upper gastrointestinal tract in vivo
in women with ileostomies JOURNAL OF NUTRITION 132 (9): 2597-2600 SEP
2002

Humphrey BD, Huang N, Klasing KC Rice expressing lactoferrin and
lysozyme has antibiotic-like properties when fed to chicks JOURNAL OF
NUTRITION 132 (6): 1214-1218 JUN 2002


6: Mycoses. 2000;43(5):197-202. 
Valenti P, Berlutti F, Conte MP, et al. Lactoferrin functions -
Current status and perspectives JOURNAL OF CLINICAL GASTROENTEROLOGY
38 (6): S127-S129 Suppl. S JUL 2004

Takakura N, Wakabayashi H, Ishibashi H, et al. Effect of orally
administered bovine lactoferrin on the immune response in the oral
candidiasis murine model  JOURNAL OF MEDICAL MICROBIOLOGY 53 (6):
495-500 JUN 2004

Orsi N The antimicrobial activity of lactoferrin: Current status and
perspectives  BIOMETALS 17 (3): 189-196 JUN 2004

Teraguchi S, Wakabayashi H, Kuwata H, et al. Protection against
infections by oral lactoferrin: Evaluation in animal models BIOMETALS
17 (3): 231-234 JUN 2004

Yamaguchi H, Abe S, Takakura N Potential usefulness of bovine
lactoferrin for adjunctive immunotherapy for mucosal Candida
infections  BIOMETALS 17 (3): 245-248 JUN 2004

Yamauchi K, Soejima T, Ohara Y, et al. Rapid determination of bovine
lactoferrin in dairy products by an automated quantitative
agglutination assay based on latex beads coated with F(ab ')(2)
fragments BIOMETALS 17 (3): 349-352 JUN 2004

Wakabayashi H, Kurokawa M, Shin K, et al. Oral lactoferrin prevents
body weight loss and increases cytokine responses during herpes
simplex virus type 1 infection of mice  BIOSCIENCE BIOTECHNOLOGY AND
BIOCHEMISTRY 68 (3): 537-544 MAR 2004

Maruyama R, Hiruma M, Yamauchi K, et al. An epidemiological and
clinical study of untreated patients with tinea pedis within a company
in Japan MYCOSES 46 (5-6): 208-212 JUN 2003

Clare DA, Catignani GL, Swaisgood HE Biodefense properties of milk:
The role of antimicrobial proteins and peptides CURRENT PHARMACEUTICAL
DESIGN 9 (16): 1239-1255 2003

Wakabayashi H, Takakura N, Teraguchi S, et al. Lactoferrin feeding
augments peritoneal macrophage activities in mice intraperitoneally
injected with inactivated Candida albicans MICROBIOLOGY AND IMMUNOLOGY
47 (1): 37-43 2003

Katsambas A, Stefanaki C  Cutaneous diseases of the foot: Unapproved
treatments  CLINICS IN DERMATOLOGY 20 (6): 689-699 NOV-DEC 2002

Wakabayashi H, Takakura N, Yamauchi K, et al.  Effect of lactoferrin
feeding on the host antifungal response in guinea-pigs infected or
immunised with Trichophyton mentagrophytes JOURNAL OF MEDICAL
MICROBIOLOGY 51 (10): 844-850 OCT 2002

Tomita M, Wakabayashi H, Yamauchi K, et al. Bovine lactoferrin and
lactoferricin derived from milk: production and applications 
BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE 80 (1):
109-112 FEB 2002

Clarification of Answer by librariankt-ga on 16 Jan 2005 18:16 PST
Hi there -
Part two of the clarification.  I found 74 articles using a query of
lactoferrin clinical trials in humans, not bovine:
"lactoferrin"[MeSH Terms] AND clinical trial[ptyp] AND "humans"[MeSH
Terms] NOT (("cattle"[TIAB] NOT Medline[SB]) OR "cattle"[MeSH Terms]
OR bovine[Text Word]).
Note that I chose to do lactoferrin as a subject heading rather than a
text word, since that limited my results to articles actually about
lactoferrin, and weeds out the ones that just mention it in passing.

Since 74 articles is a bit too many to paste in here, here's the URL
for the citations in PubMed:

"lactoferrin"[MeSH Terms] AND clinical trial[ptyp] AND "humans"[MeSH
Terms] NOT (("cattle"[TIAB] NOT Medline[SB]) OR "cattle"[MeSH Terms]
OR bovine[Text Word])

PubMed is the public interface to MEDLINE, so you can access it from
Australia without a problem.  Some of the articles will be available
for free, others will allow you to order them online from the
publisher.  The default will be to give you just the citations - you
can get an individual abstract by clicking on the hyperlinked authors'
names, or you can get the whole list with abstracts by choosing
"Abstract" from the pull-down menu next to Display, and click the
Display button.

Hope that does it!  Let me know - LKT

Clarification of Answer by librariankt-ga on 16 Jan 2005 18:17 PST
Doh!  Sorry, didn't give you the URL.  Here 'tis:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=pubmed&term=lactoferrin[mh]+AND+clinical+trial[ptyp]+AND+humans[mh]+NOT+bovine

Request for Answer Clarification by prorag1-ga on 16 Jan 2005 19:23 PST
Hello again LKT.  Thanks for the updates.  That should do it for now. 
Appreciate your help on this.  I'll now use this information and see
what a colleague can find on the peptides of Lacrtoferrin -
Lactoferricin via our scientific databases in Aus.

Now, since I am a novice aqt Google Answers, how do amake sure you get
paid?  Do I just rate the answer etc?

Thanks again,  Rudi

Clarification of Answer by librariankt-ga on 16 Jan 2005 21:10 PST
Glad to be of help.

RE payment - I'm automatically paid for having answered the question,
no further action is required on your part.  I do appreciate feedback
(particularly if it's good!) as that is part of my publicly available
summary, and if you're interested in giving a tip (again, not
mandatory, up to you) you do that at the same time as giving feedback.

I hope you use Google Answers again, and thanks for a very interesting question!

Librariankt

Clarification of Answer by librariankt-ga on 27 Jan 2005 13:48 PST
Thank you for the generous tip!  I hope I can provide service for you
again!  If you do choose to use Google Answers again, feel free to ask
for me by name - or you can open up your question to any researcher to
answer.  We're always happy to welcome back questioners!  Librariankt
prorag1-ga rated this answer:5 out of 5 stars and gave an additional tip of: $25.00
Great resource and excellent service from Librariankt.

Comments  
There are no comments at this time.

Important Disclaimer: Answers and comments provided on Google Answers are general information, and are not intended to substitute for informed professional medical, psychiatric, psychological, tax, legal, investment, accounting, or other professional advice. Google does not endorse, and expressly disclaims liability for any product, manufacturer, distributor, service or service provider mentioned or any opinion expressed in answers or comments. Please read carefully the Google Answers Terms of Service.

If you feel that you have found inappropriate content, please let us know by emailing us at answers-support@google.com with the question ID listed above. Thank you.
Search Google Answers for
Google Answers  


Google Home - Answers FAQ - Terms of Service - Privacy Policy