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Planet Muscle Magazine, Pg. 72, Vol. 4:2,
2001
Dr. Sam Bernal earned his doctorate in biochemical
pathology from the University of Chicago. His medical degree is in internal
medicine and associated research in human biochemistry from Johns Hopkins
Hospital in Baltimore. Dr.
Bernal continued training in internal medicine at the Peter Brigham
Hospital and then trained as a fellow in the Department of Medicine at
Harvard Medical School studying cancer. He is now a professor of medicine
at UCLA.
Dr. Hatfield:
I have seen the clinical data on a
scientific study known as the Lipotropin [LipoForce ™] Project
and you were the major research force involved. I understand the delivery
base is liposomes. What directed you to the study of liposomes for this
innovative research and formula?
Dr. Bernal:
We have been doing research on
liposomes for more than 10 years, mostly on liposomes as they relate to
the delivery of anticancer drugs. We have found an advantage in terms of
lower toxicity and greater absorption of these drugs with liposomes. We
saw the same enhanced delivery when we used nutritional supplements
including growth hormone, so we then applied the same type of
pharmaceutical technology to the nutritional supplement
area.
Dr. Hatfield:
But why the interest in
nutritional supplements?
Dr. Bernal:
From a commercial point of view,
it was fairly recent because when we were still in Boston, our group of
scientists had formed a collaboration between several faculty members from
Harvard and MIT. And one of the things we were guided by was that a lot of
our research remained in the laboratory. Very often we were directed to
research that really took 10 to 15 years sometimes to really come to
clinical Session. Going through the FDA process is a lengthy process.
So even though most of us continued to do the FDA process, we felt that
many of the research findings we had in the laboratory could be applied to
commercial products more quickly if we went into the nutritional
area. Many of my colleagues
who are also working with us in the research and in the commercial
development, had backgrounds that were often in nutritional biochemistry,
in protein biochemistry, in drug delivery, in pharmaco-kinetics. So it was
a natural progression for us to apply these technologies to the
nutritional scene. We have people in our group with Ph.D.s in nutritional
biochemistry.
Dr. Hatfield:
I am familiar with liposomal
delivery, but please explain more to PLANET MUSCLE
readers.
Dr. Bernal:
The key to successful ingestion
and use of very large molecular substances like human growth hormone is
stability. Liposomes provide an advantage in keeping the structure of a
molecule in its native form. There is a tendency for large molecules, in
particular, to become de-natured by the gut and hepatic system. They are
left without any protection. They must be made to stay stable. Another
principal is cellular interaction. We know from studies done on other
ingredients that the presence of the liposome increases the interaction
with the target cell.
Stability and biological activity are critical.
Dr.
Hatfield:
So the liposomes are crucial in keeping the three dimensional
structure of the hGH molecule in solution?
Dr.
Bernal:
Yes. Human growth hormone, just like other polypeptide hormones, is
linear in structure, a linear three dimensional chain. In order for it to
act biologically, it has to maintain its three-dimensional structure. This
allows the molecule to interact with the cell receptor and to be able to
perform its biological action on the cell. Keeping the three-dimensional
structure of the molecule in solution by itself is very difficult.
However, the more concentrated you keep it, the mere likely it is to keep
its native three-dimensional structure and do its work. Liposome is able
to trap molecules inside a fat carrier. Once inside the carrier, it is
kept in a concentrated form and 3-dimensional structure, instead of
jettisoning into solution.
Dr.
Hatfield:
Assuming this Lipotropin [LipoForce] formula has efficacy, is it
safer than injecting pharmaceutical, recombinant growth
hormone?
Dr.
Bernal:
Well, it certainly is less likely to cause local problems at the
site of injection and is much more convenient and less expensive by some
hundred-fold. You don’t have to worry about sterile technique and are less
likely to overdose. Because you are able to administer it several times
during the day, it is easier to achieve a stable level. As you know with
many injections, you get a big infusion of dose and a spike all of a
sudden, but the rest of the time, there is not much remaining to affect an
outcome.
Dr.
Hatfield:
Clinically, why did you use kidney cells to measure an
effect?
Dr.
Bernal:
Kidney cells are important targets for the action of growth
hormones. In fact, the three major targets of a growth hormone are liver,
muscle, and kidney. Kidney cells are important for another reason. Its
that for many of our drug studies particularly involving anti-cancer drugs
or in nutritional supplements, one of the things that we watch for is
toxicity to the kidney. So when we culture-study kidney cells, we
accomplish two things. We assay the biological effect of a hormone and
observe whether or not there is any toxicity that might be directed to
other organs.
Dr. Hatfield:
In one portion of your research, you
showed the total cellular protein output of the kidney cells treated with
Lipotropin [LipoForce] and hGH, was greater than the kidney cells treated
with growth hormone alone. Can you comment?
Dr. Bernal:
In solution, the growth hormone
alone showed some binding to the target cells, in this case, the kidney
cells. But the presence of the liposome allowed much higher amounts of the
growth hormone to bind to the kidney cells. We felt the enhanced binding
due to stability was responsible for the increase in the total cellular
protein output increase. In order for the target to respond by increasing
their prosynthesis, they have to be proportional to the amount of hormone
that bound to the cell receptor.
So the action of the liposome was to increase the amount of hormone
bound to the target and, because there was an increased level of the
hormone bound, there was also logical action resulting in protein
synthesis by the cells.
Dr. Hatfield:
I understand microscopic examination
reveals that the kidney cell membrane and liposome fuse. Does this have
significance?
Dr. Bernal:
After the administration of the
liposomal growth the liposomes bind to the surface membrane of the target
cell. By monitoring the amount of the growth hormone that is actually
bound to the surface, plus the amount of growth hormone that is present
inside the cells, we find
that after the liposome binds to the cell membrane, there is fusion. The
membrane of the liposome, being similar to the normal human cell
membrane, starts to fuse with it they become one. The next step is when the liposome
combines with the cell membrane of the cell, practically all of the
contacts within the liposome are delivered inside the cell. We can see the
shift in the presence of the growth hormone from outside the cell, to the
membrane of the cell, finally to inside the cell -- into the cytoplasm and
eventually to the nucleus.
When we tried to do this with a growth hormone alone without the
presence of the liposome, there was much less binding to the cell membrane
and much less growth hormone that winds up inside the cell, cytoplasm and
nucleus. The liposome radically increases the amount of hGH ultimately
delivered to the nucleus.
Dr.
Hatfield:
Once fusion occurs, the growth hormone that is trapped within
the liposome is able to remain inside the cell and presumably affect
function -- growth?
Dr. Bernal:
We believe this is correct.
Dr.
Hatfield:
And the same thing that happens with the kidney cells also
happens with muscle and liver?
Dr. Bernal:
Yes.
Dr.
Hatfield:
Did you expect to see such a high protein output from the cells
treated with Lipotropin [LipoForce]?
Dr. Bernal:
No. This was a pleasant
surprise. Normally when we try to increase the activity of a drug, we see
increases in activity by 30 to 50 percent. In this case, we clearly
observed 200 to 300 percent. Protein synthesis increased radically as a
result of the liposome plus the growth hormone as compared to growth
hormone in solution by itself.
Dr.
Hatfield:
Unreal. Is it unique that the liposomes aid in the delivery of
the growth hormone molecule to the nucleus of the
cell?
Dr. Bernal:
Yes, we are using varying size pharmaceutical liposomes, similar
to what we use in cancer treatment. In this case the liposomes are
designed to react. And they
will react as soon as they come into contact with a target cell. The
pharmaceutical liposomes are more dynamic.
Dr. Hatfield:
Have you formed any preliminary
conclusion that Lipotropin [LipoForce] will raise growth hormone levels from
the research that you have performed?
Dr. Bernal:
Yes. The cell culture models that we used in the laboratory for
the growth hormone research was the same cell culture system that we would
use in pharmaceutical drug development. The advantage of this model system
is that we can make correlations about what we find in the laboratory with
what we ultimately find in the clinic. The result we have from the model
system in the laboratory is extremely favorable.
Dr. Hatfield:
Well let’s speculate.
Will this increased circulating growth hormone affect IGF- 1 and
add muscle with training?
Dr. Bernal:
Yes. In fact,
compared to the administration of only growth hormone (in solution) by
itself, definitely. We would predict that if you only administered the
growth hormone or even a growth-hormone-releasing factor by itself in
solution [without a liposome carrier] it is not likely to be able to have
enough of a biological effect. This biological effect, by the
dministration of these supplements through a buccal route, we would
predict, would be highly accelerated by the use of liposomes. Of course,
injected human growth hormone is effective, as it avoids being in a
solution.
[Editor’s note: The entire point of this interview
is that LipoForce is clinically proven to speed protein synthesis. The key quote: “In this case, we
clearly observed 200 to 300 percent. Protein synthesis increased radically
as a result of the liposome plus the growth hormone as compared to growth
hormone in solution by itself.” The
liposome delivery system used in LipoForce™
is the key to this process.
Of course, increased protein synthesis relates to increased muscle
size and strength, as well as many other (anti-aging)
benefits.] | 
Fred Hatfield,
Ph.D. interviews Sam Bernal, M.D.