Whey
Protein Isolate
Protein is the building block of life. Essential to a balanced diet and
strong muscles, both serious athletes and serious life extensionists use protein
to enhance their health and performance.
Because so much evidence supports the benefits of whey as a fitness, strength
and health enhancer, there should be every effort made to find the best. And
it is whey protein that is increasingly coming to the public's attention as one
of the most comprehensive forms of protein available.
In fact, in many aspects, whey protein, which is often mixed into a delicious
shake, is even superior to soy.
Whey protein is a potent ally to the general immune system. The protein in whey
has been shown to dramatically raise glutathione levels, which is an essential
water-soluble antioxidant that protects cells and serves to neutralize toxins
such as peroxides, heavy metals, carcinogens, and many others. In animal studies,
whey protein concentrate consistently raised glutathione levels beyond those
of any other protein studied, including soy (Bounous G. and Gold P., Clin. Invest.
Med. 1991).
In fact, glutathione is so necessary to a healthy immune system that it appears
immunity itself can be modulated by glutathione levels (Rosanne K., Fidelus and
Min Fu Tsan. Cellular Immunology, 1986). Sufferers of diseases such as AIDS,
atherosclerosis, Alzheimer's and Parkinson's often exhibit reduced glutathione
levels; however, a small pilot study of HIV-positive men who ate whey protein
found dramatic increases in glutathione levels, with two out of the three men
reaching an ideal weight (Bounous G., Baruchel S., Faiutz J., Gold P., Clin.
Invest. Med. 1992).
In its ability to enhance the immune system, whey protein also fights infections.
Animals fed whey protein showed increased response from both the humoral and
cellular immune systems to a variety of challenges, such as salmonella and streptococcus
pneumonia (Bounous G., Konshavn P., Gold P. Clin. Invest. Med. 1988). Again,
this effect was not seen with other proteins.
Perhaps the most exciting potential of whey protein is its ability to fight cancer.
In vitro research has shown that the growth of breast cancer cells is strongly
inhibited when exposed to low concentrations of whey protein (Baruchel S. and
Vaiu G., Anti Cancer Research 1996).
Another recent clinical study showed a regression in some cancerous tumors when
patients were administered 30 grams per day of whey protein powder (Kennedy R.S.,
Konok G.P., Bounous G., Baruchel S., Lee T.D., Anti Cancer Research 1995). Likewise,
animals fed whey protein before being subjected to dimethylhydrazine (DMH), a
strong cancer-causing agent, mounted a much more vigorous immune response than
animals fed any other type of protein. More importantly, any resulting tumors
were smaller and far fewer in number in the animals fed whey protein (Bounous
G., Clin. Invest. Med. 1988).
This study was confirmed by additional research showing that rats subjected to
DMH and fed whey protein showed fewer tumors and a reduced pooled area of tumors.
The researchers concluded that whey protein offered "considerable protection
to the host," compared with other proteins, including soy (McIntosh G.H.,
et al. Journal of Nutrition 1995).
It is interesting to note that the concentration of glutathione in tumor cells
is often much higher than in surrounding normal cells, meaning that cancer cells
will respond differently to nutrients and drugs that alter glutathione status.
This discrepancy in glutathione status between normal cells and cancer cells
also makes it harder to kill cancer cells with chemotherapy. Because the surrounding
cells have lower levels of glutathione to begin with, anything that further suppresses
glutathione puts normal healthy cells in danger long before cancer cells are
affected.
Instead, cancer patients need a compound that can target cancer cells and deplete
only their glutathione. Whey protein appears to be just such a compound. When
introduced in studies, cancer cells responded to whey protein by losing glutathione,
while normal cells actually increased in glutathione and cellular growth (Baruchel
S. and Vaiu G., Anti Cancer Research 1996). No other protein reported the same
effect. Even the mechanism by which whey protein acts is not fully understood.
It appears that whey protein interferes with the cancer cells' ability to regulate
glutathione.
Whey protein is effective because of its abnormally high biological value, which
is a measure of the nitrogen retained for growth or maintenance, expressed as
a percentage of the nitrogen absorbed (Renner E., 1983). Whey, with the highest
biological value of any protein, is absorbed, utilized and retained in the body
better than other proteins. This has caused athletes to make whey protein concentrate
a best-seller. In fact, one recent pilot study found whey protein isolate corrected
the immune suppression often seen in athletes suffering from over-training syndrome
(C.M. Colker, D. Kalman, W.D. Brink, and L.G. Maharam. Med. Sci. in Sports in
Exercise 1998)
And proteins with a high biological value are more tissue-sparing, making whey
protein concentrate a good choice for people suffering from wasting diseases
such as AIDS, cancer, and/or aging-related muscle losses.
In addition, some animal research suggests whey can prevent atherogenesis by
preventing LDL cholesterol from oxidizing (M.Kajikawa et al. Biochemica et Biophysica
Acta 1994). A complementary study found that whey may reduce LDL levels as well
as triglycerides (Zhang X. and Beynen A.C. Brit. J. of Nutri. 1993). Whey also
appears to have a direct in vitro effect on bone cell growth. It was found to
stimulate protein synthesis, DNA content, and increased hydroxyproline contents
of bone cells (Takada Y., Aoe S., Kumegawa M., Biochemical Research Communications
1996).
Coupled with the observation that animals fed whey protein powder had stronger
bones, researchers concluded, "These findings suggest that whey protein
contains active components that can activate osteoblast cell proliferation and
differentiation. Also these active components can probably permeate or be absorbed
by the intestines. We propose the possibility that the active component in the
whey protein plays an important role in bone formation by activating osteoblasts."
Finally, whey is a highly complex protein that is made up of many sub-fractions,
including beta-lactoglobulin, immuno-globulins, bovine serum albumin (BSA), lactoperoxidases,
lysozyme, lactoferrin and others. Each of these subfractions has its own unique
biological properties and benefits.
Even a brief discussion of lactoferrin, for instance, illustrates the many positive
effects of this one sub-fraction. Lactoferrin is found in tiny amounts in the
human body, yet appears to be a first-line immune system defense. It binds to
iron so strongly that it inhibits the growth of iron-dependent bacteria (Oram,
J., Reiter, B. Biochem. Biophys. Acta, 1968), and can block the growth of many
pathogenic bacteria and yeast (Bellamy W. et al., J. Appl. Bacteriol. 1992).
Its antimicrobial action may even improve antibiotics (Ellison, R.T., Infect.
and Immun. 1988).
In the digestive tract, lactoferrin may help by stimulating intestinal cell growth
(Hagiwara, T., et al., Biosci. Biotech. Biochem. 1995), and enhancing the growth
of "good" intestinal microflora (Petschow, B., et al., Pediat. Res.
1991). A strong antioxidant, lactoferrin has positive immunomodulatory effects
and scavenges free iron, which prevents uncontrolled iron-based free radical
reactions (Eugine. P. et al., 1993) and protects certain cells from lipid peroxidation
(Gutteridge et al., 1981).
It would be wise to incorporate whey protein into a supplement program just to
receive the benefits of lactoferrin. But when these positive influences are combined
with whey protein's many other strengths, including helping the immune system
and fighting cancer, it should become a valuable element of any program.
Fighting Cancer With Whey
By Will Brink
http://www.brinkzone.com/
Recent studies on whey demonstrate it's an even better protein supplement than
previously thought.
Although whey protein's health benefits have only recently been elucidated,
the use of whey protein for medicinal purposes has been prescribed since the
time
of Hippocrates. In fact, there are two ancient proverbs from the Italian city
of Florence that say, "If you want to live a healthy and active life, drink
whey," and, "If everyone were raised on whey, doctors would be bankrupt."
In previous issues, we've chronicled the extensive research showing the many
potential health benefits of whey protein concentrate. The majority of that research
was done in the 1980s and early 1990s, and was extremely persuasive (see sidebar
story). Recently, scientists have continued their research on whey proteins with
even more impressive results. What follows is some of the more current, interesting
and useful research on whey proteins.
Whey and Cancer
Additional studies have been done on animals regarding cancer-causing chemicals
to see what effects whey protein concentrate would have on cancer prevention
or treatment. Scientists fed rats various proteins and then subjected them to
the powerful carcinogen dimethylhydrazine.
As with the previous research, the rats fed whey protein concentrate showed
fewer tumors and a reduced pooled area of tumors (tumor mass index). The researchers
found whey protein offered "considerable protection to the host" over
that of other proteins, including soy.
McIntosh G.H., et al., Journal of Nutrition, 1995)
Even more exciting, in vivo research on cancer and whey showed whey protein concentrate
inhibited the growth of breast cancer cells at low concentrations (Baruchel S.
and Vaiu G., Anti Cancer Research, 1996). Finally, and most importantly, a fairly
recent clinical study with cancer patients showed a regression in some patient's
tumors when fed whey protein concentrate at 30 grams per day.
(Kennedy R.S., Konok G.P., Bounous G., Baruchel S., Lee T.D., Anti Cancer Research,
1995)
Whey and Glutathione
This new research using whey protein concentrate led researchers to an amazing
discovery regarding the relationship between cancerous cells, glutathione (GSH)
and whey protein concentrate. It was found that whey protein concentrate selectively
depletes cancer cells of their glutathione, thus making them more susceptible
to cancer treatments such as radiation and chemotherapy.
It has been found that cancer cells and normal cells will respond differently
to nutrients and drugs that affect glutathione status. What is most interesting
to note is the fact that the concentration of glutathione in tumor cells is higher
than that of the normal cells that surround it. This difference in glutathione
status between normal cells and cancer cells is believed to be an important factor
in cancer cells' resistance to chemotherapy.
As the researchers put it, "Tumor cell GSH concentration may be among
the determinants of the cytotoxicity [poisonous to cells] of many chemotherapeutic
agents and of radiation, and an increase in GSH concentration appears to be
at
least one of the mechanisms of acquired drug resistance to chemotherapy."
They further state, "It is well-known that rapid GSH synthesis in tumor
cells is associated with high rates of cellular proliferation. Depletion of
tumor GSH in vivo decreases the rate of cellular proliferation and inhibits
cancer
growth."
The problem is, it's difficult to reduce glutathione sufficiently in tumor cells
without placing healthy tissue at risk and putting the cancer patient in a worse
condition. What is needed is a compound that can selectively deplete the cancer
cells of their glutathione, while increasing, or at least maintaining, the levels
of glutathione in healthy cells.
This is exactly what whey protein appears to do. In this new research it was
found that cancer cells subjected to whey proteins were depleted of their glutathione,
and their growth was inhibited, while normal cells had an increase in GSH and
increased cellular growth.
These effects were not seen with other proteins. Not surprisingly, the researchers
concluded, "Selective depletion of tumor GSH may in fact render cancer cells
more vulnerable to the action of chemotherapy and eventually protect normal tissue
against the deleterious effects of chemotherapy." The exact mechanism
by which whey protein achieves this is not fully understood, but it appears
that
it interferes with the normal feedback mechanism and regulation of glutathione
in cancer cells.
It is known that glutathione production is negatively inhibited by its own synthesis.
Being that baseline glutathione levels in cancer cells are higher than that of
normal cells, it is probably easier to reach the level of negative-feedback inhibition
in the cancer cells' glutathione levels than in the normal cells' glutathione
levels.
Whey and LDL Cholesterol
The positive health benefits of whey protein concentrate does not end with its
effects on immunity and cancer prevention and treatment. Whey protein concentrate
also was found to be a potent inhibitor of oxidized low density lipoprotein cholesterol.
Current research suggests that the conversion of LDL to oxidized LDL is the trigger
that leads to atherogenesis...the formation of the plaque and lesions associated
with atherosclerosis.
Therefore, any substance that prevents the oxidation of LDL is thought to be
anti-atherogenic. Though animal-based proteins have traditionally been implicated
as being pro-atherogenic, whey proteins appear to be an exception to the rule.
whey protein is made up of several minor and major fractions, such as beta-lactoglobulin,
alpha-lactalbumin, albumin, lactoferrin and immunoglobulin. It was discovered
that the minor constituent responsible for the ability of whey protein concentrate
to prevent the oxidation of LDL appears to be the lactoferrin fraction of the
protein. (M. Kajikawa et al. Biochemica et Biophysica Acta, 1994)
Lactoferrin in Whey
When the lactoferrin was removed from the protein, the ability of the whey-protein
concentrate to prevent LDL oxidation was greatly reduced, leading the researchers
to speculate, "Our results suggest that LF (lactoferrin) is the main factor
responsible for the inhibitory effect of whey protein (on LDL) and it may function
synergistically together with other factors in the whey protein, for example,
alpha-lactalbumin."
Another study using rats examined the effects of whey protein concentrate and
casein on cholesterol and the risk factors of heart disease. Though casein
(another milk-based protein commonly used in research) is known to raise cholesterol
in
humans and animals, whey protein has the opposite effect, leading the researchers
to note, "At the high dietary protein level [300 gram per kilogram of feed]
, whey protein significantly lowered plasma and liver cholesterol and also plasma
triacylglycerols." (Zhang X. and Beynen A.C. Brit. J. of Nutri., 1993)
The cholesterol-lowering effects of whey protein concentrate in this study also
was associated with a reduction in LDL cholesterol. Most interesting was the
fact that this effect on cholesterol was not seen when the animals were fed amino
acid mixtures that simulated whey protein, so it is clear that there are properties
within the whey that have these effects beyond that of its amino acid profile.
Whey and Bone Growth
Finally, whey protein appears to play a direct role in bone growth. Researchers
found that rats fed whey protein concentrate showed increased bone strength and
bone protein such as collagen. This discovery led researches to test whether
or not whey protein directly stimulated osteoblast (bone cell) growth in vitro.
Whey protein was found to stimulate, dose dependently, total protein synthesis,
DNA content, and increased hydroxyproline contents of bone cells.
(Takada Y., Aoe S., Kumegawa M., Biochemical Research Communications, 1996)
It should be noted that not all whey protein concentrates are created equal.
Processing whey protein to remove the lactose and fats without losing its biological
activity takes special care by the manufacturer. The protein must be processed
under low temperature and low acid conditions so as not to "denature" the
protein. Maintaining the natural state of the protein is essential to its biological
activity.
These research findings, combined with the previous decade of study on whey protein,
should convince anyone that whey protein concentrate is truly the life-extension
protein.
Higher Glutathione Levels and Whey:
A decade-and-a-half of findings on the benefits of whey protein are far-reaching.
Previous studies include the following:
-
Whey
protein concentrate dramatically raises glutathione
levels. Glutathione is an essential water-soluble
antioxidant in the body that protects cells and serves
as a primary detoxifier of harmful compounds such
as peroxides, heavy metals, carcinogens and other
toxins.
-
Glutathione
also is intimately tied to immunity, and reduced
glutathione levels have been associated with disease
such as AIDS, atherosclerosis, Alzheimer's disease
and Parkinson's disease, to name only a few. In fact,
glutathione levels appear to be one way of modulating
immunity. (RosanneK., Fidelus and Min Fu Tsan. Cellular
Immunology, 1986)
-
Whey
protein concentrate was found to consistently raise
this extremely important immune stimulating antioxidant
beyond that of any protein studied (including soy)
to higher than normal levels in multiple animal studies.
(Bounous G. and Gold P., Clin. Invest. Med. 1991)
-
A
small pilot study with HIV-positive men who were
fed whey protein concentrate found dramatic increases
in glutathione levels of all the study participants,
with two out of three men reaching their ideal body
weight. (Bounous G., Baruchel S., Faiutz J., Gold
P., Clin. Invest. Med. 1992)
-
In
fact, there have been several U.S. and international
patents granted for the treatment of AIDS and improving
immunity with whey protein concentrates.
-
Whey
protein improves immune function and fights infections.
Animals fed whey protein concentrate consistently
showed dramatic enhancement of both the humoral and
cellular immune response to a variety of immune challenges,
such as salmonella, streptococcus pneumonia (Bounous
G., Konshavn P., Gold P., Clin. Invest. Med. 1988)
and extreme cancer-causing chemicals. This effect
on immunity was not seen with other proteins.
|
The
Benefits of Whey (Abstracts)
Whey protein as cancer treatment adjuvant, antibiotic, and anti-aging
agent
Whey and Chemotherapy
In vitro selective modulation of cellular glutathione
by a humanized native milk protein isolate in normal cells and
rat mammary carcinoma
model
Baruchel S Viau G. In: Anticancer Res (1996 May-Jun)16(3A):1095-9
We report the in vitro selective inhibitory activity of a humanized
whey protein concentrate Immunocal on growth of mammary carcinoma
cells and Jurkat T cells in comparison to normal peripheral blood
mononuclear cells. We relate this inhibitory activity to a selective
depletion of intracellular glutathione synthesis. The use of humanized
whey protein concentrate as a food supplementation may have direct
implication in clinical trial with adjuvant chemotherapy.
-----------------------------------
Whey and Diseases of Aging
The influence of dietary whey protein on tissue glutathione and
the diseases of aging
Bounous G Gervais F Amer V Batist G Gold P. In: Clin Invest Med
(1989 Dec) 12(6):343-9
This study compared the effects of a whey-rich diet (20 g/100 g
diet), with that of Purina mouse chow or casein-rich diet (20 g/100
g diet), on the liver and heart glutathione content and on the
survival of old male C57BL/6NIA mice.
The study was performed during a limited observation period of
6.3 months. In mice fed the whey protein-rich diet between 17 months
and 20 months of age, the heart tissue and liver tissue glutathione
content were enhanced significantly above the corresponding values
of the casein diet-fed and Purina-fed mice.
Mice fed the whey protein diet at the onset of senescence at 84
weeks exhibited increased longevity as compared to mice fed Purina
mouse chow over the 6.3-month observation period extending from
the age of 21 months (corresponding to a human age of 55 years)
to 26-27 months of age (corresponding to a human age of 80 years),
during which time 55% mortality was observed. The corresponding
mean survival time of mice fed the defined casein diet is almost
identical to that of Purina-fed controls.
Body weight curves were similar in all three dietary groups. Hence
a whey protein diet appears to enhance the liver and heart glutathione
concentration in aging mice and to increase longevity over a 6.3-month
observation period.
-----------------------------------
Whey and Cholesterol Concentrations
Lowering effect of dietary milk-whey protein v. casein on plasma
and liver cholesterol concentrations in rats
Zhang X Beynen AC. In: Br J Nutr (1993 Jul) 70(1):139-46
The effect of dietary whey protein versus casein on plasma and
liver cholesterol concentrations was investigated in female, weanling
rats. Balanced, purified diets containing either whey protein or
casein, or the amino acid mixtures simulating these proteins, were
used.
The high-cholesterol diets (10 grams of cholesterol per kg feed)
had either 150 or 300 grams protein or amino acids/kg feed. The
diets were given for 3 weeks. At the low dietary protein level,
whey protein versus casein did not affect plasma total cholesterol,
but lowered the concentration of liver cholesterol.
At the high dietary-protein level, whey protein significantly lowered
plasma and liver cholesterol and also plasma triacylglycerols.
The hypocholesterolemic effect of whey protein was associated with
a decrease in very-low-density-lipoprotein cholesterol.
At the high dietary protein concentration, whey protein reduced
the fecal excretion of bile acids when compared with casein. The
effects of intact whey protein versus casein were not reproduced
by the amino acid mixtures simulating these proteins. It is suggested
tentatively that the cholesterol-lowering effect of whey protein
in rats is caused by inhibition of hepatic cholesterol synthesis.
-----------------------------------
Lactoferrin's Antibacterial Synergy
Damage of the outer membrane of enteric gram-negative bacteria
by lactoferrin and transferring
Ellison RT 3d Giehl TJ LaForce FM. In: Infect Immun (1988 Nov)
56(11):2774-81
We hypothesized that the iron-binding proteins could affect the
gram-negative outer membrane in a manner similar to that of the
chelator EDTA. The ability of lactoferrin and transferrin to release
radiolabeled lipo polysaccharide (LPS) from a UDP- galactose epimerase
deficient Escherichia coli mutant and from wild-type Salmonella
typhimurium strains was tested. Initial studies in barbital-acetate
buffer showed that EDTA and lactoferrin cause significant release
of LPS from all three strains. Further studies found that LPS release
was blocked by iron saturation of lactoferrin, occurred between
pH 6 and 7.5, was comparable for bacterial concentrations from
10(4) to 10(7) CFU/ml, and increased with increasing lactoferrin
concentrations. Studies using Hanks balanced salt solution lacking
calcium and magnesium showed that transferrin also could cause
LPS release. Additionally, both lactoferrin and transferrin increased
the antibacterial effect of a subinhibitory concentration of rifampin,
a drug excluded by the bacterial outer membrane. This work demonstrates
that these iron-binding proteins damage the gram-negative outer
membrane and alter bacterial outer membrane permeability.
-----------------------------------
Antibacterial Activity of Lactoferrin
Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin
peptide fragment
Yamauchi K Tomita M Giehl TJ Ellison RT 3d. In: Infect Immun (1993
Feb) 61(2):719-28
Recent work has indicated that in addition to binding iron, human
lactoferrin damages the outer membrane of gram-negative bacteria.
In this study, we determined whether bovine lactoferrin and a pepsin-
derived bovine lactoferrin peptide (lactoferricin) fragment have
similar activities. We found that both 20 microM bovine lactoferrin
and 20 microM lactoferricin release intrinsically labeled [3H]lipopolysaccharide
([3H]LPS) from three bacterial strains, Escherichia coli CL99 1-2,
Salmonella typhimurium SL696, and Salmonella montevideo SL5222.
Under most conditions, more LPS is released by the peptide fragment
than by whole bovine lactoferrin. In the presence of either lactoferrin
or lactoferricin there is increased killing of E. coli CL99 1-2
by lysozyme. Like human lactoferrin, bovine lactoferrin and lactoferricin
have the ability to bind to free intrinsically labeled [3H]LPS
molecules. In addition to these effects, whereas bovine lactoferrin
was at most bacteriostatic, lactoferricin demonstrated consistent
bactericidal activity against gram-negative bacteria. This bactericidal
effect is modulated by the cations Ca2+, Mg2+, and F3+ but is independent
of the osmolarity of the medium. Transmission electron microscopy
of bacterial cells exposed to lactoferricin show the immediate
development of electron-dense "membrane blisters." These
experiments offer evidence that bovine lactoferrin and lactoferricin
damage the outer membrane of gram-negative bacteria. Moreover,
the peptide fragment lactoferricin has direct bactericidal activity.
As lactoferrin is exposed to proteolytic factors in vivo which
could cleave the lactoferricin fragment, the effects of this peptide
are of both mechanistic and physiologic relevance.
-----------------------------------
Whey's Antibacterial Spectrum
Antibacterial spectrum of lactoferricin B, a potent bactericidal
peptide derived from the N-terminal region of bovine lactoferrin
Bellamy W Takase M Wakabayashi H Kawase K Tomita M. In: J Appl
Bacteriol (1992 Dec) 73(6):472-9
A physiologically diverse range of Gram-positive and Gram-negative
bacteria was found to be susceptible to inhibition and inactivation
by lactoferricin B, a peptide produced by gastric pepsin digestion
of bovine lactoferrin. The list of susceptible organisms includes
Escherichia coli, Salmonella enteritidis, Klebsiella pneumoniae,
Proteus vulgaris, Yersinia enterocolitica, Pseudomonas aeruginosa,
Campylobacter jejuni, Staphylococcus aureus, Streptococcus mutans,
Corynebacterium diphtheriae, Listeria monocytogenes and Clostridium
perfringens. Concentrations of lactoferricin B required to cause
complete inhibition of growth varied within the range of 0.3 to
150 micrograms/ml, depending on the strain and the culture medium
used. The peptide showed activity against E. coli O111 over the
range of pH 5.5 to 7.5 and was most effective under slightly alkaline
conditions. Its antibacterial effectiveness was reduced in the
presence of Na+, K+, Mg2+ or Ca2+ ions, or in the presence of various
buffer salts. Lactoferricin B was lethal, causing a rapid loss
of colony-forming capability in most of the species tested. Pseudomonas
fluorescens, Enterococcus faecalis and Bifidobacterium bifidum
strains were highly resistant to this peptide.
-----------------------------------
Garlic and Cancer
Effects of garlic thioallyl derivatives on growth, glutathione
concentration, and polyamine formation of human prostate carcinoma
cells in culture
Pinto JT Qiao C Xing J Rivlin RS Protomastro ML Weissler ML Tao
Y Thaler H Heston WD. In: Am J Clin Nutr (1997 Aug) 66(2):398-405
This study investigated whether naturally occurring garlic derivatives
and synthetic S-cysteinyl compounds that resemble garlic constituents
have antiproliferative effects on human prostate carcinoma (LNCaP)
cells. Studies also examined whether S-allylmercaptocysteine and
S-allylcysteine affect two important molecular targets, namely
reduced glutathione and polyamines. Results showed that S-allylmercaptocysteine
(50 mg/L) diminished LNCaP cell growth whereas the antiproliferative
effect of S-allylcysteine was not as pronounced. Studies using
synthetic S-cysteinyl analogues revealed that growth inhibition
was most effective with compounds containing a disulfide or an
active diallyl moiety. Marginal-to-no inhibitory effect was observed
with monosulfinic analogues. Both S-allylmercaptocysteine and S-allylcysteine
caused an increase in LNCaP cell reduced glutathione concentrations.
Putrescine and spermine concentrations decreased and spermidine
increased 3 days after S-allylmercaptocysteine treatment. At 5
days after S-allylmercaptocysteine treatment, polyamine concentrations
were similar to those of saline-treated controls. Diminished cell
growth and altered polyamine concentrations suggest that S-allylmercaptocysteine
may impede the polyamine synthesizing enzyme, ornithine decarboxylase,
either by enhancing the formation of reduced glutathione, a known
inhibitor of ornithine decarboxylase, or by reacting directly with
ornithine decarboxylase at its nucleophilic thiol moiety. Because
S-allylcysteine also increases reduced glutathione formation but
does not significantly inhibit growth, the latter mechanism may
be more likely for this compound. These data provide further evidence
that nonessential nutrients derived from garlic may modulate tumor
growth.
-----------------------------------
Folic Acid, Gingival Overgrowth
Effect of folic acid on recurrence of phenytoin-induced gingival
overgrowth following gingivectomy
Poppell TD Keeling SD Collins JF Hassell TM. In: J Clin Periodontol
(1991 Feb) 18(2):134-9
This study examined the effect of folic acid supplementation on
the recurrence of phenytoin-induced gingival overgrowth following
gingivectomy. Eight residents of an institution for the developmentally
disabled were randomly assigned to a treatment (N = 4) or control
(N = 4) group. Subjects in the treatment group received an oral
supplementation of 5 mg of folic acid daily during the study; those
in the control group did not. A gingivectomy with an external beveled
incision made to the crest of the alveolus was completed by quadrants.
The following data were obtained prior to gingivectomy, 2 weeks
following the last quadrant of surgery, and at 3 and 6 months post-surgery:
plaque and gingival index scores, red blood cell folic acid levels,
free phenytoin blood levels, photographs, and impressions. Percent
change in overgrowth was determined from cross- sectional area
measurements made on dies obtained from bucco-lingual cuts on stone
models. The groups did not differ in plaque and gingival index
scores or free phenytoin blood levels. The treatment group had
significantly higher red blood cell folic acid levels (p less than
or equal to 0.0001). Reduction in gingival overgrowth as a result
of surgery was similar in both groups. Although the treatment group
had significantly less recurrence of gingival overgrowth (p less
than or equal to 0.05), the mean differences amounted to only 6-7%
at 3 and 6 months.
-----------------------------------
Folate, Phenytoin Hyperplasia
Effect of folate on phenytoin hyperplasia
Drew HJ Vogel RI Molofsky W Baker H Frank O. In: J Clin Periodontol
(1987 Jul) 14(6):350-6
There have been some reports that folic acid inhibits phenytoin-
induced gingival hyperplasia. The purpose of this double-blind
study was to quantify clinically the effects of both systemic and
topical administration of folic acid on phenytoin-induced gingival
overgrowth in man. For a period of 6 months, one group of phenytoin
patients received 2 daily topical applications of a folate solution.
An additional group received 2 daily doses of systemic folate while
a control group received placebo medication. Results indicate that
throughout the 180-day period of the study, the topical folate
significantly inhibited gingival hyperplasia to a greater extent
than either systemic folate or placebo groups.
-----------------------------------
Folate Mouthwash
Effects of folate mouthwash on experimental gingivitis in man
Pack AR .In: J Clin Periodontol (1986 Aug) 13(7):671-6
Although the experimental gingivitis model has been used extensively
since 1965, some doubts exist concerning the nature of the tissue
response in this model. Accordingly, the present study was designed
to determine whether or not experimental gingivitis responded to
0.1% folate mouthwash (MW) in a similar manner to that already
reported for established gingivitis. Twenty male dental students
took part in a double blind cross-over study which involved two
3-week experimental periods with random allocation to folate or
placebo MW. The experimental site was the lower anterior area and
24 points of gingival examination were made at baseline and weeks
1, 2 and 3. Inflammation was assessed by presence or absence of
color change, and bleeding being slight, profuse or absent when
gingivae were stroked with a blunt probe. A plaque sample was evaluated
using dark field microscopy, and dry weight of accumulated plaque
was measured at the end of each experimental period. Folate MW
did not appear to have any statistically significant effects on
accumulated plaque, or clinical signs of experimental gingivitis
in this study. The different response of experimental gingivitis
to folate MW, compared with the response of established gingivitis
already reported, further suggests that experimental gingivitis
may not represent an authentic replica of the cellular and immunological
responses occurring in established gingivitis.
> Return to Ingredient List
> Return Home
|
