Promato is a nutritional supplement with antioxidant properties. Its active ingredients are Lycopene, Ellagic acid and Zinc Picolinate. Free radicals have been implicated in many diseases. As an antioxidant formulation, Promato acts as free-radical scavenger and quenches singlet oxygen, enhances the immune function and maintains the function of the prostate gland.
Lycopene is a bright red pigment that gives fruits and vegetables such as tomatoes their red colour. Its name is derived form the tomato species classification, Solanum lycopersicum. Lycopene has exceptional antioxidant activity against singlet-oxygen free radicals. Studies have shown that men who eat substantial amounts of tomatoes appear to have a lower incidence of prostate cancer. It is also related to a reduced risk of oesophageal, colon skin, bladder and mouth cancers.
Ellagic acid is a natural occurring phenolic compound in many plants, particularly strawberries (Fragaria x ananassa Duch.), raspberries (Rubus species), blackberries [Rubus L. subgenus Rubus (Eubatus)] and pomegranates (Punica granatum). It is a powerful antioxidant derived form raspberries in particular with the ability to support cell structures with regards to DNA replication and cell division.
Zinc Picolinate provides elemental zinc to the body. It is essential for normal growth and development and life span. Its primary mode of action is by participating in over twenty key enzyme reactions in the body. It supports a healthy immune system, is needed for wound healing, and is needed for DNA synthesis. Zinc reduces the body’s level of prolactin, a hormone that stimulates synthesis of dihydrotestosterone, DHT, believed to promote malignant growth of prostate cells.
Lycopene
1 Inhibition of cancer cell proliferation
The inhibitory effects of lycopene on mammary and prostate cancer cell
growth were not accompanied by apoptotic (programmed) or necrotic
(resulting from injury or disease) cell death, a mechanism related to
the action of some drugs but not to micronutrients frequently consumed
in the human diet. This effect was accompanied by inhibition of cell
cycle progression from the G0/G1 to the S phase as measured by flow
cytometry (Nahum A, 2001). The inhibition of cell proliferation
correlated with a decrease in cyclin D1 protein levels which is a key
regulator of this process. It is well documented that growth factors
affect the cell cycle apparatus (primarily during G1 phase) and that
the main components acting as growth factor sensors are the D-type
cyclins (Sherr CJ, 195).Moreover, cyclin D1 is known to act as an
oncogene (a gene whose dysregulation causes normal cells to become
cancerous) and is found to be over-expressed in many breast cancer cell
lines as well as in primary tumors (Buckley MF, 1993). Thus, the
decrease in cellular cyclin D1 level by Lycopene provides a mechanistic
explanation for the anticancer activity of the carotenoid.
2 Interference with growth factors stimulation of cancer cell proliferation
The growth stimulation of mammary cancer cells by insulin-like growth
factor 1 (IGF-1) was markedly reduced by physiological concentrations
of lycopene in experimental in vitro studies (Levy J, 1995; Karas M,
2000). The significance of this finding for cancer prevention is
related to independent epidemiological findings that elevated IGF-1
levels increase lifetime risks of breast and prostate cancer (Chan JM,
1998;
Hankinson SE, 1998).
3 Cancer prevention by inducing phase II enzymes
Induction of phase II enzymes, which conjugate reactive electrophiles
(chemicals that are attracted to electrons or tend to accept electrons
from other chemicals) and act as indirect antioxidants, appears to be
an effective means for achieving protection against a variety of
carcinogens in animals and humans. Bhuvaneswari et al (Bhuvaneswari V,
Dec 2001) associated the chemopreventive (cancer-preventive) effect of
lycopene on the incidence of DMBA-induced hamster buccal (cheek, mouth)
pouch tumours with a simultaneous rise in the level of reduced
glutathione, enzymes of the glutathione redox cycle, and glutathione
S-transferase (GST) in the buccal pouch mucosa. (Note: DMBA is a
9,10-dimethylbenz-aanthracene, a potent tumour-initiating compound.)
These results suggest that the lycopene-induced increase in the levels
of GSH and the phase II enzyme GST inactivates carcinogens by forming
conjugates (chemicals formed by two or more compounds), products that
are less toxic and readily excreted.
4 Regulation of transcription
Transcription is the process whereby genetic information is carried
from the DNA molecule via the RNA molecule acting as a messenger. This
biochemical route leads to the formation of new proteins by the process
called translation. Lycopene modulates the basic mechanisms of cell
proliferation, growth factor signalling, and gap junctional
intercellular communication (Aust O, 2003). Additionally, lycopene
produces changes in the expression of many proteins participating in
these processes, e.g., connexins, cyclins, and phase II enzymes. The
changes in the expression of multiple proteins suggest that the initial
effect of lycopene involves modulation of transcription; this process
is reviewed by Sharoni et al., in a recent publication (Sharoni Y,
2004). This may be due to either direct interaction of the carotenoid
molecules or their derivatives with transcription factors (e.g., with
ligand-activated nuclear receptors (Stahl W, 2000) or indirect
modification of transcriptional activity (e.g., via changes in status
of cellular redox, which affects redox-sensitive transcription systems
(Levy J, 2004).
5 Lycopene and benign prostate hyperplasia
A Pilot study was conducted at the University of Hohenheim and recently
published in the Journal of Nutrition (Schwarz S etal; 2008). Men given
15mg daily of a Lycopene supplement showed lycopene’s benefit against
benign prostate hyperplasia with no signs of cancer, a condition said
to affect more than half of all men over the age of 50. At the end of
six months they reported that levels of prostate-specific antigen
(PSA), a marker of prostate health, were reduced in the lycopene group
showing improvement in the health of the tissue with no changes
recorded in the placebo group. No enlargement in the Lycopene group was
observed whereas growth in the placebo group was observed after the
trial. As a result, the researchers have been able to conclude that
lycopene supplements can inhibit progression of BHP.
"Symptoms of the disease, as assessed via the International Prostate
Symptom Score questionnaire, were improved in both groups with a
significantly greater effect in men taking lycopene supplements," the
researchers wrote.
Ellagic acid
Data for Ellagic acid from Dr. Daniel Nixon’s (see The Cancer Recovery
Eating Plan, Times Books, NY, 1994) studies at the Hollings Cancer
Centre in the Medical University of South Carolina and other
investigators indicates that it:
- activates detoxifying enzymes in the liver resulting in the clearing of cancer-causing chemicals (mutagens) in the serum,
- prevents the binding of carcinogens to cellular DNA,
- serves as an antioxidant in the scavenging and clearance of
highly destructive oxygen free radicals, 4) induces apoptosis
(programmed cell death) in cancerous cells, and
- stimulates the immune system for the destruction of cancerous cells.
During the normal process of cell division, the replicating cell is
“carried off” as trash just as if a bacterium had died. The body
signals the dismantling of the old cell and the new cell takes over its
processes. This is called apoptosis, or natural cell death.
Cancer cells, however, are different. Cancer cells do not die; they
rapidly multiply by cell division (mitosis), making 2 cancer cells,
then 4, 8, 16, 32 and so on. Dr. Nixon found that in both laboratory
and clinical studies, red raspberry ellagitannins caused cancer cells
to go through a non-toxic, normal apoptosis process without damaging
the healthy cells. This is a remarkable improvement over standard
treatment such as chemotherapy and radiation that kill healthy cells
too - destroying the immune system in the process.
Cancer
Oxidative stress is recognized as one of the major contributors to the increased risk of cardiovascular disease and cancer.
Ellagic acid is a dietary supplement which is used to prevent and treat
cancer. Lycopene has been found to inhibit proliferation of several
types of cancer cells, including those of breast, prostate, lung, and
endometrium.
Oxidative stress is recognized as one of the major contributors to
increased risk of cancer, and in chemical assays lycopene is the most
potent antioxidant among various common carotenoids. In addition, in
vivo studies have shown lycopene has tumour-suppressive activity. Other
studies support the hypothesis that carotenoid-containing plant
products, such as lycopene, exert a cancer protective effect via a
decrease in oxidative and other damage to DNA in humans.
1. Prostate cancer
Cancer of the prostate is the most commonly diagnosed solid malignancy
and the second-leading cause of cancer-related death in men in
developed countries. Certain studies suggests even a short course of
lycopene prior to surgery has the potential to decrease the growth of
prostate cancer (Mills PK, 1989; Hadley CW etal, 2002).
A number of studies, examining tomato products, lycopene intake, or
circulating lycopene levels in relation to prostate cancer risk,
suggest high consumption or high circulating concentrations are
associated with a reduction in risk of prostate cancer (Lu QY etal,
2001; Kucuk O etal, 2001).
The greatest concentration of zinc is found in the male prostate (10 times more than in any other organ).
Zinc has a normalising effect on the prostate and zinc levels decrease
significantly during the incidence of BPH and prostatitis. Zinc reduces
the body’s level of prolactin, a hormone that stimulates synthesis of
dihydrotestosterone, DHT, believed to promote malignant growth of
prostate cells.
2. Breast Cancer
Some studies have found a significant inverse association between
lycopene in breast tissue and breast cancer risk. In cell cultures,
lycopene has been found to inhibit breast cancer tumour cell growth
more efficiently when compared to alpha and beta-carotene (Levy J etal,
1995; Karas M, 2000).
Coronary Heart Disease
Oxidative stress induced by reactive oxygen species (ROS) is also
considered to play an important part in the etiology of coronary heart
disease. Dietary lycopene has been shown in in-vitro studies to prevent
the formation of oxidized LDL, a key player in the pathogenesis of
atherosclerosis and CHD (Fuhrman B, 1997).
Evidence from a multi-centre case-control study (the EURAMIC study) in which subjects from 10
European countries were evaluated for a relationship between their
antioxidant status and acute myocardial infarctions. After adjusting
for a range of dietary variables, only lycopene levels, not
beta-carotene levels, were found to be protective (Kohlmeier L, 1997).
These results were also confirmed by another study (the Rotterdam
Study) (Klipstein-Grobusch K, 2000).
Serum lycopene concentration may play a role in the early stages of
atherosclerosis. Increased thickness of intima-media (the innermost
lining of a blood vessel, including the middle, muscular layer in the
wall of the blood vessel) has been shown to predict coronary events. A
low serum lycopene concentration, prevalent in eastern Finland, was
associated with an increased thickness of the intima-media (Rissanen
TH, 2001; Rissanen TH, 2003). In Lithuanian and Swedish populations
showing diverging mortality rates from CHD, lower blood lycopene levels
were found to be associated with increased risk and mortality from CHD
(Kristenson M, 1997). Recently a prospective, nested, case-control
study was conducted by Harvard University researchers on 39,876 women.
The study showed that higher plasma lycopene concentrations are
associated with a lower risk of cardiovascular disease in middle-aged
and elderly women (Seeso HD, 2004).
Moreover, as noted previously by the same group,(Seeso HD, 2003) the
possible inverse associations with cardiovascular disease for higher
levels of tomato-based products (particularly tomato sauce and pizza),
suggest that dietary lycopene or other phytochemicals consumed as
oil-based or oil-containing tomato products confer cardiovascular
benefits.
It was recently found that lycopene can also inhibit cholesterol
synthesis, and thereby stimulate the LDL receptor activity in
macrophages. Stimulating the LDL receptor activity in macrophages leads
to enhanced rates of cellular LDL degradation and to the increased
removal of LDL from extra-cellular spaces, including the plasma
environment.
Researchers from The Ramban Medical Centre Haifa, Israel (Aviram M)
administered 60 mg of lycopene a day to 6 healthy males over a three
month period, they realized a significant 14% reduction in the plasma
LDL cholesterol concentrations (Fuhrman B, 1997). Thus, in addition to
protecting LDL from oxidative modification, tomato’s lycopene is an
inhibitor of cholesterol synthesis, and therefore a hypolipidemic
nutrient (Fuhrman B, 1999).
A recent study at the University of Negev (Englehard Y., 2006) has
shown that patients with moderate or Grade-1 hypertension taking a
Lycopene supplement daily for 4 weeks experienced a ten and four point
reduction in their systolic and diastolic blood pressure. The effects
were attributed to the anti-oxidant activity of lycopene which prevents
reactive oxygen attack of endothelium which results in impaired
dilation and thus high blood pressure.
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