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Print ISSN: 2278 - 2648
Online ISSN: 2278 - 2656
International Journal of
Research in Pharmacology and
Research article
Sumit Agarwal
Director, Sain Medicaments Pvt. Ltd., Hyderabad, A.P.
Damage to cells caused by free radicals is believed to play a central role in the aging process and in disease
progression. Antioxidants are our first line of defense against free radical damage, and are critical for
maintaining optimum health and well being. The need for antioxidants becomes even more critical with
increased exposure to free radicals. Pollution, cigarette smoke, drugs, illness, stress, and even exercise can
increase free radical exposure. As many factors can contribute to oxidative stress, individual assessment of
susceptibility becomes important. Many experts believe that the Recommended Dietary Allowance (RDA) for
specific antioxidants may be inadequate and, in some instances, the need may be several times the RDA. As part
of a healthy lifestyle and a well-balanced, wholesome diet, antioxidant supplementation is now being recognized
as an important means of improving free radical protection. Based on these facts a super antioxidant
multivitamin, multimineral formulation LYCOZEN-GT of Lycopene, GreenTea Grape seed has been developed
by R&D Centre, Sain Medicaments Pvt Ltd, Hyderabad. This paper Reviews the Role of LYCOZEN-GT in
maintaining optimum health and well being.
KEYWORDS: Lycozen-GT, Antioxidant, Multivitamin, Multimineral, Grape seed.
The ability to utilize oxygen has provided humans
with the benefit of metabolizing fats, proteins, and
carbohydrates for energy; however, it does not
come without cost. Oxygen is a highly reactive
atom that is capable of becoming part of potentially
damaging molecules commonly called “free
radicals.” Free radicals are capable of attacking the
healthy cells of the body, causing them to lose their
structure and function. Cell damage caused by free
* Corresponding author:
Sumit Agarwal, M.Pharm.,
Sain Medicaments Pvt.Ltd,
E-mail address: [email protected]
radicals appears to be a major contributor to aging
and to degenerative diseases of aging such as
cancer, cardiovascular disease, cataracts, immune
system decline, and brain dysfunction.
Overall, free radicals have been implicated in the
pathogenesis of at least 50 diseases. Fortunately,
free radical formation is controlled naturally by
various beneficial compounds known as
antioxidants. It is when the availability of
antioxidants is limited that this damage can become
Sumit Agarwal et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-1(2) 2012 [103-120]
cumulative and debilitating. Free radicals are
electrically charged molecules, i.e.; they have an
unpaired electron, which causes them to seek out
and capture electrons from other substances in
order to neutralize themselves. Although the initial
attack causes the free radical to become
neutralized, another free radical is formed in the
process, causing a chain reaction to occur. And
until subsequent free radicals are deactivated,
thousands of free radical reactions can occur within
seconds of the initial reaction. Antioxidants are
capable of stabilizing, or deactivating, free radicals
before they attack cells. Antioxidants are absolutely
critical for maintaining optimal cellular and
systemic health and well-being.
Reactive oxygen species (ROS) is a term which
encompasses all highly reactive, oxygen-containing
molecules, including free radicals. Types of ROS
include the hydroxyl radical, the superoxide anion
radical, hydrogen peroxide, singlet oxygen, nitric
oxide radical, hypochlorite radical, and various
lipid peroxides. All are capable of reacting with
membrane lipids, nucleic acids, proteins and
enzymes, and other small molecules, resulting in
cellular damage. ROS are generated by a number of
pathways. Most of the oxidants produced by cells
occur as:
• A consequence of normal aerobic metabolism:
approximately 90% of the oxygen utilized by the
cell is consumed by the mitochondrial electron
transport system.
• Oxidative burst from phagocytes (white blood
cells) as part of the mechanism by which bacteria
and viruses are killed, and by which foreign
proteins (antigens) are denatured.
• Xenobiotic metabolism, i.e., detoxification of
toxic substances. Consequently, things like
vigorous exercise, which accelerates cellular
metabolism; chronic inflammation, infections, and
other illnesses; exposure to allergens and the
presence of “leaky gut” syndrome; and exposure to
drugs or toxins such as cigarette smoke, pollution,
pesticides, and insecticides may all contribute to an
increase in the body’s oxidant load.
Sumit Agarwal et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-1(2) 2012 [103-120]
To protect the cells and organ systems of the body
against reactive oxygen species, humans have
evolved a highly sophisticated and complex
antioxidant protection system. It involves a variety
of components, both endogenous and exogenous in
synergistically to neutralize free radicals.
These components include:
• Nutrient-derived antioxidants like ascorbic acid
(vitamin C), tocopherols and tocotrienols (vitamin
E), carotenoids, and other low molecular weight
compounds such as glutathione and lipoic acid.
• Antioxidant enzymes, e.g., superoxide dismutase,
glutathione peroxidase, and glutathione reductase,
which catalyze free radical quenching reactions.
• Metal binding proteins, such as ferritin,
lactoferrin, albumin, and ceruloplasmin that
sequester free iron and copper ions that are capable
of catalyzing oxidative reactions.
• Numerous other antioxidant phytonutrients
present in a wide variety of plant foods
Fig:3: How do antioxidants operate
Hydroxyl radical
Superoxide radical
Hydrogen peroxide
Lipid peroxides
Vitamin C, glutathione, flavonoids, lipoic acid
Vitamin C, glutathione, flavonoids, SOD
Vitamin C, glutathione, beta carotene, vitamin E,
CoQ10, flavonoids, lipoic acid
Beta carotene, vitamin E, ubiquinone, flavonoids,
Glutathione peroxidase
Vitamin C, vitamin E, and beta carotene are among
the most widely studied dietary antioxidants.
Vitamin C is considered the most important watersoluble antioxidant in extracellular fluids. It is
capable of neutralizing ROS in the aqueous phase
before lipid peroxidation is initiated. Vitamin E, a
major lipid-soluble antioxidant, is the most
effective chain-breaking antioxidant within the cell
membrane where it protects membrane fatty acids
from lipid peroxidation. Vitamin C has been cited
as being capable of regenerating vitamin E. Beta
carotene and other carotenoids are also believed to
provide antioxidant protection to lipid-rich tissues.
Sumit Agarwal et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-1(2) 2012 [103-120]
Research suggests beta carotene may work
synergistically with vitamin E.
A diet that is excessively low in fat may negatively
affect beta-carotene and vitamin E absorption, as
well as other fat-soluble nutrients. Fruits and
vegetables are major sources of vitamin C and
carotenoids, while whole grains and high quality,
properly extracted and protected vegetable oils are
major sources of vitamin E.
A number of other dietary antioxidant substances
exist beyond the traditional vitamins discussed
above. Many plant-derived substances, collectively
termed “phyto nutrients,” or “phyto chemicals,” are
becoming increasingly known for their antioxidant
activity. Phenolic compounds such as flavonoids
are ubiquitous within the plant kingdom:
approximately, 3,000 flavonoid substances have
been described.
In plants, flavonoids serve as protectors against a
wide variety of environmental stresses while, in
humans, flavonoids appear to function as
“biological response modifiers.”
Flavonoids have been demonstrated to have antiinflammatory, antiallergenic, anti-viral, anti-aging,
and anti-carcinogenic activity.
The broad therapeutic effects of flavonoids can be
largely attributed to their antioxidant properties. In
addition to an antioxidant effect, flavonoid
compounds may exert protection against heart
disease through the inhibition of cyclooxygenase
and lipoxygenase activities in platelets and
In addition to dietary antioxidants, the body relies
on several endogenous defense mechanisms to help
protect against free radical-induced cell damage.
The antioxidant enzymes – glutathione peroxidase,
catalase, and superoxide dismutase (SOD) –
metabolize oxidative toxic intermediates and
require micronutrient cofactors such as selenium,
iron, copper, zinc, and manganese for optimum
catalytic activity. It has been suggested that an
inadequate dietary intake of these trace minerals
may compromise the effectiveness of these
antioxidant defense mechanisms. Research
indicates that consumption and absorption of these
important trace minerals may decrease with aging.
Intensive agricultural methods have also resulted in
significant depletion of these valuable trace
minerals in our soils and the foods grown in them.
antioxidant, is synthesized from the amino acids
glycine, glutamate, and cysteine. Glutathione
directly quenches ROS such as lipid peroxides, and
also plays a major role in xenobiotic metabolism.
Exposure of the liver to xenobiotic substances
upregulation of detoxification enzymes, i.e.,
cytochrome P-450 mixed-function oxidase. When
an individual is exposed to high levels of
xenobiotics, more glutathione is utilized for
conjugation (a key step in the body’s detoxification
process) making it less available to serve as an
antioxidant. Research suggests that glutathione and
vitamin C work interactively to quench free
radicals and that they have a sparing effect upon
each other.
Lipoic acid, yet another important endogenous
antioxidant, categorized as a “thiol” or “biothiol,”
is a sulfur-containing molecule that is known for its
involvement in the reaction that catalyzes the
oxidative decarboxylation of alpha-keto acids, such
as pyruvate and alphaketoglutarate,in the Krebs
cycle. Lipoic acid and its reduced form,
dihydrolipoic acid (DHLA), are capable of
quenching free radicals in both lipid and aqueous
domains and as such has been called a “universal
antioxidant.” Lipoic acid may also exert its
antioxidant effect by chelating with pro-oxidant
metals. Research further suggests that lipoic acid
has a sparing effect on other antioxidants. Animal
studies have demonstrated supplemental lipoic acid
to protect against the symptoms of vitamin E or
vitamin C deficiency.
Additional physiological antioxidants are listed in
Table: II.
Sumit Agarwal et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-1(2) 2012 [103-120]
Dietary Antioxidants
Vitamin C
Albumin (copper)
lipoic acid,
N-acetyl cysteine
Vitamin E
copper/zinc and manganesedependent superoxide dismutase
Iron-dependent catalase
Beta carotene and other
carotenoids and oxycarotenoids,
e.g., lycopene and lutein
e.g., flavonoids,
flavonols,and proanthocyanidins
Vitamin C
Vitamin E
Beta carotene and other
carotenoids and oxycarotenoids,
e.g., lycopene and lutein
(coenzyme Q10)
Uric acid
Selenium-dependent glutathione
Ferritin (iron)
Myoglobin (iron)
Transferrin (iron)
Albumin (copper)
As remarkable as our antioxidant defense system
is, it may not always be adequate. The term
“oxidative stress” has been coined to represent a
shift towards the pro-oxidants in the prooxidant/antioxidant balance that can occur as a
result of an increase in oxidative metabolism.
Increased oxidative stress at the cellular level can
come about as a consequence of many factors,
including exposure to alcohol, medications, trauma,
cold, infections, poor diet, toxins, radiation, or
strenuous physical activity. Protection against all of
these processes is dependent upon the adequacy of
various antioxidant substances that are derived
either directly or indirectly from the diet.
Consequently, an inadequate intake of antioxidant
nutrients may compromise antioxidant potential,
thus compounding overall oxidative stress.
Oxidative damage to DNA, proteins, and other
macromolecules has been implicated in the
pathogenesis of a wide variety of diseases, most
notably heart disease and cancer.
A growing body of animal and epidemiological
studies as well as clinical intervention trials
suggests that antioxidants may play a pivotal role
in preventing or slowing the progression of both
heart disease and some forms of cancer.
• Atherosclerosis
• Cancer
• Pulmonary dysfunction
Sumit Agarwal et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-1(2) 2012 [103-120]
• Cataracts
• Arthritis and inflammatory diseases
• Diabetes
• Shock, trauma, and ischemia
• Renal disease and hemodialysis
• Multiple sclerosis
• Pancreatitis
• Inflammatory bowel disease and colitis
• Parkinson’s disease
• Neonatal lipoprotein oxidation
• Drug reactions
• Skin lesion & Aging
administration. The quantity of cobalamin detected
following a small oral dose of methylcobalamin is
similar to the amount following administration of
cyanocobalamin. But significantly more cobalamin
accumulates in liver tissue following administration
of methylcobalamin. Human urinary excretion of
methylcobalamin is about one-third that of a
similar dose of cyanocobalamin, indicating
substantially greater tissue retention.1
Clinical Indications
Bell’s Palsy
Evidence suggests methylcobalamin dramatically
shortened the recovery time for facial nerve
function in Bell’s palsy.2
Role of LYCOZEN-GT in Preventing
Oxidative Damage caused by free
LYCOZEN-GT, A SuperAntioxidant Multivitamin,
Multimineral Formulation with goodness of
Lycopene,GreenTea Extract,Grapeseed Extract
Composition of LYCOZEN-GT Tablet
Each Film Coated Tablet Contains:
Grape Seed Extract
Folic acid
Calcium Pantothenate
Pyridoxine Hydrochloride 3mg
Thiamine Mononitrate
Vitamin A acetate
10 I.U.
Vitamin E acetate
10 I.U.
Vitamin C
Cell culture and in vivo experimental results
indicated methylcobalamin can inhibit the
proliferation of malignant cells.3 Methylcobalamin
enhanced survival time and reduced tumor growth
following inoculation of mice with Ehrlich ascites
tumor cells.4 Methylcobalamin has been shown to
increase survival time of leukemic mice. Under the
same experimental conditions, cyanocobalamin
was inactive.5 Although more research is required
to verify findings, experimental evidence suggested
methylcobalamin might enhance the efficacy of
Diabetic Neuropathy
Oral administration of methylcobalamin (500 mcg
three times daily for four months) resulted in
subjective improvement in burning sensations,
numbness, loss of sensation, and muscle cramps.
An improvement in reflexes, vibration sense, lower
motor neuron weakness, and sensitivity to pain was
also observed.7
Role of Methylcobalamin in LYCOZEN-GT
Methylcobalamin is one of the two coenzyme
forms of vitamin B12 (the other being
adenosylcobalamin). It is a cofactor in the enzyme
methionine synthase, which functions to transfer
methyl groups for the regeneration of methionine
from homocysteine.
Evidence indicates methylcobalamin is utilized
more efficiently than cyanocobalamin to increase
levels of one of the coenzyme forms of vitamin
B12. Experiments have demonstrated similar
absorption of methylcobalamin following oral
Eye Function
Experiments indicated chronic administration of
methylcobalamin protected cultured retinal neurons
accommodation following visual work has also
been shown to improve in individuals receiving
Heart Rate Variability
Heart rate variability is a means of detecting the
relative activity and balance of the sympathetic/
Methylcobalamin produces improvements in
Sumit Agarwal et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-1(2) 2012 [103-120]
several components of heart rate variability,
suggesting a balancing effect on the nervous
Under experimental conditions, methylcobalamin
inhibited HIV-1 infection of normal human blood
monocytes and lymphocytes.11
Elevated levels of homocysteine can be a metabolic
methylcobalamin form of vitamin B12. Therefore,
it is not surprising that elevated homocysteine
levels were reduced from a mean value of 14.7 to
10.2 nmol/ml following parenteral treatment with
Male Infertility
In one study, methylcobalamin, at a dose of 6 mg
per day for 16 weeks, improved sperm count by
37.5 percent.13 In a separate investigation,
methylcobalamin, given at a dose of 1,500
micrograms per day for 4-24 weeks, resulted in
sperm concentration increases in 38 percent of
cases, total sperm count increases in 54 percent of
cases, and sperm motility increases in 50 percent of
Sleep Disturbances
The use of methylcobalamin in the treatment of a
variety of sleep-wake disorders is very promising.
Although the exact mechanism of action is not yet
elucidated, it is possible that methylcobalamin is
needed for the synthesis of melatonin, since the
biosynthetic formation of melatonin requires the
donation of a methyl group. Supplementation
appears to have a great deal of abilities to modulate
melatonin secretion, enhance light-sensitivity,
normalize circadian rhythms, and normalize sleepwake rhythm.15-20
Role of lycopene in LYCOZEN-GT
Lycopene, a carotenoid without provitamin-A
activity, is present in many fruits and vegetables. It
is a red, fat-soluble pigment found in certain plants
and microorganisms, where it serves as an
accessory light-gathering pigment and protects
these organisms against the toxic effects of oxygen
and light.
Tomato products, including ketchup, tomato juice,
and pizza sauce, are the richest sources of lycopene
in the U.S. diet, accounting for greater than 80
percent of the total lycopene intake of Americans.21
In addition to tomatoes (Lycopersicon esculentum)
and tomato-based products, lycopene is also found
in watermelon, papaya, pink grapefruit, and pink
guava. Lycopene from both processed and cooked
tomato products is more bioavailable than from
fresh tomatoes.22 Dietary intakes of tomatoes and
tomato products containing lycopene have been
shown in cell culture, animal, and epidemiological
investigations to be associated with a decreased
risk of chronic diseases, such as cancer and
cardiovascular disease.23-25 In addition, serum and
tissue lycopene levels have been inversely
correlated with risk of lung and prostate cancers.26
Biochemistry and Pharmacokinetics
Lycopene, also known as psi-carotene, is a
lipophilic compound, an acyclic isomer of betacarotene, and is insoluble in water. It is a C40,
open-chain carotenoids with 11 conjugated double
bonds. Because of the abundance of double bonds
in its structure, there are potentially 1,056 different
isomers of lycopene, but only a fraction is found in
nature.27 Lycopene is converted to beta-carotene by
the action of lycopene beta cyclase.28
Among the carotenoids, lycopene is found in the
serum,25 testes, adrenal glands, and prostate.24 In
contrast to other carotenoids, its serum values are
not regularly reduced by smoking or alcohol
consumption, although levels are reduced by
increasing age.29. The linear all-trans configuration
is the predominant form of lycopene, making up
approximately 90 percent of its dietary sources.30
Stahl et al found that heating tomato juice resulted
in trans-to-cis isomerization of lycopene, and on
ingestion, the cis isomers of lycopene appeared to
predominate in human serum over all-trans
isomers.31 Gartner et al showed that more than half
of total lycopene in human serum is in the cis
form.32 The exact functions and relative activities
of these different isomers are currently unknown.
However, several research groups have suggested
cis isomers of lycopene are better absorbed than the
all-trans form.30 Investigations are meanwhile
underway to determine whether there are biological
differences between all-trans and various cis
isomers of lycopene regarding its antioxidant
properties and other biological functions.
Mechanisms of Action
Lycopene has the capacity to prevent free-radical
damage to cells caused by reactive oxygen species.
Sumit Agarwal et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-1(2) 2012 [103-120]
It is a potent antioxidant in vitro and in human
studies, reducing the susceptibility of lymphocyte
DNA to oxidative damage,33 inactivating hydrogen
peroxide and nitrogen dioxide,14 and protecting
lymphocytes from nitrogen oxide induced
membrane damage and cell death twice as
efficiently as beta-carotene.34 Evidence is
accumulating to suggest other mechanisms of
action for lycopene, including modulation of
intercellular gap junction communication, an
anticancer mechanism.25,26 In addition, lycopene at
physiological concentrations has been shown to
inhibit human cancer cell growth by interfering
with growth factor receptor signaling and cell cycle
progression, specifically in prostate cancer cells.26
Clinical Indications
Cardiovascular Disease
Lycopene may reduce lipids by inhibiting the
enzyme macrophage 3-hydroxy-3-methyl glutaryl
coenzyme A (HMG-CoA) reductase (an important
step in cholesterol synthesis)15 and by enhancing
LDL degradation.21 In addition, available evidence
suggests intimal wall thickness and risk of
myocardial infarction (MI) are reduced in persons
with higher adipose tissue concentrations of
lycopene.21 Recent epidemiological studies have
shown an inverse relationship between tissue and
serum levels of lycopene and mortality from
coronary heart disease (CHD), cerebrovascular
disease, and MI.36-38 The strongest populationbased evidence on lycopene and MI comes from
the European Community Multicenter Study on
Antioxidants, Myocardial Infarction and Breast
Cancer (EURAMIC) that evaluated the relationship
between adipose tissue antioxidant status and acute
MI.16 The study recruited 1,379 individuals (662
patients, 717 controls) from 10 European countries.
Needle aspiration biopsy samples of adipose tissue
were taken shortly after the infarction, and levels of
alpha- and beta-carotenes, lycopene, and alphatocopherol were measured. After adjusting for age,
body mass index, socioeconomic status, smoking,
hypertension, and maternal and paternal history of
heart disease, only lycopene levels were found to
be protective. The protective potential of lycopene
was maximal among individuals with the highest
polyunsaturated fat stores, supporting the
antioxidant theory. Results also showed a doseresponse relationship between each quintile of
adipose tissue lycopene and the risk of MI.
Similarly, lower blood lycopene levels were also
found to be associated with increased risk and
mortality from CHD in a concomitant crosssectional study comparing Lithuanian and Swedish
populations.37 In a recent clinical trial, 60 healthy
individuals (30 men/30 women) were randomized
to examine the change in plasma lycopene and
resistance of lipoproteins to oxidative stress.
Fifteen days of tomato product consumption
significantly enhanced the protection of
lipoproteins to oxidative stress as measured by a
significant increase (p< 0.05) in the lag period (a
measure of antioxidant capacity) after consumption
of lycopene.39 Increased thickness of the intimamedia has been shown to predict coronary
events.40 Rissanen et al investigated the
relationship between plasma concentrations of
lycopene and intima- media thickness of the
common carotid artery wall (CCA-IMT) in 520
males and females (age 45-69).41 The authors
conclude that low plasma lycopene concentrations
are associated with early atherosclerosis in men,but
not women, as manifested by increased CCA-IMT.
Oxidative stress is recognized as one of the major
contributors to increased risk of cancer48, and in
chemical assays, lycopene is the most potent
antioxidant among various common carotenoids. 42
Lycopene has been found to inhibit proliferation of
several types of human cancer cells, including
endometrial, breast, and lung.43-45 In addition, in
vivo studies have shown lycopene has tumorsuppressive activity.46 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.47 Lycopene has
also recently been shown to elevate levels of
hepatic reduced glutathione and biotransformation
enzymes, potentially playing a key role in
preventing cancer development at extrahepatic
sites.48 In one epidemiological review regarding
intake of tomatoes, tomato-based products, and
blood lycopene levels in relation to the risk of
various cancers, 72 studies were identified.49 Of
those, 57 reported inverse associations between
tomato intake or blood lycopene level and the risk
of cancer at a defined anatomic site; 35 of these
inverse associations were statistically significant.
The evidence for a benefit was strongest for
cancers of the prostate, lung, and stomach. Data
were also suggestive of a benefit for cancers of the
Sumit Agarwal et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-1(2) 2012 [103-120]
pancreas, colon and rectum, esophagus, oral cavity,
breast, and cervix.50-58
In a case-control study conducted between 1993
and 1999, examining the relationship between 17
micronutrients and breast cancer risk in 289 women
with confirmed breast cancer and 442 controls,
lycopene was significantly inversely associated
with breast cancer risk.60 Median intake of
lycopene in the “high intake” group was 6.2
In a 1998 study, samples taken from the Breast
Cancer Serum Bank in Columbia, Missouri, were
analyzed to evaluate the relationship of levels of
carotenoids (including lycopene), selenium, and
retinol with breast cancer.61 Only lycopene was
found to be associated with a reduced risk for
developing breast cancer.
In another study involving 32 women with cervical
dysplasia (cervical intraepithelial neoplasia (CIN) I,
CIN II, and CIN III/carcinoma in situ) and 113
controls with normal cervical cytology, women
with higher levels of lycopene in the blood were
found to have a 33- percent decreased risk of
developing cervical cancer.64 Lycopene is one of
the micronutrients currently being examined in
National Cancer Institute- sponsored, phase I, II, or
III chemoprevention trials for prostate, breast, and
colon cancers.65 These studies suggest lycopene
may have anti proliferatives and chemo preventive
Data from phase I of the Third National Health and
Nutrition Examination Survey (1988- 1991) were
used to examine concentrations of lycopene and
other carotenoids in 40- to 74-year old persons with
normal glucose tolerance (n =1,010), impaired
glucose tolerance (n = 277), newly diagnosed
diabetes (n = 148), and previously diagnosed
diabetes (n = 230), based on World Health
Organization criteria.66 After adjustment for age,
sex, race, education, serum cotinine (a metabolic
byproduct of nicotine), serum cholesterol, body
mass index, physical activity, alcohol consumption,
vitamin use, and carotene and energy intake,
lycopene was inversely related to fasting serum
insulin after adjustment for confounders (p<0.05).
These data suggest a possible role for lycopene in
the pathogenesis of insulin resistance and diabetes.
A study investigated the relationship between
hyperglycemia and serum carotenoids, including
lycopene, and intake of vegetables and fruits.
Subjects were recruited with a history of diabetes
mellitus (n=133) or with hyperglycemia diagnosed
using a conservative 5.6-percent cutoff value for
hemoglobin A1c (n=151).67 Serum levels of
carotenoids and retinol were measured using highperformance liquid chromatography. The authors
concluded that an intake of vegetables and fruits
rich in carotenoids, including lycopene, might be a
protective factor against hyperglycemia.
Other Clinical Indications
Studies have also investigated the relationship
and/or use of lycopene for cataracts,68 longevity,69
malaria,70 digestive-tract cancers,71,72 immune
modulation,73 Alzheimer’s disease, 74 and
preeclampsia.75. Patients with HIV infection or
inflammatory diseases may have depleted lycopene
serum concentrations.76
Drug-Nutrient and Nutrient-Nutrient
mineral oil, fat substitutes, and pectin79 may
decrease the absorption of lycopene; whereas, betacarotene,80 medium-chain triglycerides, and dietary
oils such as olive oil may enhance the absorption of
Therapeutic dosages of lycopene range from 6-60
mg daily. Dosages include 6 mg for reducing the
risk of prostate cancer; 83 6.5 mg for reducing the
risk of lung cancer in non-smoking women;64 12
mg for reducing the risk of lung cancer in nonsmoking men;84 30 mg for decreasing the growth of
prostate cancer38 and preventing exercise-induced
asthma;85 and 60 mg for reducing LDL
Grape seed extract is a source of potent
antioxidants called pro anthocyanidins, also known
as oligomeric pro anthocyanidin complexes
(OPCs), a type of flavonoid.
Research supports benefits for chronic venous
insufficiency, varicose veins, prevention of blood
clots while flying, and reducing post-surgical
edema. Preliminary research suggests benefits for
ADHD, PMS, erectile dysfunction, asthma,
allergies, hemorrhoids, and prevention of
atherosclerosis. It is very well tolerated, but may
cause minor upset stomach. It may enhance the
effect of blood-thinning drugs.
Sumit Agarwal et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-1(2) 2012 [103-120]
Mechanisms of Action
anticarcinogenic, anti-inflammatory, and antiviral
The potent antioxidative properties of OPCs
account for their therapeutic benefit in disease
states characterized by oxidative stress. OPCs also
demonstrate potent, concentration-dependent, free
radical scavenging ability. Studies in mice show
peroxidation, DNA fragmentation, and subsequent
apoptosis (indicators of oxidative tissue damage) in
a dose-dependent manner in hepatic and brain
tissue. Human studies also demonstrate an
antioxidative mechanism as evidenced by
decreased lipid peroxidation of LDL cholesterol
and increased free-radical trapping capacity after
consumption of red wine containing OPCs. OPCs
appear to have an affinity for vascular tissue and
strongly inhibit several enzymes involved in
degradation of collagen, elastin, and hyaluronic
acid, the main structural components of the
extravascular matrix. These effects are perhaps
attributable to trapping reactive oxygen species and
endothelium. In vitro studies have also found OPCs
increase resistance of cell membranes to injury and
endothelium dependent relaxing (EDR) activity in
blood vessels by increasing nitric oxide
production,16 and stimulate vascular endothelial
growth factor, a signaling factor involved in
initiation of wound healing. OPCs may also protect
the microvasculature of the retina and increase
visual acuity, possibly by increasing the rate of
rhodopsin regeneration. In a rabbit model of
ischemia/ reperfusion, OPCs’ beneficial effects
were attributed to binding of copper and iron
liberated from myocardial tissue, thereby reducing
their oxidative effects. The positive effects of
OPCs on microcirculation are also attributed to
their inhibition of LDL oxidation and decreased
incidence of foam cells, markers of early stage
atherosclerosis. Grape seed proanthocyanidins may
have a vitamin E-sparing effect. A clinical study of
10 healthy volunteers examining the effect of OPC
supplementation on markers of oxidative stress
showed significantly increased levels of alphatocopherol in red cell membranes.
OPCs from pine bark decrease symptoms of
chronic inflammation. In vitro, studies demonstrate
anti-inflammatory effects may be due to inhibition
of peroxide generation by macrophages.
addition, animal studies demonstrate OPCs from
grape seed significantly inhibit the formation of
pro-inflammatory cytokines, interleukin 1-beta, and
tumor necrosis factor-alpha.
OPCs possess natural antimutagenic properties
when exposed to certain strains of bacteria.
Although the exact mechanism is not known, an in
vitro study found OPCs exhibit selective
cytotoxicity for certain cancerous cell lines, while
remaining non-toxic to normal human gastric
mucosal cells and macrophages. An in vitro study
in a mouse skin tumor model demonstrated OPCs’
inhibition of two markers of tumor promotion.
Antimicrobial Effects
Flavonoids and associated polyphenol, particularly
OPCs, elicit an inhibitory effect on human
immunodeficiency virus (HIV). A possible
mechanism may be inhibition of gene expression
regulating virus binding to cell receptors on normal
lymphocytes, thus preventing infection.
Green tea is derived from the plant Camellia
sinensis. Unlike black and oolong tea, it is not
fermented, which preserves the active constituents.
It provides a high level of antioxidants called
polyphenol, particularly the catechin called
epigallocatechin gallate (EGCG). It is used for
heart health, cancer prevention, cervical dysplasia,
weight loss, liver disease, and gum health. Green
tea contains caffeine, but less so than black tea and
coffee. Side effects are rare; large amounts may
cause insomnia and nervousness.
Clinical Summary
Tea polyphenol are powerful antioxidants that may
reduce LDL oxidation and the formation of
oxidized DNA metabolites, thus contributing to
lower risks of CVD and cancer. They may also
promote oral health and help with weight control.
Catechins have been found to be anti-oxidant,
antimutagenic, antibacterial, anti-inflammatory,
and antiviral.
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Green tea can reduce food intake4, lipid absorption
and blood triglyceride, cholesterol, and leptin
levels, as well as stimulating energy expenditure,
fat oxidation, HDL levels, and faecal lipid
excretion. Both tea catechins and heat-treated tea
triglyceridaemia. Ikeda suggests that this, along
with the properties of lowering cholesterol and
preventing LDL oxidation, makes green tea a
suitable substance for prevention of coronary heart
disease. Liu lists additional properties of green tea
such as reducing body weight, body fat, and blood
levels of glucose and lipid in leptin receptordefective obese rats. EGCG protects pancreatic
cells, enhances insulin activity, represses hepatic
glucose production, reduces food uptake and
absorption, stimulates thermogenesis and lipid
excretion, and modulates insulin-leptin endocrine
systems. It also inhibits the sodium-dependent
glucose transporter and represses various enzymes
related to lipid metabolism, such as acetyl-CoA
carboxylase, fatty acid synthase, pancreatic lipase,
gastric lipase, and lipoxygenase.
Green tea extract may prevent the development of
hepatic steatosis and reduces liver injury without
altering hepatic alpha-tocopherol and ascorbic acid.
Role of Folic Acid in LYCOZEN-GT
Folic acid, also known generically as folate or
folacin, is a member of the B-complex family of
vitamins, and works in concert with vitamin B12.
Folic acid functions primarily as a methyl-group
donor involved in many important body processes,
including DNA synthesis. Therapeutically, folic
acid is instrumental in reducing homocysteine
levels and the occurrence of neural tube defects. It
may play a key role in preventing cervical
dysplasia and protecting against neoplasia in
ulcerative colitis. Folic acid also shows promise as
part of a nutritional protocol to treat vitiligo, and
may reduce inflammation of the gingiva.
Furthermore, certain neurological, cognitive, and
psychiatric presentations may be secondary to
folate deficiency. Such presentations include
peripheral neuropathy, myelopathy, restless legs
syndrome, insomnia, dementia, forgetfulness,
irritability, endogenous depression, organic
psychosis, and schizophrenia-like syndromes.
Folic acid is required for cell division, growth,
amino acid metabolism, enzyme reactions, and
production of RNA, DNA, and red blood cells.
Folic Acid is used for heart health (lowers
homocysteine) and prevention of cancer (colon and
cervical) and birth defects (neural tube). Folic Acid
Deficiency occurs in alcoholics and those with poor
diets, and causes anemia, fatigue, weakness,
headache, hair loss, diarrhea, and poor immune
function. Pregnancy or cancer results in increased
rates of cell division and metabolism, increasing
the need for folate. Drugs that deplete folate: nonsteroidal anti-inflammatory drugs (NSAIDs) such
as ibuprofen and aspirin, phenytoin, methotrexate
trimethoprim, and sulfasalazine.
Folic Acid Supplements are recommended for most
adults for heart and cancer protection, and
especially for pregnant women; multivitamins
typically provide the recommended amount of 400
mcg per day.
Folic acid is composed of three primary structures,
a hetero-bicyclic pteridine ring, para-aminobenzoic
acid (PABA), and glutamic acid. Because humans
cannot synthesize this compound, it is a dietary
requirement. Although folic acid is the primary
form of folate used in dietary supplements or
fortified foods, it comprises only 10 percent or less
of folates in the diet. Dietary folic acid, or the form
naturally found in foods, is actually a complex and
variable mixture of folate compounds, such as poly
glutamate (multiple glutamate molecules attached)
conjugate compounds, reduced folates, and tetra
hydro folates. Although folates are abundant in the
diet, cooking or processing destroys these
compounds. The best folate sources in foods are
green, leafy vegetables; sprouts, fruits, brewer’s
yeast, liver, and kidney also contain high amounts
of folates.
Role of Calcium Pentothenate in LYCOZENGT
Pantothenic acid (vitamin B5) is a water-soluble Bcomplex vitamin that was identified in 1933,
isolated and extracted from liver in 1938, and first
synthesized in 1940.1 R. J. Williams is credited
with coining the name from the Greek word
panthos, which translates as “from everywhere.” It
was given this name because of its widespread
presence in food. Most vitamin B5, and its
derivatives or precursors, added to foods and
beverages, or used in dietary supplements, is made
by chemical synthesis. Only the Dextrorotatory (D)
isomer of pantothenic acid – D-pantothenic acid –
possesses biologic activity. Pure D-pantothenic
acid can be used as a dietary supplement: it is
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water-soluble, viscous, and yellow in color.
Because D-pantothenic acid is relatively unstable –
it can be destroyed by heat and acid and alkaline
conditions – the more stable calcium pantothenate
is the form of vitamin B5 usually found in dietary
supplements. It is water-soluble, crystalline, and
white in color. Ten mg of calcium pantothenate is
approximately equivalent to 9.2 mg of pure Dpantothenic acid.
Calcium Pantothenate is required for carbohydrate
metabolism, adrenal function, enzyme reactions,
and production of fats, cholesterol, bile acids,
hormones, neurotransmitters, and red blood cells.
Deficiency of calcium pantothenate is rare, except
in malnutrition, and causes burning/tingling in
hands and feet, fatigue, and headache. Drugs that
contraceptives, amitriptyline, imipramine, and
desipramine. Most people get adequate niacin from
diet and/or a multivitamin.
Role of Vitamin B6 (Pyridoxine) in LYCOZENGT
Pyridoxine is necessary for protein and fat
metabolism, hormone function (estrogen and
testosterone), and the production of red blood cells,
niacin, and neurotransmitters (serotonin, dopamine,
and norepinephrine). Pyridoxine is also used
therapeutically for PMS, depression, morning
sickness, carpal tunnel syndrome and heart health
(lowers homocysteine, an amino acid that, at high
levels, can cause arteriosclerosis and build up
arterial plaque). Deficiency of pyridoxine is
uncommon, except in alcoholics and the elderly,
and causes seizures, irritability, depression,
confusion, mouth sores, and impaired immune
B6(Pyridoxine): antibiotics, oral contraceptives,
isoniazid, penicillamine, and Parkinson’s drugs.
Supplementation of Pyridoxine is recommended for
the elderly, alcoholics, and those with poor diets.
Role of Thiamine Mononitrate in LYCOZENGT
Thiamine or thiamin or vitamin B1 named as the
"thio-vitamine" ("sulfur-containing vitamin") is a
water-soluble vitamin of the B complex. First
named aneurin for the detrimental neurological
effects if not present in the diet, it was eventually
assigned the generic descriptor name vitamin B1.
Its phosphates derivatives are involved in many
cellular processes. The best-characterized form is
thiamine pyrophosphate (TPP), a coenzyme in the
catabolism of sugars and amino acids. Thiamine is
used in the biosynthesis of the neurotransmitter
acetylcholine and Gamma-Amino Butyric Acid
Thiamine derivatives and thiamine-dependent
enzymes are present in all cells of the body, thus a
thiamine deficiency would seem to adversely affect
all of the organ systems. However, the nervous
system and the heart are particularly sensitive to
thiamine deficiency, because of their high oxidative
Thiamine deficiency commonly presents sub
acutely and can lead to metabolic coma and death.
A lack of thiamine can be caused by malnutrition, a
diet high in thiaminase-rich foods (raw freshwater
fish, raw shellfish, ferns) and/or foods high in antithiamine factors (tea, coffee, betel nuts) and by
grossly impaired nutritional status associated with
gastrointestinal diseases, HIV-AIDS, and persistent
vomiting. It is thought that many people with
diabetes have a deficiency of thiamine and that this
may be linked to some of the complications that
can occur. Well-known syndromes caused by
thiamine deficiency include beriberi, Wernicke Korsakoff syndrome, and optic neuropathy.
Role of Riboflavine in LYCOZEN-GT
Riboflavin, also known as vitamin B2 is an easily
absorbed colored micronutrient with a key role in
maintaining health in humans and animals. It is the
central component of the cofactors FAD and FMN,
and is therefore required by all flavoproteins. As
such, vitamin B2 is required for a wide variety of
cellular processes. It plays a key role in energy
metabolism, and for the metabolism of fats, ketone
bodies, carbohydrates, and proteins.
Riboflavin is continuously excreted in the urine of
healthy individuals, making deficiency relatively
common when dietary intake is insufficient.
However, riboflavin deficiency is always
accompanied by deficiency of other vitamins.
A deficiency of riboflavin can be primary - poor
vitamin sources in one's daily diet - or secondary,
which may be a result of conditions that affect
absorption in the intestine, the body not being able
to use the vitamin, or an increase in the excretion of
the vitamin from the body.
In humans, signs and symptoms of riboflavin
deficiency (ariboflavinosis) include cracked and
red lips, inflammation of the lining of mouth and
tongue, mouth ulcers, cracks at the corners of the
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mouth (angular cheilitis), and a sore throat. A
deficiency may also cause dry and scaling skin,
fluid in the mucous membranes, and irondeficiency anemia. The eyes may also become
bloodshot, itchy, watery and sensitive to bright
Riboflavin deficiency is classically associated with
the oral-ocular-genital syndrome. Angular cheilitis,
photophobia, and scrotal dermatitis are the classic
remembered signs.
Role of Vitamin A in LYCOZEN-GT
Vitamin A is a fat-soluble vitamin that is derived
from two sources: preformed retinoids and
provitamin carotenoids. Retinoids, such as retinal
and retinoic acid, are found in animal sources like
liver, kidney, eggs, and dairy produce. Carotenoids
like beta-carotene (which has the highest vitamin A
activity) are found in plants such as dark or yellow
vegetables and carrots.
Natural retinoids are present in all living
organisms, either as preformed vitamin A or as
carotenoids, and are required for a vast number of
biological processes like vision and cellular
growth. A major biologic function of vitamin A (as
the metabolite retinal) is in the visual
cycle.Research also suggests that vitamin A may
reduce the mortality rate from measles, prevent
some types of cancer, aid in growth and
development, and improve immune function.
Recommended daily allowance (RDA) levels for
vitamin A oral intake have been established
by the U.S. Institute for Medicine of the National
Academy of Sciences to prevent deficiencies in
vitamin A. At recommended doses, vitamin A is
generally considered non-toxic. Excess dosing may
lead to acute or chronic toxicity. Vitamin A
deficiency is rare in industrialized nations but
remains a concern in developing countries,
particularly in areas where malnutrition is common.
Prolonged deficiency can lead to xerophthalmia
(dry eye) and ultimately to night blindness or total
blindness, as well as to skin disorders, infections
(such as measles), diarrhea, and respiratory
Role of Vitamin C (Ascorbic Acid) in
Vitamin C is required for synthesis of collagen
(structural component of blood vessels, tendons,
and bone), norepinephrine (neurotransmitter), and
carnitine (amino acid involved in energy
production); It promotes wound healing; It supports
immune function and gum health; and has
antioxidant properties. It used to prevent cataracts,
macular degeneration, heart disease, stroke, cancer,
and colds; improve wound healing and response to
stress; reduce bronchial spasms in asthmatics; and
prevent lead toxicity. Severe deficiency causes
scurvy (bleeding, bruising, hair and tooth loss, joint
pain, and swelling), which is rare today. Marginal
deficiencies are common among the elderly,
alcoholics, and those with cancer, chronic illness,
or stress. Symptoms include fatigue, easy bruising,
poor wound healing and appetite, anemia, and sore
joints. Drugs that deplete vitamin C: oral
contraceptives, aspirin, corticosteroids, and
furosemide. Large doses of vitamin C (greater than
1,000 mg/day) may reduce the effect of warfarin
(blood-thinning drug). The Linus Pauling Institute
recommends 400 mg of vitamin C daily, which is
higher than the RDA, yet much lower than the UL.
Most multivitamin supplements provide 60 mg of
vitamin C. Natural and synthetic forms are
chemically identical and have the same effects on
the body. Mineral salts of ascorbic acid (i.e.,
calcium ascorbate) are buffered and therefore, less
acidic and less likely to cause upset stomach.
Role of Niacinamide in LYCOZEN-GT
Numerous studies have shown that niacin can
lower LDL, triglyceride, and lipoprotein-A levels
and raise HDL. Niacin can cause liver
inflammation at higher dosages (more than 500 mg
daily) Niacin is required for energy metabolism,
enzyme reactions, skin and nerve health, and
digestion. High doses of nicotinic acid (3 g daily)
can lower cholesterol (reduce LDL and
triglycerides and increase HDL) and reduce the risk
of heart attack and stroke. Deficiency causes
pellagra, the symptoms of which are skin rash,
diarrhea, dementia, and death. Deficiency may be
caused by poor diet, mal absorption diseases,
dialysis, and HIV. Drugs that deplete vitamin B3:
(chemotherapy). High-dose niacin, taken along
with statin drugs (i.e., lovastatin), may increase the
risk of rhabdomyolysis (muscle degeneration and
kidney disease). Most people get adequate niacin
from diet and/or a multivitamin; supplements may
be recommended for those with high cholesterol.
Role of Biotin in LYCOZEN-GT
Biotin is a Part of the B-vitamin family; involved in
the synthesis of fat, glycogen, and amino acids and
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enzyme reactions; required for DNA replication;
important for healthy hair and nails. It used
Deficiency is rare except in those with hereditary
disorders of biotin metabolism, liver disease, and
during pregnancy (due to increased needs). It can
also occur in those who consume raw egg white for
prolonged periods (weeks to years) because a
protein found in egg white (avidin) binds biotin and
prevents its absorption or in those given
supplementation. Deficiency symptoms include
hair loss; scaly red rash around the eyes, nose,
mouth, and genital area; depression; lethargy;
hallucination; numbness and tingling of the
extremities; and impaired glucose utilization and
immune system function. Drugs that deplete biotin:
phenytoin, valproic acid, and antibiotics. Most
people get adequate biotin from diet and/or
Role of Selenium in LYCOZEN-GT
Selenium is an essential component of enzymes
that function as antioxidants; involved in
detoxification; selenium converts thyroid hormone
to its active form; It supports immune function; It
enhances the antioxidant activity of vitamin E.
Selenium is used to strengthen immune function
and prevent infection, to protect against colon and
prostate cancer, and to prevent oxidative stress and
support immune system function in those with
HIV/AIDS. Deficiency of selenium is uncommon,
but may occur in those with poor diets, those who
live in areas where the soil is depleted in selenium,
Crohn’s disease, and mal absorption syndromes
(celiac disease). Symptoms disease).Symptoms
Symptoms of deficiency of selenium is muscular
weakness and wasting, cardio myopathy
(inflammation of the heart), pancreatic damage, and
impaired immune function. Drugs that deplete
selenium are valproic acid and corticosteroids
Role of Zinc in LYCOZEN-GT
Zinc is involved in numerous enzyme reactions;
required for growth and development, immune
and neurological function, reproduction and
regulation of gene expression stabilize the structure
of proteins and cell membranes.
Zinc is used to support immune function, reduce
severity and duration of the common cold, and
delay the progression of macular degeneration.
Severe deficiency of Zinc is rare, except in those
with a genetic disorder, severe malnutrition or mal
absorption, severe burns, or chronic diarrhea.
Marginal deficiency of Zinc is common in
malnourished people, vegetarians, pregnant
women, the elderly, and those with celiac disease,
Crohn’s disease, colitis, and sickle-cell anemia.
Symptoms of deficiency include impaired growth
and development, skin rashes, severe diarrhea,
immune system deficiencies, impaired wound
healing, poor appetite, impaired taste sensation,
night blindness, clouding of the corneas, and
behavioral disturbances. Drugs that deplete zinc are
diuretics, anticonvulsants, iron supplements,
penicillamine, ACE-inhibitor drugs, acid-reducing
drugs, and oral contraceptives.
Zinc supplements can reduce absorption of
antibiotics (tetracycline and quinolones), so
separate intake of zinc supplements from these
products by two hours. Since the average zinc
intake is below the RDA and many conditions and
drugs deplete zinc levels, a supplement should be
Functional Use:
It helps to prevent high blood pressure,
hyperhomocysteinemia, atherosclerosis, diabetes,
skin disorders, cancer, etc.
Safety Details:
Methylcobalamin: It is used as a safe agent in the
treatment of diabetic neuropathies.
EGCG from Green tea extract: is safe & does not
cause any toxic effect.
Proanthocyanidins (Grape seeds extract): The
results of our studies indicate a lack of toxicity and
support the use of proanthocyanidin-rich extract
from grape seeds for various foods.
Lycopene: In humans, there is a very long history
of use with respect to dietary exposure, and even in
the case of very high exposures from dietary
sources, there is no indication of any significant
adverse effects.
Vitamins and Minerals: The results of our studies
indicate a lack of toxicity and support the use of
Vitamins and Minerals in above quantity & dosage
in this formulation.
Dosage and Administration:
1-2 tablets daily with meals or as directed by the
health care practitioner.
Sumit Agarwal et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-1(2) 2012 [103-120]
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