Research Article on Shilajit

 

 

 

 

Effect of shilajit on blood glucose and lipid profile in alloxan-induced diabetic rats

Department of Pharmacology, Medical College, Baroda – 390 001, India

To study the effect of shilajit (a herbomineral preparation) on blood glucose and lipid profile in euglycemic and alloxan-induced diabetic rats and its effects on the above parameters in combination with conventional antidiabetic drugs. MATERIAL AND METHODS: Diabetes was induced in albino rats by administration of a single dose of alloxan monohydrate 5% (125 mg/kg, i.p.). Effects of three different doses of shilajit (50, 100 and 200 mg/kg/day, orally), alone for 4 weeks and a combination of shilajit (100 mg/kg/day, orally) with either glibenclamide (5 mg/kg/day, orally) or metformin (0.5 g/kg/day, orally) for 4 weeks were studied on blood glucose and lipid profile. RESULTS: In the diabetic rats, all the three doses of shilajit produced a significant reduction in blood glucose levels and also produced beneficial effects on the lipid profile. The maximum effect was observed with the 100 mg/kg/day dose of shilajit. Combination of shilajit (100 mg/kg) with glibenclamide (5 mg/kg/day) or metformin (0.5 gm/kg/day) significantly enhanced the glucose-lowering ability and improvement in lipid profile than any of these drugs given alone. CONCLUSION: Shilajit is effective in controlling blood glucose levels and improves the lipid profile.

Effects of Shilajit on memory, anxiety and brain monoamines in rats

The effect of Shilajit was investigated for putative nootropic and anxiolytic activity, and its effect on rat brain monoamines using Charles Foster strain albino rats. Nootropic activity was assessed by passive avoidance learning and active avoidance learning acquisition and retention. Anxiolytic activity was evaluated by the elevated plus-maze technique. Rat brain monoamines and monoamine metaboliteswere estimated by a HPLC technique. The results indicated that Shilajit had significant nootropic and anxiolytic activity. The biochemical studies indicated that acute treatment with Shilajit had insignificant effects on rat brain monoamine and monoamine metabolite levels. However, following subacute (5days) treatment, there was decrease in 5-hydroxytryptamine and 5-hydroxyindole acetic acid concentrations and an increase in the levels of dopamine, homovanillic acid and 3.4-dihydroxyphenyl-acetic acid concentrations, with insignificant effects on noradrenaline and 3-methoxy-4- hydroxyphenylethylene glycol levels. The observed neurochemical effects induced by Shilajit, indicating a decrease in rat brain 5-hydroxytryptamine turnover, associated with an increase in dopaminergic activity, helps to explain the observed nootropic and anxiolytic effects of the drug.

Effects of Shilajit on the development of tolerance to morphine in mice.

Phytother Res. 2001 Mar;15(2):177-9.
Effects of concomitant administration of Processed Shilajit in Swiss mice were evaluated on the development of tolerance to morphine induced analgesia in the hot plate test. Chronic administration of morphine to mice over a duration of 10 days resulted in the development of tolerance to the analgesic effect of morphine. Concomitant administration of Shilajit with morphine, from day 6 to day 10, resulted in a significant inhibition of the development of tolerance to morphine induced analgesia. Processed Shilajit per se, in the doses used, did not elicit any significant analgesia in mice; nor did the chronic concomitant administration of Processed Shilajit alter the morphine-induced analgesia. These findings with Processed Shilajit indicate its potential as a prospective modifier of analgesic tolerance to morphine.

Systemic administration of defined extracts from Withania somnifera and Shilajit differentially affects cholinergic but not glutamatergic and GABAergic markers in rat brain.

Neurochem Int. 1997 Feb;30(2):181-90.
Sitoindosides VII-X, and withaferin-A, isolated from aqueous methanol extract from the roots of cultivated varieties of Withania somnifera, as well as Shilajit, a pale-brown to blackish brown exudation from steep rocks of the Himalaya mountain, are used in Indian medicine to attenuate cerebral functional deficits, including amnesia, in geriatric patients. The present investigation was conducted to assess whether the memory-enhancing effects of plant extracts from Withania somnifera and Shilajit are owing to neurochemical alterations of specific transmitter systems. Therefore, histochemistry to analyse acetylcholinesterase activity as well as receptor autoradiography to detect cholinergic, glutamatergic and GABAergic receptor subtypes were performed in brain slices from adult male Wistar rats, injected intraperitoneally daily with an equimolar mixture of sitoindosides VII-X and withaferin-A (prepared from Withania somnifera) or with Shilajit, at doses of 40 mg/kg of body weight for 7 days. Administration of Shilajit led to reduced acetylcholinesterase staining, restricted to the basal forebrain nuclei including medial septum and the vertical limb of the diagonal band. Systemic application of the defined extract from Withania somnifera, however, led to differential effects on AChE activity in basal forebrain nuclei: slightly enhanced AChE activity was found in the lateral septum and globus pallidus, whereas in the vertical diagonal band AChE activity was reduced following treatment with sitoindosides VII-X and withaferin-A. Treatment with Shilajit or the defined extract from Withania somnifera affected neither GABAA and benzodiazepine receptor binding nor NMDA and AMPA glutamate receptor subtypes in any of the cortical or subcortical regions studied. The data suggest that Shilajit and the defined extract from Withania somnifera affect preferentially events in the cortical and basal forebrain cholinergic signal transduction cascade. The drug-induced increase in cortical muscarinic acetylcholine receptor capacity might partly explain the cognition-enhancing and memory-improving effects of extracts from Withania somnifera observed in animals and humans.

Antiulcerogenic and anti inflammatory studies with shilajit.

Ethnopharmacol. 1990 Apr;29(1):95-103.
In folk medicine, shilajit has been used to treat diverse clinical conditions ranging from peptic ulcer to bone healing. The present study was conducted to evaluate the possible antiulcerogenic and antiinflammatory activities of shilajit obtained from the rocky mountains of Zarlek, Badekshan, Afghanistan. Shilajit increased the carbohydrate/protein ratio and decreased gastric ulcer index, indicating an increased mucus barrier. Shilajit was found to have significant antiinflammatory effect in carrageenan-induced acute pedal oedema, granuloma pouch and adjuvant-induced arthritis in rats. The results of the present study thus substantiate the use of shilajit in peptic ulcer and inflammation.

Shilajit: A Humic Matter Panacea for Cancer

Available online on www.ijtpr.com
International Journal of Toxicological and Pharmacological Research 2012; 4(2): 17-25
ISSN: 0975-5160
Author for correspondence: Email: pant.kishor1@gmail.com
Review Article
Shilajit: A Humic Matter Panacea for Cancer
1
Kishor Pant, Bimala Singh, Nagendra Thakur
Department of Microbiology, School of Life Sciences, Sikkim University 6th Mile Samdur, Tadong, Gangtok, Sikkim,
India


ABSTRACT
Cancer is the leading cause of death after cardiovascular disease. The primary etiologic agents for cancer include
mutagens, toxins, free radicals, heavy metals, blood sugar, virus, radiations apart from many other factors including
inflammation which can increase the risk of cancer development and progression. Shilajit is a blackish–brown coloured
herbomineral medicine, collected from the high altitude mountains of many parts of the world. Shilajit refers to the
humic matter that contains 60-80% of fulvic acid (FA) and humic acid (HA). The biological activity of Shilajit is mainly
attributed to these humic compounds HA and FA. In this review we have focused on the cancer chemopreventive and
therapeutic properties of Shilajit and humic compounds. Shilajit and HA possess anti-inflammatory, antioxidant,
antimutagenic, antitoxic, antiviral, heavy metal chelating, antitumor, apoptotic and photo-protective properties. These
properties make Shilajit useful agents for cancer therapy and prevention. In addition, Shilajit has no reported side effects
and can be administered as a nutritive and rejuvenating tonic and combats age related problems.

INTRODUCTION
Cancer is the second leading cause of death after the
cardiovascular disease and is the major public health
problem, causing approximately 7 million deaths every
year worldwide. The existing treatment approaches and
surgical techniques have not been able to cope effectively
with this dreaded disease. The conventional therapies like
chemotherapy, radiotherapy, immunotherapy and surgical
approaches for cancer treatment are not very efficient.
Thus, there is an imperative requisite for the development
of the mechanism-based approaches for the cancer
management and chemoprevention by non-toxic and
natural agents. Shilajit is blackish-brown herbal compound
and composed mainly of humic acid components namely
humic acid and fulvic acid. Humic acid and fulvic acid
have been reported to possess cancer preventive properties
(23). It has been shown that these compounds can inhibit
mutagenesis and have free radicals scavenging,
photoprotecting, anti-inflammatory and toxic compound
removing properties that can inhibit the cancer
development. Shilajit is non-expensive, non-toxic
compound which can be taken orally or as a part of the
daily diet. Therefore, it is logical that future clinical
studies should focus on examining the efficacy of Shilajit
and its active constituents in chemoprevention as an
alternative to pharmacological agents. In this review, we
address the use of Shilajit and its constituents for the
prevention and management of cancer.
Chemoprevention is the use of pharmacological or natural
agents to check, detain or render the null and void the
process of the cancer development (Carcinogenesis) (1). It
is accepted that an effective and acceptable
chemopreventive agent should have certain properties like:
(a), little or no toxic effects in healthy cells; (b), high
efficacy against various factors; (c), potential of oral
consumption; (d), identified mechanism of action; (e), low
cost; and (f), acceptance by humans (1). Shilajit is one
such compound, which has been used in Ayurveda for
centuries. The humic compounds of Shilajit can be a
potential cancer chemopreventive agent. Antiinflammatory, anti- oxidative, antiviral, anti-mutagenic,
immunomodulatory and several other effects of Shilajit
have been already reported.
Shilajit: Shilajit is considered as the wonder drug of the
ancient Indian medicinal practice (Ayurveda). It is a
blackish-brown coloured partly solid matter having sharp
odour of the cow’s fusty urine and contain the pungent
tang, formed by the long-term humification process of
many plants (2, 3). Shilajit means ‘Shilaras’ in Sanskrit (4)
and its other meanings are ‘conqueror of the rocks’ and
‘destroyer of the weaknesses’(5). Shilajit is referred to as
silajatu in Bengali (4), Uerangyum or Perangyum in Tamil
(4, 6), Hajar-ul-musa in Arabic (4), Mummio or Mumie in
Russian (7), Asphalt, Mineral Pitch and Jew’s pitch in
English (4, 6), Asphaltum in Latin (8), and in Botanical
terms it called as Bitumen mineral (9). Shilajit is
considered as a vital prescription in the ancient Hindu
material remedies and presently also extensively used by
the Hindu physicians for a variety of diseases. Prehistoric
ayurvedic writings ‘the Charaka Samhita’ and ‘Susruta
Samhita’ explain the use of Shilajit as a treatment for all
ailment of body as well as a rasayana (rejuvenative) to
increase the longevity (10). Shialjit is usually isolated
from the high altitude rocks of the Himalayan regions
mainly from Kashmir, Arunachal Pradesh, Uttrakhand,
Himachal Pradesh, Australia, Afghanistan, Russia, Nepal,
Bhutan and Norway (4, 11). There are several varieties of
Shilajit described by the Charaka Samhita namely rajat Kishor Pant et.al./ Shilajit: A Humic
IJTPR, June – August 2012, 4(2): 17-25
Page18
(silver Shilajit), tamra (copper Shilajit), lauha (iron
Shilajit) and sarvana (gold Shilajit) (4, 12). Shilajit
contains a humic substance fulvic acid (FA) and humic
acid (HA) (60-80%), minerals (20-40%) and up to 5% of
trace elements (Fe, Ca, Cu, Zn, Mg, Mn, Mo, P) (13, 14).
The primary and key active components responsible for
the Shilajit activities is the fulvic acid (FA) and humic
acid. By the virtue of the FA Shilajit has many biological
functions and uses (15, 16), which acts as carrier
molecule. The low molecular weight bioactive organic
compound such as oxygenated dibenzo-α-pyrones is also
present in Shilajit. Shilajit has been used for the treatment
of hypersensitivity, diabetes, digestive disorder, nervous
ailment, tuberculosis, chronic bronchitis, asthma, anemia,
eczema, bone fractures, genitourinary ailment and many
other diseases (17, 18). Fulvic acid is the main constituent
of Shilajit and along with FA and HA it also contains
minerals in ionic form. These minerals are transported to
cells and tissues by fulvic acid, which maintains the
electric potential of the cells of the body and thus possibly
prevents its death, provides the longevity and might act as
a rejuvenator. It helps in metabolism and energy
production in the body. It can also act as detoxifying agent
in the body and can function as immunomodulator and
helps in haematopoiesis.
Pharmacological Actions Of Shilajit And Ha In Cancer
Prevention: It is assumed that Shilajit can play an
important role in cancer chemoprevention and possibly in
its treatment. The general pharmacological actions of
Shilajit in cancer therapy are summarised below:
Anti-Oxidant Properties: Free radicals are molecules with
incomplete electron shells, which make them more
chemically reactive than those with complete electron
shells. Exposure to various environmental factors,
including tobacco smoke and radiation, can also lead to
free radical development. In humans, the most widespread
form of free radicals is oxygen. When an oxygen molecule
(Oâ‚‚) becomes electrically charged, it tries to take electrons
from other molecules, and thus can cause damage to DNA
(20), proteins and cell membrane. Eventually, such
damage specially damage in DNA could become
irreversible and might lead to ailment including cancer
(21). Antioxidants are substances that may
protect cells from the damage caused by unstable
molecules (free radicals) by neutralizing their electrical
charge and thus can avert the free radical damage in cells
(21). Free radicals which are generated during cancer
chemotherapy and radiation therapy, can damage the
normal cell around the vicinity of the tumor cell, which
makes the cancer treatment rather painful. The anti cancer
drugs damages the cellular DNA by producing the reactive
oxygen species (ROS) hence the antioxidants can be used
with the cancer therapy to reduce the pain and the severity
of the side effects (21). HA compounds are excellent
antioxidants (22, 23) along with anti-lipid peroxidative
activity(23). Shilajit has free radical scavenging or
antioxidant properties against the NO & OH (24) and this
antioxidant activity depends on the increasing
concentration of the humic compounds present in Shilajit
(22). It has been found that the use of antioxidants are
effective in Grave’s disease (25).
Anti-Aging Properties: The elderly patients (above 65
years old) are more at risk for development of cancer, 12–
36 times higher than the 25–44 year old patients and 2–3
times higher than the individuals aged between 45–64
years. Moreover, 70% of total deaths among the people
above 65 years of age occur due to cancer (26). DNA
repair capacity decreases with increase in age mainly due
to decrease in endogenous antioxidants in the body (21)
which might lead to the development of cancer. Therefore,
intake of antioxidant with increasing age is suggested to
arrest the oxidative damage (21). It has been shown that
Shilajit can delay the aging process and possibly lower the
risk of cell impairment and damage (27, 28). Moreover,
Charaka Samhita describes Shilajit as a natural rejuvenator
(28) which restore vitality and youthfulness of the body.
Anti-Ulcerative Properties: The relationship between
peptic ulcer and gastric cancer is an important aspect,
mainly after the infection of Helicobacter pylori which
plays an important role in the development of duodenal
ulcer, gastric ulcer, as well as gastric cancer. earlier
history of gastric ulcer or duodenal ulcers in patients
increases the risk of development of gastric cancer or
duodenal cancers (29). In duodenal ulcers, Shilajit pretreatment notably reduced the occurrence of ulcers induce
by means of cysteamine in rats and by histamine in guinea
pigs. Moreover Shilajit pre-administration orally at the
dose of 100mg/kg was found to reduced ulcer index in
immobilization and aspirin induced gastric ulcers (17).
Anti-Inflammatory Properties: The inflammation is
considered to induce the cancer progression, development
and the metastasis (20). It has been shown that the HA
matters has anti-inflammatory properties (23). Shilajit has
anti-inflammatory properties confirmed in the study of the
Goel et al (30). They have shown that the Shilajit can
reduce the inflammation such as pedal oedoma and
granulama pouch in rats induced by the carrageenan. In
addition, Shilajit can also reduce the adjuvant induced
arthritis in rats. In another study the humic compounds
derived from the coal was found to inhibit the
inflammation responded ear swelling in the rats (31).
Lowen et al have described that HA alone or HA
combined with other anti-inflammatory drugs such as
indomethacin were beneficial for the chronic and acute
inflammation in the male Sparague Dwley rats(32). Van
Rensburg et al have shown that the presence of potassium
humate reduces the level of proinflammatory cytokines
like TNF-α, IL-1β, IL-6 and IL-10 produced by
mononuclear cells and also the compliment activation
(33). HA can inhibit the degranulation of the neutrophils
during inflammation (34), moreover it is an anti-allergic
agent (34, 35). It has been Oxifulvic acid may be
beneficial in the clinical treatment of inflammatory skin
conditions in humans as FA possesses anti-inflammatory
properties (36).
Photo Protective Properties: The exposure to the radiation
as the ultraviolet (UV) rays can leads to the long-term
DNA damage by forming the thymine dimer in the DNA
which can lead to mutations and cancer. Shilajit can Kishor Pant et.al./ Shilajit: A Humic
IJTPR, June – August 2012, 4(2): 17-25
Page19
function as photoprotective agent, as reviewed by Meena
et al 2010 (27). It has been shown that Shilajit can save the
mountaineers from the sunburn, skin and eye problems by
high intensity of the UV light at high altitudes. HA can
absorb the luminous radiation including UV and provides
photoprotective properties to E. Coli in aqueous solution
(37). HA has capacity to absorb radiations and can reduce
the amount of energy of radiation reaching to the cells.
Akran et al have reported that the harmful effect of UV
radiation on E. coli were reduced in water due to
absorption of UV light by humic compounds. Increasing
concentrations of fulvic acid emerged to improve its effect
with elevated doses of UV radiation tested on the bacterial
growth (38). The HA is UVB-absorbing chromophore,
which reduces the penetration of the high-energy
wavelength lights and thus protects the zooplankton
population from UV exposure (39).
Anti-Viral Properties: Several studies have shown that
many viral infections are associated with the development
of cancer. The possibility of Hodgkin lymphoma is
directly related to state of the immunosuppression and
HIV (40), whereas AIDS is reported to support the
development of the Brukitt’s lymphoma (41). Human
Papilloma virus (HPV) are directly associated with
cervical cancer (41) and Kaposi sarcoma herpes virus
(KSHV) infections are also linked to lymphomas and
sarcomas in HIV patients (42, 43). It has been suggested
that HA can prevent some of these cancers and cancercausing viruses (23). For example, HA can decrease the
HIV infection and replication (44, 45) and also inhibits the
viral fusion between the T-cell (44). Furthernore, humic
acid can activate the T-lymphocytes (44) and also
increases the IL-2 production by TH1 cells in HIV patients
(45-47).
In another study, Gupta et al have treated HIV patients
with antiretroviral therapy along with Shilajit and they
found that the patients improved their appetite, nausea,
vomiting, depression, diarrhoea, weight loss, fever,
anaemia and they have elevated level of the CD4 along
with several other advantages. Therefore, Shilajit and
similar humic compounds could be the ray of hope for the
immunocompromised patients (48). Herpes simplex virus-
1 (HSV-1) can cause genital and oral infections and it is
linked to oropharyngeal cancer (49). It has been found that
HA posses antiviral and cytotoxic activity in the HSV-1
infected cells (50) and can block the HSV replication (51).
The antiviral effect of HA depends upon the increased
content of acidic functional groups (carboxyl groups)
along with the hydroxyl group (51).
Anti-Mutagenic And Detoxification Properties: In daily
routine we are exposed to several harmful chemicals and
some of them are potential carcinogens. Exposure to the
polycyclic aromatic hydrocarbons (PAH), pesticides,
herbicides, toxins and other carcinogenic compound can
occur accidently or occupationally (52), which may lead to
cancer development. Mutagens such as aflatoxins or
mycotoxins, benzo (a) pyrene and pesticides are the most
common types of the carcinogenic compounds.Kishor Pant et.al./ Shilajit: A Humic
IJTPR, June – August 2012, 4(2): 17-25
Page20
Marova et al have shown that processed HA can inactivate
the mutagens which were tested on the yeast (53). They
used 4-nitroquinoline-N-oxide (4-NQO), a mutagen on
Saccharomyces cerevisiae D7 to check the anti-mutagenic
properties of the sodium or potassium humate and found
that the sodium humate have significant antimutagenic
property against the 4-NQO. Furthermore, Zhang et al
checked the toxicity and bioavailability of the ionic liquids
(ILs), 1-butyl-3-methylimidazolium chloride and 1-octyl-
3-methylimidazolium chloride, in the presence of the HA
(54). These results illustrated that the HA reduces the
bioavailability and toxicity of these two ILs and also HA
increases the viability around 50% of HepG2 cell line
against the two ILs. Moreover, the death rate of the model
fish Medaka decreased against the lethal dose of two ILs
when the HA was present in the water (54).
Potassium humate was observed to detoxify the mutagenic
matters, N-methyl-N-nitrosourea and N-nitrosodiumethylamine in Arabidopsis thaliana (55). HA can inactivate
the aflatoxins produced by the fungi. Rensburg et al have
shown that the liver damage, stomach and heart
enlargement in boiler chicken which occur after intake of
aflatoxins were reduced in presence of oxihumate (56). In
addition, the serum toxicity caused by the toxin was also
found to be reduced significantly (P Ë‚ 0.005). In another
study, Santosa et al (57) checked the absorption of the
aflatoxins by the humic acid polymer in the digestive
system (oral cavity, stomach and intestines) at different pH
of monogastric animals. They found that humic acid can
absorb polycyclic aromatic hydro-carbons (58, 59). Humic
acid can also inactivate 2, 4, 6-Trichlorophenol which can
cause lymphomas, leukemia and liver cancer in animals by
means of oral contact (60).
The humic compounds have been proved to be excellent
agents for reduction of gene mutation caused by pollutants
and mutagens. Toxins, pesticides, radioactive metals,
petroleum products, polyaromatic hydro-carbons and
heavy metals can be inactivated by HA (61, 62).
Moreover, it reduces bioavailability of the hazardous
matters (62) and averts the formation of the mutagenic or
carcinogenic compound and prevent DNA damage in the
cell. Anti-Diabetic Property: Several studies have proved
that Diabetes is a key factor contributing to the increase in
solid organ malignancies or tumor including liver,
pancreas, colorectal, breast, endometrial, uterine, and
bladder(63, 64). Shilajit can maintain the blood glucose
profile and studies on diabetic rats have shown that Shilajit
can reduce the blood sugar level and improve the lipid
profile by reducing the total cholesterol, triglyceride and
high-density lipoproteins in the rats (65). In another study
with 32 type II diabetes patients, Upadhyay et al have
shown that the uptake of aqueous extract of Ashwagandha
(Withania somnifera)-250mg and pure Shilajit extract-
250mg for one month led to a decrease in blood sugar
level along with low-density lipids, very low-density
lipoprotein and fewer ratios of the total cholesterol/ highdensity lipoprotein (66). Anti-Tumor Activity; It has been
shown that Shilajit and HA are effective anti-tumor and
anti-cancer agents (23, 67) which is effective for both
malignant and benign tumors (28). HA can increase the
production of active oxygen during the wound healing
process and in anti-tumor process. Reports by Jurcsik
have shown that when HA was incubated with Hep-2
cancer cell line for 24 hours, the proliferation of the HEp-2
cancer cell line was found to be decreased by 65% as
compared to the control cell line (68). HA can inhibit the
tumor cell multiplication by intercalating with DNA,
blocks the DNA opening and destroys the DNA by
producing the reactive oxygen derivatives (68).
Hiroshi et al in 2007 have shown that 3% of HA extract
has antitumor activity on L1210 lymphocytic leukemia
cell line with delay of tumor formation and significant
reduction in size of tumor. The mice administered with the
HA extract may survive for longer time than untreated
mice after development of tumor (69). They concluded
that antitumor effect was due to direct killing of L1210
and not due to the stimulation of apoptotic cell. This
antitumor activity is due to the activation of the innate
immune system by humus extracts (69). In another study
on mouse breast cell line (Ptas64), the 1:1 ratio of the HA
and glucan was found to inhibit the tumor growth up to
92% in the Ptas64 cell line (70).
It has been shown that HA possesses significant cytotoxic
activity in the CEM (acute T lymphoblastic leukaemia)
cell line (24). HA have been found to exert antiproliferative action and growth inhibition on HL-60 cells
through induction of apoptosis by activating the caspase-3
and mitochondrial cytochrome-c in these cells (67). HA
has also been found to induce the apoptosis and inhibit the
growth in the human smooth muscle cells. Hseu et al, have
reported that HA has been found to inhibit the
proliferation of the smooth cells in the G1 phase of the
cell cycle and led to the apoptotic cell death of smooth
muscles cells (71).
Shilajit and HA matters are immunomodulatory agents
(22). Shilajit helps the immune system for increased
cytokine production by activated immunological cells and
maintains the cell integrity (72). It has been shown that
Shilajit can activate the murine peritoneal macrophages
and activate splenocytes in tumor bearing animals at initial
and later stage of the tumor growth (72). In this study
glucan and HA works in synergy for the stimulation of the
immune reaction. The glucan and HA were reported to
stimulate phagocytosis by stimulating the macrophage
and neutrophil. Moreover HA increases the secretion of
IL-2 by spleen cells (70, 73). HA and FA can also increase
the antibody titre in the plasma (73) and it can stimulate
the immune response and extend it for longer period of
time (73). HA is reported to induce apoptosis in the
Human Primary Fibroblasts and furthermore HA arrest
cell growth at G1 phase and also provoke the cell death in
the Vascular Smooth Muscle Cells (71). The cancer cells
lose the property of apoptotic cell death and thus the
application of anti-cancer agents like Shilajit and HA can
induce apoptosis thereby providing an alternative in the
treatment of cancer (74).
Detoxification of The Heavy Metals: Heavy metals enter
the environment by several anthropogenic activities and
creates adverse effects on human, animal and plants (75).
Accumulation of heavy metals in plant tissues can be Kishor Pant et.al./ Shilajit: A Humic
IJTPR, June – August 2012, 4(2): 17-25
Page21
hazardous if they are consumed by the humans or animals.
This gradual saturation of heavy metals in the human body
can lead to mutagenic and carcinogenic effects resulting in
many diseases (75). It has been shown that the elevated
level of the iron, zinc and copper in the serum could lead
to the development of cancer (76). Therefore, it is essential
to restrict access of heavy metals from the soil into the
plants and the human body.
HA can interact with heavy metals in the soil rendering
them as poorly soluble compound and thus can avoid the
heavy metal entrance into the organisms (75).
Many experiments support the capacity of the HA to
detoxify the heavy metals and lessen the bioavailability in
plant and animals. Experiments by Tao et al have shown
that the availability of copper was reduced for fish uptake
via their gills in presence of fulvic acid in water (77).
Zralý et al have demonstrated that the feeding of lead
along with HA reduces the accumulation of lead in
chicken organs such as bone, muscle, liver and kidney,
compared to the chicken feed without HA (78). Similarly,
in the other study of Herzig et al states that accumulation
of cadmium were reduced in the presence of HA by 39.6%
in kidney, 34.2% in liver and 80.8% in muscle as
compared to the chicken feed with Cd in the absence of
HA. Sanmanee et al have shown that FA treatment reduces
the toxicity of copper in the mammalian cell, porcine
oviductal epithelial cells (80). In plants, humic compounds
have been reported to decrease the toxicity of the copper
(Cu) and vanadium (V) in Zea mays (81) and the uptake of
the Zinc and Cadmium were reduced in Ceratophyllum
demersum (82).
Dosage And Administration: According to Ayurveda,
Shilajit should be consumed in a very small amount (500
mg/ml) with milk or water twice a day, to ensure the
optimal level of the Shilajit in the body. The optimal level
of Shilajit in the body is attained after 10-12 hours post
consumption and it is not recommended with a heavy diet
and in individuals possessing a high uric acid count (107).
Toxicity of Shilajit: Shilajit has no reported side effects
and is non toxic. Velmurugan et al checked the safety
profile of the Shilajit. They regularly administrated Shilajit
for 3 months (91 days) in mice and concluded that Shilajit
is completely safe for long-term usage and can function as
a vital drug for anaemia or iron deficiency (108).
CONCLUSION
Shilajit is an ancient medicine and wonder drug of the
Ayurveda used by the Hindu physicians for the treatment
of several body disorders. The humic matter component of
Shilajit has numerous beneficial effects on the human
body. Charaka Samhita recommends Shilajit as a cure for
numerous human ailments and is highly recommended by
the Ayurvedic practitioners. Shilajit and its humic
components have anti oxidant, antiviral, antiinflammatory, anti ulcerative, antimutagenic and heavy
metal chelating properties. Therefore, Shilajit and humic
compounds with these properties would possibly be a
useful cancer chemopreventive agent and may be
beneficial in cancer therapy. In addition, Shilajit is useful
in arthritis, can function as anti fungal agent as well as
nutritive tonic that help in the nutrient transfer to the
deeper tissues of our body. Shilajit has immense
therapeutic properties and certainly can be proved to be a
boon for mankind possibly in cancer prevention and
therapy.


REFERENCES
1. Mukhtar H, Ahmad, N. Cancer chemoprevention:
future holds in multiple agents: contemporary issues
in Toxicology. Toxicol Appl Pharmacol
1999;158:207-10.
2. Agarwal SP, Khanna, R., Karmarkar, R., Anwer,
M.K., Khar, R.K. Shilajit: a Review. Phytother Res.
2007;21:401-5.
3. Ghosal S, Lal, J., Singh,S.K., Goel, R.K., Jaiswal,
A.K., Bhattacharya,S.K. The Need for Formulation
of Shilajit by Its Isolated Active Constituents-9.
Phytother Res. 1991b;5:211-6.
4. Chopra RN, Chopra, I.C., Handa,K.L., Kapur,L.D.
Chopra’s Indigenous drugs of india 2nd ed. B
Calcutta India; K Dhur of academic Publishers.
1958.
5. Murkherjee B. Traditional Medicine, New delhi.
proceedings of an international seminar, Calcutta
India Oxford and IBH Publishing. november
1992:308-19.
Table 1; – List of the heavy metals inactivated by HA compounds and types of cancer associated with the heavy metals
S.N. Heavy Metals
inactivated by
HA
References

Cancers associated to metals
1 Copper (Cu) (61, 81, 83-88) Oral, head and neck (89), non-Hodgkin’s lymphoma.
2 Lead (Pb) (61, 78, 83, 88,
90)
Kidney (91), Lung (92), Breast (93) and Stomach cancer (92).
3 Cadmium (Cd) (61, 82, 84, 87) Breast (94), Lung (91), Kidney (92), and Prostate cancer (92).
4 Nickel (Ni) (87) Nasal (91), Lung (91) and Oral cancer (95).
6 Aluminium (Al) (96) Lung (97), Bladder (97), Breast (98).
7 Zink (Zn) (82, 83, 87) Prostate cancer (99, 100).
8 Arsenic (As) (61, 101-103) Lung (91, 92, 104, 105), Skin (104, 105) and Bladder cancer (92, 105,
106).Kishor Pant et.al./ Shilajit: A Humic
IJTPR, June – August 2012, 4(2): 17-25
Page22
6. Nadkarni KM. Indian Materia Medica. 3rd edition.
Popular Prakashan Private Ltd Bombay, India.
1954;2:23.
7. Bucchi LR. Selected herbals and human exercise
performance. American Society for Clinical
Nutrition. 2000;72(2):624S-36S.
8. Tirtha SSS. The Ayurvedic Encyclopedia. Bayville,
NY: Ayurveda Holistic Center Press; 1998.
9. Puri HS. Rasayana. Taylor & Francis London,
England. 2003.
10. Talbert R. Shilajit a materia medica monograph,
Degree paper Grass Valley, California: California
College of Ayurveda; 2004.
11. Srivastava RS, Kumar Y, Singh SK, Ghosal S.
Shilajit, its source and active principles. Proc 16
IUPAC (Chemistry of Natural Products). Kyoto
Japan. 1988:524.
12. Sharma PV. In Darvyaguna Vijnan, 4th edn.
Chaukkhamba Sanskrit Sansthan Varanasi. 1978:63.
13. Ghosal S, Lal J, Singh SK. The Core Structure of
Shilajit Humus. Soil Biol Biochem. 1991a;23:673–
80.
14. Frolova LN, Kiseleva TL. Chemical Composition of
Mumie and Methods for Determination of Its
Authenticity and Quality. ChemPharm J. 1996;8:49–
53.
15. Ghosal S, Singh SK, Kumar Y, Srivastava RS, Goel
RK Dey, Bhattacharya SK. Anti-Ulcerogenic
Activity of Fulvic Acids and 4′-Methoxy-6-
Carbomethoxybiphenyl Isolated From Shilajit.
Phytother Res. 1988;2:187-91.
16. Schepetkin I, Khlebnikov A, Kwon BS. Medical
Drugs From Humus Matter: Focus on Mumie. Drug
Dev Res. 2002;57:140-59.
17. Goel RK, Banerjee RS, Acharya SB.
Antiulcerogenic and Antiinflammatory Studies With
Shilajit. J Ethnopharmacol. 1990;29:95-103.
18. Acharya SB, Frotan MH, Goel RK, Tripathi SK, Das
PK. Pharmacological Actions of Shilajit. Indian J
Exp Biol. 1988;26:775-7.
19. Islam KMS, Schuhmacher A, Gropp J.M. Humic
Acid Substances in Animal Agriculture. Pakistan
Journal of Nutrition. 2005;4(3):126-34.
20. Wiseman H, Halliwell B. Damage to DNA by
reactive oxygen and nitrogen species : role in
inflammatory disease and progression to cancer.
Biochem J 1996;313:17-29.
21. Borek C. Dietary Antioxidants and Human Cancer.
integrative cancer therapies 2004;3(4):333-41.
22. Schepetkin IA, Khlebnikov AI, Ah SY, Woo SB,
Jeong CS, Klubachuk ON, Kwon BS.
Characterization and Biological Activities of Humic
Substances from Mumie. J Agric Food Chem
2003;51:5245-54.
23. Peña-Méndez EM, Havel, J, Patočka J. Humic
substances – compounds of still unknown structure:
applications in agriculture, industry, environment,
and biomedicine. Appl Biomed. 2005;3:13-24.
24. Vašková J, Veliká B, Pilátová M, Kron I, Vaško L.
Effects of humic acids in vitro. In Vitro
CellDevBiol—Animal. 2011;47:376-82.
25. Guerra LN, Moiguer, S, Karner M, de Molina MRC,
Sreider CM, Burdman JA. Antioxidants in the
Treatment of Graves Disease. IUBMB Life.
2001;51:105-9.
26. Caruso C, Lio D, Cavallone L, Franceschi C. Aging,
Longevity, Inflammation, and Cancer. Ann NY Acad
Sci. 2004;1028:1-13.
27. Meena H, Pandey HK, Arya MC, Ahmed Z. Shilajit:
A panacea for high-altitute problems. International
Journal of Ayurveda Research. 2010;1(1):37-40.
28. Murthy KRS. Astanga Hrdayam: Krishnadas
Academy, Varanasi, India,; 2001.
29. Molloy RM, Sonnenberg A. Relation between gastric
cancer and previous peptic ulcer disease. Gut
1997;40:247-52.
30. Goel RK, Banerjee RS, Achrarya SB.
Antiulcerogenic and antiinflammatory studies with
Shilajit. J Ethnopharmacol. 1990;29:95-103.
31. Van Rensburg CEJ, Snyman J R, Mokoele T,
Cromarty A D. Brown Coal Derived Humate Inhibits
Contact Hypersensitivity; An Efficacy, Toxicity and
Teratogenicity Study in Rats. Inflammation.
2007;30(5).
32. Lown JF, Gill K, Cutler SJ, Cutler HG, Pollock SH,
inventor; Anti-inflammatory humate compositions
and metohs of use thereof. Dallas, TX (US)2006.
33. van Rensburg CEJ, and Naude PJ. Potassium
Humate Inhibits Complement Activation and the
Production of Inflammatory Cytokines In Vitro.
Inflammation. 2009;32(4):270-6.
34. Gisela K, Elizabeth C, Rensburg JV. An In Vitro
Investigation of the Anti-Inflammatory Properties of
Potassium Humate. . inflammation. 2004;28:169-74.
35. Amada PY, Isoda H, Yamaguchi T, Talorete TPN,
Abe Y . Inhibitory Effect of Fulvic Acid Extracted
from Canadian Sphagnum Peat on Chemical
Mediator Release by RBL-2H3 and KU812 Cells. .
Biosci Biotechnol Biochem 2007;71:1294-305.
36. Van Rensburg CEJ, Malfeld SCK, Dekker J. Topical
Application of Oxifulvic Acid Suppresses the
Cutaneous Immune Response in Mice. Drug
development research. 2001;53:29-32.
37. Muela A, Garcia-Bringas JM, Barcina AI. Humic
Materials Offer Photoprotective Effect to
Escherichia coli Exposed to Damaging Luminous
Radiation. Microb Ecol. 2000;40:336-44.
38. Alkan U, Teksoy A A, Baskaya HS. Influence of
humic substances on the ultraviolet disinfection of
surface waters. Water and Environment Journal
2007;21:61-8.
39. Clair TA, Ehrman J, Kaczmarska I, Locke A,
Tarasick DW, Day KE, Maillet G. Will reduced
summer UV-B levels affect zooplankton populations
of temperate humic and Clearwater lakes?
Hydrobiologia. 2001;462:75-89.
40. Biggar RJ, Jaffe, E. S., Goedert, J. J., Chaturvedi, A.,
Pfeiffer, R., Engels, E. A.,. Hodgkin lymphoma and Kishor Pant et.al./ Shilajit: A Humic
IJTPR, June – August 2012, 4(2): 17-25
Page23
immunodeficiency in persons with HIV / AIDS,.
Blood. 2011;108:3786-91.
41. Harrington WJ, Wood, C. AIDS and Associated
Malignancies. DNA Tumor Viruses2009. p. 683-
702.
42. Franceschi S, Maso LD, Rickenbach M, Polesel J.
Hersal B, Cavassini M, Bordoni A, Elzi L, et al.
Kaposi sarcoma incidence in the Swiss HIV Cohort
Study before and after highly active antiretroviral
therapy. British Journal of Cancer. 2008;99:800-4.
43. Emuss V, Boshoff C. Kaposi ’ s sarcoma and the
lymphatics.: Springer Science+Business Media B.V;
2009.
44. Mauizio Z, inventor; Treatment of HIV infection
with Humic acid. Paris2002.
45. Dekker J, Medlen CE, inventor; Oxihumic acid and
its use in the treatment of the various
conditions2003.
46. Botes ME, Dekker J, van Rensburg CEJ. Phase I
Trial With Oral Oxihumate in HIV-Infected Patients.
Drug Development Research 2002;57:34-9.
47. Jooné GK, DekkerJ , van Rensburg CE. Investigation
of the immunostimulatory properties of oxihumate. Z
Naturforsch C. 2003;58:3-4.
48. Gupta GD, Sujatha, N., Dhanik, A., Rai, N.P.
Clinical Evaluation of Shilajatu Rasayana in patients
with HIV Infection. AYU. 2010;31(1):28-32.
49. Starr JR, Janet R, Daling E, Fitzgibbons F, Margaret
M, Ashley MR, Denise A, Galloway DA, Schwartz
SM. Serologic Evidence of Herpes Simplex Virus 1
Infection and Oropharyngeal Cancer Risk. Cancer
res. 2001;61:8459-64.
50. Helbig B, Klöcking R, Wutzler P. Anti-herpes
simplex virus type 1 activity of humic acid-like
polymers and their o-diphenolic starting compounds.
Antiviral chemistry & chemotherapy. 1997;8(3):265-
73.
51. Klöcking R, Helbig B, Schötz G, Schacke M,
Wutzler P. Anti-HSV-1 activity of synthetic humic
acid-like polymers derived from p-diphenolic
starting compounds. Antiviral Chemistry &
Chemotherapy. 2002;13:241-9.
52. Boffetta P, Jourenkova N, Gustavsson P . Cancer
risk from occupational and environmental exposure
to polycyclic aromatic hydrocarbons. Cancer Causes
and Control. 1997;8:444-72.
53. Marova I, Kucerik J, Duronova K, Mikulcova A,
Vlckova Z. Antimutagenic and/or genotoxic effects
of processed humic acids as tested upon S. cerevisiae
D7. Environ Chem Lett 2011;9:229-33.
54. Zhang Z, Liu J, Cai X, Jiang W, Luo W. Jiang G.
Sorption to Dissolved Humic Acid and Its Impacts
on the Toxicity of Imidazolium Based Ionic Liquids.
Environ Sci Technol. 2011;45:1688-94.
55. Gichner T, Badaev SB, Pospisil F, Velemimnsky J.
The Effect of Humic Acids, Fractionated According
to Molecular Mass, on the Formation and
Mutagenicity of N-MethyI-N-Nitrosourea. Biologia
plantarum (Praha). 1989;31(5):392-9.
56. Van Rensburg CJ, Van Rensburg, CEJ, Van Ryssen
JBJ, Casey NH, Rottinghaus GE. In Vitro and In
Vivo Assessment of Humic Acid as an Aflatoxin
Binder in Broiler Chickens. Poultry Science
2006;85:1576-83.
57. Santosa SS, Vermeulena, S., Haritovab, A., FinkGremmels, J. Isotherm modeling of organic activated
bentonite and humic acid polymer used as mycotoxin
adsorbents. Food Additives and Contaminants
2011;28(11):1578-89.
58. Kollist-Siigur K, Nielsen T, Grøn C, Hansen PE,
Helweg C, Jonassen KEN, Jørgensen O, Kirso U.
Sorption of Polycyclic Aromatic Compounds to
Humic and Fulvic Acid HPLC Column Materials.
Published in J Environ Qual 2001;30:526-37.
59. Nielsen T, Siigur K, Helweg C, Jørgensen O, Hansen
PE, Kirso U. Sorption of Polycyclic Aromatic
Compounds to Humic Acid As Studied by HighPerformance Liquid Chromatography. Environ Sci
Technol 1997;31:1102-8.
60. Wang XP, Shan XQ, Luo L, Zhang SJ, Wen B.
Sorption of 2,4,6-Trichlorophenol in Model Humic
Acid-Clay Systems. J Agric Food Chem 2005, 53, .
2005;53:3548-55.
61. Yates LM, Wandruszka, R.V. Decontamination of
Polluted Water by Treatment with a Crude Humic
Acid Blend. Environ Sci Technol. 1999;33:2076-80.
62. Perminova IV, Hatfield, K. . Remediation Chemistry
of Humic Substances: Theory and Implications for
Technology. In: Perminova IV, editor. Use of Humic
Substances to Remediate Polluted Environments:
From Theory to Practice. NetherlandS: Springer;
2005. p. 3-36.
63. Huxley R, Moghaddam AA, deGonzalez AB, Barzi
F, Woodward M. Type-II diabetes and pancreatic
cancer: a meta-analysis of 36 studies. British Journal
of Cancer. 2005;92:2076-83.
64. Smith U, Gale EAM. Does diabetes therapy
influence the risk of cancer? Diabetologia. 2009.
65. Trivedi NA, Mazumdar, B J, Bhatt D, Hemavathi K
G. Effect of Shilajit on blood glucose and lipid
profile in alloxaninduced diabetic rats. Indian J
Pharmacol 2004;36(6):373-6.
66. Upadhyay AK, Kumar, K., Mishra, H. Effects of
combination of Shilajit extract and Ashwagandha
(Withania somnifera) on fasting blood sugar and
lipid profile. Journal of Pharmacy Research
2009;2(5):897-9.
67. Yanga HL, HseuYC, Yi-Ting Hseua, Luc FJ, Linb E,
Laid JS. Humic acid induces apoptosis in human
premyelocytic leukemia HL-60 cells. fe Sciences.
2004;75(15):1817-31.
68. Jurcsik I. Possibilities of applying humic acid in the
medicine (wond healing and cancer theraphy). In:
Senesi N, Miano, T.M., editor. Humic substances in
the global Environment and implications on human
health: Elsevier Science B.V.; 1994.
69. Hiroshi K, Denso. Antitumor Effect of Humus
Extract on Murine Transplantable L1210 Leukemia.
J Vet Med Sci. 2007;69(10):1069-71.Kishor Pant et.al./ Shilajit: A Humic
IJTPR, June – August 2012, 4(2): 17-25
Page24
70. Vetvicka V, Baigorri, R., Zamarreiio, A.M., GarciaMina, J.M., Yvin, J.C. Glucan and Humic Acid:
Synergistic Effects on the Immune System. J of Med
Food. 2010;13(4):863-9.
71. Hseu YC, Lin E, Chen JY, Liua R, Huang CY, Lu
FJ, Liao JW, Chen SC, Yang HL. Humic Acid
Induces G1 Phase Arrest and Apoptosis in Cultured
Vascular Smooth Muscle Cells. Environmental
Toxicology. 2008;24:243-58.
72. Ghosal S. Chemistry of Shilajit, an
immunomodulatory Ayurvedic rasayan. Pure & Appl
Chern. 1990;62(7):1285-8.
73. Vucskits AV, Hulla, I., Bersenyi, A., Andrasofszky,
E, Kulcsar M, Szabo J. Effect of fulvic and humic
acids on performance, immune response and thyroid
function in rats. Journal of Animal Physiology and
Animal Nutrition 2010;94:271-728.
74. Gerl R, Vaux, D.L. Apoptosis in the development
and treatment of cancer. Carcinogenesis
2005;26(2):263-70.
75. Gorova A, Skvortsova, T., Klimkina, I., Pavlichenko,
A. . Cytogenetic effects of humic substances and
their use for remediation of polluted environments.
Use of Humic Substances to Remediate Polluted
Environments: From Theory to Practice. Netherland:
Springer; 2005. p. 311-28.
76. Wu T, Sempos CT, Freudenheim JOL, Muti P, Smit
E. Serum Iron , Copper and Zinc Concentrations and
Risk of Cancer Mortality in US Adults. Ann
Epidemiol 2004;14:195-201.
77. Tao S, Xu S, Cao J, Dawson R. Bioavailability of
Apparent Fulvic Acid Complexed Copper to Fish
Gills. Bull Environ Contam Toxicol. 2000;64:121-7.
78. Zralý Z, PísaÅ™íková B, Trčková M, Navrátilová M.
Effect of Humic Acids on Lead Accumulation in
Chicken Organs and Muscles. ACTA Vet brno.
2008;77:439-45.
79. Herzig I, Navratilova, M, Suchy P, Vecerek V, Totus
J. Model trial investigating retention in selected
tissues using broiler chicken fed cadmium and humic
acid. Veterinarni Medicina. 2007;52:162-8.
80. Sanmanee N, Areekijseree, M. The Effects of Fulvic
Acid on Copper Bioavailability to Porcine Oviductal
Epithelial Cells. Biol Trace Elem Res 2010;135:162-
73.
81. Ullah SM, Gerzabek, M.H. Influence of fulvic and
humic acids on Cu-toxicity and V-toxicity to Zea
mays. Bodenkultur. 1991;42:123-34.
82. Bunluesin S, Pokethitiyook P, Lanza GR, Julian FT,
Maleeya K, Baoshan X, Suchart U. Influences of
Cadmium and Zinc Interaction and Humic Acid on
Metal Accumulation in Ceratophyllum Demersum.
Water Air Soil Pollut. 2007;180:225-35.
83. Kezhong G, Jack P, Jeniffer J, Colin T, Colin T.
Interaction between peat, humic acid and aqueous
metal ions. Environmental Geochemistry and Health.
1999;21:13-26.
84. Xue H, Sigg L. Comparison of the Complexation of
Cu and Cd by Humic or Fulvic Acids and by Ligands
Observed in Lake Waters. Aquatic Geochemistry.
1999;5:313-35.
85. Winner RW. Bioaccumulation and toxicity of copper
as affected by interactions between humic acid and
water hardness. Water Res. 1985;19:449-55.
86. Sanmanee N, Areekijseree M. The Effects of Fulvic
Acid on Copper Bioavailability to Porcine Oviductal
Epithelial Cells. Biol Trace Elem Res.
2010;135:162-73.
87. Chen Y, Mao X, Zhu D, Synthesis of macroporous
Humic acid resins and their Chelating properties for
heavy metal ions. Polymer communications.
1984:159-68.
88. Christl I, Metzger A, Heidmann I, Kretzschmar R .
Effect of Humic and Fulvic Acid Concentrations and
Ionic Strength on Copper and Lead Binding.
Environmental Science & Technology.
2005;39:5319-26.
89. Coates RJ et al . Cancer Risk in Relation to Serum
Copper Levels Cancer res. 1989;49:4353-6.
90. Malcova R, Gryndler M, Hrselova H, Vosatka, M.
The Effect of Fulvic Acids on the Toxicity of Lead
and Manganese to Arbuscular Mycorrhizal Fungus
Glomus intraradices. Folia Microbio.
2002;47(5):521-6.
91. Hayes RB. The carcinogenicity of metals in humans.
Cancer causes and control. 1997;8:371-85.
92. Järup L. Hazards of heavy metal contamination.
British Medical Bulletin 2003;68:167-82.
93. Mcelroy JA, Shafer MM, Gangnon RE, Crouch LA,
Newcomb P.A . Urinary Lead Exposure and Breast
Cancer Risk in a Population-Based Case-Control
Study. Cancer Epidemiol Biomarkers Prev.
2008;17:2311-7.
94. Gallagher CM, Chen, JJ , Kovach JS. Environmental
cadmium and breast cancer risk. aging. 2010;1:804-
14.
95. Su C-c, Lin,Yo-Yu., Chang,Tsun-Kuo., Chiang, ChiTing., Chung, Jian-An., Hsu, Yun-Ying., Lian, IeBin.,. Incidence of oral cancer in relation to nickel
and arsenic concentrations in farm soils of patients ’
residential areas in Taiwan. BMC Public Health.
2010;10:1-10.
96. Gardner JL, Al-Hamdani S H. Interactive effects of
aluminum and humic substances on Salvania.
Journal of Aquatic Plant Management. 1997;35:30-4.
97. Romundstad P, Haldorsen T. Andersen A . Lung and
bladder cancer among workers in a Norwegian
aluminium reduction plant. Occupational and
Environmental Medicine. 2000;57:495-9.
98. Exley C, Charles L M, Barr L, Martin C, Polwart A,
Darbre PD. Aluminium in human breast tissue.
Journal of Inorganic Biochemistry. 2007;101:1344-
36.
99. Krone CA, Harms LH . Zinc Supplement Use and
Risk of Prostate Cancer. Journal of the National
Cancer Institute 2003;95:95-6.
100. Gallus Sea. Dietary Zinc and Prostate Cancer Risk :
A Case-Control Study from Italy. european urology.
2007;52:1052-7.Kishor Pant et.al./ Shilajit: A Humic
IJTPR, June – August 2012, 4(2): 17-25
Page25
101. Weng L, Williem H, Van R, Tjisse H. Effects of
Fulvic and Humic Acids on Arsenate Adsorption to
Goethite: Experiments and Modeling. Environ Sci
Technol. 2009;43:7198-204.
102. Palmer NE, Wandruszka RV. Humic acids as
reducing agents: the involvement of quinoid moieties
in arsenate reduction. Environ Sci Pollut Res.
2010;17:1362-70.
103. Buschmann J, Kappeler A, Lindauer U, Kistler D,
Berg M, Sigg L Arsenite and Arsenate Binding to
Dissolved Humic Acids: Influence of pH, Type of
Humic Acid , and Aluminum. Environmental
Science & Technology. 2006;40:6015-20.
104. Mazumder DNG. Chronic arsenic toxicity & human
health. Indian Journal Of Medical Research.
2008;128:436-47.
105. Huang C, Ke Q, Costa M, Shi X Molecular
mechanisms of arsenic carcinogenesis. Molecular
and Cellular Biochemistry. 2004;255:56-66.
106. Moore LE, et al. Arsenic-Related Chromosomal
Alterations in Bladder Cancer. Journal of the
National Cancer Institute. 2002;94:1688-96.
107. Thirtha SSS. The Ayurveda Enccyclopedia. Bayville,
NY: Ayurveda Holstic Center Press; 1998.
108. Velmurugan C, Vivek, B, Wilson E, Bharathi T,
Sundaram T. Evaluation of safety profile of black
Shilajit after 91 days repeated administration in rats.
Asian Pacific Journal of Tropical Biomedicine.
2012:210-114