Abstract – Shilajit is truly a remarkable substance with a long history of human usage for healing for the urinary system and for diabetes. Unfortunately, many of those who sell shilajit or products containing it, make many wild claims for shilajit’s ability to cure diseases.[…] I excluded Internet sources for this information as I felt their claims were exaggerated beyond reality. [….]this summary of current research on shilajit show that some claims are substantiated and others are not.
We are currently the only ones outside of Russia that offer raw, unprocessed Black Mumijo (or Shilajit as Ayurvedic medicine calls it) for sale.
It is an extremely rare natural substance, only found in some mountain ranges like the Himalaya and the Altai mountains. Because of its rarity and its hyped reputation as a panacea (it is also one of the last remaining ‘rasayana’s’ in Ayurveda) a lot of people smell good business opportunities.
Resulting in a lot of fake, flooding the -online- market. Like mixes of burnt sugar with propolis, Ozokerite, herbal shilajit (!?), you name it…
Let’s face it, a natural substance, more rare than gold or diamonds, that takes several decades to form a layer one millimeter thick can never be available in the quantities that are currently offered online, and definitely not for low prices.
‘Guaranteed levels of fulvic acid !’ some sellers claim; but how can you guarantee this in a natural product without processing it to bits and/or spiking it ?
Processing Shilajit • Mumijo (e.g. when turning it into tablets, powder, tinctures) involves heat and adding stabilizers, additives etc, and probably involves the use of metal equipment, which means the natural composition of Mumijo • Shilajit (and the resulting synergy) is affected, many of the amino acids will be destroyed (because of heat) and several other components will oxidize and change properties (by getting in touch with metal).
You don’t have to take our word for it. Please have a look at our resources section where we have collected quite a few research publications about Mumijo •Shilajit). http://www.oriveda.com/JAM/jrox.php?id=144_1 As they say mercury either giveth life or taketh it. A lot of few pdf’s that elaborate on all of this information, the real juice, manuka for you to get those mental cogs feeling invigorated.
This is a very healing medicine. From a pristine ley of the land, the mountains glacial soup. Purity from fire.
Some Himalayan tribal villagers, who were observing white monkeys migrating to the higher mountains in summer months, made the discovery of shilajit. The monkeys were observed to lick the semi-solid substance exuding out the rock crevices. Since observing the animal behaviors were an important part of healthcare research in ancient times, those villagers attributed the great strength, longevity and wisdom of those monkeys to this substance. Curious by the thought, they themselves started taking the substance and reported a broad spectrum of improvement in their health and stamina. It gave them more energy.
Abstract – Herbs have been used throughout history to enhance physical performance, but scientific scrutiny with controlled clinical trials has only recently been used to study such effects. The following herbs are currently used to enhance physical performance regardless of scientific evidence of effect: Chinese, Korean, and American ginsengs; Siberian ginseng, mahuang or Chinese ephedra; ashwagandha; rhodiola; yohimbe; Cordyceps fungus, shilajit or mummio; smilax; wild oats; Muira puama; suma (ecdysterone); Tribulus terrestris; saw palmetto berries; Beta-sitosterol and other related sterols; and wild yams (diosgenin). Controlled studies of Asian ginsengs found improvements in exercise performance when most of the following conditions were true: use of standardized root extracts, study duration (>8 wk, daily dose >1 g dried root or equivalent, large number of subjects, and older subjects. Improvements in muscular strength, maximal oxygen uptake, work capacity, fuel homeostasis, serum lactate, heart rate, visual and auditory reaction times, alertness, and psychomotor skills have also been repeatedly documented. Siberian ginseng has shown mixed results. Mahuang, ephedrine, and related alkaloids have not benefited physical performance except when combined with caffeine. Other herbs remain virtually untested. Future research on ergogenic effects of herbs should consider identity and amount of substance or presumed active ingredients administered, dose response, duration of test period, proper experimental controls, measurement of psychological and physiologic parameters (including antioxidant actions), and measurements of performance pertinent to intended uses.
Abstract – Shilajit is a rejuvenator (�Rasayana�) of traditional Hindu Ayurvedic origin, which clearly has attracted considerable interest in India. Shilajit is a blackish-brown exudation of variable consistency exuding from layers of rocks in many mountain ranges of the world, especially the Himalayas and Hindukush ranges of the Indian subcontinent. Shilajit has been used as a folk medicine for general physical strengthening, anti-aging, blood sugar stabilization, urinary tract rejuvenation, enhanced brain functioning potency, kidney rejuvenation, immune system strengthening, arthritis, hypertension as well as for treating many other conditions. Shilajit (botanical name: Asphaltum), also known as mineral pitch, is a natural exudate oozed from rocks during hot weather. Shilajit is a compact mass of vegetable organic matter, which is composed of a gummy matrix interspersed with vegetable fibers and minerals.
This next image personifies the bio sphere and how we are what we eat, and that all is connected to the things we know.
hope you enjoy this valuable research and insight and will share with your friends. The minerals/herbs we are offering are second to no other.
The Charaka Samhita states that, “Stones of metal like gold etc., in the mountains get heated up by the sun and the exudates that comes out of them in the form of smooth and clean gum is called çiläjatu”. Sharma adds that metals like gold do not produces exudates and what was actually intended was that stones containing gold would produce shilajit (Sharma 2000).
The Sushruta Samhita states that “A gelatinous substance that is secreted from the side of the mountains when they have become heated by the rays of the sun in the months of Jyaishta and Ashadha. This substance is what is know as Çilájatu and it cures all distempers of the body.” (Bhishagratna 1998). Jyaishta is May-June and Ashadha is June-July. It is found in abundance in the lower Himalayan hills near Hardwar, Simla and also in Nepal. (Chopra 1958)
Shilajit is a blackish-brown exudation, of variable consistency, obtained from steep rocks of different formations found in the Himalayas at altitudes between 1000 to 5000 meter, from Arunachal Pradesh in the
2East to Kashmir in the West. It is also found in Afghanistan, Nepal, Bhutan, Pakistan, China, Tibet and U.S.S.R (Tien-Shan, Ural and Caucasus) (Jaiswal 1992).
Types of Shilajit:
The Charaka Samhita states that there are four types based on stones of four types of metals from which it exudes: gold, silver, copper and black iron. The shilajit from the last type is the best. If administered according to proper procedure, it produces rejuvenating and aphrodisiac effects and cures diseases (Sharma 2000).
The Sushruta Samhita states that there are six types based on their origins (shad-yoni). In addition to the four types listed above he added tin and lead. Each type has the same taste (rasa) and potency (virya) as the metal to whose essence it owes its origin. He goes on to note that tin, lead, and iron, copper, silver, gold are progressively more efficacious, so the different types of shilajit that derive from these metals are also progressively more efficacious in their application (Bhishagratna 1998).
The Astanga Hrdayam also notes the six types but notes that the shilajit coming out of iron is the best (Murthy 2001).
The description of six types in Sushruta relates to both the rejuvenation therapy and treatment of diseases. Caraka describes only the rejuvenating effects of shilajit, and this effect is available in the four types that he lists. (Sharma 2000).
Chopra (1958) states there are four types each with its own unique color; gold (red), silver (white), copper(blue), iron(blackish brown).
There are several varieties of the substance, of which the black color has the main therapeutic properties (Frawley 2001).
The black form of shilajit is the most commonly used medicinal form (Halpern 2003).
relieve digestive problems, increase sex drive, improve to memory etc., with the passage of the time traditional health practitioners established the methods to purify the substance (Dabur 2003).
Shilajit is an important drug of the ancient Hindu material medica and was used extensively by the Hindu physicians in a variety of diseases. This section sites uses as described in the Caraka Samhita, Susruta Samhita and Astanga Hrkayam.
The Caraka Samhita discusses shilajit in a chapter on rejuvenation therapy (rasayana). It has been proposed that the modern equivalent of a rasayana is an adaptogenic substance. (Ghosal 1998). The Caraka Samhita states that there is no curable disease in the universe, which is not effectively cured by shilajit when it is administered at the appropriate time, in combination with suitable drugs and by adopting the prescribed method. When administered to a healthy person, with similar conditions it produces immense energy. In the Sushruta Samhita, it is noted that there is no bodily distemper, which does not yield to shilajit’s highly curative virtues. When gradually taken, (in adequate doses) it tends to improve the strength and complexion of the body. (Bhishagratna 1998). The is echoed in the Astanga Hrdayam which also states that it is the best rejuvenator (Murthy 2001).
The Caraka states that it enables the user to witness a hundred summers on earth, free from disease and decay. Each tulä weight (7.75 lbs. or 3.5 kilos) of shilajit taken successively, adds a century to the duration of the human life, while ten tulä weight (77.5 lbs. or 35 kilos) measures extend it to a thousand years (Sharma 2000). Enables the user to witness a hundred summers on earth, free from disease and decay. Additional quantities are said to extend lifetime in increments of a century up to one thousand years. (Bhishagratna 1998).
Traditional Indications: Cardiovascular
Kushtha (obstinate skin diseases including leprosy) (Bhishagratna 1998) (Murthy 2001)
Endocrinology, reproductive system, obstetrics/ gynecology, prostate
Ama (disorders of poor digestive activities) (Murthy 2001) Enlargement of the abdomen (Murthy 2001). Hemorrhoids(Bhishagratna 1998). Rectal distula (Murthy 2001)
Worms (Murthy 2001)
Hematology, lymphatic, cancer
Jaundice (Bhishagratna 1998). Çopha (edema) (Bhishagratna 1998). Elephantiasis(Bhishagratna 1998). Poison begotten distempers(Bhishagratna 1998). Fever(Murthy 2001). Chronic fever(Bhishagratna 1998).
Immunology, aids, infectious diseases
Phthisis (wasting of the body) (Bhishagratna 1998). Gulma (internal tumors) (Bhishagratna 1998). Malignant tumor (Murthy 2001) Benign tumor (Murthy 2001)
Liver and gallbladder
Loss of consciousness (Murthy 2001) Epilepsy (apasmára) (Bhishagratna 1998). Insanity (Bhishagratna 1998).
Respiratory (lower and upper respiratory tract including ears, nose, throat, sinuses)
Cough (Murthy 2001)
Scrofula (tuberculous cervical lymphadenitis) (Murthy 2001).
Rheumatological, orthopedic, muscles, contusions
Obesity (Murthy 2001).
Urinary tract system (kidney, ureter, bladder)
Dysuria (Murthy 2001). Madhu-Meha (vata type diabetes mellitus -type I) (Bhishagratna 1998) (Murthy 2001) Gravel or stones in the bladder (Bhishagratna 1998).
What follows is a list of suggested usage from reputable sources. I purposefully chose not to include any claims made by anyone who was selling shilajit, as these sources tend to inflate its usefulness.
Modern Indications: Cardiovascular
Päìòutä (anemia) (Dash 1991). Rakta (vitiation of blood) (Dash 1991). Reduces blood sugar (Tierra 1988).
Parasitic diseases of the skin (Chopra 1958). Skin diseases (Frawley 2001).
Leprosy (Chopra 1958).
Endocrinology, reproductive system, obstetrics/ gynecology, prostate
Sexual debility (Frawley 1989) (Frawley 2001). Sexual vitality (Puri 2003). Infertility (Tierra 1988). Menstrual disorders(Frawley 2001).
Post partum health (Puri 2003).
Thyroid disfunction (Lad 2002).
Digestive troubles (Chopra 1958). Chardi (vomiting) (Dash 1991). Arças (piles or hemorrhoids ) (Dash 1991) (Frawley 2001). Krimi (parasitic infestation) (Dash 1991) (Frawley 2001).
Hematology, lymphatic, cancer
Edema (dropsy) (Chopra 1958) (Frawley 1989) (Frawley 2001). Spleen enlargement (Halpern 2003). Cancer (Frawley 1989).
Immunology, aids, infectious diseases
Weakness (Frawley 2001). Debility (Frawley 2001). Kñaya (comsumption) (Dash 1991) (Tierra 1988). Immunomodulater (Puri 2003). AIDS (Frawley 1989).
Liver and gallbladder
Jaundice (Frawley 2001). Gall stones (Frawley 2001). Udara (obstinate abdominal diseases including ascites) (Dash 1991).
Nervous diseases (Chopra 1958). Antistress (Frawley 1989)(Puri 2003). Epilepsy (Frawley 2001). Unmade (insanity) (Dash 1991) (Frawley 2001).
Respiratory (lower and upper respiratory tract including ears, nose, throat, sinuses)
Çväsa (dyspnoea) (Dash 1991). Chronic bronchitis (Chopra 1958). Asthma (Chopra 1958) (Frawley 2001). Mouth diseases (Dash 1991).
Rheumatological, orthopedic, muscles, contusions
Obesity (Frawley 1989)(Frawley 2001). Fractures (Chopra 1958) (Tierra 1988) (Puri 2003). Arthritis (Halpern 2003-2) Osteoarthritis (Tierra 1988). Spondylosis (Tierra 1988).
Bodybuilding (Muscular hypertrophy) (Bucci 2000)
Urinary tract system (kidney, ureter, bladder)
Pameha (obstinate urinary disorders including diabetes) (Dash 1991) (Frawley 1989). Seeta meha (renal glycosuria, a type of Kapha diabetes) (Qutab 1996) Sikata meha (Lithuria, a type of Kapha diabetes) (Qutab 1996) Shanai meha (Frequent urination caused by a stone in prostate area) (Qutab 1996) Shukara meha (spermoruia) (Qutab 1996)
Diabetes (Frawley 1989)(Frawley 2001). Kidney stones (renal calculi) (Chopra 1958) (Frawley 2001). Cystitis (Frawley 2001). Dysuria (Frawley 1989)(Frawley 2001). Chronic urinary tract problems (Tierra 1988). Urinary tract infections (Frawley 1989). Urinary Tonic (Halpern 2003). Kidney Tonic (Frawley 1989)(Frawley 2001).
Yogavähi, which means that it enhances the properties of other herbs (Dash 1991). It acts as a catalytic agent for promoting the action of the other tonic agents. (Frawley 2001). Geriatric tonic (Frawley 1989) (Puri 2003). Tonic (Vata and Kapha) (Frawley 2001).
Rejuvenative (Frawley 2001).
† Sharma clarifies that the virya of shilajit is a point of confusion in the text. In verse 48 it states it is “Neither hot nor very cold” and here the virya seems of mixed virya based on its type. His conclusion is that the virya of shilajit is not very powerful and should be considered neither hot or cold (Sharma 2000).
‡Sharma clarifies that according to the general rule, a substance having a pungent taste should have a pungent vipaka. But for the Silver type of shilajit is an exception to the rule (Sharma 2000).
Astringent (Sharma 2000) Bitter and pungent (Bhishagratna 1998) Astringent, pungent, bitter (Frawley 2001) Astringent, pungent, bitter, salty (Halpern 2003)
Anu-rasa (after taste):
Astringent (Bhishagratna 1998)
Neither hot nor very cold (Sharma 2000) Heating (Bhishagratna 1998) Warm (Frawley 2001) (Halpern 2003) Hot (Dash 1991)
Vipaka (post digestive effect):
Pungent (Sharma 2000) Pungent (Bhishagratna 1998) Pungent (Frawley 2001) (Halpern 2003) Pungent (Dash 1991)
V-P+K- (Frawley 2001) V-P-K-, P + in excess (Tirtha 1998) V-P+e,K- (Halpern 2003)
Tissues and Systems:
Shilajit effects the nerve and reproductive tissues and the urinary, nervous and reproductive systems (Frawley 2001). It also has specific action on the endocrine system and affects all tissue systems (dhatus). It also strengthens agni (digestive fire) and reduces ama (toxins) (Halpern 2003).
Herbal actions are alterative, diuretic, lithotroptic, antiseptic, tonic, rejuvenative (Frawley 2001). Other actions include anodyne, anthelmintic and blood sugar reducer. (Halpern 2003, 2003-2). It also has a laxative effect and has absorbing and purifying (chhedana) properties (Bhishagratna 1998).
The general appearance of shilajit is that of a compact mass of vegetable organic matter composed of a dark- red gummy matrix interspersed with vegetable fibers, sand and earthy matter. The gummy substance dissolves in water and when washed away leaves an earthy matter, vegetable fibers and a few black round button-like masses (1/8 in. in diameter) resembling peas (Chopra 1958).
Chemical analysis shows that it contains besides gums, albuminoids, traces of resin and fatty acid, a large quantity of benzoic and hippuric acids and their salts. From the medicinal point of view, the chief active substances in it are benzoic acid and benzoates (Chopra 1958).
A study of vegetation of the areas of shilajit-exuding rocks indicated that Euphorbia royleana Boiss. (family Eurporbiaceae), a latex-bearing plant abundantly growing in the Western Himalayas, is the source of organic constituents of shilajit. The major amino acid composition in the latex of E. royleana was similar to that of shilajit (Ghosal 1976). E. royleana, a member of the cactus family, is commonly known as churee.
Trifolium repens L. (family Leguminosae) has also been found growing abundantly in the vicinity of shilajit-bearing rocks and are responsible, at least in part, for the formation of shilajit (Ghosal 1987). Trifolium repens is commonly known as white clover.
Shilajit is naturally high in iron and other valuable minerals (Tierra 1988).
Shilajit has long been regarded as a bitumen (asphalt) or mineral resin, or as a plant fossil exposed by elevation of the Himalayas, has now been subjected to extensive chemical investigations and it has now been shown to contain significant quantities of organic compounds, including bioactive oxygenated dibeno-alpha-pyrones, tirucallane triterpenes, phenolic lipids and small tannoids. Shilajit, obtained from different sources, has now been standardized on the basis of its major organic constituents (Ghosal 1991).
Shilajit is essentially constituted of fresh and modified remnants of humus (10-70% of the water-soluble fraction of shilajit), admixed with plant and microbial metabolites occurring in the rock rhizosphere of its natural habitat (Mukherjee 1992).
©Larry Allain. USGS NWRC.
Tucson Botanical Garden
The following summary of current research on shilajit show that some claims are substantiated and others are not. Note that all studies used animal subjects.
• Analgesic activity: Aqueous suspension of an authentic sample of shilajit was found to have significant analgesic activity in albino rats. Observed analgesic activity of shilajit probably justifies its use in different painful conditions. (Acharya 1988).
• Anti-Alzheimer: Shilajit holds a potential in the treatment of the apparently untreatable and incurable Alzheimer’s disease (Mukherjee 1992).
• Anti-inflmmatory activity: Aqueous suspension of an authentic sample of shilajit was found to have significant anti-inflammatory activity in albino rats. This research supports the use of shilajit in Ayurvedic medicine for rheumatism. (Acharya 1988). Shilajit was found to have significant anti- inflammatory effect in carrageenan-induced acute pedal oedema, granuloma pouch and adjuvant- induced arthritis in rats. These results substantiate the use of shilajit in inflammation (Goel 1990).
• Anti-ulcerogenic activity: Shilajit treatment produced decreased ulcerogenicity in 4 hr pylorus ligated rats. This finding lends credence to the suggested use of shilajit for peptic ulcers. (Acharya 1988). Shilajit increased the carbohydrate/protein ratio and decreased gastric ulcer index, indicating an increased mucus barrier. These results substantiate the use of shilajit in peptic ulcer (Goel 1990). Some active constituents isolated from shilajit are Fulvic acid and 4/-methoxy 6-carbomethoxy bi phenyl. These active constituents were found to have ulcer protective effect as a result a per se decrease in acid-pepsin secretion and cell shedding (Ghosal 1988)
• Anxiolytic activity: (anti-anxiety activity) The results indicate that shilajit has significant anxiolytic activity, comparable qualitatively with that induced by diazepam (valium), in doses lower than that required for nootropic activity (Jaiswal 1992). Ayurvedic use of shilajit as a tonic has some support from studies of the humic acids, fulvic acids, coumarins, and triterpenes that have shown anti-stress effects in animals (Ghosal 1988).
• Morphine-tolerance: In Swiss mice, the concomitant administration of proceeded shilajit with morphine, from day 6 to day 10, resulted in a significant inhibition of the development of tolerance to morphine induced analgesia (Tiwari 2001).
• Nootropic activity: Nootropic is a word coined by Dr. Giurgea to describe a new class of drugs that act as cognitive enhancers with no side effects or toxicity, from Greek words noos, meaning mind and tropein meaning toward (Giurgea 1973). It has been proposed that the modern equivalent of a medha rasayanas are those substances with nootropic activity (Ghosal 1998). Medhya is defined as causing or generating intelligence, mental vigor or power. The research found significant nootropic effects, which are
consistent with shilajit’s use as a medha rasayana (enhancer of learning acquisition and memory retrieval) (Mukherjee 1992). Shilajit can be regarded as a nootropic agent in view of its facilitatory effect on retention of acquired learning, though it ha d minimal effect on the acquisition of active avoidance learning (Jaiswal 1992).
• Nutritive Tonic: The effect of shilajit was investigated on the body weight of young rats for a period of one month. The body weight of the rats was found to be significantly greater in the rats taking shilajit compared with a control group. Researchers suggest a better utilization of food as a cause of the weight gain (Gupta 1966).
Research does not support
• Cardiac depressant action: Findings using frog’s hearts, do not support the therapeutic use of shilajit in cardiac failure as claimed in Indian System of Medicine (Acharya 1988).
• Cardiovascular system: no significant action on blood pressure, heart rate and respiration of an anaesthetized dog (Acharya 1988).
• Smooth and Skeletal muscles: Shilajit had neither any per se effect nor could modify the responses of nicotine, acetylcholine and histamine on isolated guinea pig ileum. Shilajit neither had any per se effect nor it could modify acetylcholine response on isolated rectus abdominis muscle of frog. (Acharya 1988).
• Central Nervous System: Shilajit in the doses of 50 to 200mg/kg had no significant effect on the general behavior of mice. (Acharya 1988).
• Bronchial asthma: Shilajit did not offer any protection against histamine-induced bronchospasm in guinea pigs. (Acharya 1988).
More research needed
• Anti-Alzheimer: Data clearly demonstate that shilajit affects some events in cortical and basal forebrain cholinergic singnal transduction cascade in rat brain. The study suggests that more research is needed where the treatment period is longer than seven days. Drugs that enhance cholinergic activity have been investigated as potential therapeutic agents in the treatment of Alzheimer’s disease (Schliebs 1997).
DOSAGE AND ADMINISTRATION
According to the Caraka Samhita, impregnating shilajit with a decoction of drugs, which alleviate vayu, pitta and kapha, increases the shilajit potency. Impregnation can be done by these drugs individually or by all of them taken together. A shilajit rasayana is described where shilajit is immersed into a hot decoction of herbs that are prescribed for alleviating the aggravation of dosha. This process is repeated for seven days and processed shilajit is mixed with powdered iron. Administered with milk this elixir brings long life and
happiness and prevents aging and disease. Administration of 48 gm for seven weeks is said to have excellent effects (Sharma 2000). According to the Astanga Hrdayam the minimum, moderate and maximum does of shilajit are karña, half-pala (17.5 grams) and pala (35 grams) respectively and the duration of use one week, three weeks and seven weeks respectively (Murthy 2001). Shilajit can be expensive but does not require large dosages (Frawley 2001). One suggested dosage is to take shilajit powder with milk, 1 oz or more a day for severe diseases; 0.25 – 1 tsp three times per day otherwise (Tirtha 1998). Shilajit is important for edema, particularly in weak types, 1-2 grams twice a day with water or milk (Frawley 1989). The dose of shilajit is usually quite low at around 125-250mg twice per day. However, in diabetes, it has been recommended in much higher doses such as 1 g twice per day. Shilajit mixes well with ashwagandha for seminal debility and with gokshura as a urinary tonic (Halpern 2003). For the treatment of both male and female infertility, it can be taken in unusually high doses of 1 tsp twice per day. For men combine with ashwagandha and for women with shatavari. Consider shilajit in all vata and kapha urinary disorders. As a tonic for vata, combine it with Goksura. Shilajit is among the best herbs for the long-term management of diabetes mellitus where it should be combined with gumar (Halpern 2003-2).
Should not be used with a heavy diet. Milk is an exception to the rule here as the Caraka specifically recommends recipes be taken with milk. Kulattha or horse gram, which is a type of bean, is noted as a special heavy dietary item. Some physicians prohibit the use of kulattha for the period that shilajit remains in the body and others prohibit it for the remaining period of ones life (Sharma 2000). Susruta also notes that persons impregnated with shilajit should avoid the meat of kapota (pigeon). The Astanga Hrdayam adds käkamäci (Solanum nigrum, black nightshade) to the list of substances to avoid during the use of shilajit (Murthy 2001). (Bhishagratna 1998). Do not use with high uric acid count (Tirtha 1998). Shilajit is not for febrile diseases (Frawley 2001). Although shilajit is used to treat kidney stones, use caution if the stones are made of uric acid or if uric acid crystals are in the urine as uric acid increases with the administration of shilajit. For this same reason, shilajit is contraindicated in gouty arthritis. (Halpern 2003).
Shilajit may be utilized safely in clinical practice because shilajit is reported to be quite safe up to a dose of 3 g/kg in mice (24h mortality) (Frotan 1984).
No drug interactions were found at the time of writing this paper.
Sources of commercial shilajit:
(all prices as of Aug 2004)
Shilajit 90 tablets (300mg/tablet) $18.95
Bazaar of India:
Shilajit 60 vegicaps (650mg/cap) $15.99 Shilajit 1 lb pwd $69.75 Shilajit 8 oz pwd $54.99 Shilajit 3 oz pwd $23.99
Shilajit 1 oz raw crystals $18.00
Purified extract from 500 mg of raw shilajit, 100 capsule $17.99
Shilajit in compounded products:
Banyan Botanicals sells Chandraprabha as a traditional ayurvedic formula. Its contents include guggulu, shilajit, chitrak, musta and nishoth. They say that Chandraprabha acts on the urinary tract and reproductive organs, and is used to remove excess kapha from the system. Chandraprabha 90 tablets (300mg/tablet) $18.95. Chandraprabha is recommended for management of Medhu meda (Diabetes Mellitus) and Ikshu meha (Alimentary glycosuria) (Qutab 1996). Dr Frawley also recommends Chardraprabha for Diabetes (Frawley 1989).
Pills made with equal quantities of guggul and shilajit are prescribed during fractures (Puri 2003). A highly nutritious preparation, called Rativallabh pak is made from a number of ingredients including a significant qanitity of Kikar (Acacia nilotica) also know as gum arabica and a minor amount of shilajit. This compound promotes “the proper sexual life of both males and females” (Puri 2003). It also is of immense use after childbirth as it imparts beauty and health to mother and infant. As part of the geriatric tonic, Navratnakalpa Amrit, shilajit assists in the formula’s effect of strengthening all parts of the body, stabilizing vata, pitta and kapha (Puri 2003).
In an antistress immunomodulater formulation, Trasina by Dey’s Medical Stores, shilajit assists (Puri 2003). Each capsule contains: Aswagandha 80 mg., Tulsi 190 mg., Silajit 20 mg., Guduchi 10 mg., Katuka 10 mg., Bhringaraj 10 mg.
Shilajit also assists in a number of formulations to increase sexual vitality. Shilajit plays a role in an aphrodisiac formulation from Deesons called Mucuna Forte, in an sex tonic formulation, Spy by Yogi Pharmacy, in a vitality and tonifying formula called Strenex by Zandu, in a sexual stimulant formula for men called Tentex forte by Himalaya Drug, and in a formula that increasing sexual activity and libido called Ashree Forte, from Aimil pharmacy (Puri 2003).
The Ayurvedic jelly Chyavanprash contains shilajit as one of its main ingredients (Frawley 2001). Chyavanprash sold by Banyan Botanicals, Tri-Health, Bazaar of India, Himalaya Herbal Healthcare and Nature’s Formulary do not contain shilajit.
Shilajit is truly a remarkable substance with a long history of human usage for healing for the urinary system and for diabetes. Unfortunately, many of those who sell shilajit or products containing it, make many wild claims for shilajit’s ability to cure diseases. While compiling the list of modern indications for shilajit, I chose to only include what I considered “reputable” sources and excluded any sources that were selling shilajit. I purposefully also excluded Internet sources for this information as I felt their claims were exaggerated beyond reality. Even still, examining the list of modern indications for shilajit, one can hardly believe that it could have such a wide and varied effect on the human body. Herbal dietary supplements are big business in the United States. More than 40% of adult Americans use some form of alternative medicine, including herbals, massage, chiropractic, and hypnosis, and spent $5.1 billion out of pocket for herbal therapies in 1997. Herbal use increased by 380% and megavitamin use by 130% from 1990-1997. More than 60% of people do not disclose their use of complementary medicine to physicians (Eisenberg 1998). As herbal supplements have gained popularity, many botanicals most Americans had never even heard of a decade ago have become widely available. Echinacea, ginseng and St. John’s wort, for example, are now sold in supermarkets, pharmacies and discount stores. More exotic botanicals, meanwhile, can be purchased at health food stores, specialty shops, through catalogs and the Internet. If shilajit were available at your local pharmacy would self-prescribed usage be the best thing for everyone? In light of this, one hopes that shilajit not be consumed by this money making machine and exploited for profit only. My fear is that shilajit might become a modern snake oil, reminiscent of 19th century preparations, only to be cast aside by modern researchers. The clinical studies on shilajit, conducted have so far; have been conducted on animals only. These studies seem very preliminary and my hope is that respected scientists, in the United States, India and throughout the world, continue their investigations into the healing substance – shilajit.
Acharya SB, Frotan MH, Goel RK, Tripathi SK, Das PK. Pharmacological actions of Shilajit. Indian J Exp Biol. 1988 Oct; 26(10): 775-7.
Bhishagratna KK. Susruta Samhita Vol 2, Chapter XIII. Varanasi, India: Chowkhamba Sanskrit Series Office, Varansi-1, 1998.
BucciLR. Selectedherbalsandhumanexerciseperformance.AmericanSocietyforClinicalNutrition, 2000 Aug; 72(2 Suppl): 624S-36S. Review.
Chopra, R N, Chopra I C, Handa K L & Kapur L D. Chopra’s Indigenous Drugs of India. 2nd Ed. B. K. Dhur of Academic Publishers, Calcutta India, 1958
Dabur. Shilajit: How was it discovered. From website copyright 2003. http://www.dabur.com/EN/General/faqs.asp?ID=44&FaqID=283&showAns=y#F1
Dash B. Materia Medica of Ayurveda B. Jain Publishers,New Delhi, 1991 Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the United States,
1990-1997: results of a follow-up national survey. JAMA 1998;280:1569-75.
Frawley, David. Ayurvedic Healing. Salt Lake City, UT: Passage Press, 1989.
Frawley, David and Lad, Vasant. The Yoga ofHerbs. 2nd edition. Pg 250. Lotus Press. Twin Lakes, WI, 2001.
Frotan, M.H., and Acharya, S.B. Pharmacological studies of shilajit. Indian Journal of Pharmacolgy 1984 16,45.
Ghosal S, Lal J, Singh SK, Goel RK, Jaiswal AK, Bhattacharya SK. The need for formulation of Shilajit by its isolated active constituents. Phytotherapy Res 1991; 5: 211-6.
Ghosal S, Lal J, Srivastava RS, Bhattacharya SK, Upadhyay SN, Jaiswal AK, Chattopadhyay U. Immunomodulatory and CNS effects of sitoindosides IX and X. Phytotherapy Res 1989; 3: 201- 6.
Ghosal S, Singh SK, Kumar Y, Srivatsava R. Antiulcerogenic activity of fulvic acids and 4-metoxy-6- carbomethyl biphenyl isolated from shilajit. Phytother Res. 1988;2:187-91.
Ghosal S, Standardization of Ayurvedic drugs and preparations. Proceedings of Captain Srinivasa Murthi Drug Research Institute, Madras, India, 1987, 29-34.
GhosalS,ReddyJP,LalVK. ShilajitI:chemicalconstituents.JournalofPharmaceuticalSciences 1976 May; 65(5): 772-3.
Giurgea C. The nootropic approach to the pharmacology of the integrative action of the brain. Cond Reflex 1973; 8: 108-15.
GoelRK,BanerjeeRS,AcharyaSB. Antiulcerogenicandantiinflammatorystudieswithshilajit. Journal of Ethnopharmacology. 1990 Apr; 29(1): 95-103.
GuptaSS,SethCB,MathurVS. EffectofGurmarandshilajitonbodyweightofyoungrats.IndianJ Physiol Pharmacol. 1966 Apr; 9(2): 87-92.
Halpern, Marc. Principles of Ayurvedic Medicine. 5th edition. Grass Valley, CA: California College of Ayurveda, 2003.
Halpern, Marc. Clinical Ayurvedic Medicine. 4h edition. Grass Valley, CA: California College of Ayurveda, 2003.
Jaiswal AK, Bhattacharya SK. Effects of Shilajit on memory, anxiety and brain monoamines in rats. Indian Journal of Pharmacology 1992; 24:12 – 17.
Lad, Vasant. Textbook of Ayurveda. Ayurvedic Press, Albuquerque, NM, 2002. Mukherjee, Biswapati. Traditional Medicine, Proceedings ofan International Seminar. Nov. 7-9 1992, pg 308-
319. Hotel Taj Bengal, Calcutta India. Oxford & IBH Publishing, New Delhi, 1992.
Murthy, KRS. Astanga Hrdayam. 5th edition. Krishnadas Academy, Varanasi, India, 2001
Nadkarni, KM. Indian Materia Medica. 3rd edition. Vol 2, pg 23. Popular Prakashan Private Ltd. Bombay, India, 1954
Puri HS. Rasayana. Taylor & Francis. London, England 2003
Schliebs R, Liebmann A, Bhattacharya SK, Kumar A, Ghosal S, Bigl V. Systemic administration of defined extracts from Withania somnifera (Indian Ginseng) and Shilajit differentially affects cholinergic but not glutamatergic and GABAergic markers in rat brain. Neurochem Int. 1997 Feb; 30(2):181-90.
Sharma, R. K. and Bhagwan Dash, trans. Caraka Samhita. Vols III, Chap I:3 pg 50-54. Varanasi, India: Chowkhamba Sanskrit Series Office, Varansi-1, 2000.
Tierra, Michael. Planetary Herbology. Lotus Press. Twin Lakes, WI, 1988.
Tirtha, Swami Sada Shiva. The Ayurvedic Encyclopedia. Ayurveda Holistic Center Press. Bayville, NY,
Tiwari P, Ramarao P, Ghosal S. Effects of Shilajit on the development of tolerance to morphine in mice. Phytother Res. 2001 Mar; 15(2): 177-9.
Qutab A. Ayurvedic Specific Condition Review: Diabetes Mellitus. Protocol Journal of Botanical Medicine, Winter 1996:138-139
Shilajit is a blackish brown exudation found in the serene surroundings o␣␣Himalayas. It is also found in most of the sedimentary rocks especially in Afghanistan, Bhutan, China, Nepal, Pakistan, USSR, Tibet as well in Norway, where they are gathered from steep rock faces at attitudes between 1000 and 5000 m.
In Ayurveda, Shilajit is classified as a ‘rasayan’ (meaning rejuvenator and immunomodulator in Sanskrit) and as a ‘medhya rasayan’ [rejuvenator of ‘medha’ (intellect)]. Shilajit is believed to slow down the process of aging by rejuvenation and immunomodulation1.
Until the mid 80’s, Shilajit was variously described as an inorganic mineral, a bitumen, an asphalt, a mineral resin, a plant fossil exposed by elevation of the Himalayas, and so forth.
Focused research has now shown that Shilajit is essentially constituted of fresh and modified remnants of humus– the characteristic organic constituent of soils.
SHILAJIT – BIOACTIVE CHEMICAL CONSTITUENTS:
The biologically important classes of compounds of shilajit include2, 3:
• Dibenzo-alpha pyrones, phospholipids, triterpenes and phenolic acids of low molecular weight • Fulvic acids: “carrier molecules” • Humins and humic acids • Trace elements (Fe, Ca, Cu, Zn, Mg, Mn, Mo, P)The low MW bioactive organic compounds, e.g. oxygenated dibenzo- α – pyrones (or equivalent biphenyl carboxylates) are the major entities. The medium MW fulvic acids (FA), act as carrier molecules to the bioactive substances during their systemic transport. The trace elements contribute to the healthful properties. Differences in the biological effects of native shilajit can be attributed to qualitative and quantitative variations of both bioactive organic compounds and the fulvic acids in Shilajit samples from different locations.
Characterization of the biologically active compounds in Shilajit:
Among the low molecular weight compounds, are the dibenzo-α-pyrones and biphenylcarboxylates:
• • •
3,4’, 5-trimethoxybiphenyl (C15H16O3) methyl 4’-methoxybiphenyl-2-carboxylate (C15H14O3) methyl 2’, 4’ –dimethoxybiphenyl-2-carboxylate (C16H16O4)
The organic compounds in shilajit can be broadly grouped into humic and non-humic substances. The non-humic substances are the low molecular weight organic compounds discussed above. They can be characterized by the chemical and spectroscopic methods. The humic substances, however, do no exhibit any specific physical and chemical characteristics like sharp m.p., consistent elemental composition, well-defined spectra etc. Humic substances are produced by interaction of plants, algae, mosses and microorganisms.
After separation of the low MW organic compounds, the remaining mass of shilajit (80-85%) consists of a mixture of high MW humic substances- fulvic acids (FA), humic acids (HA) and residual humic acids (RHA). Humic (HA) and fulvic acids (FA) are metal-organic complexes of soil humus, which contain nitrogen, oxygen and sulphur as heteroelements in their molecules4. FA and HA are usually separated by
pH-gradient extraction followed by charcoal chromatography as polydispersed mixtures of amorphous substances. In the isolation of the chemical components of Shilajit, retained low molecular weight organic compounds are removed from the humic acids by exhaustive solvent extraction. The humic acids are then hydrolyzed by boiling with water. Extraction of the hydrolysate with solvents of graded polarity lead to the separation of C16-C30 fatty acids, p-hydroxy – and 2, 5-dihydroxybenzoic acids, the triterpenic acids (1 and 2) and the conjugated dihydroxydibenzo-α-pyrones 5.
BIOLOGICAL POTENTIAL OF SHILAJIT IN INTEGRATED MEDICINES:
The biological effects of Shilajit are ascribable to two distinct classes of compounds viz. oxygenated di-benzo-alpha pyrones and the fulvic acids.
The following pharmacological actions have been observed consistently in various biological models.
1. Anti-ulcerogenic / Anti-stress – Adaptogenic Activity:
Shilajit was found to possess anti-ulcerogenic effects by its ability to decrease gastric acid secretion and peptic output and was also found to be effective in restrain stress models. The adrenocortical response to stress appears to be a common mechanism for the anti-stress / adaptogenic activity. Shilajit treatment produced decreased ulcerogenicity in 4 hr pylorus ligated
rats. This finding lends credence to the suggested use of shilajit for peptic ulcers6. Shilajit increased the carbohydrate/protein ratio and decreased gastric ulcer index, indicating an increased mucus barrier. These results substantiate the use of shilajit in peptic ulcer7. Some active constituents isolated from shilajit are Fulvic acid and 4/-methoxy 6-carbomethoxy bi phenyl. These active constituents were found to have ulcer protective effect as a result a per se decrease in acid-pepsin secretion and cell shedding8. They studied the effects of the Shilajit constituents, fulvic acids (FA) and 4’ –methoxy-6-carbomethoxybiphenyl (MCB) against gastric ulcers induced by restraint stress and aspirin in pylorus ligated albino rats as well as in cysteamine- induced duodenal ulcers in rats. Both FA and MCB were effective and decreased the incidence of duodenal ulcers in the experimental model.
For the first part of the study, to determine the efficacy of Shilajit constituents on the development of restraint stress and aspirin-induced ulcers, albino rats were divided into groups 8 groups of 7- 12 animals each.
• Group 1 was given saline (control group). • Group II received FA at 50 mg/kg level twice daily for 6 weeks. • Group III received 100 mg/kg FA twice daily for 6 weeks. • Group IV received MCB 100 mg/kg twice daily for 6 weeks • Group V received FA+MCB (25 + 25 mg/kg) once daily for four weeks • Group VI received aspirin (ASP, an ulcerogenic agent) 200 mg/kg once daily for 3 weeks • Group VII received ASP + ACB (200 mg/kg once daily for 3 weeks + 50 mg/kg once daily for
four weeks. • Group VIII received Aspirin +FA (200 mg/kg once daily for 3 weeks + 50 mg/kg once daily for
In the second part of the study, FA (50 mg/kg) or MCB (100 mg/kg) was administered twice daily for 5 days. The animals were fasted overnight and then treated with 30 mg/kg cysteamine subcutaneously.
Both FA and MCB isolated from Shilajit significantly decreased the restraint-stress ulcer index in pylorus ligated albino rats as compared to the control and the aspirin-treated groups, FA being more
ULCER INDEX (M+/-SEM)
effective (Fig. 1). FA+MCB also retained the efficacy in the duodenal ulcers experimental model (Fig. 2).
In the first part of the study, evaluation of the results with MCB revealed that the compound alone and in the presence of aspirin decreased the volumes of gastric secretion and the acid and peptic output significantly, as compared to the control as well as the aspirin treated groups. MCB had practically no effect on the protein content of the gastric juice, but it reversed the adverse effects of aspirin. MCB had a favorable effect on the total carbohydrate: protein ratio in the gastric juice, indicating that it stimulates the secretion of mucus.
(The numbers in the legend refer to the dose in mg/kg body weight)
Fig. 1 : Anti-ulcerogenic effects of Shilajit constituents against restraint stress and aspirin induced ulcers in rats.
25 20 15 10
Control FA 50 FA 100 ASP 200 ASP + FA
** = p<0.01 as compared to controls aa indicates P<0.001 as compared to controls # # indicates P<0.05 as compared to aspirin
90% 80% 70% 60% 50% 40% 30% 20% 10%
FULVIC ACIDS FROM SHILAJIT ON CYST EAMINE INDUCED DUODENAL ULCERS
n = 12
n = 12
n = 12
Cysteamine FA 50 + CYS FA 100 + CYS
Fig. 2: Effect of fulvic acids on cysteamine induced duodenal ulcers in rats 2. Immunomodulator :
Ghosal et al.9 also investigated the immunomodulatory potential of shilajit constituents. The screening was done on three crucial parameters, viz.
1. 2. 3.
elicitation and activation of peritoneal macrophages, their effect on the lysosomal marker enzyme (acid phosphatase), effects on tumor cells.
In all the selected immunological parameters, FA and MCB showed significant immunostimulatory effects. This makes shilajit a useful agent as promoter of non-specific immunological defense. Shilajit treatment not only induced morphological and morphometric changes on the peritoneal macrophages, it also dose dependently augments the phagocytic activity. This was validated in another study by the same authors, wherein they studied the effects of processed Shilajit on mouse peritoneal macrophages10. In this study, the dose and time-dependent effects of processed Shilajit (SJP) on the structure and functions of mouse peritoneal macrophages was evaluated. 0.025 to 900 mcg per mouse intraperitoneally for
different periods of time upto several hours. SJP (300-900 mcg ) produced morphological changes in the adherant cells in the peritoneum in a dose-dependent manner. The results on cell size are shown in Fig. 3. The shape of the macrophage cell body appeared to be heterogeneous and the cells were found to be constituents of an intricate network. There were round and elongated cells and the axes of extension increased progressively with time (Fig. 4)
Fig. 3: Effects of processed Shilajit on morphological changes in mouse peritoneal macrophages.
Fig. 4: Dose and time dependent morphometric changes of mouse peritoneal macrophages induced by processed Shilajit
60 50 40 30 20 10
Control **=P< 0.001 WITH RESPECT TO CONTROL
SJP 600MCG SJP 900MCG
100 90 80 70 60 50 40 30 20 10 0
600 mcg/SJP Round
900 mcg/SJP Round
PERIOD OF INCUBATION
600 mcg/SJP Elongated
900 mcg/SJP Elongated
CELL SIZE (MICRONS)
The dose and time dependent effects exhibited by SJP (Fig. 4) lend support to the postulate made by earlier researchers that the immunological response could be due to a direct interaction with the target cells or through secretory-type cells11. The phagocytic index depended on the function of the individual activated macrophage and not upon the number of macrophages present. A significant observation from this study was that higher doses of SJP (7.5 to 15 mcg) produced “greedy” macrophages that were subjected to lysis and disintegration. This observation is significant in that it indicates that the dose and duration of administration of Shilajit should be carefully configured to avoid impairment in the immunological response of the users. The dose dependent effect of systemic exposure to Shilajit on the phagocytic activity is shown in Fig 5.
Fig. 5: Effect of systemic exposure to Shilajit on phagocytic activity
3. Antioxidant Activity :
Shilajit was found to be a strong regulator of enzymic and non enzymic anti oxidant activity. It is a powerful radical captodative agent of NO and hydroxy radical generated from Fenton reaction. Shilajit is known to mimic the actions of the systemic antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). These actions are believed to be due to the presence of iron-containing quinone-semiquinone-hydroquinone complex structures in the core of Shilajit. The regenerative cycle of antiradical-antioxidant effects of
180 160 140 120 100
80 60 40 20
TREATMENT / DOSE(mcg/mouse)
SJP 0.25 SJP 2.5 SJP 25 SJP 50 SJP 100 SJP 200 SJP 250
processed shilajit (SJP) on reactive oxygen species (ROS) and nitric oxide (NO) and the attendant H2O2 cleaving effect is well-researched12. SJP containing fulvic acids and DBP provided complete protection against hydroxyl radical induced polymerization of MMA (methylmethacrylate) and was shown to be a reversible nitric oxide- captodative agent.
The observed absorption and desorption is through the reaction
SJP-NO ␣␣ SJP + NO. This is a distinctly remarkable phenomenon that is probably mediated by the iron-nitrosyl complex.
SJP (20 and 50 mg/kg/day, i.p., for 21 days) induced a dose-related increase in superoxide dismutase (SOD) (Fig. 6), catalase (CAT) (Fig. 7) and glutathione peroxidase (GPx) (Fig. 8), activities in frontal cortex and striatum in experimental animals (rats). The numbers in the legend sections of these figures correspond to the dose level in mg given once daily for 7, 14, 21 days. The results presented are for the 21 day treatment13.
40 35 30 25 20 15 10
** = P<0.01 with respect to Control.
VEHICLE SJP20 SJP50 DEPRENYL 2
Fig. 6: Effect of shilajit administration on superoxide dismutase activity in the brain in rats
SOD ACTIVITY (U/mg protein)
V E H IC L E SJP 20 SJP 50 DEPRENYL
40 35 30 25 20 15 10
TREATMENT ** = P<0.01 with respect to Control.
Fig. 7: Effect of shilajit administration on catalase activity in the brain in rats
Fig. 8: Effect of shilajit administration on glutathione peroxidase activity in the brain in rats
The effectiveness of Shilajit was comparable to that of (-) deprenyl (2mg/kg/day, i.p. x 21 days) with respect to SOD and CAT levels and better than (-) deprenyl for the GPx levels. The radical scavenging activity of SOD should be followed by the actions of CAT and GPx in order to
0.25 0.2 0.15 0.1 0.05 0
** ** ** **
** = P<0.01 with respect to Control
VEHICLE SJP 20 SJP 50 DEPRENYL 2
GPX ACTIVITY (U/mg Protein) CAT ACTIVITY (U/mg protein)
remove the hydrogen peroxide generated by SOD, which is a toxic metabolite. Thus Shilajit provides comprehensive antioxidant support by increasing the effectiveness of all three antioxidant enzymes. Additionally, the authors reported that unlike (-) deprenyl, Shilajit is not a monoamine oxidase inhibitor.
4. Analgesic activity:
Aqueous suspension of an authentic sample of shilajit was found to have significant analgesic activity in albino rats. Observed analgesic activity of shilajit probably justifies its use in different painful conditions6. In Swiss mice, the concomitant administration of proceeded shilajit with morphine, from day 6 to day 10, resulted in a significant inhibition of the development of tolerance to morphine induced analgesia14 .
5. Anti-inflammatory activity:
Aqueous suspension of an authentic sample of shilajit was found to have significant anti- inflammatory activity in albino rats. This research supports the use of shilajit in Ayurvedic medicine for rheumatism6. Shilajit was found to have significant anti-inflammatory effect in carrageenan-induced acute pedal oedema, granuloma pouch and adjuvant-induced arthritis in rats. These results substantiate the use of shilajit in inflammation7.
6. Nutritive Tonic:
The effect of shilajit was investigated on the body weight of young rats for a period of one month. The body weight of the rats was found to be significantly greater in the rats taking shilajit compared with a control group. Researchers suggest a better utilization of food as a cause of the weight gain15.
7. Blood sugar lowering effects of Shilajit:
A formulation containing processed Shilajit along with Withania somnifera, Tinospora cordifolia, Eclipta alba, Ocimum sanctum, Picrorrhiza kurroa was orally administered at the level of 50 and
100 mg/kg, to male rats once daily for 28 days along with streptozotocin (STZ, 45 mg/kg, s.c x 2days, an agent that induces diabetes). The formulation attenuated the hyperglycemic response of STZ in a dose related manner, as observed by assessing the superoxide dismutase (SOD) activity of pancreatic islet cells on days 7, 14, 21 and 28. Although the formulation did not reduce blood sugar levels as such, a dose- related decrease in STZ induced hyperglycaemia and attenuation of STZ induced decrease in islet SOD activity was observed. The authors concluded that the results indicate that the earlier reported anti-hyperglycaemic effect of the formulation may be due to free radical scavenging activity of the ingredients in the pancreatic islet cells, The hyperglycaemic activity of STZ is believed to be due to a decrease in islet SOD activity leading to the accumulation of degenerative oxidative free radicals in islet beta-cells16.
8. Shilajit modulates neurochemicals:
Shilajit (25 and 50 mg/kg, intraperitoneal) administration to rats was found to modulate the brain monoamines17. Processed Shilajit (SJP) augments the levels of Dopamine (DA) and Norepinephrine (NE) and their metabolism in various regions of the brain including the striatum. Furthermore, the treatment decreases serotonin (5HT) and its metabolism in the frontal cortex. These neurochemical changes substantiate the observed behavioral effects of shilajit in animal models, such as anxiolytic activity and nootropic activity these actions are attributable to decreased 5HT levels. Fig. 9 depicts the percentage change in the levels of various neurotransmitters on Shilajit administration18.
40 30 20 10
0 -10 -20 -30 -40
5HIAA DA DOPAC NA MHPG
SJP 25 SJP 50
BRAIN MONOAMINES AND METABOLITES
SHILAJIT AND BRAIN NEUROTRANSMITTER LEVELS
Fig. 9: Effects of Shilajit on brain neurochemicals
PERCENT CHANGE IN LEVELS
Additionally, the systemic administration of shilajit differentially affected the cholinergic nerves in the basal fore brain nuclei including medial septum and the vertical limb of the diagonal band, when subjected to autoradiographic studes and histochemical analysis the treatment did not affect either GABAA and benzodiazepine receptor binding nor NMDA and AMPA glutamate receptor subtypes in any of the cortical or subcortical regions studied. The findings validate the use of Shilajit as a nootropic especially during aging 19
Short-term memory is more dependent on the neurotransmitter dopamine, whereas long-term memory is more dependent on the neurotransmitter acetylcholine.
Medications which increase the amount of acetylcholine in the brain, improve memory function in patients with Alzheimer’s disease. The effects of Shilajit on acetylcholineesterase, the enzyme that reduces acetylcholine levels is shown in Fig. 10.
Fig. 10: Effects of Shilajit and Withania somnifera (WS) on acetylcholinesterase activity in various regions of the brain
Aphrodisiac/Reproductive Health support:
Shilajit has been used as a rejuvenator and an adaptogen for thousands of years, in one form or another, as part of traditional systems of medicine in a number of countries20.
Shilajit treatment also stabilizes mast cells and prevents its degranulation. The effects of Shilajit and its constituents, the fulvic acids (FA), 4’-methoxy-6-carboxyphenylmethyl (MCB) and 3, 8- dihydroxy-dibenzo-a-pyrone (DDP) were studied for protective effects against mast cell degranulation21. Mast cells are pivotal in the allergic response type I or the anaphylactic type – a rapidly progressing chain reaction that causes the allergic response. Mast cells are ubiquitous and are found around blood vessels in the connective tissue, in the lining of the gut and importantly in the lining of the upper and lower respiratory tract. These are large mononuclear cells heavily granulated, with granules containing a host of pharmacologically active substances. The allergen (antigen) enters into the human body through the respiratory tract, skin and/or gastrointestinal Tract (GIT). After the exposure to antigens, antibodies directed against specific antigens. (i.e., IgE, immunoglobulin E) are formed and are fixed to their respective receptors on the surface of the mast cells. This process is called sensitization of mast cells. During the second exposure to antigens, the antigens react with these antibodies at the cell surface. This event leads to a series of biochemical reactions. These migrate to the periphery in the secretory expulsion of the mast cell granules containing active substances (vasoactive amines and chemolytic amines) causing allergy symptoms. This process is called “mast cell degranulation”. Shilajit or its combined active constituents were found to offer significant protection against experimental mass cell degranulation induced by allergens (Fig. 11). Shilajit or its combined constituents produced a dose-dependent inhibition of spasms in the sensitized guinea pig ileum, induced by antigens (Fig. 12).
Fig. 11: Effects of Shilajit and its constituents in vitro against antigen-induced degranulation of sensitized mast cells
Shilajit (100 mcg/mL)+antigen
M CB (50 mcg/mL)+antigen
M CB (100 mcg/mL+antigen
DDP (50 mcg/mL)+antigen
FA (50 mcg/mL)+antigen
FA (100 mcg/mL)+antigen
M CB (25 mcg/mL)+DDP (25 mcg/mL)+FA (50 mcg/mL)+antige n
D C G + a ntig e n
Fig. 12: The effects of Shilajit and its constituents against active anaphylaxis against guinea pigs
90 80 70 60
% 50 Maximum
Histamine 4 0 Response
30 20 10
Control + chicken Shilajit + CEA (100 Shilajit + CEA (200 Shilajit + CEA (400 MCB+DDP+FA+CEA MCB+DDP+FA+CEA MCB+DDP+FA+CEA
egg albumin (CEA) mg/mL+1 mg) mg/mL+1 mg) mg/mL+1 mg) (10+10+30 mg/ml+1 (20+20+60 mg/ml+1 (40+40+120
Thus Shilajit treatment in experimental models augments the lytic potential of macrophages without increasing the dead tumor cells. Shilajit is further postulated to assist in normal physiological functions by acting as a biocatalyst. The trace elements present in shilajit are likely to be of importance in this action. Major amounts of nutrient metals from shilajit have been found to be bioavailable22.
Shilajit was found to augment learning acquisition and memory retrieval in the battery of validated animal models while native Shilajit was found to exhibit inconsistent response. These findings also suggested the role of Shilajit in facilitating communication between immune and the central nervous systems. Further this cognition enhancing property was located to the dibenzo- alpha-pyrones and fulvic acids. Shilajit was also found to be effective in animal models of Alzheimer’s disease. This nootropic activity was due to its ability to enhance the acetyl choline levels and muscarnic cholinergic receptors binding activities coupled with decreased serotonergic activity in the hippocampus and frontal cortex.
In a battery of tests, shilajit has been found to augment learning acquisition as well as short and long-term memory (retention) in rats 11, 24, 25. A positive effect of shilajit is postulated to be mediated by facilitating communication between the immune and the central nervous systems.
To test the effects of Shilajit administration on learning and memory, rats were subjected to two sets of tests26: The active avoidance learning and re-learning test, in which rats were exposed to a conditioning stimulus followed by electric shock. Avoidance response was measured by how quickly the rats moved to the unelectrified chamber, to avoid the electric shock. The rats were administered the test compound (either processed Shilajit (SJP), unprocessed native Shilajit (SJN) or the extract containing Fulvic acids and dibenzo-α- pyrones (FAA+DBP) at doses of 5, 10, 25 or 50 mg/kg body weight.
2. The elevated plus-maze test for learning and memory: Here the rats were individually placed at the end of one arm that faced away from a central platform. The time taken by the rats to move from the open arm to either of two enclosed arms at the platform was measured.
3. Electroconvulsive shock(to induce amnesia) was administered to the test animals and they were subjected to the plus maze test
4. An open field behavior test to assess anxiety symptoms and behavior.
Fig. 13 – 16 provides the results of these tests. It is observed that there was significant shortening in the number of trials for active avoidance learning and memory (as measured by relearning capability), in rats treated with processed Shilajit or the extract. It was also observed that higher doses of unprocessed Shilajit reversed the learning process, further validating the need for purification of Shilajit. Processed Shilajit was found to be more effective than the isolated active principles.
Fig. 13: Effects of Shilajit and its active constituents on active learning in rats
SHILAJIT AND FULVIC ACIDS ON LEARNING AND MEMORY
50 45 40 35 30 25 20 15 10
** ** **
**P<0.05WITHRESPECTTOCONTROL. SJP=PROCESSEDSHILAJIT,SJN=NATIVESHILAJIT FA-DBP= FULVIC ACID- DIBENZO ALPHA PYRONE . ACTIVE AV OIDANCE LEARNING
CONTROL SJP 5 SJP 10 FA-DBP 10 SJN 5
SHILAJIT AND FULVIC ACIDS ON LEARNING AND MEMORY ON ELEVATED PLUS MAZE
60% 50% 40% 30% 20% 10%
** P<0.01 WITHRESPECTTOCONTROLANIMALS
CONTROL SJP 5 SJP 10 SJP 25 FA-DBP 10 FA-DBP 25 SJN 5 SJN 10 SJN 25
Fig. 14: Effect of Shilajit and the isolated active principles on learning and memory as measured by the elevated plus maze test in rats.
Similar results were observed in the plus maze test and by rats subjected to electric shock as well as animals that were not subjected to electric shock.
SHILAJIT AND FULVIC ACIDS ON ELECTROCONVULSIVE SHOCK INDUCED AMNESIA IN RATS
70 60 50 40 30 20 10
aa= P< 0.05 with respect to control. ** = P< 0.001 with respect to ECS treated group. N=8 in each group
Control ECS ECS+SJP 5 ECS+SJP 10 ECS+SJP 25 ECS+FA 10 ECS+FA25 ECS+ SJN 25 ECS+SJN 50
Fig. 15: Effect of Shilajit and fulvic acids on electroconvulsive shock induced amnesia in rats
TRANSFER LATENCY (DAY 10,MIN) PERIOD
REDUCTION IN TRANSFER LATENCY
120 100 80 60 40 20 0
SHILAJIT AND FULVIC ACIDS ON THE ANXIETY PARADIGMS IN OPEN FIELD BEHAVIOU R
Control Diaz epam SJP10 SJP 50 SJN 10 SJN 50 FA-DBP 10 FA-DBP 50
Fig. 16: Effect of Shilajit and isolated active principles on anxiety paradigms in open field behavior in rats.
In the open field behavior test, processed Shilajit and the isolated active constituents showed significant efficacy in diminishing anxiety symptoms. However, native Shilajit was not very effective, probably on account of the free radical contamination in such material, further validating the need for purification.
Shilajit can be used in antioxidant and anti-aging formulations and to act as a delivery system for other therapeutic agents in mixed formulations.
These applications advocated in the ancient Ayurvedic texts, have been validated by recent research into the chemistry and biological actions of this ancient panacea.
Shilajit has been used historically for general physical strengthening, anti-aging, blood sugar stabilization, libido, injury healing, enhanced brain functioning potency, support immune system, arthritis management, hypertension and obesity.
1. Sharma, P.V. (1978) Introduction to Dravyaguna, p 63, 4th edition, Chaukhamba Orientalia, India. 2. Ghosal. S. 1990. Chemistry of shilajit, an immunomodulatory Ayurvedic Rasayana. Pure and
Appl.Chem., 62 (7), 1285-1288. 3. Kong, Y.G., et al. (1987) Chemical studies on the Nepalese panacea-shilajit. Int. J. Crude Drug
Res. 25:179-182. 4. Cheshire, M.V., P.A. Cranwell, C.P. Falshaw, A.J Floyd, and R.D Haworth. 1967. Humic acids.
2. Structure of humic acids. Tetrahedron 23, 1669-1682. 5. Ghosal S, Jawahar Lal, Singh S.K. (1991). The core structure of shilajit humus. Soil. Biol.
Biochem., 23 (7), 673-80. 6. Acharya SB, Frotan MH, Goel RK, Tripathi SK, Das PK. Pharmacological actions of Shilajit.
Indian J Exp Biol. 1988 Oct; 26(10): 775-7. 7. Goel RK, Banerjee RS, Acharya SB. Antiulcerogenic and antiinflammatory studies with shilajit.
Journal of Ethnopharmacology. 1990 Apr; 29(1): 95-103. 8. Ghosal S, Singh SK, Kumar Y, Srivatsava R. Antiulcerogenic activity of fulvic acids and 4-
metoxy-6-carbomethyl biphenyl isolated from shilajit. Phytother Res. 1988;2:187-91. 9. Ghosal, S. 1989, The facets and facts of Shilajit. In Research and Development of Indigenous
Drugs ed. P.C Dandiya and S.B. Vohora pgs 72-80. 10. Ghosal, S., Bhattacharya, S.K. (1995). Shilajit-induced morphometric and functional changes in
mouse peritoneal macrophages. Phytother. Res. 9:194-198. 11. Schliebs R, Liebmann A, Bhattacharya SK, Kuram A, Ghosal S and Bigl V (1997). Systemic
administration of defined extracts from Withania somnifera (Indian Ginseng) and Shilajit defferntially affects cholinergic but not glutamatergic and gabeargic markers in rat brain. Neurochem Int 30 (2), 181-190
12. Ghosal S, Jawahan L, Singh SK, Goel RK, Jaiswal AK, Bhattacharya SK (1991). The need for formulation of Shilajit by its isolated active constituents. Phytotherapy Res. 5, 211-216.
13. Bhattacharya, Sen AP and Ghosal S (1995). Effects of Shilajit on biogenic free radicals. Phytotherapy Res. Vol 9, 56-59.
14. Tiwari P, Ramarao P, Ghosal S. Effects of Shilajit on the development of tolerance to morphine in mice. Phytother Res. 2001 Mar; 15(2): 177-9.
15. Gupta SS, Seth CB, Mathur VS. Effect of Gurmar and shilajit on body weight of young rats. Indian J Physiol Pharmacol. 1966 Apr; 9(2): 87-92.
16. Bhattacharya SK, Satyan KS, Chakrabarti A (1997) Effect of Trasina, an Ayurvedic herbal formulation, on pancreatic islet superoxide dismutase activity in hyperglycaemic rats. Indian J Exp Biol; 35(3):297-299
17. Bhattacharya SK, Sen AP (1992) Effect of Shilajit on rat brain monamines. Phytotherapy Res. Vol 6, 163-164.
18. Jaiswal, A.K and S.K Bhattacharya. 1992 . Effects of shilajit on memory, anxiety and bran monoamines in rats. Indian J. Pharmacol, 24 (1), 12-17.
19. Schliebs R, Liebmann A, Bhattacharya SK, Kuram A, Ghosal S and Bigl V (1997). Systemic administration of defined extracts from Withania somnifera (Indian Ginseng) and Shilajit defferntially affects cholinergic but not glutamatergic and gabeargic markers in rat brain. Neurochem Int 30 (2), 181-190.
20. Shilajit: a review Phytotherapy Research Volume 21, Issue 5 , Pages 401 – 405. 21. Ghosal, S., J. Lal and S.K Singh. et al. 1989. Mast cell protecting effects of Shilajit and its
constituents. Phytother. Res. 3(6):249-252. 22. Peerzada, N.H., M. Nojek, M.I. Bhatti and S.A. Tariq. 1992. Shilajit: Part 1. Bioavailability of
nutrient metals, biological, thermal and spectroscopic properties of shilajit from Australia and
Pakistan. Sci. Int. (Lahore),4 (1), 39-44. (CA: 117: 205044y). 23. Mukherjee, Biswapati. Traditional Medicine, Proceedings of an International Seminar. Nov. 7-9
1992, pg 308-319. Hotel Taj Bengal, Calcutta India. Oxford & IBH Publishing, New Delhi, 1992. 24. Ghosal S, Jawahan L, Singh SK, Goel RK, Jaiswal AK, Bhattacharya SK (1991). The need for
formulation of Shilajit by its isolated active constituents. Phytotherapy Res. 5, 211-216. 25. Ghosal, S., J. Lal, A.K Jaiswal and S.K Bhattacharya. 1993. Shilajit. XII Effects of shilajit and its
active constituents on learning and memory in rats. Phytother. Res, 7 (1), 29-34.
Pure & Appl. Chern., Vol. 62, No. 7,pp. 1285-1288, 1990. Printed in Great Britain. @ 1990 IUPAC
Chemistry of shilajit, an immunomodulatory Ayurvedic rasayan
Shibnath Ghosal Department of Pharmaceutics, Banaras Hindu University, Varanasi-5, India
Abstract – The chemical polemics in the reported literature on shilajit are resolved. This study shows that humification of latex and resin-bearing plants is responsible for the major organic mass (80-85%) of shilajit. The low mol. w t . chemical markers ( & l o % ) , viz. aucuparins, oxygenated dibenzo-K -pyrones and triterpenic acids of the tirucallane type (free and conjugated), occurring in the core structure of shilajit humus, are the major active constituents of Himalayan shilajit. The therapeutic effects of shilajit are the consequences of hormonal control and regulation of immunity.
Shilajit is a blackish-brown exudation, from steep rocks of different formations, commonly found in the Himalayas, at altitudes between 1000-5000 m, from Arunachal Pradesh in the East to Kashmir in the West. It is also found in other countries, e.g. Afganisthan (Hindukush), Bhutan, China, Nepal, Pakistan, Tibet (Himalayan belt) and the USSR (Tien Shan,Ural). Shilajitisbelievedtoarrestagingandproducerejuvenation(ref.11,-two important attributes of a rasayan (refs. 2 , 3 ) .
Considerable controversy had existed in the reported literature (ref. 3 ) when we initiated our study on the nature and chemical constituents of shilajit about fourteen years ago. It was variously described, as a bitumen or mineral resin varying greatly in consistency from a free-flowing liquid to a hard brittle solid; a plant fossil exposed by a elevation of the Himalayas; a substance of mixed animal and plant origin (refs. 3 , 4 ) . Twelve years after the publication of the circumstantial evidence for the contribution of plants in shilajit formation (ref.51, we obtained further direct evidence regarding the chemical characterofshilajit(refs.6,7). Itwouldnowrequiresummationofourearlierfindings for resolving the chemical polemics (refs. 3 , 4 ) on this subject and to report our recent findings, from analyses of shilajit from different regions, to show the generality of our conclusion.
The first major advance in our understanding of the chemical character of shilajit was the observation that shilajit, from different regions, contained a large variety of organic compounds that can be broadly grouped into humic and non-humic substances (refs. 6,7). The non-humic substances, in soil-sediment humus (ref. 81, are low mol. w t . organic compounds that are characterizable by chemical and spectroscopic methods. The humic substances, by contrast, do not exhibit any specific physical and chemical characteristics (e.g. sharp m.p., consistent elemental composition, consistent pH, well-defined IR and NMR spectra), normally exhibited by characterizable organic compounds. Humic substances are producedbyinteractionofplants,algae,mosses,andmicroorganisms. Thephytochemistry of vegetation around shilajit-bearing rocks, therefore, constituted an important part of our investigation.
The coamon plant sources of humus, in mountain soils, are the perennial grasses and legumes, which possess finely branched root systems capable of regeneration. Other importantsourcesofhumusarethelitterandlatexofplants. Variationinthequality of shilajit humus (both chemical and biological) is, therefore, conceivable. The other factors that cause variations in shilajit humus are: (i) altitude and the nature of shilajit-bearing rocks; (ii) atmospheric conditions (e.g. alternate wetting and drying); (iii) pH and moisture content of the rock source; and (iv) activity of the rhizospheric microorganismsandtheirexo-enzymes. Thestabilityofthehumusreservedependsonone or more of these factors. Shilajit samples collected from different places, as expected, exhibit variations in chemical characteristics and bioactivities. Furthermore, the hazards of collection of shilajit and the scanty amount generally available in any one locale prompt unscrupulous traders to .adulterate it with rock soil, plant debris and quercus gums. It was, therefore, thought imperative to determine certain standards of shilajit on the basis of bioactivity-directed investigation of its chemical constituents.
12851286 S. GHOSAL CHEMISTRY OF SOURCE MATERIALS OF SHlLAJlT
During our bioactivity-directed investigation of shilajit samples, from different countries, some striking similarities were observed in respect of their contained low mol. w t . bioactive compounds. Several phenylpropanoid-acetate-derived aucuparins, oxygenated biphenylcarboxylates, isolated and characterized as their permethylated derivatives (1-3)
(ref. 7), and oxygenated dibenzo-or’-pyrones (3-5) (refs. 6,7)were found to occur ubiquitously,albeitindifferentamounts,inallauthenticsamplesofshilajit. Wealso located some of the living plant ancestors of these compounds.
Over eighty different plant species were reported (ref. 9) in and around the shilajit rocks in Kumaon itself. One species which was consistently found to be present in shilajit-bearing rocks, throughout the Eastern and the Western Himalayas, was a rich latex producingplant,EuphorbiaroyleanaBoiss. (Euphorbiaceae). Someotherlatexandresin producing common species, in these regions, are the legumes, e.g. Trifolium, (family,
-T. ripens (Leguminosae), collected from different places in the Himalayan belt, yielded several phenylpropanoid-acetate-derived metabolites including (1)to (2). E. royleana (latex and debris), putrefied by shilajit rhizospheric microorganisms, yieldez the three other important shilajit marker compounds (5-5)along with several other equivalent metabolites. A conceptual model for the genesis of (1)to (51, involving an intermediate (I),wasenvisaged(ref.10). Anotherkeyintermediate(i),isolatedfromafree-flowing (premature) sample of shilajit, provided strong circumstantial evidence in support of the aforesaidbiogeneticroute(ref.10). Thereactiveintermediate(8) wasautoxidized,in presence of light and air, to give a mixture of (6)and (57, presumably via the endo-peroxide (2).
Anacardiaceae), Ficus (Moraceae), and Juniperus (Cuprassaceae)
Continuing the phytochemical investigation, we have now isolated and characterized from
cotinus and E. succedanea (Anacardiaceae), several phenolic lipids of the type ( 2 )and
R. triterpenoids (both free and conjugated,- oligoglycosides) of the tirucallane types
(11-12). Enzymatic hydrolysis of a major triterpenoid saponin fraction, with hesperidinase, followed by column chromatography (Si gel using n-BuOH saturated with water) of the sapogenin fraction afforded a mixture of 24(Z)-3/j-hydroxytirucalla- 7,24- dien-26-oic acid (ga) and 24(2)-3p -hydroxytirucalla-8,24-dien-26-oic acid (gal. From the aqueous hydrolysate, L-arabinose, L-rhamnose, D-xylose and D-glucose were isolated, as their alditol acetates, and identified by GLC. In case of shilajit, from different regions, both E- and Z-isomers of the triterpenoid sapogenins (Ga-b) and (ga-b) and the phenolicconstituentswereisolatedandcharacterized. Thestructuresofthesecompounds were established by comprehensive spectroscopic analyses, crucial chemical transformations and synthesis, where possible. Pharmacological and immunological screening of these compounds, individually and in combination, established their significant contribution to the therapeutic efficacy of shilajit. Among the other organic compounds contributing to the bioactivity of shilajit, humic and fulvic acids, from shilajit humus, are noteworthy. However, the main task that confronts researchers in this field (study of humus) today is to decipher the complexity of the building units of humus and their allignments, after polycondensation, in the core structures of humic substances.
HUMIC SUBSTANCES FROM SHlLAJlT
Scanning electron microscopy and viscosity measurements of humic acids (HAS) and fulvic acids (FAs), from shilajit, suggested for the FAs a relatively open, flexible structure punctured by voids (micropores) of different diameters, at different pH. FAs from biologically equiactive shilajit samples exhibited a number of similarities in respect of: (i) elemental and micronutrient (trace metal ions) compositions; (ii) aromatic and aliphatic carbon ratio; (iii) absorbance ratio at 465/665 nm (E-4/E-6); (iv) viscosity and particle size; and (v) PMR and CMR spectra.
Relatively mild degradation of shilajit-HAS, by boiling with water, yielded several aliphatic (‘2-16 to C-20) and phenolic acids together with common sugars, glucose, arabinose, rhamnose and xylose. These compounds were, presumably, loosely held in the core structures of shilajit HAs either by weak bonding or by adsorptionJintercalation in theirinternalvoids. Theplantsecondarymetaboliteswhicharetrappedintheinternal voids o f humic substances are spared from and resistant to common chemical and biological decomposition. This is consistent with the observed ubiquitous occurrence of the aucuparins and dibenzo–:-pyrones in the core of shilajit from different regions. During systemic administration of shilajit, these constituents, even i f , p r e s e n t a s m i n o r e n t i t i e s , elicit their potent biological effects and are, therefore, regarded as markers of shilajit.
According to accepted tenets, biogenesis of humus (ref. 8) involves a two-stage process: (i) fragmentation of plant and microbial constituents into small molecules (monomers), and (ii) heteropolycondensation of the monomers into high mol. w t . humus. Our results of
12 (lla) R =C02H, R =Me
(llb) R’=Me, R2=C02H
c15 H31-n n =0,2,4
Chemistry of shilajit 1287
investigation of shilajit HAS, however, suggested participation, at least in part, of some plant-derived intact phenolic metabolites, viz. biphenyl carboxylates (and equivalents), in their core structure. These phenolic moieties were transformed into polynuclear aromatic hydrocarbons, phenanthrene, 2-methylphenanthrene and 2,3-benzofluorene, on Zn dustdistillationofshilajitHAS. Thesamedegradationproductswerealsoobtainedwhen soil-sediment HAS were subjected to Zn dust distillation. Thus, some inherent structural similarities were indicated for shilajit and other common HAS.
Variations in chemical characteristics and biological actions were observed in the humic substances of shilajit itself having different consistencies, e.g. dark brittle (over exposed),brownviscous(mature),andfree-flowingliquid(prematureshilajit). Thismay be due to the fact that humus reserve is a complex mass whose complexity is determined by the intensity of several factors: (a) the rate of formation of fresh humus; (b) adsorption of plant root exudates and leached materials from debris of plants and microorganisms to humusreserve;(c)therateofdecompositionofthecagedandfreelowmol.wt. compounds; and(d)therateofdecompositionofHASandFAs intohuminandotherintractableproducts. Hence the quality of humus, which primarily acts as the liposomic carrier of low mol. w t . bioactive compounds of shilajit, would constitute an important determinant to the therapeuticpotentialofshilajit. Itwas,therefore,thoughtnecessarytodeterminethe biologicalactivityprofilesofthelowmol.wt. organiccompoundsandtheHASandFAsof shilajit, individually and in combinations, to evaluate their additive and synergistic potential.
.. (11R1=R4=H, R2=R3=OMe
(2) R1=RgR$H R4= C02Me (3) R1=OMe,R2;R3=H,RkCO2Me
&: Ho 400
(4)R~=R~=H (51 R1= Me, R2=H (6)R1=H,R2=OH
BlOACTlVlTY OF SHlLAJlT AND ITS CONSTITUENTS
Clinical applications of shilajit in Ayurveda, as a rasayan, are well documented (refs. 1,3). However,nomodernscientificstudywascarriedoutbeforeonthemodeofactionof shilajit. The effects of shilajit, as reported in the Ayurvedic literature, seem t o suggest its influence on endocrine, autonomic, and brain functional changes. The discovery that these changes can be mediated by cytokines, released by activated immunologic cells (ref. 11>, has opened up possibilities for similar mechanism of action
(12a) R1=C02H, R2=Me (12b) R1 =Me, R2= C02H
of shilajit. Certain combinations of the phenolic and triterpenoid constituents, and the FAs of shilajit produced significant effects against restraint stress-induced ulcers (ref. 6). Themechanismofanti-ulcerogenicactionsofshilajitanditsconstituentswasalso evaluated (ref.6). This was based on their effects on mucin contents, and on the concentrations of DNA and protein in the gastric juice. The combinations provided significant resistance to mucosa against the effects of ulcerogens and also prevented the shedding of mucosal cells. The anti-allergic action of these compounds was successfully tested against antigen- and compound 48/80 (histamine releaser)- induced degranulation of mastcells(ref.12). Theanti-stressactivityofthesecompoundswassuggestedbytheir augmentation of murine swimming endurance exercises. Shilajit and its combined constituents also elicited and activated, in different degrees, murine peritoneal macrophages and activated splenocytes of tumour-bearing animals at early and later stages
(unresponsive) of tumour growth (tested according to ref.13). Shilajit from USSR, and its corresponding combined fractions, acted essentially as cell-growth factors in both normal and tumour cells by maintaining membrane integrity. The results obtained till now are sufficiently impressive to warrant expectation that more extensive and comprehensive studies on shilajit and its constituents would validate the Ayurvedic rasayan, shilajit, as more effective than several currently available clinically efficacious immunomodulators
(refs. 14, 15).
1. U.C.DattaandG.King,MateriaMedicaoftheHindus,p.33-37,MachinePress,Calcutta, India (1877).
2. P.V.Sharma,IntroductiontoDravyaguna,p.63,4thEdn.,Chaukhamba,Orientalia,India (1978).
3. V.P. Tiwari, K.C. Tiwari and P. Joshi, J. Res. Ind. Med., 8, 53-60 (1973). 4. Y.C. Kong, P.P.H. But, K.H. Ng, K.F. Cheng, R.C.Cambie and S.B. Malla, Int. J. Crude
Drug Res., 25, 179-182 (1987).
5. S. Ghosal, J.P. Reddy and V.K. Lal, J. Pharm. Sci., 65, 772-773 (1976).
6. S. Ghosal, S.K. Singh, Y. Kumar, R.S. Srivastava, R.K. Goel, R. Dey and S.K. Bhattacharya, Phytother. Res.,2, 187-191 (1988).
7. S. Ghosal, S.K. Singh and R.S. Srivastava, J. Chem. Res. ( 5 ) 196-197 (1988). 8. M. Schnitzer, Soil Organic Matter (M. Schnitzer and S.U. Khan, Eds.) Ch.3, Elsevier,
New York (1978).
9. H.C. Pandey and V.P. Tiwari, J. Res. Ind. Med., 12,113-115 (1977).
10. S. Ghosal, J. Lal, S.K. Singh, Y. Kumar and F. Soti, J. Chem. Res. (s)(1989).
11. H.O. Besedovsky,A.E. Dei-Rey and E. Sorkin, J. Immunol., 135,750-754s (1985).
12. S. Ghosal, J. Lal, S.K. Singh, G. Dasgupta, J. Bhaduri, M. Mukhopadhyay and S.K. Bhattacharya, Phytother. Res., 3 , (1989).
13. U. Chattopadhyay, S. Das, S. Guha and S. Ghosal, Cancer Lett., 2 , 293-299 (1987). 14. H. Wagner and A. Proksch, Economic and Medicinal Plant Research, p. 113-153 (H. Wagner,
H. Hikino and N.R. Farnsworth, Eds.), Academic, New York (1985). 15. R. Bomford, Phytother Res., 2, 159-164 (1988).
Mumijo Traditional Medicine: Fossil Deposits from Antarctica (Chemical Composition and Beneficial Bioactivity)
Anna Aiello1, Ernesto Fattorusso1, Marialuisa Menna1, Rocco Vitalone1, Heinz C. Schro ̈der2 and Werner E. G. Mu ̈ller2
1Dipartimento di Chimica delle Sostanze Naturali, Universita` di Napoli ‘Federico II’, via D. Montesano 49, 80131 Napoli, Italy and 2Abteilung fu ̈r Angewandte Molekularbiologie, Institut fu ̈r Physiologische Chemie, Johannes Gutenberg-Universita ̈t Mainz, Duesbergweg 6, 55099 Mainz, Germany
Mumijo is a widely used traditional medicine, especially in Russia, Altai Mountains, Mongolia, Iran Kasachstan and in Kirgistan. Mumijo preparations have been successfully used for the prevention and treatment of infectious diseases; they display immune-stimulating and antial- lergic activity as well. In the present study, we investigate the chemical composition and the biomedical potential of a Mumijo(-related) product collected from the Antarctica. The yellow material originates from the snow petrels, Pagodroma nivea. Extensive purification and chemical analysis revealed that the fossil samples are a mixture of glycerol derivatives. In vitro experiments showed that the Mumijo extract caused in cortical neurons a strong neuroprotective effect against the apoptosis-inducing amyloid peptide fragment b-fragment 25–35 (Ab25–35). In addition, the fraction rich in glycerol ethers/wax esters displayed a significant growth-promoting activity in permanent neuronal PC12 cells. It is concluded that this new Mumijo preparation has distinct and marked neuroprotective activity, very likely due to the content of glycerol ether derivatives.
Keywords: cell growth stimulation – chemical composition – Mumijo – petrel stomach oil – traditional medicine
‘Reports on the high biodiversity of marine animals date back to Aristotle (384–322 BC) (1), who gave—in his 5th book on the History of Animals—extensive descriptions on those sponge species near the island of Lesbos that have been commercially used later (reviewed in 2)’. Likewise, since Aristotle (1) the tar-like substance, of white over yellow to black color, which is used in traditional medicine, has been termed collectively Mumijo, Mumie or Mumiyo (3). Pfolsprundt (4) also mentioned the alleviating remedy in his compendium. This traditional drug is widely
For reprints and all correspondence: Professor Dr W. E. G. Mu ̈ ller, Institut fu ̈ r Physiologische Chemie, Abteilung Angewandte Molekularbiologie, Universita ̈ t, Duesbergweg 6, D-55099 Mainz, Germany. Tel: +49-6131-392-5910; Fax: +49-6131-392-5243; E-mail: firstname.lastname@example.org
distributed in Russia (termed there Mumie or Mumiyo), India (Saljit), Birma [Kao-tun (blood of the mountain)], Altai Mountains [Barachgschin (oil of the mountain)], Mongolia [Brogschaun (mountain juice)] and Iran Kasachstan, and Usbekistan as well as in Kirgistan [Arakul dshibal (mountain sweat)] (3). The origin of the word ‘Mumijo’ goes back to the Greek and means ‘saving the body’. The Asian Mumijo is found at high altitudes as deposits in walls and caves where they are embedded into rocks. These organic accumulations of unknown origin may reach weights of up to 500 kg; some are considered to be up to 3000-years old (3,5,6). The chemical composition of Asian Mumijo of 20% of minerals, 15% of proteins, 5% of lipids and 5% of steroids has been described in detail (3); the rest are carbohydrates, alkaloids and amino acids. A series of medical applications has been described (reviewed in 3), including immune-stimulating and
ß 2008 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
eCAM 2008;Page 1 of 8
2 of 8 Mumijo traditional medicine
antiallergic activity as well as an ameliorating effect against gastric and intestinal ulcers and finally healing of bone fractures. Furthermore, a protective effect against radiation and a favorable nootropic property (7) have been described.
The term Mumijo is not only restricted to the black, tar-like substance from Asia (3), but it is also used for the paleoenvironmental records—subfossil stomach oil deposits from Antarctica (8). This material is yellow and originates from the snow petrels, Pagodroma nivea. The cross composition of this waxy organic material, found in petrel-breeding colonies, had been determined by Warham et al. (9). These authors reported that the stomach oil of the Petrels consists primarily of triglycerides from which the birds obtain their energy through their inter- mediary metabolism. The fatty acid ‘oil’ composition was published earlier by Lewis (10), while a more detailed analysis was given by Place et al. (11) who reported that the stomach oil of the Leach’s Storm-Petrel, Oceanodroma leucorhoa, is composed to >90% of neutral lipids (e.g. triglycerides, wax esters and glycerol ethers). As expected, the composition of these organic ingredients is dynamic. The amount of deposition of the oil is depends on the environmental living conditions of the birds; Warham (12) underscored also the ecological importance of the stomach oil for the seasonal requirements of the animals. However, a state-of-the-art analysis especially of the fossil deposits is missing. The material, investigated in the present contribu- tion was collected during the ‘GeoMaud’—Geoscientific Expedition to Dronning Maud Land (Antarctica) (http:// http://www.bgr.bund.de/cln_011/nn_322990/DE/Themen/Meer Polar/Polarforschung/Projekte/Antarktis_Projekte/GEO MAUD.html) during expeditions between November 1, 1995 and August 25, 2005. The yellow stony Mumijo material was collected from the Schirmacher Oasis (11350 E, 70450 S) as described (13,14) and determined to be 3000-years old. One reason for the intense study also of the antarctic Mumijo is its value as palaeoclimate biomarker (8). Especially for the Late Quaternary paleoen- vironmental history, this material is suitable to obtain further information about the climate changes and the local ice retreats, moraines and Petrel occupation history. The layers of fossil stomach oil can become 50cm thick and are deposited only on ice- and snow-free locations. The deposits are indicative for the breeding places of the Petrels and can hence give answers to paleoclimate-related questions, e.g. the retreat of glaciers.
In the present study, we report about the chemical composition of the fossil sample of Mumijo as well as about its neuroprotective and cell growth stimulatory effects. Our results correlate this latter activity partic- ularly to the presence of a-glyceryl ethers in this material. However, it can not be ruled out that Mumijo causes, as a complex formulation, in addition also an amelioration of a series of afflictions and may act also as an antimicro- bial, antiviral, antitumor, antiallergic, immunomodulat- ing or anti-inflammatory medicine, similar to the active
compounds from mushrooms (15), or of Propolis (16), or ‘Kampo’ compounds (17) as well as of Arabic medical herbs (18).
Materials and Methods
Alzheimer-b fragment [Ab25–35] (A 4559), 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (thiazolyl blue; MTT; M 2128), as well as additional chemical substances were obtained from Sigma (St Louis, MO, USA).
Electrospray ionization (ESI) mass spectra were obtained on an API 2000 mass spectrometer. Nuclear magnetic resonance (NMR) experiments were performed on a Varian Unity INOVA 500 spectrometer; chemical shifts refer to the residual solvent signal (CD3OD: H = 3.31, C = 49.0; CDCl3: H = 7.26; C = 77.0). Medium- pressure liquid chromatographic (MPLC) analyses were carried out on a Bu ̈ chi 861 apparatus with SiO2 (230–400 mesh) packed columns. High-performance liquid chroma- tography (HPLC) separations were achieved on a Knauer 501 apparatus equipped with an RI detector. GC-MS spectra were performed with a Hewlett- Packard 5890 gas chromatograph equipped with a split/splitness injector and connected to a Mass Selective Detector (MSD) HP 5970 MS using electron impact ionization (EI) at a ionization energy of 70eV. HPLC was achieved with a Varian Prostar 210 apparatus equipped with a Varian 350 refractive index detector or a Varian 325 UV detector.
The material was obtained from Dr Ulrich Wand (Alfred-Wegener-Institut Bremerhaven) and collected during the ‘GeoMaud’—Geoscientific Expedition to Dron- ning Maud Land (Antarctica) (http://www.bgr.bund.de/ cln_011/nn_322990/DE/Themen/MeerPolar/Polarforsc hung/Projekte/Antarktis__Projekte/GEOMAUD.html) November 1, 1995 to August 25, 2005. The location had been the Schirmacher Oasis (11350 E; 70450 S). The yellow stony material from Antarctica (Fig. 1B) is compared with the brownish tar-like deposits, which had been obtained from Samarkand (Turkestan) (Fig. 1A).
Extraction and Isolation
A first Mumijo extract was obtained by grinding the Antarctic material in a mortar and suspending it in dimethyl sulfoxide. After shaking for 24 h at 4C the clear
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extract was obtained by centrifugation (5000g; 10min; 4C). The concentration cited under Results section refers to the amount of solid Mumijo used for extraction.
For the chemical analysis, the fossil material (8.5g dry weight after extraction) was homogenized and extracted first with methanol (3 300 ml) and then with chloroform (3 200 ml). Combined extracts were concen- trated in vacuo and a crude extract (5.8 g) was obtained. This was subjected to fractionation by silica gel MPLC to give six fractions, A to F, using hexane, EtOAc and MeOH as a progressively polar solvent system series. All fractions were subjected to a preliminary spectroscopic inspection (1H NMR, ESIMS). Fractions B to D were showed to be neutral lipid mixtures and were subse- quently separated and/or analyzed, as indicated.
Fraction B (4 g) contained wax esters, whose fatty acid and alcohol compositions were determined by GC-MS in their natural state. GC-MS analysis was performed on a fused silica column (25 m 0.20 mm HP-5; cross-linked 25% Ph Me silicone; 0.33-mm film thickness). The oven temperature was programmed from 150 C to 350 C at a rate of 10C/min and held at the final temperature for 10 min. Helium was used as carrier gas at a constant flow
Figure 1. Mumijo samples. (A) Mumijo from Samarkand (Turkestan) (black). (B) Mumijo from Antarctica (yellow). In addition, the extract used in traditional formulation as medicine in Russia (in the back- ground). A, Mumijo Altai; B, Mumijo Panacea.
rate of 1.0 ml/min and a gas inlet pressure of 13.3 psi. Quantitative determination was based on the area of GLC peaks (Table 1). Wax esters (fraction B): 1H NMR (CDCl3): 0.86 (t, J = 6.6 Hz, 6 H), 1.23 (broad signal, alkyl chain protons), 1.52–1.58 (br., 4H), 2.26 (t, J=7.5Hz, 2H), 4.03 (t, J=6.7Hz, 2H) p.p.m.
Fraction C (1.1g) was shown to be a mixture of fatty acids. These had been methylated with diazomethane and the resulting esters were analyzed by GC-MS analyses on a fused silica column as above. The tem- perature of the column was changed 5min after injec- tion from 150 C to 300 C with a slope of 5 C/min. The quantitative determination was based on the area of GLC peaks and the results of the analysis are summarized in Table 2. Fatty acid methyl esters (fraction C): 1H NMR (CDCl3): 0.85 (t, J = 6.6 Hz, 3 H), 1.23 (broad signal,
Table 2. Fatty acid composition of monoglycerides and free fatty acids fraction, and fatty alcohol composition of monoalkyl glyceryl ethers
Table 1. Wax esters in fossil stomach oil—isomer composition, content and fragments
34 508 508 257
[R1CO2H2]+ Intensity [R1CO]+ [R21]a [R1CO2H2]+ (%)
Total carbon atoms [M]+ of wax esters chains [R1COOR2]
28 424 424 285 7.7 267
196 140 224 196 252 210 238
(182) 224 (252)
C14 C18 C14 C16 C18 C16 C14 C18 C18 C16
C14 C10 C16 C14 C12 C16 C18 C14 C16 C18
229 92.3 211
30 452 452 257 15.5 239
229 83.6 211 452 285 0.90 267
32 480 480 229 5.9 211
257 91.3 239 480 285 2.8 267
aFragments in brackets are not visible in the spectrum.
285 55.8 267 44.2 239
14:0 14:1 16:0 16:1 18:0 18:1 20:0 20:1 22:0 22:1 24:0 24:1
Monoglyceridesa Glyceryl ethersa
18.7 17.0 0.6 0.4 44.3 48.7 2.3 0.7 5.7 6.6 12.1 2.2 2.6 3.7 2.3 2.3 6.2 10.4 3.0 1.1 1.1 0.5 0.7 6.4
Free fatty acidsb
21.3 0.4 36.0 7.8 6.4 13.6 5.3 3.3 3.0 1.8 0.9 0.2
aQuantitative estimation (%) was based on the relative intensity of the peaks in the ESI mass spectrum. bQuantitative determination (%) was based on the area of GLC peaks.
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alkyl chain protons), 1.58 (m, 2 H), 2.30 (t, J = 7.5 Hz, 2H), 3.65 (s, 3H) p.p.m.
Fraction D (0.4 g) was re-chromatographed on an RP-18 column by MPLC (H2O ! MeOH ! CHCl3), thus giving a monoglycerides fraction (160mg, Fraction D/2) eluted with H2O/MeOH 2:8, and a monoalkyl glycerol ethers fraction (90 mg, Fraction D/3) eluted with 100% MeOH. An aliquot each of fractions D/2 and D/3 (20 mg each) was dissolved in pyridine (500ml) and allowed to react with Ac2O (200ml) for 12h. The reaction mixtures were con- centrated and the residues were purified by normal phase HPLC (Luna Silica 5mm, 2504.60mm, hexane/AcOEt 9:1 as the eluent). Monoglyceride diacetates from fraction D/2: 1H NMR (CDCl3): 0.86 (t, J=6.7Hz, 3H), 1.23 (broad signal, alkyl chain protons), 2.04 (m, 4H), 2.06 (s, 3H), 2.07 (s, 3H), 2.30 (t, J = 7.5 2 H), 4.11–4.16 (over- lapped signals, 2H), 4.25–4.31 (overlapped signals, 2H) 5.23 (m, 1H), 5.33 (m, 2H) p.p.m. ESI (positive ion mode): m/z: 407, 409, 435, 437, 463, 465, 491, 493, 521, 549 [M + Na]+ series. The quantitative estimation, reported in Table 2, is based on the relative intensity of the peaks. Glyceryl ethers diacetates from fraction D/3: 1H NMR (CDCl3): = 0.86 (t, J = 6.6 Hz, 3 H), 1.23 (broad signal, alkyl chain protons), 1.54 (m, 2H), 2.04 (m, 4H), 2.05 (s, 3H), 2.07 (s, 3H), 3.41 (m, 2 H), 3.51 (d, J = 5.2, 2 H), 4.14 (dd, J=12.0, 6.4Hz, 1H) 4.31 (dd, J=12.0, 3.6Hz, 1H), 5.16 (m, 1H), 5.33 (m, 2H) p.p.m. ESI (positive ion mode): m/z: 393, 395, 421, 423, 449, 451, 477, 479, 507, 535 [M+Na]+ series.
Cell Culture: Cortical Cells
Primary cortical cells were prepared according to a modified procedure (19,20) from the brains of 19-day-old Wistar rat embryos by dissociation (0.025% trypsin in Hanks’ balanced salt solution without Ca2+ and Mg2+). The cell suspension was centrifuged and the pellet was resuspended in Dulbecco’s modified Eagle’s medium (4500 mg of glucose/l), supplemented with 100 mU/l insulin, 2 mM glutamate and 10% fetal calf serum. After incubation for 48 h in poly-L-lysine-coated plastic 96-well plates, the medium was supplemented with 10 mM uridine, 10 mM fluorodeoxyuridine and 1 mM cytosine arabinofur- anoside (to eliminate proliferating non-neuronal cells) for 3 days. The cultures contained >85% neurons; the other cells were glial fibrillary acidic protein-positive (20,21). Cells were routinely exposed to the Ab fragment Ab25–35 at a concentration of 1mM for 5 days. The Ab25–35 was prepared in a stock solution of 900mM in distilled water and stored for 5 days at 4C before use. Mumijo extract was added at the indicated concentrations 2 h before incubation of the cells with Ab25–35.
Cell Culture: PC12
In parallel, the extracts were tested in the permanent PC12 cell line that is derived from pheochromocytoma of
the rat adrenal medulla. The tumor cells were grown as described earlier (22), but with the modification that RPMI-1640 medium, enriched with 10% fetal calf serum, was used. All cells were kept in a humidified atmosphere of 5% CO2 and 95% air. Cells were seeded in 96-well plates at a density of 5 103 cells per well with or with- out the extracts. After 72h, plates were analyzed on a microplate reader and the ED50 concentrations were determined (23).
Evaluation of Viable Cells
The viability of total cells was determined with the MTT colorimetric assay system (24), followed by evaluation with an ELISA plate reader (Bio-Rad model 3550, equipped with the program NCIMR IIIB). Ten parallel assays were performed for each concentration of the respective extracts. The results were analyzed by paired Student’s t-test (23).
Chemical Analysis of Mumijo Extract
The wax esters fraction was analyzed by GC-MS using EI, according to the method proposed by Reiter et al. (25). This rapid method allows to analyze the composi- tion of a wax in its natural state and to obtain a reliable and complete profile of wax esters. EI spectra of wax esters [R1COOR2] contain a single molecular ion [M]+ alongside a set of dominant ions [R1CO2H2]+ deriving from a double hydrogen rearrangement fragmentation at the ester group. These ions show a difference of 28amu and lead to the conclusion that the individual GC peaks contain wax ester isomers with the same carbon number and same degree of unsaturation, but different position of the esters moiety within the wax ester due to differ- ent chain lengths of carbonyl- and ester components. In our case, due to the relatively high abundance of [R1CO2H2]+ ions, the assignment of the individual was esters isomers was possible, as shown in Table 1; further evidence for our results was provided by the presence of [R2-H]+ ions and [R1CO]+ acylium ions.
Fractions D/2 and D/3 were shown (by NMR) to be a mixture of glycerol derivatives; the identification of their components was carried out by NMR and ESIMS. An aliquot each of fractions D/2 and D/3 was acetylated by treatment with acetic anhydride and pyridine and then purified by normal phase HPLC. The fractions turned out to be mixtures of monoglyceride diacetates (fraction D/2) and glyceryl ethers diacetates (fraction D/3) by NMR analysis (see Materials and Methods section). A confirmation was also achieved by comparing their spectroscopic properties with those reported in literature (26,27). The ESI mass spectra (positive ion mode) of
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fractions D/2 and D/3 showed a [M + Na]+ peak series, indicating their composition of homologs; the high field region of the 1H-NMR spectra of both fractions revealed that all the homologs were unbranched. The assessment of fatty acid and alcohol composition of monoglycerides and monoalkyl glycerol ethers diacetates, reported in Table 2, was based on the estimation of the relative intensity of the peaks in their ESI spectra. Table 2 shows also the free fatty acid composition determined by GC-MS analysis performed on their methyl esters.
Mumijo Extract Protects Cortical Neurons against Ab25–35-caused Reduction of Cell Viability
The toxic effect of the Ab fragment, Ab25–35, was assessed in primary rat cortical neurons. Application of the fragment at a concentration of 1mM caused within the 5-day incubation period a significant reduction of viable cells to 27.86.1% (P<0.001). Mumijo extract alone was found to have no effect on the viability of the neurons. However, if the neurons were pre-incubated with Mumijo extract prior to addition of the Ab25–35, a significant higher cell viability was determined (Fig. 2). At concentrations of 3mg/ml or higher of Mumijo extract, the percentage of viable cells increased from 27.86.1% (in the absence of extract) to 98.69.3% (10 mg/ml) and 82.4 8.9% (30 mg/ml) (P < 0.001), respectively. The neuroprotective effect displayed by the Mumijo extract was still significant at 1mg/ml (not shown).
Figure 2. Effect of Mumijo extract on Ab25–35-induced cell toxicity. Neurons have been treated with 1mM of Ab25–35 for 5 days. During this period the viability of the cells dropped from 100% (hatched bar) to 28% (solid black bar) if no Mumijo extract had been added. How- ever, if the cultures had been pre-incubated with increasing concentra- tions of Mumijo extract (3–100mg/ml) the b25–35-induced cell toxicity is reduced. Control values are set to 100% (hatched bar); n = 10. The meansSEM are given. *P<0.001 [versus controls (plus Ab 25–35)]. Cell viability was determined applying the MTT assay procedure.
eCAM 2008 5 of 8 Mumijo Extract Promotes PC12 Cell Growth
The permanent PC12 cell line, a model system for neuronal differentiation (28), was used as a second cell system to assess the biological activity of Mumijo (Fig. 3). The non-purified extract displaced no significant growth stimulatory effect between 0.1 and 10mg/ml. However, after purification, Mumijo fraction D/3 was effective and resulted in a significant stimulation of cell growth. Already at a concentration of 0.3mg/ml, a significant increase in the growth stimulatory activity could be measured (114.06.8%; P<0.001), while the maximal growth promoting function was determined between 3.0 and 10.0 mg/ml (139.2 12.3% or 129.210.3%, respectively).
A detailed description of the components in Mumijo from Central Asia revealed (3) primarily inorganic com- ponents, e.g. minerals (18–20%)], considerable amounts of organic components, primarily of proteins (13–17%), steroids (3.3–6.5%), carbohydrates (1.5–2%) and nitrogen-containing compounds (0.05–0.08%), in addi- tion to lipids (4–4.5%). By our activity-guided isolation procedure, using neuronal cells, we identified that the major organic, bioactive components are wax esters. The mineral content of the Antartican Mumijo has not yet been determined, leaving room also for a potential application in the treatment of bone diseases (29). Likewise the potential biomedical activity of the mono- glycerides, known to possess potent antimicrobial/micro- bicidal activity (30), and of the neutral glyceroglucolipids (31), comprising anti-stomach ache effectiveness, are not addressed here.
The chemical analysis of the fossil sample of Mumijo actually revealed that its composition parallels those previously reported for other samples of non-fossil material, with some substantial differences. The organic extract of Antarctic Mumijo contained mainly wax esters (70% wt), with considerable amounts of free fatty acids (20% wt). Monoglycerides and free monoalkyl glycerol ethers were also detected in significant amounts (3% wt and 1.6% wt, respectively). Monoalkyl glycerol ethers are most frequently found as alkyldiacylglycerols (similar to triacylglycerols). However, these compounds, whose occurrence in petrel stomach oils has been reported (9,10,31,32), as well as triglycerides and/or diglycerides, present in large amounts in other previously examined oil samples, were not detected at all in the Mumijo sample investigated. This difference might be ascribed to the age of the sample and, as a consequence, to the effect of a slow lipolysis. Our sample also lacked cholesterol esters, found in some other Mumijo oils.
Glyceryl ethers were identified by Tsujimoto and Toyama (33) in the fraction of some fish liver oils and,
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Figure 3. Effect of Mumijo on the cell growth of neuronal PC12 cells. (A) Effect of non-purified Mumijo extract on growth of permanent PC12 cells. (B) Fraction D/3, containing glyceryl ether diacetates caused a dose-dependent stimulation of proliferation. Incubation conditions are given under Materials and methods section.
subsequently, they have been found in diverse sources, including most of the petrel stomach oils investigated (10,12). The major monoalkyl ethers are: 1-O-hexadecylglycerol (16:0 alkyl or chimyl alcohol), 1-O-octadecylglycerol (18:0 alkyl or batyl alcohol) and 1-O-octadec-9-enyl glycerol (18:1 alk-9-enyl or selachyl alcohol). The trivial names go back to the fish species from which they have originally been isolated. In 1948, Berger (34) reported the central depressant action of a-substituted glycerol ethers, and of chimyl and batyl alcohols. Since then, reports have appeared claiming a number of further pharmacological activities, such as antimicrobial (35), tubercolostatic (36) and Lactobacillus growth-promoting activities (37), as well as a protective effect against radia- tion sickness (38) and radiation-induced leucopenia (37). Bodman and Maisin (39) reported that topical applica- tion of a-glyceryl ethers as well as of batyl and selachyl alcohols significantly accelerated the rate of wound healing in man when the healing process had been pathologically inhibited. Burford and Gowdey (40) claimed that batyl and selachyl alcohols showed anti-inflammatory effects comparable to hydrocortisone in rats when administered p.o. In 1972, Ando et al. (41) reported the antitumor activity of fatty alcohols and a-glyceryl ethers of fatty alcohols. These properties could explain some medical applications of Mumijo in oriental medicine, such as its use for gastric and intestinal ulcers, healing of fractures, burns and skin diseases, tuberculosis, respiratory disease and inflammations (3).
The present finding that Mumijo is rich in (a-glyceryl ethers of) fatty alcohols is in accordance with recent data, which demonstrate that distinct fatty alcohols present strong potential for the treatment of neurological diseases, and are able to modulate neuroinflammation via induc- tion of differentiation of neural stem cells into mature neurons. Based on these data, it had been proposed that those compounds might represent an approach for the treatment (or cure) of neuropathies (42). Very well
established is also the neuroprotective action of polyunsa- turated fatty acids in Parkinson’s as well as in Alzheimer’s disease (43). In addition, since >50 years shark liver oil has been used as a therapeutic and preventive agent. In this preparation, the most active ingredients are the ether- linked glycerols, which have been suspected to act via activation of protein kinase C resulting in a immunosti- mulating action on the macrophage (44).
Taken together, our data presented here show that the Antarctic Mumijo is rich in glyceryl ether derivatives which—according to the data given—display distinct and marked neuroprotective activity. Schematically, the bio- medical potential of Antarctic Mumijo is summarized in Fig. 4. The main organic components, the wax esters and the glycerol ethers, are known to display neuroprotective potential. Future studies will prove if the monoalkyl ethers display also anti-stomach ache capacity. Finally, the triglycerides have to be studied for their putative antimicrobial activity. The inorganic component(s), the minerals existing in Mumijo, may have their ameliorating function in bone diseases. An outline of the exploitation strategies for traditional and modern drugs applicable in the biomedicine has been given for the Mediterranean region (45).
European Bundesministerium fu ̈ r Bildung und Forschung (Health of marine ecosystems).
We thank C. Eckert for the gift of the Mumijo samples. Mass and NMR spectra were recorded at the ‘Centro Interdipartimentale di Analisi Strumentale’, Universita’ di Napoli ‘Federico II’.
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Figure 4. Main biomedical activity (established as well as expected from literature data) of the different organic fractions, which have been separated from Antarctic Mumijo. A further potential can be supposed from the inorganic component(s), the minerals, with respect to their ameliorating function in bone diseases. The scheme shows also a cross section through a Mumijo sample from Antarctica (size: 2.5 cm). The layered deposition of the waxy organic material is self-evident.
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Received July 8, 2008; accepted October 10, 2008
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Selected herbals and human exercise performance1–3
Luke R Bucci
ABSTRACT Herbs have been used throughout history to enhance physical performance, but scientific scrutiny with con- trolled clinical trials has only recently been used to study such effects. The following herbs are currently used to enhance phys- ical performance regardless of scientific evidence of effect: Chinese, Korean, and American ginsengs; Siberian ginseng, mahuang or Chinese ephedra; ashwagandha; rhodiola; yohimbe; Cordyceps fungus, shilajit or mummio; smilax; wild oats; Muira puama; suma (ecdysterone); Tribulus terrestris; saw palmetto berries; -sitosterol and other related sterols; and wild yams (diosgenin). Controlled studies of Asian ginsengs found improve- ments in exercise performance when most of the following con- ditions were true: use of standardized root extracts, study dura- tion (>8 wk, daily dose >1 g dried root or equivalent, large number of subjects, and older subjects. Improvements in muscu- lar strength, maximal oxygen uptake, work capacity, fuel home- ostasis, serum lactate, heart rate, visual and auditory reaction times, alertness, and psychomotor skills have also been repeat- edly documented. Siberian ginseng has shown mixed results. Mahuang, ephedrine, and related alkaloids have not benefited physical performance except when combined with caffeine. Other herbs remain virtually untested. Future research on ergogenic effects of herbs should consider identity and amount of substance or presumed active ingredients administered, dose response, duration of test period, proper experimental controls, measurement of psychological and physiologic parameters (including antioxidant actions), and measurements of performance pertinent to intended uses. Am J Clin Nutr 2000;72(suppl):624S–36S.
KEY WORDS Herbs, dietary supplements, exercise, physi- cal performance, ginseng, ephedra, ergogenic aids, antioxidants
This review explores the scientific evidence for use of herbs and herbal extracts as ergogenic aids for humans who exercise. For the purposes of this review, herbs are defined as plants or plant extracts ingested for other than caloric or culinary benefit. Despite their long tradition of use by physically active persons, herbs have seldom been studied scientifically as a possible aid to physical performance. This review will stop short of considering the effects of purified or synthesized compounds found in plant foods and classified as essential nutrients, such as -carotene, tocopherol, and ascorbate. This review will also not consider one of the most popular herbal extracts, caffeine, which has been
studied extensively as an ergogenic aid, usually as the pure com- pound added to decaffeinated coffee so that doses are controlled. Caffeine has consistently shown ergogenic effects for both endurance and short-term exercise, as indicated by several reviews (1–4). Noncoffee herbal sources of caffeine commonly found in dietary supplement products include guarana (Paullinia cupana), kola nut (Cola acuminata), green tea (Camilla sinen- sis), and maté (Ilex paraguayensis). Only ginseng preparations and ephedrine alkaloids have also been studied repeatedly for their effects on human physical performance.
This review will consider such common physiologic measures of exercise performance as oxygen utilization, fuel homeostasis, and lactate accumulation as well as several other measures of inter- est. Psychological, psychomotor, and antioxidant effects of herbs will be presented when available. Brief descriptions of proposed mechanisms of action may require citation of animal studies.
Humans consume herbs to enhance their long-term endurance performance (eg, in running, cycling, rowing, swimming, walk- ing, dancing, aerobics, cross-country skiing, and mountain climb- ing), to induce muscular hypertrophy and strength (eg, for bodybuilding, weight lifting, wrestling, strength sports, and track and field events), or to enhance performance in sport events, both skill sports and those that are recreational. Tradition, identity of ingredients, advertisements, personal endorsements, use by other athletes, and the desire to succeed represent the extent of valida- tion for most herbs used for physical performance.
REGULATORY STATUS OF HERBS
Currently in the United States, herbs can be defined as drugs, foods, or dietary supplements. The Dietary Supplement Health Education Act (DSHEA) of 1994 [the final version of which was published in 1997 (5)], which amended the Food, Drug and Cos- metic Act of 1938, defines dietary supplements as certain foods intended to supplement the diet that are not represented as con- ventional foods. Herbs or other botanicals and their extracts or concentrates are specifically mentioned as dietary supplements. To be subject to DSHEA regulations the statement “dietary sup-
1 From Weider Nutrition International, Salt Lake City.
2 Presented at the workshop Role of Dietary Supplements for Physically Active People, held in Bethesda, MD, June 3–4, 1996.
3 Address reprint requests to LR Bucci, Weider Nutrition International, 2002 South 5070 West, Salt Lake City, UT 84104-4726. E-mail: lukeb@ weider.com.
624S Am J Clin Nutr 2000;72(suppl):624S–36S. Printed in USA. © 2000 American Society for Clinical NutritionEFFECTS OF HERBAL SUPPLEMENTS ON PERFORMANCE 625S
plement” must appear on the principal display panel. DSHEA allows claims of structure or function to be made for dietary sup- plement products but not foods. Claims are based on the manu- facturer’s interpretation of the scientific literature and are limited to effects of ingredients on the body’s structure or function or on a person’s health or well-being. A disclaimer that the Food and Drug Administration has not evaluated claims must be present on dietary supplement labels that make structure or function claims. Product distributors are required to keep substantiation on hand derived from reliable and competent scientific research, usually reported in peer-reviewed articles and texts, for any claims on file. Although herbs can be conventional foods or drugs, all of the herbs described in this review are available as dietary sup- plements in the United States.
Distributors of herbal products are also under the jurisdiction of the Federal Trade Commission (FTC), which monitors adver- tising for truthful statements that do not mislead. FTC guidelines for substantiation differ from DSHEA guidelines, a fact that may produce confusion as new regulations are enforced. It is hoped that distributors of herbal dietary supplements will disclose fac- tual information based on peer-reviewed scientific literature, as the DSHEA intended.
Other countries classify herbs as foods, drugs, or both. In Germany, some herbs are prescription drugs that have passed stringent safety and efficacy requirements, but these drugs (herbs) are also available without a prescription. Herbal medi- cines are described in the German Commission E Monographs, recently translated into English by the American Botanical Council (6). Herbal drug products to treat cerebrovascular deficiency that are made from Ginkgo biloba leaf extracts are one of the most frequently prescribed drugs in Germany, with > 5.4 million prescriptions written in 1988 as well as over-the- counter sales (6, 7).
HERBS AS ERGOGENIC AIDS
The herbs used most commonly at present to enhance physi- cal performance and reasons for their use by consumers are shown in Table 1. Some herbs are classified as adaptogens, ie, they assist normalization of body system functions altered by stress rather than exerting a stimulatory effect (7). Persons who exercise often use adaptogens because exercise is considered a form of stress. Various combinations of traditional Chinese herbs, traditional Indian (Ayurvedic) herbs, or combinations of herbs listed in Table 1 are available in the marketplace and tar- geted toward physical performance, but they are not considered in this paper because of a lack of scientific substantiation and because their use is uncommon.
Herbs are used to improve performance (both endurance and strength), improve recovery, maintain health during intense periods of exercise, build muscle mass, and reduce body fat (Table 1). Because of the paucity of research in this area, studies from obscure sources will be among those included in this review.
The most-studied herb for human physical performance is ginseng, which includes several species in the Araliaceae fam- ily and is prepared by various methods. The term ginseng usu- ally refers to the species Panax ginseng, known as Chinese gin- seng or Korean ginseng. The use of ginseng is a dietary and
medicinal custom in many Asian countries, especially China and Korea. Ginseng is available in many forms: whole root, root powder (white ginseng), steamed root powder (red gin- seng), teas, tinctures, and standardized root extracts containing known and reproducible amounts of ginsenosides in every batch (9). Panax quinquefolium (American ginseng) is more popular in China than the United States. Siberian ginseng (Eleutherococcus senticosus) will be considered separately in this paper.
Other plants similar to ginseng by taxonomy or traditional use include tienqi ginseng (Panax notoginseng or Panax pseudoginseng), zhu je or Japanese ginseng (Panax japonica), false ginseng (Codonopsis pilosula), prince’s ginseng (Pseu- dostellaria heterophylla), dong quai (Angelica sinensis), and glehnia root (Glehnia littoralis) (9–12). Only P. ginseng preparations have been studied in human clinical trials of physical performance.
Chinese ginseng (P. ginseng)
Ginseng roots contain ≥13 positively identified, glycosylated steroidal saponins (ginsenosides) as likely active agents (12–16). Roots are harvested after ≥5 y of growth and contain 1–2% ginsenosides. Standardized extracts (exemplified by G115; GPL Ginsana Products, Lugano, Switzerland) contain 4% ginseno- sides. Traditional use of ginseng is 3–9 g/d of powdered root, almost always combined with other herbs (12). This dose range should be borne in mind in evaluations of human studies per- formed in the United States.
Many mechanisms of action have been proposed for ginseng. The traditional use is to restore Qi, or life energy, but ginseng preparations are used for many specific purposes (6, 9–14, 17). The herb is thought to be a tonic to increase vitality, health, and longevity, especially in older persons. Isolation of ginsenosides and administration to animals has revealed activities that stimu- late the central nervous system as well as those that depress it (9, 10, 12–14, 17–22). Other possible mechanisms for ginseng include increased production of corticotropin and cortisol in animals and humans (9, 12–14, 23, 24) and anabolic actions (stimulation of DNA, RNA, and protein synthesis in tissues) in animals (9–14, 17, 25, 26). Ginseng has shown immunoenhanc- ing effects in animals and humans (12–14, 27–29) and antioxi- dant activity (increased liver glutathione content) in vitro and in animals (12–14, 30–33). Ginsenosides are also credited with stimulation of nitric oxide production in immune system cells, vascular endothelial cells, arteries, and erectile tissues (34–39). This mechanism, which was not discussed in the most recent reviews of ginseng, could account for many of the clinical effects observed. Thus, multiple mechanisms that have rele- vance to human physical performance may account for the pos- sible antistress effects of ginseng.
The results of many animal studies of ginseng show improve- ments in exercise performance, but the use of large doses or par- enteral administration (bioconversion of ginsenosides is known to occur in stomach acid and gut microbial actions before uptake) weakens extrapolation of these data to humans (1, 12–14). Previous reviews of ginseng and human physical perfor- mance reported mixed results (1, 12–14). An examination of available data reveals a dose-response and duration effect, which accounts for most of the variation in results. Data from available human studies (both controlled and uncontrolled) on P. ginseng preparations are shown in Table 2. As shown, properly controlled
Herbs currently used to enhance physical performance
Herb Reason for use Potential or known hazards1
Arctic rose (Rhodiola crenulata, R. rosea)
Ashwagandha (Withania somnifera)
Asian ginseng (also Chinese, Korean) (Panax ginseng)
-Sitosterol and other sterols (soy, alfalfa, and other plants)
Chinese ephedra (mahuang) (Ephedra sinica)
Cordyceps (Cordyceps sinensis) Potency wood (muira puama)
(Ptychopetalum olacoides) Saw palmetto berries (Serenoa repens)
Schizandra (wu-wie-tza) (Schisandra chinesis)
Siberian ginseng (ci-wu-jia) (Eleutherococcus senticosus)
Smilax (sarsaparilla) (Smilax officinalis or medica)
Suma (Pfaffia paniculata) Tribulus terrestris (Tribestan) 2
Truffles Wild oats (Avena sativa) (combined with nettle root)
Wild yam, Mexican yam (Dioscorea villosa) Yohimbe (Pausinystalia yohimbe)
Adaptogenic (antistress) properties, enhance endurance and strength
Adaptogenic (antistress) properties, enhance endurance and strength
Adaptogenic (antistress) properties, enhance endurance and strength
Testosterone-like effect (anabolic)
Central nervous system stimulant, enhance endurance, strength, and body fat loss
Adaptogenic (antistress) properties, enhance endurance and strength
Testosterone-like effect (anabolic) Testosterone-like effect (anabolic)
Adaptogenic (antistress) properties, enhance endurance and strength
Adaptogenic (antistress) effects, enhance endurance and strength
Adaptogenic (antistress) properties, enhance endurance and strength
Testosterone-like effect (anabolic)
Ecdysterone source, testosterone-like effect (anabolic)
Increases testosterone (anabolic effects) Contain androst-16-en-3-ol (weak androgen),
testosterone-like effect (anabolic) Testosterone-like effect (anabolic) Testosterone-like effect (anabolic) -Adrenergic agonist, potentiate caffeine and
ephedrine effects, increase male performance
May potentiate effects of barbiturates.
Possible adulteration with stimulant drugs; contraindicated in hypertension.
Not recommended for long-term use; limit daily intake of total alkaloids to 120 mg in 4 equal doses. Seek advice from a health care practitioner before use if you are pregnant or nursing, or if you have high blood pressure, heart or thyroid disease, diabetes, difficulty in urination due to prostate enlargement, or if taking a monoamine oxidase inhibitor or any other prescription drug. Reduce or discontinue use if nervousness, tremor, sleeplessness, loss of appetite, or nausea occur. Not recommended for use by persons under 18 y of age. Keep out of reach of children.
Rare cases of stomach upset. German Commission E suggests regular consultation with physician if one has an enlarged prostate, because Serenoa may treat symptoms without changing hypertrophy.
Rare cases of appetite suppression, stomach upset, urticaria.
Rare cases of insomnia. German Commission E contraindicates in high blood pressure.
German Commission E warns of gastric irritation and temporary kidney impairment and potential drug interactions with hypnotics, digitalis glycosides, and bismuth (unsubstantiated)
None reported. None reported.
None reported. None reported. Not recommended for long-term use.
Contraindicated in liver and kidney diseases and in chronic inflammation of sexual organs or prostate gland. May potentiate monoamine oxidase inhibitor drugs.
1 From reference 8. 2 Tribestan; Sopharma, Sofia, Bulgaria.
studies exhibiting statistically significant improvements in physical or psychomotor performance almost invariably used higher doses (usually standardized to ginsenoside content equiv- alent to ≥ 2g dried root/d), longer durations of study (≥ 8 wk), and larger subject numbers, indicating greater statistical power (9, 40–58). Also evident were the lower doses, durations, and
subject numbers of studies that did not find any significant dif- ferences in performance, physiologic, or psychomotor measure- ments (46, 59–67).
Thus, under appropriate conditions, ginseng root extracts may increase muscular strength and aerobic work capacity. Require- ments are sufficient daily dose (≥2000 mg P. ginseng root pow-
EFFECTS OF HERBAL SUPPLEMENTS ON PERFORMANCE 627S
Results of human studies with Panax ginseng on physical and mental performance1
Study Subject Study Subject Daily Preparation Study Effects (statistically significant (reference) n design age range dose type duration unless otherwise stated)
Popov and Goldwag 1973 (9)
Sandberg 1974 (59) Revers et al 1976 (40)
Simon 1977 [cited in Carr 1986 (13)] Bae 1978 [cited in
Hobbs 1996 (12)]
Schmidt 1978 [cited in Hobbs 1996 (12)]
Sandberg 1980 (42)
Johnson 1980 [cited in Hobbs 1996 (12)]
Dorling et al 1980 (41)
Forgo and Kirchdorfer 1981 (43)
Forgo et al 1981 (44)
Forgo and Kirchdorfer 1982 (45)
Hallstrom et al 1982 (46)
Forgo 1983 (47)
12 night shift nurses 30 elite athletes
DB, PC DB
PC DB, PC
? DB, PC
DB, PC, CO
DB, PC NC
DB, PC DB, PC
Elderly 21–23 y
18–31 y 30–60 y
Elite young athletes
21–27 y 19–31 y
22 ± 1 y 18–21 y,
38–70 y 20–30 y 20–24 y
200 mg 200 mg
1200 mg 200 mg
2 capsules for 30 d, 1 capsule for 30 d 200 mg
40% ethanol tincture
2 types of standardized extract ?
Standardized extract Standardized extract
Standardized extract, 4% or 7% ginsenoside content Korean white ginseng powder Standardized extract
1.5% glycosides ARM229 standardized extract
? 90 d
90 d ?
? 12 wk
? 12 wk
9 wk 12 wk
4wk 60 d
9wk 12 wk
Decreased errors in radio transmission of coded messages (17% compared with 31%); NS for number of characters transmitted
NS for spiral maze tracing test, letter cancellation test
Improved vitality, alertness, rigidity, concentration, visual-motor coordination, positive outlook, visual and auditory reaction times
Improved concentration, and mental accuracy; NS for attention
Reduced telegraphy mistakes (17% compared with 31%); NS for mental concentration, coordination
Improved subjective and objective indexes; normalized blood glucose and blood pressure
Improved spiral maze tracing test, letter cancellation test, and oxygen metabolism (15-min step test)
NS for mathematics performance, blood cortisol and epinephrines, proofreading error detection, mood, and fatigue indexes
Improved visual and auditory reaction times, postexercise recovery (stair climbing), 2-hand coordination, alertness, and subjective assessments
Increased aerobic capacity; reduced lactate production, and heart rate
Improved vital capacity, forced expiration volume, maximum expiratory flow, maximal breathing capacity, reaction times, subjective assessments of mood, work output, sleep, concentration, vitality; NS for serum LH, FSH, testosterone, estradiol, blood chemistries
Improved aerobic capacity; reduced lactate production, and heart rate; NS for difference between 4% and 7% ginsenoside content
Improved tapping rate test; NS for mood, somatic symptoms, blood glucose (all trends); negative effects on sleep quality
Improved oxygen uptake, maximal breathing capacity, vital capacity, and forced expiration volume; reduced lactate production, and heart rate; NS for serum LH, testosterone, and cortisol
NS for R values, glucose, lactate, free fatty acids, glycerol, insulin, cortisol, and growth hormone
NS for run time to exhaustion, aerobic capacity, heart rate, VE, and RPE Older group: improved performance in
Cooper test (12-min run time); younger group: NS trend in Cooper and Harvard step tests
Improved oxygen uptake, forced expiration volume, vital capacity, visual reaction times, and heart rates
Improved mental arithmetic calculations; NS trend for attention, choice reaction time, auditory reaction time; NS for tapping test, recognition, and visual reaction time
Knapik et al 1983 (60) 11 marathon runners
Teves et al 1983 (61) Murano et al 1984 (48)
Forgo and Schimert 1985 (49)
D’Angelo et al 1986 (50)
12 marathon runners 65
28 elite athletes
TABLE 2 (Continued)
Study Subject Study Subject Daily Preparation Study Effects (statistically significant (reference) n design age range dose type duration unless otherwise stated)
Ng and Ng 1986 [cited in McNaughton et al 1989 (53)]
Macareg and Ramos 1986 [cited in McNaughton et al 1989 (53)]
von Ardenne and Klemme 1987 (51) Tesch et al 1987 (52)
McNaughton et al 1989 (53)
Pieralisi et al 1991 (54)
van Schepdael 1993 (55) Wiklund et al 1994 (56)
Morris et al 1994, 1996 (62, 65)
Smith et al 1995 (63) Engels et al 1995 (64)
Marasco et al 1996 (57)
Sorensen and Sonne 1996 (58)
Engels and Wirth 1997 (66)
Allen et al 1998 (67)
15 women, 15 men
43 female triathletes 390
1 woman, 7 men
19 women 19 women
112 healthy volunteers 36 men
8 women, 20 men
R, DB, PC, CO
R, DB, PC, CO
R, DB, PC, CO
R, DB, PC, CO PC
R, DB, PC
R, DB, PC
R, DB, PC R, DB, PC R, DB, PC, CO
? ? ? ???
Improved endurance, maximal oxygen uptake, postexercise recovery, simple reaction time
NS for time to exhaustion, glucose, and lactate
Improved resting PO2 uptake (arteriovenous difference) by 29%
Improved heart rate and lactate production (> 180 W), RPE (60, 80, 120 W workloads); NS for lactate production up to 180 W
Improved aerobic capacity, pectoral strength (27%), quadriceps strength (18%), postexercise recovery; NS for grip strength
Improved total work load, time to exhaustion, aerobic capacity, ventilation, oxygen consumption, carbon dioxide production, lactate production, and heart rate; NS for RER
Prevented loss of physical fitness after 10 wk
Improved alertness, relaxation, appetite, overall score, and general well-being (3 scales)
NS for cycle time to exhaustion and physiologic responses
NS for POMS and PANAS (psychological tests) and RPE
NS for exercise recovery (heart rate, lactate production, oxygen consumption, and ventilation)
Improved quality of life, prevention of increased body weight and high blood pressure
Faster reaction times, better abstract thinking; NS for memory, concentration, well-being
NS for oxygen consumption, RER, RPE, lactate, and heart rate during exercise
NS for oxygen uptake, exercise time, workload, lactate production, hematocrit, heart rate, ratings of perceived exertion at 150 W, 200 W, or peak
50 y 50–54 y
? 21–47 y
24–36 y Middle-age
27 ± 5 y
>40 y ? 23±3y
200 mg 80 mg
1000 mg 200 mg
400 mg 200 mg
8 or 16 mg/kg
200 mg 200 mg
200 or 400 mg 200mg
Standardized extract Standardized extract, vitamins, minerals Ginseng
Standardized extract plus DMAE, vitamins, minerals Standardized extract Standardized extract plus vitamins, minerals Panax quinquefolium Water-ethanol extract Standardized extract Standardized extract
Standardized extract plus vitamins, minerals Standardized extract Standardized extract 7% ginsenoside standardized extract
20 wk 12 wk
8 wk 8 wk
8–9 wk 8 wk 3 wk
1 ?, data not listed or unavailable; CO, crossover; DB, double-blind; DMAE, dimethylaminoethanol; FSH, follicle stimulating hormone; LH, luteinizing hormone; NC, not controlled; PANAS, positive and negative affect schedule; PC, placebo-controlled; POMS, profile of mood survey; R, randomized; RER, respiratory exchange ratio; RPE, ratings of perceived exertion; VE, expiratory ventilation.
2 Unless otherwise specified, standardized extract refers to G115, a proprietary ginseng extract standardized to 4% ginsenosides. G115 is a registered trademark of GPL Ginsana Products, Lugano, Switzerland, and Pharmaton Ltd, Switzerland.
der or an equivalent amount of root extract with standardized ginsenoside content), sufficient duration for effects to develop (≥8 wk), and sufficient intensity of physical or mental activity (especially in untrained or older subjects).
Studies finding performance enhancement from ginseng were not universally positive; some parameters were not significantly affected. For example, after baseline testing, McNaughton et al (53) randomly divided 30 subjects (15 females, 15 males) into 3 groups of 10 and administered placebo, Chinese ginseng, or Siberian gin- seng (1 g/d of an uncharacterized powder of each) for 6 wk, when
each subject was retested. Subjects were crossed over to the other 2 substances in 2 more 6-wk periods. Compared with placebo, Chi- nese ginseng significantly improved maximal oxygen uptake (V·O2max; tested on a Monark model 686 cycle ergometer, Monark Exercise AB, Vansbro, Sweden), postexercise recovery (heart rate lowered 6 beats/min for the 6 min after exercise), pectoral strength (by 22% as measured by a dynamometer), and quadriceps strength (by 18% as measured by dynamometer). However, grip strength (measured by a Harpenden grip strength dynamometer) did not improve significantly (53).
EFFECTS OF HERBAL SUPPLEMENTS ON PERFORMANCE 629S
Similarly, Forgo et al (44) studied 120 subjects aged 30–60 y for 12 wk in a double-blind study: subjects were given either placebo or 200 mg/d of a standardized ginseng extract. Sup- plementation was associated with significantly reduced reac- tion times for subjects aged 40–60 y but not for those aged 30–39 y. Men in this youngest group showed no significant effect from ginseng on pulmonary functions (vital capacity, forced expiratory volume, maximum expiratory flow, and maximum breathing capacity). Women aged 30–39 y and both sexes aged 40–60 y showed significant improvements in all 4 measurements of pulmonary function after 12 wk of supple- mentation. No significant changes by age or sex were found for serum concentrations of luteinizing hormone, testosterone, or estradiol. As with pulmonary function, subjective self- assessment showed significant improvements in women of all ages but only in men aged 40–60 y. Importantly, changes became significant after 6 wk of supplementation and were more significant at 12 wk, suggesting a slow-acting effect. Thus, studies lasting <12 wk (46, 60–67) may not have been long enough to show a significant effect.
Is ginseng safe? A long tradition (>2000 y) and an extensive history of use (millions of people, many elderly or infirm) sug- gests an affirmative answer (9–14), but recent reports have iden- tified possible adverse effects. A “ginseng abuse syndrome” was described from case reports (68), but the reported symptoms of sleeplessness, nervousness, hypertension, skin eruptions, morn- ing diarrhea, and euphoria may have been attributable to the very large caffeine intakes of most of the subjects. A few cases of estrogen-like effects (mastalgia and vaginal bleeding) were reported in postmenopausal women using topical creams or tak- ing pills containing ginseng (69–73). Findings that a few ginseng products were adulterated with prescription medications (ephedrine or pseudoephedrine, for example) could account for unexplained side effects (12–15).
Conceivably, ginseng interacts with monoamine oxidase inhibitor medications, but more data are needed to confirm this (74). If true, another mechanism of action (inhibition of cyclic AMP phosphodiesterase) may account for some of the observed mental effects. In general, animal toxicity studies found ginseng to be very safe, with no teratogenicity or mutagenicity (12–14). In addition, the use of ginseng does not result in positive test results for any banned substances after urine testing of elite ath- letes, even though ginsenosides and their metabolites are detectable in the serum and urine of athletes after ingestion of ginseng products (75–77). Currently, there appears to be no risk of disqualification from drug-tested sporting events from use of ginseng (14). Given the generally positive results for ginseng on improving reaction times, long-term supplementation with stan- dardized extracts may maintain or improve performance in skill sports that rely on quick reactions and quick thinking. This appears valid for recreational athletes > 40 y of age but less valid for younger athletes. Well-trained, elite athletes may not notice any benefits beyond a placebo effect except possibly during times of increased physical stress.
In summary, P. ginseng supplements may enhance physical and mental performance if taken long enough and in sufficient doses. Ginseng may exert greater benefits for untrained or older (>40 y) subjects. Ginseng does not appear to exert any acute effects on physical performance. In general, ginseng supple- ments are safe, although individual variability exists and poten- tiation with stimulants such as caffeine may occur.
Siberian ginseng (E. senticosus or Acanthopanax senticosus)
Developed and studied by Russian researchers, Siberian gin- seng is only distantly related to the Panax species, with both being members of the Araliaceae family. Siberian ginseng con- tains unique steroidal saponins termed eleutherosides that appear to be structurally similar to, but are distinct from, Panax ginsenosides (14, 17). A review by Brekhman and Dardymov (17) of early Soviet research on Eleutherococcus preparations involving thousands of subjects from entire towns, schools, factories, and hospitals in field tests showed improvements in subjects’ work output and decreases in absences due to illness. These studies are difficult to interpret, however, because the data are almost inaccessible and the experimental designs are suspect. The results amount almost to epidemiologic findings, given the large number of subjects, but they offer only limited scientific evidence for the effectiveness of Siberian ginseng in improving human performance.
Other Soviet trials published in obscure symposia proceedings or Russian-language books were briefly reviewed by Walker (78) in a journal that was not peer reviewed. Improved muscular strength, resistance to fatigue, and recovery from exercise were reported for 35 weightlifters and wrestlers, 36 gymnasts, military personnel, 60 000 factory workers, and 52 laborers, but no exper- imental details were given. Thus, these results must be viewed with skepticism until more data become available.
Asano et al (79) administered 4 mL/d of an Eleutherococcus extract or placebo·to 6 baseball players for 8 d in a single-blind, crossover study. VO2max was significantly improved, but the order of administration of control, placebo, and Siberian ginseng meant that an order effect rather than an ergogenic effect may have been observed. In another study, McNaughton et al (53) administered 1 g/d of Siberian ginseng powder for 6 wk to 30 sub- jects and used a randomized, double-blind, placebo-controlled, crossover design. Fifteen female and 15 male athletes from the Tasmanian State Institute of Technology were studied. Pectoral strength was increased by 13% and quadriceps strength rose 15%, with both changes statistically significant. However,
V·O2max, heart rate recovery from exercise, and grip strength were unchanged by Siberian ginseng in a comparison with the placebo group.
Dowling et al (80) studied the effects of administering 3.4 mL of an Eleutherococcus extract for 6 wk in 10 elite distance runners, who were compared with a matched placebo group (compliance was verified). The Eleutherococcus extract did not affect run time to exhaustion, heart rate, lactate production, ventilation measure- ments, oxygen consumption, ratings of perceived exertion, or res- piratory exchange ratio. However, the authors stated that statistical power for measured indexes ranged from 0.16 to 0.52, casting great doubt on the ability of this study to detect any significant changes if they were present.
In 1996 a Siberian ginseng (Eleutherococcus) supplement identified as Ciwujia or A. senticosus (Endurox; Pacific Health Laboratories, Woodbridge, NJ) was heavily advertised as having caused a mean 43% increase in fat utilization and decreased blood lactate concentrations during graded cycle ergometry in 8 subjects (unpublished observations, 1996; see http://www.endurox. com/research). These results were obtained in China and publica- tion in the Chinese Journal of Hygiene Research was reportedly in press. However, in early 1999 the Endurox Web site had no new information on publication of the results, and thus these enticing findings still await critical examination.
Given the paucity of human studies and the poor or inadequate experimental designs for studies investigating Siberian ginseng and physical performance, inferences must be conservatively drawn. This herb appears to possess either no ability or just a limited ability to improve the aerobic performance of well- trained individuals, but in one study with 30 subjects it was asso- ciated with improved muscular strength in untrained and trained subjects alike. Like P. ginseng, a slow-acting effect may become more apparent after 8 wk of observation, a time period not reached in controlled studies but achieved in Russian field stud- ies. These conclusions must be considered as tentative until ade- quately controlled studies with sufficient statistical power and consistent identity and intake of eleutherosides are reported.
Mahuang (Chinese ephedra) and ephedrine alkaloids
Another important herb commonly used to enhance exercise performance is mahuang, or Chinese ephedra (Ephedra sinica). Ephedra species have a long tradition of use (>5000 y) for respiratory ailments (81). Unlike other herbs, the active ingre- dients are well characterized and consist of ephedrine and related alkaloids (mostly ephedrine, pseudoephedrine, nor- ephedrine, and norpseudoephedrine) (81). Synthesized ephedrine alkaloids are found in hundreds of prescription and over-the- counter pharmaceutical products as antiasthmatic bronchodila- tors, antihistamines, decongestants, appetite suppressants, and weight-loss aids (81–83).
Recently, dietary supplements labeled as containing ephedra sold outside usual channels of commerce and marketed specifi- cally to young adults to achieve a legal high, sexual ecstasy, euphoria, or increased energy have attracted considerable media and legislative scrutiny. In reality, these products are spiked with synthetic ephedrine alkaloids (ephedrine, pseudoephedrine, and phenylpropanolamine) and combined with other stimulants such as caffeine (Bucci, unpublished observations, 1997). Such prod- ucts are not comparable with either traditional Chinese herbal products or other dietary supplements that contain only ephedra herb or standardized extracts (usually with ≤24 mg ephedrine and related alkaloids per unit dose). Dietary supplement trade associations have issued guidelines for safe use of ephedrine- containing products that are followed by most major companies. Typical guidelines suggest no more than 25 mg of ephedrine alkaloids per unit dose and no more than100 mg total ephedrine alkaloids daily.
Ephedrine and related alkaloids are sympathomimetic agents that mimic epinephrine effects (81–83). Like other stimulants, they may cause adverse effects when used chronically and in sustained high doses (>100 mg/d), especially when overdosed. Nervousness, anxiety, heart palpitations, headaches, nausea, hyperthermia, hypertension, cardiac arrhythmias, and occasional deaths have occurred with ephedrine alkaloid overdoses (81–83). Dietary supplement products reported to the Food and Drug Administration as causing side effects have almost always con- tained large amounts of caffeine (150–300 mg per unit dose) (L Bucci, unpublished observations, 1997). Thus, particular caution must be exercised when consuming products containing both ephedrine alkaloids and caffeine.
Studies examining the effects of acute administration of ephedrine, pseudoephedrine, or phenylpropanolamine on exer- cise performance (time to exhaustion, muscular strength) in humans have shown no enhancements at usual dosages consid- ered to be safe (≤120 mg) (84–88). Sidney and Lefcoe (84)
administered 24 mg ephedrine to 21 males and found no signifi- cant differences, compared with placebo, in muscle strength, endurance or power, lung function, reaction time, hand-eye coor- dination, anaerobic capacity, speed, cardiorespiratory endurance,
V·O2max, ratings of perceived exertion, or recovery. Blood pres- sure and heart rate were slightly, but significantly, elevated and learning of simple psychomotor tasks was facilitated. Bright et al (85) found no significant changes in heart rate, blood pressure, glucose, or insulin after acute administration of 60 or 120 mg pseudoephedrine to 6 males undergoing submaximal exercise. Sinus arrhythmias were increased at the high dose.
In another study, DeMeersman et al (86) found no significant effects of acute ephedrine administration on fuel homeostasis, ventilation, oxygen consumption, heart rate, blood pressure, or ratings of perceived exertion in 10 subjects engaged in graded cycle ergometry. More recently, Swain et al (87) administered typical doses of pseudoephedrine (1 and 2 mg/kg) and phenyl- propanolamine (0.33 and 0.66 mg/kg) to 10 trained cyclists. Sub- jects underwent bicycle ergometer testing and urine drug testing after ingesting either placebo or the compound doses. There was no significant difference between trials for either compound in
V·O2max, ratings of perceived exertion, maximum systolic or diastolic blood pressures, peak pulse rate, or time to exhaustion. However, the 1-mg/kg dose of pseudoephedrine significantly raised peak systolic blood pressure by an average of 10.6 mm Hg. Urine concentrations of each compound were variable between subjects and persisted the day after exercise. Gillies et al (88) measured the effect of 120 mg pseudoephedrine or placebo on 1 h of high-intensity exercise (40-km cycle ergome- try) in 10 subjects in a randomized, double-blind, placebo-con- trolled, crossover study design with a nonexercise control period. Performance in a time trial or muscle function was not changed significantly by pseudoephedrine. Exercise caused increases in urinary concentrations of pseudoephedrine compared with those during resting states.
In summary, individual ephedrine alkaloids at doses greater than those found in herbal extract products resulted in no enhancement of physical performance. There remains a possibil- ity that mental functions were improved, which in effect would cause a placebo-like response in real-life settings such as sport- ing events or training sessions.
Combining ephedrine with caffeine has been associated with improvements in physical performance. Bell et al (89) studied 8 male subjects in a repeated-measures design with high-intensity exercise on a cycle ergometer. Placebo administration led to a 12.6 ± 3.1 min time to exhaustion, whereas 5 mg caffeine/kg (14.4 ± 4.1 min) or 1 mg ephedrine/kg (15.0 ± 5.7 min) alone caused nonsignificant increases in times to exhaustion. However, the caffeine-ephedrine combination significantly improved time to exhaustion (17.5 ± 5.8 min). Ratings of perceived exertion were significantly lower after the combination, but heart rate was significantly elevated after both caffeine and the combination. Caffeine and the combination increased lactate, glucose, glycerol, and free fatty acid concentrations, similar to other trials (1–4, 13, 82). Oxygen consumption, carbon dioxide production, minute ventilation, and respiratory exchange ratio were unchanged by caffeine, ephedrine, or the combination. Catecholamine availabil- ity was increased after the combination, suggesting central ner- vous system stimulation. Thus, the combination of ephedrine with caffeine, but not either compound alone, was associated with prolonged exercise time to exhaustion. The doses used are easily
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reached by doubling the serving size of typical sports supple- ments containing both ephedrine and caffeine.
In obese women consuming a low-energy diet, an ephedrine and caffeine combination (2 25 mg and 2 200 mg, respec- tively) increased heart ejection fraction during cycle ergometer exercise but not during rest (90). When yohimbine (2 5 mg) was added to ephedrine and caffeine, cardiac performance was attenuated during rest and cardiac work during cycle ergometer exercise was increased, whereas the ejection fraction was decreased. Yohimbine is sometimes added to dietary supple- ments containing ephedrine and caffeine to try to prolong effects or reduce possible side effects, such as increases in heart rate and blood pressure. In this study, ephedrine and caffeine only weakly affected cardiovascular measurements during rest or exercise, which corresponds with results of other studies.
Another aspect of ephedrine that is ignored in reviews on ergogenic effects is its documented thermogenic ability both without (91–96) and with (97–99) caffeine. This ability leads to reduced body fat during hypoenergetic diets in obese subjects (100, 101), especially when ephedrine is combined with caffeine (102–107), theophylline (108), or caffeine and aspirin (109–113). Some athletes (especially bodybuilders) want to maximize body fat loss while maintaining muscle mass, and frequently resort to supplements containing ephedrine and caffeine to aid in fat loss. Evidence from obese subjects has shown that lean mass is pre- served better with ephedrine-containing combinations during weight loss (103, 106, 114); obese subjects consuming hypoen- ergetic diets reproducibly showed increased loss of body fat from ephedrine-containing preparations. It is outside the scope of this review to describe in detail studies of ephedrine or caf- feine in weight-loss settings, and application to lean athletes or sports settings was not studied until recently.
An unpublished study examined the effects of a placebo meal, a meal with ephedrine and caffeine, and a meal with p-synephrine and caffeine on body temperature, metabolic rate, and other indexes for 195 min. Ten healthy, active females and 10 healthy, active males (recreational athletes) were studied in a randomized- order, double-blind, placebo-controlled, crossover study design (115). All active ingredients were from standardized herbal sources only, and they contained other herbal ingredients with hypothetical synergistic effects (yohimbe for yohimbine, Lede- bouriella divaricata, Schizonepeta tenuifolia, and quercetin). Ephedrine (24 mg) was from E. sinica, p-synephrine (10 mg) was from zhi shi or bitter citrus (Citrus aurantium), caffeine (300 mg) from guarana (Paullinia cupana) and green tea (Camellia sinensis), and yohimbine (12 mg) from yohimbe (Pausinystalia yohimbe) herbal extracts. In comparisons with the placebo meal, a signifi- cant increase in core body temperature (0.5C) was found for each herbal group. The ephedrine-plus-caffeine group showed a significant increase in metabolic rate, respiratory exchange ratio, heart rate, and blood pressure, whereas the p-synephrine-plus- caffeine group exhibited only a smaller increase in blood pressure and improved vigor on a Profile of Mood Survey. When results were extrapolated to 24 h, the p-synephrine group had a signifi- cant increase in resting metabolic rate. These findings suggest that herbal combinations containing ephedrine plus caffeine or p-synephrine plus caffeine and other herbs may reproduce short- term thermogenic and metabolic effects that are conducive to body fat loss; this conclusion is supported by results with other healthy volunteers and obese subjects given ephedrine, caffeine, or both in purified form. Other studies have verified that
ephedrine from purified or herbal (E. sinica) sources has equiva- lent bioavailability in humans (116, 117).
Ephedrine is a banned substance for amateur sporting events, and use of mahuang (Chinese ephedra) from dietary supple- ments is likely to disqualify athletes in drug-tested events. Recently, another herb, Sida cordifolia, was said to contain ephedrine alkaloids, but firm data on amounts are lacking, even from suppliers. Actual analysis of S. cordifolia has found vary- ing results. One report found ephedrine and related alkaloids (118) and another found the alkaloid vasicine, but not ephedrine (119). Thus, S. cordifolia and other Sida species may contain ephedrine alkaloids. It is not known whether ingestion of dietary supplements containing Sida herbs will cause a positive drug test in athletic events, but the possibility is likely.
A variety of other herbs and herbal combinations have been used to enhance physical performance, but few have been tested in human clinical trials. Rationales for use of other herbs as well as herbs that have already been reviewed are shown in Table 1. Other herbs generally fall into 1 of 2 categories: 1) adap- togen or tonic (ginseng-like) or 2) anabolic (increase muscle mass). Tonic herbs are presumed to enhance aerobic perfor- mance and anabolic herbs are presumed to mimic or be con- verted in the body into anabolic steroids, mostly for use in bodybuilding and weightlifting communities. Although anec- dotal and testimonial “evidence” abounds, the rationale for use of other herbs is strictly hypothetical, conjectural, or based on results of animal studies.
Administration of 1.5 g/d for 75 d of Rhodiola crenulata root extract led to increased work capacity (run time to exhaustion), V·O2max, and ventilation in a comparison with placebo (120). An unpublished study found that a combination of wild oats (Avena sativa), stinging nettle root (Urtica dioica), sea buckthorn (Rham- nus frangula), and vitamin C produced improvements in strength, anaerobic power, endurance time, and feelings of well-being (Exsativa; Swisstonic, New York, 1995). This investigation was a double-blind, crossover study that lasted 6 wk, but no experimen- tal details, including error or statistical analysis, were given, and thus no valid conclusions can be drawn. Walker reported Soviet tests with schizandra (Schisandra chinensis) that led to better 3000-m run times and tests with combinations of Siberian gin- seng and Aralia, Rhaponticum, Rhodiola, and schizandra that led
to better performance, but no details were given (78). Other adaptogenic herbs, such as ashwagandha (Withania somnifera), have shown antistress effects in animal tests (includ- ing swim times and anabolic activity) that were equal to or better than results with Korean ginseng (26). Interestingly, both ashwa- gandha and ginseng root powders were shown to contain starch. At the high doses (100 mg/kg) used in animal swim time studies, the results may have been due to carbohydrate supplementation rather than inherent effects of herbal constituents. This may be a good example of why animal research must be interpreted care-
fully before results are extrapolated to humans. Shilajit (mummio) is a tarry exudate from rock crevices found
at high altitudes in the Himalayas and Caucasus mountains that is derived from long-term humification of Euphorbia and Trifolium (clover) plants (121). Eastern European weightlifters have been using mummio as part of an “herbal anabolic stack” to promote better strength, recovery, and muscular hypertrophy. Traditional Ayurvedic use of shilajit as a tonic has some support from studies
Antioxidant activities in humans of selected herbs
Herb Reference Antioxidant compounds and activity
Tea (green, black, oolong) (Camellia sinensis) Ginkgo biloba
126, 127 7, 128
Epigallocatechin gallate, and theaflavin gallates, and thearubigens (flavonoid polyphenols): LDL oxidation, 8-hydroxyguanosine
Flavonoid glycosides and ginkgolide terpenoids: scavenge superoxides, hydroxyl radicals, nitric oxide, and oxoferryl radicals; peroxidation, LDL oxidation; and cyclosporin A-induced peroxidation
Glutathione, sulfhydryls, selenium: lipid peroxidation Procyanidins: lipid peroxidation LDL oxidation Procyanidins and resveratrol: LDL oxidation
LDL oxidation Silymarin flavolignan: LDL oxidation Lycopene: most efficient singlet oxygen scavenger Lutein: free radical scavenger
Garlic (Allium sativa) Maritime pine (Pinus maritima) Quercetin (many plants) Grape skins and seeds (Vitis spp.) Tannic acid (many plants) Milk thistle seed (Silybum marianum) Tomatoes 131 Green vegetables and marigold flowers 131, 132
129 130 127 127, 130 127
of the humic acids, fulvic acids, coumarins, and triterpenes that have shown antistress effects in animals (121). However, human data on this and other adaptogenic herbs are sorely lacking.
Other herbs or plant extracts are believed to provide or mimic testosterone-like (anabolic) effects in humans because of their similarity of chemical structure. These herbs contain sterols, ecdysterone, or steroidal saponins (Table 1). Anabolic effects are particularly sought by bodybuilders and weightlifters. With the exception of truffles, which contain trace amounts of a very weak androgenic steroid, androst-16-en-3-ol (122), there is no evidence to support the conversion of plant sterols to testosterone in the human body (122, 123). Possible steroid receptor effects from ecdysterone in animal studies (124) indicate that further study is necessary to rule out a possible effect of certain steroid-like com- pounds found in these herbs that is mediated by receptor or feed- back loop regulation rather than bioconversion into steroids. Possible mechanisms include anticatabolic effects from blocking cortisol receptors and stimulation of anabolic or androgenic steroid receptors, similar to that seen for ginsenosides.
An extract of Tribulus terrestris (Tribestan; Sopharma, Sofia, Bulgaria) has gained recent interest following promotional presentations of English language translations of Bulgarian pharmaceutical company research. Reportedly, the Tribulus extract elevated circulating testosterone and luteinizing hormone amounts that were depressed in men who were part of infertile couples (125). Until the original research becomes available for scrutiny, these results must be regarded with caution, and extrap- olations to normal, exercising individuals should not be made. In summary, hypothetical mechanisms, but a paucity of data in humans, characterize the known evidence for other herbs pur- ported to affect human physical performance.
Because consumers have access to a wide variety of herbal dietary supplements, and because there is some mechanistic research from in vitro or animal studies, future studies would be most pertinent if they would focus on outcomes important to consumers. These outcomes should include measurements of exercise performance (time to exhaustion, strength or torque changes for resistance training, changes in body composition, hormone concentrations, race times, mood changes, and neuro- muscular changes). Such studies should examine dose-response
curves, which are lacking for most herbal supplements. A neces- sary criterion is identification of hypothetical or known active ingredients, which should measure multiple types of marker compounds (eg, steroidal saponins and phenolic acid and total fiber). Herbs contain a wide variety of potentially active or sup- portive compounds in addition to the hypothetical active com- pounds that may provide important attributes not immediately apparent. Standardized herbal extracts, if extracted in a consis- tent manner, are the best type of material for studies at this time.
Instead of a single, very large study, a series of smaller studies with sufficient statistical power to evaluate performance measure- ments is probably the desirable approach and more feasible as well. In such studies, specific questions and concerns are more easily investigated and study populations can be better defined. As herbal supplements with apparent merit are identified, further detailed studies on mechanisms would be more efficiently performed.
Many herbs have well-documented antioxidant activities in humans (Table 3) (126–132). Whether these activities would affect human physical performance or protect human tissues from exercise-induced free radical damage is unexplored. However, given the protective effects shown by the essential nutrient antiox- idants (carotenoids, tocopherols, ascorbate, and selenium) during exercise in humans (133–135) and the performance-enhancing attributes of sulfur-based antioxidants (136–138), there is enough evidence to suspect that plant antioxidant preparations may have a similar ability and further studies are warranted. Combinations of herbs with vitamins, minerals, metabolites, or other herbs is another promising area of research that is virtually unexplored.
I suggest that a unified theory of the mechanistic actions of herbs will eventually become apparent. Major commonalities between herbs to investigate should include their 1) antioxidant effects, 2) hormone or other regulatory receptor effects, and 3) spe- cific enzyme inhibitions or enhancements. Combinations of the 3 may account for most of the effects seen for herbs.
SUMMARY AND CONCLUSIONS
Except for studies on the effects of ginseng, there is a dearth of controlled scientific studies on the effects of herbs or herbal extracts on human physical performance. Factors that have dis- couraged controlled investigations of herbs and physical performance include difficulties with taxonomic classification, identification and consistency of active components of herbs,
EFFECTS OF HERBAL SUPPLEMENTS ON PERFORMANCE 633S
variability in growing conditions, lack of dose-response data in humans, limited duration of response studies, lack of interest from funding agencies, negative bias from investigators, and eco- nomic disincentives for pharmaceutical exploration of unpatented natural products. As a result, much of the human research on herbs and exercise performance has occurred outside of the United States, which has prevented widespread dissemination of research results because of language barriers and inaccessibility of journals. Nevertheless, considerable research has been per- formed with humans with the various preparations of ginseng, which allows some conclusions to be drawn.
When doses of P. ginseng are given that resemble amounts used in traditional Chinese medical practice (3–9 g of dried root powder or equivalent amount of ginsenosides from standardized extracts) for durations of ≥8 wk, some aspects of performance, both physical and mental, may be enhanced or their decline pre- vented. However, the higher incidence of positive effects in phys- ical performance studies of subjects not living in the United States may reflect life-long differences in diet (such as food for- tification) (139) that would make ginseng more efficacious. Evi- dence for this idea is seen in studies using ginseng extracts com- bined with vitamins, minerals, and other metabolites (52, 54, 56).
Although Siberian ginseng (E. senticosus) and R. crenulata extracts both have at least one positive outcome in human stud- ies, the evidence is preliminary or contradictory at this time. Herbal stimulants, such as mahuang or its constituent alkaloids, do not appear to have affected physical performance signifi- cantly in a limited number of studies. However, a combination of ephedrine alkaloids with caffeine led to significant changes in performance and physiologic parameters over that obtained for either ingredient alone in several studies. Other herbs remain completely unstudied for outcomes on physical perfor- mance in humans.
In conclusion, a comprehensive literature review found that P. ginseng products taken with sufficient dosage (200–400 g/d of standardized P. ginseng root extracts containing ≥ 4% ginsenosides) and duration (≥8 wk) may prevent deleterious effects of overtrain- ing or enhance physical performance, especially in persons > 40 y of age. Recommendations include use by trained subjects undergo- ing continuous training or untrained subjects embarking on a stren- uous exercise program. In brief, herbal supplementation to enhance human physical performance has had little scientific study, but it represents a large and valid field for future study.
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