Garlic: The spice / herb is a bulbous perennial plant that grows about a meter high above the ground bearing pinkish, greenish or white flowers. The bulb inside the ground is arranged in cloves which are actually the useful ingredient but occasionally the greens are also used for cooking as vegetable. It is a native of Central Asia, Western China and Mediterranean. Its use is recorded since several millennia for both culinary and medicinal reasons. If crushed the bulbs release very strong characteristic smell widely perceived as the “garlic smell”. Until crushed the intact cloves within bulbs otherwise remain as odorless.
History of garlic use: The exact origin of garlic is noticed in Western China possibly at the Tien Shan Mountains of Kazakhstan and Kyrgyzstan. From there it is spread to the far eastern Asian regions like, Japan and Korean peninsula. According to the record, ~ 3000 – 2500 BC the Sumerians were using it for healing purposes. Around that period the Chinese used to use as anti-depressant so they included it in the category of Yang. But in Japan it was not much appreciated since Buddhists did not accept in their diet for its strong smell and stimulating effects. It is the reason why many Japanese cuisines lack in garlic. In ancient Indian medicine, garlic was frequently used to cure appetite, common weaknesses, cough, rheumatism, hemorrhoids and several skin diseases. In Vedas (Charak & Sushruta), garlic was categorized as one of the important medicinal plants. The use of garlic in regular diet was authenticated (~ 3200 BC) among the Egyptians especially forcibly introduced to the slaves during building of Pyramids for gaining strengths and energy. The Phoenicians, Israelis, Babylonians and Persians, mostly the people of desert, semi- desert and Mediterraneans, all regularly used garlics in their diet. In 7th century AD the Slavic people used garlic against lice, spider bite, ulcers and scabs. In the middle ages the Arabian physicians understood many of its remedial properties. From there it spread to the Western world. It arrived at Britain in 1548 AD from the Mediterranean voyage. It was later recommended against helminthes and its topical application was allowed curing various skin diseases including dandruff. Knowing its effectiveness, the English started its cultivation around 16th century believing further to have the aphrodisiac effect which is still unfounded. In France it saved a significant number of population in 1720 from the epidemic of Plague. The great Louis Pasteur discovered and published articles that garlic can kill the bacteria efficiently. He also confirmed that it can kill the Helicobacter pylori, a virulent stomach bacteria. The antiseptic property of garlic was confirmed further for its effectiveness in lowering the incidences of typhoid, cholera and diphtheria in several occasions. Later the French therapists recommended it also for preventing the spreading of influenza epidemic for its deterrent action against cough and flu. The identification of chemical contents of garlic was started from 1844. In 1944, Allicin, a colorless oily unstable compound was discovered which showed strong bactericidal property. Another component named Allin was isolated but it does not carry any smell also show no bactericidal actions. But adding the enzyme, Allinase from the fresh crushed garlic source it produces Allicin releasing the characteristic garlic smell. The medicinal properties of garlic are appreciated to be manifold particularly preventing coughs, common cold, heart diseases, cancers and number of others.
Chemistry behind the garlic odor and its metabolism: It is proven that the crushing of peeled cloves releases Allinase, an enzyme, that afterward while coming in contact with the sulfur containing compound Allin produces Allicin spreading the characteristic smell of garlic. The further breakdown products of Allicin also carry the similar smell. Allin [natural S – allyl cysteine sulfoxide having two anomeric centers with R – and S – configuration] is produced inside the cells of bulbs by natural process of alkylation with any allyl derivative followed by the subsequent intracellular oxidation of L- cysteine. Allin is somewhat transient and undergoes enzymic cleavage producing Allicin which is metabolized further to several sulfur containing fragments as seen in the animal studies but unfounded in the human even after ingestion of 25 gm of fresh garlic. This indicates that Allicin and its derived compounds could be quickly metabolized in the human and for that reason the level of volatile allyl methyl sulfide (CH2 = CH – CH2 – S – CH3) having strong smell increases in breath depending on the quantity of garlic consumption. It could be the final metabolite detected in human. But the consumption of aged garlic producing γ – Glutamyl-cysteine which is hydrolyzed to S – allyl cysteine and S – propyl cysteine in human can be traced in the urine. The ingestion of commercial garlic preparations that always possess S – allyl cysteine is ably traced in the human plasma.
The chemical & biochemical constituents of garlic: Followings are the major ingredients found inside the garlic cloves. Enzymes – Allinase, Peroxidase and Myrosinase; Sulfur compounds – Allin, Allicin, Di-allyl sulfide, Di – allyl tri-sulfide, Allyl methyl tri-sulfide, S – allyl mercapto cysteine, Ajoene, 2-vinyl-4H-1,3 dithiin, 2-vinyl-4H-1,2-dithiin, S- allyl cysteine, Allixin, Glucosinolates; Lipids – Phospho-lipids and glycolipids; Amino acids – Essential amino acids and higher level of arginine and higher levels of cysteine and methionine; Anthocyanins – Quercitin, flavone, aglycones, Kaempferol glycosides and Scordinins. Traces of Tellurium complexes are also identified in the garlic whose role is presumably the further anti-oxidants like its sulfur and selenium analogs.
Action of Allinase:
llin formation from L – Cysteine and its conversion to Allicin and other metabolites
Action of Myrosinase: This particular enzyme catalyzes Glucosinolate hydrolysis forming various isothiocyanates that has profound effect on the Phase-I biotransformation enzymes preventing cancers. Usually, most pro-carcinogens need biotransformation which is often catalyzed by the Phase I enzymes of cytochrome P 450 family in order to be activated to the actual carcinogens. Afterward carcinogens bind to the DNA inducing mutations imposing tumors or cancers. Inhibition of certain categories of cytochrome enzymes (CYP 450) especially those involved in the activation of pro-carcinogens would prevent developing any cancers which is confirmed by experiments using the animal models. The studies clearly pointed out that isothiocyanates can inhibit them efficiently. It is also noticed that among the smokers Phenyl ethyl isothiocyanate decreases the activation of pro-carcinogens found in the tobacco. Besides garlic, isothiocyanates are abundant among the cruciferous vegetables (broccoli, cabbages, Brussels sprouts, mustards, water cress, garden cress, Indian cress, radish horse radish etc).
The action of peroxidase: Normally peroxidases catalyze the reduction of H2O2 by accepting the electrons from various compounds during metabolism of flavonoids and other phenolic derivatives. In garlic the enzyme is involved in Quercitin catabolism and also lignification which occurs during cell wall formation.
Medicinal and biological effects of garlic: It has been documented that Mediterranean people have lower incidences and mortality from the cardiovascular diseases. The identified cause is noted to be due to the daily consumption of large amount of garlic in the diet. Numerous studies have proven the facts that organosulfur compounds play dominant roles by inhibiting cholesterol synthesis, platelet aggregation and some other factors related to the heart diseases. Further, those compounds wield profound antioxidant effects also by enhancing the glutathione synthesis. The additional antioxidant effects provided by the polyphenolics are also present in the garlic. Studies on extracts and many of the isolated components show immense health benefits, claiming to prevent the risks of cardiovascular diseases, several types of cancers and anti-bacterial actions in human. It is claimed that garlic as a whole exerts versatile beneficial actions in the body e,g; it boosts the immune system to fight against infectious diseases by bacteria and viruses (particularly effective against cold and flu), helps detoxification by eliminating the heavy metals, reduces prostate size during benign prostate hyperplasia (BPH), strengthens bone in women by elevating the estrogen level, helps maintain cognitive function for the elderly persons. All these could be possible due to super high level of antioxidants in this spice. Followings are the verifiable effects noted for garlic.
Prevention of cardiovascular diseases
A) Lowering of Cholesterol: A large number of studies using either intact garlic or its supplementation support the fact of low risk factors involved regarding the cardiovascular diseases which appears to be particularly effective among those having high level of LDL cholesterol. It is proven that garlic and many of its sulfur containing compounds (particularly effective S – allyl cysteine and Ajoene) decrease the cholesterol synthesis within liver by inhibiting HMG-CoA reductase and sterol 4 – α – methyl oxidase.
B) Effect on Platelet aggregation: The activation of circulating platelets is the major cause to initiate blood clots that finally leads to the heart attack or ischemic stroke. The clotting phenomenon obstructs the coronary and cerebral arteries which imposes the risks. Many organo-sulfur compounds of garlic inhibit the inflammatory enzymes like Cyclooxygenase (COX) and Lipoxygenase (LOX) that in effect decreases the production of Thromboxane thereby lowering the possibility of platelet activation and subsequent clot formation. The garlic derived compounds also prevent the production of other inflammatory signaling molecules produced by the white cells (macrophages) in circulating human blood.
C) Prevention of arterial smooth muscle cell proliferation: The migration as well as proliferation of inactive / dormant cells is thought to be another major cause behind the atherosclerosis and also narrowing of coronary arteries. The use of garlic having various organo-sulfur compounds acts as a good remedy while inhibiting those processes.
D) Effect on Blood pressure: The lowering of blood pressure by diet enriched in garlic is somewhat debatable because the significance to establish its validity swings at the borderline. Still there are certain claims for its validity. The lowering is a bit significant only for those suffering from high diastolic pressures compared to its systolic counterpart.
E) Effect on Atherosclerosis: Although the inhibition of platelet aggregation and lowering of LDL cholesterol by the garlic components has been established but still no significant differences concerning the data on atherosclerosis when compared to the placebo is ever detected. It is speculated that possible formation of Hydrogen sulfide (H2S) from the organosulfur compounds in vivo offers a cardio-protective action since the molecule is known to act as a good vaso-dilator.
Prevention of cancers:
Role on Gastric cancers: It is noticed that garlic consumption significantly lowers the risks (~ 50%) of gastric and colorectal cancers. The credibility largely goes to organosulfur compounds inside the garlic cloves. Various studies using large groups of subjects including many Asian nations show significant differences in the incidences of gastric cancers between the garlic and non-garlic eaters in their daily diet. Further it has been identified that infections due to several types of Helicobacter pylori increases the risks of gastric cancers. Intact garlic and some of its organosulfur compounds markedly inhibit the growth of H. pylori although it could not eradicate the bacteria completely.
Role on Colorectal cancers: A number of careful studies have proven the fact that, in case of colorectal cancers (adenomas) the risk is ~ 30% less among those who consume few cloves of garlic daily in their diet. Further, studies based on the results of sigmoidoscopy also shows that daily intake of garlic for nearly a year tends to reduce the size and recurrence of colorectal adenomas in substantial number of patients. A significant reduction in the tumor size is observed if aged garlic extracts are fed at higher doses (~ 2.4 ml / day) for a considerable amount of time (> 12 weeks).
Role of garlic derived chemicals behind cancer prevention: Organosulfur compounds derived from garlic provide number of physiologically active medicinal factors that find different ways to prevent the cancers. For example, behind the tumor reduction event, A) the inhibition of one of the Phase I biotransformation enzymes, CYP2E1 by di-allyl sulfide (CH2=CH–CH2–S–CH2–CH=CH2), a metabolite from garlic plays a significant role. B) The enhancement of Phase II biotransformation enzymes like Glutathione S-transferase or Quinone reductase by the actions of allyl sulfides especially the di-allyl-trisulfide (CH2=CH-CH2-S-S-S-CH2-CH=CH2) help prevent the tumor formation by promoting the elimination of carcinogens from the body. C) The increment of intracellular Glutathione synthesis is caused by organosulfur compounds of garlic which is possible due to the enhancement of a vital gene responsible during the synthesis while promoting the translocation of Nrf2 (transcription factor) to the nucleus and subsequent binding of ARE (Antioxidant response element) which in turn increases the transcription of ARE containing genes. The animal experiments using di-allyl sulfide proves the fact by enhancing the level of Quinone reductase. D) Cell cycle arrest – It is known that uncontrolled cell division is the characteristic of any cancers. In normal condition the cell cycles are uniquely regulated for secured DNA replication as well as segregation of chromosomes occurring before the cell division. Occasional damage often arrest the cycle intended for the repair of DNA. It is noticed that di-allyl di -sulfide, di-allyl tri-sulfide, Ajoene and S – allyl-mercapto-cysteine can successfully perform the act of arresting the cell cycle. E) Apoptosis – It is a normal physiologic event that occurs in order to self-destruct the aged or genetically spoiled unnecessary cells. It is proven that, cancer cells which are genetically altered are resistant to apoptosis therefore they proliferate uninhibitedly. Many of the garlic derived components like Allicin, Ajoene, di-allyl sulfides, di-allyl-disulfide, di-allyl-tri-sulfide and S-allyl-mercapto-cysteine can induce the apoptosis in many cancer cells while using the animal models.
Anti-microbial and anti-fungal actions:
Garlic extracts are known to possess anti-microbial properties. The active compounds are Allicin and few of its organosulfur components. But Allicin plays the dominant role. Several studies show that oral ingestion of garlic in human (raw or cooked) also produce significant effect. The randomized controlled trials while applying 1 % Ajoene cream on skin is shown to be effective in treating the fungus, Athlete’s Foot (Tinea pedis) which is comparable to 1 % Terbinafine (Lamisil) cream.
Drug interactions
he use of garlic or its supplements certainly provides a good deal of health benefits but the practice may cause some adverse effects within those who are taking the following medications.
Isoniazid – If undergoing treatment for tuberculosis then garlic would make the drug less effective.
Birth control pills – It would make the drug less efficient.
Cyclosporine – Immune suppressing drug used after organ transfer or for any other reasons would be less effective by the use of garlic.
Blood thinning agents – Warfarin (Coumadin), Clopidogrel (Plavix) or Aspirin are normally used as blood thinning agents to prevent blood clot. Garlic makes them more active thus enhancing the chances of bleedings.
Anti HIV / AIDS drugs – Garlic might lower their levels in the blood.
Nonsteroidal anti- inflammatory drugs (NSAIDS) – These are Ibuprofen, Naproxen or Aspirin. Garlic may increase the risk of bleeding while using those medications.