Role of green tea as an antioxidant in periodontal disease: The Asian paradox.

Green tea is a popular beverage nowadays and intake of green tea polyphenols has shown preventive effect against cancer and cardiovascular disease in experimental and epidemiologic studies. Several studies have suggested that green tea catechins, such as epigallocatechin gallate, inhibit periodontal pathogens and reduce the destruction of periodontal tissue. This paper aims to review the role of green tea in inflammatory diseases, especially in periodontal diseases.

INTRODUCTION

Green tea has been consumed throughout the ages in India, China, Japan, and Thailand. Today, hundreds of millions of people drink tea around the world, and studies are now suggesting that green tea (Camellia sinesis) in particular has many health benefits. Numerous biological effects of green tea and its constituents have been reported. These include anti-carcinogenic activity, anti-inflammatory effect, the alleviation of cardiovascular disease, etc. This review aims at describing the various benefits of green tea in general and the role of it in periodontitis in particular.[1]

PERIODONTAL DISEASE AND OXIDATIVE STRESS

Periodontal disease is a chronic disease that is more prevalent in adults. The incidence and progression of periodontal disease is related casually to periodontal pathogens, as well as to various host and environmental factors. The aberrant response is characterized by exaggerated inflammation, involving the release of excess proteolytic enzymes[2] and reactive oxygen species (ROS).[3] A growing body of evidence implicates oxidative stress in the pathobiology of many human diseases and recently in periodontitis. Several studies have demonstrated increased levels of biomarkers for tissue damage induced by ROS in periodontitis patients relative to controls.[4-6] Eating habits and nutritional intake affect periodontal disease. Health interest has therefore re-emerged in the relation between antioxidant micronutrients and periodontitis.[7]

Reactive oxygen species

Healthy periodontium is characterized by steady formation of ROS. These species include oxygen-derived free radicals [superoxide (O2¯), hydroxyl (OH), and nitric oxide (NO)] and non-radical derivatives of oxygen [hydrogen peroxide and hypochlorous acid]., Therefore, they are highly toxic and destructive in nature and have been implicated in the pathogenesis of over 100 conditions including periodontal disease.

A free radical may be defined as “any species capable of independent existence that contains one or more unpaired electrons.” Free radicals occur naturally in the body, but environmental toxins (including ultraviolet rays from the sun, radiation, cigarette smoke, and air pollution) also give rise to these damaging free radical particles. Free radicals are the damaging compounds in the body that alter cells, tamper with DNA (genetic material), and even cause cell death. The direct role of oxygen radicals in microbial killing is well established. Free radicals have been implicated in interleukin (IL)-1-induced osteoclastic bone resorption.

The removal of ROS by antioxidant defense systems is essential for healthy periodontium. Antioxidants scavenge the free radicals. The balance is maintained between oxidants and antioxidants. Under pathologic conditions, a disturbance in favor of ROS production results in oxidative stress. Antioxidants may be regarded as "those substances which when present at low concentrations, compared to those of an oxidizable substrate, will significantly delay or inhibit oxidation of that substrate." Antioxidants function either by preventing oxidative stress by literally scavenging radicals as they form or by sequestering transition metal ions and preventing Fenton reactions or by catalyzing the oxidation of other molecules.[8]

PLANT DESCRIPTION

There are three main varieties of tea - green, black, and oolong, all derived from the leaves of the C. sinensis plant. The difference between the various teas lies in their processing. Green tea is prepared from unfermented leaves, the oolong tea leaves are partially fermented, and black tea is fully fermented. Fermentation leaches out some of these beneficial ingredients. As green tea is made from unfermented leaves, it contains the highest concentration of powerful antioxidants called polyphenols.[9]

POLYPHENOLS AS ANTIOXIDANTS

Antioxidants such as polyphenols in green tea can neutralize the free radicals and may reduce or even help prevent some of the damages they cause. The healthful properties of green tea are largely attributed to polyphenols, chemicals with potent antioxidant properties. The antioxidant effects of polyphenols appear to be greater than those of vitamin C. Polyphenols contained in teas are classified as catechins. Green tea contains six primary catechin compounds: catechin, gallaocatechin, epicatechin, epigallocatechin, epicatechin gallate (Ecg), and epigallocatechin gallate (also known as EGCg). EGCg is the most studied polyphenol component in green tea. The scavenging capacity of catechin and epicatechin molecules depends on their hydrogen donating ability. It is demonstrated that polyphenols have inhibitory effect on the ROS generation as well as on the release of lysosomal enzymes.

Green tea also contains alkaloids including caffeine, theobromine, and theophylline. These alkaloids provide green tea's stimulant effects. l-theanine, an amino acid compound found in green tea, has been studied for its calming effects on the nervous system. Green tea also contains carotenoids, tocopherols, ascorbic acid (vitamin C), minerals such as chromium, manganese, selenium or zinc, and certain phytochemical compounds. Most green tea dietary supplements are sold as dried leaf tea in capsule form. There are also liquid extracts made from the leaves and leaf buds. An average cup of green tea contains between 50 and 150 mg polyphenols (antioxidants).[10]

REVIEW OF LITERATURE ON GREEN TEA

Green tea has been extensively studied in people, animals, and laboratory experiments, and has been useful for many health conditions.

A study by Cellular and Molecular Life Sciences found that “a new potential application of epigallocatechin-3-gallate has a role in the prevention or treatment of inflammatory processes.”[11] In May 2006, researchers at Yale University School of Medicine looked at more than 100 studies on the health benefits of green tea. They pointed to what they called an “Asian paradox,” which refers to lower rates of heart disease and cancer in Asia despite high rates of cigarette smoking. They theorized that 1.2 L of green tea that is consumed by many Asians each day provides high levels of polyphenols and other antioxidants.[12] These compounds may work in several ways to improve cardiovascular health, including preventing blood platelets from coagulation and improving cholesterol levels. Specifically, green tea may prevent the oxidation of low density lipoprotein (LDL) cholesterol, which, in turn, can reduce the buildup of plaque in arteries. Theaflavin-enriched green tea extract can be used together with other dietary approaches to reduce low density cholesterol.[13]

A study suggested that the oral intake of l-theanine, an amino acid found in green tea, could cause anti-stress effects via the inhibition of cortical neuron excitation.[14] Antioxidants in green tea may prevent and reduce the severity of rheumatoid arthritis.[15] A German study found that an extract of green tea applied externally to the skin for 10 minutes, three times a day, could help people with damaged skin from radiation therapy (after 16-22 days).[16]

A study concluded that the ingestion of catechins might be useful in the prevention and improvement of lifestyle-related diseases, mainly obesity. Green tea has thermogenic properties and promotes fat oxidation beyond that explained by its caffeine content per se. The green tea extract may play a role in the control of body composition via sympathetic activation of thermogenesis, fat oxidation, or both.[17] In lab tests, EGCg, found in green tea, was found to prevent HIV from attacking T-cells. However, it is not yet known if this has any effect on humans.[18]

An epidemiological study indicated that drinking green tea reduced the risk of esophageal cancer in Chinese men and women by nearly 60%. University of Purdue researchers recently concluded that a compound in green tea inhibits the growth of cancer cells. Many studies have demonstrated the inhibitory effects of tea preparations and tea polyphenols against tumor formation and growth. This inhibitory activity is believed to be mainly due to the antioxidative and possible antiproliferative effects of polyphenolic compounds in green and black tea.[19] The results obtained from a study suggested that fluoride in green tea may play a role in increasing the cariostatic action in cooperation with other components in tea.[20]

GREEN TEA AND PERIODONTITIS

The gingival crevice, a readily formed space between the gums and the tooth margin, typically contains a large number of microbes, the majority of which are anaerobes. In periodontal disease, the space enlarges to become a pocket, with local infiltration, an increasing number of polymorphs and serum exudates. Oxidative stress plays an important role in the pathogenesis of periodontal disease as well as many other disorders. Anaerobic black pigmented bacteria such as Prevotella spp. and Porphyromonas gingivalis are intimately associated with periodontal disease.[10]

Previous in vitro studies showed that green tea catechin inhibits the growth of P. gingivalis, Prevotella intermedia, and Prevotella nigrescens. It inhibits the adherence of P. gingivalis onto human buccal epithelial cells. In addition, green tea catechins with the steric structures of 3-galloyl radial, epigallocatechin gallate (EGCg), Ecg, and gallocatechin gallate, which are major tea polyphenols, inhibit the production of toxic metabolites of P. gingivalis. A study showed that green tea catechins, EGCg and Ecg, inhibit the activity of P. gingivalis-derived collagenase.[1] In addition, EGCg inhibited osteoclast formation in a co-culture of primary osteoblastic cells and bone marrow cells, and induced the apoptotic cell death of osteoclast-like multinucleated cells in a dose-dependent manner. Recently, EGCg has been shown to inhibit the activity and expression of collagenase or gelatinase [matrix metalloproteinase (MMP)-2 and MMP-9]. Studies suggested that EGCg caused the reduction in MMP activities by inhibiting the gene expression of MMP-2 and MMP-9 by suppressing the phosphorylation of extracellular signal regulated kinase (ERK) in cancer cells. The protein kinase belongs to the mitogen-activated protein kinase (MAPK) family of enzymes, which is known to regulate MMP expression. Furthermore, several studies have provided evidence suggesting that EGCg inhibits MAPK, resulting in the downregulation of MMPs.

Bone resorbing activity of osteoclasts plays a crucial role in bone resorption. EGCg, with its ability to inhibit the formation of osteoclasts, might have the potential to be used in the treatment of bone diseases such as periodontitis. Furthermore, it has been reported that EGCg could induce the apoptotic cell death of osteoclasts. However, the biological effect of EGCg on alveolar bone destruction has not been documented. These findings suggest that P. gingivalis may contribute to the alveolar bone loss observed in periodontal diseases by stimulating host osteblastic cells to produce MMP.[21]

A recent study evaluated the relationship between intake of green tea and periodontal disease and found that there is modest inverse association between intake of green tea and periodontal disease. The intake of green tea was inversely correlated with mean pocket depth, mean clinical attachment level, and bleeding on probing.[1] Green tea catechin local delivery system using Hydroxypropylcellulose (HPC) strips showed that it is absorbed by oral epithelial cells in the subgingival pocket and may inhibit the growth of bacteria. Continuous application of green tea catechin has been shown as an effective method for improvement of periodontitis.[22]

Kaneko et al. found that a 4-week regimen of mouth washing with a dilute catechin solution reduced the halitosis associated with periodontal disease.[23] It was subsequently established that tea catechins deodorized methyl mercaptan, the main cause of halitosis.[24]

RECOMMENDED USAGE OF GREEN TEA

Depending on the brand, two to three cups of green tea per day (for a total of 240-320 mg polyphenols) or 100-750 mg per day of standardized green tea extract is recommended.[25] There is evidence that dietary components rich in polyphenols cause tooth staining. However, there are no studies available establishing the relationship of green tea consumption and tooth staining. Caffeine-free green tea products are available and are recommended.[26]

PRECAUTIONS

Herbs contain active substances that can trigger side effects and interact with other herbs, supplements, or medications. However, pharmacological and toxicological evidence does indicate that green tea polyphenols can in fact cause oxidative stress and liver toxicity in vivo at certain concentrations. Patients on Warfarin should not take green tea as green tea contains vitamin K. Green tea should not be taken with aspirin because it prevents platelets from clotting. In people who drink excessive amounts of caffeine (including caffeine from green tea), it may cause nausea, vomiting, diarrhea, headache, and loss of appetite, and so it should be avoided.[25]

CONCLUSION

Various studies suggest that there is a modest association between daily intake of green tea and its preventive role. Drinking green tea at meals is a relatively easy habit to maintain a healthy periodontium. In order to improve the success rate in the treatment of periodontitis, usage of green tea is a novel approach aimed at early intervention, enhancing the host resistance and inhibiting the inflammatory mediators involved in the onset of gingivitis and periodontitis. However, mechanical plaque control, non-surgical and surgical periodontal therapy are the gold standards in the treatment of periodontal disease.More studies are necessary to fully elucidate and better understand green tea's method of action, particularly at the cellular level. The evidence is strong that green tea consumption is a useful dietary habit to lower the risk for, as well as to treat, a number of chronic diseases including periodontitis.