Modern Research on Turmeric
by Dr. Robert Keith Wallace
Turmeric (Curcuma longa) has been used for thousands years as a household remedy in both India and China. A relative of ginger, this tall plant is found in the forests and tropical regions of Southeast Asia. It has trumpet-shaped yellow flowers and its roots, rhizomes or bulbs, are used as both food and medicine. Turmeric is a key ingredient in many South Asian and Middle Eastern recipes. Marco Polo was said to have discovered it in 1280, and he believed it related to the more expensive saffron spice because of its yellow color. We now realize that turmeric is far more than merely a common spice. It is a super-food that has numerous beneficial effects for health.
Research on turmeric and especially curcumin (diferuloylmethane), its the active ingredient, is more extensive than almost any other natural product. It has been estimated that turmeric and curcumin have been the subject of over 5600 peer-reviewed and published biomedical studies, and there are 600 potential preventive and therapeutic applications, as well as 175 distinct beneficial physiological effects. (1). Most of the initial research on turmeric and curcumin has been done on animals and in the laboratory, but an increasing number of new studies are being done on humans. In September 2012, the U.S. National Institutes of Health had seventy-one registered clinical trials completed or underway to study curcumin for a variety of clinical disorders (2).
In Ayurveda, turmeric is known as Haridra and is said to decrease or pacify both Kapha and Vata dosha; also, due to its bitter taste, it pacifies Pitta, making it a tridoshic spice. Its tastes are pungent, bitter, and astringent, and its energetic effect is heating. Traditionally it has had numerous uses, for example, for problems in the liver, digestive and circulatory systems, congestion, and to help heal wounds and various skin diseases.
In western medicine the preventative and curative effects of turmeric have been ascribed to curcumin, the active ingredient in turmeric. Curcumin is a powerful antioxidant, anti-inflammatory and anti-cancer agent. It can turn off the genes that promote cancer, shrink cancer cells, and stop the growth of blood vessels that supply the cancer cells. Studies have shown that it can even enhance the effects of chemotherapy or radiation therapy in destroying cancer cells.
Research suggests that curcumin may help prevent or treat as many as 20 different types of cancers, including prostate, breast, and colon cancer. The reason curcumin is so effective against cancer is that it affects not a single target but dozens of targets and pathways involved in cancer (3-5). The incidence of the top four cancers in the United States—colon, breast, prostate and lung—is 10 times lower in India, where turmeric is regularly used in cooking, especially in curry dishes (6-7).
One of the best examples of the potential anti-cancer effects of curcumin is in breast cancer, which is highly resistant to chemotherapy, and is the leading cancer in women worldwide. Over 60 pre-clinical trials have shown that curcumin exerts anti-breast cancer activity in addition to enhancing conventional chemotherapy. For example, in one study it was shown to enhance the effects of two well-known chemotherapeutic agents, paclitaxel and docetaxel (8-11). This is an interesting example of integrative medicine in which natural products are combined with modern therapeutic treatments. The results showed that curcumin not only enhanced the effects of the drugs, but also reduced their adverse side effects. Numerous other studies have gone into the mechanism of why curcumin is potentially so effective against breast cancer (12-16).
Hundreds of studies have also shown promising results for the effects of curcumin on colon, pancreatic, cervical, lung, prostate, liver, esophageal, and skin cancers (17-27). Several studies have shown that curcumin can help in the prevention of the polyps that may lead to colon cancer (28,29). In one study, patients waiting for colorectal cancer surgery, when given curcumin supplements, were shown to have a number of improvements in their health as compared to a placebo (30). Prostate cancer, like breast cancer, is often resistant to chemotherapy. When curcumin is combined with chemotherapy the results are better (31). In the case of cervical cancer, curcumin eliminates papillomarvirus, which is its primary cause (32). One reason for this effectiveness may be because it is uniquely able to immediately attack multiple targets linked with cancer promotion. For example, it can simultaneously affect many cell signalling pathways, including those that mediate inflammation, survival, proliferation, invasion, and metastasis.
Studies at a number of universities have conducted independent research showing the positive effects of curcumin on cardiovascular health (33,34). Atherosclerosis, one of the major types of cardiovascular disease, has been linked to the inflammatory process, as well as platelet migration, abnormal oxidation, and lipid metabolism. The anti-thrombotic, anti-proliferative, and anti-inflammatory effects of curcumin, along with its anti-oxidant properties and its ability to both influence lipid metabolism and to inhibit platelet aggregation, suggests a protective role in cardiovascular disease (35-38).
Studies on animals show that curcumin can reduce atherosclerotic lesions, lower LDL or so-called “bad” cholesterol and trigycerides, andincreases HDL “good” cholesterol (39-41). Human studies have also shown a reduction in LDL cholesterol and an increase in HDL cholesterol (42-44). A study conducted at Ohio State University and using lower doses of curcumin in more absorbable form, showed lowered triglycerides and lowered inflammatory markers associated with heart disease, as well as an improvement in two other cardiovascular markers: an increase in plasma contents of nitric oxide, which helps lower blood pressure, and a decrease in the intercellular adhesion molecule linked to atherosclerosis. In addition, this study also revealed reduced plasma alanine amino transferase activity, a liver injury marker, as well as reduced beta-amyloid protein, one of the factors involved in brain aging and Alzheimer’s disease (45).
Several studies have shown the positive effects on cardiac hypertrophy. Researchers in both Toronto and Tokyo used animal models and it was found that if the animals were given a daily dose of curcumin they did not have the predicted enlarged heart or heart failure. Both of research groups found that the protective mechanism was due to curcumin’s remarkable ability to affect a type of enzyme called the Histone Acetyl Transferases, or HATs, which normally causes the increased production of inflammatory molecules (46,47).
Following coronary artery bypass surgery, patients in Thailand were given a curcumin mixture, and it was found that these patients had a decreased incidence of heart attacks that was more than two and half times less than patients who did not receive curcumin. Other measures of heart function, such as incidence of left ventricular dysfunction, were also dramatically improved and measures of inflammation were reduced. (48). In another study in Japan, researchers studied postmenopausal women who were given small doses of readily absorbed curcumin for 8 weeks. The group given the curcumin showed significantly improvement in several cardiovascular tests, with about the same benefit as those involved in regular exercise (49).
Alzheimer’s disease has doubled over the last 25 years, and it has become a major concern among the elderly. It seems to be triggered by the production of beta-amyloid protein, which clumps together and hardens, causing the accumulation of plaque between nerve cells. A number of different studies have confirmed that curcumin reduces the beta-amyloid and plaque burden and also improves cognitive performance in elderly individuals (50-52).
Curcumin also seems to act as a neuroprotective agent, slowing oxidation to neurons and causing a significant reversal in lipid peroxidation, as well as an enhancement of glutathione, an antioxidant that protects the brain (53-59). One of the unique features of curcumin is its ability to cross the delicate blood-brain barrier. A recent study at University of Michigan published in the Journal of Biological Chemistry showed that curcumin was able to prevent the destructive formation of another group of proteins called alpha-synuclein, which are linked to neurodegenerative diseases such as Parkinson’s and Alzheimer’s (60).
Both laboratory and animal studies have shown the effectiveness of curcumin for the treatment of both osteoarthritis (the destruction of the cartilage that covers and cushion the ends of the bones) and rheumatoid arthritis (an autoimmune disease that attacks the joints) (61- 65).Curcumin has been shown to markedly improve the progression and severity of arthritis by the regulation of the genes and biochemical pathways associated with chronic inflammation.
A recent study in India compared patients with rheumatoid arthritis who took either curcumin or a standard drug, diclofenac sodium, and the curcumin group was found to have significant improvements as compared to the drug group (66). Another study in Thailand looked at the effects of turmeric extracts in patients with osteoarthritis of the knee and compared it with ibuprofen, and again it was found that curcumin was effective in relieving both pain and mobility. This is a particularly important study since the curcumin treatment was found to be safe and without any of the ordinary side effects of standard drugs (67).
Turmeric and curcumin have also been shown to help other diseases and conditions such as: ulcerative colitis (69), liver disorders (70,71), HIV and other viral infections (72-74), indigestion (75), ulcers (76,77), diabetes (78,79), and eye problems. Further, curcumin compares favourably to a number of major drugs including: Lipitor, corticosteroids, Prozac, aspirin, diclofenac, and celecoxib (80). As we mentioned earlier, curcumin can be used to enhance the actions of both chemotherapy and radiation therapy in cancers.
We will not attempt to examine the hundreds of biochemical pathways and cell behavior that turmeric and curcumin influence, however, it is useful to appreciate at least some of the mechanisms by which they produce their beneficial effects. The field of epigenetics has revealed that many environmental factors can influence the turning on and off of genes that regulate key pathways that affect our health. For example, both cancer and chronic inflammation are conditions, which are not pre-programmed in our genes, but, rather, are triggered by environmental factors. As we have mentioned, curcumin is a powerful regulator of the genes involved in the promotion of both cancer and chronic inflammation. Let’s briefly examine how it affects the genes that are involved in chronic inflammation and cancer.
Inflammation is a useful biological process, which helps our body fight the invasion of bacteria and other microorganisms. If we have a simple cut in the skin, we almost immediately see swelling in that area. This swelling is part of the inflammatory pathways and allows more blood to flow to the injury bringing key immune cells that are able to fight invading bacteria. After some time we may then see the formation of pus, which is an indication that through the inflammatory process, these immune cells have been able to kill the bacteria. There are other aspects of the inflammatory process that involve the production of key chemicals and the migration of different immune cells. We now know that many major diseases such as heart disease, arthritis, autoimmune disease, and even cancer, may be initiated or provoked by chronic inflammation. One of the most important effects of curcumin is its ability to turn off certain genes and enzymes that are involved in this chronic inflammation process.
There is a particular protein complex called nuclear factor kappaB (NF-kappaB), which is involved in the expression of a number of key genes. When there is some malfunction in our system this complex can become overactive and the result is that certain genes in the inflammation process are chronically turned on at a low level of activity. Curcumin’s power lies in its ability to block this factor and thereby turn off the genes that promote the expression of pro-inflammatory factors, such as prostaglandins and cytokines. Curcumin accomplishes this by inhibit NF-kappaB activation at several steps in the NF-kappaB signaling pathways (81).
NF-kappaB factors also play a critical role in cancer. When improperly regulated NF-kappaB factors cause cancer cells to resist the natural process of preprogramed cell death control called apoptosis. Cancer is a result of both abnormally high proliferation as well as abnormally low cell death. Curcumin, by affecting NF-kappaB factors, restores the normal process of apoptosis and causes cancer cells to die. Curcumin also counters NF-kappaB ability to create more blood vessels that nourish a cancerous tumor (tumor angiogenesis).
In addition to curcumin’s ability to influence gene expression, it can also regulate the activity of enzymes such as COX-2 and MMP, which influence inflammation, proliferation, migration, differentiation, and apoptosis. It can affect cell cyclins, which helps regulate cell cycles and affect protein kinase B (Akt), which helps regulate proliferation and migration. In can influence cell adhesion molecules (CAMs), which govern how one cell binding to another and it can affect tumor necrosis factors (TNF), caspase proteins, and Bcl-2 regulatory proteins, which are also involved in the process of apoptosis (82).
One of the most important biological effects of turmeric and curcumin is their role as powerful antioxidants. Oxidation can cause damage to our physiology. We are familiar with the oxidation of metals, resulting in rust. In our own cells, oxidation results in the creation of compounds known as free radicals. These chemicals are highly reactive and can cause all sorts of problems, including the triggering the inflammatory process via stimulation of NF-kappaB and damaging our DNA. Curcumin can neutralize the effects of these free radicals molecules and thereby help prevent and cure the many diseases and disorders, which are either promoted or further complicated by unchecked free radical activity (83).
Therapeutic Use of Turmeric and Curcumin
Many researchers have proposed the use of turmeric and curcumin for improving the quality of health throughout the world (84). Clinical trials have shown that turmeric and curcumin are safe for humans even at high doses (12g/day) (85).
One concern noted by a number of researchers is that curcumin has poor bioavailability, either due to poor absorption into the system or because of its rapid metabolism and elimination (86). The bioavailability of curcumin has been improved by adding other substances to it, such as piperine, an extract of pepper (87). Other approaches include incorporating curcumin into artificial particles or delivery systems, such as nanoparticles, liposomes, micelles, and phospholipid complexes, which seem to increase its absorption and concentration into the blood and tissue (88-92).
This leads us to inquire if it is appropriate to isolate the active ingredient, curcumin, since there may well be other beneficial substances in turmeric that could interact synergistically with the curcumin to increase and enhance its effects? This is an important question for any natural substance and requires further investigation and research. The isolation of curcumin from turmeric is not in accord with the principles of traditional medicine, but it is part of the scientific process. It also means that a smaller amount is needed to produce a measurable biological effect. For example, in order to take a recommended dose of 500 milligrams of curcumin per day, it would be necessary to consume approximately 2 tablespoons of dried turmeric powder and traditional Ayurveda would never recommend such a large quantity—unless it was prepared according to Ayurvedic principles. The reason for this is, that according to Ayurveda, turmeric is both heating and drying, and because of these properties it could overheat and damage the liver unless taken in combination with certain other substances and spices. For example, to counter its drying effect it could be cooked with ghee (clarified butter), and to counter its heating effect it could be combined with a more cooling herb, such as coriander. Ayurveda has its own pharmacology, called Dravyaguna, which offers an understanding of the unique properties of each herb. It is hoped that the field of integrative medicine will thoroughly investigate and make use of the time-tested principles of Dravyaguna and integrate them into their recommendations for the use of turmeric.
The final step for the approval of turmeric or curcumin into our modern health system. involves the Food and Drug Administration or FDA. Before any substance is advertised or prescribed as a drug that can be used to treat or cure a particular disease it must go through a series of tests and clinical trials. The conclusive phase III clinical trials can cost billions of dollars. Drug companies make the investment needed for these trials based on their expectation of receiving a large return on their investment once the drug is approved. Turmeric, however, is a natural product that is freely available at a very low cost, so there is no incentive for a drug company to make this investment. The very system we have created to protect us from the adverse side effects of modern drugs makes the approval of natural products extremely difficult. While the current research on turmeric and curcumin is very promising it will be necessary, under the current system, for these expensive phase III trials to be conducted before the medical establishment can formally acknowledge and recommend this remarkable spice.
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