– Causes of inflammation
Inflammation is a complex biological reaction and compromises of both acute inflammation and chronic inflammation. Acute inflammation is a natural part of the healing process and usually lasts no longer than a 24 hours. Chronic inflammation is a serious ailment which can cause pain and may lead to other diseases including cancer. Although there are many mediators for the development of inflammation, a primary mediator is cyclooxygenase-2 (COX-2). This is an enzyme that makes prostaglandins that cause inflammation, and blocking the production or action of this enzyme alone can significantly reduce inflammation (Navtej S. Buttar et al, 2003). Another significant attribute to inflammation (although to a lesser extent than COX-2) is lipoxygenase (LOX), which is required for the synthesis of leukotrienes, key mediators of inflammation. The action of both COX-2 and LOX in causing inflammation is both well documented and well understood.
– Turmeric and Inflammation
The evidence that turmeric can prevent and reduce inflammation is both thorough and extensive. One paper reviewing the anti-inflammatory properties of turmeric in six human trials found that in all studies turmeric was found to inhibit the action of a large number of pro-inflammatory agents including phospholipase, lipooxygenase, cyclooxygenase 2, leukotrienes, thromboxane, prostaglandins, nitric oxide, collagenase, elastase, hyaluronidase, monocyte chemoattractant protein-1 (MCP-1), interferon-inducible protein, tumour necrosis factor (TNF) and interleukin-12 (IL-12) (Chainani-Wu N, 2003). Dosages used in these trials were 1.25g-8g/day, which indicates that effective dosages can be obtained from levels which can be obtained from diet, although it will be difficult. These findings are further supported by research conducted by Menon V.P et al in 2007 which specifically investigated the relationship between consumption of turmeric and cyclooxygenase-2 (COX-2) and lipoxygenase (LOX). The study demonstrated that turmeric had a profound ability to inhibit both enzymes. Both cyclooxygenase-2 (COX-2) and lipoxygenase (LOX) are pro-inflammatory enzymes which are known to contribute to chronic inflammation as well as certain types of cancer. By reducing the actions of these pro-inflammatory enzymes turmeric will reduce inflammation at the site of production. These enzymes are not the only causes of inflammation, but are primary contributors to the ailment, and drugs which specifically reduce their action reduce inflammation. The inhibition of COX-2 and LOX by turmeric appears to be primarily at a transcriptional level, and so prevents the enzymes being synthesised as opposed to inhibiting their action in the body (Rao C.V, 2007).
Research into the individual components of turmeric have also been investigated. The finding of the research showed that a combination of several of the components of turmeric was more effective than the curcuminoids alone at inhibiting PGE2. While curcumin inhibited COX-2 expression, turmeric oils (which only contain fat soluble nutrients of turmeric) had no effect on levels of COX-2 mRNA (R.C. Lantz, 2005). This suggests that taking turmeric extracts will not be as effective at preventing inflammation as taking whole turmeric.
Reducing Oxidative Stress
– Causes of Oxidative Stress
The body is exposed to oxidative stress from the environment, from toxins produced by pathogens and from natural biological functions such as respiration. Oxidative stress is caused by unstable molecules called radicals, which readily react with other molecules in the body – damaging them. Oxidative stress on the body is responsible for contributing towards the development of a vast number of ailments including the development of cancer and cardiovascular diseases, and so protecting the body against reactive species is important to maintain a healthy body. The body protects itself from these reactive species by the immune system and dietary antioxidants. The immune system creates enzymes which are capable of neutralising vast numbers of radicals, where as antioxidant compounds are only capable of savaging a small number before requiring to be recycled.
– Turmeric as an antioxidant
Turmeric contains a soluble compound called turmerin and lipid soluble compound called curcumin, both of which have demonstrated potent antioxidant properties in vitro (Hari H.P et al, 1998). Curcumin is a member of the curcuminoid family of polyphenols which are unique to turmeric, and turmerin is a antioxidant peptide which is found in turmeric. Both compounds have a typical antioxidant structure, which readily allows a hydrogen ion to be released without becoming unstable.
Human studies have supported the antioxidant capacity of curcumin, and shown that curcumin has the same protective effects against hydrogen peroxide as the fat soluble vitamin E in renal epithelial cells (Hari H.P et al 1998). These findings have been further supported in other human studies, and have demonstrated that curcumin can neutralise a number of harmful radicals such as N3·, Br2−··, CCl3O2 glutathione radicals (Sujata M. Khopde et al, 1999) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) (Ya-Jing Shang et al, 2010) throughout the body. As these are a number of human trials supporting curcumin as an antioxidant, and a strong understanding of the mechanism by which it acts we can confidently say that curcumin offers antioxidant protection.
In vitro studies on turmerin have shown that turmerin offers significant protection for cell membranes and DNA against induced oxidative stress, which was shown to prevent mutagenic activity (Leela Srinivas et al, 1992). This supports Hari H.P et al, but this study was in vitro and so may not translate the same to in vivo. Further in vitro studies have supported the findings of Leela Srinivas et al, and have demonstrated that turmerin can also prevent neurological degeneration by protecting neurons from oxidative damage (Ke Cui et al, 2004) but there are no human trials to solidify these findings. However, it is a reasonable assumption that turmerin will act in the same way in humans. In vitro, its antioxidant properties have been replicable with use of a variety human cells demonstrating it can be utilised effectively in the cell. This does still need to be confirmed in human studies, and its integrity needs to be investigated after oral administration.
– Turmeric inducing antioxidant enzymes
Aside from containing the antioxidants curcumin and turmerin which will directly protect the body from oxidative stress, turmeric can also protect the body via an indirect pathway which has the potential to be more powerful than its direct protection. Studies in humans have shown that turmeric supplementation administered orally can increase the production of superoxide dismutase and catalase by 30% and 54% respectively (Sally K. Nelson et al, 2006). These enzymes are responsible for neutralising reactive oxygen species such as superoxide and hydrogen peroxide, and so by up regulating the production of these enzymes you will be significantly increasing your protection. These enzymes are regulated by Nrf2, and it has been demonstrated that curcumin is an activator of this pathway (Giudice et al, 2006) and (Surh et al, 2008).
The most common health benefit claim of turmeric is its benefits to the liver, and the primary reason for this is the induction of antioxidant enzymes (as discussed above). The extent of liver protection has been demonstrated in animal models where liver damage has been caused via iron-induced lipid peroxidation in rats (A.Ch. Pulla Reddy, 1994). The findings consistently shown that turmeric lowers lipid peroxidation in the liver. Studies in animals do not always translate to humans with the same effects, however, with ethical and moral constraints involved with inducing damage in human cells there have been no human studies to confirm these findings. These findings are further supported with in vitro evidence using human liver cells which had ethanol induced cytotoxicity which also showed turmeric reduced liver peroxidation.
There is limited but promising evidence that turmeric (thought to be due to the curcumin) can increase the levels of xenobiotic enzymes, which are most abundant in the liver (V. K. Goud, 1993). These findings showed that UDPGT was significantly elevated and GSHT registered a significant increase in 5-10% in rats fed 10% turmeric. By increasing these enzymes turmeric can reduce the damage of foreign compounds on the liver, and increase the rate at which the liver can process these compounds.
Digestive Health and Turmeric
Helicobacter pylori (H.pylori) is a pathogenic bacteria which infects the stomach of approximately 50% of the UK population. It burrows into the cell lining of the stomach and produces a range of toxins which cause inflammation, discomfort and can lead to serious illness and the bodies immune system cannot kill it. Infection by H.pylori is strongly associated to peptic ulcers and stomach cancer. One of the bodies response to H.pylori is increasing the levels of NF-κB at the area of infection. NF-κB is a protein which regulates the immune response of inflammation, and regular stimulation is associated with stomach cancer. Research has shown that NF-κB response in blocked by the consumption of turmeric (Anna Foryst-Ludwig et al, 2004). This will reduce inflammation in the area and reduce the development of stomach ailments such as peptic ulcers. It was shown that the active component in this investigation was curcumin, which makes up to 95% of curcuminoids in turmeric. As this study was conducted in humans it has a strong relevance to other humans infected, and turmerics ability to reduce inflammation is also thoroughly understood (see above).
Curcumin has also shown in a number of studies to posses anti-bacterial properties against H.pylori, but the extent of this is still undetermined. The results of these studies vary from having the symptoms of infection completely alleviated to partially alleviated (Chuchart Koosirirat et al, 2010). These studies have been conducted in both humans and animals, and both had had varying results (Ronita De, 2008). In order to eradicate H.pylori the recommendation is still to take OAM (Omeprazole, Amoxicillin and Metronidazole) treatment, but it is thought to be more effective when taken alongside turmeric.
It is clear from research that curcumin does inhibit the proliferation of H.pylori, but it would appear that other variables also contribute to the extent. Never the less, curcumin will contribute to stomach health, and by suppressing the population of H.pylori will aid with preventing peptic ulcer/ stomach cancer development.
Apoptosis in Cancer Cells
Turmeric can help to prevent the development of cancer by reducing oxidative stress, reducing inflammation and reducing pathogens (as discussed above), but its most potent anti-cancer properties lie in its ability to induce apoptosis in established cancer cells (Anerjee, Ranajit K. 2004). Human studies have focused primarily on breast cancer and colon cancer, with only a few studies on various other types of cancer. These studies have revealed that turmeric induces apoptosis in cancer cells by increasing the expression of Bax, cytochrome C, p53 (Tathagata Choudhuri, 2002) and p21 but inhibit the expression of Bcl-2 (Ching-Cheng Su, 2006). These studies have been conducted in human trials, have been replicated and the mechanism is well understood. It is also well known that turmeric can influence gene expression in the body which further supports these findings.
Turmeric’s anti-cancer properties can only be attributed to colon cancer and breast cancer with any certainty as this is the area the majority of research has been conducted on. However, other research on other types of cancer such as leukemia (Min-Liang Kuo, 1996) and prostate cancer (Dorai T, 2000) have all shown similar results, which strongly indicates the potential that turmeric can induce apoptosis in a vast number of cancer cells.
There is very strong and extensive research which shows that turmeric can effectively reduce inflammation and provide antioxidant protection via 3 pathways (fat soluble curcumin, water soluble turmerin and inducing antioxidant enzymes). Liver health, which turmeric is often attributed to, can be improved, and it has been shown that turmeric can reduce lipid peroxidation in the liver. There is also evidence to show turmeric can stimulate xenobiotic enzyme production, but more research is needed to confirm this. Turmeric has also shown to be able to reduce the proliferation of H.pylori, but as the research is inconclusive as to the extent of this inhibition which suggests more research is needed to fully understand the interaction. Turmeric does however aid to improve stomach health as it can reduce the effects of H.pylori which will reduce the risk of developing related diseases such as stomach cancer and peptic ulcers. Turmeric can reduce the risk of cancer by the mechanisms discussed above, and can also induce apoptosis in established cancer cells. There is strong evidence for this in colon cancer and breast cancer, and preliminary studies have also indicated that these results are likely to be very similar in other types of cancer.
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