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Understanding Turmeric Anti-Inflammatory effects and Its Clinical Use.

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 Understanding Turmeric Anti-Inflammatory effects and Its Clinical Use. Page 1

Understanding Turmeric Anti-Inflammatory effects and Its Clinical Use.

Marcela Di Savoia R.N. B.Sc.

Research 501 Assessment and Integration of Research

American College of Healthcare Sciences

May 11, 2014

 Understanding Turmeric Anti-Inflammatory effects and Its Clinical Use. Page 2

Abstract

Background:

Turmeric (Curcuma Longa) one of the most widely researched rhizomatous herbaceous plant,

has been effectively utilized in its native India for thousands of years. However in these last one

hundredth years, Turmeric has captured the attention of western medicine for its anti-inflammatory

effects with the bulk of its clinical studies having taken place since the early 70’s.

Objective:

This research paper objective is to bring clinical based evidence to both practitioners and

consumers as to how Turmeric really renders its anti-inflammatory effect in the body, why it’s

effective on inflammatory conditions and what is the best way of delivery for optimal absorption.

Methods:

Research of computerized literature was performed to identify clinical placebo-controlled trials

of Turmeric (Curcuma longa). Databases searched were Med-Line and Cochrane Library. Double-

blind, placebo controlled studies were chosen that utilized subjects with chronic inflammatory diseases

especially that of the digestive system.

Results:

Turmeric Anti-Inflammatory effects were confirmed up to 85% of success throughout the

various databases, after review of information from the controlled clinical studies. Research also

yielded information on how to best utilize Turmeric supplements based on its absorption rate.

Conclusion:

I was able to consolidate solid scientific information based on clinical evidence to bring a better

understanding as to how Turmeric supplementation must be used, and for what type of inflammatory

conditions its use is most optimal.

 Understanding Turmeric Anti-Inflammatory effects and Its Clinical Use. Page 3

Introduction

There is no doubt to the efficacy of Turmeric (Curcumin Longa), in its medicinal properties,

especially of its anti-inflammatory use. Its use has been well documented in India through the use of

Ayurveda well before any western research study had ever been done. Turmeric (Curcumin Longa) is a

fairly risk free rhizomatous herbaceous perennial plant that has been used for centuries in food, Ayur-

vedic medicine and as a component ingredient of many other products used in the body such as

coloring, liniments, cosmetics etc..

In reviewing the average herbal books however, and even some more conventional medically

inclined herbal books such as in example The Physicians’ Desk Reference (PDR) for Herbal

Medicines, they all seem to fail to give a deeper understanding of how and why Turmeric is effective

as an anti-inflammatory agent in the human body and the research behind it.

Since the early 70’s, focus was placed on Turmeric’s’ anti-inflammatory use and many clinical

studies (NYU, 2012) took place in India as well as other places such as Thailand and China. Study

documentation and publishing soon caught the attention of countries such as England, France and the

United States, which in turn conducted clinical studies of their own.

Much of the clinical research test done supportive the results of its anti-inflammatory

properties, but at times fail to address the actual mechanism by which Turmeric yielded particular

results.

Journal published materials are often reviewed by scientist, field physicians and research

advocates making the conclusions of the studies on Turmeric as well-established herb which

effectiveness in its anti-inflammatory effects has become a reality for many. To this effect many in the

conventional medicine world, pharmaceutical world and other herbal supplementation companies have

jumped on the van wagon of this ‘wonder herb supplement’.

 Understanding Turmeric Anti-Inflammatory effects and Its Clinical Use. Page 4

However, what about the average consumer who will most likely never take an interest in

reviewing journals of medicine both conventional or complementary to establish an educated decision

of how to treat their inflammatory condition appropriately with Turmeric, with the adequate dosage

and if in fact Turmeric is the right herbal product to take for a particular type of inflammatory

condition.

Practitioners as well as consumers often rely on direction from labels and insert. Seldom

questioning the information, consumers take it and practitioners recommended or prescribe it, falling

prey to many unscrupulous fabricants who may not be utilizing the best possible process for Turmeric

to be actually effective, because they do not understand the basic mechanisms of action of Turmeric in

the body.

There is much clinical study evidence of its anti-inflammatory effects, but minimal

understanding as to how Turmeric interacts with our bodies. It will be my objective through this

research paper to establish information through the analysis of the body’s inflammatory process and

how Turmeric works on a cellular level to achieve the anti-inflammatory response for which Turmeric

is presently well known for.

Hopefully this information will give the reader a deeper understanding on how Turmeric binds

with our body, thereby empowering the reader to also make an educated decision on how to best

approach the purchase and use of this herb in its natural or supplemental form.
 Understanding Turmeric Anti-Inflammatory effects and Its Clinical Use. Page 5

Methods

Research of computerized literature was performed to identify clinical placebo-controlled trials

of Turmeric (Curcuma longa). Databases searched were Med-Line and Cochrane Library. Double-

blind, placebo controlled studies were chosen that utilized subjects with chronic inflammatory diseases

especially that of the digestive system.

There was no discrimination in the population block utilized in terms of age, sex, gender or

culture. Clinical studies utilized were not only from the United States and are no older than twenty five

years, these were studies published by verifiable journal publications. In addition to this computerized

search, other publications were utilized to substantiate the information about the plant in terms of

cultural, historical and medicinal use.

The number of controlled clinical trials chosen were narrowed down to ten, since those selected

met the criteria and had clear data about the potency, dosage in relation to the use in the medical

conditions outlined and the results validated the potency of Turmeric in relation to the mechanism of

absorption in the body.

Main Proposed Uses of Curcumin:

• Ulcerative Colitis, Dyspepsia (Indigestion), Crohn's Disease, Gallbladder,

Additional Proposed Uses of Curcumin:

• Diabetes, High Cholesterol, Depression, Alzheimer’s disease, Rheumatoid Arthritis,

Osteoarthritis, Chronic Anterior Uveitis and Multiple Sclerosis.

Keywords:

Turmeric, Curcuma Longa, Curcumin, Clinical Trials, placebo controlled, Anti-Inflammatory

Effects, Inflammatory Response. Anti-inflammatory action, anti-carcinogenic, anti-mutagenic, anti-

thrombotic action, anti-microbial action, anti-viral action, anti-parasitic action and hepatic-protective

action.
 Understanding Turmeric Anti-Inflammatory effects and Its Clinical Use. Page 6

Discussion

In Ayurveda, a traditional natural medicinal practice of India, Turmeric (Curcumin Longa)

known in India as Haridra, Gauri has been prescribed for ailments affecting the digestive, respiratory

and urinary system via the circulatory system (Ayurveda Encyclopedia, 2005) which means that it’s a

substance that must be ingested in order to render effect. If we analyze what the digestive, respiratory

and urinary system have in common, in relation to the circulatory system, we have to understand the

different type of tissues that make up the body. In the human body there are four type of main tissues

the epithelial, connective, muscle and nervous tissue.

Organs in the body most usually share a bit of all four type of tissues, however some organs are

made up of more of a particular type and in the case of the digestive, respiratory and urinary system the

four are made of epithelial tissue that is highly vascular (Siumed, 2007). By design, tissue needs to

have vascularity in order to be supplied with the adequate nutrients, oxygen, red blood cells and white

blood cells, therefore a strong and non-occlusive circulatory system is essential in order to maintain the

tissue healthy and intact. It’s ultimately through the circulatory system that the delivery of nutrition or

supplements will help decrease the inflammatory process in the body.

In order to understand how Turmeric anti-inflammatory agents works, one must also understand

the basics of the inflammatory process in the body, how Turmeric chemical properties interpolate with

the bodies anti-inflammatory process, why Turmeric is recommended mostly for particular systems in

the body more so than others, how does the absorption of Turmeric works in the body and ultimately

how to utilize Turmeric to yield the most medicinal effect possible.

Understanding the inflammatory process in the body:

The inflammatory process of the body can be summarized as a response of the body to injury,

infection or irritation; the inflammatory response can start as a result of damage or injury, exposure to

bacteria, and virus, it can also be a result of the ischemia, inadequate intake of nutritional factors,

toxins and exposure to extreme temperatures or radiation. The typical inflammation we know and
 Understanding Turmeric Anti-Inflammatory effects and Its Clinical Use. Page 7

recognized is when we actually are able to visualize signs of redness, swelling, pain and heat in the

body. However, there are other type of inflammatory process that occur internally in our bodies, this

type of inflammation is often referred as the “silent inflammation” (Sears, 2007), this kind of

inflammatory process occurs in the body with or without signs or symptoms perhaps for many years

before they actually appear.

The inflammatory process occurring in the internal systems or organs can be caused by many

factors that create impaired epithelialization such as nutritional deficiencies, inadequate circulation or

oxygenation of tissues causing hypoxemia, and the frequent use of certain drugs in the body that lower

the immune system such as in the case of the use of steroids as an example.

When internal inflammation in the body occur, we can utilize certain makers to measure

inflammation. Measuring the level of C - reactive protein (CRP) produce and released by the liver is

the most common type of blood test utilized to determine the level of inflammation, and along with the

CRP there are also other indicators in the blood that indicate an increase in inflammation such as the

elevated erythrocyte count and sedimentation rate, (Clyne & Olshaker, 1999). All these indicators are a

result of the increase of neutrophil production in the bone marrow that are caused by the increase of

cytokines proteins otherwise known as cell communicators when an inflammation occurs.

The Inflammatory response has various mediators which kick the response itself, mediators

include Histamine response, Prostaglandins P GE 2, and PGI2, Bradykinin, Serotonin and

Leukotrienes. In the case of Turmeric, the mediator in which its two main curcuminoids ensures its

work is with the Prostaglandins and Leukotrienes in the body.

Currently there are also other indicators to this “silent inflammation”, and that is the

measurement of Arachidonic acid (AA) ratio to Eicosapentanoic acid (EPA), it’s presumed that this

ratio can warn a person well in advance to the development of a degenerative or chronic condition

(Schacky, Fischer & Weber 1985). AA and EPA both have an essential fatty acid interaction which

allows the body to signal each other in the presence of inflammation, to collaborate and help inhibit the
 Understanding Turmeric Anti-Inflammatory effects and Its Clinical Use. Page 8

inflammatory process via vasodilation, especially in the muscles, liver and brain which is where most

is mostly found and metabolized. These type of essential fatty acids are abundantly found in the

Omega-3 fatty acids, according to The US National Institute of Health MedlinePlus (NIH, 2013) but

what makes it interesting in relation to Turmeric, is that Turmeric chemical properties work in

repressing Arachidonic Acid ration to decrease inflammation while aiding Eicosapentanoic acid to also

decrease inflammation therefore making each curcumoids substance in Turmeric a balancing act in the

control and decrease of inflammation, this very same action in Turmeric has yielded results in research

to suggest that it is an effective treatment in helping the body lower inflammation and in addition it

helps improve chemotherapy response in patients.

 How Turmeric composition interpolate with the bodies anti-inflammatory process:

Turmeric molecular formula of C21 H20 O6 yields two main curcuminoids, Curcumin

Demethoxycurcumin and Bisdemethoxycurcumin (Cayman Chem, 2010), both curcuminoids have

been extensively studied in pre-clinical studies utilizing animals, and time after time. Turmeric

chemical properties have yielded jaw dropping results its anti-inflammatory effects and even inhibition

of certain cancerous cells.

Turmeric anti-inflammatory chemical properties come from its derivatives of the hydroxyl and

phenol groups molecules, these molecules have been shown to be essential in the inhibition of

prostaglandin synthetase and leukotrienes synthesis (Kohli,.; Ali.; Ansari & Raheman,2005).

Prostaglandin synthetase, simply refers to the process in which the group of lipid compounds derived

from the fatty acids of the Prostaglandin are catalyzed by enzymes, breaking them down to a molecular

level to produce energy derived from the process itself.

Leukotrienes synthesis on the other hand, refers to the forming of complex substances deriving

from the Leukotrienes which are formed in the leukocytes and other immune cells to mediate

eicosanoid inflammatory substance by way of oxidation of arachidonic acid. Together the

prostaglandin synthetase and leukotrienes synthesis form by far one of the most potent anti-
 Understanding Turmeric Anti-Inflammatory effects and Its Clinical Use. Page 9

inflammatory process in the tissue, which is why the Turmeric chemical properties work so

wonderfully in the body to reduce inflammation.

 Turmeric application to clinical studies:

In these last thirty years, Curcumin has finally been the center of actual clinical studies among

different populations. PubMed has over three hundredth thirty six research clinical studies reports over

these past ten years, most of them centering on the effects of Curcumin in the use of its chemical

properties in relation to anti-inflammatory effects focusing on various chronic inflammatory conditions

that deal with the digestive, respiratory and urinary system its progression into cancer and how

Turmeric is utilized to decrease inflammation and therefore also aiding in the treatment of some

cancers, (Turmeric info, 2009) most recently researchers have attributed the main components of

Turmeric Curcumoids (diferuloylmethane), exhibiting the inhibition and proliferation of various types

of tumor cells and in some cases producing a cytotoxic effect to these cancerous cells (Oxford Journals,

2001).

Various pharmaceutical companies have now isolated both Demethoxycurcumin and

Bisdemethoxycurcumin and both are now being further studied in different types of cancerous

conditions. (Cayman Chem, 2010) Bisdemethoxycurcumin has been found to act in the process of

phagocytosis of macrophages and interacting with Vitamin D3 it also acts as an amyloid-β

macrophages clearance which is substantial in the suppression and proliferation in cancer. In addition

Demethoxycurcumin also suppresses proliferation in cancer cells by regulating the coactivator

transcriptional process suppressing the pathway and inhibiting lipopolysaccharide from which

cancerous cells feed from. Therefore, Turmeric disrupts cancerous chemical processes that can

instigate propagation of the malignancy.

Other studies conducted by the immunology department in Boston University indicate that

Turmeric has shown to slow down cellular replication of HIV in laboratory animals and is currently
 Understanding Turmeric Anti-Inflammatory effects and Its Clinical Use. Page 10

under investigation in humans (Sabinsa, 2010) and may indeed play a role in the therapeutic treatment

of HIV.

Another important feature of Turmeric is its effect as an antioxidant in the body. The chemical

properties of Turmeric (Sabinsa, 2010) having clinical tested to prevent the buildup of free radicals

responsible for injuring tissue, much of this effect acquiescent in the cardiovascular and cerebral areas.

For the purpose of formulating and meeting the objective of this research paper, to establish

relevant information in regards to the cellular process of Turmeric in our bodies, and in order to be able

to utilize the recommended guidelines through the analysis of the dosages in the clinical studies (as

described prior in the methods section), I have limited the use of the data to that which addresses only

chronic inflammatory conditions in the digestive system which is what has been treated traditionally in

Ayurvedic medicine, and have not placed emphasis in the data used in relation to cases of Diabetes,

High Cholesterol, Depression, Alzheimer’s disease, Rheumatoid Arthritis, Osteoarthritis, Chronic

Anterior Uveitis and Multiple Sclerosis, which are other conditions that currently are also treated

through the use of Turmeric, in Complementary Alternative Medicine.

Conclusions

Turmeric as demonstrated in various studies through the effects of Demethoxycurcumin and

Bisdemethoxycurcumin (Srivastava; Dikshit; Srimal & Dhawan, 1985), both are inhibitors of platelet

aggregation, therefore maintaining the vascular system with a healthy flow and protecting humans from

strokes and heart attacks. This was also a focus of a study (Mishra & Palanivelu, 2008) among

populations in two different regions in India that consumed more curry than the other, not only was

there a significant decrease in heart attack and strokes by 60% percent, but in addition another very

important finding was that Alzheimer’s disease was found to be about 79% less in the population

where curry was also consumed. Since a strong circulatory system is essential in order to maintain the

tissue healthy and intact as established prior, then it makes perfect sense that Turmeric not only
 Understanding Turmeric Anti-Inflammatory effects and Its Clinical Use. Page 11

delivers the curcumoids to decrease inflammation, but it does this by maintaining a healthy flow in the

vascular system.

In the review of the ten clinical studies utilized to formulate the information in this research

paper, it was found that one of the greatest challenge in the utilization of Turmeric, was the poor

absorption and solubility rate in the body. According to UCLA professor, Greg Cole higher dosage are

to be utilized in the treatment of conditions (UCLA, 2008), because of the poor solubility and

absorption of Turmeric curcumoids. In addition according to Anderson M.D. who conducted a 10 year

study, he mentions that it’s important to understand that to increase absorption of the Curcumin Longa

into the body at a cellular level, there needs to be a certain way that Curcumin needs to be processed

for better absorption. There are certain other ingredients (Pantry TV, 2012) that can be utilized to

increase the rate of absorption in the body such as adding pepper. In addition because of the poor oral

absorption in relation to serum concentration, the need to utilize higher dosages of Turmeric causes

many of the participants to experience increased gastro-intestinal bowel movements and bile

production, to eliminate these side effects clinical researchers have focused their attention on

developing ways to increase absorption without the need to utilize high doses.

For instance in (Dulbecco &Savarino, 2013) the Journal of Gastroenterology recent findings

demonstrate that there is a new lecithin formulation that enables to increase absorption 29 times higher

than traditional Turmeric products, in addition a new technology called phytosome allows the

Curcumins in Turmeric to become water soluble with the Phytosomes making the absorption through

the bio-membranes in the body easier to reach the circulatory system.

 Turmeric use implication

Since many chronic inflammatory conditions go on for many years, even before sign and symptoms

occur, often this repetitive inflammatory process or constant exposures to irritants cause permanent

damage in normal cell reproduction and eventually cells molecular formation becomes damaged. The

inflammatory process becomes chronic and the immune system is overwhelmed and actually starts to
 Understanding Turmeric Anti-Inflammatory effects and Its Clinical Use. Page 12

work against the body, this is when cell apoptosis occur and cancerous cells are formed and multiplied

in an uncontrolled cellular division process (Anto; Mukhopadhyay; Denning & Aggarwal1, 2001),

eventually resulting in the demise of a particular organ tissue. Therefore it’s safe to assume that the

utilization of Turmeric (Curcumin Longa) decreases the chronic inflammatory episodes in the

digestive, system thereby potentially aiding in the prevention of cancerous cells from forming and

multiplying.

The dosages of clinical trials utilized in the treatment of chronic inflammatory disease, the

utilization and the most effective means of delivery of Turmeric in order to yield the most medicinal

effect possible are further discussed in the conclusions and recommendations portion of this paper.

Turmeric is not only an herb utilized in Ayurveda or other complementary disciplines but now has

become a mainstream, well studied substance utilized in conventional medicine. Its applications are

constantly being tested and its components Demethoxycurcumin and Bisdemethoxycurcumin have

been isolated to the degree where each component is being tested and utilized presently in the treatment

of various types of cancer, especially those of the Gastro-intestinal system.

Recommendations

In the analysis of the various clinical research studies, and with the well-established fact of its

clinical results in terms of the legitimate effect in the body; the clinical use of it now becomes the focus

in establishing recommendations in its use. It’s valid to state that Turmeric (Curcuma Longa) is indeed

most effective in its anti-inflammatory use, especially that of the Gastro Intestinal inflammations and

additionally serving as an agent of cancer prevention. Its use as an additional therapeutic agent in

conjunction with other cancer treatments is presently well documented. In addition, it is being used as a

preventative medicine agent for optimal circulatory system health and its effects is also showing

promising effects in the use of inflammatory process in Alzheimer’s. For the purpose of this paper

though the clinical indications and dosage, as well as contraindications have been limited to the Gastro-

Intestinal (GI), Pulmonary and Urinary systems with the majority of them going to the GI system as it’s
 Understanding Turmeric Anti-Inflammatory effects and Its Clinical Use. Page 13

the system that has been most clinically tested in relation to the use of Turmeric, which includes the

gall bladder, liver, stomach, pancreas, and intestines.

 Safety / Side Effects:

There are no real contraindications to the use of Turmeric as the Food and Drug Administration has

label it under the food category and has given the approval and status of ‘Generally Recognized as

Safe’ (GRAS) in the United States and approves it consumption up to 20 mg per serving (FDA, 2014).

However, most recently the FDA has listed Turmeric in doses utilized for Cancer preventative model

dosages of a Dietary administration of ethanolic turmeric extract in for 14 days, in percentages that

surpass the usual dosage for consumption and are generally quite high, these have been found to have a

hepatotoxic effect in mice and have produced coagulative necrosis in cells of liver (FDA, 2014). These

results are not substantiated by any clinical research that has been done by human consumption, but

warning is always granted for those patients with liver conditions or susceptible to liver conditions.

There are no side effects to the ingestion of the standard dosage of Curcumin utilized as a

preventative supplement or treatment of mild inflammation. However people with gallbladder chronic

problems should avoid using it more than once a day since Turmeric intake increases contractions in

the gallbladder, thereby increasing bile release (Rasyid & Lelo 1999). People receiving standardized

cancer treatment should consult with their physician, however in the clinical trials, subjects received up

to 8 g/day for four months with no results of toxicities, (Antony; Benny & Kaimal 2007). However in

these trials, subjects did not have any prior indication or history of liver problems. Long term use

though is not recommended with doses higher than 10,000 mg and should be closely monitored by a

health care provider.

 Dosing:

According to the Recommended Daily Intake, Dietary Reference Intake (DRI), Curcumin can be

utilized 400-600 mg three times a day (NIH, 2014), it’s recommended to be taken with food to avoid

gastro-intestinal distress. The 2008 issue of the journal Biochemical Pharmacology reports the safe use
 Understanding Turmeric Anti-Inflammatory effects and Its Clinical Use. Page 14

of higher doses of turmeric, especially in cancer patients, but it should be closely monitor for liver

toxicity. The best indication that you are taking more than what you need is if you continue having

symptoms of nausea, vomit, and diarrhea. If this symptoms are present, it’s recommended to lower the

dosage, especially if there is no real chronic inflammatory condition going on and it’s being taken as a

supplement.

 Rate of absorption:

The rate of absorption is a real issue when it comes to the consumption of Turmeric, since Turmeric

bio-viability is low once it enters into the digestive system. If Turmeric is taken by itself without any

having gone through any special process or added ingredients to aid in the absorption, 80% of it will be

secreted in feces and urine and therefore traditionally higher doses have been administered.

Currently though along with clinical studies dealing with its effects, many pharmaceutical

companies or supplemental preparation companies have also been doing research of their own in

formulating ways for Turmeric to be absorbed more effectively. For example, Bioperine (Sabina, 2009)

which is the main component of black pepper aids in the rate of Curcumin absorption up to 80% more

than without it. Utilizing black pepper by itself along with Turmeric increases the rate of absorption by

60%. Theracumin (Integrative Therapeutics, 2014), has been one Turmeric supplementation that has hit

the market with great success among many Naturopathic Doctors (Trutt, 2013). The supplement itself

is treated by chemically vaporizing it and chemically stabilizing the derived components, rendering the

absorption rate up to 90% according to blood level test performed. There are other preparation houses

that are utilizing Lecithin to increase absorption levels, according to them up to 95% rate of absorption

(Healthy Source, 2012).

Some pharmaceutical companies have actually isolated the two main curcumoids in Turmeric

for Scientific studies, especially in the area of Oncology. Demethoxycurcumin and

Bisdemethoxycurcumin (Cayman Chem, 2010), these two components are not usually available to the
 Understanding Turmeric Anti-Inflammatory effects and Its Clinical Use. Page 15

public, but are almost 100% absorbed in the system once used and therefore higher doses can be

effectively utilized in clinical trials.

Summary

After copious research, I have not only learned about Turmeric (Curcuma Longa) more

intimately, but also have a solid understanding how it should be utilized and for what type of

conditions its use is most optimal. In conclusion, I have established a solid link between legitimate

clinical trials results and scientific data through the explanation of how the physiology of the body and

the chemical process of Turmeric work to yield its anti-inflammatory effect, giving the reader whether

a clinician or a consumer, valid information based on evidence based medicine. The information

presented herein, is given primarily to help make a more judicious choice and decision on the health

intervention of a client utilizing Turmeric supplements. Ultimately is about bringing scientific based

facts in to give a better understanding to the consumer or providers on the properties of Turmeric and

its clinical effects in a more comprehensible manner.

 Understanding Turmeric Anti-Inflammatory effects and Its Clinical Use. Page 16

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