Friday, March 26, 2010


Big Pharma, which is a popular name for massive pharmaceutical companies, are always on the lookout for new drugs. While many such drugs appear to be new and revolutionary in their curative powers, it’s also true that many provide a plethora of potentially serious side effects. Indeed, a pharmacology adage states that unless a drug produces possible side effects, it won’t work. Many of the new drugs that appear on the market are often synthesized versions of natural compounds, whose efficacy can be traced back in history. Of the 877 small molecule drugs introduced between 1981 and 2002, 61% can be traced back to their origins in natural products. Despite this, modern science often downplays the usefulness of such natural compounds in favor of the more isolated drug compounds. In developing countries, however, natural compounds have an established history of success. Surveys reveal that 80% of the people living in such countries depend more on natural products to meet their health care needs. Even in the United States and other developed nations, people are turning more to natural compounds, feeling that such naturally derived substances are both safer and even more effective than many drugs routinely prescribed by doctors.

This focus on the health benefits imparted by natural substances had resulted in the popularity of formerly esoteric plant compounds, such as various herbs. Green tea, which was the topic of a recent Ironman feature, is an example of a natural substance with pleiotropic effects. The term “pleiotropic” refers to a substance that provides various beneficial effects. Another natural plant substance, also recently featured in Ironman is resveratrol, found naturally in red wine, peanuts, and other foods. While drugs often target just one effect, the natural compounds affect many body functions in a beneficial way, and thus offer a multitude of potential health benefits.

Another emerging natural substance is curcumin, which is derived from a spice called turmeric. Turmeric is an ingredient in curry, a popular spice consumed in Asian countries, particularly India. The curcumin content of curry is what imparts the yellow color to curry. This yellow color of turmeric, with its high curcumin content, is also used as a food coloring in cheese, butter, and other foods, so it’s likely that you at some point have ingested some curcumin. Turmeric has been around a long time, with use dating back to 600 B.C. Marco Polo, writing about his travels in China in the 13th century, described turmeric. Turmeric is related to ginger, and is cultivated mainly in southeast Asia. The active ingredient of turmeric is curcumin, which comprises 2 to 5% of the spice.

While turmeric has long been a popular spice in Indian cuisine, more recently the medicinal properties of its active ingredient, curcumin, has been extensively investigated. Some of the benefits attributed to turmeric/curcumin include:
• Prevention of digestive disorders- turmeric induces the flow of bile, which is required for the digestion of dietary fats and absorption of all fat-soluble vitamins.
• Arthritis and joint pain- Curcumin provides potent anti-inflammatory and antioxidant activity, both of which serve to relieve and protect joints.
• Cardiovascular disease protection- curcumin may help prevent the onset of cardiovascular disease through various mechanisms
• Cancer- preliminary animal and test tube studies show that curcumin may help prevent the occurrence of various types of cancer, again through a variety of mechanisms.
• Brain protection- While the incidence of the dreaded Alzheimer’s disease is rising in the United States, people in India where curry is a popular food additive, show less than a 1% incidence of Alzheimer’s in those over age 65. Curcumin may also provide antidepressant effects
• Improved exercise recovery and sparing of muscle tissue- Preliminary studies of curcumin show that it may blunt exercise-induced muscle damage, allowing for more rapid recovery between workouts. Through its potent anti-inflammatory effects, curcumin may help prevent excess muscle catabolism.

One thing to keep in mind about turmeric/curcumin is that the majority of studies that show beneficial results have involved animals and isolated cell studies. The same is true for other natural compounds, such as resveratrol. On the other hand, it’s also true that the suggested beneficial effects promoted by curcumin have plausible scientific mechanisms, and indirect evidence, such as the low rate of Alzheimer’s in India, and the effects produced in animals, are highly suggestive that these effects can be replicated in humans.

How does curcumin work?

As noted, curcumin is the active ingredient of the spice, turmeric. It works its health magic through a variety of pathways. For one, curcumin provides potent anti-inflammatory effects through blocking the activity of nuclear factor kappa beta (NFKB). NFKB can be viewed as the conductor of all inflammatory reactions in the body. It’s known as a transcription factor, in that when produced in the body, it signals the release of a host of various inflammatory chemicals, such as cytokines, kinases, and others. The fact that curcumin seems to offer preventive effects against so many diseases is explained by the fact that most degenerative diseases, including cardiovascular disease and cancer, have an underlying inflammatory cause. A lack of sufficient antioxidant activity also contributes to inflammation and subsequent disease, and curcumin works in this regard, too, offering antioxidant activity comparable to vitamins C and E.

A recent study found that curcumin exerts its effects through a previously unknown mechanism. Many diseases, including cancer, are induced through unstable cellular membranes. Cellular membranes, when working properly, act as the cell’s gatekeeper, allowing beneficial substances in, and preventing the entry of toxic substances that could harm the cell. Anything toxic that penetrates into the cell can induce damage to the nucleic acids in the cell, leading to cell mutations. This, in turn, can result in anything from cancer to death of the cell. In addition, having effectively operating cell membranes also promotes increased efficacy of hormone receptors in the membrane, thus allowing such hormones as testosterone, insulin, and others to interact with the cell receptors that allow them to work in the cell. It turns out that curcumin increases the stability and orderliness of cell membranes.

The strength of curcumin is that it interacts with so many biological targets in the body. Thus, it can bind to and inhibit the activity of many enzymes, growth factor receptors, metals, and other molecules. Among the proteins that curcumin binds to is beta amyloid, a protein in the brain. When beta amyloid binds excessively, nerve damage results, which is thought to be the underlying cause of Alzheimer’s disease. By downgrading the activity of enzymes called kinases, curcumin prevents the formation and spread of cancerous tumors in the body. Since cancer also has an inflammatory component, curcumin works in this regard by blunting the activity of inflammatory enzymes, such as COX2. This enzyme works by converting the arachidonic fatty acid derived from food into inflammatory eicosandoids that are linked to pain and inflammation. Curcumin also regulates the activity of various genes involved in processes related to cancer growth and spread, including cell invasion, adhesion, and angiogenesis, or the growth of new blood vessels, which is required by tumors in order to spread throughout the body.

These properties offered by curcumin may help prevent a variety of cancers. Some studies suggest that curcumin combined with other natural protectants, such as resveratrol, increase the protective efficacy of both substances. For example, one study found that combining curcumin with resveratrol proved effective in blocking colon cancer. Another study found that a combination of curcumin and omega-3 fatty acids seemed to help prevent the onset of the deadliest cancer, pancreatic cancer. Combining the two substances resulted in a 72% drop in the volume of pancreatic tumors. A 2003 study published in the journal, Blood, found that adding curcumin to human cells afflicted with the cancer multiple myeloma first stopped the cells from replicating, then killed the cancer cells. sophisticated medical imaging machines show that the uptake of curcumin is greater in cancer cells than it is in normal cells. A recent study found that curcumin disrupts the Mtor pathway. This same pathway is involved in muscle protein synthesis, and is stimulated by amino acids. But in tumors, it also promotes growth and spread.

Curcumin may help prevent cardiovascular disease through several mechanisms. Curcumin, through its antioxidant activity, prevents oxidative damage to the heart. Through its cell membrane stabilizing effect, it also prevents diabetic complications in the heart, which is significant because cardiovascular complications are the primary cause of death in diabetics. Curcumin may help prevent atherosclerosis, and decrease elevated cholesterol levels.

As noted earlier, one of the most potentially exciting effects of curcumin may involve its role in preventing Alzheimer’s disease. Isolated cell studies show that curcumin prevents the clumping of beta amyloid protein that forms the core of AD. Animal studies show that not only can curcumin prevent the clumping of BA, but it may also gradually remove it from the brain. Scientists who study the effects of curcumin in the brain warn however, that these results are preliminary. They suggest that curcumin may provide some preventive effect if ingested regularly. Another tantalizing clue involved a study of people over 65 who regularly consume curry in food. This study found that these people scored higher on tests of brain function compared to others that didn’t consume curry. One notable advantage of curcumin is its ability to cross into the brain through the formidable blood-brain barrier. Excess amounts of aluminum are often implicated in Alzheimer’s and other brain diseases. A recent rat study found that providing curcumin to rats prevented the brain damage incurred by aluminum. Another study found that through modifying brain levels of serotonin and dopamine, curcumin may help prevent depression.

What about curcumin and exercise? The anti-inflammatory effects offered by curcumin have been shown to prevent the degenerative joint changes that produce pain while training. Another study, this time involving rats who ran with a high eccentric component that causes maximal muscular damage during exercise, found that providing curcumin reduced inflammation. This would result in greater exercise recovery and strength gains.
Excessive inflammation also promotes catabolic reactions in muscle. Indeed, out-of-control inflammation is thought to be a primary underlying cause of the loss of muscle with age (sarcopenia). This occurs because of an increase in the production of inflammatory mediator substances in the body. Curcumin may block this effect through inhibiting the central power of inflammation, NFKB, as well as activating heat shock proteins that help to conserve muscle. The antioxidant and blockage of cytokines by curcumin also help in this regard. The main role,however, is the blockage of NFKB, which many researchers believe is the primary inducer of muscle loss with age.

Curcumin may also aid bodyfat loss. A study of isolated fat cells and mice showed that providing the rodents with curcumin prevented the development of new fat cells on a high fat diet, and also promoted the death of existing fat cells. The prevention of blood vessel formation induced by curcumin in the fat cells also played a role. Curcumin also promoted the release of several substances known to play a major role in fat oxidation.

While curcumin doesn’t show significant side effects even with ingestion of large doses, the main problem with curcumin is that it’s difficult for the body to absorb. Some curcumin supplements add piperine, a substance extracted from black peppers that can increase oral absorption of curcumin by 2000% more than plain curcumin. Another commercial preparation called BCM-95 was shown in one study to increase curcumin uptake nearly 7-times more than plain curcumin, and also led to longer retention of curcumin in the body. Another approach involves producing tiny particles of curcumin called nanoparticles. One recent study found that a nanoparticle encapsulation of curcumin increased the oral absorption of curcumin 9-times more than curcumin with piperine. Still another suggested improved delivery vehicle for curcumin is to package it wrapped up in fat particles called liposomes. Another possible carrier are cyclodextrins, which were used in past prohormone supplements to increase oral absorption.Phospholipid complexes of curcumin have been shown to extend the solubility and circulation time of curcumin in rats, as does another process called PEGylation. Heating curcumin in boiling water for 10 minutes may increase the solubility of curcumin 12-fold, although others say that curcumin remains insoluble after this technique.

Again, while nearly all the existing research related to curcumin has involved animal or test tube studies, the effects are favorable and look promising for future human usage. This is particularly true when a form of curcumin that is easily absorbed is produced. But considering its benign nature and long history of safe use, those who suffer from inflammation should probably consider either adding curry to the menu, or ingesting a curcumin supplement.

 ©,2015 Jerry Brainum. Any reprinting in any type of media, including electronic and foreign is expressly prohibited

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