Spice of Life

Big Pharma, the popular designation for the world’s top two dozen or so multibillion-dollar pharmaceutical companies, is constantly on the lookout for new drugs. While many compounds seem to have revolutionary curative powers, a good number of them come with a plethora of potentially serious side effects. Indeed, a pharmacology adage states that unless a drug has side effects, it won’t work.

Many new drugs are synthesized versions of natural compounds that have proven effective. Of the 877 small-molecule drugs introduced between 1981 and 2002, 61 percent had their origins in natural substances. Despite that, modern science often downplays the usefulness of natural compounds in favor of the more isolated drug formulations.

In developing countries, however, natural compounds have an established history of success. Surveys reveal that 80 percent of the people in the developing world 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 they are both safer and more effective than some of the drugs doctors routinely prescribe. While drugs often target just one effect, natural compounds benefit many body functions that can improve health.

The result is that some formerly esoteric plant compounds have become quite popular. Green tea, for example, has pleiotropic properties, meaning that it has beneficial effects. So does resveratrol, found in red wine, peanuts and other foods.

Curcumin, derived from turmeric rhizomes, is related to ginger and cultivated mainly in southeast Asia. It’s been around a long time, its use dating back to about 600 B.C. Marco Polo described turmeric in his account of travel in China in the 13th century.

Powdered turmeric is an ingredient in curry. Curcumin accounts for the yellow color of curry, and that same yellow is used as a coloring in cheese, butter and other foods—so it’s likely that you’ve eaten some of it.

The medicinal properties of curcumin have been extensively investigated in recent years. The benefits attributed to it include:

• Prevention of digestive disorders. Turmeric induces the flow of bile, which is required for the digestion of dietary fats and the absorption of all fat-soluble vitamins.

• Reduction of arthritis and joint pain. Curcumin has potent anti-inflammatory and antioxidant properties, which help relieve pain and protect joints.

• Cardiovascular disease protection. Curcumin may help prevent cardiovascular disease through various mechanisms.

• Cancer prevention. Preliminary animal and test-tube studies show that curcumin may help prevent various types of cancer.

• Brain protection. The incidence of Alzheimer’s disease is rising in the United States. Yet in India, where curry is popular, there’s a less than 1 percent incidence of the dread disease in people over age 65. Curcumin may also provide antidepressant effects.

• Improved exercise recovery and sparing of muscle tissue. Preliminary studies show that curcumin 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 research showing beneficial results has involved animals and isolated-cell study designs. The same is true for other natural compounds, such as resveratrol. On the other hand, the suggested benefits of curcumin have plausible scientific mechanisms. Indirect evidence, such as the low rate of Alzheimer’s in India and the effects produced in animals, are highly suggestive that the effects can be replicated in humans.

Curcumin works its health magic through a variety of pathways. For one thing, it provides potent anti-inflammatory effects by blocking the activity of nuclear factor kappa beta. NFKB is basically the conductor of all inflammatory reactions in the body. It’s known as a transcription factor, in that it signals the release of a host of various inflammatory chemicals, such as cytokines and kinases.

That curcumin seems to help prevent so many diseases is explained by the fact that most degenerative conditions, including cardiovascular disease and cancer, have an underlying inflammatory cause. Insufficient antioxidant activity also contributes to inflammation and disease, and curcumin works in that regard, too, offering antioxidant activity comparable to vitamins C and E.1

A recent study found that curcumin exerts its effects through a previously unknown mechanism.2 Many diseases, including cancer, are induced through unstable cellular membranes. When working properly, the membranes act as the cell’s gatekeeper, letting beneficial substances in and keeping toxins out. Anything toxic that penetrates the cell can induce damage to the nucleic acids in the cell, leading to cell mutations. That, in turn, can result in anything from cancer to death of the cell. In addition, having effectively operating cell membranes makes hormone receptors more effective in the membrane, thus enabling such hormones as testosterone and insulin to interact with the cell receptors and do their work. 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. It can bind to and inhibit the activity of many enzymes, growth factor receptors, metals and other molecules. Among them is beta-amyloid, a protein in the brain. When beta-amyloid molecules bind excessively to their receptors, 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. Cancer also has an inflammatory component, and curcumin blunts the activity of inflammatory enzymes like COX2, which converts the arachidonic fatty acid derived from food into inflammatory eicosanoids that are linked to pain and inflammation. Curcumin also regulates the activity of genes involved in processes related to cancer growth and spread, including cell invasion, adhesion and angiogenesis, or the growth of new blood vessels, which tumors need in order to spread. That implies that curcumin may help prevent a variety of cancers.

Some studies suggest that curcumin, combined with other natural protectants such as resveratrol, increases the protective attributes of both substances. For example, one study proved that combining curcumin with resveratrol effectively blocked colon cancer.3 Another study found that a combination of curcumin and omega-3 fatty acids seemed to help prevent the deadliest cancer, pancreatic cancer. Combining the two substances resulted in a 72 percent drop in the volume of pancreatic tumors.4

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 in normal cells.5 A recent study found that curcumin disrupts the mTOR pathway, the name given to a protein complex stimulated by amino acids and involved in muscle protein synthesis.6 In tumors, however, it also promotes growth and spread.

Curcumin may help prevent cardiovascular disease through several mechanisms.7 Its antioxidant activity prevents oxidative damage to the heart. Because it helps stabilize cell membranes, it helps prevent diabetic complications in the heart, which is significant because cardiovascular complications are the primary cause of death in diabetics. It may also help prevent atherosclerosis and decrease elevated cholesterol.8

As noted earlier, one of the most potentially exciting aspects of curcumin may be its role in preventing Alzheimer’s disease. Isolated-cell studies show that it prevents the clumping of beta-amyloid, the protein that forms the core of Alzheimer’s. Animal studies show that not only can curcumin prevent the clumping of beta-amyloid, but it may also gradually remove the protein from the brain.

Scientists who study the effects of curcumin in the brain warn, however, that the results are preliminary. They suggest that curcumin may provide some preventive effect if taken regularly. Another tantalizing clue involved a study of people over 65 who regularly ate curry. They scored higher on tests of brain function than others who didn’t eat curry.

One notable advantage of curcumin is its ability to cross 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 giving curcumin to rats prevented the brain damage fostered by aluminum.9 Another study found that curcumin may help prevent depression by modifying serotonin and dopamine in the brain.10

What about curcumin and exercise? The anti-inflammatory effects of curcumin have been shown to prevent the degenerative joint changes that produce pain during training.11 Another study, one involving rats that ran with a high eccentric component—which causes maximal muscular damage—found that the ones given curcumin experienced reduced inflammation. That would translate into greater exercise recovery and strength gains.12

Excessive inflammation also sets off catabolic reactions in muscle. Indeed, out-of-control inflammation is thought to be a primary underlying cause of sarcopenia, a.k.a. the loss of muscle with age. That occurs because of an increase in the production of inflammatory mediator substances in the body. Curcumin may block that effect by inhibiting NKFB, the central power of inflammation, as well as activating heat shock proteins, which help conserve muscle. Curcumin’s antioxidant factors and blockage of cytokines also help in that regard. Its main role, however, is the blockage of NFKB, which many researchers believe is the primary cause of muscle loss with age.13

Curcumin may aid bodyfat loss. A study of isolated fat cells and mice showed that giving curcumin to rodents on a high-fat diet prevented the development of new fat cells and helped kill existing fat cells. Curcumin’s prevention of blood vessel formation also played a role, as did its involvement in the release of several substances known to play a major role in fat oxidation.14

While curcumin doesn’t show significant side effects even in large doses, it is difficult for the body to absorb. Some curcumin supplements add piperine, a substance extracted from black peppers that can increase absorption of curcumin by 2,000 percent. A commercial preparation called BCM-95 was shown in one study to increase uptake nearly seven times more than plain curcumin, and it was retained longer in the body.

Another approach involves producing tiny particles of curcumin called nanoparticles. One recent study found that a nanoparticle encapsulation of curcumin increased oral absorption nine times more than curcumin with piperine.15 An alternative suggestion is to wrap curcumin in fat particles called liposomes. Still another possible carrier: cyclodextrins, which have been used in pro-hormone supplements to increase absorption. Phospholipid complexes of curcumin have been shown to extend its solubility and circulation time in rats, as does a process called PEGylation. Heating curcumin in boiling water for 10 minutes may increase its solubility 12-fold, although there is a view that it remains insoluble after that technique.

While nearly all the research related to curcumin has involved animal or test-tube studies, it looks promising for human use. That’s particularly true when a form of curcumin that is easily absorbed is produced. Considering its benign nature and long history of safe use, however, those who suffer from inflammation should probably consider either adding curry to the menu or taking a curcumin supplement.

Editor’s note: Jerry Brainum has been an exercise and nutrition researcher and journalist for more than 25 years. He’s worked with pro bodybuilders as well as many Olympic and professional athletes. To get his new e-book, Natural Anabolics—Nutrients, Compounds and Supplements That Can Accelerate Muscle Growth Without Drugs, visit www.JerryBrainum.com. IM

References

1 Maheshwari, R.K., et al. (2006). Multiple biological activities of curcumin: a short review. Life Sci. 78(18):2081-7.

2 Baray, J., et al. (2009). Determining the effects of lipophilic drugs on membrane structure by solid-state NMR spectroscopy: The case of the antioxidant curcumin. JACS. 131(12):4490–4498.

3 Majumdar, A.P., et al. (2009). Curcumin synergizes with resveratrol to inhibit colon cancer. Nut Cancer. 61:544-553.

4 Swamy, M.V., et al. (2008). Prevention and treatment of pancreatic cancer by curcumin in combination with omega-3 fatty acids. Nut Cancer. 60:81-89.

5 Kunwar, A., et al. (2008). Quantitive cellular uptake, localization, and cytotoxicity of curcumin in normal and tumor cells. Biochem Biophys Acta. 1780:673-79.

6 Beevers, C.S., et al. (2009). Curcumin disrupts the mammalian target of rapamycin-raptor complex. Cancer Res. 69(3):1000-8.

7 Wongcharoen, W., et al. (2009). The protective role of curcumin in cardiovascular disease. Int J Cardiol. 133(2):145-51.

8 Soni, K.B., et al. (1992). Effect of oral curcumin administration on serum peroxides and cholesterol levels in human volunteers. Ind J Physiol Pharmacol. 36:273-75.

9 Sharma, D., et al. (2009). Curcumin counteracts the aluminum-induced aging-related alterations in oxidative stress, NA+, K+ ATPase and protein kinase C in adult and old rat brain regions. Biogerontol. 10(4):489-502.

10 Kulkarni, S.K., et al. (2008). Antidepressant activity of curcumin: Involvement of serotonin and dopamine system. Psychopharmacol. 201:435-42.

11 Shakibaei, M., et al. (2007). Suppression of NF-kB activation by curcumin leads to inhibition of expression of cyclo-oxygenase-2 and matrix metalloproteinase-9 in human articular chondrocytes: Implications for the treatment of osteoarthrtis. Biochem Pharmacol. 73:1434-1445.

12 Davis, J.M., et al. (2007). Curcumin effects on inflammation and performance recovery following eccentric-induced muscle damage. Am J Physiol Regul Integr Comp Physiol. 292(6):R2168-73.

13 Alamdari, N., et al. (2009). Curcumin and muscle wasting: A new role for an old drug? Nutrition. 25:125-129.

14 Ejaz, A., et al. (2009). Curcumin inhibits adipogenesis in 3T3-L1 adipocytes and angiogenesis and obesity in C57/BL mice. J Nutr. 139(5):919-25.

15 Shaikh, J., et al. (2009). Nanoparticle encapsulation improves oral bioavailability of curcumin by at least ninefold when compared to curcumin adminstered with piperine as absorption enhancer. Eur J Pharmaceut Sci. 37:223-30. IM