Life Extension Magazine June 2014
A New Way To Manage Depression Without Drugs
By Michael Downey
One in 10 American adults suffers from depression.1
Standard care is prescription drugs that are laden with side effects.2-7 For many patients, the effectiveness of these drugs can diminish over the course of treatment,8 forcing depressed individuals to learn to live with their mood disorder.
Researchers have found that a specialized complex of curcumin fights the crippling effects of depression9 by attacking multiple underlying targets.10
A team of internationally recognized scientists has published an impressive clinical trial on the antidepressant benefits of a superior-absorbing curcumin that Life Extension® members have used for many years.9
In this 2013 study of depressed human subjects, curcumin’s effectiveness was similar to that of a standard antidepressant medication. However, curcumin contains none of the side effects associated with commonly used drug therapies9 and provides additional health benefits as well.
These results are in keeping with earlier research showing that curcumin increases levels of “feel good” neurotransmitters such as serotonin and dopamine.10
Landmark Clinical Trial On Curcumin
A breakthrough clinical study recently published in Phytotherapy Research should be welcome news to anyone afflicted with depression, which by 2020 is expected to become the world’s second-leading cause of disability.11
Depression continues to escalate despite “more than half a century of modern psychopharmacology, with billions of dollars spent on antidepressants annually world-wide.”12 And about 63% of patients who take antidepressants experience at least one of the numerous potential side effects,2 which include anxiety, thoughts of suicide, insomnia, weight gain, and sexual dysfunction.2-7 And the payoff for all these risks? Many depressed patients do not respond at all to drug antidepressants and most patients fail to achieve complete remission!13 Some evidence indicates response rates as low as 17% after taking specific antidepressants.14
Scientists have been seeking safer and effective alternatives to pharmaceutical medications.
The antidepressant activity of curcumin was initially suggested by various animal models of depression.10,15-19 But no evidence had been found on the clinical effectiveness of curcumin against depression.
So researchers designed a clinical experiment that was randomized and observer-masked. This means the observers were not told what treatment had been allotted to the patients, and the patients were instructed not to discuss their treatment regimens with the observers.9
The researchers randomly divided volunteers diagnosed with major depressive disorder into three study groups of 20 patients each. The first group took 20 mg of the antidepressant Prozac® (fluoxetine) every morning. The second group took a total of 1,000 mg of absorption-enhanced curcumin in two divided doses of 500 mg each. And the third group took both the once-daily fluoxetine and the twice-daily curcumin.9
The results were measured using the Hamilton Rating Scale for Depression (HAM-D scale).20 This scale provides a way to rate the severity of depression by assessing mood, anxiety, feelings of guilt, suicidal ideation, insomnia, agitation or motor retardation, weight loss, and other body symptoms.9
Efficacy and safety were evaluated after two, four, and six weeks. The HAM-D scale showed that the proportion of patients responding well to treatment was 62.5% in the curcumin group of the study, 64.7% in the fluoxetine group, and 77.8% in the combination group.9
The study team concluded that there was no statistically significant difference in the improvements among the three treatment arms.9 In other words, there was no difference in the effectiveness of the enhanced curcumin formulation compared to the prescription antidepressant fluoxetine in improving symptoms of depression between baseline and six weeks of treatment.9
The study team concluded that this “is the first randomized clinical trial that clearly highlights that curcumin may be an effective and safe agent when used as a modality of treatment in patients of MDD [major depressive disorder].”9
The advantage of curcumin as an antidepressant is its benign profile of adverse events as compared to other antidepressants.9 Curcumin is known to be safe—even in a huge dose of 8 grams (8,000 mg) a day.9
This remarkable clinical trial used a unique formulation—as we’ll learn next—one that overcomes a longstanding problem with curcumin: limited absorption.
Increasing Curcumin’s Absorption
The form of curcumin used to achieve the impressive results in this human study was an enhanced-absorption formulation—known as BCM-95®—now considered the gold standard of curcumin. Its absorption in the body is far superior to that of other curcumin extracts.21
Development of curcumin as a human nutraceutical has been hampered by a major obstacle. As one study report put it, “The use of curcumin in clinics for the treatment of major depression is limited due to its poor gastrointestinal absorption.”13 In addition, curcumin appears to be rapidly broken down both in the intestine and after absorption into the bloodstream.21-23
To overcome this problem, very large doses of curcumin have been needed—doses so large that in some cases, people have balked at the size and number of capsules required to achieve a good effect.21,24,25 Doses as high as 12,000 mg—that’s 12 grams or more than a third of an ounce—have been used in efforts to get significant amounts of curcumin into the bloodstream.24 At such high doses, curcumin can produce uncomfortable symptoms such as abdominal fullness, although no true toxicity has been demonstrated.25
In 2008, researchers showed that curcumin’s absorption (bioavailability) could be enhanced through a very simple process.21 Curcumin is first extracted from the turmeric root. Next, it is highly purified, and then reconstituted with certain other compounds from the original turmeric plant. These constituents are thought to increase intestinal absorption of curcumin in the body.21 The reconstituted curcumin mixture is called BCM-95®, which was the form of curcumin used in this study.
Clinical studies of BCM-95® in human volunteers have shown that its bioavailability is nearly seven times greater than that of a standard extract of curcumin.21,26 BCM-95® was also more than six times as bioavailable as a leading mixture of curcumin that was combined with two other natural products, lecithin and piperine.21 Not only is the BCM-95® formulation better absorbed, it achieves significant blood levels and remains in the blood longer26 so that the body reaps the beneficial effects of curcumin for considerably more time.
This enhanced-absorption advantage has been shown to apply to other conditions in the past, such as rheumatoid arthritis27—and now to depression.9
But how exactly is curcumin able to so effectively target depression? Let’s take a look at the apparent mechanisms.
The progressive loss of the function of brain neurons—neurodegeneration—often occurs simultaneously with depression.28 This condition is more common in aging individuals.28 Neuroinflammation is considered a major contributing factor in both diseases.28 Sustained stress and elevated levels of a class of steroid hormones called glucocorticoids reduce the creation of new brain neurons (neurogenesis).29
Despite all their negative side effects, chronic treatment with antidepressants such as fluoxetine and imipramine may increase neurogenesis.13,29,30
Similarly, the curcumin molecule has been shown in animal studies to boost the neurogenesis process by increasing the number of newly generated cells in a particular area (dentate gyrus) in a brain region known as the hippocampus.19,31 Curcumin is believed to prevent—and even reverse—stress-induced decreases in levels of brain-derived neurotrophic factor (BDNF),a protein that supports the survival of existing neurons and encourages the growth and differentiation of new neurons.13
Modulates Neurotransmitter Levels
High-risk antidepressants called monoamine oxidase inhibitors (MAOIs) work by inhibiting the activity of monoamine oxidase, a family of enzymes that supports the breakdown of neurotransmitters such as serotonin, norepinephrine, and dopamine.32
Other antidepressants known as selective serotonin reuptake inhibitors (SSRIs) specifically increase the extracellular level of serotonin by inhibiting its reabsorption (reuptake) after it has been released in areas of the brain known as synapses.33 Altering serotonin levels is believed to assist brain cells in the sending and receiving of chemical messages—which in turn boosts mood.33
Safely mimicking the mechanisms of both of these types of antidepressants, curcumin has been shown to modestly inhibit two types of monoamine oxidase enzyme (MAO-A and MAO-B)13 and to also modulate the levels of norepinephrine, dopamine, and serotonin in the brain.10,13
By boosting norepinephrine, curcumin may improve attentiveness, emotions, sleeping, dreaming, and learning. Higher levels of dopamine may improve pleasure, emotion, and locomotion. And enhancement of serotonin can play a key role in mood, appetite, sleep, memory, learning, sexual behavior, temperature regulation, and other functions.13
Inflammation plays a major role in depression. Chronic inflammation has been shown to influence almost every pathway involved in the development of depression, including neurotransmitter metabolism.34
Curcumin is a potent anti-inflammatory compound. It is known to inhibit multiple compounds that help produce inflammation in the body.13,35 Studies demonstrate that curcumin:13
- Inhibits the enzyme cyclooxygenase-2 (COX-2), in turn reducing inflammation.
- Inhibits nuclear factor-kappa B (NF-kappa B), a protein complex that controls many genes involved in inflammation.
- Blocks the synthesis of an enzyme called inducible nitric oxide synthase (iNOS), in turn decreasing the release of inflammatory nitric oxide (NO).
- Lowers, by about 60%, levels ofinterleukin-1, a group of cytokines that plays a central role in the regulation of inflammation.
- Reduces the expression of inflammatory markers of astrocytes, cells that support and protect brain neurons.36
Scientists believe that these anti-inflammatory mechanisms contribute to curcumin’s antidepressant activity.
It is curcumin’s remarkable capacity to modulate all of these antidepressant pathways—neurogenesis, neurotransmitter levels, and inflammation—that explains the impressive results of the newly published clinical findings.
However, it is curcumin’s anti-inflammatory activity that underlies a host of other health benefits that go far beyond curcumin’s antidepressant impact. Let’s review some of these broader effects.
Curcumin And Osteoarthritis
Osteoarthritis , long thought to be a purely “degenerative” disease, is now recognized to have multiple inflammatory components. The breakdown of joint-lining cartilage is triggered by pro-inflammatory signaling molecules.37
In the joint-lining membranes, curcumin suppresses the growth of the inflammatory cells that are responsible for cartilage destruction38,39 and even inhibits the “cartilage-eating” compounds that carry out the destructive process itself.40,41
Human studies show that joint pain decreased and joint function improved in patients taking an enhanced-bioavailability curcumin complex42 and they show improvements in blood tests measuring inflammation.42
Curcumin And Rheumatoid Arthritis
A team of scientists conducted a 2012 study of rheumatoid arthritis patients who suffered from high levels of inflammation.27
Superior-absorbing curcumin beat the standard arthritis drug diclofenac on most measures of effectiveness, but was free of the side effects that so often accompany drug therapy.27
Curcumin directly attacks the source of the problem—inflammation—rather than simply masking pain and other symptoms.27,42
Curcumin And Cancer
Inflammation can contribute to the proliferation, survival, and migration of cancer cells.43
Fortunately, curcumin has emerged as a potent cancer-preventing agent. It intervenes at each stage in the complex sequence of events that must occur in order for a cancer to develop and ultimately metastasize to healthy tissue.
The multi-targeted mechanisms of curcumin have yielded compelling results in combating a remarkably broad array of cancers—including cancers of the breast,44,45 uterus,46 cervix,47,48 prostate,49-55 and gastrointestinal tract.56-70
Rapidly accumulating research also demonstrates curcumin’s potential to counter cancers of the blood,71-73 brain,74 lung,75,76 bladder,77-80 head,81-83 throat,84,85 and pancreas86-90 (one of the most lethal forms of cancer).
Also, curcumin may have special benefits for individuals undergoing radiation cancer treatment. Radiation therapy is often limited due to its side effects.91 For example, prostate cancer patients undergoing external beam radiotherapy suffer, among other effects, urinary tract problems such as painful urination.92 Since curcumin’s radioprotective effects had earlier been suggested,93-95 scientists conducted a pilot clinical study on 40 prostate cancer patients undergoing external beam radiotherapy.96
They randomly assigned half of the patients to receive 3 grams daily of the enhanced curcumin formulation BCM-95® while the rest took a placebo. After three months of radiotherapy, the curcumin group experienced much milder urinary problems than the placebo patients, especially reduced urination frequency.96 It has been suggested these results stem partly from curcumin’s ability to reduce radiation-induced inflammation.96
These results have implications for radiotherapy for other cancers. Similar results were found in a 2013 study finding that curcumin—using the non-enhanced extract, but in larger doses of 6 grams daily—reduced the severity of radiation dermatitis, or radiation-induced skin inflammation, in breast cancer patients.97
Depression afflicts one in 10 American adults.1 The majority of patients prescribed antidepressant drugs experience at least one of their serious side effects.2,8
A highly specialized complex of curcumin known as BCM-95®—with bioavailability nearly seven times greater than that of standard curcumin—fights the crippling effects of depression9 by attacking multiple underlying targets.
A study published in 2013 showed remarkable outcomes in depressed individuals using a highly absorbable curcumin complex. Curcumin targets depression by promoting neurogenesis, increasing levels of key neurotransmitters—serotonin, norepinephrine, and dopamine—and inhibiting inflammation.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.