- Curcumin may be helpful against depression, especially atypical depression. No significant difference in efficacy between high and low dosages were found
- Two active components in saffron, crocin and safranal, also have antidepressant effects, and at least three studies have found saffron is as effective as generic Prozac
- One of the mechanisms behind curcumin’s beneficial impact on depression appears to be its ability to tame the flames of inflammation, which is now thought to be a foundational cause of depression
By Dr. Mercola
Curcumin, the active ingredient in the Indian spice turmeric, is a polyphenol with over 160 potentially therapeutic activities, including antioxidant, anti-inflammatory and anticancer effects.1
Importantly, it has the ability to cross your blood-brain barrier and exhibits potent neuroprotective properties, suggesting it may be useful for neurodegenerative disorders such as Parkinson’s disease. Recent research also suggests it may be helpful against depression.
Remember, though, that curcumin is very poorly absorbed, so if you want to use it therapeutically, make sure you use a supplement that is optimized for maximum absorption; otherwise you won’t get the results described below. Many believe that using black pepper helps. And while it does, it is only a marginal increase.
Curcumin Helps Relieve Depressive Symptoms
According to a meta-analysis2 of six short-term, placebo-controlled clinical trials, curcumin “appears to be safe, well-tolerated and efficacious among depressed patients,” and could serve as a “novel antidepressant.” Three of the trials also reported significant anti-anxiety effects.
Another recent study3,4 evaluating curcumin’s effect on depression was done in Australia. A total of 123 people diagnosed with major depressive disorder were included in the double-blind, randomized study, receiving one of four treatments for 12 weeks:
- Low-dose (250 mg) curcumin extract
- High-dose (500 mg) curcumin extract
- Low-dose curcumin extract with 15 mg of saffron
Compared to placebo, all three treatment groups experienced improvement in their symptoms. Curcumin was particularly effective for those with atypical depression. Interestingly, there was no significant difference in efficacy between high and low dosages. According to the authors:
“These findings suggest that there was insufficient power in the study to detect group differences, or that there was a ceiling antidepressant effect of these natural spices. This ceiling may have been achieved with the administration of the low-dose curcumin alone. The inclusion of a stand-alone saffron condition would be desirable in future studies.”
Saffron Also Has Antidepressant Effects
Indeed, saffron may actually have antidepressant effects in its own right. Other studies have shown two of its active components, crocin and safranal, have antidepressant effects.5
In one study,6 depressed patients taking 30 mg of Crocus sativus (saffron) each day for eight weeks experienced the same amount of relief as those taking 20 mg of fluoxetine (generic Prozac). Two additional studies7,8 have confirmed saffron has an effectiveness equal to that of fluoxetine.
Curcumin May Benefit Many Neuropsychiatric Disorders
Another scientific review9 in the Journal of Psychopharmacology, which assessed curcumin’s beneficial effect on depression and other psychiatric disorders, noted that:
“[C]urcumin can influence an array of biological activities. Many of these, such as its anti-inflammatory, antioxidant, neuroprotective and monoaminergic effects are dysregulated in several neuropsychiatric disorders …
[I]n vitro, animal and human studies investigating … curcumin as a treatment for neuropsychiatric disorders such as major depressive disorder, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), bipolar disorder … and autism are reviewed … It is concluded that curcumin is a promising, natural agent for many of these conditions …”
One of the mechanisms behind curcumin’s beneficial impact on neuropsychiatric disorders such as depression appears to be its ability to tame the flames of inflammation, which can wreak havoc on your psychiatric health.
Gastrointestinal Inflammation Raises Depression Risk
Previous research10 suggests gastrointestinal (GI) inflammation in particular may play a critical role in the development of depression, as depression is often found alongside GI inflammation and/or autoimmune diseases, cardiovascular diseases, neurodegenerative diseases, type 2 diabetes and cancer.
Chronic low-grade inflammation is a hallmark of and significant contributing factor to all of these conditions, leading researchers to suggest “depression may be a neuropsychiatric manifestation of a chronic inflammatory syndrome.” The study of these connections is known as psychoneuroimmunology, i.e., the impact of inflammation on behavior. As noted in a 2012 study:11
“Elevated biomarkers of inflammation … have been found in depressed patients, and administration of inflammatory stimuli has been associated with the development of depressive symptoms.
Data also have demonstrated that inflammatory cytokines can interact with multiple pathways known to be involved in the development of depression, including monoamine metabolism, neuroendocrine function, synaptic plasticity and neurocircuits relevant to mood regulation …
Psychosocial stress, diet, obesity, a leaky gut and an imbalance between regulatory and pro-inflammatory T cells also contribute to inflammation and may serve as a focus for preventative strategies relevant to both the development of depression and its recurrence.”
Controlling Inflammation Is Best Done Through Lifestyle Changes
According to Dr. Hyla Cass,12 whom I’ve interviewed on this topic, approximately one-third of depressed patients have high levels of inflammation, and anti-inflammatory drugs have actually been shown to favorably alter neurochemical pathways involved in depression.13
The arthritis drug sirukumab is currently being tested on depressed patients. GlaxoSmithKline and others are also working on developing anti-inflammatory drugs targeting depression. The problem with this approach is that most drugs have side effects — sometimes terminal, as the 60,000 who died from the anti-inflammatory Vioxx. Fortunately, you don’t need drugs to combat inflammation.
One of the most effective ways to quell inflammation is to eat a cyclical ketogenic diet. In fact, one of the most remarkable effects of nutritional ketosis is that your C-reactive protein (CRP) level (an inflammatory marker) virtually disappears. It can really drive your inflammation levels about as low as they can go.
Other important anti-inflammatory strategies that are strongly recommended for prevention and treatment of depression are animal-based omega-3 and vitamin D. It appears curcumin may be a valuable adjunct as well, judging by recent studies. Another crucial contributor to inflammation is to reduce your exposure to EMF. This means keeping your cellphone in airplane mode unless you are using it and never holding it next to your ear. Turning off your Wi-Fi router at night is also crucial.
Aside from general GI inflammation, a number of studies have concluded the primary cause of inflammation is related specifically to dysfunction of the gut-brain axis,14 which is largely lifestyle driven. Diet, exercise and toxic exposures, for example, all have the ability to influence your gut microbiome, thereby affecting your gut-brain axis.
One of the reasons sugar is so detrimental to your mental health is because it triggers a cascade of chemical reactions — starting with elevated insulin — that promote chronic inflammation. Excess sugar and processed fructose also distort the ratio of good to bad bacteria in your gut. Sugar does this by serving as a fertilizer/fuel for pathogenic bacteria, yeast and fungi that inhibit the beneficial bacteria in your gut.
Chronic Inflammation May Be More Than a Risk Factor for Depression
What this all boils down to is that chronic inflammation not only disrupts the normal functioning of many bodily systems, it can also wreak havoc in your brain and affect your psychological health. In fact, at least one previous study15 has suggested chronic low-grade inflammation may be the very root cause of depression. Published in the International Breastfeeding Journal, the researchers stated:
“Research in the field of psychoneuroimmunology (PNI) has revealed that depression is associated with inflammation manifested by increased levels of proinflammatory cytokines. The old paradigm described inflammation as simply one of many risk factors for depression. The new paradigm is based on more recent research that has indicated that physical and psychological stressors increase inflammation.
These recent studies constitute an important shift in the depression paradigm: inflammation is not simply a risk factor; it is the risk factor that underlies all the others. Moreover, inflammation explains why psychosocial, behavioral and physical risk factors increase the risk of depression. This is true for depression in general and for postpartum depression in particular …
[L]evels of proinflammatory cytokines significantly increase during the last trimester of pregnancy … Moreover, common experiences of new motherhood, such as sleep disturbance, postpartum pain and past or current psychological trauma, act as stressors that cause proinflammatory cytokine levels to rise.”
Inflammation and Depression 101
In this model, depression is the result of your body’s attempts to protect itself from an inflammatory response, and involves hormones and neurotransmitters. Depressive symptoms most strongly associated with chronic inflammation include:16
- Flat mood
- Slowed thinking
- Alterations in perception
- Metabolic changes
Cytokines in your blood, or inflammatory messengers such as CRP, interleukin-1, interleukin-6 and TNF-alpha are all predictive of17 and correlate18 to depression. In melancholic depression, bipolar disorder and postpartum depression, white blood cells called monocytes express pro-inflammatory genes that provoke secretion of cytokines.19
At the same time, cortisol sensitivity goes down, and cortisol is a stress hormone that buffers against inflammation. Together, these inflammatory agents transfer information to your nervous system, typically by stimulating your vagus nerve, which connects your gut and brain.20
During inflammatory states, brain cells called microglia are activated. When this happens, an enzyme called indoleamine 2 3-dioxygenase directs tryptophan away from the production of serotonin and melatonin, instructing it instead to produce an NMDA (an amino acid derivative) agonist called quinolinic acid, which can trigger anxiety and agitation.21
Curcumin Goes Head-to-Head With Blockbuster Antidepressant
One last study22 on curcumin and depression worth mention is a randomized controlled trial comparing the efficacy of curcumin and fluoxetine (generic Prozac) in patients diagnosed with major depressive disorder. Sixty patients were given one of three treatment protocols:
- 20 mg fluoxetine
- 1,000 mg curcumin (500 mg standardized curcumin extract taken twice a day)
- Combination of fluoxetine and curcumin
According to the authors:
“The proportion of responders as measured by the HAM-D scale was higher in the combination group (77.8 percent) than in the fluoxetine (64.7 percent) and the curcumin (62.5 percent) groups; however, these data were not statistically significant. Interestingly, the mean change in HAM-D score at the end of six weeks was comparable in all three groups.
This study provides first clinical evidence that curcumin may be used as an effective and safe modality for treatment in patients with [major depressive disorder] without concurrent suicidal ideation or other psychotic disorders.”
Certain Supplements Boost Effectiveness of Antidepressants
Other research has shown nutritional supplements can boost the effectiveness of antidepressants. Unfortunately, they did not look at supplementation only, which might have offered valuable insights. The analysis in question looked at 40 clinical trials in which supplements were added to the drug regimen.23,24,25
Four supplements were found to improve the impact of the medication — which included serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants — compared to medication only:
- Animal-based omega-3 (in the form of fish oil)
- Vitamin D
- Methylfolate (an effective form of folic acid)
- S-adenosylmethionine (SAMe)
In my view, there’s reason to suspect the supplements provided the true benefit. Other studies have shown both omega-3 and vitamin D can improve mental health all on their own — in part by regulating inflammatory processes and responses — and studies have repeatedly demonstrated that antidepressants are right on par with placebo in terms of effectiveness.
In one vitamin D study,26 seniors with the lowest vitamin D levels were 11 times more prone to be depressed than those who had normal levels. It makes little sense to take the extra risks with a drug if they don’t add anything of real value.
Addressing GI Inflammation May Ease Your Depressive Symptoms
If you suffer from depression, it may be well worth your effort to take steps to reduce the level of inflammation in your body. Remember, no drugs are necessary for this. In fact, the most effective strategies for this are to:
• Address your diet. Limiting net carbs in all its forms (think added sugar, processed fructose, refined grains and most processed foods in general) is a key step. A ketogenic diet, high in healthy fats, low in net carbs with a moderate amount of protein can really drive inflammation levels way down.
• Make sure to get enough animal-based omega-3.
• Optimize your vitamin D level, ideally through sensible sun exposure, as sunlight has been shown to improve depression in ways that are unrelated to vitamin D as well.
• Address your gut health, as impaired gut flora is frequently involved in depression. Regularly “reseed” your gut with beneficial bacteria (probiotics and prebiotics), as this is the foundation of a healthy GI tract. Eating plenty of fermented foods is your best bet. It’s also the most economical.
If you do not eat fermented foods, taking a high-quality probiotic supplement makes of sense considering how important probiotics are for your mental health. In fact, probiotics are thought to have a direct effect on brain chemistry, transmitting mood- and behavior-regulating signals to your brain via the vagus nerve.