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:
Placebo
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.
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
Avoidance
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:
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.
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