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A Doctor Explores the Surprising Immune-Mood Connection

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Based on a review of emerging research, health and nutrition educator Dr. Joseph Mercola suggests inflammation may be THE risk factor for mood disorders, the primary source being dysfunction in the gut. This review of the science – including several well-documented suggestions for addressing inflammation and mood – is reproduced with kind permission from Dr. Mercola’s educational website (Mercola.com).

It was first published Oct 6, 2011. See footnote* for links to more.


Could Inflammation in the Gut Be Linked to Symptoms of Depression?

“I became acutely aware of the importance of managing depression in the early 80s. Unfortunately, at that time the only tools I had in my toolbox were drugs and exercise. So I became an expert in the first generation antidepressants and literally prescribed them for thousands of patients…. It took me nearly 10 years to break out of the drug model and realize that the drugs never treated the cause and only served to palliate the symptoms [see appendix on depression symptoms]. They simply were NOT the solution.” – Joseph Mercola, MD

Recent studies have shown that inflammation may be involved in the pathogenesis of depression.

In fact, some research has demonstrated that depression is frequently associated with gastrointestinal inflammations and autoimmune diseases as well as with other ailments in which chronic low-grade inflammation is a significant contributing factor. It is possible that depression could be a neuropsychiatric manifestation of a chronic inflammatory syndrome. And the primary cause of inflammation may be the dysfunction of the “gut-brain axis.” According to a study reprinted on the website Green Med Info:

“…[A]n increasing number of clinical studies have shown that treating gastrointestinal inflammations with probiotics, vitamin B, D and omega 3 fatty acids, through attenuating proinflammatory stimuli to the brain, may also improve depression symptoms and quality of life. All these findings justify an assumption that treating gastrointestinal inflammations may improve the efficacy of the currently used treatment modalities of depression and related diseases.”(1)

The notion that inflammation in your gut could be linked to your symptoms of depression may sound far-fetched, but it actually makes perfect sense when you understand the intricate connection between your brain and your digestive tract.

Perhaps the simplest example to use is getting butterflies in your stomach when you’re nervous, thus your thoughts – i.e., brain – are manifesting symptoms in your gut. But another route of connection is via low-grade inflammation, which is a significant contributing factor to numerous diseases that often occur alongside depression, and may, in fact, be manifesting your depressive symptoms.
Is Depression the Result of Chronic Inflammation?

A recent review (Sep 2011) has pointed out several mechanisms by which gastrointestinal inflammation may play a critical role in the development of depression. Among them:

1. Depression is often found alongside gastrointestinal inflammations and autoimmune diseases as well as with cardiovascular diseases, neurodegenerative diseases, type 2-diabetes and also cancer, in which chronic low-grade inflammation is a significant contributing factor. Thus researchers suggested “depression may be a neuropsychiatric manifestation of a chronic inflammatory syndrome.”

2. Research suggests the primary cause of inflammation may be dysfunction of the “gut-brain axis.” Your gut is literally your second brain – created from the identical tissue as your brain during gestation – and contains larger amounts of the neurotransmitter serotonin, which is associated with mood control.

It’s important to understand that your gut bacteria are an active and integrated part of your body, and as such are heavily dependent on your diet and vulnerable to your lifestyle. If you consume a lot of processed foods and sweetened drinks, for instance, your gut bacteria are likely going to be severely compromised because processed foods in general will destroy healthy microflora, and sugars of all kinds feed bad bacteria and yeast, as well as promote systemic inflammation.

3. An increasing number of clinical studies have shown that treating gastrointestinal inflammation with probiotics, vitamin B, vitamin D and omega-3 fats may also improve depression symptoms and quality of life by attenuating proinflammatory stimuli to your brain.

What this all boils down to is that chronic inflammation in your body disrupts the normal functioning of many bodily systems, and can wreak havoc on your brain. But it appears inflammation may be more than just another risk factor for depression; it may in fact be THE risk factor that underlies all others.

Although this refers to postpartum depression, the inflammatory response is the same in its impact on all forms of depression. Published in the International Breastfeeding Journal [“A New Paradigm for Depression in New Mothers: The Central Role of Inflammation…”], researchers stated:

“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.

“Puerperal women [during pregnancy & following childbirth] are especially vulnerable to these effects because their levels of proinflammatory cytokines significantly increase during the last trimester of pregnancy – a time when they are also at high risk for depression. 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.”

This is Why Sugar is Also a Major Factor in Depression

There’s a great book on this subject, The Sugar Blues. The central argument Duffy makes in the book is that sugar is an extremely health-harming addictive drug, and that simply making that one dietary change – eliminating as much sugar as possible – can have a profoundly beneficial impact on your mental health.

He even advocated eliminating sugar from the diet of the mentally ill, stating it could be an effective treatment in and of itself for some people.

It’s become increasingly clear that one route by which sugar is so detrimental to your mental health is because sugar consumption triggers a cascade of chemical reactions in your body that promote chronic inflammation.

Further, excess sugar and fructose will distort the ratio of good to bad bacteria in your gut, which also plays an integral role in your mental health. Sugar does this by serving as a fertilizer / fuel for pathogenic bacteria, yeast, and fungi that negatively inhibit the beneficial bacteria in your gut.

For instance, recent research showed the probiotic Lactobacillus rhamnosus was found to have a marked effect on GABA levels in certain brain regions and lowered the stress-induced hormone corticosterone, resulting in reduced anxiety- and depression-related behavior [see “Probiotics in gut support anxiety-easing GABA balance in brain”]. But if you consume a lot of processed foods and sweetened drinks (which are typically fructose-heavy), your gut bacteria are likely going to be severely compromised and so is your mental health! So the dietary answer for treating depression is to severely limit sugars, especially fructose, as well as grains.

It’s worth noting that sugar can also lead to excessive insulin release that can lead to hypoglycemia, which, in turn, causes your brain to secrete glutamate in levels that can cause agitation, depression, anger, anxiety, panic attacks and an increase in suicide risk.

So radically reducing your sugar intake, especially fructose, to less than 25 grams per day will be one of the most powerful interventions for dealing with depression – as well as fighting chronic inflammation and supporting healthy gut bacteria.

[Ed Note: Dr. Kenny De Meirleir, a Belgian researcher working in collaboration with the new Mt. Sinai ME/CFS Research Center, has reported that large percentages of his ME/CFS patients test for compromised gut lining and fructose absorption problems, which contribute to immune activation. Reportedly he treats initially with antibiotics to bring harmful pathogen levels down, then probiotics to restore healthy microflora function.]

Consuming more than 25 grams of fructose a day will clearly push your brain biochemistry, and your overall health, in the wrong direction. [Average daily consumption in the US is about 3 times that, and 1/3 pound of total sugar.]

Relieving Gastrointestinal Inflammation May Ease Your Depressive Symptoms

We discussed the importance of limiting sugar and fructose, which is one of the primary ways to treat gastrointestinal inflammation, above. You will also want to be sure your gut is regularly “reseeded” with good bacteria, or probiotics, which are the foundation of a healthy gastrointestinal tract.

My recommendations for optimizing your gut bacteria are as follows:

Fermented foods. These are still the best route to optimal digestive health, as long as you eat the traditionally made, unpasteurized versions. Healthy choices include lassi (an Indian yoghurt drink, traditionally enjoyed before dinner), fermented raw (unpasteurized) grass-fed organic milk such as kefir, various pickled fermentations of cabbage, turnips, eggplant, cucumbers, onions, squash and carrots, and natto (fermented soy). See “Soy bad, soy good: The pluses of fermented soy.”

If you regularly eat fermented foods such as these that, again, have not been pasteurized (pasteurization kills the naturally occurring probiotics), your healthy gut bacteria will thrive.

Probiotic supplement. Although I’m not a major proponent of taking many supplements (as I believe the majority of your nutrients need to come from food), probiotics are definitely an exception. I have used many different brands over the past 15 years and there are many good ones out there. If you do not eat fermented foods, taking a high-quality probiotic supplement certainly makes a lot of sense considering how important they are to optimizing your mental health.

Probiotics have a direct effect on brain chemistry, transmitting mood- and behavior-regulating signals to your brain via the vagus nerve, which is yet another reason why your intestinal health can have such a profound influence on your mental health, and vice versa.

Two other important factors to treat gastrointestinal inflammation and also help relieve depression are:

Animal-based omega-3 fats. These not only regulate inflammatory processes and responses, but also positively influence outcome in depressive disorders. So if you are currently struggling with depression, taking a high-quality, animal-based omega-3 fat supplement like krill oil daily is a simple and smart choice.(2)

Vitamin D. Most people are not aware that vitamin D deficiency is associated with inflammation and depression. One previous study found that people with the lowest levels of vitamin D were 11 times more prone to be depressed than those who had normal levels, so you will want to be sure your levels are in the healthy range by getting proper sun exposure or using a safe tanning bed. As a last resort, you can also take a high-quality vitamin D3 supplement, but make sure you have your levels monitored if you choose this route.

There’s a wealth of evidence showing gastrointestinal involvement in a variety of neurological diseases. With this in mind, it should also be crystal clear that nourishing your gut flora with good bacteria is extremely important, from cradle to old age.

Because in a very real sense you have two brains, one inside your skull and one in your gut, and each needs its own vital nourishment.

* * * *

Appendix: What is Depression? Diagnostic Criteria for Major Depressive Disorder**

A. The patient has depressed mood (e.g., sad or empty feeling) or loss of interest or pleasure most of the time for 2 or more weeks, plus 4 or more of the following symptoms:

Sleep: Insomnia or hypersomnia [sleeping a lot] nearly every day
Interest: Markedly diminished interest or pleasure in nearly all activities most of the time
Guilt: Excessive or inappropriate feelings of guilt or worthlessness most of the time
Energy: Loss of energy or fatigue most of the time
Concentration: Diminished ability to think or concentrate; indecisiveness most of the time
Appetite: Increase or decrease in appetite
Psychomotor: Observed psychomotor agitation/retardation
Suicide: Recurrent thoughts of death/suicidal ideation

B. The symptoms do not meet criteria for mixed episode (major depressive episode and manic episode)

C. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning

D. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition

E. The symptoms are not better accounted for by bereavement.

* * * *

Other Resources:
1. “Gastrointestinal inflammation may play a critical role in the pathogenesis of depression.”

2. See for example “The Revolutionary ‘Good Fat’ That Promotes Heart, Brain, Bone and Joint Health,” “Natural Relief for Soreness, Pain and Swelling – Putting Out the Fire,” and “Omega-3s from fish oil / krill oil may lighten depression, help steady cognitive status in older adults.”

* Source:

Dr. Mercola is the founder of the world’s most visited natural health web site, Mercola.com. You can learn the hazardous side effects of OTC Remedies by getting a FREE copy of his latest special report The Dangers of Over the Counter Remedies by going to his Report Page.

**Note: This information (© 1997-2011 Dr. Joseph Mercola. All Rights Reserved) has not been reviewed by the FDA. It is general information, based on the research and opinions of Dr. Mercola unless otherwise noted, and is not meant to prevent, diagnose, treat or cure any condition, illness, or disease. It is not intended to replace a one-on-one relationship with a qualified healthcare professional and is not intended as medical advice. It is always very important that you make no change in your healthcare plan or health support regimen without researching and discussing it in collaboration with your professional healthcare team.

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2 thoughts on “A Doctor Explores the Surprising Immune-Mood Connection”

  1. aarongarrison says:

    A very informative article. Thank you.

  2. Tootstook says:

    Absolutly brilliant. Thank you.

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