If depression can be induced with pro-inflammatory drugs, might an anti-inflammatory diet be effective in preventing and treating mood disorders?
Flashback Friday: Anti-Inflammatory Diet for Depression
Depression affects more than 150 million people worldwide, making it a leading cause of losing healthy years of life as a result of disability. In fact, by 2020, depression may be the second leading cause of healthy years of life lost, second only to heart disease. Why is depression so common? Well, it is said, “Nothing in biology makes sense except in the light of evolution.” But, why would we evolve to get depressed?
Depression poses a baffling evolutionary puzzle. It has such negative effects, but remains so common and heritable, meaning a big chunk of risk is passed down through our genes. So, there must be some kind of adaptive benefit. Otherwise, presumably, it would have been naturally selected against. Maybe, depression is an evolutionary strategy for defense against infection.
Infection has been the leading cause of mortality throughout human history. The average life expectancy was 25, and it was not uncommon for half our kids to die. With such stark capabilities, infection has been a critical and potent driving force in natural selection.
When we become infected, there is a surge of inflammation as our body mounts a counterattack, and then what happens? We feel lousy. We feel sick. We get weak, tired, slow, and sleepy. We don’t see anyone; we don’t want to do anything; all we want to do is sleep. It’s like we’re depressed—and that’s great for fighting infection. Not only does that help us conserve energy so we can put up a good fight, but it reduces social contact. We’re not running around infecting everyone.
It’s the same reason we evolved to think poop doesn’t smell good, or decaying flesh. That keeps us safe from infection. In fact, we see this phenomenon with other social animals, like honeybees and mole rats, who feel impelled to crawl off and die alone when they get sick, which reduces the risk to the rest of the community.
The relationship between mental health and inflammation was first noted in 1887, for which the only psychiatrist to ever win the award got a Nobel Prize. But what evidence have we accumulated in the century since that inflammation causes depression? Well, people who are depressed have raised inflammatory markers, such as C-reactive protein, and inflammatory illnesses are associated with greater rates of major depression. Indeed, that’s what’s found in a variety of inflammatory conditions including more benign inflammatory conditions, such as asthma and allergies. And, that’s important, suggesting the mood symptoms are not simply ‘feeling bad about having a terrible disease,’ but may be directly tied to the inflammation. Most powerfully, you can actually induce depression by inducing inflammation, like when we give interferon for certain cancers or chronic infections—up to 50% go on to suffer major depression. Even just giving a vaccine can cause enough inflammation to trigger depressive symptoms. Taken together, these studies are strongly suggestive of inflammation being a causative factor of mood symptoms.
So, can an anti-inflammatory diet help prevent depression? We didn’t know, until about 43,000 women without depression were followed, along with their diets, for about a dozen years to see who became depressed, and it was those who ate a more inflammatory dietary pattern, characterized by more soda, refined grains and meat, suggesting that chronic inflammation may underlie the association between diet and depression. Normally, we think of omega-3’s as anti-inflammatory, but they found fish to be pro-inflammatory, associated with increased C-reactive protein levels consistent with recent findings that omega-3’s don’t seem to help with either depression or inflammation. The most anti-inflammatory diet is a plant-based diet, which can cut C-reactive protein levels by 30% within two weeks, perhaps because of the anti-inflammatory properties of antioxidants.
I’ve talked about this before, but never explained why antioxidants are anti-inflammatory. Oxidative damage caused by free radicals may cause an autoimmune response in the body by changing the chemical structure of otherwise ubiquitous molecules to generate new structures that the body attacks as foreign. For example, when LDL cholesterol gets oxidized, our body creates antibodies against it and attacks it. And, so, clinical depression can be accompanied by increased oxidative stress and the autoimmune inflammatory responses it creates.
Where else does inflammation come from in our diet? Endotoxins. It’s worth reviewing how the endotoxins in animal products can cause a burst of inflammation within hours of consumption. What does that do to our mood? If you inject endotoxin into people, within a few hours, inflammation shoots up, and so do feelings of depression, as well as feelings of social disconnection from people.
Although previous research has demonstrated that inflammatory activity contributes to depressive symptoms, no work in humans has examined the effect of experimentally induced inflammation on anhedonia, the lack of reaction to pleasurable stimuli, a key diagnostic feature of depression. No work has been done, that is, until now. Within hours of endotoxin hitting their bloodstream, these experimental subjects not only started to feel depressed, but they had significant reductions in activity in the reward center of the brain. They were less excited about winning money playing video games, for example, in the study.
But by eliminating animal products, and eating antioxidant rich diets, we may be able to prevent or treat depression.
To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video. This is just an approximation of the audio contributed by Katie Schloer.
Please consider volunteering to help out on the site.
- A D Lopez, C C Murray. The global burden of disease, 1990-2020. Nat Med. 1998 Nov;4(11):1241-3.
- Y Milaneschi, S Bandinelli, B W Penninx, A M Corsi, F Lauretani, R Vazzana, R D Semba, J M Guralnik, L Ferrucci. The relationship between plasma carotenoids and depressive symptoms in older persons. World J Biol Psychiatry. 2012 Dec;13(8):588-98.
- A Sánchez-Villegas, M A Martínez-González, R Estruch, J Salas-Salvadó, D Corella, M I Covas, F Arós, D Romaguera, E Gómez-Gracia, J Lapetra, X Pintó, J A Martínez, R M Lamuela-Raventós, E Ros, A Gea, J Wärnberg, L Serra-Majem. Mediterranean dietary pattern and depression: the PREDIMED randomized trial. BMC Med. 2013 Sep 20;11:208.
- M A Beydoun, H A Beydoun, A Boueiz, M R Shroff, A B Zonderman. Antioxidant status and its association with elevated depressive symptoms among US adults: National Health and Nutrition Examination Surveys 2005-6. Br J Nutr. 2013 May;109(9):1714-29.
- M Maes, P Galecki, Y S Chang, M Berk. A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Apr 29;35(3):676-92.
- N I Eisenberger, E T Berkman, T K Inagaki, L T Rameson, N M Mashal, M R Irwin. Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward. Biol Psychiatry. 2010 Oct 15;68(8):748-54.
- J D Rosenblat, D S Cha, R B Mansur, R S McIntyre. Inflamed moods: a review of the interactions between inflammation and mood disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2014 Aug 4;53:23-34.
- N I Eisenberger, T K Inagaki, N M Mashal, M R Irwin. Inflammation and social experience: an inflammatory challenge induces feelings of social disconnection in addition to depressed mood. Brain Behav Immun. 2010 May;24(4):558-63.
- S Anders, M Tanaka, D K Kinney. Depression as an evolutionary strategy for defense against infection. Brain Behav Immun. 2013 Jul;31:9-22.
- M Lucas, P Chocano-Bedoya, M B Schulze, F Mirzaei, E J O'Reilly, O I Okereke, F B Hu, W C Willett, A Ascherio. Inflammatory dietary pattern and risk of depression among women. Brain Behav Immun. 2014 Feb;36:46-53.
- T N Raju. The Nobel chronicles. 1927: Julius Wagner-Jauregg (1857-1940). Lancet. 1998 Nov 21;352(9141):1714.
- M Berk, L J Williams, F N Jacka, A O'Neil, J A Pasco, S Moylan, N B Allen, A L Stuart, A C Hayley, M L Byrne, M Maes. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med. 2013 Sep 12;11:200.
- A M Hashmi, Z Butt, M Umair. Is depression an inflammatory condition? A review of available evidence. J Pak Med Assoc. 2013 Jul;63(7):899-906.
- A Madeeh Hashmi, M Awais Aftab, N Mazhar, M Umair, Z Butt. The fiery landscape of depression: A review of the inflammatory hypothesis. Pak J Med Sci. 2013 May;29(3):877-84.
- D J Jenkins, C W Kendall, A Marchie, D A Faulkner, J M Wong, R de Souza, A Emam, T L Parker, E Vidgen, K G Lapsley, E A Trautwein, R G Josse, L A Leiter, P W Connelly. Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and C-reactive protein. JAMA. 2003 Jul 23;290(4):502-10.
- N DellaGioia, J Hannestad. A critical review of human endotoxin administration as an experimental paradigm of depression. Neurosci Biobehav Rev. 2010 Jan;34(1):130-43.
Images thanks to Ars Electronica via Flickr.
Depression affects more than 150 million people worldwide, making it a leading cause of losing healthy years of life as a result of disability. In fact, by 2020, depression may be the second leading cause of healthy years of life lost, second only to heart disease. Why is depression so common? Well, it is said, “Nothing in biology makes sense except in the light of evolution.” But, why would we evolve to get depressed?
Depression poses a baffling evolutionary puzzle. It has such negative effects, but remains so common and heritable, meaning a big chunk of risk is passed down through our genes. So, there must be some kind of adaptive benefit. Otherwise, presumably, it would have been naturally selected against. Maybe, depression is an evolutionary strategy for defense against infection.
Infection has been the leading cause of mortality throughout human history. The average life expectancy was 25, and it was not uncommon for half our kids to die. With such stark capabilities, infection has been a critical and potent driving force in natural selection.
When we become infected, there is a surge of inflammation as our body mounts a counterattack, and then what happens? We feel lousy. We feel sick. We get weak, tired, slow, and sleepy. We don’t see anyone; we don’t want to do anything; all we want to do is sleep. It’s like we’re depressed—and that’s great for fighting infection. Not only does that help us conserve energy so we can put up a good fight, but it reduces social contact. We’re not running around infecting everyone.
It’s the same reason we evolved to think poop doesn’t smell good, or decaying flesh. That keeps us safe from infection. In fact, we see this phenomenon with other social animals, like honeybees and mole rats, who feel impelled to crawl off and die alone when they get sick, which reduces the risk to the rest of the community.
The relationship between mental health and inflammation was first noted in 1887, for which the only psychiatrist to ever win the award got a Nobel Prize. But what evidence have we accumulated in the century since that inflammation causes depression? Well, people who are depressed have raised inflammatory markers, such as C-reactive protein, and inflammatory illnesses are associated with greater rates of major depression. Indeed, that’s what’s found in a variety of inflammatory conditions including more benign inflammatory conditions, such as asthma and allergies. And, that’s important, suggesting the mood symptoms are not simply ‘feeling bad about having a terrible disease,’ but may be directly tied to the inflammation. Most powerfully, you can actually induce depression by inducing inflammation, like when we give interferon for certain cancers or chronic infections—up to 50% go on to suffer major depression. Even just giving a vaccine can cause enough inflammation to trigger depressive symptoms. Taken together, these studies are strongly suggestive of inflammation being a causative factor of mood symptoms.
So, can an anti-inflammatory diet help prevent depression? We didn’t know, until about 43,000 women without depression were followed, along with their diets, for about a dozen years to see who became depressed, and it was those who ate a more inflammatory dietary pattern, characterized by more soda, refined grains and meat, suggesting that chronic inflammation may underlie the association between diet and depression. Normally, we think of omega-3’s as anti-inflammatory, but they found fish to be pro-inflammatory, associated with increased C-reactive protein levels consistent with recent findings that omega-3’s don’t seem to help with either depression or inflammation. The most anti-inflammatory diet is a plant-based diet, which can cut C-reactive protein levels by 30% within two weeks, perhaps because of the anti-inflammatory properties of antioxidants.
I’ve talked about this before, but never explained why antioxidants are anti-inflammatory. Oxidative damage caused by free radicals may cause an autoimmune response in the body by changing the chemical structure of otherwise ubiquitous molecules to generate new structures that the body attacks as foreign. For example, when LDL cholesterol gets oxidized, our body creates antibodies against it and attacks it. And, so, clinical depression can be accompanied by increased oxidative stress and the autoimmune inflammatory responses it creates.
Where else does inflammation come from in our diet? Endotoxins. It’s worth reviewing how the endotoxins in animal products can cause a burst of inflammation within hours of consumption. What does that do to our mood? If you inject endotoxin into people, within a few hours, inflammation shoots up, and so do feelings of depression, as well as feelings of social disconnection from people.
Although previous research has demonstrated that inflammatory activity contributes to depressive symptoms, no work in humans has examined the effect of experimentally induced inflammation on anhedonia, the lack of reaction to pleasurable stimuli, a key diagnostic feature of depression. No work has been done, that is, until now. Within hours of endotoxin hitting their bloodstream, these experimental subjects not only started to feel depressed, but they had significant reductions in activity in the reward center of the brain. They were less excited about winning money playing video games, for example, in the study.
But by eliminating animal products, and eating antioxidant rich diets, we may be able to prevent or treat depression.
To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video. This is just an approximation of the audio contributed by Katie Schloer.
Please consider volunteering to help out on the site.
- A D Lopez, C C Murray. The global burden of disease, 1990-2020. Nat Med. 1998 Nov;4(11):1241-3.
- Y Milaneschi, S Bandinelli, B W Penninx, A M Corsi, F Lauretani, R Vazzana, R D Semba, J M Guralnik, L Ferrucci. The relationship between plasma carotenoids and depressive symptoms in older persons. World J Biol Psychiatry. 2012 Dec;13(8):588-98.
- A Sánchez-Villegas, M A Martínez-González, R Estruch, J Salas-Salvadó, D Corella, M I Covas, F Arós, D Romaguera, E Gómez-Gracia, J Lapetra, X Pintó, J A Martínez, R M Lamuela-Raventós, E Ros, A Gea, J Wärnberg, L Serra-Majem. Mediterranean dietary pattern and depression: the PREDIMED randomized trial. BMC Med. 2013 Sep 20;11:208.
- M A Beydoun, H A Beydoun, A Boueiz, M R Shroff, A B Zonderman. Antioxidant status and its association with elevated depressive symptoms among US adults: National Health and Nutrition Examination Surveys 2005-6. Br J Nutr. 2013 May;109(9):1714-29.
- M Maes, P Galecki, Y S Chang, M Berk. A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Apr 29;35(3):676-92.
- N I Eisenberger, E T Berkman, T K Inagaki, L T Rameson, N M Mashal, M R Irwin. Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward. Biol Psychiatry. 2010 Oct 15;68(8):748-54.
- J D Rosenblat, D S Cha, R B Mansur, R S McIntyre. Inflamed moods: a review of the interactions between inflammation and mood disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2014 Aug 4;53:23-34.
- N I Eisenberger, T K Inagaki, N M Mashal, M R Irwin. Inflammation and social experience: an inflammatory challenge induces feelings of social disconnection in addition to depressed mood. Brain Behav Immun. 2010 May;24(4):558-63.
- S Anders, M Tanaka, D K Kinney. Depression as an evolutionary strategy for defense against infection. Brain Behav Immun. 2013 Jul;31:9-22.
- M Lucas, P Chocano-Bedoya, M B Schulze, F Mirzaei, E J O'Reilly, O I Okereke, F B Hu, W C Willett, A Ascherio. Inflammatory dietary pattern and risk of depression among women. Brain Behav Immun. 2014 Feb;36:46-53.
- T N Raju. The Nobel chronicles. 1927: Julius Wagner-Jauregg (1857-1940). Lancet. 1998 Nov 21;352(9141):1714.
- M Berk, L J Williams, F N Jacka, A O'Neil, J A Pasco, S Moylan, N B Allen, A L Stuart, A C Hayley, M L Byrne, M Maes. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med. 2013 Sep 12;11:200.
- A M Hashmi, Z Butt, M Umair. Is depression an inflammatory condition? A review of available evidence. J Pak Med Assoc. 2013 Jul;63(7):899-906.
- A Madeeh Hashmi, M Awais Aftab, N Mazhar, M Umair, Z Butt. The fiery landscape of depression: A review of the inflammatory hypothesis. Pak J Med Sci. 2013 May;29(3):877-84.
- D J Jenkins, C W Kendall, A Marchie, D A Faulkner, J M Wong, R de Souza, A Emam, T L Parker, E Vidgen, K G Lapsley, E A Trautwein, R G Josse, L A Leiter, P W Connelly. Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and C-reactive protein. JAMA. 2003 Jul 23;290(4):502-10.
- N DellaGioia, J Hannestad. A critical review of human endotoxin administration as an experimental paradigm of depression. Neurosci Biobehav Rev. 2010 Jan;34(1):130-43.
Images thanks to Ars Electronica via Flickr.
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Flashback Friday: Anti-Inflammatory Diet for Depression
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Content URLDoctor's Note
Whoa, I packed a lot into this video! If you’re as much of a sucker for evolutionary biology theory as I am, check out:
More on endotoxins in:
- The Leaky Gut Theory of Why Animal Products Cause Inflammation
- The Exogenous Endotoxin Theory
- Dead Meat Bacteria Endotoxemia
I’ve got gazillions of videos on inflammation, including:
- Which Spices Fight Inflammation?
- How Tumors Use Meat to Grow: Xeno-Autoantibodies
- Potassium and Autoimmune Disease
- Anti-Inflammatory Antioxidants
- Modern Meat Not Ahead of the Game
The study showing that dramatic decrease in inflammation within weeks on a plant-based diet was the one I featured in Biblical Daniel Fast Put to the Test.
And, finally, for more on the effect diet can have on mental health:
- Fighting the Blues with Greens?
- Aspartame and the Brain
- Improving Mood Through Diet
- Exercise vs. Drugs for Depression
- Do Antidepressant Drugs Really Work?
- Antioxidants and Depression
- Can Dehydration Affect Our Mood?
- Plant-Based Diets for Improved Mood and Productivity
- Are Happier People Actually Healthier?
- Which Foods Increase Happiness?
- Best Food for Antidepressant-Induced Sexual Dysfunction
If you haven’t yet, you can subscribe to my videos for free by clicking here. Read our important information about translations here.