In 1955, there were 38,000 people in the United States that were diagnosed as depressed. In recent years, the latest statistics showed 9 million people suffered from depression. That's a huge rise from just decades, less then 60 years of gap. We're not talking about a little bit depressed. Depressed enough that they're disabled, unable to go to work. It's the number two leading cause of disability now in terms of people not being able to show up for work anymore. It's clearly on the rise. This is happening all over the world, in many industrialized countries.
When we talk about mood issues or depression, serotonin is the first word usually comes into mind. But how many people or even health or medical professionals know who the word serotonin means? Sero, serum, like blood, and tonin or tonifier. When they first discovered serotonin, one of its actions is that it constricts the blood vessels. Before they understood that it was a neurotransmitter, it was operating in your brain, they could see it outside the brain in the blood vessels causing things to constrict.
Serotonin is both inside your brain and outside your brain. Now we're talking about the serotonin outside the brain. It's mostly made in your gut in these enterochromaffin cells in the digestive tract. They produce 95-96% of all the serotonin in the body in the digestive tract. Your gut or also known as your second brain makes it. In the gut itself, it causes peristaltic action or contraction of the gut. That's its job there. You get tons of serotonin, you would get loose stools or diarrhea.You don't have enough serotonin you could get constipated. This again is just the serotonin in the gut.
In today's post. let's talk about toxins and free radicals affect on the brain and depression. First off, there is report from American Academy of Pediatrics that 74 billion pounds of chemicals that are being imported or produced in the United States every single day! Is it possible then that the rise in chemicals could be associated with the rise in many of the chronic diseases we're seeing today?
When you look at these chemicals and each and every one of them has some component of degrading mitochondrial function, whether it's in the electron transport chain, complex 1, complex 2, or whether it's in the Kreb's cycle or intermediates or co-factors.
Let's go down to the basics. What is the mitochondria? It's the energy powerhouse of the cell. What it means is it's where you take in your outside sources of fuel. Your carbohydrates, your amino acids. your fatty acids, and you turn them into what would be considered cellular currency, something called adenosine triphosphate or ATP. It's the powerhouse. It takes in the nutrients and makes energy out of them. I'm not going to explain too much of details as you can do further research on mitochondria from the internet.
Now, let's discuss about oxidative stress. Oxidative stress basically means destabilization, stealing of an electron from the outer orbital of a compound. Let's say you had alpha lipoic acid. Alpha lipoic acid normally has a very generous ability to give somebody an electron. When it gives somebody an electron, it's missing an electron. Alpha lipoic acid doesn't behave badly when it's missing an electron but if you have a toxin. Another example could be some benzene compound from cigarette smoke, and you're missing an electron, that substance will circulate around in the body. It will find a tissue and it will steal an electron from that substance. In doing so, it causes instability. Think of someone who always borrow money from you. Let's say your colleague or friend who always come to you and say " I need to borrow 30 bucks from you", and this loaning money activity keeps repeating again and again and causes instability. And of course, you know that something is really wrong here.
On the other hand, then there is the 'anti-oxidant' groups of people. These people often very generous and offer a helping hand. They are often giving and reduce the damage caused by the borrowers. Basically, oxidative stress means there are too many environmental people or constituents in your cell that are stealing all the time, these electrons.
The question is, what oxidative stress has to do with depression? What you can do is you can cause oxidative stress by exciting the immune system. Sometimes the immune cells will go around and attack constituents, let's say harmed cells, or let's say bacterial invaders. They’ll actually form oxidants in order to combat that particular damage or that particular organism. You can actually form radicals, what they call free radicals, that are unstable and steal electrons by activating the immune system constantly.
On the other hand, then there is the 'anti-oxidant' groups of people. These people often very generous and offer a helping hand. They are often giving and reduce the damage caused by the borrowers. Basically, oxidative stress means there are too many environmental people or constituents in your cell that are stealing all the time, these electrons.
The question is, what oxidative stress has to do with depression? What you can do is you can cause oxidative stress by exciting the immune system. Sometimes the immune cells will go around and attack constituents, let's say harmed cells, or let's say bacterial invaders. They’ll actually form oxidants in order to combat that particular damage or that particular organism. You can actually form radicals, what they call free radicals, that are unstable and steal electrons by activating the immune system constantly.
One good example, inflammation itself can cause that. If you don't have enough of the antioxidants around, you can destabilize in so many different ways. Any chemical that comes in that can pull off an electron. Mercury, another example, is a known toxin that everybody knows about. It can rob really, really quickly, destabilize the cell and form free radicals.
Think about it for a second. Digestion is the key for activating the inflammatory response, for activating the immune cells. You have more then 70% of your immune cells in your intestinal tract. All you have to do is excite them and then they'll secrete those inflammatory cytokines which will then end up next stop in the liver, activating the Kupffer cells there.The next step after that is the brain, activating the microglia and opening up the blood-brain-barrier. We now see there is a tight association with intestinal permeability and blood-brain-barrier permeability.
Think about it for a second. Digestion is the key for activating the inflammatory response, for activating the immune cells. You have more then 70% of your immune cells in your intestinal tract. All you have to do is excite them and then they'll secrete those inflammatory cytokines which will then end up next stop in the liver, activating the Kupffer cells there.The next step after that is the brain, activating the microglia and opening up the blood-brain-barrier. We now see there is a tight association with intestinal permeability and blood-brain-barrier permeability.
Lifestyle factors such as poor diet, smoking tobacco, things of that sort all cause oxidative stress. Now what does the oxidative stress have to do with depression? So many different ways. Let's take a simple one that everybody will understand. Let's take, for example, tryptophan metabolism. Many people when they're depressed, they'll take something called an SSRI, a selective serotonin re-uptake inhibitor. This is to keep serotonin around in the synapse longer so you will actually have activation from serotonin, the feel-good neurotransmitter. That feel-good neurotransmitter has to be made from something right?
There are building blocks for serotonin. The prime building block is tryptophan. Tryptophan is the
least common amino acid in the human body. You're lucky if you're getting couple of grams per day. It's tough to have it around so you really want to be efficient at turning tryptophan into things that you
need for proper mood like 5-HTP and serotonin but, guess what? The first step in the metabolic process, the biochemical step from taking tryptophan into 5-HTP needs a co-factor.
The co-factor is called BH4. This co-factor is very prone to oxidative stress and unstable. BH4 is also needed for other neurotransmitters such as dopamine. Phenylalanine to tyrosine and tyrosine to L-Dopa, and this very co-factor is needed but extremely prone to oxidative stress. Dopamine is known as the reward neurotransmitter. You feel accomplished in life. You feel secure with yourself.
So, if you have high level of inflammation and oxidative stress, a basic math calculation and common sense will tell you that you may not feel as happy and secure in your life due to depleted BH4 co-factor. The end products of needed neurotransmitters are low and insufficient. You may suffer from mood swings or feeling lousy most of the time.
On the other side of the coin, In states of inflammation, in states of oxidative stress, you will up regulate certain enzymes, an enzyme called IDO. This IDO enzyme actually will degrade tryptophan. Instead of pushing tryptophan through the serotonin pathway, when you have a lot of inflammation, when you're activating the microglia in the brain, for example, and you have chemical exposures, you've got stress, you have whatever it is that's activating the microglia, then you'll actually turn on these cytokines, and in turn, it turn on IDO enzymes. Cytokines is inflammatory, can activate IDO enzymes, and cause oxidative stress.
This IDO enzyme then will, instead of taking tryptophan to serotonin, will take tryptophan down this kynurenine pathway. The kynurenine pathway can actually end up producing something called quinolinic acid. It is neurotoxic and a toxin that actually binds to a very excitatory receptor in the brain called NMDA. It can lead to anxious and depressive type symptoms. In a nutshell, inflammation, oxidative stress play a crucial role in brain health and arguably one of the most important variables in determining if one is at risk of depression.
References/Journals:
http://www.ncbi.nlm.nih.gov/pubmed/26130057
http://www.ncbi.nlm.nih.gov/pubmed/26028548
http://www.ncbi.nlm.nih.gov/pubmed/25900439
http://www.ncbi.nlm.nih.gov/pubmed/25865484
http://www.ncbi.nlm.nih.gov/pubmed/25825158
http://www.ncbi.nlm.nih.gov/pubmed/26083579
http://www.ncbi.nlm.nih.gov/pubmed/25907742
There are building blocks for serotonin. The prime building block is tryptophan. Tryptophan is the
least common amino acid in the human body. You're lucky if you're getting couple of grams per day. It's tough to have it around so you really want to be efficient at turning tryptophan into things that you
need for proper mood like 5-HTP and serotonin but, guess what? The first step in the metabolic process, the biochemical step from taking tryptophan into 5-HTP needs a co-factor.
The co-factor is called BH4. This co-factor is very prone to oxidative stress and unstable. BH4 is also needed for other neurotransmitters such as dopamine. Phenylalanine to tyrosine and tyrosine to L-Dopa, and this very co-factor is needed but extremely prone to oxidative stress. Dopamine is known as the reward neurotransmitter. You feel accomplished in life. You feel secure with yourself.
So, if you have high level of inflammation and oxidative stress, a basic math calculation and common sense will tell you that you may not feel as happy and secure in your life due to depleted BH4 co-factor. The end products of needed neurotransmitters are low and insufficient. You may suffer from mood swings or feeling lousy most of the time.
On the other side of the coin, In states of inflammation, in states of oxidative stress, you will up regulate certain enzymes, an enzyme called IDO. This IDO enzyme actually will degrade tryptophan. Instead of pushing tryptophan through the serotonin pathway, when you have a lot of inflammation, when you're activating the microglia in the brain, for example, and you have chemical exposures, you've got stress, you have whatever it is that's activating the microglia, then you'll actually turn on these cytokines, and in turn, it turn on IDO enzymes. Cytokines is inflammatory, can activate IDO enzymes, and cause oxidative stress.
This IDO enzyme then will, instead of taking tryptophan to serotonin, will take tryptophan down this kynurenine pathway. The kynurenine pathway can actually end up producing something called quinolinic acid. It is neurotoxic and a toxin that actually binds to a very excitatory receptor in the brain called NMDA. It can lead to anxious and depressive type symptoms. In a nutshell, inflammation, oxidative stress play a crucial role in brain health and arguably one of the most important variables in determining if one is at risk of depression.
References/Journals:
http://www.ncbi.nlm.nih.gov/pubmed/26130057
http://www.ncbi.nlm.nih.gov/pubmed/26028548
http://www.ncbi.nlm.nih.gov/pubmed/25900439
http://www.ncbi.nlm.nih.gov/pubmed/25865484
http://www.ncbi.nlm.nih.gov/pubmed/25825158
http://www.ncbi.nlm.nih.gov/pubmed/26083579
http://www.ncbi.nlm.nih.gov/pubmed/25907742
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