Click to listen to the audio…
Transcript of “How antioxidants REALLY work”
You’ve got a FIRE burning somewhere….
- Maybe it’s in your belly (diabesity),
- Maybe in a joint (arthritis) or in your bones (osteoporosis),
- Maybe in a blood vessel (atherosclerosis) etc.
It’s a PROBLEM.
You’re not sure of all the details, but you know free radicals, are behind this inflammatory FIRE. These pesky electron fireballs, are zooting around your body, creating havoc. The trouble arises, when they accidently smash into a membrane or a piece of DNA or a protein, oxidizing it in the process – the impact has dire consequences.
You can mitigate this damage, by sending in an anti-oxidant. Well that’s the theory.
It’s the FIRE of life
Free radicals are created as part of normal biology……
- They are produced as fuel is burned in the mitochondria
- The immune system, uses them to kill foreign invaders and
- The detoxification system, creates them when it kick starts the clean up process
They’re not BAD per se. When the levels of production are moderate.
But, a cell that is “burning the candle at both ends”, inevitably produces more of these reactive oxygen species (ROS). And when ROS levels begin to rise…… things can become unpleasant.
So, cells make a plan. They have a sophisticated anti-oxidant system of their own……..
When cells get a little stressed
They activate this system…… via the Nrf2/keap1/ARE pathway.
In a jiffy, 500 odd genes are engaged, some are “switched” on, some are “switched” off – a multitude of enzymes and proteins are released, including glutathione, the body’s number one, anti-oxidant.
The ROS problem is taken care of…………
The cell goes from REDOX 3 back down to REDOX 2.
Assuming the switch is triggered…….
So, what triggers the system ?
The keaper of the keys
Keap1 serves as the cell’s ROS Guard. Keap1’s official title is Kelch-like ECH-associated protein – what a mouthful, we’ll just call him Keap1. He is a cool as a cucumber, stoic zinc metalloprotein, which keeps a close eye on the cell’s redox status, while at the same time, keeping the highly strung nrf2, in check.
Nrf2, the nuclear factor (erythroid derived 2) -like 2, is a worry-wart.
As far as nrf2 is concerned – the sky is always falling. And, everyone in the cell should take action……..
Ignoring a psychotic little transcription factor, is challenging.
One or two enzymes, if they come face to face with the shrieking transcription factor, silence it – permanently. Keap1 on the other hand, keeps nrf2 silent, when the cells redox status is comfortable, but when the redox status, starts to slip, the shrieks of nrf2, help save the day.
So in times of REDOX trouble, Keap1 lets nrf2 go.
The sky is falling
The little transcription factor, makes a run for it – heading towards the cell’s headquarters. It does need a little help, getting through the door of the nucleus, but once inside………
It searchers for allies.
The allies it is looking for sections of the DNA, marked with the antioxidant response element (ARE). These sign posts are typically found at the start of genes that make proteins that help deal with an oxidative crisis.
The cries of the nrf2, spark a flurry of transcription activity inside the nucleus.
The cell begins to build up it’s antioxidant defence force, to take care of the ROS problem………….
With the ROS defence system deployed, the cell’s REDOX status, drops back down, to normal and life continues.
What changes the cell’s redox status ?
Obviously increases in ROS species……….
But, there is a difference between REDOX levels. A cell has 5 REDOX levels.
- At level 1. The cell is close to deceased. Little to no ROS is being produced, this means vital cell processes are not proceeding smoothly, a cell in REDOX 1 has checked out.
- At level 2. Things are swinging along nicely, it is business as usual – this is a happy, healthy cell.
- At level 3. Things are starting to get a little dangerous, but the situation can be contained.
- At level 4. The situation is SERIOUS. The option to contain has been exhausted, the commitment is made to go to full out war. Another transcription factor, NF-kB is on the loose – this little guy is known as the INFLAMMASOME. His deployment only happens when the cell goes to war…..
- At level 5. The cell is engaged in an all out war. And war is ugly ! The cell may survive, but it may not, if apoptosis is triggered – either way, there is going to be collateral damage.
If a cell is producing enough ROS to hit REDOX 4, the ship has sailed.
You want a worry-wart controlling gene expression, not the INFLAMMASOME !
What causes the worry wart to be released ?
Yup. Those chemicals we’ve been told are mopping up free radicals, are actually releasing them…….
Not in a bad way. The release is just enough to move the cell to take action. Like exercise, it’s a hormetic response……
Let’s face it, exercising is HARD GOING on the body. All the pushing and pulling is STRESSFUL. But, what doesn’t kill you, makes you stronger, it builds muscle and charges up the nitric oxide battery.
Antioxidants are working the same way…..
Antioxidants are TOXINS
Mmmmm….. humans are BIG BUGS !
Luckily, dose makes the poison.
The tiny amount ingested by us, is not enough to KILL us, but it is enough to move our cells from REDOX 2 to REDOX 3.
A very necessary precaution, if you’ve just ingested a TOXIN.
Our detoxification system, comes on line and starts DETOXIFYING…………..
Keap1 has his hands full
Curcumin, polyphenols, carotenoids, capsicum etc. torment our ROS guard – when he responds…..
And the full force of the detoxification system is unleashed – on the “tormenting” phytochemicals and everything else.
REDOX 4 is never reached…..
The cell lives happily ever after.
The dose makes the poison
- A little gets things going
- A lot, releases the INFLAMMASOME, NF-kB and………..ALL HELL BREAKS LOOSE.
Eat your fruits and vegetables on a regular basis. If you don’t, your cells won’t bother assembling the defence team, leaving you vulnerable to infernos.
The most effective strategy to decrease oxidative stress, is to simply eat less, but starving is not actually required…. burning fat is all that is needed.
Red heads don’t just have explosive personalities, the chemistry which creates those rusty locks is pretty explosive too causing metabolic troubles
Those nasty free radicals are needed to hit the appetite off switch in the brain. The obese don’t heed the message because of overactive anti-oxidant systems.
Interested in discovering more tips and strategies that will help you create BETTER BODY CHEMISTRY ?
Enter your e-mail address to get regular updates from the blog.
NOTE : Privacy & spam policy. Spoonful of Science will not rent, trade or sell the e-mail list to anyone. You can unsubscribe at any time by following the unsubscribe link.