I needed to disable self sign-ups because I’ve been getting too many spam-type accounts. Thanks.
Rat liver mitochondria suffers oxidative damage from retinol
https://www.sciencedirect.com/science/article/pii/S0304416505002096
Biological actions of retinoids on modulation of cellular gene expression by nuclear receptors are widely known. Recently, extra-nuclear effects of retinoids have been proposed, but remain to be better elucidated. Considering that retinoids induce apoptosis in tumor cells by an unknown mechanism, and that mitochondria play a key role in controlling apoptosis via cytochrome c (cyt c) release, we exposed rat liver mitochondria to 3–40 μM of retinol (vitamin A), and observed that retinol causes mitochondrial permeability transition (MPT) and cyt c release, in a concentration-dependent pattern. Increased superoxide anion generation and lipoperoxidation were also observed. Cyclosporin A or trolox co-administration reverted all parameters tested. In view of these findings, we conclude that retinol induces mitochondria oxidative damage, leading to MPT and cyt c release by opening of the permeability transition pore, thus suggesting a putative mechanism of apoptosis activation by retinol.
@somuch4food - I was so overwhelmed last year around this time, by Grant's books and blog posts, and making the diet-shift, and yakking every day to those who would give me their ear for 5 minutes - that somehow maybe I missed the import of the studies you were finding, or more likely, that they were adding nitroglycerine to the fuel-mix Grant provided. Like this paper. Just wow! I think that if I did read this last December, (can't imagine not having done so) it was having an effect like the scene in 2001 - A Space Odyssey, where the guy is going through the rings of Saturn and the g-force is almost ripping his cheeks off. I'm kind of in-orbit these days, paying more attention, slowing down, and just wanted to say thanks for your help getting me there/here.
While rummaging through the Science topics, I saw that you also posted the University of Wisconsin, 2006 paper - The Acute and Chronic Toxic Effects of Vitamin A - about a year ago. Another wow! That one has sort of changed my understanding of the meaning of hypervitaminosis-a. The parts about "...subtoxicity without clinical signs of toxicity" and about osteoporosis and hip-fractures resulting from a mere 2x RDA level of retinol-intake are such significant findings, that they should be in the headlines at least once a week across the planet.
It's sounding like "hypervitaminosis-a", as the term is being used in some papers, is very close to our "subclinical" designation. For some reason, I had HVA pictured at one end of an acute-chronic spectrum. It appears that it's being described at both ends. It may come in handy to have a brief history of the terminology being used, easily at hand for some later date. It's kind of similar to the usage of the term "Vitamin A", evolving from meaning just retinol to meaning a large family of molecules. How words are used and subtle shifts that ultimately change their meaning is always in-play. I read one VA-metabolism review paper that actually stated that retinol was a "derivative of Vitamin A", as if the abstraction/category is what's generating real molecules. I think RA was included in the same sentence; like some cornucopia was spewing them both out. Maybe I'm just verbalizing my own learning-curve (usually quite slow) and these things are obvious background-noise for most, I have no idea.
It would be great if we had some kind of expert-system like Stephanie Seneff uses at MIT, or something that could help keep track of what we're finding and maybe help prioritize these studies on some kind of relevance-scale. This one here is a great example of not only 'hitting all the buttons', but putting them in a context that gives us a visualization of what's really happening. Their choice of doses is puzzling though.
Cyclosporin has been used in studies to completely halt hairloss and start regrowth, although I believe has some severe side effects, now could these side effects be the dumping of VA? The listed side effects look a lot like VA toxicity.
Nice find! FWIW here is a review paper on "Vitamin A and Retinoids as Mitochondrial Toxicants." This is the same author who wrote the review on "The Neurotoxic Effects of Vitamin A and Retinoids." He is a Brazilian researcher who seems to have realized how toxic vitamin A can be.
On a related note, one of the world's leading experts on Autism, Dr. Andrew Zimmerman, has concluded that vaccinations can cause autism in children with mitochondrial disorders, and he posits specific mechanisms that as far as I know are untested. One has to wonder to what extent this apparent connection is spurious, and in fact it is vitamin A toxicity (induced by vaccine damage to the liver a la Mawson) that is causing both the mitochondrial damage and the autism.
Thanks Josh, nothing like a couple of reviews to bring new and interesting things to light. Did you see that he linked a paper by Anthony Mawson. Haven't read it yet but it looks like another good one. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718722/
One paper came in handy in that I've been thinking about changing my bean selections, in order to reduce oxalates. de Oliviera discussed that mitochondria use 'manganese-SOD' for protection. I found Lima beans on a list of high-manganese foods - a perfect match - low oxalate and their manganese might help mitochondria fight VA-induced ROS effects.
I struggle with the chemistry, but look forward to these kind of data-dense papers that get into that side of things.
One day I hope to find the time to read through the growing collection of studies both here and archived at home and make a bullet-point list of all the negative things that retinoids are proven or suspected of doing.
Quote from hillcountry on December 26, 2019, 11:55 amThanks Josh, nothing like a couple of reviews to bring new and interesting things to light. Did you see that he linked a paper by Anthony Mawson. Haven't read it yet but it looks like another good one. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718722/
One paper came in handy in that I've been thinking about changing my bean selections, in order to reduce oxalates. de Oliviera discussed that mitochondria use 'manganese-SOD' for protection. I found Lima beans on a list of high-manganese foods - a perfect match - low oxalate and their manganese might help mitochondria fight VA-induced ROS effects.
I struggle with the chemistry, but look forward to these kind of data-dense papers that get into that side of things.
One day I hope to find the time to read through the growing collection of studies both here and archived at home and make a bullet-point list of all the negative things that retinoids are proven or suspected of doing.
@hillcountry Yes I've seen that paper. I just went to his google scholar page. He has been on retinol's trail since the late 1970s:
https://scholar.google.com/citations?hl=en&user=F2NvKeQAAAAJ&view_op=list_works&sortby=pubdate
A list of negative things that retinoids are proven or suspected of doing would be great. You could start with Garrett's mega symptom list: https://nutritionrestored.com/blog-forum/topic/the-mega-symptom-list-of-poison-vitamin-a-toxicity-and-detox-symptoms/
The references at the bottom of that post are worth checking out.
Cheers!