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The false carotenoid conversion factors for vitamin A
(This is a repost of a comment I made on another thread: https://ggenereux.blog/discussion/topic/intake-limit-beta-carotene/?part=2#postid-14016)
I have looked a bit into the carotenoid conversion factors and I can say that they are all false and blatantly wrong. I can start by falsify it by showing that the absorption of beta-carotene varies by huge amounts depending on intake. One huge flaw is the assumption that absorption is the same independent of beta-carotene intake which is blatantly false even by a 1985 study cited in the IoM (Institute of Medicine, now National Academy of Medicine) 2001 report that are the one report that made-up the new RAE standard (Retinol Activity Equivalent). Link to the IoM 2001 report: https://www.nap.edu/read/10026/chapter/1
See the abstract of that 1985 study by Brubacher and Weiser called "The Vitamin A activity of beta-carotene". It says how absorption depends on intake, at low intakes absorption can be as high as 2 beta-carotene = 1 retinol. The also recommends against using a fixed carotenoid conversion factor and recommends just writing out Beta-carotene amount in mcg: https://pubmed.ncbi.nlm.nih.gov/3997397/
Just the fact there had been three different standards for vitamin A (IU, RE and RAE) and the only difference between them being that they make carotenoids look more and more harmless by each new iteration. That is very telling as of how bad these carotenoid conversion factors really are, they never seem to get it right when they are simply lying and cherry-picking about studies. See the table at wikipedia vitamin A under the headline "Equivalencies of retinoids and carotenoids (IU)": https://en.m.wikipedia.org/wiki/Vitamin_A
I don't know the real conversion factor of carotenoids, and no one else seems to really know either since human trials on low vitamin A diets are deemed "un-ethical" because they say vitamin A deficiency is so horrible. Maybe there exists some helpful older human study on this, I don't know.
The closest I have found was one 2010 rat study on just beta-carotene and alpha-carotene absorption, and about 1/3 of these carotenoids ingested got stored in the rat's liver, as 1 unit retinol per 3 units of beta- or alpha-carotene ingested. This is not expressed in the study but can be calculated from the values presented in Table 2. It is a really well done 2010 study, which even measures the vitamin A content of the vitamin A deficiency diet. The study is called "Bioconversion Efficiency of Beta-carotene from Mango Fruit and Carrots in Vitamin A" by : https://www.thescipub.com/abstract/10.3844/ajabssp.2010.301.308
Note that retinol is mainly stored as retinyl esters in the liver, retinol is always used as measuring unit, which together with the awful carotenoid conversion factors hides the fact of how bad super-high carotenoid foods really are for most people. The newest and worst vitamin A standard, RAE, has mainly been used about the last 10 years, together with the promotion of for example sweet potatoes.
So if you want an easy number to go by I think you can assume 3 mcg beta-carotene/alpha-carotene = 1 mcg retinol. Carotenoids eaten with fat had a bit higher absorption in that 2010 study, so lower fat is better.
PS. Also note that I haven't really seen any vitamin A animal study that is not flawed. That is since they use highly processed casein as the main protein source. Casein contains some retinol which probably, in some degree, gets converted into retinoic acid during high temperature processing and then feed to the test animals. @ggenereux2014 can probably add other things that are flawed with the diets of these types of animal studies. Assuming a low vitamin A diet while feeding casein will skew these animal studies, making them flawed. With casein as a main protein source it will be a co-founding factor which makes is hard to make any really good conclusion from these types of studies. The 1/3 factor I mentioned above is also from these kinds of flawed animal studies. So take it with a grain of salt. Personally I wonder where does the rest of carotenoids go?
-Are the carotenoids absorbed in the lymph fluids and then stored in fat and tissues other than the liver, and how much is just excreted in the stool (never absorbed)?
EDIT: All the calculations in this comment are wrong, see my newer post just below this one for updated calculations (presented in a table).
WRONG CALCULATIONS:
Here are the simple calculations using values from Table 2 that seems to show the correlation between total carotenoid intake (mainly alpha- and beta-carotene) and retinol accumulated in the liver:
LRA = Liver Retinol AccumulationI_TC = Intake of total carotenoids (mainly alpha- and beta-carotene)
For the mango (M): LRA / I_TC = 32% which only increases to 41% when mixed with oil (M+O) but may be due to the already high-fat diet.
For carrots (C): LRA / I_TC = 35%
As I said in the original post, I believe the carotenoid conversion factors for RAE/RE are all totally bogus. When just comparing carotenoid content of different foods I think the main factor to look at is the total amount carotenoids in micro-gram.
Uploaded files:
Update: Correcting my errornous calculations I did in the posts above and if a general estimation of a carotenoid conversion factor should be used (while being mostly wrong), I think about 1/6 (~17%) of eaten carotenoids can be absorbed from the diet. More factors than just intake of carotenoids are mentioned at the end of the post.
The 2010 Mexican study mention in my original post looked at how VA storage in rat livers increased after the rats first have had their liver VA storage reduced and then four different groups where fed supplemental betacarotene+fat, mango+fat, mango or carrot with the a very similar beta-carotene amount in weight per rat (122.1-132.1 µg beta-carotene per rat). Please also note that all the rats were fed a non-low fat diet consisting of 10.75wt% (% by weight) soy bean oil.
From that study I made a glaring fault in that I forgot to account that the rats didn't have zero VA liver storage at the start but about 0.525 mg VA per g of liver. I believe rats are very good at converting carotenoids into retinol/retinaldehyde which means that most of the absorbed carotenoids should get stored in the rat's liver, instead of storing beta-carotene un-altered in other tissues. This might not be 100% correct and some of the absorbed and converted beta-carotene might quickly be converted into retinoic acid which isn't measured in this study.
After I corrected the mistake I got a little bit different results which I present in the attached table where I chose to compare how well the old and present official carotenoid conversion standards (IU, RE, RAE) compare to the results from this 2010 study. I think none of them really looks good other than all of them calculate almost the correct amount for betacarotene+oil which is the most uninteresting case for the real world in my opinion. I took the carotenoid conversion factors from the wikipedia page on vitamin A under the headline "Equivalencies of retinoids and carotenoids (IU)": Vitamin A - Wikipedia.
Instead I tried to find a better way for a carotenoid absorption factor (beta- and alpha-carotene) which doesn't take into account extra added fat (the opposite of the official standards). I found that using a general absorption factor of 1/6 (16.7%) for both beta- and alpha-carotene gave some quite good results for both the mango (99% of measured) and the carrot (139% of measured). I think the carrot was overestimated since I believe it is raw in the study and many the carrots carotenoids are locked into some crystal pattern and are more difficult to absorb. Just like a carrot is harder than a mango which is soft and more easily digested.
Anyway using any estimation of how much carotenoids are absorbed when eaten is likely to be wrong because there are many more factors, known and unknown, that are influencing carotenoid absorption.
Here are some factors besides total carotenoid amount that I can think of:
Fat consumption of course
Different carotenoid retention in different foods
Cooking versus raw
Human absorption variability
Carotenoid absorption decreasing quickly with increased consumption (see the 1984 Brubacher et. al study mentioned in the first post)
Using a general 1/6 absorption factor for carotenoids would then also seem to mean that fat increases absorption by about 50% in foods. Beta-carotene supplements still seems to have a 1/2 absorption factor as per all the official standards. Supplemental beta-carotene with fat is the worst kind of carotenoids and is present in a ton of pre-made meals, snacks and other food-like items.
When I first miscalculated the values from this 2010 Mexican study I made the mistake of thinking that a general carotenoid absorption factor of 1/3 seemed correct. After correcting for my mistake (there was VA liver storage at the start of experiment) I think using 1/6 as a general carotenoid factor seem reasonable but of course not perfect as there are many other factors than just total carotenoid consumption. The 1/6 absorption factor is also used for beta-carotene in the older RE standard but instead I apply it to both beta- and alpha-carotene.
I think a 1/6 carotenoid absorption factor is conservative since there are probably some carotenoids in the rats that has been absorbed and then excreted in some way or just stored in some other tissue than the liver.
PS. A quote from a 2016 study talking about how there seems to be variability in carotenoid absorption between fruits and vegetables but I haven't looked into the quoted sources:
"A number of studies in developing countries examined the bioavailability of β-carotene from individual vegetables and fruit. The bioavailability and bioconversion were low from vegetables (30, 77) and better from orange fruit (78). The determining bioaccessibility factor (i.e., release from the plant matrix) influencing the bioavailability appears to be the location of carotenoids within the chromoplast as opposed to the chloroplasts. In addition, the crystalline form, such as carotene crystals in carrots, may also negatively affect overall bioavailability (79). Cooking and heat processing also disrupt the plant matrix (80), and these processes usually result in greater bioavailability (79)."
Biomarkers of Nutrition for Development (BOND)—Vitamin A Review (nih.gov)
Absorption and conversion of betacarotene is supposed to be under negative feedback control via a transcription factor called ISX. This is why people shouldn’t get toxic from eating betacarotene (so we are taught in nutrition school). This is clearly not true.
I stumbled upon this old article today, I haven't read the studies, but I was not aware that BC could be split in more than one way. Maybe it could be a clue in why some are more sensetive than others? @david have you come across this?
https://www.sciencedaily.com/releases/2012/05/120501134414.htm
Some tidbits:
Previous research has already established that when beta-carotene is metabolized, it is broken in half by an enzyme, which produces two vitamin A molecules.
In this new study, the Ohio State researchers showed that some of these molecules are produced when beta-carotene is broken in a different place by processes that are not yet fully understood and act to antagonize vitamin A.
peared to function as inhibitors of vitamin A action based on how they interacted with receptors that would normally launch the function of vitamin A molecules.
"The original idea was that maybe these compounds work the way vitamin A works, by activating what are called retinoic acid receptors. What we found was they don't activate those receptors. Instead, they inhibit activation of the receptor by retinoic acid," Curley said. "From a drug point of view, vitamin A would be called an agonist that activates a particular pathway, and these are antagonists. They compete for the site where the agonist binds, but they don't activate the site. They inhibit the activation that would normally be expected to occur."
Once that role was defined, the researchers sought to determine how prevalent these molecular components might be in the human body. Analyzing blood samples obtained from six healthy human volunteers, the scientists in the Schwartz lab found that some of these anti-vitamin-A molecules were present in every sample studied, suggesting that they are a common product of beta-carotene metabolism.
The compounds also have been found previously in cantaloupe and other orange-fleshed melons, suggesting humans might even absorb these molecules directly from their diet.
Edit: added the last bit about those compounds being found naturally in orange fleshed melons, meaning they are not just something that comes from synthetic BC. Once again I think of @michele 's success with a fruit diet... (found here: https://ggenereux.blog/discussion/topic/documenting-my-experience/ )
The study (can also be found at the bottom of the article posted above):
https://www.jbc.org/article/S0021-9258(20)46236-2/fulltext
Edit: I skimmed through the study. The conclusion is interesting. This can go 2 ways: either vA from animal sources is a poison, and the "new" end product of BC has a protective effect. Or, vA is essential (albeit probably in way less amounts than currently believed), and this "new" end product cause deficiency, or perhaps both a deficiency and toxicity, as vA cannot attach to receptor and is also flooding the system. Especially when given as a juice or supplement without any potentially protective co-factors (like fiber). I remember a study I read some years back that came to the conclusion BC in the form as fruits and veg was protective but as supplement was not. That study had me question the A is poison theory at the beginning. I think I made a comment about it in one of Grants earlier blog posts...
Today BC is in everyting...
Non-symmetrically cleaved carotenoids (by enzyme or not) becomes classified as part of the group called 'apocarotenoids'. See the attached picture from the 2018 study below on how beta-carotene might be broken down in several different ways with only two of them known to be done by enzymes.
If you are interested in apocarotenoids you can read this 2018 review study, available sci-hub, called:
"Apocarotenoids: Emerging Roles in Mammals"
https://doi.org/10.1146/annurev-nutr-082117-051841
Though it seems like at least some amount of apocarotenoids can be converted into retinal and retinoic acid as per the info-graphic figure from the Linus Pauling Institute at Oregon State University, also attached in the post.
https://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/carotenoids
Thanks @david. Too bad the first one is behind a paywall.
May I ask what your take is on carotenoids in foods (raw vs cooked) vs synthetic? You have read a lot about it I assume. It is believed in here that all forms are poison, but I no longer believe it is that black and white. And the whole point with this forum is getting to the truth, which includes discussing things that goes against our current beliefs. I was hoping for an interesting discussion in this thread 🙂
Science believes carotenoids in food being helpful in preventing disease, while as a concentrated supplement being problematic, potentially causing disease. Absorption of carotenoids depends on cooked vs raw and the presence of fats and soluble fiber.
Anecdotally, @michele got rid of her accutane poisoning on a fruit diet, whereas she failed on Grants diet. She ate raw fruit, with tons of fiber and no added fats (other than the occational avocado as I understood it), meaning absorption of carotenoids must have been low(er), maybe even passning through the system while bound to fibre? Just speculation, but either way if her diet was so horrible, and all A is poison no matter what, she for sure would not have improved. She was poisoned by accutane, so a pretty clear case. I do wonder how she is doing today though, it's been I think 2 years almost since her last update. And she had been on the fruit diet for 2 years or so when she provided her update.
I also come to think of Karen Hurds protocol. Vegetables with every meal, all varieties. Eat nothing sweeter than a carrot. Plenty of PUFA. Beans and psyllium husk. Eggs. If carotenoids was a poison in every situation, she would not have success with autoimmune disease and eczema, as Grant believes A is behind our modern diseases.
And the Wahls protocol. Those suckers should have been melting from the inside out with those huge amounts of veggies taken in every day, Many raw. They also stay away from dairy. Not everyone recoveres from MS (a disease which also has been improved by surgery in the neck, details I have forgotten).
And recently, the thread called Antidote, where the animals getting EFA recovered, despite getting a high dose A (taking from memory)
And case study examples of patients with A poisoning who get better while still eating A, no strict fakir diet necessary.
Grant is proving a point with his diet. But we don't know how much A he is getting from his grass fed beef. A low A diet for sure, but a no A diet? What we do know, is not everyone mimicing his diet gets the same result.
There has been a lot of talk about detox, dumping too much A into the system etc, the egg theory has been ridiculed despite it actually helping people with their symptoms. Because eggs has vA and therefore is poison. And the only reason people are feeling better is because their bodies stop dumping A. I guess time will tell in the end. Those stickning with "no A" diet not improving, and those eating low A improving. The whole point with this theory is to improve ones health? If ones health is not improving, the theory is probably flawed, and one should probably dare to try something different.
The hostile environment showing its ugly face in here from time to time really suck! Science is not about narrowmindedness. It is about finding the truth. No matter how far away it might be from ones personal belief.
Edit: sub carotenoid rich vegetables and fruits for "carotenoids" as clearly (according to science) the "loose" form is proven problematic, whereas in the fruit/veggie it is bound to the fibre (and comes with protective co-factors?) Also, I am by no means saying everyone should start eating carrots, or start eating anything for that matter.
I have edited my previous comment to mention that the 2018 apocarotenoid review study is available at sci-hub.
Too bad that the first link in the original post is unavailable (perhaps deleted by the original poster), I had written about what you were asking about there. But I here is at least a short thought of mine:
I think eating excess fat with excess lutein can be especially problematic in the long run. Lutein and zeaxanthin are two of the most hydrophobic carotenoids and are known to accumulate in the mammalian brain and probably its nerves as well. It might be an explaination as to explain how lutein and zeaxanthin in adipose tissue correlates with heart attacks but not beta-carotene in adipose tissue. As is correlated in a 2005 study found by tim called "Some dietary and adipose tissue carotenoids are associated with the risk of nonfatal acute myocardial infarction in Costa Rica".
https://ggenereux.blog/discussion/topic/lutein-and-zeaxanthin-but-not-beta-carotene-positively-associated-with-heart-disease-risk/
If you go to the very end of the 2018 study "Apocarotenoids: Emerging Roles in Mammals" you can read them saying that there is minimal research about most of the less common apocarotenoids:
"In addition to the most-studied β-carotene, lycopene, lutein, and zeaxanthin, other carotenoids are emerging as beneficial for mammalian health, such as β-cryptoxanthin and astaxanthin (19, 70). To date, these benefits have been mainly attributed to the anti-inflammatory and antioxidant effects of the parent compounds. Nevertheless, it cannot be excluded that their potential beneficial role may be driven by their derivatives. This issue remains to be ascertained. Lastly, many other apocarotenoids are generated in plants that are then ingested as a food. Do these less common apocarotenoids have a biological function?"
If you really are interested in proving that certain carotenoids are essential and beneficial:
Could you design and run a similar experiment as Grant Genereux and others have done with rats/gerbils but feeding one group a specific carotenoid to test out your theory?