Research Forum
Carotenoid metabolism in humans/mammals versus other species is VERY different
Quote from Dr. Garrett Smith on April 5, 2019, 4:17 pmBirds and fish, for example, may process and tolerate carotenoids much better than humans and mammals do. Note how the author talks about EXPECTED HEALTH PROBLEMS in humans at very high levels of carotenoids! They are not innocent at all.
Is There an Immunological Cost to Carotenoid‐Based Ornamental Coloration?
As a matter of fact, the very high levels of circulating carotenoids observed in birds and fish may have serious detrimental health effects if they occur in mammals. For instance, in the 1980s canthaxanthin tablets (a red carotenoid that is used by some species of birds and fish for ornamental coloration) were sold as tanning pills (Roueche 1991). The concentrated dose of canthaxanthin caused various maladies in humans who took them, including aplastic anemia (Bluhm et al. 1990). High carotenoid doses are also known to cause crystal-like deposits in the retina of humans and other primates (Leyon et al. 1990, Goralcyzk 1997). In contrast, I fed male house finches very high doses of canthaxanthin over 4 yr and the birds suffered no apparent ill effects--they simply grew red plumage (Hill 1992, 1993). How birds and fish maintain very high levels of circulating carotenoid pigments without ill effects is unknown. The point is that the differences in levels in circulating carotenoid pigments affect birds and mammals differently and indicate that extrapolating between organisms that are so different in their use of carotenoids may lead to oversimplifications.
What is probably happening here? I'm going to guess that birds don't actually convert carotenoids ("plant Vitamin A") into retinoids ("animal Vitamin A") very much at all, and they can simply hold/store them in their feathers and other places. How did I come to this theory? Because there are multiple studies of people poisoning their lorikeet birds with Poison/"Vitamin A" by giving them "pre-formed Vitamin A" (this means retinoids, not carotenoids), when the birds in the wild would have NEVER eaten any retinoids, but only carotenoids.
Birds and fish, for example, may process and tolerate carotenoids much better than humans and mammals do. Note how the author talks about EXPECTED HEALTH PROBLEMS in humans at very high levels of carotenoids! They are not innocent at all.
Is There an Immunological Cost to Carotenoid‐Based Ornamental Coloration?
As a matter of fact, the very high levels of circulating carotenoids observed in birds and fish may have serious detrimental health effects if they occur in mammals. For instance, in the 1980s canthaxanthin tablets (a red carotenoid that is used by some species of birds and fish for ornamental coloration) were sold as tanning pills (Roueche 1991). The concentrated dose of canthaxanthin caused various maladies in humans who took them, including aplastic anemia (Bluhm et al. 1990). High carotenoid doses are also known to cause crystal-like deposits in the retina of humans and other primates (Leyon et al. 1990, Goralcyzk 1997). In contrast, I fed male house finches very high doses of canthaxanthin over 4 yr and the birds suffered no apparent ill effects--they simply grew red plumage (Hill 1992, 1993). How birds and fish maintain very high levels of circulating carotenoid pigments without ill effects is unknown. The point is that the differences in levels in circulating carotenoid pigments affect birds and mammals differently and indicate that extrapolating between organisms that are so different in their use of carotenoids may lead to oversimplifications.
What is probably happening here? I'm going to guess that birds don't actually convert carotenoids ("plant Vitamin A") into retinoids ("animal Vitamin A") very much at all, and they can simply hold/store them in their feathers and other places. How did I come to this theory? Because there are multiple studies of people poisoning their lorikeet birds with Poison/"Vitamin A" by giving them "pre-formed Vitamin A" (this means retinoids, not carotenoids), when the birds in the wild would have NEVER eaten any retinoids, but only carotenoids.
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Quote from Loskala on April 6, 2019, 5:19 amHi Dr. Smith,
The study below supports your guess that the birds are simply storing the carotenoids directly with no need to convert them to retinol. It describes how proteins are used to bind the carotenoid pigments to the feather follicles.
Variation in carotenoid–protein interaction in bird feathers produces novel plumage coloration
Also, I found the following study that demonstrates that carotenoids by themselves can cause problems in mammals, not just the downstream retinol metabolites. They used a genetic knockout for the BCDO2 enzyme, which is a beta-carotene oxygenase found in the mitochondria. This lead to an accumulation of carotenoids in several tissues, which the author's state "induced key markers of mitochondrial dysfunction" particularly in the liver. For another enzyme BCMO1 they had this to say:
The β,β-carotene-15,15′-monooxygenase (BCMO1) localizes to cytoplasm and converts a limited number of carotenoids, such as β,β-carotene, to retinoids (8). Studies in knockout (KO) mice and humans show that BCMO1 is the critical enzyme for vitamin A production (9, 10).
A mitochondrial enzyme degrades carotenoids and protects against oxidative stress
CMO1 Deficiency Abolishes Vitamin A Production from β-Carotene and Alters Lipid Metabolism in Mice
The author they referenced in (9, second link above) sees this KO as causing Vitamin A deficiency (he means retinol), and thus assumes the various problems (fatty liver, elevated lipid levels, excessive weight gain, etc) the mice then have as being related to Vitamin A production being stopped, not grasping the implications of finding elevated levels of carotenoids stored in the fat. Which seems to be the body's last ditch effort to get the toxin out of the blood, since with the genetic KO it can no longer be metabolized into retinol, and instead the carotenoids must be esterfied with fatty acids for storage? I'm not sure about carotenoids, but a similar esterfication process happens with both retinol and ethanol for storage until removal is possible (see the last two links for more info).
Alcohol and Aldehyde Dehydrogenases: Retinoid Metabolic Effects in Mouse Knockout Models
Hi Dr. Smith,
The study below supports your guess that the birds are simply storing the carotenoids directly with no need to convert them to retinol. It describes how proteins are used to bind the carotenoid pigments to the feather follicles.
Variation in carotenoid–protein interaction in bird feathers produces novel plumage coloration
Also, I found the following study that demonstrates that carotenoids by themselves can cause problems in mammals, not just the downstream retinol metabolites. They used a genetic knockout for the BCDO2 enzyme, which is a beta-carotene oxygenase found in the mitochondria. This lead to an accumulation of carotenoids in several tissues, which the author's state "induced key markers of mitochondrial dysfunction" particularly in the liver. For another enzyme BCMO1 they had this to say:
The β,β-carotene-15,15′-monooxygenase (BCMO1) localizes to cytoplasm and converts a limited number of carotenoids, such as β,β-carotene, to retinoids (8). Studies in knockout (KO) mice and humans show that BCMO1 is the critical enzyme for vitamin A production (9, 10).
A mitochondrial enzyme degrades carotenoids and protects against oxidative stress
CMO1 Deficiency Abolishes Vitamin A Production from β-Carotene and Alters Lipid Metabolism in Mice
The author they referenced in (9, second link above) sees this KO as causing Vitamin A deficiency (he means retinol), and thus assumes the various problems (fatty liver, elevated lipid levels, excessive weight gain, etc) the mice then have as being related to Vitamin A production being stopped, not grasping the implications of finding elevated levels of carotenoids stored in the fat. Which seems to be the body's last ditch effort to get the toxin out of the blood, since with the genetic KO it can no longer be metabolized into retinol, and instead the carotenoids must be esterfied with fatty acids for storage? I'm not sure about carotenoids, but a similar esterfication process happens with both retinol and ethanol for storage until removal is possible (see the last two links for more info).
Alcohol and Aldehyde Dehydrogenases: Retinoid Metabolic Effects in Mouse Knockout Models