Quote from Dr. Garrett Smith on November 14, 2018, 9:58 pm

Below are the studies directly linking carotenoids (especially beta-carotene) to multiple mechanisms of toxicity.  I will cover the diseases associated with excess carotenoids in the system first, then I'll go over the science that delves deeper into the mechanisms.  In this first paper, as I have said before, notice how almost EVERY system in the body is affected by these poisons.  I will be adding the layperson's terms for the disease states in brackets:

Carotenemia

Yellow skin discoloration has been reported in uncontrolled diabetes with no history of excess carotene ingestion. Often, the yellow pigmentation resolves with regulating blood sugar.[16] Hypercarotenemia may also be seen in anorexia nervosa.[17][18][19] Lycopenemia, a variant of carotenemia, is a yellow skin pigmentation caused by excessive tomato ingestion.[20][21]. Carotenemia has also been associated with a variety of other conditions such as hypothyroidism [low thyroid function], hypopituitarism [low pituitary function], hypothalamic amenorrhea [lack of menstrual cycles], liver disease, inborn errors of metabolism, nephritic and nephrotic syndromes.[6] [kidney disease] In most of the above condition, Hypercarotenemia is probably associated with hyperlipidemia [high cholesterol and/or triglycerides] or impaired conversion of carotene to vitamin A.[9] [humans need to break carotenoids into retinoids to DETOX them, so if this conversion is not running well, carotenoid toxicity develops] Ingestion of some other chemicals besides carotene could lead to yellow skin staining. Examples include saffron [authors are quite wrong here, saffron is yellow precisely due to carotenoids], quinacrine, tetryl, picric acid, and dinitrophenol.[6] Carotenemia was also reported as a presentation for systemic lambda-type AL amyloidosis.[22] Neurological degenerative diseases and brain tumor seem (through unclear mechanisms) to affect carotene metabolism and could lead to carotenemia in the context of normal dietary carotene intake.[23] [note that a certain nutrition group that heavily pushes Poison/"Vitamin A" seems to be having a high number of members come down with brain cancer, and remember what I said previously about some not being able to DETOX carotenoids, causing more problems?] Some studies also suggested a correlation between biliary dyskinesia [sluggish/slow/lazy gallbladder], celiac disease [autoimmune reaction to gluten], and high carotene levels.[24][25]

That should wake you up to the idea that maybe carotenoids are NOT GOOD FOR YOU.

It must be noted that it has been shown that the skin itself can convert beta-carotene into retinyl esters.  Retinyl esters are the primary storage form of Poison/"Vitamin A" in the liver, and their measurement can directly show hypervitaminosis A and chronic insidious Vitamin A toxicity.

Carotenoids and DNA damage

[...] the provitamin A carotenoids show a more varied spectrum of effects, sometimes protecting and sometimes enhancing DNA damage. The tendency to exacerbate damage is seen mainly at high concentrations, and might be accounted for by pro-oxidant actions of these carotenoids.

Oxidative DNA damage in human lymphocytes: correlations with plasma levels of α-tocopherol and carotenoids

Carotenoids have been shown to exert antioxidant properties in vitro and to have some protective role in tumor promotion and progression (29), but there is little direct evidence that they protect biological structures against free radicals in vivo. On the contrary, it has recently been demonstrated that administration of β-carotene greatly increases several CYP450 isoforms in rat lung and this increase is positively associated with the overgeneration of superoxide (30). The question of whether carotenoids are significant antioxidants in plasma is difficult to answer. Carotenoids are easily degraded and undergo auto-oxidation. The antioxidant effect of β-carotene depends on oxygen pressure as a result of competition between two reactions, one producing a chain terminator peroxyl radical and the other producing a chain propagator carotenyl radical in the absence or presence of oxygen, respectively (31,32). It has also been shown that lycopene and β-carotene protect cells against oxidatively induced DNA damage (as measured by the Comet assay) only at relatively low concentrations, but increase the extent of damage at higher concentrations (33). It is also possible that carotenoids exert an antioxidant effect when other antioxidants, including vitamin C, are low.

Toxicity of oxidised beta-carotene to cultured human cells

Carotenoids are effective antioxidants in vitro, but they are also susceptible to autoxidation, which generates volatile and biologically active aldehydes and ketones. In a previous study, we showed that autoxidized beta-carotene inhibits Na+-K+-ATPase activity more effectively than aldehydic products derived from lipid peroxidation, such as 4-hydroxynonenal. In this study, we compared mitochondrial dysfunction in cultured human K562 erythroleukaemic and 28 SV4 retinal pigment epithelium (RPE) cells in response to the degradation products of beta-carotene autoxidation using the MTT assay. We found that oxidized beta-carotene is cytotoxic and that mitochondrial function is decreased in both K562 and RPE cells. In addition, the RPE cells were more resistant to this form of oxidative stress, suggesting that its cytotoxicity may depend on cellular antioxidant capacity.

A mitochondrial enzyme degrades carotenoids and protects against oxidative stress

Surprisingly, we found that the third family member, β,β-carotene-9′,10′-oxygenase (BCDO2), is a mitochondrial carotenoid-oxygenase with broad substrate specificity. In BCDO2-deficient mice, carotenoid homeostasis was abrogated, and carotenoids accumulated in several tissues. In hepatic mitochondria, accumulated carotenoids induced key markers of mitochondrial dysfunction, such as manganese superoxide dismutase (9-fold), and reduced rates of ADP-dependent respiration by 30%. This impairment was associated with an 8- to 9-fold induction of phosphor-MAP kinase and phosphor-AKT, markers of cell signaling pathways related to oxidative stress and disease. Administration of carotenoids to human HepG2 cells depolarized mitochondrial membranes and resulted in the production of reactive oxygen species. Thus, our studies in BCDO2-deficient mice and human cell cultures indicate that carotenoids can impair respiration and induce oxidative stress. Mammalian cells thus express a mitochondrial carotenoid-oxygenase that degrades carotenoids to protect these vital organelles.

Beta-carotene breakdown products may impair mitochondrial functions 

Carotenoid breakdown products (CBP) including very reactive aldehydes and epoxides are formed during oxidative attack in the course of antioxidative action. Carotenoid breakdown products inhibit state 3 respiration of isolated rat liver mitochondria at concentrations between 0.5 and 20 microM. In vivo stimulated neutrophils might represent an important source for the generation of CBP, and the lung might be a critical organ in CBP formation. The inhibition of mitochondrial state 3 respiration by CBP is accompanied by a reduced content of protein sulfhydryl groups, decreasing glutathione levels and redox state, and also elevated accumulation of malondialdehyde. Changes in mitochondrial membrane potential favour functional deterioration of the adenine nucleotide translocator (ANT). The findings reflect a basic mechanism of the side effects of BC [Beta-Carotene] supplementation in circumstances of severe oxidative stress induced by CBP representing a class of lipid oxidation products.

Beta-carotene cleavage products after oxidation mediated by hypochlorous acid--a model for neutrophil-derived degradation.

After beta-carotene failed in certain clinical efficacy trials, there is evidence that the carotenoid might even be harmful, especially to smokers, when given in high dosages. These negative effects might be mediated in part also by carotenoid cleavage products (CPs) having a high reactivity towards biomolecules. The authors postulate that in certain tissues oxidative, nonenzymatic cleavage of carotenoids is carried out primarily by oxidants liberated by polymorphonuclear leukocytes (PML). In this study, we show that beta-carotene is degraded by stimulated PML in vitro. This gives the pathophysiological meaning to our further experiments in which beta-carotene degradation by hypochlorous acid and consecutive CP formation were investigated. While formation of apo-carotenals under these conditions has been studied before, this was not the case for short chain products. Performing gas chromatography mass spectrometry, we were able to identify for the first time 5,6-epoxi-beta-ionone, ionene, beta-cyclocitral, beta-ionone, dihydroactinidiolide, and 4-oxo-beta-ionone as CPs formed after degradation of beta-carotene mediated by hypochlorous acid. Our findings may be of biological relevance because beta-carotene CPs are highly reactive and, therefore, potentially toxic.

And finally, the accumulation of carotenoids and retinoids (both Poison/"Vitamin A") in the eyes has been implicated in multiple mechanisms of eye disease:  Carotenoids and retinoids--Poison/"Vitamin A" absolutely do accumulate in many tissues, especially the EYES--and cause long-term problems.

Carotenoids are not innocent or even helpful. They are toxic and lead to Poison/"Vitamin A" toxicity.  The evidence is right here.

It is quite possible that people who are genetically LESS able to cleave carotenoids into retinoids (for further detoxification) may end up in even more health trouble sooner, as the body lacks good detox pathways for carotenoids themselves.