Low Toxin Diet Grant Genereux's Theory Of Vitamin A Toxicity

[Amazoniac]

- Vitamin D Disorders in Chronic Kidney Disease | Abdominal Key

Spoiler

 

[Sulcuscentralis]

Hey guys,

I did an interview with Dr. Garrett Smith on my podcast: Ep. 63 Interview Dr. Garrett Smith: Vitamin A is Still a Poison and Other Discoveries - Quax Podcast

I know some of you guys can't stand him, but I respect his willingness to commit to an idea, make predictions, and admit when he is wrong.

In this interview he definitely admits to giving people supplements he now thinks are disastrous

Definitely a controversial figure. Let me know what you think.

Listened to the whole thing. The part about the autopsied liver biopsies was really convincing.Would be great to find out why exaclty were those people liver toxic. The only thing I don't understand is that how can a molecule that is so ubiquitous in foods be toxic in this context? Toxicity is a broadly loaded term in this case.

 

[Tarmander]

Listened to the whole thing. The part about the autopsied liver biopsies was really convincing.Would be great to find out why exaclty were those people liver toxic. The only thing I don't understand is that how can a molecule that is so ubiquitous in foods be toxic in this context? Toxicity is a broadly loaded term in this case.

Thanks for listening

I wouldnt be surprised if the childhood diseases we used to have were a significant form of vitamin A detox and now that we vaccinate against those, we have higher levels.

 

[Lollipop2]

I wouldnt be surprised if the childhood diseases we used to have were a significant form of vitamin A detox and now that we vaccinate against those, we have higher levels.

This is smart and makes sense.

 

[tim333]

Helminth infections, viral infections, smoke exposure, sunlight exposure, frequent pregnancies, many things reduced vA stores in ancient man.

Liver consumption among paleolithic humans was universal however it wasn't always frequent. American indian tribes knew of xeropthalmia which means many american indians had low vA intakes.

HISTORY OF NIGHT BLINDNESS THERAPY
In the history of treating night blindness, the ancient Egyptian, the Babylonians, the Greeks, and many other cultures after them, used animal liver as treatment, like what we did in RAK.

In the Egyptian papyrus Ebers (1500 B.C.) the recommended cure was:[1] “Roasted ox liver, pressed, applied (topical to the eye).” Another ancient Egyptian papyrus, Kahun 1 (1825 B.C.), a gynecological treatise, mentions “instructions for a woman, cannot see, to eat raw liver of an ****.”[2]

The Assyrian medical texts (700 B.C.) describe night blindness. They thought it was caused by rays of the moon and cured by application of ****'s liver to the eyes. They did not put the liver itself in the eye but used the extracted oil and probably enjoyed eating the cooked liver. It is very likely that the ancient Egyptian ritual treatment also ended with the patient eating the liver.

The Greeks shifted the recommendation from topical application to frank eating “raw beef liver, soaked in honey, to be taken once or twice (daily) by mouth.” Galen (130 AD-210 AD), recommends: “Continuous eating of… liver of goats.”[3]

It is clear that the choice of the animal is influenced by its availability in the community. The Chinese Sun-szu-mo (7th century AD) in his 1000 Golden Remedies describes a cure by administration of pig's liver.[4]

As recently as 1978 Hussaini et al.:[5] Observed several treatment sessions of night blindness in rural Java. The juice of lamb liver was applied topically to the eyes of night-blind children. The procedure was exactly as described by the ancient Egyptians, “except for one small addition: Rather than discarding the remaining organ, the (practitioners) fed it to the affected child… This was never considered part of the therapy itself.” Similarly, in 1928 Aykroyd[6] wrote: “I have been told of a custom of steaming the eyes over cooking liver, which is then eaten,” as a remedy for night blindness in the Canadian Newfoundland Island.

With respect to Arab civilization I found that the Abbasid Physician Hunayn Ibn Ishaq (809–873) recommended in his book “Seven Articles on the Eye” the same procedure of rubbing the liver oil in the eye, but also added two more suggestions: “Get the smoke from the cooking liver goes into the eye” plus eat the liver. He specified goat liver.

Now we know that the cause of night blindness is deficiency in Vitamin A and the real therapeutic benefit comes from eating the liver. Animal liver, including that of fish, is very rich with Vitamin A, because the liver is the store house of Vitamin A in the body. Some ancient medical practitioners prescribed rubbing the liver oil in the eye, but patients could not resist eating the tasty barbequed liver. The Greeks frankly recommended eating the liver as treatment for night blindness. Hunayn Ibn Ishaq took the idea from them because he is credited for translating several Greek medical books to Arabic. In ancient time, they must have realized that there was a nutritional deficiency as the cause of that disease. Arabic poetry written by Hunayn's contemporary poet ibn Duraid (837–933) who lived in the same city of Bagdad, said that night blindness (asha) was caused by dinner (asha), that is, lack of dinner:

The eye asha
Is caused by asha

The two words in Arabic not only rhyme together but actually sound the same, hence the poetic effect.

In the later middle ages, the Dutch Physician Jacob van Maerlandt (1235–1299) wrote the following poem recommending eating the liver:[7]

Who does not at night see right
Eats the liver of the goat
He will then see better at night

So, from the above historical review, it was not surprising that such ancient treatment of night blindness was transmitted over centuries to the Arabs and reached RAK for me to witness.

Night Blindness and Ancient Remedy

If the above is not convincing enough to discount the idea that vA is a toxin please read:

Experimental Induction of Vitamin A Deficiency in Humans

Can we please put to rest the idea that vA is a toxin? It's flat earther style science denialism. Chronic subclinical Hypervitaminosis A is an important public health concern and it is important to separate fact from fiction if the issue of chronic subclinical Hypervitaminosis A is to gain more public awareness and acceptance.

 

[Lollipop2]

Can we please put to rest the idea that vA is a toxin? It's flat earther style science denialism. Chronic subclinical Hypervitaminosis A is an important public health concern and it is important to separate fact from fiction if the issue of chronic subclinical Hypervitaminosis A is to gain more public awareness and acceptance.

+1 Sanity.

 

[Recoen]

For those who think they have vitamin A toxicity, have you had your glucuronidation checked?

 

[tim333]

For those who think they have vitamin A toxicity, have you had your glucuronidation checked?

How does one do that?

UDP-glucuronyltransferase/UDP-glucuronosyltransferase is riboflavin dependent so I'm guessing riboflavin deficiency (which studies show over 60% of people suffer from) is a major cause of poor glucuronidation. I want to add though that I don't recommend riboflavin supplementation.

 

[tim333]

+1 Sanity.

 

[mrchibbs]

Can we please put to rest the idea that vA is a toxin? It's flat earther style science denialism. Chronic subclinical Hypervitaminosis A is an important public health concern and it is important to separate fact from fiction if the issue of chronic subclinical Hypervitaminosis A is to gain more public awareness and acceptance.

@tim333

I appreciate your knowledge and balanced perspective on this topic. Personally, I suspect that it is the continuous decline in metabolism and thyroid function over the last century that is allowing the vitamin A (and cholesterol) to accumulate and oxidize in the tissues, thereby causing a host of ‘toxicity’ symptoms. From what I understand the turnover of vA is extremely fast when thyroid function is optimal. There is a layer of complexity because zinc for instance is needed for vA metabolism, like the b-vitamins, and a deficiency of those nutrients itself causes hypothyroidism. Vitamin C and E seem to be therapeutic in high supra-physiological amounts as antioxidants, perhaps because of this accumulation of vA in the tissues. It would seem, to me at least, that the best way to ‘detox’ is to become slightly hyperthyroid, at least for a while.

 

[tim333]

@tim333

I appreciate your knowledge and balanced perspective on this topic. Personally, I suspect that it is the continuous decline in metabolism and thyroid function over the last century that is allowing the vitamin A (and cholesterol) to accumulate and oxidize in the tissues, thereby causing a host of ‘toxicity’ symptoms. From what I understand the turnover of vA is extremely fast when thyroid function is optimal. There is a layer of complexity because zinc for instance is needed for vA metabolism, like the b-vitamins, and a deficiency of those nutrients itself causes hypothyroidism. Vitamin C and E seem to be therapeutic in high supra-physiological amounts as antioxidants, perhaps because of this accumulation of vA in the tissues. It would seem, to me at least, that the best way to ‘detox’ is to become slightly hyperthyroid, at least for a while.

Thank you mrchibbs. Yes I think you are spot on. It is a vicious cycle, hypothyroidism encourages Hypervitaminosis A and vice versa. People's liver and serum retinol increases with age while thyroid function declines. When thyroid function is optimal, my understanding also is that both beta-carotene and retinol is metabolized much faster.

Pretty every much other vitamin is depleted by Hypervitaminosis A: thiamin, riboflavin, pantothenic acid, folate, biotin, choline, C, D, E, K2. I haven't tried megadoses of E but I haven't found supplementation of thiamin, riboflavin, C, choline or D to be helpful. At the moment I take tiny amounts of both taurine (couple of cans of Red Bull per week) and D. Taurine helps with actual excretion. With Hypervitaminosis A we don't want to stimulate the dehydrogenase enzymes that convert retinol to retinoic acid in my opinion, we just want to optimize the physiology responsible for actually excreting retinoids.

With increasing thyroid function are you thinking along the lines of glandular supplementation?

 

[tim333]

It's been established that there are important genetic differences in vA tolerance as well. Inuit children may feast on liver regularly without issue but many non-Inuit would get sick from doing that. People of European descent are mostly descended from peasants that had grain and legume based diets low in iron and vA.

Inuit child enjoying raw liver:

Pottage and bread, a staple of the middle age peasant:

 

[gaze]

this debate should have ended once grant stated his cholesterol is 110 and heart rate is 50. Thats not health, that sounds more like an entire hormonal shutdown

 

[Amazoniac]

- A mitochondrial enzyme degrades carotenoids and protects against oxidative stress

Spoiler

"Mammalian genomes encode 3 related proteins that belong to an ancestral family of carotenoid-cleaving enzymes (5). The structures of RPE65 and a bacterial apocarotenoid-oxygenase recently have been solved (27, 28). One of the most prominent structural features of these proteins is that the active center, defined by a coordinated ferrous iron, is accessible through a large kinked tunnel. Biochemical analysis of the insect carotenoid-oxygenase NinaB revealed that the enzyme interacts with one of the two ionone ring sites of its carotenoid substrates in a positioned manner (20). For mammalian BCMO1, this interaction clearly requires a nonsubstituted β-ionone ring site, explaining its specificity for a limited number of proretinoid carotenoids, such as β,β-carotene (8). We found that BCDO2 catalyzed the conversion of both β,β-carotene and xanthophylls, such as lutein. This finding indicates that the enzyme can interact both with β- and ε-3-OH-ionone ring sites of carotenoids. In this reaction, BCDO2 removed both ionone ring sites from its substrates by oxidative cleavage at position C9,C10, and C9′,C10′, resulting in the formation of the C14-dialdehyde rosafluene and 2 inone molecules. BCDO2 has been previously shown to metabolize even noncyclic carotenoids, such as lycopene (12). We also found a marked difference in the subcellular localization of the two mammalian carotenoid-oxygenases. BCMO1 is a cytoplasm protein (8), whereas BCDO2 localized to mitochondria both in vitro in the experimental cell line and in vivo. Thus, BCDO2 is a mitochondrial protein that displays broad substrate specificity for carotenoids."

"BCDO2 is expressed in various tissues, including liver, heart, and skeletal muscle (30). To answer the question of the requirement of a mitochondrial carotenoid-oxygenase in such tissues, we established a BCDO2-deficient mouse model. In BCDO2-deficient mice, zeaxanthin and lutein accumulated in several tissues in the form of their oxidized 3-dehydro metabolites." "We chose these xanthophylls because they cannot be metabolized by BCMO1 that is still expressed in BCDO2-deficient mice." "This accumulation also was evident in HET animals, indicating that the loss of one allele causes haploinsufficiency, thus highlighting the importance of BCDO2 for carotenoid homeostasis. A production of 3-dehydrocarotenoids from xanthophylls has also been described in humans (31, 32). In WT mice, a 7-fold induction of BCDO2 mRNA expression largely prevented this accumulation. Interestingly, we found no accumulation of apocarotenoid cleavage products, such as 3-OH-10′-apocartenoids and rosafluene, in WT mice, indicating that these compounds are rapidly degraded and/or secreted by pathways that await molecular description."

Spoiler

"In agreement with its subcellular localization, carotenoid accumulation was evident in isolated hepatic mitochondria in BCDO2−/− mice. In contrast, no carotenoids were detected in hepatic mitochondria of WT mice that express BCDO2. Carotenoids are lipophilic molecules with an extended polyene chromophore that can act as an electron sink (1). In addition, these rigid lipids may disturb membrane topology of mitochondria. We showed for isolated hepatic mitochondria that accumulated carotenoids directly interfered with the mitochondrial electron transport chain. ADP-dependent respiration, respiration with high ADP, and uncoupled respiration of BCDO2-deficient mitochondria were all significantly reduced in different complexes in mice fed the lutein diet. The levels of MnSOD, a classical marker for mitochondrial dysfunction, were increased 9-fold in BCDO2−/− mice as compared to WT mice fed supplemental carotenoids. Disturbances of mitochondrial electron transport chain can result in the production of ROS (25). In this context, we found that carotenoids induced ROS production in human HepG2 cells. With JC-1 staining of cells, we showed that carotenoids can even depolarize mitochondrial membrane potential in HepG2 cells. This impairment was not only induced on 3-dehydrocarotenoid treatment but also on treatments with β,β-carotene, zeaxanthin, and lutein. Expression of recombinant murine BCDO2 in HepG2 cells prior to β,β-carotene treatment significantly reduced ROS production and also protected against mitochondrial membrane depolarization. Previously, it has been reported that lycopene treatment of human cell lines can impair mitochondrial function (33). These findings explain the broad substrate specificity of BCDO2 that protects mitochondria against diverse carotenoids."

"Carotenoid-induced oxidative stress also was evidenced in BCDO2−/− mice, as observed by significantly increased protein levels of HIF1α. HIF1α protein is stabilized in response to increased generation of ROS in mitochondria to activate cellular responses that counteract this condition (34). Moreover, protein levels of phosphorylated AKT and MAPK were significantly increased in the liver. These proteins are key players in oxidative stress-induced pathways that regulate various cellular activities, such as cell proliferation and cell survival/apoptosis (35, 36). Interestingly, this response also was obvious in heterozygous mice that accumulated much lower levels of carotenoids and was not just restricted to the liver but was found in the heart. The induction of pathways related to oxidative stress in the heart of heterozygous animals indicated that carotenoids can induce oxidative stress already at relatively low concentrations (0.2 nmol/g). Moreover, both heterozygous and homozygous animals accumulated triacylglycerides and developed liver steatosis, an impairment that has been associated with mitochondrial dysfunction and oxidative stress (37). Thus, BCDO2 plays a critical role for the protection of tissues against carotenoid-induced mitochondrial dysfunction that can result in oxidative stress and disease."

"Carotenoids are a major source for vitamin A in the human diet and act as scavengers of free radicals and filters of phototoxic blue light in certain tissues. Recent research showed mammals have evolved efficient mechanisms to control carotenoid homeostasis. A negative feedback control mechanism depending on the carotenoid-oxygenase BCMO1 has been elucidated that is responsible for adaptation of intestinal carotenoid absorption to the fluctuating levels in staple food (21). Here, we showed that the second carotenoid-oxygenase plays an even more diversified role for carotenoid homeostasis and degrades both carotenes and xanthophylls to apocarotenoid breakdown products to prevent carotenoid accumulation in mitochondria. However, large clinical trials suggest that high-dose supplementation could be harmful for smokers (for review, see ref. 38), indicating that these control mechanisms can be bypassed under certain circumstances. Studies in rats show that high doses of β,β-carotene induce ROS production in liver and other tissues (39). In ferrets, high-dose supplementation with β,β-carotene induces pathways related to cell proliferation and cancer (40). In part, this limitation is explained by relatively low turnover rates of carotenoid-oxygenases, estimated to be one carotenoid molecule per minute (20). In humans, genetic predisposition may also play a role in this process. Frequent polymorphism in the human BCMO1 gene occurs, and afflicted individuals have increased carotenoid blood levels (15, 41, 42). For BCDO2, a single base pair polymorphism in intron 2 has been identified and correlates with altered blood levels of interleukin 18, a proinflammatory cytokine associated with type 2 diabetes and cardiovascular disease (18). Oxidative stress has been identified as a key element underlying a plethora of human disease such as cancer, diabetes, and cardiovascular and neurodegenerative disease. Thus, our findings likely explain harmful effects of high-dose carotenoid supplementation in people at risk of such disease and identify BCDO2 as a key defender against oxidative stress."

 

[Sulcuscentralis]

this debate should have ended once grant stated his cholesterol is 110 and heart rate is 50. Thats not health, that sounds more like an entire hormonal shutdown

In the interview posted above by Tarmander with Garrett Smith he said that Grant eats nothing but beans and red meat.

 

[gaze]

In the interview posted above by Tarmander with Garrett Smith he said that Grant eats nothing but beans and red meat.

no more white rice?

 

[gaze]

People of European descent are mostly descended from peasants that had grain and legume based diets low in iron and vA.

but a grain and legume based died is extremely high in iron?

 

[Orion]

In the interview posted above by Tarmander with Garrett Smith he said that Grant eats nothing but beans and red meat.

Grant's staples are rice, brown rice, black beans, lean ruminant meat, peeled apples.

 

[Kvothe]

In the interview posted above by Tarmander with Garrett Smith he said that Grant eats nothing but beans and red meat.

He is the true incarnation of the Anti-Peat.

 

[Lollipop2]

@tim333

I appreciate your knowledge and balanced perspective on this topic. Personally, I suspect that it is the continuous decline in metabolism and thyroid function over the last century that is allowing the vitamin A (and cholesterol) to accumulate and oxidize in the tissues, thereby causing a host of ‘toxicity’ symptoms. From what I understand the turnover of vA is extremely fast when thyroid function is optimal. There is a layer of complexity because zinc for instance is needed for vA metabolism, like the b-vitamins, and a deficiency of those nutrients itself causes hypothyroidism. Vitamin C and E seem to be therapeutic in high supra-physiological amounts as antioxidants, perhaps because of this accumulation of vA in the tissues. It would seem, to me at least, that the best way to ‘detox’ is to become slightly hyperthyroid, at least for a while.

+1