Amazoniac
Member
0.01%, the reason to put 'supplementation' before 'diet' in the graph above from the previous post* is for a worst scenario, antecipating the claim that some people are blessed in disguise: incapable of cleaving macabrotenes into poisons. I forgot to point out that the added horizontal line is for the 0.1 umol PA / g liver.
Regarding the dietary component, the contribution is predictable when preformed:
- Genetic Variations Associated with Vitamin A Status and Vitamin A Bioavailability
You know that hypothyroidism and diabetes are associated with poor cleavage of macabrotenoids and macabrotenemia, it can be tempting to supplement the preformed toxin liberally presuming that the body is too pure, but what can be perplexing is that liver reserves of poison A are particularly elevated in these conditions as well (detected through biopsy; open Grant's thread or any anesthesiology book for more details , part or all there)) Perhaps the excess stores is one factor downregulating cleavage on purpose.
In terms of genetic variations that affect proteins function, we is usually concentrated on the main carotenoid oxygenase (that cleaves centrally), but alterations can occur at other levels of poison A metabolism and are overlooked. It's possible to have more of them occuring together with a counteracting effect on status. Example from the link:
Just like before, a poor cleaver may be a poor mobilizer too, and there's no need to invoke genes.
Despite being inferior, it remains possible to derive poisonoids from macabrotenes when the main enzyme fails. I'm bringing this up because there are various factors to consider that can be conflicting.
- Knockout of the Bcmo1 gene results in an inflammatory response in female lung, which is suppressed by dietary beta-carotene
- Challenges to Quantify Total Vitamin Activity: How to Combine the Contribution of Diverse Vitamers?
Generalizing, the consumption of animal products here is high and the plant pattern is the opposite, with lots of fruits. If a person counts on nutrition apps' estimations for poisonol activity, the efficiency of conversion may be underestimated.
Stunts are not uncommon (such as 120 mg of b-macabrotene) and can be misleading:
- A review of vitamin A equivalency of b-carotene in various food matrices for human consumption
And you'll come across more questionable stuff:
- Variability in conversion of β-carotene to vitamin A in men as measured by using a double-tracer study design
Thankfully some were low responders.
We need to use our privilege to protect people as much as we possibly can, how can you not see this? Because if we don't, who will? What we may need is a reformulation and I think that the suggestion to reduce the dose is not unfounded.
In food experiments, they get the average response, which will include the low responders; nonresponders must be rare. Preformed poison A can be assigned to cover the minimum effective dose while the rest is left for macabrotenoids, they is safer in uncertainty of excess. Since most of the requirement will be taken care of by poisonol, a person won't need exorbitant amounts of macabrotenes to make up for an inefficiency.
Various of these links were shared elsewhere on the forum.
*I'm not falling for it anymore, last post was #780 (20/20), which means that this one should be on a new page.
Regarding the dietary component, the contribution is predictable when preformed:
- Genetic Variations Associated with Vitamin A Status and Vitamin A Bioavailability
"A recent analysis of the results of 11 studies in eight developed countries (representing ≈ 120,000 participants) has shown that preformed VA intake accounted for about 65% of total VA intake, while provitamin A carotenoids represented 35% of total VA intake (βC: 86%; α-carotene: 10%; β-cryptoxanthin: 4% thereof, respectively) [13]."
You know that hypothyroidism and diabetes are associated with poor cleavage of macabrotenoids and macabrotenemia, it can be tempting to supplement the preformed toxin liberally presuming that the body is too pure, but what can be perplexing is that liver reserves of poison A are particularly elevated in these conditions as well (detected through biopsy; open Grant's thread or any anesthesiology book for more details , part or all there)) Perhaps the excess stores is one factor downregulating cleavage on purpose.
In terms of genetic variations that affect proteins function, we is usually concentrated on the main carotenoid oxygenase (that cleaves centrally), but alterations can occur at other levels of poison A metabolism and are overlooked. It's possible to have more of them occuring together with a counteracting effect on status. Example from the link:
"Kovarova et al. [94] showed that an SNP in PNPLA3, a gene involved in the mobilization of retinyl esters stored in stellate cells [64], was associated with increased RP liver storage in a group of 42 patients undergoing liver surgery. Interestingly, the minor allele of the SNP is highly prevalent in populations from Latin American (about 70%), whereas it is found at a much lower frequency (around 20%) in populations from Europe and Africa [95]. We suggest that the effect of this SNP could be due both to a lower hydrolysis of liver RP, but also to a lower hydrolysis of intracellular triglycerides that solubilize RP. Indeed, it has been demonstrated that a loss-of-function mutation in PNPLA3 impairs triglyceride hydrolysis [65] and promotes intracellular lipid accumulation by reducing the lipidation of VLDL [96]. Furthermore this mutation, as well as mutations in ATGL, which is the other lipase known to hydrolyze both RP and triglycerides [63], are genetic determinants of chronic liver diseases [97,98,99]."
"For the time being, there are only three studies dedicated to identifying genetic variations associated with postprandial blood VA concentration (Table 1)." "These studies were dedicated to βC metabolism and measured either postprandial chylomicron βC [113] or postprandial triglyceride-rich lipoprotein βC and RP concentrations [114,115] after test meals that provided βC."
↳ [113] A Combination of Single-Nucleotide Polymorphisms Is Associated with Interindividual Variability in Dietary β-Carotene Bioavailability in Healthy Men
↳ [114] Single Nucleotide Polymorphisms Upstream from the -Carotene 15,15'-Monoxygenase Gene Influence Provitamin A Conversion Efficiency in Female Volunteers
↳ [115] Two common single nucleotide polymorphisms in the gene encoding -carotene 15,15'-monoxygenase alter -carotene metabolism in female volunteers
↳ [114] Single Nucleotide Polymorphisms Upstream from the -Carotene 15,15'-Monoxygenase Gene Influence Provitamin A Conversion Efficiency in Female Volunteers
↳ [115] Two common single nucleotide polymorphisms in the gene encoding -carotene 15,15'-monoxygenase alter -carotene metabolism in female volunteers
Just like before, a poor cleaver may be a poor mobilizer too, and there's no need to invoke genes.
Despite being inferior, it remains possible to derive poisonoids from macabrotenes when the main enzyme fails. I'm bringing this up because there are various factors to consider that can be conflicting.
- Knockout of the Bcmo1 gene results in an inflammatory response in female lung, which is suppressed by dietary beta-carotene
- Challenges to Quantify Total Vitamin Activity: How to Combine the Contribution of Diverse Vitamers?
"Vast discrepancy exists between conversion factors reported for different foods and across settings (44, 45). A relatively small number of studies have attempted to assess the conversion factor of β-carotene from an oil-based matrix to retinol, which overall ranged from 2.1 to 3.8. Conversion factors are expressed as the amount (μg) of ingested provitamin A required to form 1 μg of retinol. Until 2001, the average conversion factor of β-carotene from food was considered to be 6, whereas it was 12 for other provitamin A carotenoids. This difference was based on chemical structure, which allows central cleavage of β-carotene to produce 2 retinol molecules, whereas α-carotene and β-cryptoxanthin will only yield 1 retinol molecule. This has resulted in reporting of provitamin A concentrations as retinol equivalents (REs) in food composition tables, taking these conversion factors into account. Based on a range of studies conducted at the end of the previous century [IIIIIIIIIIIIIIIIIII], conversion factors for specific fruits and vegetables were shown to vary from 3 to 12 for tubers and fruits, and from 10 to 77 for cooked and raw vegetables (not including tubers) (44, 45). This prompted the Institute of Medicine in the United States to increase the conversion factors to 12 for β-carotene and 24 for other provitamin A carotenoids (RAEs). This was based on food patterns estimated to deliver ∼20% of provitamin A carotenoids from fruit and ∼80% from vegetables, thereby weighing conversion factors for vegetables more heavily than for fruit. Although many countries have followed suit by using the RAE rather than RE in their national food composition tables and nutrient intake recommendations, the WHO has not yet renewed its intake recommendations published in 2004 and therefore still uses the outdated RE (46). Even so, the revised vitamin A intake recommendations for Europe by the European Food Safety Authority in 2015 retained the old conversion factors (47). This is confusing for anyone trying to assess adequacy of dietary vitamin A intake, and especially relevant for populations with a high dependency on provitamin A intake to fulfill their vitamin A requirements (48)."
Generalizing, the consumption of animal products here is high and the plant pattern is the opposite, with lots of fruits. If a person counts on nutrition apps' estimations for poisonol activity, the efficiency of conversion may be underestimated.
Stunts are not uncommon (such as 120 mg of b-macabrotene) and can be misleading:
- A review of vitamin A equivalency of b-carotene in various food matrices for human consumption
"The fourteen reported VEB measured with labelled b-carotene in oil, presented in Table 2, have a wide range from 2·0:1(54) (healthy children) to 55:1(65) (in one female adult after a pharmaceutical dose of 126 mg b-carotene). In this latter study, a VEB of 3·8:1 was obtained after a labelled dose of 6 mg b-carotene given to the same female subject over 21 d(65). In another study in one male adult, the VEB was 15·9:1 after a very high dose of 16·2mg b-carotene over 23 d(69). These large variations in VEB stress the importance of carrying out experiments to measure VEB using physiological doses of b-carotene."
And you'll come across more questionable stuff:
- Variability in conversion of β-carotene to vitamin A in men as measured by using a double-tracer study design
"We found that 11 healthy men having a vitamin A status that was neither deficient nor toxic could be grouped as 6 responders and 5 low responders to D6 β-carotene. We had previously found 5 responders and 6 low responders among 11 healthy women (7). In the present study, the 2 responders (subjects 3 and 8) with the highest prestudy intakes of vitamin A (10797 and 9283 IU/d) and β-carotene (6.4 and 4.05 μmol/d) within their group had the lowest absorption of D6 β-carotene and the smallest bioconversion to D3 retinol. Furthermore, the 3 low responders (subjects 6, 11, and 12) with prestudy intakes of vitamin A (47171, 46363, and 68828 IU/d) and β-carotene (34.30, 19.33, and 46.73 μmol/d) far above the recommended dietary allowance may have down-regulated the activity of their β,β-carotene 15,15′-dioxygenase. It may be that, except for subjects 2 and 9, a prestudy intake of vitamin A of ≈15000 IU/d and of β-carotene of ≈20 μmol/d is sufficient to set the vitamin A activity of β-carotene to approximately zero in men fed a mixed diet."
Thankfully some were low responders.
We need to use our privilege to protect people as much as we possibly can, how can you not see this? Because if we don't, who will? What we may need is a reformulation and I think that the suggestion to reduce the dose is not unfounded.
In food experiments, they get the average response, which will include the low responders; nonresponders must be rare. Preformed poison A can be assigned to cover the minimum effective dose while the rest is left for macabrotenoids, they is safer in uncertainty of excess. Since most of the requirement will be taken care of by poisonol, a person won't need exorbitant amounts of macabrotenes to make up for an inefficiency.
Various of these links were shared elsewhere on the forum.