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

[dbh25]

Food ain't innocent either.

Uh-huh- that doesn't explain the paradox posed by the video

 

[Amazoniac]

@Amazoniac I hear what you are saying, but think for a second about the hamsters and Grant himself. Your basic premise, and correct me if I am wrong, is that just getting rid of vitamin A could have consequences and it is not fixing an underlying issue. You have been mocking the "poison" part. Fair enough.

What about the hamsters? If it will take several generations to deplete hamsters of A, if Grant consuming little to no A for so long does not seem detrimental, then by reason, if there is a need for A, and there probably is, that need is much more contextual then anyone has assumed. Or the amount needed is much lower and the amount of liver we have all consumed is enough for a lifetime.

Basically, the point you are putting across is not playing out with regards to people's actual vitamin A needs.

Grant's experience is surprising, but so is how the current RDA was defined. You might be just as surprised if you haven't check it out yet.

- Recommended dietary intakes (RDI) of vitamin A in humans

"The structural requirements for the biological activity of vitamin A are generally very strict: for example, the growth-promoting activity of vitamin A is reduced or eliminated by isomerization of the double-bond system, lengthening or shortening of the central chain, oxidation of the trimethyl-cyclohexene ring, and removal of the methyl groups (4). The same structural requirements apply to the carotenoids. Thus, of more than 500 carotenoids found naturally, only about 50 have provitamin A activity (3, 5,6)."

"In food, preformed vitamin A is present mainly as retinyl ester. In the stomach retinyl esters and various carotenoids are released from the food by proteolytic activity and then aggregate into globules with other dietary lipids. In the intestine retinyl esters are hydrolyzed, and the products are associated first with lipid globules and then with bile salt-containing micelles in the intestinal lumen. Both vitamin A and carotenoids are absorbed best in the upper part of the small intestine; absorption efficiency decreases lower in the gut. The absorption of retinol and b-carotene also differs in several ways:

1. In physiological amounts retinol is more efficiently absorbed than are carotenoids; eg, 70-90% vs 20-50% (7, 10).
2. As the amount ingested increases, the efficiency of retinol absorption remains high (60-80%) whereas that of carotenoid absorption falls markedly (< 10%) (7, 11).
3. Retinol is well absorbed from a micelle formed either with bile salts or with nonionic detergents, such as polyoxyethylene sorbitan derivatives, whereas carotenoids are absorbed in the presence of bile salts but not of nonionic detergents alone (12, 13). Indeed, the structure of the bile salts present affects the absorption of both vitamin A and carotenoids (12, 13).
4. At low physiological intakes, ie, 20-200 nM in lumen fluid, vitamin A is transported across the intestinal cell membranes by a carrier-mediated process (12, 14) whereas carotenoid absorption seems to occur by diffusion from a micellar phase. At high concentrations, vitamin A also seems to diffuse into intestinal cells through a micellar phase."

"Absorbed retinol is largely esterified with palmitic acid in intestinal mucosal cells and incorporated into the lipid phase of chylomicrons. b-carotene and other biologically active carotenoids are cleaved in the cytoplasm of intestinal cells to retinaldehyde, which is reduced mainly to retinol and then esterified to retinyl palmitate and other similar esters. Some carotenoids are incorporated directly into chylomicrons and some retinaldehyde is oxidized to retinoic acid."

"Chylomicrons, which contain uncleaved carotenoids and most of their vitamin A in ester linkage, pass first into the lymph and then into the systemic circulation. They are then converted rapidly by the action of lipoprotein lipase to chylomicron remnants, which are taken up mainly by hepatocytes in the liver (15). When initial liver reserves of poison/"vitamin" A are low, part ofthe newly absorbed vitamin A is released into the blood as a 1:1 complex with plasma retinol-binding protein (RBP) and part is stored as retinyl ester in hepatocytes (15, 16) with very little transferred to stellate cells. When liver reserves of vitamin A are adequate (> 20 mcg/g or > 0.07 umol/g), however, much of the newly absorbed vitamin A is transferred to stellate cells of the liver and is stored as retinyl ester (15, 17-19). In well-nourished individuals, the storage efficiency of ingested vitamin A in the liver is > 50% (20) [Values have lowered since the publication]. In contrast, depleted animals store ingested vitamin A poorly (21)."

"Vitamin A is released from the liver as holo-RBP. The RBP in holo-RBP is recognized by surface receptors on target cells, retinol is transferred across the plasmalemma into the cell, and the resultant apo-RBP is modified and released. Modified apo-RBP is removed and hydrolyzed mainly in the kidney (22,23). Approximately 80% of the retinol transported to peripheral target cells is recirculated back to the liver (24-26). The relatively short half-life (11-12 h) of plasma holo-RBP (27, 28) and the extensive recycling of retinol between peripheral tissues and the liver attest to the dynamic homeostatically controlled relationship between blood and these tissues (26)."

"In well-nourished persons, the liver contains >90% of the total-body stores of vitamin A. In poorly or marginally nourished individuals, however, the kidneys as well as other tissues contain an appreciable amount (10-50%) of the total-body reserve of the vitamin."

"Unlike vitamin A, carotenoids are deposited mainly in human adipose tissues; relatively small amounts are stored in the liver. The corpus luteum contains a very high concentration of carotenoids."

"Vitamin A is metabolized in two major ways: by oxidation of the C-4 position of the cyclohexene ring (30) and by oxidation of the C-is position to retinaldehyde and then irreversibly to retinoic acid. Except for vision and in testicular development, retinoic acid is essentially as active biologically as ingested vitamin A. Subsequent events involve oxidative cleavage of the unsaturated carbon chain and conjugation with glucuronic acid or taurine with or without chain cleavage (31, 32). Most of these conjugated polar metabolites are secreted into the bile, and a significant portion (~30%) of retinoyl b-glucuronide is recycled back to the liver in an enterohepatic circulation (31). Of the total vitamin A metabolized, approximately equal amounts appear in the feces and in the urine. Essentially all of these excreted products are modified biologically inactive metabolites of vitamin A; very little intact vitamin A is excreted."

"Because only a few carotenoids serve as provitamin A and because many other yellow and orange pigments are present in plants, the color intensity of a fruit or vegetable is not necessarily a good indicator of its content of propoison A."

"Adequate intakes of vitamin A have been estimated on the basis of the amounts needed 1) to correct impaired dark adaptation among vitamin A-depleted subjects, 2) to raise the concentrations of vitamin A into normal range in the plasma of depleted subjects, and 3) to maintain a given body-pool size of vitamin A in well-nourished subjects."

"Large doses of a-tocopherol [] inhibit b-carotene uptake by the intestine (66)."

"Deficiencies of a variety of other nutrients, including protein, a-tocopherol, iron [coughper], and zinc also adversely affect vitamin A transport, storage, and utilization (3, 6, 24)."

"In large doses vitamin A and other retinoids show dramatic chemopreventive effects in animals against some forms of cancer (2,68,69)."

"Unlike vitamin A, most carotenoids trap free radicals at low oxygen tensions (72) and quench singlet oxygen, which can cause neoplastic changes in cells. Because only ~10% of carotenoids in nature show propoison A activity, however, any anticancer effects that carotenoids possess would seem more properly to be attributed to their rather unique antioxidant properties than to their conversion into poison/"vitamin" A (73). This viewpoint is supported by the recent observation that the ingestion of carrots, which are rich in nutritionally active carotenoids, was not associated with any protection against neoplasm (74), whereas the intake of tomatoes, which mainly contain the nutritionally inactive carotenoid lycopene, was."

"Plasma poison/"vitamin" A values often are not good indicators of total-body reserves even when the latter are low (43, 46). Indeed, Sauberlich et al (20) also reported that two of eight subjects showed fairly high plasma retinol levels even after significant periods of depletion."

"The full recovery of the complex homeostatic system for the control of plasma vitamin A values is slow in fully depleted subjects and usually requires either a long period at moderate doses (20, 40) or single large doses."

"Healthy individuals with adequate liver reserves of vitamin A in many world cultures can show plasma values <30 mcg/dL (<1.05 uM)."

"Infections, drugs, and other forms of stress can transiently lower plasma retinol values below 30 mcg/dL (1.05 uM) without having any apparent effect on vitamin A status."​

- Poison/"vitamin" A | Linus Pauling Institute

"Vitamin A deficiency in animal models was found to interfere with the pituitary-thyroid axis by (1) increasing the synthesis and secretion of thyroid-stimulating hormone (TSH) by the pituitary gland, (2) increasing the size of the thyroid gland, (3) reducing iodine uptake by the thyroid gland and impairing the synthesis and iodination of thyroglobulin, and (4) increasing circulating concentrations of thyroid hormones (reviewed in 51)."​

- Vitamin A concentration in human tissues collected from five areas in the United States

- Vitamin A - Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc - NCBI Bookshelf

"Evidence Considered in Estimating the (Adult) Average Requirement

The calculation described below can be used for estimating the vitamin A requirement and is calculated on the basis of the amount of dietary vitamin A required to maintain a given body-pool size in well-nourished subjects. Olson (1987) determined the average requirement of vitamin A by this approach using the calculation:

A × B × C × D × E × F"

A = Percent of body vitamin A stores lost per day when ingesting a vitamin A-free diet

"The portion of body vitamin A stores lost per day has been estimated to be 0.5 percent based on the rate of excretion of radio-activity from radiolabeled vitamin A and by the calculation of the half-life of vitamin A."

In the experiment that served as base, the half-life of stored poison varied a lot. According to their extremes, in one person it took 75 days to deplete the body content in half; in other, 241 days. Of the 8 people being monitored (including those 2), the mean half-life of the reserves was 154 days. If it takes 154 days to deplete 50% of the stores, they assume that 0.32% (50% ÷ 154) is lost a day.

- Vitamin A Metabolism and Requirements in the Human Studied with the Use of Labeled Retinol (posted in this thread before)

There's a different approach to it, but the researcher didn't provide enough details, so it has been tough to get how he arrived at it. I'm not sure if I'll try to work it out, however it doesn't change the rate of depletion because in both they round them to 0.5% like savages.

The percentages above are gross simplifications because it's considering that the process is linear at all times. Yeet! The rate of utilization is high at the beginning and lowers the closer you get to depletion. You might deplete half of your stores relatively fast, but the other half is more difficult; and if you divide the second half in two, the last period lasts longer than the previous, and so on if you continue half-lifeing them.

Either way, in rounding to this higher percentage (0.5%) they is assuming it to be depleted faster, which in turn reflects in recommending higher intakes to replenish what's used/lost daily. But at the same time, unless you remain without ingesting poison for the entire specified half-life, the actual depletion rate in the initial moment might be that great, if not greater than that. Fragmentation of the periods also minimize problems when you consider each of them linear. So these aspects might cancer each other out.

So perhaps it makes sense to use it for practical purposes given that they have regular consumption in the minds. The variation between gurus is still insane, but it will be taken into consideration later on (although by pushing recommendations higher as solution).​

B = Minimum acceptable liver vitamin A reserve

"The minimal acceptable liver reserve is estimated to be 20 μg/g and is based on the concentration at which (1) no clinical signs of a deficiency are observed, (2) adequate plasma retinol concentrations are maintained (Loerch et al., 1979), (3) induced biliary excretion of vitamin A is observed (Hicks et al., 1984), and (4) there is a protection against a vitamin A deficiency for approximately 4 months while the person consumes a vitamin A-deficient diet."

Quoting a part from the previous publication:

"[A] crucial step is the selection of a satisfactory total-body reserve, or more conveniently, a liver vitamin A concentration that prevents deficiency, provides a suitable reserve for periods of stress and/or low intake, and is fully consistent with good health. A liver vitamin A concentration of 20 mcg vitamin A, expressed as retinol, per gram liver (0.07 umol/g) meets the following tests of adequacy:

1. no clinical signs of deficiency have been noted in individuals with this or higher liver concentration;
2. the liver is capable of maintaining steady-state plasma retinol values at this concentration, as determined by the relative dose response test (42, 43), but not at a concentration of < 10 mcg/g liver (<0.035 umol/g);
3. mechanisms for the inactivation and biliary excretion of vitamin A are induced in the liver when liver stores rise significantly above this concentration (44), and[..]
4. this concentration is sufficient to protect an adult ingesting a diet free of vitamin A from a deficiency state for ~4 mo as well as to meet vitamin A needs during shorter periods of stress, such as infection, exposure to extremes of temperature, etc. Furthermore, this liver concentration is used increasingly in the international scientific literature as a reference point of vitamin A adequacy (43, 45-48)."

C = The liver weight:body weight ratio

"The liver weight:body weight ratio is 1:33 (0.03) and is an average of ratios for infants and adults."

When you calculate using their 3% of body weight as suggested above, you end up with livers weighting 2.3 kg for pimps (76 kg) and 1.9 kg for pimpesses (62 kg).

Here are various formulas proposed to estimate liver weight based on body weight:
- Estimating liver weight of adults by body weight and gender

It's based on volume (ml) but they provide a conversion factor: 1.19 ml/g.
Some require surface area, which was already discussed elsewhere.​

They comment that some formulas are better suited for certain populaces. Read the articulo for more information.

But as an example, for a guru that weights those 76 kg and is 175 cm tall, the liver weights [. . . Brewing a random formula . . .] 1.65 kg; which is about 2% of total weight instead.

Now compare our 2% (which is more accurate) with their 3%. 1% might not seem a lot, but it's an assumption that the liver is 50% bigger: a brutal owaestimation of reserves, which ends up increasing the requirement that should provide a minimum desirable amount to maintain adequacy.

One of the reasons for the distortion is their grouping of the proportions for fetuses (4.2%) (their liver weight:body weight ratio is higher) with those for adults (2.4%): (4.2% + 2.4%)/2 = 3.3% and they round it to 3%. Wtf (kine, 2018).​

D = Reference weight for a specific age group and gender

"The reference weights for adult women and men are 61 and 76 kg, respectively (see Chapter 1 [No (Wagner, 2018).])."​

E = Ratio of total body:liver vitamin A reserves

"The ratio of total body:liver vitamin A reserves is 10:9 (1.1) and is based on individuals with adequate vitamin A status."

Since the calculation is based on liver (which concentrates about 90% of the body poison), they's adding the remaining 10% to obtain the total body stores.

Liver stores = Body stores * 90/100
Liver stores = Body stores * 9/10
Liver stores * 10/9 = Body stores​

It's rounded to 1.1 for convenience.​

F = Efficiency of storage of ingested vitamin A

"Finally, the efficiency of storage can be determined by isotope dilution methods following the administration of either radioactive or stable-isotopically labeled vitamin A to subjects adequate in vitamin A (Bausch and Reitz, 1977; Haskell et al., 1997). Recent studies by Haskell and coworkers (1997) suggest that the efficiency of storage is approximately 40 percent, rather than the 50 percent that was previously reported (Olson, 1987)."

As they pointed out, adsorption of preformed poison is relatively constant in relation to propoison.

Efficiency of storage can be tricky because if you have low reserves, a greater portion tends to be utilized before it has a chance to be deposited, so it's lower. In the experiment it was about 30% compared to those with adequate reserves, which stored something close to 40% of the dose. So the more poisoned you is, the more you tend to accumulate it rather than use it right away.

GeForce driver is ready to be downloaded. Ok.

Therefore an estimated requirement without this factor will be suggesting (in theory) only about 40/100 of the need amount. Since the factor is known, they group it with the other factors on one side of the equation:

A × B × C × D × E = EAR * 40/100
A × B × C × D × E = EAR * 1/2.5
A × B × C × D × E × 2.5 = EAR

EAR: Estimated Average Requirement​

"By using this approach, a daily vitamin A intake can be determined that will assure vitamin A reserves to cover increased needs during periods of stress and low vitamin A intake. That value can be used for estimating the average requirement for vitamin A.

Based on these current estimations, the EAR of preformed vitamin A required to assure an adequate body reserve in an adult man is:

0.005 × {[20 μg/g × (0.03 × 76000 g)] × 1.1} × 2.5 = 627 μg RAE/day.
With a reference weight of 61 kg for women, the EAR would be 503 μg RAE/day."

(Liver weight from body weight)
[Total poison in liver]
{Total poison in the entire body} multiplied by the rate of depletion to know how much is lost a day so that you ingest at least this to maintain the burden and prevent a depletion, and the corrective factor for inefficiency. It's the essence of the current RDA.​

The 'Estimated Average Requirements' of 627 and 503 mcg of 'Retinol Activity Equivalents' for pimps and pimpesses now goes through more adjustments to cover those that use up the reserves faster (at the expense of those that doesn't), this goes back to the issues discussed in factor A (above).

"Based on the study of Sauberlich and coworkers (1974), Olson (1987) estimated that the liver vitamin A concentration was less than 10 μg/g at the time the first clinical signs of vitamin A deficiency appeared. From this assumption, it was estimated that the half-life of vitamin A is approximately 128 days, and the CV is 21 percent. Because the portion of this variability that is due to experimental error is not known, a CV of 20 percent is used for setting the RDA."

"The RDA for vitamin A is set by using a CV of 20 percent (see Chapter 1) using the EAR for adequate body stores of vitamin A. The RDA is defined as equal to the EAR plus twice the CV to cover the needs of 97 to 98 percent of the individuals in the group (therefore, for vitamin A the RDA is 140 percent of the EAR). The calculated values for the RDAs have been rounded to the nearest 100 μg."

To cover the need of those that need more, you have to recommend more for those that needed less, whose requirements will be inflated. But it's challenging to provide generalized recommendations for a population.

- 627 mcg RAE * 140% = 878 mcg → 900 mcg RAE (3000 IU)/day for men
- 503 mcg RAE * 140% = 704 mcg → 700 mcg RAE (2300 IU)/day for women​

 

[Blossom]

Blossom, out of cordiality.

And Love and Duty. Seriously though I enjoy your contributions. I’ve learned some very helpful information from your posts so thank you.

 

[Amazoniac]

And Love and Duty. Seriously though I enjoy your contributions. I’ve learned some very helpful information from your posts so thank you.

There are certain details in the research that are baffling when you start to read them with more care.

When researchers were reviewing one of the experiments that served as foundation for the recommendations, they've estimated the liver weight based on body weight. If I'm not wrong, the publication didn't provide body proportions and other important information such as sex,* body fat, and so on. Without knowing these, you can end up with calculations that are quite off. The only reason for not being disconcerting is because recommendations for poison A are simply ignored, just like its content in foods that pass as invisible in nutrition apps.

*A correction: the experiment was only on men.

But as an example, there was someone weighting almost 100 kg and other 60 kg. If the 100 kg person is a beast, the liver might increase proportionally, but otherwise it can be a gadget with more body fat. It's concerning by itself to admit the liver weight as 3% of body weight, those 100 kg will give you a 3 kg liver; but it gets worse if the subject in question wasn't Hulk, but a gadget.. imagine how flawed that is. Applying a standard factor on everyone is an assumption that liver weight is always following body weight.

 

[Blossom]

When researchers were reviewing one of the experiments that served as foundation for the recommendations, they've estimated the liver weight based on body weight. If I'm not wrong, the publication didn't provide body proportions and other important information such as sex, body fat,

For ventilating lungs we calculate the estimated volume of air needed based on ideal body weight because the size of a person’s lungs doesn’t change if they have excess or lacking muscle or fat mass. Perhaps that doesn’t work with the liver or maybe it was done and not mentioned.

 

[Amazoniac]

For ventilating lungs we calculate the estimated volume of air needed based on ideal body weight because the size of a person’s lungs doesn’t change if they have excess or lacking muscle or fat mass. Perhaps that doesn’t work with the liver or maybe it was done and not mentioned.

Most formulas to estimate liver weight have height added to them (or indirectly through body surface area); it helps to inform how the weight is distributed. I've read some articles claiming it's desirable to have it, others that it's not needed. I don't know what to think of it yet.

Given that the maximum value reported below was 2.9 kg, Hulk's 3 kg of liver is already suspicious (but perhaps possible). Even though body weight has way more importance than other aspects, I can't imagine them not making a difference or making the formulas less accurate (at least for liver, I have no clue about dispensable organs). A 100 kg person could be 200 or 160 cm tall for example, however the experiments must avoid people that are too far from the norm.

I find it unlikely that they have considered this because they seemed to attempt to simplify the process whenever they could and apply just a standard factor for everyone. But not sure.

- Normal Organ Weights in Men: Part II—The Brain, Lungs, Liver, Spleen, and Kidneys

Spleen has no function in the body, I don't know why they included it. Lungs are questionable. Brain, kidneys and liver are needed.

"Previous studies have found the mean weight of the liver in adult human males to range from 1677 to 1807 g,[1,7,8] with an overall range of 670 to 2900 g,[7,9,10] which is consistent with the present study that found the mean liver weight to be 1561 g with a range of 838 to 2584 g. Liver weight has also been previously shown to be positively correlated with height, BMI, and body weight.[7,8,10] In their study of 355 adult human males, de la Grandmaison et al[7] found the coefficient of determination (R²) for liver weight and height to be 0.88 and 0.61 for liver weight and BMI, whereas Kasiske and Umen[8] found R² values of 0.56 for weight, 0.32 for height, and 0.45 for BMI. Garby et al[1] correlated liver weight with body weight, body height, and age using multivariate regression analysis, obtaining an R² of 0.534 for their population."

"The correlations found previously are much greater for height than those found in the current study (R² = 0.06). In addition, the study of de la Grandmaison et al[7] shows a much greater correlation with weight and BMI than seen in the present study (R² = 0.41 for BMI) or in Kasiske and Umen's.[8] One reason for this difference may be in the study design. Although all 3 studies had similar demographics for body height/length, the current study examined healthy individuals aged between 18 and 35 years who died of traumatic causes only. Both de la Grandmaison et al[7] and Kasiske and Umen[8] studied older individuals (mean [SD] age, 42 [17] vs 35.6 [19.9] years, respectively). The decedents in the study of de la Grandmaison et al[7] also tended to weigh less (mean weight, 68 kg; mean BMI, 22.8 kg/m2) than either those in the present study or in Kasiske and Umen’s[8] study (mean [SD] weight, 72.1 [24.2] kg; BMI, 24.2 [5.3] kg/m2). In addition, de la Grandmaison et al[7] examined "forensic" cases but did not specifically define the cases studied. Presumably, this would include trauma, intoxication, and natural disease in their population, although they did exclude organs with gross or microscopic evidence of disease. The range of liver weights found in the study of de la Grandmaison et al[7] was also greater than in the present study (607-2900 vs 838-2584 g), leading one to question if perhaps individuals with underlying liver pathologic disease were inadvertently included in the study of de la Grandmaison given the design. Kasiske and Umen[8] also used forensic cases, but they stated that most of their cases were due to trauma and they also excluded cases with significant systemic disease, including heart disease and diabetes mellitus."

"Although the current study did not specifically address the issue of age, as the design was meant to establish reference ranges in the young, healthy population before the onset of systemic disease, several other studies have addressed this issue. Both de la Grandmaison et al[7] and Boyd[9] found that liver weight decreases with age after approximately 50 years [?]. Kasiske and Umen,[8] however, found no effect of age on liver weight, although their study population was considerably younger (mean age, 35.6 years) than that of de la Grandmaison et al[7] or Boyd.[9] Kasiske and Umen[8] also showed that there was no difference in the weights of livers based on race."

"Boyd[9] examined 239 livers of men aged 20 years or older who died of trauma or poisoning and found that hemorrhage decreased liver weight, which is consistent with the data obtained in this study. They did not address the issue of visceral congestion in their study."

"Given the results of the current study as well as those discussed above, it can be concluded that: (1) race does not significantly affect the weight of the liver; (2) liver weights seem to decrease with age, presumably secondary to hepatic involution as either a result of either aging or disease processes; (3) although positively correlated, there is insufficient accuracy to predict liver weights based on body height, body weight, or BMI; and (4) significant blood loss can lead to a decrease in liver weight. It can also be postulated that a reference range for liver weight can be established for healthy men aged 18 to 35 years using the criteria proposed by the Clinical and Laboratory Standards Institute and International Federation of Clinical Chemistry and Laboratory Medicine[6] given parametric data in a normal, healthy population. Using the data obtained in this study, the reference range for liver weights proposed is 968 to 1860 g (95% inclusion) with the caveat that deaths due to or with excessive blood loss may result in weights at the lower end of the reference range."

 

[Amazoniac]

In one of the studies that claim body height to be unnecessary, it still shows that as you become taller, the liver tends to get bigger in both sexes but especially in men:

It's difficult to think otherwise. But there are some curious outliers!

I guess it's worth mentioning that the population was lean in general (so perhaps in this population it's less of an issue to exclude how the body weight is distributed):

 

[InChristAlone]

In one of the studies that claim body height to be unnecessary, it still shows that as you become taller, the liver tends to get bigger in both sexes but especially in men:

View attachment 12337​

It's difficult to think otherwise. But there are some curious outliers!

Hm... I didn't read the study but when they look at liver size do they take into account hepatomegaly (enlarged liver)? Because it is not good to have an abnormally large liver when it shows underlying problems like congestive heart failure or liver disease.

 

[Amazoniac]

Hm... I didn't read the study but when they look at liver size do they take into account hepatomegaly (enlarged liver)? Because it is not good to have an abnormally large liver when it shows underlying problems like congestive heart failure or liver disease.

The range of liver weights found in the study of de la Grandmaison et al[7] was also greater than in the present study (607-2900 vs 838-2584 g), leading one to question if perhaps individuals with underlying liver pathologic disease were inadvertently included in the study of de la Grandmaison given the design.

 

[InChristAlone]

Ok I didn't see that part, you must be adding to your posts?

 

[Amazoniac]

Ok I didn't see that part, you must be adding to your posts?

You mean that part? It wasn't edited, was already there. You might be wondering because of the second image added after your reply.

 

[Amazoniac]

There have been posts on the restrictive diet being decent but lacking calcium, and for some people antidote D. These are the two pieces that Raj believes are major responsibles for deterioration of the wealth of liver and kidneys when missing. If you believe that it's common for diseases to stem from an inflammed gut, antidote D and vit K are also often missing. It's possible to get too entertained with clearing poison A and neglect them. Sometimes they's needed all at once, taken apart might not be as effective. Magnesium is likely required as well.

- Vitamin D - KMUD, 2016-11-18

RP: I think the low level of vitamin D and calcium is probably the cause of the sick liver and kidneys rather than being a product. So supplementing just with calcium and vitamin D I think in many cases will correct the whatever the liver and kidney problem is. It isn't a matter of curing the disease. So that they can make or activate vitamin D. It's a matter of getting the vitamin D and calcium into the system, and maybe, you don't need to think about the disease of the kidney and liver as having some other mysterious cause, such as a virus.

- Cholesterol Is An Important Molecule, KMUD, 2008

Caller: How does thyroid relate to Lyme disease?

RP: The whole immune system is the issue there. A very healthy immune system can throw off chronic infections like that. It's best to do it quickly with an antibiotic, but you always want to back up the antibiotic with an optimized immune system. And thyroid, calcium and vitamin D are really basic things to make your immune system not cause inflammation, but to be able to eliminate pathogens.

- C. Difficile Gut Infection Or Even IBD May Be Due To Low Vitamin D Or PPI Drugs
- IBD, IBS, Gut Bacteria - What Works For You?

 

[tankasnowgod]

Uh-huh- that doesn't explain the paradox posed by the video

What paradox?

 

[Steven Bussinger]

Grant's experience is surprising, but so is how the current RDA was defined. You might be just as surprised if you haven't check it out yet.

- Recommended dietary intakes (RDI) of vitamin A in humans

"The structural requirements for the biological activity of vitamin A are generally very strict: for example, the growth-promoting activity of vitamin A is reduced or eliminated by isomerization of the double-bond system, lengthening or shortening of the central chain, oxidation of the trimethyl-cyclohexene ring, and removal of the methyl groups (4). The same structural requirements apply to the carotenoids. Thus, of more than 500 carotenoids found naturally, only about 50 have provitamin A activity (3, 5,6)."

"In food, preformed vitamin A is present mainly as retinyl ester. In the stomach retinyl esters and various carotenoids are released from the food by proteolytic activity and then aggregate into globules with other dietary lipids. In the intestine retinyl esters are hydrolyzed, and the products are associated first with lipid globules and then with bile salt-containing micelles in the intestinal lumen. Both vitamin A and carotenoids are absorbed best in the upper part of the small intestine; absorption efficiency decreases lower in the gut. The absorption of retinol and b-carotene also differs in several ways:

1. In physiological amounts retinol is more efficiently absorbed than are carotenoids; eg, 70-90% vs 20-50% (7, 10).
2. As the amount ingested increases, the efficiency of retinol absorption remains high (60-80%) whereas that of carotenoid absorption falls markedly (< 10%) (7, 11).
3. Retinol is well absorbed from a micelle formed either with bile salts or with nonionic detergents, such as polyoxyethylene sorbitan derivatives, whereas carotenoids are absorbed in the presence of bile salts but not of nonionic detergents alone (12, 13). Indeed, the structure of the bile salts present affects the absorption of both vitamin A and carotenoids (12, 13).
4. At low physiological intakes, ie, 20-200 nM in lumen fluid, vitamin A is transported across the intestinal cell membranes by a carrier-mediated process (12, 14) whereas carotenoid absorption seems to occur by diffusion from a micellar phase. At high concentrations, vitamin A also seems to diffuse into intestinal cells through a micellar phase."

"Absorbed retinol is largely esterified with palmitic acid in intestinal mucosal cells and incorporated into the lipid phase of chylomicrons. b-carotene and other biologically active carotenoids are cleaved in the cytoplasm of intestinal cells to retinaldehyde, which is reduced mainly to retinol and then esterified to retinyl palmitate and other similar esters. Some carotenoids are incorporated directly into chylomicrons and some retinaldehyde is oxidized to retinoic acid."

"Chylomicrons, which contain uncleaved carotenoids and most of their vitamin A in ester linkage, pass first into the lymph and then into the systemic circulation. They are then converted rapidly by the action of lipoprotein lipase to chylomicron remnants, which are taken up mainly by hepatocytes in the liver (15). When initial liver reserves of poison/"vitamin" A are low, part ofthe newly absorbed vitamin A is released into the blood as a 1:1 complex with plasma retinol-binding protein (RBP) and part is stored as retinyl ester in hepatocytes (15, 16) with very little transferred to stellate cells. When liver reserves of vitamin A are adequate (> 20 mcg/g or > 0.07 umol/g), however, much of the newly absorbed vitamin A is transferred to stellate cells of the liver and is stored as retinyl ester (15, 17-19). In well-nourished individuals, the storage efficiency of ingested vitamin A in the liver is > 50% (20) [Values have lowered since the publication]. In contrast, depleted animals store ingested vitamin A poorly (21)."

"Vitamin A is released from the liver as holo-RBP. The RBP in holo-RBP is recognized by surface receptors on target cells, retinol is transferred across the plasmalemma into the cell, and the resultant apo-RBP is modified and released. Modified apo-RBP is removed and hydrolyzed mainly in the kidney (22,23). Approximately 80% of the retinol transported to peripheral target cells is recirculated back to the liver (24-26). The relatively short half-life (11-12 h) of plasma holo-RBP (27, 28) and the extensive recycling of retinol between peripheral tissues and the liver attest to the dynamic homeostatically controlled relationship between blood and these tissues (26)."

"In well-nourished persons, the liver contains >90% of the total-body stores of vitamin A. In poorly or marginally nourished individuals, however, the kidneys as well as other tissues contain an appreciable amount (10-50%) of the total-body reserve of the vitamin."

"Unlike vitamin A, carotenoids are deposited mainly in human adipose tissues; relatively small amounts are stored in the liver. The corpus luteum contains a very high concentration of carotenoids."

"Vitamin A is metabolized in two major ways: by oxidation of the C-4 position of the cyclohexene ring (30) and by oxidation of the C-is position to retinaldehyde and then irreversibly to retinoic acid. Except for vision and in testicular development, retinoic acid is essentially as active biologically as ingested vitamin A. Subsequent events involve oxidative cleavage of the unsaturated carbon chain and conjugation with glucuronic acid or taurine with or without chain cleavage (31, 32). Most of these conjugated polar metabolites are secreted into the bile, and a significant portion (~30%) of retinoyl b-glucuronide is recycled back to the liver in an enterohepatic circulation (31). Of the total vitamin A metabolized, approximately equal amounts appear in the feces and in the urine. Essentially all of these excreted products are modified biologically inactive metabolites of vitamin A; very little intact vitamin A is excreted."

"Because only a few carotenoids serve as provitamin A and because many other yellow and orange pigments are present in plants, the color intensity of a fruit or vegetable is not necessarily a good indicator of its content of propoison A."

"Adequate intakes of vitamin A have been estimated on the basis of the amounts needed 1) to correct impaired dark adaptation among vitamin A-depleted subjects, 2) to raise the concentrations of vitamin A into normal range in the plasma of depleted subjects, and 3) to maintain a given body-pool size of vitamin A in well-nourished subjects."

"Large doses of a-tocopherol [] inhibit b-carotene uptake by the intestine (66)."

"Deficiencies of a variety of other nutrients, including protein, a-tocopherol, iron [coughper], and zinc also adversely affect vitamin A transport, storage, and utilization (3, 6, 24)."

"In large doses vitamin A and other retinoids show dramatic chemopreventive effects in animals against some forms of cancer (2,68,69)."

"Unlike vitamin A, most carotenoids trap free radicals at low oxygen tensions (72) and quench singlet oxygen, which can cause neoplastic changes in cells. Because only ~10% of carotenoids in nature show propoison A activity, however, any anticancer effects that carotenoids possess would seem more properly to be attributed to their rather unique antioxidant properties than to their conversion into poison/"vitamin" A (73). This viewpoint is supported by the recent observation that the ingestion of carrots, which are rich in nutritionally active carotenoids, was not associated with any protection against neoplasm (74), whereas the intake of tomatoes, which mainly contain the nutritionally inactive carotenoid lycopene, was."

"Plasma poison/"vitamin" A values often are not good indicators of total-body reserves even when the latter are low (43, 46). Indeed, Sauberlich et al (20) also reported that two of eight subjects showed fairly high plasma retinol levels even after significant periods of depletion."

"The full recovery of the complex homeostatic system for the control of plasma vitamin A values is slow in fully depleted subjects and usually requires either a long period at moderate doses (20, 40) or single large doses."

"Healthy individuals with adequate liver reserves of vitamin A in many world cultures can show plasma values <30 mcg/dL (<1.05 uM)."

"Infections, drugs, and other forms of stress can transiently lower plasma retinol values below 30 mcg/dL (1.05 uM) without having any apparent effect on vitamin A status."​

- Poison/"vitamin" A | Linus Pauling Institute

"Vitamin A deficiency in animal models was found to interfere with the pituitary-thyroid axis by (1) increasing the synthesis and secretion of thyroid-stimulating hormone (TSH) by the pituitary gland, (2) increasing the size of the thyroid gland, (3) reducing iodine uptake by the thyroid gland and impairing the synthesis and iodination of thyroglobulin, and (4) increasing circulating concentrations of thyroid hormones (reviewed in 51)."​

- Vitamin A concentration in human tissues collected from five areas in the United States

View attachment 12334​

- Vitamin A - Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc - NCBI Bookshelf

"Evidence Considered in Estimating the (Adult) Average Requirement

The calculation described below can be used for estimating the vitamin A requirement and is calculated on the basis of the amount of dietary vitamin A required to maintain a given body-pool size in well-nourished subjects. Olson (1987) determined the average requirement of vitamin A by this approach using the calculation:

A × B × C × D × E × F"

A = Percent of body vitamin A stores lost per day when ingesting a vitamin A-free diet

"The portion of body vitamin A stores lost per day has been estimated to be 0.5 percent based on the rate of excretion of radio-activity from radiolabeled vitamin A and by the calculation of the half-life of vitamin A."

In the experiment that served as base, the half-life of stored poison varied a lot. According to their extremes, in one person it took 75 days to deplete the body content in half; in other, 241 days. Of the 8 people being monitored (including those 2), the mean half-life of the reserves was 154 days. If it takes 154 days to deplete 50% of the stores, they assume that 0.32% (50% ÷ 154) is lost a day.

- Vitamin A Metabolism and Requirements in the Human Studied with the Use of Labeled Retinol (posted in this thread before)

View attachment 12326​

There's a different approach to it, but the researcher didn't provide enough details, so it has been tough to get how he arrived at it. I'm not sure if I'll try to work it out, however it doesn't change the rate of depletion because in both they round them to 0.5% like savages.

The percentages above are gross simplifications because it's considering that the process is linear at all times. Yeet! The rate of utilization is high at the beginning and lowers the closer you get to depletion. You might deplete half of your stores relatively fast, but the other half is more difficult; and if you divide the second half in two, the last period lasts longer than the previous, and so on if you continue half-lifeing them.

View attachment 12328​

Either way, in rounding to this higher percentage (0.5%) they is assuming it to be depleted faster, which in turn reflects in recommending higher intakes to replenish what's used/lost daily. But at the same time, unless you remain without ingesting poison for the entire specified half-life, the actual depletion rate in the initial moment might be that great, if not greater than that. Fragmentation of the periods also minimize problems when you consider each of them linear. So these aspects might cancer each other out.

So perhaps it makes sense to use it for practical purposes given that they have regular consumption in the minds. The variation between gurus is still insane, but it will be taken into consideration later on (although by pushing recommendations higher as solution).​

B = Minimum acceptable liver vitamin A reserve

"The minimal acceptable liver reserve is estimated to be 20 μg/g and is based on the concentration at which (1) no clinical signs of a deficiency are observed, (2) adequate plasma retinol concentrations are maintained (Loerch et al., 1979), (3) induced biliary excretion of vitamin A is observed (Hicks et al., 1984), and (4) there is a protection against a vitamin A deficiency for approximately 4 months while the person consumes a vitamin A-deficient diet."

Quoting a part from the previous publication:

"[A] crucial step is the selection of a satisfactory total-body reserve, or more conveniently, a liver vitamin A concentration that prevents deficiency, provides a suitable reserve for periods of stress and/or low intake, and is fully consistent with good health. A liver vitamin A concentration of 20 mcg vitamin A, expressed as retinol, per gram liver (0.07 umol/g) meets the following tests of adequacy:

1. no clinical signs of deficiency have been noted in individuals with this or higher liver concentration;
2. the liver is capable of maintaining steady-state plasma retinol values at this concentration, as determined by the relative dose response test (42, 43), but not at a concentration of < 10 mcg/g liver (<0.035 umol/g);
3. mechanisms for the inactivation and biliary excretion of vitamin A are induced in the liver when liver stores rise significantly above this concentration (44), and[..]
4. this concentration is sufficient to protect an adult ingesting a diet free of vitamin A from a deficiency state for ~4 mo as well as to meet vitamin A needs during shorter periods of stress, such as infection, exposure to extremes of temperature, etc. Furthermore, this liver concentration is used increasingly in the international scientific literature as a reference point of vitamin A adequacy (43, 45-48)."

C = The liver weight:body weight ratio

"The liver weight:body weight ratio is 1:33 (0.03) and is an average of ratios for infants and adults."

When you calculate using their 3% of body weight as suggested above, you end up with livers weighting 2.3 kg for pimps (76 kg) and 1.9 kg for pimpesses (62 kg).

Here are various formulas proposed to estimate liver weight based on body weight:
- Estimating liver weight of adults by body weight and gender

It's based on volume (ml) but they provide a conversion factor: 1.19 ml/g.
Some require surface area, which was already discussed elsewhere.​

They comment that some formulas are better suited for certain populaces. Read the articulo for more information.

But as an example, for a guru that weights those 76 kg and is 175 cm tall, the liver weights [. . . Brewing a random formula . . .] 1.65 kg; which is about 2% of total weight instead.

Now compare our 2% (which is more accurate) with their 3%. 1% might not seem a lot, but it's an assumption that the liver is 50% bigger: a brutal owaestimation of reserves, which ends up increasing the requirement that should provide a minimum desirable amount to maintain adequacy.

One of the reasons for the distortion is their grouping of the proportions for fetuses (4.2%) (their liver weight:body weight ratio is higher) with those for adults (2.4%): (4.2% + 2.4%)/2 = 3.3% and they round it to 3%. Wtf (kine, 2018).​

D = Reference weight for a specific age group and gender

"The reference weights for adult women and men are 61 and 76 kg, respectively (see Chapter 1 [No (Wagner, 2018).])."​

E = Ratio of total body:liver vitamin A reserves

"The ratio of total body:liver vitamin A reserves is 10:9 (1.1) and is based on individuals with adequate vitamin A status."

Since the calculation is based on liver (which concentrates about 90% of the body poison), they's adding the remaining 10% to obtain the total body stores.

Liver stores = Body stores * 90/100
Liver stores = Body stores * 9/10
Liver stores * 10/9 = Body stores​

It's rounded to 1.1 for convenience.​

F = Efficiency of storage of ingested vitamin A

"Finally, the efficiency of storage can be determined by isotope dilution methods following the administration of either radioactive or stable-isotopically labeled vitamin A to subjects adequate in vitamin A (Bausch and Reitz, 1977; Haskell et al., 1997). Recent studies by Haskell and coworkers (1997) suggest that the efficiency of storage is approximately 40 percent, rather than the 50 percent that was previously reported (Olson, 1987)."

As they pointed out, adsorption of preformed poison is relatively constant in relation to propoison.

Efficiency of storage can be tricky because if you have low reserves, a greater portion tends to be utilized before it has a chance to be deposited, so it's lower. In the experiment it was about 30% compared to those with adequate reserves, which stored something close to 40% of the dose. So the more poisoned you is, the more you tend to accumulate it rather than use it right away.

GeForce driver is ready to be downloaded. Ok.

Therefore an estimated requirement without this factor will be suggesting (in theory) only about 40/100 of the need amount. Since the factor is known, they group it with the other factors on one side of the equation:

A × B × C × D × E = EAR * 40/100
A × B × C × D × E = EAR * 1/2.5
A × B × C × D × E × 2.5 = EAR

EAR: Estimated Average Requirement​

"By using this approach, a daily vitamin A intake can be determined that will assure vitamin A reserves to cover increased needs during periods of stress and low vitamin A intake. That value can be used for estimating the average requirement for vitamin A.

Based on these current estimations, the EAR of preformed vitamin A required to assure an adequate body reserve in an adult man is:

0.005 × {[20 μg/g × (0.03 × 76 kg)] × 1.1} × 2.5 = 627 μg RAE/day.
With a reference weight of 61 kg for women, the EAR would be 503 μg RAE/day."

(Liver weight)
[Total poison in liver]
{Total poison in the entire body} multiplied by the rate of depletion to know how much is lost a day so that you ingest at least this to maintain the burden and prevent a depletion, and the corrective factor for inefficiency. It's the essence of the current RDA.​

The 'Estimated Average Requirements' of 627 and 503 mcg of 'Retinol Activity Equivalents' for pimps and pimpesses now goes through more adjustments to cover those that use up the reserves faster (at the expense of those that doesn't), this goes back to the issues discussed in factor A (above).

"Based on the study of Sauberlich and coworkers (1974), Olson (1987) estimated that the liver vitamin A concentration was less than 10 μg/g at the time the first clinical signs of vitamin A deficiency appeared. From this assumption, it was estimated that the half-life of vitamin A is approximately 128 days, and the CV is 21 percent. Because the portion of this variability that is due to experimental error is not known, a CV of 20 percent is used for setting the RDA."

"The RDA for vitamin A is set by using a CV of 20 percent (see Chapter 1) using the EAR for adequate body stores of vitamin A. The RDA is defined as equal to the EAR plus twice the CV to cover the needs of 97 to 98 percent of the individuals in the group (therefore, for vitamin A the RDA is 140 percent of the EAR). The calculated values for the RDAs have been rounded to the nearest 100 μg."

View attachment 12332​

To cover the need of those that need more, you have to recommend more for those that needed less, whose requirements will be inflated. But it's challenging to provide generalized recommendations for a population.

- 627 mcg RAE * 140% = 878 mcg → 900 mcg RAE (3000 IU)/day for men
- 503 mcg RAE * 140% = 704 mcg → 700 mcg RAE (2300 IU)/day for women​

It's quite concerning that depleted animals do not store their vitamin A properly, in the liver. That is a paradox for anyone embarking on vitamin A depletion as a means to heal themselves. It means that depletion might be ultimately self-defeating.

 

[Blossom]

It's quite concerning that depleted animals do not store their vitamin A properly, in the liver. That is a paradox for anyone embarking on vitamin A depletion as a means to heal themselves. It means that depletion might be ultimately self-defeating.

It's hard to make sense of that phenomena for something that's supposed to be absolutely essential. There's still so many unknowns...
How is Grant not breaking down after 4.5 years?
I was pleased to see @Amazoniac's posts about estimated time for depletion earlier in the thread.

 

[Steven Bussinger]

I think the rodent experiment is fine and I was quite confused to see so many people opposed to it on ostensibly moral grounds. In Real Official Laboratories, they do stuff that would make life way more miserable and nobody makes a peep about it, so I don't understand the double standard.

I'm interested in the generational aspect, but to me a more important question that needs to be researched is: how does retinol impact the utilization and status of protein, zinc, and other nutrients?

 

[Steven Bussinger]

It's hard to make sense of that phenomena for something that's supposed to be absolutely essential. There's still so many unknowns...
How is Grant not breaking down after 4.5 years?
I was pleased to see @Amazoniac's posts about estimated time for depletion earlier in the thread.

We don't have any tissue biopsies, so we do not know if he is fully depleted of retinol. Amazoniac has posted studies that state the body guards its retinol stores more jealousy in states of depletion, which might explain his serum levels are so low. Potentially, everything is in tissue storage now.

 

[Steven Bussinger]

In obesity, serum retinol is high, but tissue VA is low

Obesity Leads to Tissue, but not Serum Vitamin A Deficiency

"Obesity negatively affects multiple metabolic pathways, but little is known about the impact of obesity on vitamin A (VA)[retinol (ROL)], a nutrient that regulates expression of genes in numerous pathways essential for human development and health. We demonstrate that obese mice, generated from a high fat diet (HFD) or by genetic mutations (i.e., ob/ob; db/db), have greatly reduced ROL levels in multiple organs, including liver, lungs, pancreas, and kidneys, even though their diets have adequate VA. However, obese mice exhibit elevated serum VA. Organs from obese mice show impaired VA transcriptional signaling, including reductions in retinoic acid receptor (RARα, RARβ2 and RARγ) mRNAs and lower intracellular ROL binding protein Crbp1 (RBP1) levels in VA-storing stellate cells. Reductions in organ VA signaling in obese mice correlate with increasing adiposity and fatty liver (steatosis), while with weight loss VA levels and signaling normalize. Consistent with our findings in obese mice, we show that increasing severity of fatty liver disease in humans correlates with reductions in hepatic VA, VA transcriptional signaling, and Crbp1 levels in VA storing stellate cells. Thus, obesity causes a “silent” VA deficiency marked by reductions in VA levels and signaling in multiple organs, but not detected by serum VA."

 

[InChristAlone]

In obesity, serum retinol is high, but tissue VA is low

Obesity Leads to Tissue, but not Serum Vitamin A Deficiency

"Obesity negatively affects multiple metabolic pathways, but little is known about the impact of obesity on vitamin A (VA)[retinol (ROL)], a nutrient that regulates expression of genes in numerous pathways essential for human development and health. We demonstrate that obese mice, generated from a high fat diet (HFD) or by genetic mutations (i.e., ob/ob; db/db), have greatly reduced ROL levels in multiple organs, including liver, lungs, pancreas, and kidneys, even though their diets have adequate VA. However, obese mice exhibit elevated serum VA. Organs from obese mice show impaired VA transcriptional signaling, including reductions in retinoic acid receptor (RARα, RARβ2 and RARγ) mRNAs and lower intracellular ROL binding protein Crbp1 (RBP1) levels in VA-storing stellate cells. Reductions in organ VA signaling in obese mice correlate with increasing adiposity and fatty liver (steatosis), while with weight loss VA levels and signaling normalize. Consistent with our findings in obese mice, we show that increasing severity of fatty liver disease in humans correlates with reductions in hepatic VA, VA transcriptional signaling, and Crbp1 levels in VA storing stellate cells. Thus, obesity causes a “silent” VA deficiency marked by reductions in VA levels and signaling in multiple organs, but not detected by serum VA."

But are obese people showing any of the typical signs of VA deficiency?

 

[Steven Bussinger]

But are obese people showing any of the typical signs of VA deficiency?

No, but perhaps the obesity is protective.

There are dozens of studies showing that lower serum retinol has a higher likelihood of cancer.

There are dozens of studies showing that RBP4 causes insulin resistance and obesity.

I'm not proposing this as a hypothesis, just throwing some ideas out.