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What is the RDA based on?
Adults Ages 19 Years and Older
Evidence Considered in Estimating the 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
B = Minimum acceptable liver vitamin A reserve
C = The liver weight:body weight ratio
D = Reference weight for a specific age group and gender
E = Ratio of total body:liver vitamin A reserves
F = Efficiency of storage of ingested vitamin A.
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.
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. 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. The liver weight:body weight ratio is 1:33 (0.03) and is an average of ratios for infants and adults. The reference weights for adult women and men are 61 and 76 kg, respectively (see Chapter 1). The ratio of total body:liver vitamin A reserves is 10:9 (1.1) and is based on individuals with adequate vitamin A status. 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). 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, or 627 μg RAE/day. With a reference weight of 61 kg for women, the EAR would be 503 μg RAE/day.
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.
To simplify this, it is mostly based on minimum acceptable total liver reserves x the estimated percentage of VA lost daily.
Super interesting!
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.
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.
A lot of estimations and assumptions. Why not just measure how much Vitamin A is depleted when VA reserves are low enough so that induced biliary excretion of vitamin A is not observed and make an RDA from that? This 0.5% figure may be quite problematic.
(3) induced biliary excretion of vitamin A is observed (Hicks et al., 1984)
This is pretty interesting. This is telling me that the body drastically shuts down excretion of Vitamin A when levels get low enough, presumably slightly less than 20 mcg/g. This also indicates that anything higher than 20 mcg/g is not optimal.
With regard to the 0.5% figure:
y = a(1-b)x
y: Final amount remaining after the decay over a period of time
a: The original amount
x: Time
The decay factor is (1-b).
The variable, b, is percent change in decimal form. Because this is an exponential decay factor, this article focuses on percent decrease.
The average person has a liver reserve of about 100 mcg/g. If they consumed no VA for a year according to an exponential decrease of 0.5% per day they would have a liver reserve of 16 mcg/g. After 5 years it should be 0.01 mcg/g.
I'd be interested in opinions on how accurate you think that formula and percentage is?
Those are interesting questions and observations. Wish I could add an opinion on the formula and percentage accuracy, but can't figure one out, other than I agree with your simpler suggestion above. I ran across a paper this morning and did some numbers just to kind of get a sense of proportion regarding one line of it that got my attention. It's sort of related to your thread so I thought I'd post it as you might find it useful.
Nutrients. 2017 Dec Disturbed Vitamin A Metabolism in Non-Alcoholic Fatty Liver Disease (NAFLD).
In times of inadequate dietary intake, the liver maintains stable circulating retinol levels of approximately 2 μmol/L, sufficient to provide the body with this vitamin for months.
240.2200 C (20*12.011) + 30.2400 H (30*1.008) + 15.9990 O (1*15.999)
C20H30O = Retinol = 286.4516 molar mass = approximately 286.45 grams = one mole of Retinol
A micromole would be .00028645 grams = .28645 milligrams
And 2 micromol/L = 2 X .28645 milligrams per liter = .57290 milligrams per liter
4.7 liters of blood on average in adults
4.7 X .57290 = 2.69263 milligrams total in circulation and maintained by the liver per the paper.
Hope I got those numbers right.
RDA = almost one milligram per day for an adult man
It's odd that we're advised to consume the equivalent of our total blood concentration of VA every three days, especially if there is a 128-day half-life and liver storage is good for months. Seems like someone in the world of the experts would want to err on the side of caution, not excess. Wasn't there a beef awhile back where the head of the Vitamin D Council was clamoring for a much lower RDA for VA? I'll see if I can dig that up to see what his argument/concern was about.
Nice calculations.
In times of inadequate dietary intake, the liver maintains stable circulating retinol levels of approximately 2 μmol/L,sufficient to provide the body with this vitamin for months.
This seems like quite an approximate figure as it looks like 2 micromoles per liter appears to be the upper range:
Normal values range from 15 to 60 micrograms per deciliter (mcg/dL) or 0.52 to 2.09 micromoles per liter (micromol/L).
Quite a few people have posted test results here where their VA levels were about that figure for months but then slowly reduced. It seems likely that the figure is based on people that had high reserves of VA already.
Grant is showing us that humans at the most need very little serum VA although it does appear that the body tries to maintain the normal values above. Perhaps these serum levels serve an anti infection purpose?
I propose that when induced biliary excretion of vitamin A is observed (20+ mcg/g) we are already in a state of mild toxicity. The body is already trying to eliminate excess VA and much of that will be reabsorbed.
At these storage levels though one wouldn't expect much toxicity from serum VA, I think it would be safely bound to RBP? At these levels I would just expect a slight toxic effect from unbound VA arriving from the intestine.
The average concentration of vitamin A in postmortem livers of American and Canadian adults is reported to range from 10 to as high as 1,400 μg/g liver (Furr et al., 1989; Hoppner et al., 1969; Mitchell et al., 1973; Raica et al., 1972; Schindler et al., 1988; Underwood et al., 1970). In developing countries where vitamin A deficiency is prevalent, the vitamin A concentration in liver biopsy samples is much lower (17 to 141 μg/g) (Abedin et al., 1976; Flores and de Araujo, 1984; Haskell et al., 1997; Olson, 1979; Suthutvoravoot and Olson, 1974). A concentration of at least 20 μg retinol/g of liver in adults is suggested to be the minimal acceptable reserve (Loerch et al., 1979; Olson, 1982). The mean liver stores of vitamin A in children (1 to 10 years of age) have been reported to range from 171 to 723 μg/g (Flores and de Araujo, 1984; Mitchell et al., 1973; Money, 1978; Raica et al., 1972; Underwood et al., 1970), whereas the mean liver vitamin A stores in apparently healthy infants is lower, ranging from 0 to 320 μg/g of liver (Flores and de Araujo, 1984; Huque, 1982; Olson et al., 1979; Raica et al., 1972; Schindler et al., 1988).
Source: https://www.ncbi.nlm.nih.gov/books/NBK222318/
Normal vitamin A concentrations in liver of adults in the United States are reported to be about 100 μg/g with a range of 14 to 160 μg/g (37). Plasma vitamin A concentrations increase when concentrations in the liver reach about 300 μg of retinol per gram, a concentration at which circulating retinyl esters also increase (5). Olson suggested that 300 μg per gram of liver indicates vitamin A toxicity (5).
Source: https://academic.oup.com/jn/article/132/9/2907S/4687703
Massive discrepancy in the data between the two sources...
If some people are as high as 1400 then some of us were likely over 1000 mcg/g before we started the low VA diet!
1000 x 0.995^273 = 254 mcg
If you started at 1000 mcg/g and you went low VA for 9 months the best formula we have says you would have 254 mcg/g, just under the figure for hypervitaminosis A! This formula is possibly generous, many of us may lose less VA...
I think it makes perfect sense that many are suffering from detox symptoms for many months.
Hi @orion,
I'm one week away from 9 months and I've still got a long way to go.
Do you think the Accutane is being detoxed?
Given that Accutane is a megadose of 13-cis-retinoic acid and that isn't part of the normal retinoid metabolic pathway I wonder how the low VA diet will help with that.
Quote from tim on November 1, 2019, 4:48 pmHi @orion,
I'm one week away from 9 months and I've still got a long way to go.
Do you think the Accutane is being detoxed?
Given that Accutane is a megadose of 13-cis-retinoic acid and that isn't part of the normal retinoid metabolic pathway I wonder how the low VA diet will help with that.
Hi @tim-2
That's a good question, not really sure the answer, but it has been hypothesized that since 13-cis is one of the end products of the retinol pathway, all the co-factors utilized in detoxing retinoic acid are used up to deficiency states (taurine, thiamine, molybdenum, etc), probably most of the Bs. Guessing that this would block all other stored and eaten VA from being excreted, while 13-cis is being consumed. Retinoic acid does not down convert to the aldehydes I believe, so body must really battle to get the RA out.
Just hoping that the long slow process of staying low VA will help out.
I have tested with taurine, Bs, allithiamine, molybdenum, zinc, etc... nothing seems to speed things up, still symptoms push and pull.