Balancing Vitamins A And E

[Amazoniac]

A more reasonable scenario is that those 10 kg of extra body fat are 30% unsaturated (perhaps still inflated), most of it being linoleate (salt form of linoleic acid).

(b) "A recommendation of 0.6 IU vitamin E activity/g linoleate in 100 g adipose tissue fatty acids is tentatively suggested."​

Not all is linoleic acid, some are more unstable, so to be conservative: 0.8*30 = 25 IU a day for the next years to secure that.

I don't know how much of the fat constitution other than adipose tissue contributes to an increased need, but it must not be a lot since the majority of toxic fats should be stored in safer places (Dinkov, 2016).


I forgot to credit Loy (previous post) for the PUFA nomenclature, he's also the author of publications (a) et (b). This guy is another ultra-pimp. And now to redeem myself with class, he wrote a chapter in a book named 'Free Radicals in PBoyology (vol. 4)', the title ist:

(h) CHAPTER 9 - Vitamin E and Lipid Antioxidants in Free-Radical-Initiated Reactions

In summary:

- Adipose tissue might not reflect diet composition after 6 years. They tried to track gurus for 14 years and the accumulation never seemed to reflect the diet composition precisely at any time.
- The estimated fat composition turnoowa rate matches those that we've been discussing.
- Adipose tissue tends to reflect the proportion of fat saturation/unsaturation in the diet more so than the amount; sounds suspicious, but all in all a very low-fat diet might not guarantee anything and might be worse than a higher-fat diet if most of its composition is unsaturated. This also matches what I read from Raj and Johannes of the Selyes:

Ray Peat
"Hans Selye did experiments studying the type of lesion in the heart produced by rapeseed oil, and he found that it was the linoleic acid in it, which is still in it. They took out the peculiar unusual fatty acid but the essential fatty acid linoleic acid is heart toxic. Hans Selye showed that if you added cocoa butter, a highly saturated stearic acid to the rapeseed oil, it no longer causes the death of the heart cells."​

<stop eating spaces>
- The usual composition of linoleate in adipose tissue is 10%.
- Absorption can be decreased from 80-50%, to 50-20%, then to 5% when intakes are 0.04 mg (tut), 20 mg (30 IU), and 200 mg (300 IU) a day respectively. One more point in favor of ingestion.
- "A vitamin E deficiency is not seen in any normal mixed diet, but the progressive increase in PUFA content of the North American diet has lead to concern in the future." Not that more can't be better, but this is a statement made by a competent vitamin E researcher. The optimal requirements might not be as high as our needs to feel safe.

I highly recommend reading his writings:

Spoiler

<stop eating spaces>
I don't agree with the last two interpretations by Zeus here because the author implies that including vegetation might (if anything) increase vit E intakes, and not make it worse, but that alone is not enough to compensate for the overall unnatural PUFA ingestion. Regarding needing 36-60 mg a day, that's because it was based on usual polyunsaturated oils consumption in people's diet, that's definitely decreased the more people lower their consumption. It's difficult to standardize these recommendations. If the diet is already consistenly low in PUFA, what will dictate the requirements the most is the stored amount from past years and perhaps stress levels.

Ps.: I'm trying to have a clearer picture of all this, if you spot the mistakes, please let me know.

 

[Amazoniac]

(d) Toxicity of Stored PUFA – Functional Performance Systems (FPS)

↳ (d2) Increase in Adipose Tissue Linoleic Acid of US Adults in the Last Half Century

The highest percentage reported here was about 25%, which must be an average and there were probably out and liers, but the values calculated above must not be too far off (yet still being conservative).​

I suspect that excessives doses of vitamin E have a greater impact on vitamin A than the opposite. This thread might leave someone with the impression that such deficiency is induced by vitamin A, but it's way more likely that something else depletes E, which in turn affects A. It is also likely that increasing A under those conditions will make the situation worse, but it wasn't the culprit for most of vitamin E's consumption in the body.

- Vitamin E: Estrogen antagonist, energy promoter, and anti-inflammatory

On stress changing the requirements:

"Many of the events involved in inflammation are increased by estrogen, and decreased by vitamin E. Estrogen causes capillaries to become leaky; vitamin E does the opposite. Estrogen increases platelet aggregation, and decreases a factor that inhibits platelet aggregation; vitamin E does the opposite."

But..

"Since the requirement for vitamin E decreases as the consumption of unsaturated fats decreases, the requirement, if any, would be very small if we didn't eat significant quantities of those fats."

"Keeping our diet as free as possible of the polyunsaturated fats, to create something like the "deficiency" state that is so protective (against cancer, trauma, poison, shock, inflammation, infection, etc.) in the animal experiments, seems preferable to trying to saturate ourselves with antioxidants, considering the imperfectly defined nature of the vitamin E products, and the known toxicity of many of the other antioxidants on the market."

"Many nutrition charts no longer list liver as a good source of vitamin E, but a large portion of an animal’s vitamin E is in its liver. This bias in the dietetic literature can be traced to various sources, but a major influence was the campaign in the 1970s by the drug companies that had patented new forms of synthetic “vitamin A.” They had physicians and professors fabricate stories about the great toxicity of natural vitamin A, and placed the stories in national magazines, to clear the field for their supposedly non-toxic products, which have turned out to be disastrously toxic. The result is that many people have fearfully stopped eating liver, because of its vitamin A. The other vitamins in liver, including vitamin K, function very closely with vitamin E, and the stably stored forms of vitamin E are likely to be a good approximation for our needs."​

- https://raypeatforum.com/community/...uld-be-used-sparingly-in-2000-interview.7498/

 

[Amazoniac]

I just want to let members know that I'm not intimidated by cracking sounds at night, I know it's not a monster.

The following publication is the reference for discussing requirements in Zeus' finding:
(i) Plasma levels of antioxidant vitamins in relation to ischemic heart disease and cancer | The American Journal of Clinical Nutrition | Oxford Academic

"The available dose-response curves in men suggest that such a vitamin E status in plasma will require at least 30 IU vitamin E (as initially suggested in 1968 as RDA for the USA and as reinforced by the dependence of the vitamin requirement on the PUFA consumption) (33-35). More likely prudent daily doses of 60-100 IU of vitamin E will be needed to reach plasma levels > 30 microM standardized vitamin E (20, 34-37) and this may be particularly prudent in case of the present common PUFA-enriched diets. Such prudent intake may roughly correspond to 4-6 times the present RDA of 15 IU in the US."

"If the dietary fat is reduced, as presently recommended, eg, to 25%-fat calories (with 9-14 g PUFA), the actual intake of vitamin E can be as low as 15 IU, which was considered deficient even by former criteria (35)."​

These were published around 1990, and the PUFA consumption has been creeping up and is reflected in adipose tissue composition (d2). If they estimated requirements that high, nowadays it can be even higher. However, (as mentioned before) these were based on PUFA-enriched diets and might not be as relevant for members.

 

[Jon]

@Amazoniac

You've answered so many questions I had!


Ha keep it comin!

 

[Amazoniac]

(f) Vitamin E - Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids - NCBI Bookshelf

"Antioxidant Interactions:

When vitamin E intercepts a radical, a tocopheroxyl radical is formed (Burton and Ingold, 1981). This radical can be reduced by ascorbic acid or other reducing agents (Doba et al., 1985; Niki et al., 1982), thereby oxidizing the latter and returning vitamin E to its reduced state.

The ability of one antioxidant to regenerate another oxidized species is dependent on the redox potential of the antioxidant (Buettner, 1993). Biologically relevant electron donors that have been shown to regenerate α-tocopherol effectively from the α-tocopheroxyl radical include vitamin C (McCay, 1985), glutathione (Niki, 1987), and ubiquinols (Stoyanovsky et al., 1995). (For further information see “Nutrient-Nutrient Interactions” in Chapter 5.) Cellular redox cycling is coupled with the energy status of the organism. Thus, it can be expected that during prolonged energy deficit or inadequate production of nicotinamide adenine dinucleotide (NADH), nicotinamide adenine dinucleotide phosphate (NADPH) or glutathione [GSSG] reductase due to dietary deficiencies of niacin (component of NADP or NADPH) or riboflavin (cofactor for GSSG reductase), the ability of the organism to produce sufficient reducing equivalents for recycling oxidized products will be compromised. Conversely, intakes of plant phenolic compounds and flavonoids may add to the total antioxidant pool (de Vries et al., 1998; Manach et al., 1998). The extent, involvement, and contribution of these newer compounds which may be acting as antioxidants to the redox cycling reactions in vitro and in vivo remain to be determined.

The regeneration of α-tocopherol from the α-tocopheroxyl radical may be faster than the further oxidation of the α-tocopheroxyl radical. The extent to which vitamin E is recycled in humans and which antioxidant species are preferentially used for recycling are not known. In human platelet homogenates, distinct chemical and enzymatic pathways for the regeneration of oxidized tocopherol, afforded by vitamin C and glutathione, have been identified (Chan et al., 1991). A metabolic study in humans designed to demonstrate the occurrence of vitamin E recycling by vitamin C had limitations since the body pools of vitamin C and E cannot be totally depleted (Jacob et al., 1996). Although the data were inconclusive, the authors did comment that there is “a trend towards sparing of tissue tocopherol by vitamin C” and that more study was warranted. This is an important area of investigation because the tocopheroxyl radical has been shown in vitro to increase lipid peroxidation in the absence of water-soluble antioxidants, and it has been proposed that this mechanism may be an important factor in potentiating in vivo atherogenesis (Stocker, 1999; Upston et al., 1999). However, there are still no data to determine whether this mechanism is operative in vivo."


"Dietary Polyunsaturated Fat:

Vitamin E requirements have been reported to increase when intakes of polyunsaturated fatty acids (PUFAs) are increased (Dam, 1962; Horwitt, 1962). Based on these data it was suggested that a ratio of at least 0.4 mg (1 µmol) α-tocopherol per gram of PUFA should be consumed by adults (Bieri and Evarts, 1973; Horwitt, 1974; Witting and Lee, 1975). However, the method of determining the vitamin E requirement generated by PUFA intakes is not universally accepted because the amount of vitamin E required to stabilize PUFAs in tissues is influenced to a greater extent by their degree of unsaturation than by their mass (Draper, 1993). Moreover, PUFAs are not deposited in the tissues in the same proportions that they occur in the diet. Finally, dietary PUFAs are modified by elongation and desaturation and are catabolized to various degrees depending on energy status (Jones and Kubow, 1999).

There are also data to suggest that low-density lipoprotein (LDL) oxidation susceptibility in vitro is dependent upon its PUFA content. A 10 percent PUFA diet with 34 percent of calories from fat increased LDL oxidation susceptibility compared to a 19 percent monosaturated fatty acid (MUFA) diet with 40 percent of the calories from fat, without changing the α-tocopherol content of the LDL (Schwab et al., 1998a). In a double-blind crossover trial in 48 postmenopausal women, supplementation with fish oil increased LDL oxidation susceptibility, while supplementation with both fish oil and α-tocopheryl acetate significantly decreased it (Wander et al., 1996).

The effect of the fatty acid composition of reduced-fat diets on the in vitro oxidation of LDL was also examined in 14 moderately hypercholesterolemic (LDL greater than 3.36 mmol/L) female and male subjects (aged 44 to 78 years). Each subject consumed each of five reduced-fat diets (30 percent of energy from total fat, 17 percent from protein, and 53 percent from carbohydrate) which included 20 percent of energy from beef tallow, canola oil, corn oil, olive oil, or rice bran oil for a period of 32 days. When the data from all dietary phases were pooled, LDL α-tocopherol levels and plasma 18:1/18:2 ratios were positively related to LDL oxidation resistance (Schwab et al., 1998b).

Although it is clear that the relationship between dietary PUFA and vitamin E needs is not simple, high PUFA intakes should certainly be accompanied by increased vitamin E intakes."

 

[Amazoniac]

For natural vitamin E equivalence:
1 mg of Dio-tocopherol *1.5 = IU
--

If you note, there's something shady about requiring more or less the same amount of vit E throughout the polyunsaturated fat-depletion years if by the end of it you'll have way less than at the beginning of PUFA restriction. In theory, the amount of vitamin E needed would have to protect all stored fat, so it could be calculated by the proportion of PUFA in the body and the amount of extra fat that the person has. If a person has 2 kg of PUFA in tissues, then requiring vitamin E to cover each gram of that.

In practice this doesn't apply and I suspect it's related to what they mentioned about different availabhbeilaeties: a great deal of adipose tissue remains less available and a smaller fractiont is "actively involved in metabolic exchange". The small part is more concerning and (if I understood it right) is responsible for consuming and demanding vitamin E the most (liver, brain, muscle, etc). But most of vit E in the body is found in adipose tissue, which in turn most is found as Dio-tocopherol in fat droplets.

They claim that the distribution of fats is homogeneous in adipose tissue, which also adds to the confusion as to why by the end of depletion you don't require way less than at the beginning, after all the constituion should have changed over time.

There's a reservoir that keeps releasing PUFA each day if you stored those for years, and this adds to what diet is already providing.


Loy (above) and Horwie have done most of the hard work on this. The others have been just refining it. Just as an example, they were the guys that (together in a publication) commented about the importance of distinguishing different requirements depending on the degree of fat unsaturation. They used linoleic acid as reference for "susceptibility to peroxidation" and how much tocopherol was required to prevent damage; the proneness of other fatty acids were all in relation to it.

The author of the publication that Zeus found simply used for his table (posted on the previous page and below) the amount of vit E in mg that was agreed to be enough to protect linoleic acid (and again using it as reference) and other values used the relations provided by Loy and Horwie. These specific requirements are still in use.

Loy et Horwie (l):

Then [from source (g)]:

The need agreed to protect linoleic acid was 0.6 mg of Dio-toco according to consensus, so there it is set as the requirement for dienoic acids. The rest are in relation to it using the ratios provided by the pimps above on the middle or right column. The german committee uses the one on the middle, and the author of Zeus' finding above used the one on the right. Since linoleic acid is the reference, it is the denominator (2) and the others are numerators. For example, for monoenoic acids: 0.6 * (0.3/2) = 0.09.​

The essential fatty acid-deficient rat (32) and monkey (33) are known to develop signs of tocopherol deficiency. [!]

Mead acid has 3 double bonds, so in theory, consuming a diet that provides only enough PUFA to prevent a true deficiency is preferable to one that induces a deficiency. Yet! If you balance n-3/n-6 as Travo suggests and you use the values in Zeus' finding for specific vit E requirements based on double bonds, as soon as you add the major forms of n-3 fatty acids, you screw things owa.

Here are the values again:

0.09 Monoenoic acids
0.60 Dienoic acids
0.90 Trienoic acids
1.20 Tetraenoic acids
1.50 Pentaenoic acids
1.80 Hexaenoic acids​

n-3 fats have 3 double bonds or more.
n-6 fats have 2 double bonds or more.

If you compare (mead acid) to (linoleic acid + ALA)..

(0.9) vs (0.6 + 0.9)/2​

..it's a comparison of 0.9 vs 0.8, but as soon as you consider arachidonic acid and DHA with more double bonds (4 and 6), things get fishy (tut) and start to tip on the other direction: more vit E is needed so animals that are deficient in the essential fatty acid must be less susceptible to damage, which is contrary to what was suggested on the previous page. Since such diet (unless supplemented) provides no vit E, some animals on extremely low-fat diets were reported to become deficient in it, which is rather surprising! It is related to one of Zeus' interpretations: the amount of vit E per PUFA in a food also matters, the title of the publication refers to a net effect. Since the body is synthesizing its own, no vitamin E is provided, so a deficiency might not be too unlikely (at least in theory).


Indirectly, the current and previous PUFA intakes, amount stored, proportion consumed, stress levels, inflammation and many other factors combined affect the needs for vit E, but it's very difficult to estimate how much each person requires, even more so, provide generalized recommendations (R and D and A).

It should also vary depending on nutrients that interact with vitamin E to enhance its function, preserve or recycle it (previous post). They experiment with different fats and vit E levels in the diet, but never considering those factors as well.


The estimations for vit E are based directly on blood levels of Dio-tocopherol and the resistance of red blood cells to hydrogen peroxid exposure in the glass. How much they can withstand the insult without crumbling gives an idea of how guarded (by vit E, etc) they are. This has some limitations: even though the circulating cells' fatty acid composition are a reflect of diet and vit E can prevent oxidative damage to them, tissues can be lacking enough vit E while circulating cells are relatively guarded; a deficiency appears soon as supplementation is discontinued, meaning that stores were depleted. It's also a test in the glasses, and the behavior in the alives might be different. But it's still used as a rough guide.
They also consider the amount of PUFA consumed because they assume that someone's diet won't vary much, so the PUFA composition of tissues should be almost a reflect of diet, almost, because it's often a bit less unsaturated than diet regardless of how long people stayed on it. The amount that end up being cleared doesn't affect requirements of vit E in the long-term.

These are current ways of finding out the status of vit E (from 'Modern Nutrition in Health and Disease' [ESPN 978-1-60547-461-8]):

Like it was commented by Loy and Horwie, the proportion of polyunsaturated fats is just as important as the amount. An effect that the amount has is on the rate of deposition, which happens to be faster the more you eat.


There are various formulas suggested to calculate recommendations for vitamin E. Most of them have one part that is fixed and other part that varies.

The fixed part (basal requirement) was based on a diet that provided 2.5 g of PUFA and 3 mg of vit E for 4 years or so (savage). Such diet was meant to be a depleting diet after they had consumed a great deal of PUFA for years. After years of this PUFA-restricted condition, blood levels of vit E still weren't on the desirable range and red blood cells were susceptible to damage by hydrogen peroxid, and (according to them) these were marked. So they decided to set a minimum of 4 mg as basal requirement. The german committee set up theirs as 5 mg. Might sound like an insignificant modification but in a more natural diet it shouldn't be. I suppose this little increase was enough to correct those issues.

According to their own words (k):
"A basal minimum of 4 mg d-a-tocopherol is allowed for normal synthesis and accumulations of PUFA into phospholipids, lipoproteins and other compounds even when the amount of PUFA in the diet is very low."​

The part of the formulas that varies is often adjusted depending on the degree of unsaturation of fats. For this, the values from the table above can be used. It goes like this:

Vit E requirement = 4 or 5 mg + [(0.09*'grams UF1')+(0.60*'grams UF2')+(0.90*'grams UF3')+(1.20*'grams UF4')+(1.50*'grams UF5')+(1.80*'grams UF6')]

UF stands for 'unsaturated fat' and each number next to it is the amount of double and bonds.​

If the diet is extremely low in PUFA, it's the reservoir that's turning owaa that is going to be the source of PUFA. Depending on extra weight that the person carries and the PUFA consumption on past years, it's possible to estimate the amount that's stored. If we consider that it takes about 4 years (350 days * 4 = 1500 days) to normalize it, you can assume a liberation of 'estimated stored PUFA' divided by those 1500 days, which might give you a gross idea of requirements, because even though the diet is barely providing more PUFA, the stores are.

When they depleted gurus for years with that diet of beef fat providing only 2.5 g of PUFA a day, they went from about 30% of linoleate in adipose tissue to 3-8% in 4 years. The decline was steady, with makes us doubt if adipose tissue is indeed homogeneous, because if it was, it was probable that it becomes more and more difficult replace PUFA as it's dispersed over time. This didn't happen (k):

The only thing I can think of is that the body has more control over the composition than what we suppose. Either way, perhaps the vit E needs do remain somewhat constant during the depletion phase.

I'm mentioning this because there wasn't any indication that too much was being freed at once to justify a lot more vit E during the beginning. However! Having more stored PUFA means that you're more vulnerable to stress damage, so more vit E initially might still be useful. To be fair, there was a slight noticeable difference on PUFA composition during the first year and plasma tocopherol levels only started to decrease (despite same intake) when % of stored PUFA dropped to 20 or so. If most of the vit E is found with PUFA in adipose tissues, it makes sense that as they're released, vit E is as well.
It might be warranted to supplement more especially for the first 2 years. But note that those people were only getting 3 mg of a-tocopherol during those years.


The digestive upset that some people experience from supplementation should not be too surprising. The absorption tends to be low and slow, we must not be adapted to 800 IU doses at once, even though it's not toxic, the body didn't have the chance to adjust to such doses because it's difficult to find foods that have more than 20 IU for each serving.

Zeus' TocoVit for example provides that much (20 IU) per drop and I guess it's better to work the way up from low doses.

But anvwav, enough of poetry.


(j) Relationship Between Vitamin E Requirement and Polyunsaturated Fatty Acid Intake in Man: a Review

"Vitamin E especially protects PUFA in phospholipids of biological membranes and in plasma lipoproteins against peroxidation [5]. Steady-state concentrations of vitamin E in membranes are determined by the efficiency of its incorporation into membranes by transfer from blood lipoproteins, and its metabolism in these membranes [9]."

"Witting and Horwitt [2] postulated that in the case of a relation between tocopherol deficiency symptoms and lipid peroxidation, the rate at which deficiency develops should be related to the degree of unsaturation of the various fatty acids rather than to the total amount of unsaturation in the dietary fat. In the kinetics of autoxidation in vitro, the overall rate of oxidation is dependent on the rate of the slowest reaction, i.e. ROO· + RH → ROOH + R·, where ROO· is a lipid peroxyl radical, RH is a PUFA, ROOH is a lipid hydroperoxide and R· is a lipid radical. Indeed, this reaction is highly dependent on the nature of the R-group. Accordingly, from in vitro experiments it is known that the peroxidizability of unsaturated fatty acids increases almost linearly with the number of double bonds present in the molecule [19]. The relative maximal oxidation rates for mono-, di-, tri-, tetra-, penta- and hexaenoic acids appeared to be 0.025/1/2/4/6/8 [middle column above], respectively [19]."

"The relative contributions of the various unsaturated fatty acids in inducing creatinuria were comparable to the relative oxidation rates of PUFA as shown in the in vitro experiments by Holman [19]. Accordingly, the relative amounts of tocopherol required to protect the various fatty acids from being peroxidized were estimated to be approximately in the ratios 0.3/2/3/4/5/6 [right column above] for mono-, di-, tri-, tetra-, penta- and hexaenoic acids respectively [2]. However, since neither the tocopherol content of the muscle membranes nor the plasma tocopherol concentration were analyzed, it [was] not possible to directly relate the amount of tocopherol required to the amount of peroxidizable PUFA in phospholipids. In addition, it is not clear whether the same ratios as obtained and estimated from animal data are applicable to humans. This study, as well as an experiment in ducklings by Jager [20], indicates that, when studying the vitamin E requirement, it is important to take into account not only the fatty acid composition and tocopherol content of the diet, but of the biomembranes as well. Furthermore, it should be evident that, although myopathy might be a valid indicator to study vitamin E requirement in animals, this method can not be used for human studies."

"A number of difficulties arise when studying the vitamin E requirement in man. Besides the ethical problems of feeding humans experimental diets, which provide minimal levels of α-tocopherol for prolonged periods of time, there are a number of variable conditions that determine vitamin E requirement. These conditions include the amount of peroxidizable compounds in tissues and diet, and the time required to deplete the stores of tocopherols which, in turn, depends on the level of peroxidizable compounds in the tissues [21]."

"The vitamin E status of erythrocytes has been evaluated by determining their resistance to hemolysis in vitro (erythrocyte hemolysis test). This test is based on the requirement for α-tocopherol to stabilize the erythrocyte membrane. Since vitamin E in the form of α-tocopherol is the major lipid-soluble antioxidant in red blood cell membranes, regulation of α-tocopherol concentrations in membranes is of critical importance in maintaining structure and function of these membranes. In the erythrocyte hemolysis test, the red blood cells are exposed to an oxidizing agent, e.g. hydrogen peroxide, under controlled conditions of time and temperature. Rose and György [22] were the first to demonstrate a protective effect of all four tocopherol isomers, both in vivo as in vitro, on erythrocyte hemolysis induced by dialuric acid in vitamin E deficient rats."

"The erythrocyte hemolysis test was also used in the Elgin project, a long-term study (up to four years) to investigate the vitamin E requirements in relation to PUFA intake, mainly linoleic acid, in humans [1, 21, 23, 24]. Up till now, this is the only experimental study on vitamin E requirement of human adults."

"According to Horwitt [21] an allowance should be made for cellular interconversion and retention of PUFA when calculating the required dietary intake of vitamin E in relation to dietary PUFA consumption. Significant amounts of PUFA are found in tissues, predominantly in the phospholipids of biological membranes, which are susceptible to peroxidation. A calculation of the vitamin E requirement based on dietary PUFA intake does not take into account these PUFA. It is generally accepted that the fatty acid composition of tissue lipids can be altered, within certain limits, by changing the dietary fatty acid composition."

"Horwitt’s analyses of the Elgin project demonstrate that it is very difficult to give exact information on vitamin E requirements in relation to PUFA intake, in particular when the erythrocyte hemolysis test is used. Horwitt [1] recognized that the hemolysis test is nothing more than an indication of the rate at which erythrocyte fatty acids can be oxidized. Furthermore, there is no evidence indicating that this in vitro assay closely reflects the stability of the erythrocyte in vivo [23, 26]."

"In conclusion, although the erythrocyte hemolysis test may be a valid indicator of vitamin E status, it has insufficienty been validated to allow assessment of the vitamin E requirement in relation to PUFA content and composition in diet and membranes."

"According to Harris and Embree [3], the results of Horwitt’s experiments showed that the minimum ratio of α-tocopherol/PUFA at which no deficiency symptoms developed, was between 0.5 and 0.8 mg/g for the experimental diets used. Analysis of the results of food consumption surveys in the United States revealed a ratio of 0.6 mg α-tocopherol per g PUFA, predominantly linoleic acid. They proposed to use the value of 0.6 as a reference ratio for an adequate supply of vitamin E, which seems to be well in agreement with ratios found in various animal experiments. However, it is difficult to compare the results of these studies because of species variation and differences in experimental techniques, including the deficiency symptoms that are under examination, time of depletion and interaction with other nutrients. Moreover, this value is mainly based on linoleic acid as the major PUFA and may not be adequate when the intake of longer-chain, more-unsaturated fatty acids is increased."

"In animals it was demonstrated that the vitamin E requirement increased only as long as an increase in the amount of dietary PUFA resulted in an increase in tissue [20, 27]. Consequently, the vitamin E/PUFA ratio for quantities of PUFA higher than those required to saturate tissue PUFA approaches zero. In addition, vitamin E requirement is not only increased during a high PUFA diet, but also for a certain period after returning to a normal mixed diet because tissue PUFA content is still high. Moreover, linoleic acid is not the only dietary unsaturated fatty acid to be considered in evaluating the vitamin E requirement [27]. According to Witting [27], the critical vitamin E/PUFA ratio is therefore not applicable to all dietary regimens."

"[..]the German Society of Nutrition proposed in 1991 a minimum daily intake of 5 mg α-tocopherol to prevent lipid peroxidation in tissue lipids at moderate PUFA intakes (< 7 g linoleic acid per day) [31]."

"As is clear from the studies and recommendations described above, there is no agreement upon the exact amount of vitamin E required when consuming various unsaturated fatty acids. Critical points are that these recommendations are based on animal experiments and food intake data that are not adequately validated. Moreover, the methods used in the studies described have several limitations, which make it difficult to quantify the relation between vitamin E and PUFA."

"Results of an observational study showed that extreme fish consumption does not affect plasma antioxidant levels. Although subjects usually consuming a high-fish diet (103 g/day) had higher EPA and DHA intakes and higher levels of plasma n-3 fatty acids than subjects on an habitual low-fish diet (5 g/day), there were no differences in vitamin E intake and concentrations of α-tocopherol in plasma between the two groups [35]. When the formula of Muggli is applied to the intake data of unsaturated fatty acids in both groups, the α-tocopherol requirement will be 8.97 and 8.28 mg/day for the high-fish and low-fish group, respectively, values that are only slightly lower than the actual vitamin E intakes (9.0 and 10.5 mg/day). However, since in this study markers of lipid peroxidation were not measured, any possible adverse effects of the more oxidation- susceptible n-3 fatty acids in fish cannot be ruled out. Therefore, it is not clear whether the vitamin E intake of 10.5 mg/day in the high-fish group is sufficient to prevent lipid peroxidation."

"[..]it is possible that nutritional co-factors play a role in the process of lipid peroxidation, for instance vitamin C. Vitamin C is the major line of antioxidative defense against radicals in the aqueous phase and lipid peroxidation in plasma, but it is also crucial for the recycling of vitamin E [42]. According to Gey [42], there is evidence that the vitamins C and E interact also in vivo in man, and that the functional coupling of these vitamins is a crucial part of the overall antioxidant potential. However, in the studies described above, the influence of vitamin C on lipid peroxidation and on the recycling process of vitamin E has not been taken into account.

Therefore, when investigating the amount of vitamin E that is needed to prevent lipid peroxidation when the consumption of fish fatty acids, e.g. EPA and DHA is increased, the influence of co-nutrients as vitamin C should also be taken into account."​

(k) Status of human requirements for vitamin E (Horwie)

"In organizing studies on man, the possibilities that irreversible damage may be produced makes it unthinkable to use experimental diets for human subjects which provide minimal levels of a-tocopherol for prolonged periods of time. In the Elgin project on vitamin E requirements (2-4), we were cautious not to feed a completely deficient diet despite the reasonable certainty that it would take at least 4 years to deplete the reserves in the average previously well-fed adult. It is extremely doubtful that it will be possible to repeat such a long-term nutritional deficiency study in the foreseeable future."

"In the study of vitamin E requirements, the problem is particularly difficult because of the indeterminate floating variables, i.e., the amount of peroxidizable unsaturated compounds in the tissues, the oxidizable components in the diet and the time required to use up the reserves of the tocopherols which, in turn, depends on the level of peroxidizable unsaturates in the tissues. Thus, one can visualize an extreme situation where 5 mg of a-tocopherol a day could supply the minimum requirement for a period of years in a previously well-fed adult with low tissue levels of unsaturates, whereas at other levels of tissue and diet composition 15 mg would not be enough."

"[..]few, if any, individuals would show any recognizable signs of scurvy or other related pathology if their diet was limited to 10 mg of ascorbic acid (5) a day. But certainly, even in this far less complicated situation one could hardly recommend so little vitamin C as a requirement."

"Most vitamins other than vitamin E have been shown to be intimately related to enzymatic or hormonal effects or to be in some manner a significant part of a chemical equation. The tocopherols may also some day be shown to have a similar specific function but for the time we are still looking. Without belittling the possibility that tocopherol has other functions, when one considers all the physiological systems that have peroxidizable lipids in the presence of traces of oxygen and metals which could catalyze peroxidations, if tocopherol had not evolved, nature would have had to invent a different antioxidant to do the job. One of the characteristics of free-radical traps that can delay the initiation and possibly the rate of reactions that may be undesirable, is that the more antioxidant that may be present in a given mixture, the greater the potential of it trapping an errant free radical. The same analysis cannot be made for vitamins with functions that can be described in stoichiometric equations where more than a prescribed amount has no additional effect. Therefore, some of us are led to wonder, in the absence of any hard proof, whether more than the established minimum requirement of this antioxidant can have a biological consequence. About all we as scientists can do while waiting for a final answer is to encourage more work and keep an open mind."

"Repetitive daily consumptions of tocopherols other than a-tocopherol can apparently be protective to man and animals. This appears to be especially true if some reasonable portion of the total tocopherols is a-tocopherol. Tests of potency which depend on rate of disappearance of different tocopherols from the tissues and body fluids have shown that a-tocopherol will persist in the erythrocytes longer than y-tocopherol (11) but as Bieni (12) has noted y-tocopherol is stored in the tissues for a longer period than previously considered."

"Actually, as will be shown, those who eat more than the usual amount of polyunsaturated fat, consume 30 IU or more of the tocopherols and those who have existed on diets low in polyunsaturated fats have tissue lipids that have lower potentials for peroxidation and they can presumably get by with less tocopherol at the tissue sites in question."

"The level of linoleic acid obtained in the depot fats, tends to approach the percentage in the diet if the diet is fed for a sufficient period of time."

"Since it is possible that 8 mg of a-tocopherol/day could be adequate when the tissues are low in polyunsaturates and more than 30 mg/day are needed when the tissues are very high in linoleates--as after long time consumption of safflower oil--there seems to be no single satisfactory figure upon which to compromise."

"To allow for the synthesis of polyunsaturated fatty acids that do not come from dietary sources it is suggested that a minimum adult requirement of 10 mg of d-a-tocopherol be allowed even if the calculation of the requirement from dietary constituents should result in a lower figure."

"Both the percentage of PUFA in the dietary fat and the amount of such fat affect the degree to which tissue lipids accumulate PUFA in the tissues. The depot fat lipids tend to achieve the same percentage of linoleic acid as in the fat consumed. Thus when 60 mg corn oil was added to the basal diet the final mixture contained about 35% linoleate and when this diet was fed for almost 5 years the depot fats reached a level of about 33% in the adult male subjects. Similarly, when 60 mg safflower oil was added to the basal diet to achieve about 55% linoleate in the dietary fats the depot fats reached approximately 50% (3, 14). Data on how much the total amount of PUFA in the diet affects the rate of achieving final equilibrium are not available but it would appear that this should be as important as the percentage of PUFA in the lipids fed. Stated differently, it may take longer to reach tissue equilibrium with lower rather than higher levels of fats in the diet, but the controlling factor in the final composition of the tissue lipids is as much related to the ratios of the individual fatty acids ingested as to the total amount of the lipid ingested."

"Any calculation of the vitamin E requirement based only on the levels of PUFA in the diet would not be complete since the tissues would have considerable amounts of polyunsaturated lipids even when the diet was practically deficient in PUFA."

"Accordingly, some allowance must be made for cellular synthesis, and retention of PUFA in any calculation of the tocopherol requirements. The least unsaturated diet used in the Elgin Project contained 60 mg of beef fat added to the basal diet. This diet provided only 2.4 g of PUFA and approximately 3 mg of d-a-tocopherol. After more than 3 years on this diet (14), one subject, not included in Fig. 2, had less than 3% linoleate in his adipose tissue lipids. All of the subjects on this diet had marked [!] increases in their erythrocyte peroxide hemolysis test results. Accordingly, we have chosen 4 mg ofd-a-tocopherol as the amount that should be allowed for tissue synthesis of peroxidizable compounds in the male adult even when the diet is practically deficient in PUFA."

"[Subjects were fed a basal diet with 60 g of beef tallow as the fat, remaining on this diet for 5 years.] These subjects had been fed the basal diet plus 60 g commercial corn oil for 6 months previously. The beef fat diet (the basal constituents of the diet remained the same) was shown by analysis of 14 composite samples to range from 2.6 to 3.9% linoleic acid with a mean of 3.0% in 80 g of total fat as consumed. The tocopherol content of this diet was no higher than in the deficient diets previously used, analyzing out to approximately 3 mg a-tocopherol/total daily diet. Despite the low intake of vitamin E, there was a rise in serum tocopherol during the subsequent 20 months while the depot fat linoleates were rapidly decreasing. Part of this increase in plasma tocopherol may have been due to the increase in serum lipoproteins as evidenced by an increase in plasma cholesterol during the first month on the beef fat. From the data, one has the choice of concluding that the depot fats were releasing stored tocopherols, which apparently did not happen during the months before beef fat was started, or that very little tocopherol is needed when the diet contains barely enough linoleic acid to supply the essential fatty acid requirement. In any case, after 20 months on the beef tallow diet a marked decrease in plasma tocopherol commenced and this was confirmed by positive peroxide hemolysis tests when the plasma tocopherols dropped below 0.5 mg/100 ml. The hemolyses test results ranged between 50 and 90% after the fourth year on the beef fat diet. Nevertheless, these analyses showed a much milder deficiency in these subjects than when unsaturated lipids had been fed as part of same basal diet and it is likely that an additional 3 mg of a-tocopherol/day would have been sufficient to repair the blood tocopherol levels in this unusual diet. Recapitulating, this beef fat diet provided 3 mg a-tocopherol in a diet which had about 3.0% linoleic acid in the total lipids and the depot fat linoleates dropped to less than 8%."

"[..]higher levels of antioxidant may be required under [] unusual conditions. One wonders how much higher the plasma tocopherol should be in order to achieve the greater protection that may be needed when the tissues have such unnatural levels of PUFA."

"The data in Table 4 make it difficult to change our original decision that the adult male vitamin E requirement ranges from a minimum of 10 to a probable maximum of 30 mg of d-a-tocopherol/day despite the fact that many individuals in apparent good health consume considerably less."​

(l) Interpretations of requirements for thiamin, riboflavin, niacin-tryptophan, and vitamin E plus comments on balance studies and vitamin B-6 (Horwie)

"The range ofthe minimum requirement for vitamin E is probably greater than for any other vitamin. Only a small amount seems to be needed in the growing rat ifthe diet contains only enough linoleic acid to assure the absence of fatty acid deficiency, whereas, the amount of vitamin E required becomes quite large if fish oils are included in the diet."​

(m) Vitamin E function and requirements in relation to PUFA

"Vitamin E has eight isoforms; it can be categorised into tocopherol isoforms, which have a saturated side chain on the chromanol ring, and into tocotrienol isoforms, which have an unsaturated side chain. Each of these types is further categorised as a-, b-, y- or z-forms, which are defined by the number and the location of the methyl groups on the chromanol ring. The 6-hydroxy group of the chromanol ring is the active site for scavenging radicals, whereas the side chain does not affect the reactivity towards free radicals. Thus, all the isoforms of vitamin E have some antioxidant activity."

"[..]the vitamin E forms are discriminated by the liver and only a-tocopherol is preferentially accumulated in the cellular membranes of tissues, whereas the other isoforms are rapidly metabolised and excreted in a similar manner as other xenobiotics (6,9). y-Tocopherol is the other vitamin E form that is present in significant amounts in the human diet as it is contained in a number of widely consumed vegetable oils( 9 ). y-Tocopherol is slightly less efficient than a-tocopherol as a scavenger of oxygen radicals, but it is an efficient scavenger of reactive nitrogen species due to the unsubstituted 5-position on the chromanol ring (9-11). However, y-tocopherol is efficiently metabolised by cytochrome P450 enzymes. This may be the reason why even after intake of high doses of y-tocopherol, its plasma concentration rarely exceeds 10% of that of a-tocopherol, and much less is found in tissues (9,12-18)."

"Atkinson et al. (40) undertook a series of biophysical experiments to describe the position of 2H-labelled a-tocopherol in the cell membrane. They concluded that the a-tocopherol molecule stands upright in the membrane bilayer (Fig. 1). The non-a-tocopherol isoforms can also be incorporated into cellular membranes. Studies in lipid model membranes indicate that the localisation of the various vitamin E forms in the membranes can slightly differ and they might alter the membrane behaviour differently due to their structural differences (20,41). However, as mentioned previously, all non-a-tocopherol isoforms are rapidly metabolised and excreted and only a-tocopherol is present in significant amounts in cell membranes."

Fig. 1

<tut>
"[..]the a-tocopherol antioxidant activity occurs at the membrane surface (42). This location of vitamin E in the membrane would also allow vitamin C, which is placed at the hydrophilic/hydrophobic interphase, to interact with the a-tocopheroxyl radical and to bring it to the energetic ground state. This is the mechanism by which vitamin E is regenerated and is ready to interact with the next peroxyl radical (7). Thus, both lipophilicity and membrane localisation of vitamin E explain its antioxidant activity."

"[An] hospital diet providing 8–12 mg/d of a-tocopherol and 4–7 g/d of PUFA was considered as being on the borderline of adequacy over the 13 years of observation based on the plasma a-tocopherol levels and the data from the erythrocyte haemolysis test (83)."

"[..]the a-tocopherol requirement in the absence of dietary PUFA was assessed by feeding subjects 60 g/d of beef tallow (a saturated fat) for 5 years. The diet provided about 2.4 g of PUFA and 3 mg of a-tocopherol daily. Plasma a-tocopherol levels decreased, whereas the sensitivity of erythrocytes to haemolysis increased. These data indicated that a minimal intake of 4–5 mg/d of a-tocopherol was needed in the basal state, even in the absence of dietary PUFA."

"Collectively, the data from the Elgin project suggest that individuals ingesting large amounts of linoleic acid (>30 g/d) require more than 30 mg/d of a-tocopherol, whereas 10 mg/d of a-tocopherol may be bordering on inadequacy in individuals ingesting about 4–7 g/d of linoleic acid (83). It was proposed that the a-tocopherol requirements in humans range from 10 to 30 mg/d depending on the amount of PUFA in the diet and the tissues( 83 )."

"The estimated optimal vitamin E:PUFA ratio seems to be relatively consistent across studies. Taking these studies together suggests an estimated additional vitamin E requirement ranging from 0·4 to 0·6 mg RRR-a-tocopherol/g of PUFA in the diet for a diet with a typical content of PUFA, mainly as linoleic acid. A ratio of 0·5 mg RRR-a-tocopherol/g of PUFA in the middle of this range may reasonably be used to calculate the vitamin E requirement. Thus, considering a basal requirement of at least 4 mg RRR-a-tocopherol as suggested by the human data from the Elgin project, the following formula can be used to calculate the vitamin E requirement: vitamin E requirement=4+(0·5× amount of PUFA in the diet in grams). However, the vitamin E requirement also depends on the degree of unsaturation of PUFA in the diet (80), and most of the studies described so far have considered linoleic acid as the main dietary PUFA. Therefore, Muggli (99) proposed to estimate the dietary vitamin E requirement by taking the relative vitamin E requirement for individual PUFA into account."

..and this is what was discussed above.​

<don't>
Finally, Howie in his most recent publication wrote this:

(n) Critique of the requirement for vitamin E

"[..]the 1989 RDA committee concluded that the requirement for men should be 10 mg tocopherol equivalents vitamin E/d, although it was known that millions of persons have lived long lives while consuming much less. An increasing in this requirement to 15 mg/d benefits only the commercial interests involved in the sale of vitamin E. To help consumers, the distinction between nutritional requirements and the possible pharmacologic benefits of an antioxidant should be emphasized. Because of common knowledge that I have been involved in the field of vitamin E research for > 65 y, “I am frequently asked by both professionals and laymen how much I take.” The answer is 200 mg RRR-dio-tocopherol/d, but often with the proviso that I am not completely certain of the benefit of such a pharmacologic dose of an antioxidant."

"It was previously shown that the antiadhesive effects of dio-tocopherol on platelets combined with the antiaggregatory effects of aspirin reduce platelet adhesion by a highly significant 40% (22, 23). This effect on platelets, which is dependent on many variables, could be considered either beneficial or undesirable in the prevention of stroke. However, inhibition of platelet function could lead to an increased tendency to bleed (24). Accordingly, it is my judgment that a tolerable upper intake level of 1000 mg RRR-dio-tocopherol/d for adults is too high. The daily intake of less than one-half that amount produces high concentrations of vitamin E in the tissues."

"Many people who supplement their diet believe that if a little is good, more is better. An official statement that 1000 mg RRR- dio-tocopherol/d is safe may encourage some consumers to take the maximum amount of vitamin E recommended regardless of their consumption of other antithrombotic compounds. The precautionary principle should be applied in this situation."​

 

[Braveheart]

For natural vitamin E equivalence:
1 mg of Dio-tocopherol *1.5 = IU
--

If you note, there's something shady about requiring more or less the same amount of vit E throughout the polyunsaturated fat-depletion years if by the end of it you'll have way less than at the beginning of PUFA restriction. In theory, the amount of vitamin E needed would have to protect all stored fat, so it could be calculated by the proportion of PUFA in the body and the amount of extra fat that the person has. If a person has 2 kg of PUFA in tissues, then requiring vitamin E to cover each gram of that.

In practice this doesn't apply and I suspect it's related to what they mentioned about different availabhbeilaeties: a great deal of adipose tissue remains less available and a smaller fractiont is "actively involved in metabolic exchange". The small part is more concerning and (if I understood it right) is responsible for consuming and demanding vitamin E the most (liver, brain, muscle, etc). But most of vit E in the body is found in adipose tissue, which in turn most is found as Dio-tocopherol in fat droplets.

They claim that the distribution of fats is homogeneous in adipose tissue, which also adds to the confusion as to why by the end of depletion you don't require way less than at the beginning, after all the constituion should have changed over time.

There's a reservoir that keeps releasing PUFA each day if you stored those for years, and this adds to what diet is already providing.


Loy (above) and Horwie have done most of the hard work on this. The others have been just refining it. Just as an example, they were the guys that (together in a publication) commented about the importance of distinguishing different requirements depending on the degree of fat unsaturation. They used linoleic acid as reference for "susceptibility to peroxidation" and how much tocopherol was required to prevent damage; the proneness of other fatty acids were all in relation to it.

The author of the publication that Zeus found simply used for his table (posted on the previous page and below) the amount of vit E in mg that was agreed to be enough to protect linoleic acid (and again using it as reference) and other values used the relations provided by Loy and Horwie. These specific requirements are still in use.

Loy et Horwie (l):
View attachment 10168

Then [from source (g)]:

The need agreed to protect linoleic acid was 0.6 mg of Dio-toco according to consensus, so there it is set as the requirement for dienoic acids. The rest are in relation to it using the ratios provided by the pimps above on the middle or right column. The german committee uses the one on the middle, and the author of Zeus' finding above used the one on the right. Since linoleic acid is the reference, it is the denominator (2) and the others are numerators. For example, for monoenoic acids: 0.6 * (0.3/2) = 0.09.​

Mead acid has 3 double bonds, so in theory, consuming a diet that provides only enough PUFA to prevent a true deficiency is preferable to one that induces a deficiency. Yet! If you balance n-3/n-6 as Travo suggests and you use the values in Zeus' finding for specific vit E requirements based on double bonds, as soon as you add the major forms of n-3 fatty acids, you screw things owa.

Here are the values again:

0.09 Monoenoic acids
0.60 Dienoic acids
0.90 Trienoic acids
1.20 Tetraenoic acids
1.50 Pentaenoic acids
1.80 Hexaenoic acids​

n-3 fats have 3 double bonds or more.
n-6 fats have 2 double bonds or more.

If you compare (mead acid) to (linoleic acid + ALA)..

(0.9) vs (0.6 + 0.9)/2​

..it's a comparison of 0.9 vs 0.8, but as soon as you consider arachidonic acid and DHA with more double bonds (4 and 6), things get fishy (tut) and start to tip on the other direction: more vit E is needed so animals that are deficient in the essential fatty acid must be less susceptible to damage, which is contrary to what was suggested on the previous page. Since such diet (unless supplemented) provides no vit E, some animals on extremely low-fat diets were reported to become deficient in it, which is rather surprising! It is related to one of Zeus' interpretations: the amount of vit E per PUFA in a food also matters, the title of the publication refers to a net effect. Since the body is synthesizing its own, no vitamin E is provided, so a deficiency might not be too unlikely (at least in theory).


Indirectly, the current and previous PUFA intakes, amount stored, proportion consumed, stress levels, inflammation and many other factors combined affect the needs for vit E, but it's very difficult to estimate how much each person requires, even more so, provide generalized recommendations (R and D and A).

It should also vary depending on nutrients that interact with vitamin E to enhance its function, preserve or recycle it (previous post). They experiment with different fats and vit E levels in the diet, but never considering those factors as well.


The estimations for vit E are based directly on blood levels of Dio-tocopherol and the resistance of red blood cells to hydrogen peroxid exposure in the glass. How much they can withstand the insult without crumbling gives an idea of how guarded (by vit E, etc) they are. This has some limitations: even though the circulating cells' fatty acid composition are a reflect of diet and vit E can prevent oxidative damage to them, tissues can be lacking enough vit E while circulating cells are relatively guarded; a deficiency appears soon as supplementation is discontinued, meaning that stores were depleted. It's also a test in the glasses, and the behavior in the alives might be different. But it's still used as a rough guide.
They also consider the amount of PUFA consumed because they assume that someone's diet won't vary much, so the PUFA composition of tissues should be almost a reflect of diet, almost, because it's often a bit less unsaturated than diet regardless of how long people stayed on it. The amount that end up being cleared doesn't affect requirements of vit E in the long-term.

These are current ways of finding out the status of vit E (from 'Modern Nutrition in Health and Disease' [ESPN 978-1-60547-461-8]):

View attachment 10169​

Like it was commented by Loy and Horwie, the proportion of polyunsaturated fats is just as important as the amount. An effect that the amount has is on the rate of deposition, which happens to be faster the more you eat.


There are various formulas suggested to calculate recommendations for vitamin E. Most of them have one part that is fixed and other part that varies.

The fixed part (basal requirement) was based on a diet that provided 2.5 g of PUFA and 3 mg of vit E for 4 years or so (savage). Such diet was meant to be a depleting diet after they had consumed a great deal of PUFA for years. After years of this PUFA-restricted condition, blood levels of vit E still weren't on the desirable range and red blood cells were susceptible to damage by hydrogen peroxid, and (according to them) these were marked. So they decided to set a minimum of 4 mg as basal requirement. The german committee set up theirs as 5 mg. Might sound like an insignificant modification but in a more natural diet it shouldn't be. I suppose this little increase was enough to correct those issues.

According to their own words (k):
"A basal minimum of 4 mg d-a-tocopherol is allowed for normal synthesis and accumulations of PUFA into phospholipids, lipoproteins and other compounds even when the amount of PUFA in the diet is very low."​

The part of the formulas that varies is often adjusted depending on the degree of unsaturation of fats. For this, the values from the table above can be used. It goes like this:

Vit E requirement = 4 or 5 mg + [(0.09*'grams UF1')+(0.60*'grams UF2')+(0.90*'grams UF3')+(1.20*'grams UF4')+(1.50*'grams UF5')+(1.80*'grams UF6')]

UF stands for 'unsaturated fat' and each number next to it is the amount of double and bonds.​

If the diet is extremely low in PUFA, it's the reservoir that's turning owaa that is going to be the source of PUFA. Depending on extra weight that the person carries and the PUFA consumption on past years, it's possible to estimate the amount that's stored. If we consider that it takes about 4 years (350 days * 4 = 1500 days) to normalize it, you can assume a liberation of 'estimated stored PUFA' divided by those 1500 days, which might give you a gross idea of requirements, because even though the diet is barely providing more PUFA, the stores are.

When they depleted gurus for years with that diet of beef fat providing only 2.5 g of PUFA a day, they went from about 30% of linoleate in adipose tissue to 3-8% in 4 years. The decline was steady, with makes us doubt if adipose tissue is indeed homogeneous, because if it was, it was probable that it becomes more and more difficult replace PUFA as it's dispersed over time. This didn't happen (k):

View attachment 10170​

The only thing I can think of is that the body has more control over the composition than what we suppose. Either way, perhaps the vit E needs do remain somewhat constant during the depletion phase.

I'm mentioning this because there wasn't any indication that too much was being freed at once to justify a lot more vit E during the beginning. However! Having more stored PUFA means that you're more vulnerable to stress damage, so more vit E initially might still be useful. To be fair, there was a slight noticeable difference on PUFA composition during the first year and plasma tocopherol levels only started to decrease (despite same intake) when % of stored PUFA dropped to 20 or so. If most of the vit E is found with PUFA in adipose tissues, it makes sense that as they're released, vit E is as well.
It might be warranted to supplement more especially for the first 2 years. But note that those people were only getting 3 mg of a-tocopherol during those years.


The digestive upset that some people experience from supplementation should not be too surprising. The absorption tends to be low and slow, we must not be adapted to 800 IU doses at once, even though it's not toxic, the body didn't have the chance to adjust to such doses because it's difficult to find foods that have more than 20 IU for each serving.

Zeus' TocoVit for example provides that much (20 IU) per drop and I guess it's better to work the way up from low doses.

But anvwav, enough of poetry.


(j) Relationship Between Vitamin E Requirement and Polyunsaturated Fatty Acid Intake in Man: a Review

"Vitamin E especially protects PUFA in phospholipids of biological membranes and in plasma lipoproteins against peroxidation [5]. Steady-state concentrations of vitamin E in membranes are determined by the efficiency of its incorporation into membranes by transfer from blood lipoproteins, and its metabolism in these membranes [9]."

"Witting and Horwitt [2] postulated that in the case of a relation between tocopherol deficiency symptoms and lipid peroxidation, the rate at which deficiency develops should be related to the degree of unsaturation of the various fatty acids rather than to the total amount of unsaturation in the dietary fat. In the kinetics of autoxidation in vitro, the overall rate of oxidation is dependent on the rate of the slowest reaction, i.e. ROO· + RH → ROOH + R·, where ROO· is a lipid peroxyl radical, RH is a PUFA, ROOH is a lipid hydroperoxide and R· is a lipid radical. Indeed, this reaction is highly dependent on the nature of the R-group. Accordingly, from in vitro experiments it is known that the peroxidizability of unsaturated fatty acids increases almost linearly with the number of double bonds present in the molecule [19]. The relative maximal oxidation rates for mono-, di-, tri-, tetra-, penta- and hexaenoic acids appeared to be 0.025/1/2/4/6/8 [middle column above], respectively [19]."

"The relative contributions of the various unsaturated fatty acids in inducing creatinuria were comparable to the relative oxidation rates of PUFA as shown in the in vitro experiments by Holman [19]. Accordingly, the relative amounts of tocopherol required to protect the various fatty acids from being peroxidized were estimated to be approximately in the ratios 0.3/2/3/4/5/6 [right column above] for mono-, di-, tri-, tetra-, penta- and hexaenoic acids respectively [2]. However, since neither the tocopherol content of the muscle membranes nor the plasma tocopherol concentration were analyzed, it [was] not possible to directly relate the amount of tocopherol required to the amount of peroxidizable PUFA in phospholipids. In addition, it is not clear whether the same ratios as obtained and estimated from animal data are applicable to humans. This study, as well as an experiment in ducklings by Jager [20], indicates that, when studying the vitamin E requirement, it is important to take into account not only the fatty acid composition and tocopherol content of the diet, but of the biomembranes as well. Furthermore, it should be evident that, although myopathy might be a valid indicator to study vitamin E requirement in animals, this method can not be used for human studies."

"A number of difficulties arise when studying the vitamin E requirement in man. Besides the ethical problems of feeding humans experimental diets, which provide minimal levels of α-tocopherol for prolonged periods of time, there are a number of variable conditions that determine vitamin E requirement. These conditions include the amount of peroxidizable compounds in tissues and diet, and the time required to deplete the stores of tocopherols which, in turn, depends on the level of peroxidizable compounds in the tissues [21]."

"The vitamin E status of erythrocytes has been evaluated by determining their resistance to hemolysis in vitro (erythrocyte hemolysis test). This test is based on the requirement for α-tocopherol to stabilize the erythrocyte membrane. Since vitamin E in the form of α-tocopherol is the major lipid-soluble antioxidant in red blood cell membranes, regulation of α-tocopherol concentrations in membranes is of critical importance in maintaining structure and function of these membranes. In the erythrocyte hemolysis test, the red blood cells are exposed to an oxidizing agent, e.g. hydrogen peroxide, under controlled conditions of time and temperature. Rose and György [22] were the first to demonstrate a protective effect of all four tocopherol isomers, both in vivo as in vitro, on erythrocyte hemolysis induced by dialuric acid in vitamin E deficient rats."

"The erythrocyte hemolysis test was also used in the Elgin project, a long-term study (up to four years) to investigate the vitamin E requirements in relation to PUFA intake, mainly linoleic acid, in humans [1, 21, 23, 24]. Up till now, this is the only experimental study on vitamin E requirement of human adults."

"According to Horwitt [21] an allowance should be made for cellular interconversion and retention of PUFA when calculating the required dietary intake of vitamin E in relation to dietary PUFA consumption. Significant amounts of PUFA are found in tissues, predominantly in the phospholipids of biological membranes, which are susceptible to peroxidation. A calculation of the vitamin E requirement based on dietary PUFA intake does not take into account these PUFA. It is generally accepted that the fatty acid composition of tissue lipids can be altered, within certain limits, by changing the dietary fatty acid composition."

"Horwitt’s analyses of the Elgin project demonstrate that it is very difficult to give exact information on vitamin E requirements in relation to PUFA intake, in particular when the erythrocyte hemolysis test is used. Horwitt [1] recognized that the hemolysis test is nothing more than an indication of the rate at which erythrocyte fatty acids can be oxidized. Furthermore, there is no evidence indicating that this in vitro assay closely reflects the stability of the erythrocyte in vivo [23, 26]."

"In conclusion, although the erythrocyte hemolysis test may be a valid indicator of vitamin E status, it has insufficienty been validated to allow assessment of the vitamin E requirement in relation to PUFA content and composition in diet and membranes."

"According to Harris and Embree [3], the results of Horwitt’s experiments showed that the minimum ratio of α-tocopherol/PUFA at which no deficiency symptoms developed, was between 0.5 and 0.8 mg/g for the experimental diets used. Analysis of the results of food consumption surveys in the United States revealed a ratio of 0.6 mg α-tocopherol per g PUFA, predominantly linoleic acid. They proposed to use the value of 0.6 as a reference ratio for an adequate supply of vitamin E, which seems to be well in agreement with ratios found in various animal experiments. However, it is difficult to compare the results of these studies because of species variation and differences in experimental techniques, including the deficiency symptoms that are under examination, time of depletion and interaction with other nutrients. Moreover, this value is mainly based on linoleic acid as the major PUFA and may not be adequate when the intake of longer-chain, more-unsaturated fatty acids is increased."

"In animals it was demonstrated that the vitamin E requirement increased only as long as an increase in the amount of dietary PUFA resulted in an increase in tissue [20, 27]. Consequently, the vitamin E/PUFA ratio for quantities of PUFA higher than those required to saturate tissue PUFA approaches zero. In addition, vitamin E requirement is not only increased during a high PUFA diet, but also for a certain period after returning to a normal mixed diet because tissue PUFA content is still high. Moreover, linoleic acid is not the only dietary unsaturated fatty acid to be considered in evaluating the vitamin E requirement [27]. According to Witting [27], the critical vitamin E/PUFA ratio is therefore not applicable to all dietary regimens."

"[..]the German Society of Nutrition proposed in 1991 a minimum daily intake of 5 mg α-tocopherol to prevent lipid peroxidation in tissue lipids at moderate PUFA intakes (< 7 g linoleic acid per day) [31]."

"As is clear from the studies and recommendations described above, there is no agreement upon the exact amount of vitamin E required when consuming various unsaturated fatty acids. Critical points are that these recommendations are based on animal experiments and food intake data that are not adequately validated. Moreover, the methods used in the studies described have several limitations, which make it difficult to quantify the relation between vitamin E and PUFA."

"Results of an observational study showed that extreme fish consumption does not affect plasma antioxidant levels. Although subjects usually consuming a high-fish diet (103 g/day) had higher EPA and DHA intakes and higher levels of plasma n-3 fatty acids than subjects on an habitual low-fish diet (5 g/day), there were no differences in vitamin E intake and concentrations of α-tocopherol in plasma between the two groups [35]. When the formula of Muggli is applied to the intake data of unsaturated fatty acids in both groups, the α-tocopherol requirement will be 8.97 and 8.28 mg/day for the high-fish and low-fish group, respectively, values that are only slightly lower than the actual vitamin E intakes (9.0 and 10.5 mg/day). However, since in this study markers of lipid peroxidation were not measured, any possible adverse effects of the more oxidation- susceptible n-3 fatty acids in fish cannot be ruled out. Therefore, it is not clear whether the vitamin E intake of 10.5 mg/day in the high-fish group is sufficient to prevent lipid peroxidation."

"[..]it is possible that nutritional co-factors play a role in the process of lipid peroxidation, for instance vitamin C. Vitamin C is the major line of antioxidative defense against radicals in the aqueous phase and lipid peroxidation in plasma, but it is also crucial for the recycling of vitamin E [42]. According to Gey [42], there is evidence that the vitamins C and E interact also in vivo in man, and that the functional coupling of these vitamins is a crucial part of the overall antioxidant potential. However, in the studies described above, the influence of vitamin C on lipid peroxidation and on the recycling process of vitamin E has not been taken into account.

Therefore, when investigating the amount of vitamin E that is needed to prevent lipid peroxidation when the consumption of fish fatty acids, e.g. EPA and DHA is increased, the influence of co-nutrients as vitamin C should also be taken into account."​

(k) Status of human requirements for vitamin E (Horwie)

"In organizing studies on man, the possibilities that irreversible damage may be produced makes it unthinkable to use experimental diets for human subjects which provide minimal levels of a-tocopherol for prolonged periods of time. In the Elgin project on vitamin E requirements (2-4), we were cautious not to feed a completely deficient diet despite the reasonable certainty that it would take at least 4 years to deplete the reserves in the average previously well-fed adult. It is extremely doubtful that it will be possible to repeat such a long-term nutritional deficiency study in the foreseeable future."

"In the study of vitamin E requirements, the problem is particularly difficult because of the indeterminate floating variables, i.e., the amount of peroxidizable unsaturated compounds in the tissues, the oxidizable components in the diet and the time required to use up the reserves of the tocopherols which, in turn, depends on the level of peroxidizable unsaturates in the tissues. Thus, one can visualize an extreme situation where 5 mg of a-tocopherol a day could supply the minimum requirement for a period of years in a previously well-fed adult with low tissue levels of unsaturates, whereas at other levels of tissue and diet composition 15 mg would not be enough."

"[..]few, if any, individuals would show any recognizable signs of scurvy or other related pathology if their diet was limited to 10 mg of ascorbic acid (5) a day. But certainly, even in this far less complicated situation one could hardly recommend so little vitamin C as a requirement."

"Most vitamins other than vitamin E have been shown to be intimately related to enzymatic or hormonal effects or to be in some manner a significant part of a chemical equation. The tocopherols may also some day be shown to have a similar specific function but for the time we are still looking. Without belittling the possibility that tocopherol has other functions, when one considers all the physiological systems that have peroxidizable lipids in the presence of traces of oxygen and metals which could catalyze peroxidations, if tocopherol had not evolved, nature would have had to invent a different antioxidant to do the job. One of the characteristics of free-radical traps that can delay the initiation and possibly the rate of reactions that may be undesirable, is that the more antioxidant that may be present in a given mixture, the greater the potential of it trapping an errant free radical. The same analysis cannot be made for vitamins with functions that can be described in stoichiometric equations where more than a prescribed amount has no additional effect. Therefore, some of us are led to wonder, in the absence of any hard proof, whether more than the established minimum requirement of this antioxidant can have a biological consequence. About all we as scientists can do while waiting for a final answer is to encourage more work and keep an open mind."

"Repetitive daily consumptions of tocopherols other than a-tocopherol can apparently be protective to man and animals. This appears to be especially true if some reasonable portion of the total tocopherols is a-tocopherol. Tests of potency which depend on rate of disappearance of different tocopherols from the tissues and body fluids have shown that a-tocopherol will persist in the erythrocytes longer than y-tocopherol (11) but as Bieni (12) has noted y-tocopherol is stored in the tissues for a longer period than previously considered."

"Actually, as will be shown, those who eat more than the usual amount of polyunsaturated fat, consume 30 IU or more of the tocopherols and those who have existed on diets low in polyunsaturated fats have tissue lipids that have lower potentials for peroxidation and they can presumably get by with less tocopherol at the tissue sites in question."

"The level of linoleic acid obtained in the depot fats, tends to approach the percentage in the diet if the diet is fed for a sufficient period of time."

"Since it is possible that 8 mg of a-tocopherol/day could be adequate when the tissues are low in polyunsaturates and more than 30 mg/day are needed when the tissues are very high in linoleates--as after long time consumption of safflower oil--there seems to be no single satisfactory figure upon which to compromise."

"To allow for the synthesis of polyunsaturated fatty acids that do not come from dietary sources it is suggested that a minimum adult requirement of 10 mg of d-a-tocopherol be allowed even if the calculation of the requirement from dietary constituents should result in a lower figure."

"Both the percentage of PUFA in the dietary fat and the amount of such fat affect the degree to which tissue lipids accumulate PUFA in the tissues. The depot fat lipids tend to achieve the same percentage of linoleic acid as in the fat consumed. Thus when 60 mg corn oil was added to the basal diet the final mixture contained about 35% linoleate and when this diet was fed for almost 5 years the depot fats reached a level of about 33% in the adult male subjects. Similarly, when 60 mg safflower oil was added to the basal diet to achieve about 55% linoleate in the dietary fats the depot fats reached approximately 50% (3, 14). Data on how much the total amount of PUFA in the diet affects the rate of achieving final equilibrium are not available but it would appear that this should be as important as the percentage of PUFA in the lipids fed. Stated differently, it may take longer to reach tissue equilibrium with lower rather than higher levels of fats in the diet, but the controlling factor in the final composition of the tissue lipids is as much related to the ratios of the individual fatty acids ingested as to the total amount of the lipid ingested."

"Any calculation of the vitamin E requirement based only on the levels of PUFA in the diet would not be complete since the tissues would have considerable amounts of polyunsaturated lipids even when the diet was practically deficient in PUFA."

"Accordingly, some allowance must be made for cellular synthesis, and retention of PUFA in any calculation of the tocopherol requirements. The least unsaturated diet used in the Elgin Project contained 60 mg of beef fat added to the basal diet. This diet provided only 2.4 g of PUFA and approximately 3 mg of d-a-tocopherol. After more than 3 years on this diet (14), one subject, not included in Fig. 2, had less than 3% linoleate in his adipose tissue lipids. All of the subjects on this diet had marked [!] increases in their erythrocyte peroxide hemolysis test results. Accordingly, we have chosen 4 mg ofd-a-tocopherol as the amount that should be allowed for tissue synthesis of peroxidizable compounds in the male adult even when the diet is practically deficient in PUFA."

"[Subjects were fed a basal diet with 60 g of beef tallow as the fat, remaining on this diet for 5 years.] These subjects had been fed the basal diet plus 60 g commercial corn oil for 6 months previously. The beef fat diet (the basal constituents of the diet remained the same) was shown by analysis of 14 composite samples to range from 2.6 to 3.9% linoleic acid with a mean of 3.0% in 80 g of total fat as consumed. The tocopherol content of this diet was no higher than in the deficient diets previously used, analyzing out to approximately 3 mg a-tocopherol/total daily diet. Despite the low intake of vitamin E, there was a rise in serum tocopherol during the subsequent 20 months while the depot fat linoleates were rapidly decreasing. Part of this increase in plasma tocopherol may have been due to the increase in serum lipoproteins as evidenced by an increase in plasma cholesterol during the first month on the beef fat. From the data, one has the choice of concluding that the depot fats were releasing stored tocopherols, which apparently did not happen during the months before beef fat was started, or that very little tocopherol is needed when the diet contains barely enough linoleic acid to supply the essential fatty acid requirement. In any case, after 20 months on the beef tallow diet a marked decrease in plasma tocopherol commenced and this was confirmed by positive peroxide hemolysis tests when the plasma tocopherols dropped below 0.5 mg/100 ml. The hemolyses test results ranged between 50 and 90% after the fourth year on the beef fat diet. Nevertheless, these analyses showed a much milder deficiency in these subjects than when unsaturated lipids had been fed as part of same basal diet and it is likely that an additional 3 mg of a-tocopherol/day would have been sufficient to repair the blood tocopherol levels in this unusual diet. Recapitulating, this beef fat diet provided 3 mg a-tocopherol in a diet which had about 3.0% linoleic acid in the total lipids and the depot fat linoleates dropped to less than 8%."

"[..]higher levels of antioxidant may be required under [] unusual conditions. One wonders how much higher the plasma tocopherol should be in order to achieve the greater protection that may be needed when the tissues have such unnatural levels of PUFA."

"The data in Table 4 make it difficult to change our original decision that the adult male vitamin E requirement ranges from a minimum of 10 to a probable maximum of 30 mg of d-a-tocopherol/day despite the fact that many individuals in apparent good health consume considerably less."​

(l) Interpretations of requirements for thiamin, riboflavin, niacin-tryptophan, and vitamin E plus comments on balance studies and vitamin B-6 (Horwie)

"The range ofthe minimum requirement for vitamin E is probably greater than for any other vitamin. Only a small amount seems to be needed in the growing rat ifthe diet contains only enough linoleic acid to assure the absence of fatty acid deficiency, whereas, the amount of vitamin E required becomes quite large if fish oils are included in the diet."​

"Vitamin E has eight isoforms; it can be categorised into tocopherol isoforms, which have a saturated side chain on the chromanol ring, and into tocotrienol isoforms, which have an unsaturated side chain. Each of these types is further categorised as a-, b-, y- or z-forms, which are defined by the number and the location of the methyl groups on the chromanol ring. The 6-hydroxy group of the chromanol ring is the active site for scavenging radicals, whereas the side chain does not affect the reactivity towards free radicals. Thus, all the isoforms of vitamin E have some antioxidant activity."

"[..]the vitamin E forms are discriminated by the liver and only a-tocopherol is preferentially accumulated in the cellular membranes of tissues, whereas the other isoforms are rapidly metabolised and excreted in a similar manner as other xenobiotics (6,9). y-Tocopherol is the other vitamin E form that is present in significant amounts in the human diet as it is contained in a number of widely consumed vegetable oils( 9 ). y-Tocopherol is slightly less efficient than a-tocopherol as a scavenger of oxygen radicals, but it is an efficient scavenger of reactive nitrogen species due to the unsubstituted 5-position on the chromanol ring (9-11). However, y-tocopherol is efficiently metabolised by cytochrome P450 enzymes. This may be the reason why even after intake of high doses of y-tocopherol, its plasma concentration rarely exceeds 10% of that of a-tocopherol, and much less is found in tissues (9,12-18)."

"Atkinson et al. (40) undertook a series of biophysical experiments to describe the position of 2H-labelled a-tocopherol in the cell membrane. They concluded that the a-tocopherol molecule stands upright in the membrane bilayer (Fig. 1). The non-a-tocopherol isoforms can also be incorporated into cellular membranes. Studies in lipid model membranes indicate that the localisation of the various vitamin E forms in the membranes can slightly differ and they might alter the membrane behaviour differently due to their structural differences (20,41). However, as mentioned previously, all non-a-tocopherol isoforms are rapidly metabolised and excreted and only a-tocopherol is present in significant amounts in cell membranes."

Fig. 1
View attachment 10172​

<tut>
"[..]the a-tocopherol antioxidant activity occurs at the membrane surface (42). This location of vitamin E in the membrane would also allow vitamin C, which is placed at the hydrophilic/hydrophobic interphase, to interact with the a-tocopheroxyl radical and to bring it to the energetic ground state. This is the mechanism by which vitamin E is regenerated and is ready to interact with the next peroxyl radical (7). Thus, both lipophilicity and membrane localisation of vitamin E explain its antioxidant activity."

"[An] hospital diet providing 8–12 mg/d of a-tocopherol and 4–7 g/d of PUFA was considered as being on the borderline of adequacy over the 13 years of observation based on the plasma a-tocopherol levels and the data from the erythrocyte haemolysis test (83)."

"[..]the a-tocopherol requirement in the absence of dietary PUFA was assessed by feeding subjects 60 g/d of beef tallow (a saturated fat) for 5 years. The diet provided about 2.4 g of PUFA and 3 mg of a-tocopherol daily. Plasma a-tocopherol levels decreased, whereas the sensitivity of erythrocytes to haemolysis increased. These data indicated that a minimal intake of 4–5 mg/d of a-tocopherol was needed in the basal state, even in the absence of dietary PUFA."

"Collectively, the data from the Elgin project suggest that individuals ingesting large amounts of linoleic acid (>30 g/d) require more than 30 mg/d of a-tocopherol, whereas 10 mg/d of a-tocopherol may be bordering on inadequacy in individuals ingesting about 4–7 g/d of linoleic acid (83). It was proposed that the a-tocopherol requirements in humans range from 10 to 30 mg/d depending on the amount of PUFA in the diet and the tissues( 83 )."

"The estimated optimal vitamin E:PUFA ratio seems to be relatively consistent across studies. Taking these studies together suggests an estimated additional vitamin E requirement ranging from 0·4 to 0·6 mg RRR-a-tocopherol/g of PUFA in the diet for a diet with a typical content of PUFA, mainly as linoleic acid. A ratio of 0·5 mg RRR-a-tocopherol/g of PUFA in the middle of this range may reasonably be used to calculate the vitamin E requirement. Thus, considering a basal requirement of at least 4 mg RRR-a-tocopherol as suggested by the human data from the Elgin project, the following formula can be used to calculate the vitamin E requirement: vitamin E requirement=4+(0·5× amount of PUFA in the diet in grams). However, the vitamin E requirement also depends on the degree of unsaturation of PUFA in the diet (80), and most of the studies described so far have considered linoleic acid as the main dietary PUFA. Therefore, Muggli (99) proposed to estimate the dietary vitamin E requirement by taking the relative vitamin E requirement for individual PUFA into account."

..and this is what was discussed above.​

<don't>
Finally, Howie in his most recent publication wrote this:

(n) Critique of the requirement for vitamin E

"[..]the 1989 RDA committee concluded that the requirement for men should be 10 mg tocopherol equivalents vitamin E/d, although it was known that millions of persons have lived long lives while consuming much less. An increasing in this requirement to 15 mg/d benefits only the commercial interests involved in the sale of vitamin E. To help consumers, the distinction between nutritional requirements and the possible pharmacologic benefits of an antioxidant should be emphasized. Because of common knowledge that I have been involved in the field of vitamin E research for > 65 y, “I am frequently asked by both professionals and laymen how much I take.” The answer is 200 mg RRR-dio-tocopherol/d, but often with the proviso that I am not completely certain of the benefit of such a pharmacologic dose of an antioxidant."

"It was previously shown that the antiadhesive effects of dio-tocopherol on platelets combined with the antiaggregatory effects of aspirin reduce platelet adhesion by a highly significant 40% (22, 23). This effect on platelets, which is dependent on many variables, could be considered either beneficial or undesirable in the prevention of stroke. However, inhibition of platelet function could lead to an increased tendency to bleed (24). Accordingly, it is my judgment that a tolerable upper intake level of 1000 mg RRR-dio-tocopherol/d for adults is too high. The daily intake of less than one-half that amount produces high concentrations of vitamin E in the tissues."

"Many people who supplement their diet believe that if a little is good, more is better. An official statement that 1000 mg RRR- dio-tocopherol/d is safe may encourage some consumers to take the maximum amount of vitamin E recommended regardless of their consumption of other antithrombotic compounds. The precautionary principle should be applied in this situation."​

That pink, or whatever that color is, has just the opposite affect of highlighting for me...quite difficult to read...anyone else?

 

[Amazoniac]

Graying of the Immune System - Can Nutrient Supplements Improve Immunity in the Elderly?

"Vitamin E is generally considered to be of low toxicity in adults.[13] At [very] high doses, vitamin E antagonizes the functions of other fat-soluble vitamins, resulting in decreased bone mineralization, reduced hepatic storage of vitamin A, and disorders of coagulation.[8] In addition, nausea, gastrointestinal upset, headache, fatigue, muscle weakness, and double vision have been noted. In a few studies,[14,15] immunologic responses were found to be impaired in subjects given large amounts of vitamin E. For this reason, close monitoring and caution are advised when vitamin E is prescribed, especially for those with liver disease or renal dysfunction or those using anticoagulants including aspirin."​

[8] The Vitamins: Fundamental Aspects in Nutrition and Health - Gerald F. Combs (978-0-12-183493-7)

"Potentially deleterious metabolic effects of high-level vitamin E status include inhibitions of retinyl ester hydrolase and vitamin K-dependent carboxylations. The former effect has been demonstrated in animals, where it results in impaired ability to mobilize vitamin A from hepatic stores. Evidence for the latter effect includes the findings that patients of normal coagulation status given high doses of vitamin E (at least 1000 IU/day) showed decreased γ-carboxylation and functionality of prothrombin.[107]"​

 

[Amazoniac]

4-5 mg/d of a-tocopherol was needed in the basal state, even in the absence of dietary PUFA

10 mg/d of a-tocopherol may be bordering on inadequacy in individuals ingesting about 4-7 g/d of linoleic acid

(g) On the problematic nature of vitamin E requirements: net vitamin E

"Considering the additional vitamin E requirement generated by PUFA intake, it follows that only the net vitamin E content (total vitamin E content minus vitamin E needed for PUFA protection) is relevant for evaluation of vitamin E supply in food containing considerable amounts of PUFA. Food rich in PUFA with low vitamin E content causes a vitamin E deficit that has to be compensated by other food constituents. This is shown in a few examples for fats and oils in Table 2."

Spoiler: Table 2

Table 1 was discussed on the previous page of this thread.

.
"Three groups can be distinguished: Oils with high net vitamin E content like cotton seed oil, sunflower oil, and wheat germ oil; fats and oils with a negative vitamin E balance like safflower oil or lard, and fats which are roughly balanced like butter or corn oil. The latter do not generate additional vitamin E requirements, but cannot be regarded as sources of vitamin E. High vitamin E content per se does not justify being labeled as a vitamin E source, unless the PUFA content is taken into account and the net vitamin E is calculated. Olive oil, for example, is rated fairly high as such; in spite of a moderate gross vitamin E content (about 12 mg/100g) there remains a net vitamin E content of 5 mg/100 g due to the predominant monoenic acid content with low additional vitamin E requirement. Fish oils, on the other hand, with high PUFA concentrations and low gross vitamin E content cause a vitamin E deficit (Table 3) which is more pronounced with oils than with native fish."

Spoiler: Table 3

.
"Nuts are popularly considered as rich vitamin E suppliers; however, taking the net vitamin E content into account, this cannot be said in general, as shown by the examples in Table 4."

Spoiler: Table 4

.

Even though coconut fat contains very little unsaturated fats, it doesn't provide vitamin E. The consequence can be seen here:

Red Palm Oil Anyone

Some other foods have to make up for it, or it has to be supplemented in low amounts.

Another aspect to consider in coconut fat is that the amount which is used for energy is high (hence the difficulty in gaining fat on it), but this also means that the proportion left for incorporation in tissues (or cleared) after you eliminate those that are used up won't be 2% or so of PUFA anymore. If the fat in tissues reflect the composition of diet, this might make some difference over time. I don't think it's something to worry about, but it's worth making sure that the vitamin E supply is adequate, perhaps including fats that can provide longer saturated chains and maybe even the n−3 fats that Travi* writes about since the PUFA in coconut are of the n−6 kind.

*The minus signs were in his honor.

 

[Amazoniac]

I was reading the material from the Elgin Project again (on antidote E requirements in relation to PUFA), and I think it might interest some of you. A few links, images and passages are repeated for convenience.

- Vitamin E: too much or not enough?

"The dietary reference intake for vitamin E is based on the best data currently available. Despite Horwitt's protestations, his studies at the Elgin Hospital defining the reversal of markers of oxidative stress by vitamin E are currently the best available data. Until α-tocopherol's physiologic role is described, optimal concentrations for function are defined and related to intakes, it is likely that Horwitt's data will remain the best available."​

The basal diet throughout it was as follows:

- Effects of Limited Tocopherol Intake in Man with Relationships to Erythrocyte Hemolysis and Lipid Oxidations

"The constituents of the three basal diets used are shown in Table I. Three different sets of recipes are available for each diet, so that, in effect, nine different daily menus are rotated in an effort to provide some variety to the regimen."

Spoiler: Table 1: Composition of Basal Diet

"Consumption at 100 per cent levels provides approximately 2200 calories, 47 g protein, and 60 g fat. Vitamin supplements are provided as follows: Poison/"vitamin" A, 2500 IU; venom D, 500 IU; thiamine mononitrate, 0.8 mg; riboflavin, 1.11 mg; niacinamide, 12.8 mg; pyridoxine hydrochloride, 2.2 mg; d-panthenol, 3.8 mg; vitamin B12, 11.0 mcg; folic acid, 0.51 mg; and biotin, 0.058 mg. In addition, 30 mg of iron in the form of ferrous sulfate are given daily.[1]"

"The lard used in the diet is stripped of tocopherol by vacuum distillation[.]" "About 30 g stripped lard per day, or about half of the fat in the diet, is worked into puddings, apple streusel, cabbage slaw, soup, cookies, and potatoes."​

- Quantitative Consideration of the Effect of Polyunsaturated Fatty Acid Content of the Diet Upon the Requirements for Vitamin E

Spoiler: Table III: PUFA Content of diets

- Vitamin E and Lipid Metabolism in Man

"[..]thirty-eight male subjects were divided into three groups: Group B (nineteen subjects) received a daily basal diet which contained approximately 2 mg. of tocopherol; group BE (nine subjects) received the same basal diet plus a supplement of 15 mg. of d-Diokine-tocopherol acetate; and group HD (ten subjects) received the hospital diet, ad libitum."

"This controlled dietary regimen was started in October 1953 and [in] April 1956, after two and a half years the lard in the basal diet was replaced by 30 gm. of stripped corn oil to increase the ingestion of linoleic acid. Nine months later (January 1957) the corn oil level of the basal diet was increased to 60 gm. per day."

"The lard used contained about 11 per cent linoleic acid, and the corn oil contained about 55 per cent linoleic acid."

Spoiler: Antidote E in blood and red blood cell instability over the times

Not sure if (couldn't access some of them) the basal diet in all phases had those 10-20 g of lard (with its intact antidote E), so this has to be considered as well. In terms of PUFAs, it's what foods contain + about 2 g from the added lard + specified fat used. It's not dismissive because they're trying to figure out if there's also a basal requirement regardless of diet composition or when the diet is quite low in them. They claim that there is, and to get it without supplementation you'd need items in the diet that have extra antidote E in relation to PUFA (as exemplified on the previous post).

After those initial phases there were two other experiments using sunnyflower and beef fat. What matters is the one using beef fat because it haddeded the least amount of PUFA, so they relied on it to determine the basal requirement. This time they didn't remove the antidote E from the fats.

- Status of human requirements for vitamin E

"The fatty acid composition of animal fats is, of course, dependent on what the animal was fed. Thus, lard linoleic acid may vary from 5 to 25%. Furthermore, the attention being paid to unsaturated lipids should not imply that these are the only compounds protected by the tocopherols. Other compounds susceptible to deterioration by chain reactions that are inhibited by the tocopherols could just as well be included in this discussion."

"[..]after about 2 years on a regimen which provided up to 60 g of stripped corn oil, the depot fats of the subjects in the supplemented group increased to about 30% linoleic acid. There was a gradual decrease in serum tocopherols soon after the stripped corn oil replaced the stripped lard, so one must assume that 25 IU of vitamin E was not adequate for subjects with 30% linoleic acid in their depot fats (3, 4). Doubling the supplement to 30 mg of d-a-tocopherol acetate reversed the downward trend of plasma tocopherol."

"In later studies (14) after feeding 60 g of safflower oil/day in a diet which had 80 g of total fat, six male adults, who had previously been fed the supplemented diet, attained over 50% linoleic acid in their depot fats but the very high levels of a-tocopherol in safflower oil which provided over 40 lU/day may have protected these subjects despite the high concentration of polyunsaturated fatty acids in the tissues (Fig. 1) [No (Wagner, 2018).]."

"In simultaneous experiments on four subjects in which beef fat instead of safflower oil was substituted for corn oil (Fig. 2) the linoleic acid levels of the tissues dropped faster than the serum tocopherol levels, but in this case, the serum tocopherol levels were already relatively low at the start of the experiment. The basal diet in both aforementioned experiments was the same as that used in the tocopherol depletion study but the oils used were not stripped of their tocopherol content. To put the data obtained from subjects on the experimental diet in proper perspective, it should be noted that in over 300 analyses of 11 patients who ate the hospital diet ad libitum, the linoleic acid content of the depot fats ranged from 5 to 11 %. Their diet varied from approximately 5 to 10% linoleic acid in about 70 g fat. The level of linoleic acid obtained in the depot fats, tends to approach the percentage in the diet if the diet is fed for a sufficient period of time. It is too bad that the depot fats which are so easily obtained for analysis do not tell us much about the levels of arachidonic and more unsaturated fatty acids in the other tissues."

"[..]even when the diet is very low in essential fatty acids, significant amounts of polyunsaturated fatty acids are found in the tissues and calculations based on the low levels of polyunsaturates in the diet would not reflect what is present in the tissues. In chicks, even on a diet that contained only 1.2% linoleate as the only lipid, the lipids of the heart contained 20% linoleic acid and 9% arachidonic acid (19). And, it is well known that on an essentially fat-free diet the body can synthesize eicosotrienoic acid from oleic acid which, of course, can be synthesized from carbohydrate and protein sources via acetyl CoA and malonyl CoA. That related effects can be obtained in primates was shown in the report by Fitch et al. (20) in which monkeys on a diet very low in fat developed vitamin E deficiency along with signs of fatty acid deficiency. The eicosotrienoic acid content of the lipids of the erythrocytes of these monkeys was as high as 7%, confirming other studies by Holman (21), whereas this fatty acid was essentially absent in monkeys fed some linoleic acid."

"To allow for the synthesis of polyunsaturated fatty acids that do not come from dietary sources it is suggested that a minimum adult requirement of 10 mg of d-a-tocopherol be allowed even if the calculation of the requirement from dietary constituents should result in a lower figure. The arachidonic acid content of animal muscle and organ fats may be higher than most nutritionists realize (22-24). At the risk of encouraging more theories regarding the benefits of vitamin E, it might be noted that heart lipids can be quite unsaturated; one report showed concentrations of 25% linoleic acid and 11% arachidonic acid in beef heart lipids (22)."

"Both the percentage of PUFA in the dietary fat and the amount of such fat affect the degree to which tissue lipids accumulate PUFA in the tissues. The depot fat lipids tend to achieve the same percentage of linoleic acid as in the fat consumed. Thus when 60 g corn oil was added to the basal diet the final mixture contained about 35% linoleate and when this diet was fed for almost 5 years the depot fats reached a level of about 33% in the adult male subjects. Similarly, when 60 g safflower oil was added to the basal diet to achieve about 55% linoleate in the dietary fats the depot fats reached approximately 50% (3, 14). Data on how much the total amount of PUFA in the diet affects the rate of achieving final equilibrium are not available but it would appear that this should be as important as the percentage of PUFA in the lipids fed. Stated differently, it may take longer to reach tissue equilibrium with lower rather than higher levels of fats in the diet, but the controlling factor in the final composition of the tissue lipids is as much related to the ratios of the individual fatty acids ingested as to the total amount of the lipid ingested."

"Any calculation of the vitamin E requirement based only on the levels of PUFA in the diet would not be complete since the tissues would have considerable amounts of polyunsaturated lipids even when the diet was practically deficient in PUFA."

Spoiler: Table 4: Vitamin E and polyunsaturated fatty acids in diet and resulting linoleates in aspirated tissue fat with calculations of requirement from equation

"The least unsaturated diet used in the Elgin Project contained 60 g of beef fat added to the basal diet. This diet provided only 2.4 g of PUFA and approximately 3 mg of d-a-tocopherol. After more than 3 years on this diet (14), one subject, not included in Fig. 2, had less than 3% linoleate in his adipose tissue lipids. All of the subjects on this diet had marked increases in their erythrocyte peroxide hemolysis test results. Accordingly, we have chosen 4 mg of d-a-tocopherol as the amount that should be allowed for tissue synthesis of peroxidizable compounds in the male adult even when the diet is practically deficient in PUFA."​

I don't know if beef fat also replaced the flavoring lard that was part of all diets. Apparently it did because their calculation was based on 80 g of fat and it seems that they have accounted for everything, the mean linoleic acid was 3% of that, or 2.4 g (value in Table 4). However! Before switching to this diet, they was on the lard-based diet + 60 g of corn oil for 6 months, which is why they started from a high level of tissue linoleic acid.

The 'linoleate in depot fat' (3-8% linoleic acid) was aspirated from the buttocks, and it's the final measure represented in Figure 2 as average.

The rice and beef diet that has been popular must contain 2.5 g or so of PUFA, which is similar to what people were consuming and their red blood cells still suffered when challenged. It's possible that supplemental iron affected it.

They have suggested that as little as 3 mg of extra antidote E on top of what was already being ingested must have been enough to prevent issues.

It's surprising that the blood antidote E levels started to decrease as the fat tissue was renewed (starting to reflect the fatty acid profile of beef fat) considering that the amount of tocopherol ingested remained the same, maybe they didn't need as much as before. Perhaps if they remained for longer, the PUFA content would drop further along with the requirements for antidote E.

From the third link:

Spoiler