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Vitamin E Value from Tocopherols and Tocotrienols
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See this article for the Vitamin A value from carotenoids.
Introduction
This technical report will clarify the definition of vitamin E, the various forms of vitamin E, their absorption and bioavailability, and their contribution towards a total vitamin E value.
Vitamin E is a generic descriptor for all tocopherol and tocotrienol derivatives (i.e., tocochromanols) that exhibit the biological activity of α-tocopherol. [1] [2] Since the 1930s, there have been eight tocochromanols that have been found to possess vitamin E activity, often referred to as vitamers of the vitamin E family. (Figure 1) However, at least 6 additional tocochromanols have been discovered in more recent years, which may also be included in the vitamin E family. [3] [4] [5] [6]
Terminology for Different Isomers of Vitamin E
Historically, naturally occurring a-tocopherol was referred to as d-α-tocopherol, while the original international standard for vitamin E was synthetic α-tocopheryl acetate, which was referred to as dl-α-tocopherol. [7] The dl- (d- and l-) represent the rotational direction of polarized light emitted from a light-irradiated sample, indicating two different molecular conformations (stereoisomers) for the synthetic dl-α-tocopherol. [1]
Up until the 1960s, synthetic dl-α-tocopherol was synthesized from natural phytol, which produced a mixture of two stereoisomers of α-tocopherol. However, since the mid-1960s, and up to the current day, synthetic α-tocopherol has been produced from synthetic isophytol which produces a mixture of eight different stereoisomers (RRR-, RSR-, RRS-, RSS-, SRR-, SSR-, SRS-, and SSS-α-tocopherol). [8] In 1973, in recognition of the stereoisomeric differences between these synthetic preparations, the IUPAC-IUB Commission on Biochemical Nomenclature abandoned the d- and l- prefixes, and replaced it with the RS naming system. The naturally occurring isomer known as d-α-tocopherol, was assigned the name RRR-α-tocopherol. [1] Synthetic vitamin E from natural phytol was renamed as 2-ambo-α-tocopherol, and synthetic α-tocopherol from synthetic isophytol was renamed as all-rac-α-tocopherol. [1] By 1980, this updated nomenclature was adopted by the International Union of Nutritional Sciences and the American Institute of Nutrition. [9] Any modern usage of the d- or dl- prefix for α-tocopherol is outdated, and shall be interpreted as RRR- and all-rac-α-tocopherol, respectively. [2]
History of Vitamin E Value
In the early 20th century, there was a need to establish requirements for dietary intake of vitamin E, and to highlight the different biological potencies of the different vitamers and isomers. [7] In 1941, the Health Organization of the League of Nations, now recognized as the World Health Organization (WHO), established the following IU for vitamin E:
The international unit (IU) is a measurement unit used for substances that have similar biological properties, but different biological potencies. Thus, an “IU of vitamin” E sums up the total quantity of “vitamin E activity” from the different forms of vitamin E. The IU for vitamin E is defined as the activity of 1 mg synthetic α-tocopheryl acetate in the rat fertility assay; i.e., an IU being the quantity “... which, when administered orally, prevents resorption-gestation in rats deprived of vitamin E.” [1] [7] Thus, the milligram amount required to match the biological activity of 1 mg synthetic α-tocopheryl acetate is equal to 1 IU of vitamin E. [9] By the 1960s, several researchers had published the biological activity of various tocopherols and tocotrienols (and isomers) as determined by the rat fertility assay. [10] [11] (Table 1)
In 1968, the Food and Nutrition Board proposed 30 IU of vitamin E as the recommended daily allowance (RDA) for humans. [12] Although the Food and Nutrition board acknowledged the vitamin E contribution from vitamers other than α-tocopherol, at that time, only α-tocopherol was included in the dietary calculations due to the lack of analytical data on the food supply. [12] [13] It was not until 1979, that the USDA published the first compilation of tocochromanol content in foods, which included quantification of α-, β, γ, and δ-tocopherols and tocotrienols. [14] However, the conversion of mg quantities to IU quantities often led to confusion. [9] In 1980, to simplify vitamin E calculations, the US Food and Nutrition Board abandoned the IU for expressing vitamin E value and recommended vitamin E be expressed in milligrams of α-tocopherol equivalents (α-TE). [9] [15] The following equivalencies were recommended, which were based on the tocochromanols with the greatest biological activity in the rat fertility assay:
Despite this guidance by the Food and Nutrition Board, ‘milligrams of α-tocopherol equivalents’ never appeared on food or supplement labels because the IU value for vitamin E was codified in the Code of Federal Regulations (CFR) for food labeling. [16] From 1973 to July 26th, 2016, the % Daily Values (%DV) seen on the Nutrition and Supplement Facts panel had to be based on the Reference Daily Intake (RDI) of 30 IU vitamin E, which was derived from the 1968 Recommended Dietary Allowances (RDA). [12] [16]
Current RDI of Vitamin E
In 2000, the Food and Nutrition Board decided to further simplify the calculation of vitamin E, and replaced the calculation of α-tocopherol equivalents, with milligrams of α-tocopherol. [19] With this new definition, the only form of vitamin E that counts towards the “vitamin E requirement” is the natural RRR-α-tocopherol, the synthetic 2R-stereoisomeric forms of α-tocopherol (RSR-, RRS-, and RSS-), and their esters. (Table 1) [19] With the IU format, all tocochromanols counted towards the vitamin E value based on their activity in the rat fertility assay. However, the new definition excludes all novel forms of vitamin E because “they are not converted to α-tocopherol in humans and are recognized poorly by the α-tocopherol transfer protein”. [19] This arbitrary designation disregards the unique, and perhaps necessary, biological functions of other tocochromanols in the vitamin E family. [20] [21] [22] [23] [24] [25] [26]
Despite this shortcoming, the FDA adopted milligrams of α-tocopherol for the RDI of vitamin E, which replaced the IU in 21 CFR § 101.9(c)(8)(iv). [27] The rule became effective on July 26th, 2016 with a final compliance date of Jan 1st, 2021 for all food and supplement manufacturers to replace the IU value of vitamin E with the mg quantity of α-tocopherol only on the Nutrition and Supplement Facts panels (Table 1). [27] [28] The WHO continues to use ‘α-tocopherol equivalents’ to calculate vitamin E value. [18]
The reference daily intake (RDI) of vitamin E is listed below:
Absorption and Bioavailability
All vitamers, isomers, and esters of vitamin E have a similar digestive absorption. [29] [30] [31] [32] [33] [34] [35] Absorption of dietary vitamin E ranges from about 33-86% and is primarily dependent on sufficient fat intake and bile release during the digestion of vitamin E. [36] [37] [38] Anything that interferes with normal fat digestion or cholesterol absorption will reduce the absorption of vitamin E. [36] [37] [39] Drugs that may hinder vitamin E absorption include; cholestyramine, ezetimibe, colestipol, isoniazid, mineral oil, orlistat (Alli), sucralfate, and olestra. 5 g of fat appears to be the minimum amount of fat for optimal absorption of vitamin E, as this is the minimum amount of fat required to trigger maximal bile release by the gallbladder from a meal. [40] [41] [42]
There does not appear to be competition between the vitamin E vitamers or isomers for absorption. [43] However, excessive intake of a single vitamer of vitamin E may cause a deficiency in other vitamers due to the increased production of metabolic clearance enzymes. [44] [45] CYP4F2 is the primary enzyme involved in breaking down vitamin E into more water-soluble metabolites. [46] This accelerates the excretion of many fat-soluble nutrients with a phytyl side chain, including vitamin E and vitamin K1. [43] [44] [45] For this reason it is advisable to avoid excessive intake of any single form of vitamin E (>150 mg/day), as it may cause a deficiency of other forms that are simultaneously deactivated by CYP4F2. [44] [45] [47] [48] [49] [50] [51]
Once vitamin E reaches the liver after digestion, the long-term retention of vitamin E is highly dependent on binding affinity for the α-tocopherol transfer protein. (Figure 2) [46] [52] The α-tocopherol transfer protein resides primarily in liver cells, where it sequesters and slowly releases vitamin E into the cell membrane, where it can be picked up by HDL and LDL cholesterol particles and distributed to the rest of the body. [53] The α-tocopherol transfer protein binds about 2–10x stronger to the naturally occurring α-tocopherol isomer than other vitamers or isomers. [54] [55] For this reason, α-tocopherol is the only vitamer found in plasma at a significant quantity during the fasted state. [31] [53]
Forms of vitamin E that do not bind well to the α-tocopherol transfer protein are mostly cleared from plasma within 6–10 hours after a meal. [29] [30] [31] The distribution and retention of vitamin E is not strictly dependent upon α-tocopherol transfer protein, since all forms of vitamin E can be carried through the lymphatic system or through the blood by LDL, HDL, and chylomicron particles. [19] [56] Although most forms of vitamin E (e.g., tocotrienols) bind poorly to α-tocopherol transfer protein, they can still accumulate and reach high concentrations in vital organs such as skin, adipose, brain, cardiac muscle, and liver within several months of regular dietary intake. [57] [58] [59]
Dietary Intake and Supplementation
The current RDI of 15 mg/day α-tocopherol is sufficient to prevent signs of overt vitamin E deficiency such as peripheral neuropathy, ataxia, or red blood cell fragility. [19] Over 95% of the US population is considered to have “normal” vitamin E levels, with blood plasma α-tocopherol above 12 µmol/L (516 mcg/dL), since α-tocopherol is found (or fortified) in many common foods. [19] [60] As a general rule, every 1 mg of dietary α-tocopherol produces a 2-3 µmol/L increase in blood plasma. [50] Blood plasma levels begin to plateau at a dosage of about 150 mg/day of α-tocopherol, as this fully saturates α-tocopherol transfer protein, and any additional intake is matched by accelerated metabolic excretion. (via CYP4F2) [51] [61]
The daily intake of more rare forms of vitamin E, such as tocotrienols is generally less than 5 mg/day, as they are not found in most common foods nor are they fortified. [60] [62] [63] [64] Research shows that the ideal intake of tocotrienols for adults is around 100 mg/day for various metabolic and cosmetic benefits. [65]
Vitamin E Toxicity
Vitamin E toxicity from high doses has not been found, as all forms of excess vitamin E are readily metabolized and cleared by the body. [43] [66] However, as mentioned earlier, prolonged intake with high doses can lead to depletion of other vitamers, such as vitamin K, which can interfere with blood clotting. [66] For this reason it is recommended to keep total vitamin E intake below 300 mg/day. [46] In addition, long-term intake of synthetic vitamin E is also associated with negative health outcomes compared to intake of plant-based vitamin E, discussed in this article about synthetic vs. plant-based vitamins.
Palm Fruit™ and its Vitamin E Contribution
Palm Fruit™ Vegetarian Liquid Capsules is a phytonutrient extract from red palm oil (Elaeis guineensis). Each 2 capsule dose provides 160 mg of total tocochromanols, which provides about 110 mg of tocotrienols and 30 mg of α-tocopherol. [3] [5] [67] Remember, due to the new 2016 labeling ruling, only the α-tocopherol counts towards the vitamin E value on the Supplement Facts. (Figure 3)
Palm Fruit™ Vegetarian Liquid Capsules provide a rich source of vitamin E in the form of tocopherols, tocotrienols, and other novel tocochromanols. For individuals with a vitamin E deficiency, Palm Fruit will serve as a safe and reliable source of vitamin E for rapid replenishment. In those with adequate vitamin E (α-tocopherol), Palm Fruit will serve as a rich source of tocotrienols and carotenoids for metabolic, genomic, and photoprotective benefits. [68] [69] [70] [71] [72]
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