Vitamin E was discovered as a “fertility factor” in 1922 and its structure was determined in 1935 [R1].
Vitamine E is represented by four molecules that are soluble in fats: α-, β-, γ-, δ-tocopherol (αT, βT, γT, δT) and α-, β-, γ-, δ-tocotrienol (αTE, βTE, γTE, δTE [R1].
The most studied forms that are also used in commercial dietary supplements are alpha-tocopherol and gamma – tocopherol [R1].
Tocotrienols known to be found in palm oil are also garnering some attention from the scientists [R3].
In nature, the members of vitamin E family are mostly found in plants [R1].
Seeds usually have the most vitamin E content: alpha-tocopherol is predominantly found in peanuts, almonds and sunflower seeds, while gamma-tocopherol is the major vitamin E in walnuts, pecans, pistachios and sesame seeds and respective plant oils [R1].
Delta tocopherol can be found in tomato seeds, rice germ oil and soybean oil [R1].
Tocotrienols are rarer and can be found in palm oil, barley and some cereal grains [R1].
The most prominent property of all vitamin E forms is blocking the activity of harmful oxygen and nitrogen species [R1].
As vitamin E readily interacts with fats, it is also an important protector of fat molecules, preventing their oxidation along with vitamin C [R4].
It was shown that low vitamin E and C levels are associated with higher oxidation of fats [R4].
As fats are crucial building blocks for all cell membranes, low intake of vitamin E or genetic inability to use it leads to severe consequences. Vitamin E deficiency is associated with severe disruption of movement and coordination in young children [R5, R6].
Vitamin E Can Improve Fertility
As was already mentioned above, when vitamin E was discovered, it was considered mainly a fertility factor [R1].
It was shown in mice that diet low on cabbage leaves that were later shown to have vitamin E led to spontaneous abortions in pregnant mothers [R1].
It may be connected to the fact that during pregnancy concentration of vitamin E – binding protein, afamin in the blood grows almost twofold [R12].
The role of afamin in pregnancy is still unclear, though [R12].
TTPA or tocopherol transfer protein transports alpha-tocopherol across cell membranes [R13].
It was shown that concentration of this protein was very high in human placenta and only human liver had higher level of TTPA [R13].
In mice, the absence of TTPA gene makes the female animals unable to give birth [R14].
If those mice were given alpha-tocopherol in the early days of pregnancy, from 6.5 to 13.5 days after conception, they could carry their pregnancy to term [R15].
It shows that alpha tocopherol is critically important for development of the placenta [R15].
In clinical trial performed in women with ovarian failure that could not be helped by hormone therapy the patients were given a combination of 1000 IU tocopherol and 800 pentoxifylline daily for at least 9 months [R16]
This therapy led to an almost twofold increase in thickness of the wall of the uterus and even resulted in three viable pregnancies in the test group [R16].
This effect on the uterus was confirmed in another study in which vitamin E was added to therapy with clomiphene citrate, a drug that helps stimulate egg cell production in women with unexplained infertility [R17].
Addition of vitamin E increases the thickness in the uteruses of the patients but did not influence other parameters [R17]
Vitamin E can help men as well. It was shown that daily supplementation with Carni-Q-Nol, a cocktail containing vitamin E and vitamin C improved several parameters in the sperm prevented in sperm of men diagnosed with infertility [R18].
After 3 months of treatment, the sperm of the patients became 48% more dense and level of DNA damage became 25% lower [R18].
The therapy also results in 45% more pregnancies in their women.
In another study, supplementation with selenium (200 μg) and vitamin E (400 units) in men with fertility problems made their sperm 52 % more mobile and improved other parameters [R19].
The vitamin therapy also led to an 10% increase in pregnancy rates in their families [R19].
The study mentioned was not designed as a proper clinical trial, which means the findings need further confirmation [R19].
Vitamin E Is Important For Development Of The Embryo
The influence of vitamin E on early development was studied both in relation of tocopherol transfer protein (TTPA) mentioned above and alpha tocopherol itself.
A group of researchers have studied how mistakes in the TTPA gene that are known to cause AVED – ataxia with vitamin E deficiency syndrome – have influenced the activity of TTPA itself in human liver cells [R20]
It was shown that substitutions of “letters” in the gene are linked to inability of the protein to transport alpha tocopherol out of the cells [R20].
It was also noted that in case of mutation that is linked to more severe form of AVED TTPA activity was more disrupted [R20]
The studies performed on zebrafish have shown that TTPA is also important for the development of eyes, head and tail regions in this animal [R21].
It means that TTPA and vitamin E influence the development of the brain and nerve cord in the spine [R21].
Combined supplementation of pregnant diabetic rats with vitamin E and folic acid lowered the risk of death for the embryos [R22].
The animals received daily injections of 15 mg/kg folic acid with 5% addition of vitamin E in the diet [R22].
This combination prevented the increase of proteins that induced cell death, leading to the survival of the embryos [R22].
It is known that cigarette smoke exposure can kill developing embryos and prevent normal pregnancy [R23].
It can also destroy egg cells in female mice and prevent normal embryonic development [R24].
The addition of vitamin E form gamma tocotrienol to the diet of mice exposed to nicotine can protect the mice embryos [R23].
From the literature, it is clear why vitamin E is called a fertility factor, as it has profound influence on early development: helps the newly fertilized egg to attach, influences the nerve development and even protects the developing babies from damage. But this is not the end, so stay tuned for more information of vitamine E properties.
How Much Vitamin E Does One Have To Take?
In the US, daily dose consists of 12 mg of alpha-tocotrienol and recommended intake is 15 mg [R5].
It is higher for women who breastfeed – 19 mg a day [R5].
Infants need to have from 4 to 5 mg of vitamin E per day depending on age [R5].
As children grow, they have to take more vitamin E as well: from 6 mg per day in the first 3 years of life up to 11 mg in the period from 9 to 13 years [R5].
It should be noted that vitamin E works differently with other vitamins: for example, overdose of vitamin E can cause bleeding and it can block the action of vitamin K that is responsible for blood vessel integrity [R5].
On the other hand, it can work in tandem with vitamin C, as they have similar properties [R5].
It is important to know that the effectiveness of distribution of vitamin E depends on many factors, most notably diet [R7].
It was shown that vitamin E was better taken up by white and red blood cells of healthy people that took the supplement with a high fat meal (high-fat toast and butter [R7].
The ingestion of vitamin E was also dependent on what genes people have (in case of the present study – ApoE3 or ApoE4 gene variants) [R7].
In a study carried out in 2001 on a small group of 6 smokers and 5 non – smokers it was shown that vitamin E disappears from the blood of smokers approximately 20 days faster compared with nonsmokers [R8].
This finding was confirmed in later study, along with the fact and vitamin C disappears faster from the blood of smokers as well [R9].
A later experiment has shown that supplementation with 500mg vitamin C twice daily for two weeks in smokers has helped to slow down the disappearance of vitamin E from blood with time approximately for 45% [R10].
Vitamin E is also less available for cells in patients with metabolic syndrome, so they need to take more vitamin E than healthy people [R11].
- It was shown that individuals with low levels of vitamin C and E had higher levels of lipid peroxidation products (such as dienes of fatty acids and malondialdehyde [R4]
- The levels of plasma alpha-tocopherol positively correlated with the amount of fat in the diet (higher alpha tocopherol levels were associated with high fat meals) [R7],
- Dyslipidemic subjects had lower levels of plasma alpha-tocopherol [R7]
- ApoE3 subjects had reduced uptake of plasma alpha-tocopherol compared to ApoE4 [R7]
- A trend towards exponential disappearance of plasma alpha-tocopherol was observed in smokers [R8]
- Ascorbic acid supplementation attenuated smokers’ plasma alpha- and gamma-tocopherol fractional disappearance rates by 25% and 45%, respectively [R10]
- Vitamin E biovailability is lower in patients with metabolic syndrome [R11]
- Vitamin E-binding glycoprotein afamin increases almost twofold during uncomplicated pregnancies from 61,9mg/ml in the first trimester up to 98,6 mg/ml in the third trimester and returned to baseline level of 54,6 mg/ml after delivery [R12]
- · In women with premature ovarian failure resistant to hormone therapy combination of pentoxifylline and vitamin E led to an increase of edematous thickness up to 7,4 mm and nice uterine crosses. Three embryonic transplantations led to viable pregnancies [R16]
- · Vit E administration may improve the endometrial response in unexplained infertile women via the likely antioxidant and the anticoagulant effects [R17]
- · Forty infertile men were supplemented daily with Carni-Q-Nol and after 3 months of treatment improved sperm density and decreased sperm pathology was observed, along with the increase in levels of alpha tocopherol and CoQ in the plasma [R18]
- · Combined therapy in 690 infertile men with idiopathic asthenoteratospermia who received supplemental daily Se (200 μg) in combination with vitamin E (400 units) for at least 100 days has resulted in 52,6% total improvement in sperm motility, morphology and other parameters and 10% increase in the quantity of spontaneous pregnancies [R19].
- · Tocopherol transfer protein is localized to the late endocytic vesicles in the hepatocytes and participates in transfer of alpha-tocopherol to the plasma membrane [R20]
- · The study of physiological impact of substitutions R59W, R221W, and A120T in the TTPA gene has shown that those mutations impair the ability of TTPA to promote secretion of vitamin E from the cells. The degree of impairment corresponded to the severity degree of AVED observed for each mutation [R20].
- · TTPA in zebrafish was shown to be similar to the one in humans and its transcripts were observed on day one of development in brain, eyes and tail bud in the embryo [R21]
- · Combined supplementation of diabetic rats with folic acid and vitamin E led to a decrease in the levels of apoptotic proteins Bax and Bcl-2 [R22]
- · Exposure to nicotine 5.0 mg/kg/day of female mice led resulted in stopped embryo development at morula. Addition of gamma tocotrienol at doses 30, 60, or 90 mg/kg/day led to fully completed embryonic development [R24].
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