Trait#83: Vitamin E Breakdown
Friday, October 16, 2020. Author FitnessGenes
Friday, October 16, 2020. Author FitnessGenes
Vitamin E is a fat-soluble micronutrient found in many foods (such as vegetable oils, nuts, and seeds) and supplements.
It is an important antioxidant – meaning it protects cells against damage from harmful substances called free radicals and reactive oxygen species.
Strictly speaking, Vitamin E is the collective name for eight different chemical forms of Vitamin E:
Of these, α-tocopherol is the form of Vitamin E preferentially used by the body. α-tocopherol is also the only form of Vitamin E that is known to meet human nutrient requirements. In this respect, when we mention Vitamin E in this trait, we are usually specifically referring to α-tocopherol.
Vitamin E predominantly functions as an antioxidant.
We have encountered antioxidants before in your Oxidative Stress Risk trait. Readers are encouraged to revisit this article for a wider overview of antioxidants and how they protect against oxidative stress.
Antioxidants are substances that neutralise, clear, and/or prevent the production of free radicals and reactive oxygen species (ROS). Free radicals are atoms and molecules that have an unpaired electron, which makes them highly reactive. ROS are also highly reactive substances, many of which are also free radicals, that are derived from oxygen. Free radicals and ROS are generated by the body during normal processes (e.g. respiration) and also from external factors (e.g. cigarette smoking, air pollutants).
As they are highly reactive, both free radicals and ROS can react with and damage key cell components (e.g. cell membranes) and molecules including proteins, DNA, and lipids/fats. Cell damage from free radicals and ROS (oxidative stress) is implicated in inflammation, ageing, and the development of Type II diabetes, cardiovascular disease and cancer.
Vitamin E acts to neutralise or “scavenge” free radicals by donating electrons to them, thereby rendering the free radicals unreactive.
Vitamin E protects lipids from damage
As it is a fat-soluble molecule, Vitamin E is particularly important for protecting fats and lipids from being damaged by free radicals. To adopt scientific lingo, we say that Vitamin E helps to prevent lipid peroxidation.
When free radicals react with lipid molecules, they generate new free radicals out of the lipids (so called lipid radicals). These new lipid radicals are also highly reactive (as they have unpaired electrons) and go on to react with and damage further lipids. This then creates new lipid radicals, and the process continues in what is known as a chain reaction.
Vitamin E helps to terminate this chain reaction by donating an electron to lipid radicals, thereby neutralising them. In this way, Vitamin E protects lipids in cell membranes and in lipoproteins (particles that transport fat around the body) from being damaged.
In addition to acting as an antioxidant, Vitamin E is important for immune function, cell signalling, and blood flow.
Vegetable oils, nuts, seeds, green leafy vegetables, and fortified cereals are all good sources of Vitamin E (α-tocopherol).
Interestingly, American diets tend to be richer in a different form of Vitamin E, γ-tocopherol, which is found in soybean, corn, and canola oil.
Listed below are some good sources of Vitamin E (α-tocopherol).
In case you’re wondering how much Vitamin E is required per day, the Recommended Dietary Allowance (RDA) is 15 mg per day for most adults.
The most commonly used measure of your body’s Vitamin E levels is fasting plasma α-tocopherol level. This is a measurement of the amount of α-tocopherol circulating in the bloodstream.
A healthy fasting plasma α-tocopherol level for adults is 5.5 – 17 mg/L.
Vitamin E is a fat-soluble vitamin, meaning it is absorbed in the small intestine along with fats in small fatty clusters called micelles. This process is aided by bile and enzymes secreted by the pancreas.
As fat is required for the absorption of Vitamin E in the intestines, people with certain fat malabsorption disorders (e.g. Crohn’s and celiac disease) may absorb Vitamin E less effectively and be at greater risk of Vitamin E deficiency.
Once absorbed by the intestine, Vitamin E and fats are packaged into particles (lipoprotein particles) called chylomicrons. Chylomicrons then circulate in the bloodstream, where they can be taken up and metabolised by other tissues (such as the liver or adipose tissue).
Chylomicrons containing newly absorbed Vitamin E and fats can be metabolised by tissues using an enzyme called lipoprotein lipase (LPL). This releases Vitamin E for tissues to use or store.
Vitamin E can also be transferred to other circulating lipoprotein particles (such as HDL), which transport fats and Vitamin E in the bloodstream to other tissues. (You can read more about the different kinds of lipoproteins in the Cholesterol and Ageing trait article).
Chylomicrons can also transport Vitamin E to the liver. When fats are removed from chylomicrons, they form smaller particles called chylomicron remnants. These are taken up by the liver, which then further metabolise Vitamin E.
Once in the liver, there are two main destinations for Vitamin E.
The liver has a system of about 40-50 enzymes, known as the cytochrome P450 system, that metabolise and break down various molecules, including hormones, drugs, and micronutrients.
One cytochrome P450 enzyme in particular, CYP4F2 (or Leukotriene-B(4) omega-hydroxylase 1), is responsible for breaking down or “catabolising” Vitamin E (α-tocopherol).
The rate at which CYP4F2 breaks down Vitamin E in your liver affects your blood and tissue levels of Vitamin E.
Your CYP4F2 gene codes for the CYP4F2 enzyme that breaks down Vitamin E in the liver.
Studies suggest that variants of your CYP4F2 gene can affect your body’s Vitamin E levels.
A SNP (Single Nucleotide Polymorphism) within the CYP4F2 gene, designated rs2108622, causes a single letter change in the DNA code from ‘C’ to a ‘T’. This creates two different gene variants or ‘alleles’: the ‘C’ allele and the ‘T’ allele.
The ‘T’ allele leads to reduced enzyme levels and, consequently, lower activity of the CYP4F2 enzyme.
Given that we inherit pairs of genes, the two CYP4F2 gene variants / alleles give rise to three different genotypes (genetic makeups):
People who inherit the T allele (i.e. those with CT and TT genotypes) will have reduced CYP4F2 activity.
Furthermore, the ‘T’ allele has an ‘additive effect.’ This means people who inherit two copies of the ‘T’ allele (i.e. TT genotype) will have lower CYP4F2 activity and more markedly reduced Vitamin E breakdown than those who inherit just one ‘T’ allele (the CT genotype).
As described earlier, the ‘T’ allele of the CYPF42 gene leads to lower enzyme levels and therefore a lower rate of Vitamin E breakdown. Studies suggest that, likely due to reduced vitamin breakdown, people with the ‘T’ allele have higher blood and tissue levels of Vitamin E.
On this note, a meta-analysis of three large studies (the Alpha-Tocopherol, Beta-Carotene Cancer Prevention study [ATBC], Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), and Nurses’ Health Study [NHS]) found that the ‘T’ allele was associated with higher plasma alpha-tocopherol levels.
For example, in the ATBC study, which followed 4014 male Finnish smokers aged 50-69 years, the following results were observed:
Again, these results highlight the additive effect of the ‘T’ allele. People with two copies of the ‘T’ allele (i.e. TT genotype) have the highest Vitamin E levels, followed by those with just one copy of the ‘T’ allele (i.e. CT genotype).
Those with the CC genotype have normal CYP4F2 enzyme levels and therefore relatively higher breakdown of Vitamin E compared to other genotypes. As a result of this, those with the CC genotype have the lowest Vitamin E levels.
Your Vitamin E breakdown trait analyses your CYP4F2 genotype and classifies your CYP4F2 enzyme levels and rate of Vitamin E breakdown. You will fall into one of three categories:
To view your trait results, please login to Truefeed.
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