Trait: Vitamin E Breakdown
Dr Haran Sivapalan
October 16, 2020
What is Vitamin E?
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 is a fat-soluble vitamin found in many foods and supplements.
- Vitamin E is an important antioxidant.
- There are 8 different forms of Vitamin E.
- α-tocopherol is the most important form of Vitamin E in the body.
- Vitamin E and α-tocopherol are often used interchangeably.
Why is Vitamin E important?
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.
- Vitamin E protects cells from damage by free radicals and reactive oxygen species.
- Vitamin E functions as an antioxidant – it donates electrons to free radicals to neutralise them.
- Vitamin E is particularly important for protecting fats and lipids (such as those in cell membranes) from damage.
- Vitamin E is also involved in immune function, cell signalling, and blood flow.
What foods are rich in Vitamin E?
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).
- Wheatgerm oil (1 tbsp) – 20.3 mg α-tocopherol per serving
- Sunflower seeds (1 ounce / 28 g) – 7.4 mg
- Almonds (1 ounce / 28 g) – 6.8 mg
- Sunflower oil (1 tbsp) – 5.6 mg
- Safflower oil (1 tbsp) – 4.6 mg
- Spinach (1/2 cup, boiled) – 1.9 mg
- Broccoli (1/2 cup, boiled) – 1.2 mg
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.
- Vegetable oils, nuts, seeds, and leafy green vegetables are good sources of Vitamin E (α-tocopherol).
- The RDA for Vitamin E is 15 mg per day.
What is a healthy Vitamin E level?
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.
- A healthy fasting plasma α-tocopherol level is 5.5 – 17mg/L.
How is Vitamin E absorbed and metabolised?
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.
- Resecretion by the liver. The liver packages Vitamin E (specifically α-tocopherol) along with cholesterol into different lipoprotein particles known as VLDLs (Very Low Density Lipoproteins). VLDLs are then secreted into the bloodstream and transport Vitamin E to other tissues (e.g. adipose tissue).
- Broken down and excreted. Enzymes in the liver break down Vitamin E. The end products can then be excreted by the kidneys into urine. Breakdown products also get incorporated into bile, which gets secreted into the small intestine to help absorb fats. Once in the small intestine, Vitamin E metabolites can then be excreted with faeces.
- Vitamin E needs to be absorbed with fat.
- People with fat malabsorption disorders (e.g. celiac disease) are at greater risk of Vitamin E deficiency.
- Vitamin E absorbed by the intestines is transported in the bloodstream inside lipoprotein particles to different tissues (e.g. fat tissue, liver).
- Vitamin E taken up by the liver is either resecreted into the bloodstream or broken down and excreted.
How is Vitamin E broken down?
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.
- Vitamin E (α-tocopherol) is broken down by the CYP4F2 liver enzyme.
- The activity of CYP4F2 affects your body’s Vitamin E levels.
What is the CYP4F2 gene?
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.
- The CYP4F2 gene encodes the enzyme that breaks down Vitamin E.
What are the different CYP4F2 gene variants?
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).
- There are two variants of the CYP4F2 gene: the ‘C’ and ‘T’ variants.
- The ‘T’ variant is associated with lower CYP4F2 enzyme levels and reduced breakdown of Vitamin E.
- In order of decreasing enzyme activity, your possible CYP4F2 genotypes are: CC, CT, TT.
How do CYP4F2 gene variants affect Vitamin E levels?
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:
- CC genotype – mean α-tocopherol level = 11.8 mg/L
- CT genotype – mean α-tocopherol level = 12.1 mg/L
- TT genotype – mean α-tocopherol level = 12.7 mg/L
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.
- The ‘T’ variant of the CYP4F2 gene causes reduced breakdown of Vitamin E, which leads to higher Vitamin E levels.
- In order of increasing Vitamin E levels, the CYP4F2 genotypes are: CC, CT, TT.
Your Vitamin E breakdown trait
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:
- Reduced enzyme activity (associated with highest Vitamin E levels)
- Moderately reduced enzyme levels (associated with intermediate Vitamin E levels)
- Normal enzyme activity (associated with lowest Vitamin E levels)
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