APOE

Fact Checked

Protein:

Apolipoprotein E

SNP ID:

C526CT
T388C

Apolipoprotein E (APOE) transports lipoproteins, vitamins and cholesterol, particularly in the brain and is encoded for by the APOE gene ¹.

Apolipoproteins are proteins which bind lipids facilitating their transport through the body. Lipids are typically insoluble in water and so are very difficult to transport in the blood, apolipoproteins bind and surround lipids greatly improving their solubility. APOE is the principal lipid carrier in the brain and central nervous system, ensuring proper neuron formation and action ².

There are three major forms of APOE, two of which are associated with poor health outcomes. The type of APOE expressed is controlled by two separate SNPs in the APOE gene, rs7412 or C526CT and rs429358 or T388C ³. Therefore, the two SNPs should be read together to identify which type of APOE gene you carry: APOE2, APOE3, or APOE4.

C526CT

Science Grade :

A-

Heart Health

rsID Number	Major Allele	Minor Allele	Minor Allele Frequency (%)	Major Amino Acid	Minor Amino Acid
rs7412	c	t	7	Arg	Cys

Risk Description

As discussed above, there are three major forms of APOE expression which are controlled by two SNPs C526CT and T388C, both listed on this page. Therefore the ‘C’ or ‘T’ allele in C526CT can be considered the risk allele, or normal, depending on which allele from T388C is present. In other words, you need to read the two SNPs listed on this page together to understand carrier status.

APOE3

APOE3 is considered the neutral form of APOE and is encoded for by the ‘C’ allele of C526CT and the ‘T’ allele of T388C, with the majority of people carrying this version of APOE ⁴.

APOE2

APOE2 is associated with an increased cardiovascular risk and is encoded for by the ‘T’ allele of C526CT and the ‘T’ allele of T388C ⁵. It is thought that APOE2 binds less well with its receptors, limiting the clearance of dietary fat from the blood, increasing the risk of clot formation ⁶.

APOE4

Conversely, APOE4 is associated with an increased risk of neurological conditions such as Alzheimer’s disease. APOE4 is encoded for by the ‘C’ allele of C526CT and the ‘C’ allele of T388C ⁷. It is unclear how APOE4 modulates increased neurological risk, one potential hypothesis is that APOE4 is associated with reduced neurite development ⁸. Neurites are small projections from neuronal cells and are one of the ways the body develops the complex neural networks found in the brain.

As the minor ‘T’ allele of C526CT is associated with an increased cardiovascular risk, beneficial dietary adjustments will be discussed below.

Dietary adjustments focused on the neurological aspects will be discussed below T388C.

Indirect Nutrients:^*

Ingredient	Active Ingredient	Effect
Nattō	Nattokinase	Nattokinase is an enzyme which is extracted and purified from a Japanese food called nattō, which is made from fermented soybeans. Nattokinase is secreted by the bacteria involved in the fermentation process and has a very strong ability to break down fibrin blood clots ⁹. A beneficial effect on blood pressure ¹⁰, and general cardiovascular health has been described ¹¹. Therefore, supplementation may benefit those carrying the ‘T’ allele of C526CT and the ‘T’ allele of T388C (APOE2) which are associated with an increased cardiovascular risk through increased clot formation.
Bromelain		Bromelain refers to an extract of plants from the Bromeliaceae family, such as pineapples. This extract is rich in two enzymes called stem and fruit bromelain which have a strong digestive capacity which strongly inhibits clot formation ¹². Supplementation may therfore benefit those carrying the ‘T’ allele of C526CT and the ‘T’ allele of T388C (APOE2) which are associated with an increased cardiovascular risk through an increase in clot formation.
Bergamot Oil	Melitidin and Brutieridin	Bergamot orange is a sour citrus fruit similar in size to an orange and is typically grown only on areas surrounding the Ionian Sea. Bergamot oranges are frequently processed into oil for a variety of uses, including most recently positive health effects. Melitidin and brutieridin are two flavone molecules found only in Bergamot oranges which exhibit statin ¹⁴ like properties, and also lower lipids present in the blood ¹⁵. As such supplementation may benefit those carrying the ‘T’ allele of C526CT and the ‘T’ allele of T388C (APOE2) which are associated with an increased cardiovascular risk through an increase in clot formation.

Ingredient

Active Ingredient

Effect

Nattō

Nattokinase

Nattokinase is an enzyme which is extracted and purified from a Japanese food called nattō, which is made from fermented soybeans.

Nattokinase is secreted by the bacteria involved in the fermentation process and has a very strong ability to break down fibrin blood clots ⁹. A beneficial effect on blood pressure ¹⁰, and general cardiovascular health has been described ¹¹.

Therefore, supplementation may benefit those carrying the ‘T’ allele of C526CT and the ‘T’ allele of T388C (APOE2) which are associated with an increased cardiovascular risk through increased clot formation.

Bromelain

Bromelain refers to an extract of plants from the Bromeliaceae family, such as pineapples. This extract is rich in two enzymes called stem and fruit bromelain which have a strong digestive capacity which strongly inhibits clot formation ¹².

Supplementation may therfore benefit those carrying the ‘T’ allele of C526CT and the ‘T’ allele of T388C (APOE2) which are associated with an increased cardiovascular risk through an increase in clot formation.

Bergamot Oil

Melitidin and Brutieridin

Bergamot orange is a sour citrus fruit similar in size to an orange and is typically grown only on areas surrounding the Ionian Sea.

Bergamot oranges are frequently processed into oil for a variety of uses, including most recently positive health effects. Melitidin and brutieridin are two flavone molecules found only in Bergamot oranges which exhibit statin ¹⁴ like properties, and also lower lipids present in the blood ¹⁵.

As such supplementation may benefit those carrying the ‘T’ allele of C526CT and the ‘T’ allele of T388C (APOE2) which are associated with an increased cardiovascular risk through an increase in clot formation.

Discuss this information with your doctor before taking any course of action.

Citations:

T388C

Science Grade :

A-

Brain Health

rsID Number	Major Allele	Minor Allele	Minor Allele Frequency (%)	Major Amino Acid	Minor Amino Acid
rs429358	t	c	18	Cys	Arg

Risk Description

T388C is one of two SNPs, in conjunction with C526CT which control expression of APOE. The combination of alleles determines which form of APOE is expressed and so alleles can be either present a risk or be normal depending on their association.

APOE3 is considered the baselines form of APOE and is encoded for by the ‘T’ allele of T388C and the ‘C’ allele of C526CT, with the majority of people carrying this version of APOE ⁴.

APOE4 is associated with an increased risk of neurological conditions such as Alzheimer’s disease. APOE4 is encoded for by the ‘C’ allele of T388C and the ‘C’ allele of C526CT ⁷. It is unclear how expression of APOE4 increases neurological disorder risk. One potential hypothesis is that APOE4 is associated with reduced neurite, small projections from neuronal cells, development; which are key in controlling neuronal interactions ⁸.

APOE2 is associated with an increased cardiovascular risk and is encoded for by the ‘T’ allele of T388C and the ‘T’ allele of C526CT ⁵. It is thought that APOE2 binds less well with its receptors, limiting the clearance of dietary fat from the blood, increasing the risk of clot formation ⁶.

As the minor ‘C’ allele of T388C is associated with an increased risk of developing neurological disorders, beneficial dietary adjustments will be discussed below. Dietary adjustments focused on the cardiovascular aspects are discussed above in relation to C526CT.

Nutritional Contraindications:^*

Ingredient	Active Ingredient	Effect
Saturated Fats triglycerides		Saturated fats, or triglycerides are fat molecules comprised where all of the bonds between carbon atoms in the fatty acid chains are single, i.e the fatty acid chain is saturated. There is much debate about the relative pros and cons of saturated and unsaturated dietary fats, and firm dietary advice is currently lacking. However, the neurological risk associated with APOE4, encoded for by the ‘C’ allele of T388C and the ‘C’ allele of C526CT (APOE4) , is significantly higher in those consuming a diet rich in saturated fats ¹³. How this impacts on those consuming a ‘normal’ diet is unclear.

Ingredient

Active Ingredient

Effect

Saturated Fats triglycerides

Saturated fats, or triglycerides are fat molecules comprised where all of the bonds between carbon atoms in the fatty acid chains are single, i.e the fatty acid chain is saturated.

There is much debate about the relative pros and cons of saturated and unsaturated dietary fats, and firm dietary advice is currently lacking. However, the neurological risk associated with APOE4, encoded for by the ‘C’ allele of T388C and the ‘C’ allele of C526CT (APOE4) , is significantly higher in those consuming a diet rich in saturated fats ¹³. How this impacts on those consuming a ‘normal’ diet is unclear.

Discuss this information with your doctor before taking any course of action.

Risk Description

APOE3

APOE2

APOE4

Indirect Nutrients:*

Citations:

Risk Description

Nutritional Contraindications:*

Citations:

Indirect Nutrients:^*

Nutritional Contraindications:^*