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AOC1

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Di-amine Oxidase (DAO – more properly called Amine Oxidase, Copper Containing 1) is an enzmye which breaks down histamine and is encoded for by the AOC1 gene 1.

Histamine plays an important role in the immune response, an in particular allergic responses. In health, histamine is released from immune cells (known as mast cells) resident in the skin, gut or lungs when a pathogen or allergen is detected. Histamine then generates three standard physiological responses .

Firstly, blood vessels are dilated to allow other immune cells to quickly reach the area where the pathogen was detected.

Secondly, smooth muscle contracts, which is thought to be a protective measure limiting other pathogens entering the body.

Finally, mucus secreting cells are stimulated, for example in the nose or gut, to protect against further pathogens reaching tissue. In health, histamine is then quickly degraded by DAO and the immune system clears the pathogen 2.

However, histamine is often fundamental in allergic reactions from mild hay-fever all the way through to severe anaphylactic shock. When non pathogenic compounds such as pollen, dust or animal hair are reconsigned as pathogenic, an immune response is generated. As these compounds are difficult, if not impossible, to avoid a chronic immune response is generated with near constant histamine release 3. For this reason many allergy sufferers are given anti-histamines which block the action of the histamine receptor. For those at more severe risk, such as those with asthma, other more potent drugs such as bronchodilators, which open the airways, are given as well.

Chronic release of histamine, combined with reduced histamine degradation, is known as histamine intolerance. There are several SNPs which are associated with reduced DAO activity and histamine intolerance.

C47T

Science Grade
B+
Immune Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%) Major Amino Acid Minor Amino Acid
rs10156191 c t 27 Thr Met

Risk Description

The risk ‘T’ allele of C47T in the AOC1 gene is associated with reduced DAO activity and histamine intolerance 4,5. For those carrying a single copy of the risk ‘T’ allele, DAO activity was reduced. Whereas for those carrying two copies of the ‘T’ allele DAO activity and expression was reduced. This suggests that the ‘T’ allele is associated with reduced expression of DAO rather than changes in its activity.

Therefore, those carrying the ‘T’ allele of C47T may be at risk of developing symptoms associated with histamine intolerance such as anxiety, body temperature issues, diarrhea, headaches, low blood pressure, flushing along with inflammation and irritation.

Direct Nutrients:*

Ingredient Active Ingredient Effect
Vitamin C Ascorbic Acid

Vitamin C is a cofactor for DAO and is required for its correct function 6, which contributes to the breakdown of histamine.

Therefore, carriers of the risk ‘T’ allele of C47T, which is associated with histamine intolerance, may benefit from vitamin C supplementation to ensure maximal DAO activity limiting the effect of histamine.

Importantly, for those with a histamine intolerance the source and components of any dietary supplement should be considered as they may contain factors which will trigger a response, negating any positive effect.

Vitamin B6 Pyridoxal phosphate

Vitamin B6 is one of three cofactors for DAO and is required for its proper function 7,8, leading to the breakdown of histamine.

To ensure maximal DAO activity, limiting the effect of histamine, carriers of the risk ‘T’ allele of C47T may consider vitamin B6 supplementation.

Importantly, for those with a histamine intolerance the composition of any dietary supplement should be considered as many contain ingredients which can trigger a response, negating any positive effect.

Copper

Copper is an essential mineral cofactor required for DAO’s histamine degrading activity 9.

To ensure maximal DAO activity, limiting the effect of histamine, carriers of the risk ‘T’ allele of C47T may wish to consider copper supplementation.

Indirect Nutrients:*

Ingredient Active Ingredient Effect
Quercetin

Quercetin is a common flavonoid molecule found in many foods with reddy or dark green vegetables being a particularly rich source 10. Apples are very high in quercetin.

Quercetin exhibits a potent inhibitory effect on the immune cells (mast cells) which release histamine. In those carrying the risk ‘T’ allele of C47T, which is associated with histamine intolerance as the result of reduced DAO activity, prevention of excessive histamine release may prove beneficial.

L-Theanine

The amino acid L-theanine, found in certain green and black teas, has been shown to inhibit the release of histamine and other inflammatory agents from mast cells 11.

Therefore those carrying the risk ‘T’ allele of C47T may benefit from supplementation to prevent, or limit excessive histamine release inducing histamine intolerance.

Nutritional Contraindications:*

Ingredient Active Ingredient Effect
Non-steroidal anti-inflammatory drugs (NSAID)

NSAID defines a drug class which provides pain killing and fever reducing effects, there are several different types however those typically available to consumers include asprin, ibruprofen (Advil or Motrin) and naproxen (Aleve or Naprosyn).

NSAID have been shown to be a common cause of drug-related hypersensitivity whereby an immune response, which involves histamine release, is generated 12.

The risk ‘T’ allele of C47T was specifically associated with an increased risk of developing a hypersensitive response. Although it was not clear if carriers were more likely to generate an immune response, or if their immune response was more severe 13.

Therefore, those carrying the risk ‘T’ allele of C47T may benefit from avoiding high dose NSAIDs or trying alternative pain relieving medication.

Histamine Rich Foods

As well as being produced in the body, histamine is also present in numerous foods including; fermented foods, bananas, avocado, dried fruits, smoked and salted fish, hard cheeses, smoked meats, pickled vegetables, vinegars and several alcoholic drinks 14.

Therefore those carrying the risk ‘T’ allele of C47T may consider avoiding, or reducing their intake of these food groups in order to limit the development of histamine intolerance.

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

C995T

Immune Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%) Major Amino Acid Minor Amino Acid
rs1049742 c t 6 Ser Phe

Risk Description

The risk ‘T’ allele of C995T in the AOC1 gene is associated with reduced DAO activity and histamine intolerance 4,5. For those carrying a single copy of the risk ‘T’ allele DAO activity was reduced, however unlike C47T described above, there was no additional effect seen in those with two copies of the ‘T’ allele.

Therefore, those carrying the ‘T’ allele of C995T may be at risk of developing symptoms associated with histamine intolerance such as headaches, diarrhea, low blood pressure as well as other common symptoms of allergy.

Direct Nutrients:*

Ingredient Active Ingredient Effect
Vitamin C Ascorbic Acid

Vitamin C is one of three cofactors required by DAO to function properly 6, resulting in the breakdown of histamine.

Therefore, carriers of the risk ‘T’ allele of C995T, which is associated with histamine intolerance may benefit from vitamin C supplementation, to ensure proper DAO activity limiting the effect of histamine.

Importantly, for those with a histamine intolerance the composition of any dietary supplement should be considered as many contain ingredients which can trigger a response, negating any positive effect.

Vitamin B6 Pyridoxal phosphate

Vitamin B6 is a key cofactor for DAO and is required for its correct function leading to the breakdown of histamine 7,8.

To ensure proper DAO activity, limiting the effect of histamine, carriers of the risk ‘T’ allele of C995T may consider from vitamin B6 supplementation.

Importantly, for those with a histamine intolerance the source and components of any dietary supplement should be considered as they may contain factors which will trigger a response, negating any positive effect.

Copper

Copper is a cofactor required for DAO activity 9, which leads to the breakdown of histamine.

Carriers of the risk ‘T’ allele of C995T may therefore benefit from copper supplementation to reduce the adverse effects associated with histamine intolerance.

Indirect Nutrients:*

Ingredient Active Ingredient Effect
Quercetin

Quercetin is a type of flavonoid which is found in many types of foods 10.

It has been shown act as a very strong inhibitor of histamine release from immune cells which release histamine. Therefore, in those carrying the risk ‘T’ allele of C995T, which is associated with histamine intolerance associated with reduced DAO activity, inhibition of histamine release may prove beneficial.

L-Theanine

L-theanine, an amino acid which is abundant in green and black tea, can inhibit the release of histamine and other inflammatory agents from mast cells 11.

Therefore those carrying the risk ‘T’ allele of C995T may benefit from supplementation to prevent, or limit, excessive histamine release inducing histamine intolerance.

Nutritional Contraindications:*

Ingredient Active Ingredient Effect
Histamine Rich Food

As well as being produced in the body histamine is also present in numerous foods including; smoked and salted fish, hard cheeses, smoked meats, pickled vegetables, vinegars and several alcoholic drinks 14.

Therefore, those carrying the risk ‘T’ allele of C995T may consider avoiding, or reducing their intake of these food groups in order to limit the development of histamine intolerance.

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

C1933G/T

Science Grade
B-
Immune Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%) Major Amino Acid Minor Amino Acid
rs1049793 c g 37 His Asp

Risk Description

The risk ‘G or T’ alleles of C1933G/T in the AOC1 gene is associated with reduced DAO activity and histamine intolerance 4.

Therefore, those carrying either the  ‘G or T’ alleles of C1933G/T may be at risk of developing symptoms associated with histamine intolerance such as headaches, diarrhea, low blood pressure as well as other common symptoms of allergy.

Direct Nutrients:*

Ingredient Active Ingredient Effect
Vitamin C Ascorbic Acid

Vitamin C is a cofactor for DAO and is required for its correct function 6, which contributes to the breakdown of histamine.

Therefore, carriers of the risk ‘C or G’ alleles of C1933G/T, which is associated with histamine intolerance may benefit from vitamin C supplementation, to ensure maximal DAO activity limiting the effect of histamine.

Importantly, for those with a histamine intolerance the source and components of any dietary supplement should be considered as they may contain factors which will trigger a response, negating any positive effect.

Vitamin B6 Pyridoxal phosphate

Vitamin B6 is one of three cofactors for DAO and is required for its proper function 7,8, leading to the breakdown of histamine.

To ensure maximal DAO activity, limiting the effect of histamine, carriers of the risk ‘C or G’ alleles of C1933G/T may consider from vitamin B6 supplementation.

Importantly, for those with a histamine intolerance the composition of any dietary supplement should be considered as many contain ingredients which can trigger a response, negating any positive effect.

Copper

Copper is an essential mineral cofactor required for DAOs histamine degrading activity 9.

To ensure maximal DAO activity, limiting the effect of histamine, carriers of the risk ‘C or G’ alleles of C1933G/T may wish to consider copper supplementation.

Indirect Nutrients:*

Ingredient Active Ingredient Effect
Quercetin

Quercetin is a common flavonoid molecule found in many foods with reddy or dark green vegetables being a particularly rich source 10.

Quercetin exhibits a potent inhibitory effect on the immune cells which release histamine. In those carrying the risk ‘C or G’ alleles of C1933G/T which is associated with histamine intolerance as the result of reduced DAO activity, prevention of excessive histamine release may prove beneficial.

L-Theanine

The amino acid L-theanine, found in certain green and black teas, has been shown to inhibit the release of histamine and other inflammatory agents from mast cells 11.

Therefore, those carrying the risk ‘C or G’ alleles of C1933G/T may benefit from supplementation to prevent, or limit excessive histamine release inducing histamine intolerance.

Nutritional Contraindications:*

Ingredient Active Ingredient Effect
Histamine Rich Food

As well as being produced in the body histamine is also present in numerous foods including; smoked and salted fish, hard cheeses, smoked meats, pickled vegetables, vinegars and several alcoholic drinks 14.

Therefore, those carrying the risk ‘C or G’ alleles of C1933G/T may consider avoiding, or reducing their intake of these food groups in order to limit the development of histamine intolerance.

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

G1437A

Immune Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%) Major Amino Acid Minor Amino Acid
rs45558339 c a 0.03 Met Ile

Risk Description

The risk allele ‘A’ of G1437A in the AOC gene is associated with reduced DAO activity and the subsequent occurrence of histamine intolerance 4. Interestingly, G1437A was found to be of particular importance in Asian populations as opposed to the population as a whole.

In certain genetic reports this SNP may be listed as being associated with the ABP1 gene, however its correct location is within AOC1.

Direct Nutrients:*

Ingredient Active Ingredient Effect
Vitamin C Ascorbic Acid

Vitamin C is a cofactor for DAO and is required for its correct function 6, which contributes to the breakdown of histamine.

Therefore, carriers of the risk ‘A’ allele of G1437A, which is associated with histamine intolerance may benefit from vitamin C supplementation, to ensure maximal DAO activity limiting the effect of histamine.

Importantly, for those with a histamine intolerance the source and components of any dietary supplement should be considered as they may contain factors which will trigger a response, negating any positive effect.

Vitamin B6 Pyridoxal phosphate

Vitamin B6 is one of three cofactors for DAO and is required for its proper function 7,8, leading to the breakdown of histamine.

To ensure maximal DAO activity, limiting the effect of histamine, carriers of the risk ‘A’ allele of G1437A may consider from vitamin B6 supplementation.

Importantly, for those with a histamine intolerance the composition of any dietary supplement should be considered as many contain ingredients which can trigger a response, negating any positive effect.

Copper

Copper is an essential mineral cofactor required for DAOs histamine degrading activity 9.

To ensure maximal DAO activity, limiting the effect of histamine, carriers of the risk ‘A’ allele of G1437A may wish to consider copper supplementation.

Indirect Nutrients:*

Ingredient Active Ingredient Effect
Quercetin

Quercetin is a common flavonoid molecule found in many foods with reddy or dark green vegetables being a particularly rich source 10.

Quercetin exhibits a potent inhibitory effect on the immune cells which release histamine. In those carrying the risk ‘A’ allele of G1437A which is associated with histamine intolerance as the result of reduced DAO activity, prevention of excessive histamine release may prove beneficial.

L-Theanine

The amino acid L-theanine, found in certain green and black teas, has been shown to inhibit the release of histamine and other inflammatory agents from mast cells 11.

Therefore, those carrying the risk ‘A’ allele of G1437A may benefit from supplementation to prevent, or limit excessive histamine release inducing histamine intolerance.

Nutritional Contraindications:*

Ingredient Active Ingredient Effect
Histamine Rich Food

As well as being produced in the body histamine is also present in numerous foods including; smoked and salted fish, hard cheeses, smoked meats, pickled vegetables, vinegars and several alcoholic drinks 14.

Therefore those carrying the risk ‘A’ allele of G1437A may consider avoiding, or reducing their intake of these food groups in order to limit the development of histamine intolerance.

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

A1975C

Immune Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%) Major Amino Acid Minor Amino Acid
rs35070995 a c 2.46 Asn His

Risk Description

The risk allele ‘C’ of A1975C in the AOC gene is associated with reduced DAO activity and the subsequent occurrence of histamine intolerance 4. Interestingly, A1975C was found to be of particular importance in those of African descent.

In certain genetic reports this SNP may be listed as being associated with the ABP1 gene, however its correct location is within AOC1.

Direct Nutrients:*

Ingredient Active Ingredient Effect
Vitamin C Ascorbic Acid

Vitamin C is a cofactor for DAO and is required for its correct function 6, which contributes to the breakdown of histamine.

Therefore, carriers of the risk ‘C’ allele of A1975C, which is associated with histamine intolerance may benefit from vitamin C supplementation, to ensure maximal DAO activity limiting the effect of histamine.

Importantly, for those with a histamine intolerance the source and components of any dietary supplement should be considered as they may contain factors which will trigger a response, negating any positive effect.

Vitamin B6 Pyridoxal phosphate

Vitamin B6 is one of three cofactors for DAO and is required for its proper function 7,8, leading to the breakdown of histamine.

To ensure maximal DAO activity, limiting the effect of histamine, carriers of the risk ‘C’ allele of A1975C may consider from vitamin B6 supplementation.

Importantly, for those with a histamine intolerance the composition of any dietary supplement should be considered as many contain ingredients which can trigger a response, negating any positive effect.

Copper

Copper is an essential mineral cofactor required for DAOs histamine degrading activity 9.

To ensure maximal DAO activity, limiting the effect of histamine, carriers of the risk ‘C’ allele of A1975C may wish to consider copper supplementation.

Indirect Nutrients:*

Ingredient Active Ingredient Effect
Quercetin

Quercetin is a common flavonoid molecule found in many foods with reddy or dark green vegetables being a particularly rich source 10.

Quercetin exhibits a potent inhibitory effect on the immune cells which release histamine. In those carrying the risk ‘C’ allele of A1975C which is associated with histamine intolerance as the result of reduced DAO activity, prevention of excessive histamine release may prove beneficial.

L-Theanine

The amino acid L-theanine, found in certain green and black teas, has been shown to inhibit the release of histamine and other inflammatory agents from mast cells 11.

Therefore, those carrying the risk ‘C’ allele of A1975C may benefit from supplementation to prevent, or limit excessive histamine release inducing histamine intolerance.

Nutritional Contraindications:*

Ingredient Active Ingredient Effect
Histamine Rich Food

As well as being produced in the body histamine is also present in numerous foods including; smoked and salted fish, hard cheeses, smoked meats, pickled vegetables, vinegars and several alcoholic drinks 14.

Therefore those carrying the risk ‘C’ allele of A1975C may consider avoiding, or reducing their intake of these food groups in order to limit the development of histamine intolerance.

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

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