NOS3

Protein:

Nitric Oxide Synthase 3

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Nitric oxide synthase 3 (NOS3) is an enzyme which is responsible for the production of the small molecule nitric oxide (NO) and is encoded for by the NOS3 gene. NOS3 is predominantly expressed in the endothelial tissue which lines the circulatory system and heart, where it plays a key role in regulation of NO 1.

NO plays numerous protective roles in the cardiovascular system when produced correctly. Acting as a vasodilator, NO, when secreted diffuses across the surface of a blood vessel into the surrounding smooth muscle tissue causing it to relax 2. Furthermore, NO also inhibits the formation of clots within blood vessels by preventing platelets, the small cells found in blood which form clots, from binding and also prevents immune cells from sticking to the walls of blood vessels 3.

NO has also been shown to increase the expression of the potent antioxidant superoxide dismutase (SOD) although it is not clear what effect this has on cardiovascular health 4.

There are three SNPs located in the NOS3 gene which are associated with poor health outcomes; rs1800779 or G51-898A, rs1799983 or T894G and rs1800783 or A-52+1009T.

G51-898A

Heart Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%)
rs1800779 a g 23

Risk Description

The risk ‘G’ allele of G51-898A in the NOS3 gene is associated with increased cardiovascular risk markers and increased risk of high blood pressure 5,6. A mechanism for either occurrence is not described, but it is possible hypothesise that the risk ‘G’ allele results in reduced NOS3 expression or activity leading to a reduction in NO production. With reduced NO production relaxation of smooth muscles surrounding blood vessels will be reduced leading to increased blood pressure.

Direct Nutrients:*

IngredientActive IngredientEffect
Tetrahydrobiopterin

Tetrahydrobiopterin (BH4 or THB), sometimes known as sapropterin is one of three co-factors required by NOS3 to function efficiently 7. As the risk ‘G’ allele of G51-898A is hypothesized to lead to reduced NOS3 activity, supplementation with BH4 may prove beneficial to those carrying the risk allele with elevated blood pressure or who are at cardiovascular risk.

Vitamin B2 Riboflavin phosphate

Vitamin B2 is one of three co-factors required by NOS3 to function correctly 8. With the risk ‘G’ allele of G51-898A proposed to be associated with reduced NOS3 activity, supplementation with vitamin B2 may prove beneficial those with elevated blood pressure or who are at cardiovascular risk.

Iron

Iron is one of three co-factors required by NOS3 in order to function 9. Iron supplementation may benefit those at cardiovascular risk, especially those carrying the risk ‘G’ allele of G51-898A. However, care should be taken with iron supplementation as excessively dietary iron is associated with increased risk of coronary heart disease 10.

Indirect Nutrients:*

IngredientActive IngredientEffect
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 11. A beneficial effect on blood pressure 12, and general cardiovascular health has been described 13. Therefore, supplementation may benefit those carrying the risk ‘G’ allele of G51-898A, especially those with elevated blood pressure or cardiovascular risk.

Ubiquinol Coenzyme Q10

Coenzyme Q10 (CQ10) is a naturally occurring coenzyme with numerous health benefits. A positive effect was seen in those with elevated blood pressure 14, but no effect was seen in healthy controls 15. Therefore, supplementation may only be recommended for those with elevated blood pressure who also carry the risk ‘G’ allele of G51-898A.

Bergamot Oil Melitidin and Brutieridin

Bergamot orange is a sour citrus fruit similar in size to an orange and is typically grown only in Mediterranean areas.

Bergamot oranges are frequently processed into oil for a variety of uses, such as providing citrus notes to perfumes and in skin creams. More recently positive health effects have been described. Melitidin and brutieridin are two flavone molecules found only in Bergamot oranges which exhibit statin (blood pressure lowering) 19 like properties, and also lower lipids present in the blood 20.

As such supplementation may benefit those carrying the risk ‘G’ allele of G51-898A. which is associated with an increased cardiovascular risk and elevated blood pressure.

Nutritional Contraindications:*

IngredientActive IngredientEffect
Sodium

The impacts of a high sodium diet are well established 16. Therefore, in those carrying the risk ‘G’ allele of G51-898A which is associated with elevated blood pressure, a reduction in sodium intake to recommended levels should be considered.

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

T894G

Women's Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%) Major Amino Acid Minor Amino Acid
rs1799983 g t 25AspGlu

Risk Description

The risk ‘T’ allele of T894G in the NOS3 gene is associated with increased cardiovascular risk markers such as total cholesterol and LDL, and increased risk of high blood pressure, especially in pregnant women 5,6,17.

An exact mechanism for either occurrence is not described, but it is possible hypothesise that the risk ‘T’ allele results in reduced NO production, arising from alterations in NOS3 activity or expression. With reduced NO production the capacity to relax blood vessels and thus reduce blood pressure is impacted.

Direct Nutrients:*

IngredientActive IngredientEffect
Tetrahydrobiopterin

Tetrahydrobiopterin (BH4 or THB), is one of three co-factors required by NOS3 to function correctly 7. The risk ‘T’ allele of T894G is hypothesized to lead to reduced NOS3 activity; therefore, supplementation with BH4 may provide benefit to those carrying the risk allele with elevated blood pressure or who are at cardiovascular risk.
Vitamin B2 Riboflavin phosphate
Vitamin B2 is a co-factor required by NOS3 to function correctly 8. With the risk ‘T’ allele of T894G proposed to be associated with reduced NOS3 activity, supplementation with vitamin B2 may prove beneficial those with elevated blood pressure or who are at cardiovascular risk.

Vitamin B2 Riboflavin phosphate

Vitamin B2 is a co-factor required by NOS3 to function correctly 8. With the risk ‘T’ allele of T894G proposed to be associated with reduced NOS3 activity, supplementation with vitamin B2 may prove beneficial those with elevated blood pressure or who are at cardiovascular risk.

Iron

Iron is one of three co-factors required by NOS3 in order to function properly 9. Therefore, iron supplementation may benefit those at cardiovascular risk, especially those carrying the risk ‘T’ allele of T894G. However, care should be taken with iron supplementation as excessively dietary iron is associated with increased risk of coronary heart disease 10.

Indirect Nutrients:*

IngredientActive IngredientEffect
Nattō Nattokinase

Nattokinase is an enzyme which is extracted and purified from the Japanese food nattō, which is made from fermented soybeans. Nattokinase, secreted by the bacteria involved in the fermentation process, breaks down fibrin containing blood clots 11. Based on this clot-busting ability a beneficial effect on blood pressure 12, and general cardiovascular health has been described 13. Supplementation may benefit those carrying the risk ‘T’ allele of T894G, especially those with elevated blood pressure or cardiovascular risk.

Ubiquinol Coenzyme Q10

The naturally occurring coenzyme Q10 (CQ10) is associated with numerous health benefits. A positive effect was seen in those with elevated blood pressure 14, however, no effect was seen in healthy controls 15. Therefore, supplementation may only be recommended for those with elevated blood pressure who also carry the risk ‘T’ allele of T894G.

Omega-3 fatty acids

Omega-3 fatty acids demonstrate a protective effect against cardiovascular disease in those with an existing cardiovascular risk 18. In those carrying the risk ‘T’ allele of T894G, dietary supplementation with omega-3 fatty acids was shown to improve cardiovascular risk by reducing triacylglycerol levels in the blood 5.

Nutritional Contraindications:*

IngredientActive IngredientEffect
Sodium

The impacts of a high sodium diet are well established 16. Therefore, in those carrying the risk ‘T’ allele of T894G which is associated with elevated blood pressure, a reduction in sodium intake to recommended levels should be considered.

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

A-52+1009T

Science Grade
B-
Heart Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%)
rs1800783 t a 32

Risk Description

The risk ‘A’ allele of A-52+1009T in the NOS3 gene is associated with increased cardiovascular risk markers and increased risk of high blood pressure 5,6. A mechanism linking the risk ‘A’ allele in either case is not described, but it is possible to hypothesize that the risk ‘A’ allele results in reduced NOS3 activity which in turn leads to a reduction in NO production. With reduced NO production the capacity to lower blood pressure will be reduced.

Direct Nutrients:*

IngredientActive IngredientEffect
Tetrahydrobiopterin

Tetrahydrobiopterin (BH4 or THB) is a co-factor required by NOS3 7. The risk ‘A’ allele of A-52+1009T is hypothesized to lead to reduced NOS3 activity; therefore, supplementation with BH4 may prove beneficial to those carrying the risk allele with elevated blood pressure or with existing cardiovascular risk.

Vitamin B2 Riboflavin phosphate

Vitamin B2 is one of three co-factors required by NOS3 to function properly 8. The risk ‘A’ allele of A-52+1009T is hypothesized to be associated with reduced NOS3 activity. Therefore, supplementation with vitamin B2 may prove beneficial those with elevated blood pressure or who are at cardiovascular risk.

Iron

Iron is a co-factor required by NOS3 in order to function correctly 9. Therefore, iron supplementation may benefit those at cardiovascular risk, especially those carrying the risk ‘A’ allele of A-52+1009T which is associated with elevated blood pressure. However, care should be taken with iron supplementation as excessively dietary iron is associated with increased risk of coronary heart disease 10.

Indirect Nutrients:*

IngredientActive IngredientEffect
Nattō Nattokinase

The Japanese food nattō, which is made from fermented soybeans, is rich in the enzyme nattokinase. Secreted by the bacteria involved in the fermentation process, nattokinase breaks down fibrin containing blood clots 11. Based on this ability a beneficial effect on blood pressure 12, and general cardiovascular health has been described 13. Therefore, supplementation may benefit those carrying the risk ‘A’ allele of A-52+1009T, especially those with elevated blood pressure or cardiovascular risk.

Ubiquinol Coenzyme Q10

Coenzyme Q10 (CQ10), a naturally occurring coenzyme with numerous health benefits, has been shown to have a positive effect in those with elevated blood pressure 14, however, no effect was seen in healthy controls 15. Therefore, supplementation may be recommended to those carrying the risk ‘A’ allele of A-52+1009T, who also display elevated blood pressure.

Nutritional Contraindications:*

IngredientActive IngredientEffect
Sodium

The impacts of a high sodium diet are well established 16. Therefore, in those carrying the risk ‘A’ allele of A-52+1009T which is associated with elevated blood pressure, a reduction in sodium intake to recommended levels should be considered.

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

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