nutrition

NOS3

Can This Gene Influence Your Response to Unsaturated Fats (NOS3)?

Written by Carlos Tello, PhD on July 29th, 2020

The NOS3 gene produces nitric oxide (NO), a key messenger molecule that protects blood vessel function. A variant of this gene increases the risk of heart disease but improves the metabolic response to unsaturated fatty acids. Read on to learn where your NOS3 gene stands.

What Is the NOS3 Gene?

The NOS3 gene codes for a protein called NOS3, short for nitric oxide synthase 3. NOS3 is most abundant in the inner lining of the blood vessels, where it produces nitric oxide (NO) from the amino acid arginine [R, R].

NO is a molecule with multiple functions in the immune and nervous systems. Importantly, NOS3-derived NO lowers the risk of heart disease by increasing blood flow [R, R].

The NOS3 gene is responsible for producing NO. This molecule acts as a messenger in several processes and reduces the risk of heart disease.

Dietary Fats and NOS3 Activity

In addition to improving blood fat profile, unsaturated fats may reduce the risk of heart disease through their interaction with NOS3.

Studies in rats showed that omega-3 fatty acids (DHA & EPA) activate NOS3 and increase NO availability in the blood vessels [R, R, R].

A study in mice found that dietary monounsaturated fatty acid (MUFA), found in olive oil, increases NOS3 activity in red blood cells, — and saturated fats reduce it [R, R].

Unsaturated fats with omega-3 and MUFAs prevent heart disease by improving blood fat profile and increasing NOS3 activity.

Your NOS3 Results for Diet

SNP Summary and Table

Primary SNP: NOS3 rs1799983

‘G’ = Normal response to unsaturated fats
‘T’ = Increased improvement in blood fat profile and vessel function in response to unsaturated fats
Almost 70% of the world population has ‘GG’
In people with European ancestry, the frequency of the ‘T’ allele is increased to 34%

SNP Table

variant	genotype	frequency	risk allele
rs1799983

Interaction of NOS3 Variants with Dietary Fats

Among the different NOS3 polymorphisms, rs179983 has been most widely studied. Its minor ‘T’ variant produces a protein that can’t reach activation sites in cell membranes, ultimately decreasing NO production [R].

This variant has been associated with a higher risk of different heart conditions, possibly because it increases blood pressure, vessel stiffness, and cholesterol [R, R, R, R, R, R, R].

The silver lining is that it provides more room for improvement. For instance, the positive effects of heart-healthy unsaturated fatty acids are generally stronger in carriers of the ‘T’ allele.

Response to Omega-3 Fatty Acids

In an Irish trial of metabolic syndrome patients, carriers of the ‘T’ variant had higher baseline blood triglyceride levels but could lower them more effectively by taking omega-3 supplements [R].

Similarly, supplementation with omega-3 fatty acids (from both fish and flaxseed oil) was more effective at lowering blood triglycerides and cholesterol in Chinese diabetics with the ‘T’ variant [R].

In a British study, high blood levels of omega-3 fatty acids from fish oil were associated with improved blood vessel function in carriers of the risk ‘T’ variant. A clinical trial replicated this result, but only in women [R, R].

However, two British trials on people with moderate risk of heart disease found fish oil beneficial in terms of blood vessel function and blood pressure regardless of the NOS3 genotype [R, R].

Response to MUFA

In a Spanish study, people with two copies of the ‘T’ variant had the highest baseline blood pressure. Possibly because the ‘T’ allele results in an underactive NOS3 protein, this genotype was insensitive to the effects of both olive oil — which lowered blood pressure in carriers of the ‘G’ variant — and saturated fats — which increased it [R].

However, carriers of this genotype saw the highest benefits from dietary virgin olive oil in terms of increased NO levels and improved blood vessel function in another Spanish study. The authors believed that the antioxidant polyphenols found in the oil were responsible for this effect [R].

A NOS3 variant resulting in reduced NO production is associated with heart disease but carriers especially benefit from dietary omega-3 fatty acids and virgin olive oil.

Recommendations

Diet

Unsaturated Fats

As has been previously discussed, carriers of the risk ‘T’ variant may especially benefit from omega-3 fatty acids to not only improve their blood fat profile but also reduce their risk of heart disease [R, R, R, R].

In the case of olive oil, only polyphenol-rich virgin oil seems to improve blood vessel function in people with this variant [R, R].

Given the well-known health benefits of these fats, we recommend that you include them in your diet and replace saturated fats with them as much as possible — even if you carry the ‘G’ variant!

Foods Rich in NO Precursors

Watermelon is very rich in the non-essential amino acid citrulline, which the body can use to make NO’s precursor arginine. Other citrulline sources include melons, pumpkins, and cucumbers. More directly, arginine-rich foods include chickpeas, peanuts, soybeans, lentils, turkey, and pork loin [R, R, R].

Similarly, foods that contain nitrates can potentially increase NO. Vegetables are rich in nitrates and roughly supply 80% of these compounds [R].

Beetroot is the most famous nitrate-rich food. Some other foods rich in nitrates include [R]:

Leafy greens
Celery
Broccoli
Chinese cabbage
Turnips
Cucumbers
Carrots
Cauliflower
Pomegranate juice

Plant Antioxidants

One of the mechanisms by which antioxidants reduce the generation of free radicals is by increasing NOS3 production. People with underactive NOS3 variants may benefit from including the following antioxidants in their diets [R, R]:

Resveratrol (found in grapes, blueberries, peanuts, pistachios, and dark chocolate)
Epigallocatechin gallate (mainly in green tea)
Genistein (in soybeans, broad beans, and lupins)
Chlorogenic acid (in coffee and tea)
Quercetin (in leafy vegetables, broccoli, apples, peppers, tea, and fruit juices)
Kaempferol (in apples, grapes, tomatoes, green tea, and potatoes)
Rutin (in oranges, buckwheat, apricots, cherries, grapes, and plums)

Vitamin C

Vitamin C reduces oxidative damage to the tissues (including the blood vessels) by breaking down free radicals. Importantly, it activates the production of NOS3-derived NO [R, R, R].

You can increase your daily intake of this vitamin by including natural sources such as bell peppers, kiwis, strawberries, oranges, broccoli, and tomatoes in your diet or by taking supplements.

Iron

Iron is required for NOS3 to function. Because excessive doses may increase the risk of coronary artery disease, it’s preferable to obtain it from iron-rich foods such as shellfish, liver, sardines, lentils, and spinaches than from supplements [R, R].

Foods rich in omega-3, monounsaturated fatty acids, antioxidants, vitamin C, and iron can increase NOS3 activity.

Lifestyle

Quitting Smoking

Cigarette smoke reduces arginine availability, which is needed for NOS3 to produce nitric oxide [R].

In carriers of the ‘T’ variant at rs1799983, smoking further reduces NO production and dramatically increases the risk of heart disease [R, R].

Avoiding Pollution

Environmental pollutants reduce both NOS3 production and NO release. People with the ‘T’ variant of rs1799983 should be especially cautious with their exposure to pollution, since they have an increased risk of developing ischemic heart disease from it [R, R].

Exercise

Moderate exercise has multiple health benefits. Interestingly, it lowers blood pressure by stimulating NOS3. Exercise is effective even in people who carry underactive NOS3 variants such as the ‘T’ allele of rs1799983 [R, R].

Research shows that giving up smoking, reducing exposure to pollution, and engaging in moderate exercise can significantly improve NOS3 function.

Supplements

Methylfolate

Tetrahydrobiopterin (BH4 ) is essential for NOS3 function. In a few studies, middle-aged and elderly people who took BH4 supplements had improved vasodilation and circulation, which the authors attributed to NOS3-derived NO. Supplements increasing BH4 availability, such as methylfolate and vitamin C, are promising subjects for additional research [R, R, R].

Supplements increasing the levels or availability of the molecules required by NOS3 to function, such as methylfolate, may increase NOS3 activity.

Carlos Tello

PhD

Carlos received his PhD and MS from the Universidad de Sevilla.

Carlos spent 8 years in the laboratory investigating mineral transport in plants. He then started working as a freelancer, mainly in science writing, editing, and consulting. Carlos is passionate about learning the mechanisms behind biological processes and communicating science to both academic and lay audiences. He strongly believes that scientific literacy is crucial to maintaining a healthy lifestyle and avoiding falling for scams.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

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Content

What Is the NOS3 Gene? Your NOS3 Results for Diet Interaction of NOS3 Variants with Dietary Fats

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