165 | id == 165
165 | category_id == 16
165 | category_order == 13
165 | category_name == Gut Health
165 | category_color == #C47AC0
165 | slug == NOS2-Gut-Inflammation
165 | title == Can This Gene Worsen Gut Inflammation? (NOS2)
165 | meta_description == NOS2 produces nitric oxide to fight diseases, but too much of it may worsen gut inflammation. Learn more about the NOS2 gene her
165 | summary == <p style="text-align:justify"><strong>The NOS2 gene produces nitric oxide (NO), which helps fight infections and cancer. When a NOS2 variant is too active, the excess NO can be transformed into free radicals that damage the body&rsquo;s cells and tissues. This may cause inflammatory conditions, including those of the gut. Read below to learn about the potential effects of your NOS2 variants on gut inflammatory issues.</strong></p>
165 | overall_score_text == Gut Inflammation Score (based on NOS2 gene)
165 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/NOS2--Gut-Inflammation-IBD.jpg
165 | author_id == 12
165 | author_name == Carlos Tello
165 | author_title == PhD
165 | author_order == 55
165 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/CarlosTello.webp
165 | author_intro == <p><strong>Carlos received his PhD and MS from the Universidad de Sevilla.</strong></p>    <p>Carlos spent 9 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 non-academic audiences. He strongly believes that scientific literacy is crucial to maintain a healthy lifestyle and avoid falling for scams.</p>
165 | author_social_media_name == linkedin
165 | author_social_media_icon == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/social-icon/linkedin.png
165 | author_social_order == 1
165 | author_social_link == https://www.linkedin.com/in/carlos-tello-lacal-b946b4a7/
165 | reviewer == None
165 | medical_reviewer_id == 11
165 | medical_reviewer_name == Puya Yazdi
165 | medical_reviewer_title == MD
165 | publish_date == 2020
165 | publish_date == 4
165 | publish_date == 28
165 | avg_rating == 5.0
165 | tags_id == 164
165 | tags_name == Cancer
165 | tags_id == 194
165 | tags_name == Gut Health
165 | tags_id == 308
165 | tags_name == Gut Inflammation
165 | tags_id == 73
165 | tags_name == IBD
165 | tags_id == 24
165 | tags_name == Inflammation
165 | tags_id == 173
165 | tags_name == NO
165 | tags_id == 189
165 | tags_name == NOS2 Gene
165 | tags_id == 39
165 | tags_name == Oxidative Stress
165 | permissions_favorite == False
165 | permissions_rate == False
165 | content_article == <p><em><span style="font-weight: 400;">This article is for informational purposes only. None of the information here should be taken as medical advice. If you suspect you may have any kind of inflammatory condition, seek medical help immediately. </span></em><em><span style="font-weight: 400;">Keep in mind that these results are based on association studies, which are correlative and aren&rsquo;t necessarily causative. In addition, any single genetic variant will typically contribute only a small proportion to the overall risk of the condition, and non-genetic factors play a large role in developing a condition as well. Therefore, just because you have one of these genotypes does not necessarily mean you are at increased risk of developing this condition!</span></em></p> <h2><strong>What Is the <em>NOS2 </em>Gene?</strong></h2> <p><span style="font-weight: 400;">The </span><a href="../article/nos2-longevity-61"><em><span style="font-weight: 400;">NOS2 </span></em><span style="font-weight: 400;">gene</span></a><span style="font-weight: 400;"> codes for a protein also called NOS2, which is short for </span><em><span style="font-weight: 400;">nitric oxide synthase 2</span></em><span style="font-weight: 400;">. NOS2 produces the messenger molecule nitric oxide (NO) from the amino acid </span><a href="http://selfhacked.com/blog/l-arginine/"><span style="font-weight: 400;">arginine</span></a><span style="font-weight: 400;">, just like its two other close relatives (</span><a href="https://www.selfdecode.com/gene/nos1/"><em><span style="font-weight: 400;">NOS1</span></em></a><span style="font-weight: 400;"> and </span><a href="https://www.selfdecode.com/gene/nos3/?utm_source=seo&amp;#38;utm_medium=selfhacked&amp;#38;utm_campaign=id00002"><em><span style="font-weight: 400;">NOS3</span></em></a><span style="font-weight: 400;">) [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/10320659/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">However, </span><em><span style="font-weight: 400;">NOS2</span></em><span style="font-weight: 400;"> is different from the other two in three main aspects [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15172174"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC508408/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">While </span><em><span style="font-weight: 400;">NOS1</span></em><span style="font-weight: 400;"> and </span><em><span style="font-weight: 400;">NOS3</span></em><span style="font-weight: 400;"> production is permanently activated, </span><em><span style="font-weight: 400;">NOS2 </span></em><span style="font-weight: 400;">expression needs to be triggered (hence its alternative name of </span><em><span style="font-weight: 400;">inducible</span></em> <em><span style="font-weight: 400;">nitric oxide synthase</span></em><span style="font-weight: 400;">, or &ldquo;iNOS&rdquo;).</span></li> <li style="font-weight: 400;"><em><span style="font-weight: 400;">NOS2</span></em><span style="font-weight: 400;"> is found in more cell types, including immune, liver, muscle, and lining tissue cells.</span></li> <li style="font-weight: 400;"><em><span style="font-weight: 400;">NOS2</span></em><span style="font-weight: 400;"> produces higher amounts of NO, and for longer periods.</span></li> </ul> <h3><strong>The Importance of NO Balance</strong></h3> <p><span style="font-weight: 400;">At moderate levels, NOS2-derived NO acts as a messenger that promotes inflammation and the development of immune cells. NO also kills invading microbes and cancer cells [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4565017/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320759/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1906415/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">However, excessive or uncontrolled release of NO by NOS2 can have harmful effects. For instance, sustained NO production can cause chronic inflammation and overactivation of </span><a href="https://selfhacked.com/blog/how-to-increase-and-decrease-white-blood-cells/"><span style="font-weight: 400;">white blood cells</span></a><span style="font-weight: 400;"> (</span><a href="https://selfhacked.com/blog/neutrophils/"><span style="font-weight: 400;">neutrophils</span></a><span style="font-weight: 400;">), thus contributing to the progression of inflammatory conditions [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19601787"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1906415/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Furthermore, excessive NO can lead to the build-up of free radicals (such as </span><em><span style="font-weight: 400;">peroxynitrite</span></em><span style="font-weight: 400;"> and </span><em><span style="font-weight: 400;">superoxide</span></em><span style="font-weight: 400;">) that damage the DNA and proteins of cells and tissues. This kills cells and impairs the function of several important enzymes [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19601787"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/11976187"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><strong>Role in the Gut</strong></h3> <p><span style="font-weight: 400;">NOS2 is found in the cells that line the inner surface of the bowels and their blood vessels. When properly regulated, nitric oxide (NO) sustains the correct functioning of the digestive tract by promoting fluid secretion and blood flow, maintaining barrier integrity, and killing infectious bacteria and cancer cells [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/10967157"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1782592/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">However, excessive NOS2 activity can contribute to the onset and progression of conditions such as </span><a href="https://selfhacked.com/blog/ibd-ulcerative-colitis-crohn-genetics-lifestyle-stress-infections/"><span style="font-weight: 400;">IBD </span></a><span style="font-weight: 400;">through the mechanisms previously described. Indeed, multiple studies have found higher NO levels and NOS2 activity in the bowels of people with IBD, especially in the case of </span><a href="https://selfhacked.com/blog/ibd-ulcerative-colitis-crohn-genetics-lifestyle-stress-infections/"><span style="font-weight: 400;">ulcerative colitis</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/8094492/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/7687730/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/7996962/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/8831582/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/8911859/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/10901620/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/9517649"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/9149061"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Similar results were found for other conditions such as pouchitis, diverticulitis, infectious colitis, and indigestion, suggesting that NOS2 overactivation is a feature of gut inflammation in general rather than being specific to IBD [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/11383584"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/8831582/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1727175/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/26586703"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Research in intestinal lining cells suggests that NOS2 production is regulated by T cell-derived cytokines. While </span><a href="../article/tnf-longevity-86"><span style="font-weight: 400;">TNF</span></a><a href="http://selfhacked.com/blog/supplements-lifestyle-factors-influence-tnf-interleukin-6-il-6/"><span style="font-weight: 400;">-alpha</span></a><span style="font-weight: 400;">, </span><a href="http://selfhacked.com/blog/interleukin-1/"><span style="font-weight: 400;">IL-1beta</span></a><span style="font-weight: 400;">, and </span><a href="https://www.selfhacked.com/blog/interferon-gamma-how-to-increase-decrease-high-low-levels/"><span style="font-weight: 400;">IFN-gamma</span></a><span style="font-weight: 400;"> induced it, the anti-inflammatory cytokines </span><a href="https://www.selfdecode.com/gene/il4/?utm_source=seo&amp;#38;utm_medium=selfhacked&amp;#38;utm_campaign=id00002"><span style="font-weight: 400;">IL-4</span></a><span style="font-weight: 400;"> and </span><a href="http://selfhacked.com/blog/interleukin-1/"><span style="font-weight: 400;">IL-1</span></a><a href="http://www.selfdecode.com/gene/IL13/?utm_source=seo&amp;#38;utm_medium=selfhacked&amp;#38;utm_campaign=id00002"><span style="font-weight: 400;">3</span></a><span style="font-weight: 400;"> blocked it [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1909228/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1727175/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;"><em><span style="font-weight: 400;">NOS2</span></em><span style="font-weight: 400;"> encodes a protein that produces nitric oxide (NO). While NO protects from infections and cancer at moderate levels, having too much of it may contribute to inflammatory diseases including those of the gut.&nbsp;</span></span></p> <h2><strong><em>NOS2 </em>Variants and Gut Inflammation</strong></h2> <p><span style="font-weight: 400;">The most widely-studied </span><em><span style="font-weight: 400;">NOS2 </span></em><span style="font-weight: 400;">polymorphism is </span><a href="https://www.selfdecode.com/snp/rs2297518/"><span style="font-weight: 400;">rs2297518</span></a><span style="font-weight: 400;">. Its minor allele &lsquo;A&rsquo; causes the gene to produce a version of the NOS2 protein that is significantly more active. This variant also reduces the expression of arginase, which competes with NOS proteins for the essential amino acid </span><a href="https://selfhacked.com/blog/l-arginine/"><span style="font-weight: 400;">arginine</span></a><span style="font-weight: 400;">. Both mechanisms result in an increased nitric oxide (NO) production [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912315/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17513437/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a study of almost 3,000 children, the &lsquo;A&rsquo; variant of rs2297518 was associated with an increased incidence of IBD (both Crohn&rsquo;s and ulcerative colitis). IBD that can be diagnosed in children is referred to as &lsquo;very early onset IBD&rsquo; and tends to be more aggressive [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912315/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">This variant was also associated with ulcerative colitis in over 1,000 adults, although less strongly. In fact, more recent studies failed to replicate this association [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17955236"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299551/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084597/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491803/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The &lsquo;A&rsquo; allele was found more frequently among those with indigestion (functional dyspepsia) in a study on over 250 people [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24114042"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Another study on over 2,000 people associated the minor variant of this polymorphism with a chronic inflammatory process of the stomach lining (atrophic gastritis) [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/18287876"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Chronic inflammation may develop into cancer in some cases. In line with this, the &lsquo;A&rsquo; variant has also been associated with colon and stomach cancer, especially in people with risk factors such as cigarette smoking, alcohol drinking, and </span><a href="https://selfhacked.com/blog/h-pylori-part-1/"><em><span style="font-weight: 400;">Helicobacter pylori</span></em></a> <span style="font-weight: 400;">infection [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372651/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572295/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447275/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5939909/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The minor allele &lsquo;A&rsquo; at </span><a href="../../snp/rs2779251/"><span style="font-weight: 400;">rs2779251</span></a><span style="font-weight: 400;">, located at the region that controls when and how much the gene is expressed (the promoter), was also associated with ulcerative colitis in the study on over 1,000 adults previously mentioned [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17955236"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;"><span style="font-weight: 400;">A </span><em><span style="font-weight: 400;">NOS2 </span></em><span style="font-weight: 400;">variant with increased NO production has been associated with IBD (especially in young children), indigestion, chronic stomach inflammation, and colon and stomach cancer. Another </span><em><span style="font-weight: 400;">NOS2 </span></em><span style="font-weight: 400;">polymorphism is only associated with ulcerative colitis.</span></span></p> <h2><strong>Your <em>NOS2 </em>Results for Gut Inflammation</strong></h2> <p>*2495896760481437*</p> <p>&nbsp;</p> <h3><strong>SNP Summary and Table</strong></h3> <p><strong>Primary SNP: </strong><strong><em>NOS2 </em></strong><strong>rs2297518</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Normal risk of gut inflammation.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Associated with IBD (especially in children), indigestion, chronic stomach inflammation, and stomach and colon cancer.</span></li> </ul> <p><strong>Other Important SNPs:&nbsp;</strong></p> <p><strong><em>NOS2 </em></strong><strong>rs2779251</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Normal risk of gut inflammation.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Associated with ulcerative colitis.</span></li> </ul> <h3><strong>Population Frequency</strong></h3> <p><span style="font-weight: 400;">The &lsquo;G&rsquo; allele of rs2297518 is clearly more common than &lsquo;A&rsquo; and approximately 70% of the world population carries 'GG'. The 'AA' genotype is relatively rare across all major ethnic groups, with a prevalence of ~1.5% to 3%, depending on the specific group.</span></p> <p><span style="font-weight: 400;">The &lsquo;A&rsquo; allele of rs2779251 is even rarer, with almost 78% of the world population carrying no copies of this variant. The variant is slightly more common in people of European ancestry (36% of carriers).</span></p> <p>*8947330506107001*</p> <p>&nbsp;</p> <h2><strong>Recommendations that May Reduce Gut Inflammation</strong></h2> <p>*5270508258775961*</p> <p>&nbsp;</p> <p><em><span style="font-weight: 400;">You may try the complementary approaches listed below if you and your doctor determine that they could be appropriate for you. Discuss the strategies listed here with your doctor. Remember that none of them should ever be done in place of what your doctor recommends or prescribes.</span></em></p> <h3><strong>Lifestyle</strong></h3> <h4><strong>Giving Up Smoking</strong></h4> <p><span style="font-weight: 400;">Smoking is clearly associated with an increased incidence of Crohn&rsquo;s disease, while its effects on ulcerative colitis are less evident &mdash; this condition seems to be more common among former smokers but </span><em><span style="font-weight: 400;">less </span></em><span style="font-weight: 400;">among people who currently smoke [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17120402"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Smoking is also associated with an increased incidence and severity of stomach and colorectal cancer [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906411/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19088354"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">While avoiding smoking is a good idea for everyone, this may be even more beneficial to people with overactive </span><em><span style="font-weight: 400;">NOS2 </span></em><span style="font-weight: 400;">variants, since cigarette smoke increases </span><em><span style="font-weight: 400;">NOS2 </span></em><span style="font-weight: 400;">production (as seen in isolated lungs and blood vessels). Importantly, the &lsquo;A&rsquo; variant of rs2297518 was associated with an even higher risk of stomach and colon cancer in smokers [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/12379773"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/10462035"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17213480/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572295/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372651/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h4><strong>Avoiding Excess Alcohol</strong></h4> <p><span style="font-weight: 400;">Some studies in rats have reported that chronic alcohol intake may increase </span><em><span style="font-weight: 400;">NOS2 </span></em><span style="font-weight: 400;">production [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/10791926"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/22286266"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In people already diagnosed with IBD, alcohol may worsen the symptoms and increase the risk of infections [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662186/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">Similar to the case of smoking, alcohol further increased the risk of stomach cancer in carriers of the overactive </span><em><span style="font-weight: 400;">NOS2 </span></em><span style="font-weight: 400;">variant of rs2297518 [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572295/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Everyone has a different threshold of alcohol that is healthy for them. If you're experiencing gut inflammation, we recommend cutting alcohol out if you have negative </span><em><span style="font-weight: 400;">NOS2 </span></em><span style="font-weight: 400;">genetic variants.&nbsp;</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Giving up smoking and drinking less alcohol may lower NOS2 activity and contribute to reducing gut inflammation.</span></p> <h3><strong>Diet</strong></h3> <h4><strong>Healthy Fats</strong></h4> <p><a href="http://selfhacked.com/blog/top-22-science-based-health-benefits-of-fish-oil/"><span style="font-weight: 400;">Omega-3</span></a><span style="font-weight: 400;"> fatty acids (such as EPA and </span><a href="http://selfhacked.com/blog/top-22-science-based-health-benefits-of-fish-oil/"><span style="font-weight: 400;">DHA</span></a><span style="font-weight: 400;">) have been reported to reduce the expression of </span><em><span style="font-weight: 400;">NOS2 </span></em><span style="font-weight: 400;">and other inflammatory markers in white blood cells [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820929/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896343/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Similarly, a compound from high-quality </span><a href="https://selfhacked.com/blog/olive-oil/"><span style="font-weight: 400;">olive oil</span></a><span style="font-weight: 400;"> (</span><em><span style="font-weight: 400;">oleocanthal</span></em><span style="font-weight: 400;">) has also reduced </span><em><span style="font-weight: 400;">NOS2 </span></em><span style="font-weight: 400;">and NO production in response to inflammation in cartilage cells [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/20201078"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/30261513"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/23044226"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Although their quality was often insufficient, several studies have associated dietary omega-3 fatty acids and olive oil with a reduced incidence of IBD, as well as improvements in its symptoms [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801729/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/32295122"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h4><strong>Antioxidant Vitamins</strong></h4> <p><span style="font-weight: 400;">Across a large number of studies, many different researchers have concluded that the negative effects of high NO levels may stem from its ability to produce free radicals. Therefore, eating sufficient amounts of antioxidant vitamins may prevent the harmful effects of NO-overproducing </span><em><span style="font-weight: 400;">NOS2 </span></em><span style="font-weight: 400;">variants [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341248/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">For instance, one study concluded that a diet rich in </span><a href="http://selfhacked.com/blog/importance-real-vitamin-retinol/"><span style="font-weight: 400;">vitamin A</span></a><span style="font-weight: 400;"> was associated with lower rates of colorectal cancer in people with the &lsquo;A&rsquo; allele of rs2297518 [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372651/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In another study on 10 people infected with the ulcer-causing microbe </span><em><span style="font-weight: 400;">Helicobacter pylori </span></em><span style="font-weight: 400;">and taking aspirin, supplementation with </span><a href="http://selfhacked.com/blog/need-know-vitamin-c-32-science-based-health-benefits/"><span style="font-weight: 400;">vitamin C</span></a><span style="font-weight: 400;"> reduced NOS2 levels and prevented damage to the stomach lining [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15588738"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In rats given toxic doses of a drug (methotrexate), pretreatment with </span><a href="https://selfhacked.com/blog/vitamin-e-can-help-fertility-pregnancy/"><span style="font-weight: 400;">vitamin E</span></a><span style="font-weight: 400;"> blocked NOS2 activation in the bowel and prevented </span><a href="https://selfhacked.com/blog/oxidative-stress-101/"><span style="font-weight: 400;">oxidative stress</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/27386629"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h4><strong>Dietary Polyphenols</strong></h4> <p><span style="font-weight: 400;">People with overactive </span><em><span style="font-weight: 400;">NOS2 </span></em><span style="font-weight: 400;">variants may also benefit from incorporating more polyphenol-containing foods into their diet. For example, one study reported that, for people with the &lsquo;A&rsquo; allele of rs2297518, eating sufficient </span><a href="https://selfhacked.com/blog/23-longevity-boosting-supplements-drugs-increase-lifespan/#18_Lutein"><span style="font-weight: 400;">lutein</span></a><span style="font-weight: 400;"> (mainly found in green leafy vegetables) was associated with lower rates of colorectal cancer [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372651/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Other food polyphenols that may reduce NOS2 activity and inflammatory or oxidative damage to the gut include:</span></p> <ul> <li style="font-weight: 400;"><a href="https://selfhacked.com/blog/top-15-scientific-health-benefits-of-resveratrol-with-references/"><span style="font-weight: 400;">Resveratrol</span></a><span style="font-weight: 400;"> (in grapes, </span><a href="https://selfhacked.com/blog/blueberries-health-benefits/"><span style="font-weight: 400;">blueberries</span></a><span style="font-weight: 400;">, peanuts, pistachios, and dark </span><a href="https://selfhacked.com/blog/chocolate-health-benefits/"><span style="font-weight: 400;">chocolate</span></a><span style="font-weight: 400;">) [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/20155626"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17923197"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> <li style="font-weight: 400;"><a href="https://www.selfhacked.com/blog/green-tea/"><span style="font-weight: 400;">Epigallocatechin gallate</span></a><span style="font-weight: 400;"> (mainly in </span><a href="http://selfhacked.com/blog/green-tea/"><span style="font-weight: 400;">green tea</span></a><span style="font-weight: 400;">) [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/21779572"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> <li style="font-weight: 400;"><a href="https://www.selfhacked.com/blog/quercetin-22-scientifically-proven-benefits-quercetin/"><span style="font-weight: 400;">Quercetin</span></a><span style="font-weight: 400;"> (in leafy vegetables, broccoli, apples, peppers, tea, and fruit juices) [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/22257724"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1575937/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> <li style="font-weight: 400;"><a href="https://www.selfhacked.com/blog/rutin/"><span style="font-weight: 400;">Rutin</span></a><span style="font-weight: 400;"> (in oranges, buckwheat, apricots, cherries, grapes, and plums) [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/21617331"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> </ul> <p><span style="font-weight: 400;">These polyphenols are also available as supplements. If you don&rsquo;t like their food sources or are intolerant to them, you can consider taking them this way.&nbsp;</span></p> <p><span style="font-weight: 400;">However, keep in mind that their effects on NOS2 function have only been tested in animals and cells &mdash; and more research will be needed to know for sure if they have similar effects in humans as well.</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;"><span style="font-weight: 400;">A number of promising studies suggest that diets rich in healthy fats, antioxidant vitamins, and polyphenols may help reduce gut inflammation in people with overactive </span><em><span style="font-weight: 400;">NOS2 </span></em><span style="font-weight: 400;">variants. However, most studies were done in animals and cells. Further clinical research is required.</span></span></p> <h3><strong>Supplements</strong></h3> <h4><strong>Probiotics</strong></h4> <p><a href="https://selfhacked.com/blog/probiotics-good-bacteria/"><span style="font-weight: 400;">Probiotics</span></a><span style="font-weight: 400;"> with different species of </span><em><span style="font-weight: 400;">Lactobacillus </span></em><span style="font-weight: 400;">(</span><a href="https://selfhacked.com/blog/health-benefits-l-plantarum/"><em><span style="font-weight: 400;">L. plantarum</span></em></a><span style="font-weight: 400;">, </span><a href="http://selfhacked.com/blog/l-acidophilus/"><em><span style="font-weight: 400;">L. acidophilus</span></em></a><span style="font-weight: 400;">, </span><a href="http://selfhacked.com/blog/l-casei/"><em><span style="font-weight: 400;">L. casei</span></em></a><em><span style="font-weight: 400;">, </span></em><span style="font-weight: 400;">and </span><a href="http://selfhacked.com/blog/l-delbrueckii/"><em><span style="font-weight: 400;">L. delbrueckii</span></em></a><span style="font-weight: 400;">) and </span><em><span style="font-weight: 400;">Bifidobacterium </span></em><span style="font-weight: 400;">(</span><a href="http://selfhacked.com/blog/b-longum/"><em><span style="font-weight: 400;">B. longum</span></em></a><span style="font-weight: 400;">, </span><a href="http://selfhacked.com/blog/b-animalis/"><em><span style="font-weight: 400;">B. animalis</span></em></a><span style="font-weight: 400;">, and </span><a href="http://selfhacked.com/blog/b-breve/"><em><span style="font-weight: 400;">B. breve</span></em></a><span style="font-weight: 400;">) improved gut inflammation and reduced NOS2 activity in multiple animal studies [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/25536541"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/30221762"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/29876980"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/22941198"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/25572742"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/23271629"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In clinical trials, these probiotics restored the </span><a href="https://www.selfhacked.com/blog/gut-bacteria-microbiome/"><span style="font-weight: 400;">gut flora</span></a><span style="font-weight: 400;"> and improved digestive conditions such as diarrhea, constipation, </span><a href="https://selfhacked.com/blog/h-pylori-part-1/"><em><span style="font-weight: 400;">H. pylori</span></em></a><span style="font-weight: 400;"> infection, IBS, ulcerative colitis, and gut discomfort [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/9815476"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/14964345"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229551/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3222668/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4475728/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19367213"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/26418574"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877827/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15076628"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4657032/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15269618"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048518/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Alternatively, some scientists have hypothesized that people with IBD may have alterations in their </span><a href="https://www.selfhacked.com/blog/gut-bacteria-microbiome/"><span style="font-weight: 400;">gut bacteria</span></a><span style="font-weight: 400;"> that result in lower production of </span><a href="http://selfhacked.com/blog/health-benefits-butyrate-derivatives-sodium-butyrate-phenylbutyrate-trybutyrine-butyric-acid-butyrate-prodrugs-butyrate-producing-bacteria/"><em><span style="font-weight: 400;">butyrate</span></em></a><span style="font-weight: 400;">. Butyrate is a short-chain fatty acid shown to lower NOS2 activity and oxidative stress in rats and cells. However, no clinical evidence supports its use in humans with IBD [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/31498864"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/25774002"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/11825662"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/27261536"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h4><strong>Whey Protein</strong></h4> <p><span style="font-weight: 400;">In mice and rats with IBD, </span><a href="https://selfhacked.com/blog/whey-protein-health-benefits/"><span style="font-weight: 400;">whey protein</span></a><span style="font-weight: 400;"> reduced intestinal inflammation by reducing the levels of NOS2-derived NO and several inflammatory cytokines [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5619769/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/20338413"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Whey protein also reduced gut inflammation and damage to the intestinal lining by increasing both antioxidant defenses and good bacteria in 30 patients with Crohn&rsquo;s disease [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/22038507"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h4><strong>Curcumin</strong></h4> <p><a href="https://selfhacked.com/blog/curcumin-cures-top-15-scientifically-proven-health-benefits-with-references/"><span style="font-weight: 400;">Curcumin</span></a><span style="font-weight: 400;"> is an antioxidant compound naturally found in turmeric. Dietary curcumin reduced gut inflammation and NOS2 production in mice with IBD and inflammation-induced colorectal cancer [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/27233000"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/20848615"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a small trial on 14 people with mild to moderate ulcerative colitis, curcumin enhanced the effectiveness of the anti-inflammatory drug mesalamine [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/25724700"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Different probiotics may improve gut inflammation in part by reducing NOS2 activity. Among them, probiotics are most promising. Preliminary research suggests that whey protein and curcumin may help too, but more clinical research is needed.</span></p>
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165 | content_learn_more_2495896760481437_text == Based on the variants we looked at, your NOS2 gene variants are associated with gut inflammation. However, this doesn't necessarily reflect your overall risk of developing this condition — just one gene related to it! Changes in your lifestyle and diet/supplements may help you rebalance your immune system — keep scrolling to find out more.
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rsIDs = rs2297518,rs2779251
rsStatus = rs2297518,NOS2,chr17,27769571,G,A,,,40,0,Normal
rsStatus = rs2779251,,chr17,27804300,G,A,,,29,0,Normal
