285 | id == 285
285 | category_id == 19
285 | category_order == 16
285 | category_name == Pain
285 | category_color == #C47AC0
285 | slug == HTR2C-serotonin-migraine
285 | title == Serotonin Genetics in Migraine Development (HTR2C)
285 | meta_description == The HTR2C gene plays crucial roles in mental health and pain control. Click to learn about its role in migraine development.
285 | summary == <p style="text-align:justify"><strong>Serotonin makes us happy, but can it trigger migraines? The <em>HTR2C</em> gene encodes a serotonin receptor with crucial roles in mental health, weight, and pain control &mdash; read on to learn about its role in migraine development.</strong></p>
285 | overall_score_text == Your Migraine Score (Based on HTR2C Gene)
285 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/HTR2C--Pain-Headaches-Migraine.jpg
285 | author_id == 9
285 | author_name == Aleksa Ristic
285 | author_title == MS (Pharmacy)
285 | author_order == 45
285 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/Aleksa.jpg
285 | author_intro == <p><strong>Aleksa received his MS in Pharmacy from the University of Belgrade, his master thesis focusing on protein sources in plant-based diets.</strong>&nbsp;&nbsp;</p>    <p>Aleksa is passionate about herbal pharmacy, nutrition, and functional medicine. He found a way to merge his two biggest passions&mdash;writing and health&mdash;and use them for noble purposes. His mission is to bridge the gap between science and everyday life, helping readers improve their health and feel better.</p>
285 | reviewer_id == 14
285 | reviewer_name == Shany Lahan
285 | reviewer_title == MS (Neuroscience)
285 | medical_reviewer_id == 11
285 | medical_reviewer_name == Puya Yazdi
285 | medical_reviewer_title == MD
285 | publish_date == 2020
285 | publish_date == 8
285 | publish_date == 25
285 | avg_rating == 5.0
285 | tags_id == 372
285 | tags_name == Blood vessels
285 | tags_id == 478
285 | tags_name == HTR2C Gene
285 | tags_id == 92
285 | tags_name == Magnesium
285 | tags_id == 31
285 | tags_name == Migraine
285 | tags_id == 71
285 | tags_name == Pain
285 | permissions_favorite == False
285 | permissions_rate == False
285 | content_article == <p><em><span style="font-weight: 400;">If you have persistent or unexplained pain, it is important to discuss these concerns with your doctor. The information in this post is presented for educational purposes only, and should not be used to replace standard medical care.</span></em></p> <h2><strong>The <em>HTR2C</em> Gene in Serotonin Functions</strong></h2> <p><a href="https://www.selfhacked.com/blog/how-to-increase-serotonin"><span style="font-weight: 400;">Serotonin</span></a><span style="font-weight: 400;"> is a crucial signaling molecule found throughout the brain and body. It is commonly known as the &ldquo;happiness neurotransmitter&rdquo; or the &ldquo;happiness hormone&rdquo; due to its prominent role in regulating </span><a href="https://get.selfdecode.com/nm/mood/"><span style="font-weight: 400;">mood</span></a><span style="font-weight: 400;"> and behavior [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921409/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864293/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The </span><a href="../../../gene/htr2c/"><em><span style="font-weight: 400;">HTR2C</span></em></a><span style="font-weight: 400;"> gene encodes a serotonin receptor, </span><a href="http://selfhacked.com/blog/5-ht2c/"><span style="font-weight: 400;">5-HT2C</span></a><span style="font-weight: 400;">, present mostly in the brain. Changes in this receptor&rsquo;s activity play a role in [</span><a href="https://www.ncbi.nlm.nih.gov/gene/3358"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/16785265/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5873585/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/18656400/"><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;">Mental health</span></li> <li style="font-weight: 400;"><a href="../../article/htr2c-weight-207/"><span style="font-weight: 400;">Weight</span></a><span style="font-weight: 400;"> and metabolism</span></li> <li style="font-weight: 400;"><a href="https://selfhacked.com/blog/pain-management/"><span style="font-weight: 400;">Pain management</span></a></li> </ul> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">The serotonin receptor encoded by the <em>HTR2C</em> gene plays crucial roles in mental health, metabolism, and pain control.</span></p> <h3><strong>Roles in Pain Control &amp; Migraine</strong></h3> <p><span style="font-weight: 400;">Impairments in serotonin signaling are among the culprits behind migraine development. According to most studies, people with migraines have lower serotonin levels during attack-free periods and higher levels during migraine attacks [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17970989/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/2475821/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Sudden changes in serotonin levels impact </span><a href="https://selfhacked.com/blog/15-ways-improve-brain-circulation/"><span style="font-weight: 400;">brain circulation</span></a><span style="font-weight: 400;">, which may trigger attacks [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117050/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The effects of serotonin also depend on the type of receptors being activated: activation of first-class receptors (</span><a href="http://selfhacked.com/blog/rs6295-the-single-and-self-transcendent-gene-5-ht1a-receptor/"><span style="font-weight: 400;">5-HT1A</span></a><span style="font-weight: 400;"> and 5-HT1B) generally relieves pain, while activation of the second class (</span><a href="http://selfhacked.com/blog/5ht2a-receptors-a-root-cause-of-anxiety-fatigue-sleep-problems-and-cirs/"><span style="font-weight: 400;">5-HT2A</span></a><span style="font-weight: 400;"> and 5-HT2C) may induce pain [</span><a href="https://link.springer.com/article/10.1134/S1819712411020085"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/18656400/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Based on the above findings, scientists have developed 5-HT2C inhibitors (such as pizotifen and methysergide) for migraine prevention [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3451809/"><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;">Serotonin controls brain blood flow and pain perception. Activation of 5-HT2C receptors may trigger migraine attacks.</span></p> <p>&nbsp;</p> <h2><strong>The Link Between <em>HTR2C</em> Variants and Migraine</strong></h2> <p><span style="font-weight: 400;">Earlier genetic studies found no link between the SNPs in the </span><em><span style="font-weight: 400;">HTR2C</span></em><span style="font-weight: 400;"> gene and migraine development [</span><a href="https://pubmed.ncbi.nlm.nih.gov/12555241/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19455600/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">However, a 2016 study of 274 Turkish subjects identified a significant effect of one variant: </span><a href="../../../snp/rs3813929/"><span style="font-weight: 400;">rs3813929</span></a><span style="font-weight: 400;">. People carrying the &ldquo;T&rdquo; allele had 53% higher rates of migraine [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977812/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Another SNP, </span><a href="../../../snp/rs6318/"><span style="font-weight: 400;">rs6318</span></a><span style="font-weight: 400;">, may change the activity of 5-HT2C receptors and influence pain perception [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/14699441/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]. In a small trial of 34 people with nerve pain, those with the &ldquo;C&rdquo; allele had 15x higher odds of a positive response to drug treatment [</span><a href="https://pubmed.ncbi.nlm.nih.gov/21614492/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">One Japanese study found a link between this variant and migraine [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15147464/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">], but other papers and one meta-analysis failed to confirm the association [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977812/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19455600/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17901921/"><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;">One <em>HTR2C</em> variant, rs3813929, may correlate with higher rates of migraine.</span></p> <h3><strong>How It Works</strong></h3> <p><span style="font-weight: 400;">A detailed analysis has revealed that rs3813929-T may increase </span><em><span style="font-weight: 400;">HTR2C</span></em><span style="font-weight: 400;"> gene expression, leading to a higher density of 5-HT2C receptors [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/10768099/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">As mentioned, activation of these receptors can contribute to migraine attacks due to brain blood flow changes. Additionally, 5-HT2C activation may inhibit </span><a href="https://selfhacked.com/blog/dopamine/"><span style="font-weight: 400;">dopamine</span></a><span style="font-weight: 400;"> and </span><a href="https://selfhacked.com/blog/norepinephrine-stress-hormone/"><span style="font-weight: 400;">norepinephrine</span></a><span style="font-weight: 400;"> &mdash; neurotransmitters that also play a role in migraine [</span><a href="https://pubmed.ncbi.nlm.nih.gov/15668911"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The </span><em><span style="font-weight: 400;">HTR2C</span></em><span style="font-weight: 400;"> gene is on the X chromosome. </span><strong>Men have only one X chromosome, so their genotypes contain only one allele</strong><span style="font-weight: 400;">. For this reason, </span><em><span style="font-weight: 400;">HTR2C </span></em><span style="font-weight: 400;">variants may affect men and women differently, but that doesn&rsquo;t seem to be the case for migraine.</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">The &ldquo;T&rdquo; allele at rs3813929 may increase <em>HTR2C</em> gene expression, leading to a higher density of migraine-triggering 5-HT2C receptors.</span></p> <p>&nbsp;</p> <h2><strong>Your <em>HTR2C</em> Results for Migraine</strong></h2> <p>*2238593094395247*</p> <h3><strong>SNP Summary</strong></h3> <p><strong>Primary SNP:</strong></p> <p><strong><em>HTR2C</em></strong> <a href="../../../snp/rs3813929/"><strong>rs3813929</strong></a></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = not associated with migraine</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = associated with higher rates of migraine</span></li> </ul> <p><em><span style="font-weight: 400;">Population Frequency</span></em><span style="font-weight: 400;">: Around 23% of European descendants carry the migraine-associated &ldquo;T&rdquo; allele. It&rsquo;s slightly less common in the general population (19%).&nbsp;</span></p> <p>*2003015529192218*</p> <p>&nbsp;</p> <h2><strong>Recommendations to Prevent Migraine</strong></h2> <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. Remember that none of them should be done in place of what your doctor recommends or prescribes.</span></em></p> <p>*5642258229072231*</p> <h3><strong>Lifestyle</strong></h3> <h4><strong>Relaxation &amp; Massage</strong></h4> <p><a href="https://selfhacked.com/blog/63-factors-raising-stress-cortisol-level-backed-science/"><span style="font-weight: 400;">Stress</span></a><span style="font-weight: 400;"> is one of the most common migraine triggers [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764678/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/30291562/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]. It may be particularly harmful to people with the </span><em><span style="font-weight: 400;">HTR2C </span></em><span style="font-weight: 400;">variant, given its potential to activate 5-HT2C serotonin receptors [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520838/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/27211696/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">According to a meta-analysis of seven studies, massage may be as effective as conventional drugs for migraine prevention. However, the authors warned that the quality of the studies was low. Massage seems to help by reducing psychological stress [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3072494/"><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;">People with rs3813929-T should do their best to avoid psychological stress and practice massage and other relaxation techniques.</span></p> <h4><strong>Acupuncture</strong></h4> <p><a href="https://selfhacked.com/blog/acupuncture-benefits-mechanisms-risks/"><span style="font-weight: 400;">Acupuncture</span></a><span style="font-weight: 400;"> is an alternative treatment approach with promising results in pain management. According to a review of 37 studies, the painkilling properties of acupuncture partly stem from its effects on serotonin receptors, including 5-HT2C [</span><a href="https://www.sciencedirect.com/science/article/abs/pii/S187638201630124X"><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 401 patients with chronic headache, mostly migraines, acupuncture provided significant pain relief and improved the quality of life [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC381326/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">A 2016 meta-analysis proclaimed acupuncture to be effective at reducing migraine frequency. It has shown a slightly higher efficacy and better safety profile compared to drug treatment [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977344/"><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;">Acupuncture may help reduce pain by balancing serotonin levels. According to current evidence, it may be a safer alternative to drugs for migraine prevention.</span></p> <h3><strong>Supplements</strong></h3> <h4><strong>Magnesium</strong></h4> <p><a href="http://selfhacked.com/blog/21-proven-science-based-reasons-magnesium-amazing-including-drawbacks/"><span style="font-weight: 400;">Magnesium</span></a><span style="font-weight: 400;"> deficiency can impair serotonin signaling and blood flow in the brain, potentially contributing to migraines [</span><a href="https://pubmed.ncbi.nlm.nih.gov/31691193/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/21352223/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">People with migraines and other pain disorders are often deficient in magnesium and may thus benefit from supplementation [</span><a href="https://pubmed.ncbi.nlm.nih.gov/22271372/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/22426836/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">According to a review of clinical trials, magnesium supplementation is possibly effective for migraine prevention. The review authors suggested high-dose magnesium citrate (600 mg) to be the most effective [</span><a href="https://pubmed.ncbi.nlm.nih.gov/29131326/"><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;">Magnesium deficiency may worsen the impact of <em>HTR2C </em>variants and trigger migraines. High-dose magnesium supplementation is possibly effective for migraine prevention.</span></p> <h4><strong>Feverfew</strong></h4> <p><span style="font-weight: 400;">Sometimes called medieval aspirin, </span><a href="https://selfhacked.com/blog/feverfew-benefits/"><span style="font-weight: 400;">feverfew</span></a><span style="font-weight: 400;"> has been traditionally used for fever, rheumatism, arthritis, toothache, psoriasis, headaches, nausea, migraine, and more [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/23875764"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">An active compound in feverfew reduces serotonin release and blocks serotonin receptors, which may be beneficial during a migraine attack -- especially for people with rs3813929-T [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/2860288"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/11603284"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In three clinical trials of almost 400 people, feverfew extract reduced the number and severity of migraine attacks [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/12230594"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16232154"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/2899663"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]. In other studies, it has shown promising results in combination with:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">Acupuncture [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/22961605"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> <li style="font-weight: 400;"><a href="https://selfhacked.com/blog/scientifically-proven-health-benefits-of-ginger/"><span style="font-weight: 400;">Ginger</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/21631494"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16127373"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Willow extract [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17163262"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> </ul> <p><span style="font-weight: 400;">However, feverfew extract did not improve migraine symptoms or prevent attacks in two trials of 50 subjects each [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/23195074"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15447697"><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;">Feverfew extract may balance serotonin levels and help reduce the number and severity of migraine attacks. Some studies failed to confirm its effectiveness.</span></p> <h4><strong>Curcumin + Fish Oil</strong></h4> <p><span style="font-weight: 400;">According to limited animal research, </span><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;"> and omega-3 fatty acids from </span><a href="https://selfhacked.com/blog/top-22-science-based-health-benefits-of-fish-oil/"><span style="font-weight: 400;">fish oil</span></a><span style="font-weight: 400;"> may reduce the activity of 5-HT2C receptors [</span><a href="https://pubmed.ncbi.nlm.nih.gov/20526668/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/17942093/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Interestingly, a combination of these two significantly reduced the frequency and severity of migraine attacks in a trial of 74 patients [</span><a href="https://pubmed.ncbi.nlm.nih.gov/30760195/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]. A combination of curcumin with </span><a href="https://selfhacked.com/blog/coenzyme-q10-benefits/"><span style="font-weight: 400;">coenzyme Q10</span></a><span style="font-weight: 400;"> helped prevent migraines in 100 young adults [</span><a href="https://pubmed.ncbi.nlm.nih.gov/31241007/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Despite the promising results, stronger clinical evidence is needed to support the effectiveness of curcumin and fish oil for migraine prevention.</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">A combination of curcumin and fish oil may reduce the activity of 5-HT2C receptors and help prevent migraine, but the evidence is scarce.</span></p>
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rsIDs = rs6295,rs3813929,rs6318
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