458 | id == 458
458 | category_id == 27
458 | category_order == 24
458 | category_name == Fatigue
458 | category_color == #C47AC0
458 | slug == TPH2-fatigue
458 | title == Dysregulated Sleep-Wake Cycles & Fatigue (TPH2)
458 | meta_description == TPH2 helps regulate sleep-wake cycles. A variant of TPH2 has been associated with elevated fatigue. Read more here.
458 | summary == <p style="text-align:justify"><strong>The <em>TPH2</em> gene codes for tryptophan hydroxylase 2, an enzyme that helps regulate sleep-wake cycles. How might a variant of <em>TPH2</em> elevate levels of fatigue? Read more to find out.&nbsp;</strong></p>
458 | overall_score_text == Your Fatigue Score (based on TPH2 gene)
458 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/TPH2-Fatigue.jpg
458 | author_id == 14
458 | author_name == Shany Lahan
458 | author_title == MS (Neuroscience)
458 | author_order == 5
458 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/Shany.webp
458 | author_intro == <p>Shany received her MSc in Neuroscience from Western University.</p>    <p>Prior to joining SelfDecode, Shany conducted research related to Alzheimer&rsquo;s disease, and taught science to undergraduate students. She believes that research should be accessible to everyone, regardless of scientific background. Shany joined SelfDecode&nbsp;with a mission to help others optimize their health and wellbeing &ndash; as well as help them understand the science behind it all.</p>
458 | reviewer == None
458 | medical_reviewer_id == 11
458 | medical_reviewer_name == Puya Yazdi
458 | medical_reviewer_title == MD
458 | publish_date == 2020
458 | publish_date == 11
458 | publish_date == 4
458 | avg_rating == 5.0
458 | tags_id == 907
458 | tags_name == Circadian Rhythms
458 | tags_id == 909
458 | tags_name == Raphe Nuclei
458 | tags_id == 309
458 | tags_name == Serotonin
458 | tags_id == 906
458 | tags_name == Sleep-Wake Cycle
458 | tags_id == 693
458 | tags_name == TPH2 gene
458 | tags_id == 905
458 | tags_name == Tryptophan Hydroxylase
458 | permissions_favorite == False
458 | permissions_rate == False
458 | content_article == <h2 style="text-align: justify;"><strong>Summary</strong></h2> <p style="text-align: justify;"><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;"><em><span style="font-weight: 400;">TPH2 </span></em><span style="font-weight: 400;">codes for tryptophan hydroxylase 2, an enzyme involved in the synthesis of the chemical messenger serotonin. Among its many roles, serotonin helps regulate sleep-wake cycles. A variant of </span><em><span style="font-weight: 400;">TPH2 </span></em><span style="font-weight: 400;">may play a role in fatigue by decreasing production of tryptophan hydroxylase 2. Lifestyle and diet modifications may counteract the effects of this variant by increasing tryptophan hydroxylase 2 production or activity.</span></span></p> <h2 style="text-align: justify;"><strong><em>TPH2</em></strong><strong> and Fatigue</strong></h2> <p style="text-align: justify;"><span style="font-weight: 400;">The </span><a href="https://selfdecode.com/gene/tph2/"><em><span style="font-weight: 400;">TPH2 </span></em><span style="font-weight: 400;">gene</span></a><span style="font-weight: 400;"> codes for tryptophan hydroxylase 2, an enzyme that helps synthesize the chemical messenger (neurotransmitter) </span><a href="https://selfhacked.com/blog/how-to-increase-serotonin/#What_is_Serotonin"><span style="font-weight: 400;">serotonin</span></a><span style="font-weight: 400;">. Serotonin plays an important role in regulating various </span><a href="https://selfhacked.com/blog/what-it-means-to-keep-to-a-circadian-rhythm/"><span style="font-weight: 400;">circadian rhythms</span></a><span style="font-weight: 400;">, such as the sleep-wake cycle [</span><a href="https://www.ncbi.nlm.nih.gov/gene/121278"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/10219711/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p style="text-align: justify;"><span style="font-weight: 400;">Tryptophan hydroxylase 2 is found within clusters of brain cells (neurons) called the raphe nuclei [</span><a href="https://pubmed.ncbi.nlm.nih.gov/10219711/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p style="text-align: justify;"><span style="font-weight: 400;">The raphe nuclei communicate with multiple brain regions, where the release of serotonin is involved in mediating either wakefulness or sleep. The sleep- or wake-inducing effects of serotonin also depend on the type of receptor it activates within these brain regions [</span><a href="https://pubmed.ncbi.nlm.nih.gov/10219711/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/12531142/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p style="text-align: justify;"><span style="font-weight: 400;">The rs4570625-T variant of </span><em><span style="font-weight: 400;">TPH2 </span></em><span style="font-weight: 400;">has been associated with heightened fatigue. rs4570625-T has also been observed to decrease production of tryptophan hydroxylase 2 [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822465/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/30309244/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p style="text-align: justify;"><span style="font-weight: 400;">Decreased production of tryptophan hydroxylase 2 may lower levels of serotonin in the raphe nuclei, which may ultimately lead to dysregulated sleep-wake cycles [</span><a href="https://pubmed.ncbi.nlm.nih.gov/30309244/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]. </span> </p> <h2 style="text-align: justify;"><strong>Your </strong><strong><em>TPH2</em></strong><strong> Results for Fatigue</strong></h2> <p style="text-align: justify;">*8659475370151637*</p> <p style="text-align: justify;"><strong>Primary SNP:</strong></p> <p style="text-align: justify;"><strong><em>TPH2</em></strong> <a href="https://selfdecode.com/snp/rs4570625/"><strong>rs4570625</strong></a> <span style="font-weight: 400;">[</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822465/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/30309244/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></p> <ul style="text-align: justify;"> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Associated with increased levels of fatigue&nbsp;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Not associated with fatigue</span></li> </ul> <p style="text-align: justify;">*9493852713615847*</p> <h2 style="text-align: justify;"><strong>Recommendations for Reducing Fatigue</strong></h2> <p style="text-align: justify;">*9921362371369082*</p> <h3 style="text-align: justify;"><strong>Lifestyle</strong></h3> <h4 style="text-align: justify;"><strong>Exercise</strong></h4> <p style="text-align: justify;"><span style="font-weight: 400;">Multiple animal studies have shown that <a href="https://selfhacked.com/blog/top-14-proven-health-benefits-exercise-references-mechanisms/" target="_blank" rel="noopener">exercise</a> may increase production of tryptophan hydroxylase 2 [</span><a href="https://pubmed.ncbi.nlm.nih.gov/24416346/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/11445277/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p style="text-align: justify;"><span style="font-weight: 400;">A sedentary lifestyle is a common cause of persistent fatigue. Several studies have reported that practicing more </span><span style="font-weight: 400;">exercise</span><span style="font-weight: 400;"> may reduce fatigue in healthy people. Paradoxically, being &lsquo;too tired&rsquo; was the most common excuse for not exercising in a study on middle-aged and elderly people [</span><a href="https://pubmed.ncbi.nlm.nih.gov/23783259/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/18277063/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816334/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/24154584/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p style="text-align: justify;"><span style="font-weight: 400;">People with chronic fatigue syndrome are at especially high risk of not meeting physical activity requirements. In people with this condition, engaging in regular physical exercise may help reduce fatigue </span><span style="font-weight: 400;">&mdash; </span><span style="font-weight: 400;">even more than in healthy controls, according to one meta-analysis</span> <span style="font-weight: 400;">[</span><a href="https://pubmed.ncbi.nlm.nih.gov/21166613/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419524/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026555/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p style="text-align: justify;"><span style="font-weight: 400;">Multiple studies have reported that exercise may also help with fatigue from other conditions, such as multiple sclerosis, cancer, rheumatoid arthritis, COPD, lupus, ALS, fibromyalgia, muscle disease, and heart failure [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068865/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931245/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168432/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937526/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/28477898/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/32452880/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911859/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/20091552/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/16713337/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p style="text-align: justify;"><span style="font-weight: 400;">However, over-exercising can lead to fatigue and several health issues. Experts recommend moderate exercise such as brisk walking, swimming, or cycling.&nbsp;</span></p> <p style="text-align: justify;"><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Exercise may reduce fatigue by increasing production of tryptophan hydroxylase 2.&nbsp;</span></p> <h4 style="text-align: justify;"><strong>Sun Exposure (Vitamin D)</strong></h4> <p style="text-align: justify;"><a href="http://selfhacked.com/blog/35proven-health-benefits-vitamin-d-part-1/"><span style="font-weight: 400;">Vitamin D</span></a><span style="font-weight: 400;"> is well known to stimulate the release of serotonin by promoting tryptophan hydroxylase 2 production [</span><a href="https://pubmed.ncbi.nlm.nih.gov/24558199/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/26071405/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/30008960/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p style="text-align: justify;"><span style="font-weight: 400;">Many studies have associated vitamin D deficiency with fatigue and muscle weakness, although not all people with this deficiency experience these symptoms [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442332/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/19835345"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/17634462/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/22020957/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p style="text-align: justify;"><span style="font-weight: 400;">A healthy exposure to </span><a href="https://selfhacked.com/blog/avoiding-sun-will-kill-14-proven-science-based-health-benefits-sun/"><span style="font-weight: 400;">sunlight</span></a><span style="font-weight: 400;">, which provides 50-90% of our vitamin D requirements, is the best way of replenishing this vitamin. In addition, you can eat food sources of this vitamin (such as fatty fish, liver, egg yolks, and dairy) or take supplements [</span><a href="https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p style="text-align: justify;"><span style="font-weight: 400;">Correcting vitamin D deficiency with supplements improved fatigue in both healthy people and those with various diseases [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5207540/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/25210673/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182952/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4158648/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6513642/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p style="text-align: justify;"><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">The sun is the best source of vitamin D. Sun exposure may reduce fatigue by increasing production of tryptophan hydroxylase 2.</span></p> <h3 style="text-align: justify;"><strong>Diet</strong></h3> <h4 style="text-align: justify;"><strong>Sufficient Iron Intake</strong></h4> <p style="text-align: justify;"><span style="font-weight: 400;">The activity of tryptophan hydroxylase 2 is dependent on the presence of </span><a href="https://selfhacked.com/blog/iron-balance-blood-test-iron-deficiency-anemia-overload/"><span style="font-weight: 400;">iron</span></a><span style="font-weight: 400;"> [</span><a href="https://pubmed.ncbi.nlm.nih.gov/10215890/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/23441081/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p style="text-align: justify;"><span style="font-weight: 400;">One of the most common causes of fatigue is iron deficiency. Most of the iron in the body is found in the protein </span><a href="https://selfhacked.com/blog/hemoglobin-good-bad-lab-tests-normal-values-reference-ranges/"><span style="font-weight: 400;">hemoglobin</span></a><span style="font-weight: 400;">, where it helps carry oxygen to cells for energy production. Iron is also needed for oxygen storage in the muscles, for brain function, and for immune system development and response [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999603/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4086762/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/12704220/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/15692603/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p style="text-align: justify;"><span style="font-weight: 400;">Several studies have associated iron deficiency (without anemia) with increased fatigue and worse overall health and well-being [</span><a href="https://pubmed.ncbi.nlm.nih.gov/11190004/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/28625177/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p style="text-align: justify;"><span style="font-weight: 400;">Iron-rich foods include meat, poultry, organ meats, fish, shellfish, pulses, seeds, green leafy vegetables, and fortified foods [</span><a href="https://pubmed.ncbi.nlm.nih.gov/1581009/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155616/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p style="text-align: justify;"><span style="font-weight: 400;">In people with low blood iron levels, replenishing them with iron supplements reduced subjective fatigue by up to 48% [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414597/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/26256281/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC156009/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892776/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/31715055/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p style="text-align: justify;"><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Sufficient iron intake may reduce fatigue by promoting tryptophan hydroxylase 2 activity.&nbsp;</span></p>
458 | content_snp_table_8659475370151637_key == 8659475370151637
458 | content_snp_table_8659475370151637_blur == True
458 | content_snp_table_8659475370151637_hidden == False
458 | content_learn_more_9493852713615847_key == 9493852713615847
458 | content_learn_more_9493852713615847_blur == True
458 | content_learn_more_9493852713615847_hidden == False
458 | content_learn_more_9493852713615847_text == Based on the variants we looked at, your TPH2 gene makes you somewhat more likely to have elevated levels of fatigue. However, this doesn't necessarily reflect your overall risk of elevated fatigue; it’s just one gene related to it. Getting adequate exercise, sun exposure, and iron may help. Keep scrolling to find out more.
458 | content_recommendation_9921362371369082_key == 9921362371369082
458 | content_recommendation_9921362371369082_blur == True
458 | content_recommendation_9921362371369082_hidden == False
rsIDs = rs4570625
rsStatus = rs4570625,TPH2,chr12,71938143,G,A,T,,30,0,Normal
