36 | id == 36
36 | category_id == 6
36 | category_order == 4
36 | category_name == Thyroid
36 | category_color == #C47AC0
36 | slug == hidden-hypothyroidism-DIO2
36 | title == The Gene Associated with "Hidden Hypothyroidism" (DIO2)
36 | meta_description == DIO2 correlates with low thyroid undetected by standard lab tests. Check your DIO2 gene here.
36 | summary == <p><strong>Struggling with fatigue, insulin resistance, and weight gain despite normal thyroid hormones? These symptoms may indicate&nbsp;&quot;hidden hypothyroidism&quot; associated with DIO2 variants. Read on to learn&nbsp;about the connection between DIO2 and thyroid hormones.</strong></p>
36 | overall_score_text == Thyroid Score (Based on DIO2 Gene)
36 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/Is-This-Gene-Causing-Your-Hidden-Hypothyroidism-DIO2_JPG.jpg
36 | author_id == 9
36 | author_name == Aleksa Ristic
36 | author_title == MS (Pharmacy)
36 | author_order == 45
36 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/Aleksa.jpg
36 | 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>
36 | reviewer_id == 1
36 | reviewer_name == Jasmine Foster
36 | reviewer_title == BSc, BEd
36 | medical_reviewer_id == 11
36 | medical_reviewer_name == Puya Yazdi
36 | medical_reviewer_title == MD
36 | publish_date == 2019
36 | publish_date == 9
36 | publish_date == 3
36 | avg_rating == 5.0
36 | tags_id == 13
36 | tags_name == Cognition
36 | tags_id == 114
36 | tags_name == DIO2 Gene
36 | tags_id == 43
36 | tags_name == Hypothyroidism
36 | tags_id == 116
36 | tags_name == Insulin Resistance
36 | tags_id == 117
36 | tags_name == Levothyroxine
36 | tags_id == 113
36 | tags_name == T3
36 | tags_id == 41
36 | tags_name == Thyroid
36 | tags_id == 115
36 | tags_name == Weight Gain
36 | permissions_favorite == False
36 | permissions_rate == False
36 | content_article == <h2><span style="font-weight: 400;">The DIO2 Gene</span></h2> <p><span style="font-weight: 400;">The </span><a href="../../gene/dio2/"><span style="font-weight: 400;">DIO2</span></a><span style="font-weight: 400;"> (Iodothyronine deiodinase 2) gene encodes an enzyme that converts T4, a storage </span><a href="https://selfhacked.com/blog/thyroid-hormones-t4t3/"><span style="font-weight: 400;">thyroid hormone</span></a><span style="font-weight: 400;">, into the active thyroid hormone, T3. It does so by removing one iodine atom from T4 [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979226/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">DIO2 is responsible for T3 production in the thyroid, muscles, brain, heart, and fat tissue. It accounts for up to 60% of all T3, which has vital roles in energy production, blood sugar control, cognitive development, and more [</span><a href="http://www.ncbi.nlm.nih.gov/pubmed/8755651"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="http://www.ncbi.nlm.nih.gov/pubmed/10614643"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://academic.oup.com/edrv/article/23/1/38/2424136"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="http://www.ncbi.nlm.nih.gov/pubmed/8754756"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h2><span style="font-weight: 400;">DIO2 Variants and Thyroid Health</span></h2> <p><span style="font-weight: 400;">At first glance, one might think DIO2 doesn&rsquo;t have much of an impact on thyroid health. Multiple studies failed to make a connection between variations in this gene and thyroid hormone levels [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17105838"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515080/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">But are they missing something?</span></p> <h3><span style="font-weight: 400;">"Hidden Hypothyroidism"</span></h3> <p><span style="font-weight: 400;">Many people have symptoms of </span><a href="https://selfhacked.com/blog/hypothyroidism-may-good-autoimmunity/"><span style="font-weight: 400;">low thyroid hormones</span></a><span style="font-weight: 400;"> despite their lab results being in the normal range.&nbsp;</span></p> <p><span style="font-weight: 400;">That </span><em><span style="font-weight: 400;">might be</span></em><span style="font-weight: 400;"> because their thyroid hormones don&rsquo;t function well on a cellular and tissue level, which cannot be measured by blood tests.</span></p> <p><span style="font-weight: 400;">One DIO2 variant may be involved in this phenomenon. The less common "C" allele on </span><a href="../../snp/rs225014/"><span style="font-weight: 400;">rs225014</span></a><span style="font-weight: 400;"> (Thr92Ala) is associated with:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">Poor response to thyroid meds [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527224/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19190113/"><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;">Obesity and </span><a href="https://www.selfhacked.com/blog/top-tips-for-fixing-insulin-resistance/"><span style="font-weight: 400;">insulin resistance</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/11872697/"><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;">Inadequate blood sugar control [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061950/"><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;">Impaired cognitive development (lower </span><a href="https://selfhacked.com/blog/best-way-to-increase-higher-level-thinking/"><span style="font-weight: 400;">IQ</span></a><span style="font-weight: 400;">) [</span><a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)60363-9/fulltext"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> </ul> <p><span style="font-weight: 400;">All of the above may indicate low thyroid hormones in DIO2 target tissues such as the brain, fat tissue, and muscles.</span></p> <p><span style="font-weight: 400;">That said, a couple of larger trials concluded that DIO2 variants have a marginal association with weight gain and </span><a href="https://selfhacked.com/blog/glucose/"><span style="font-weight: 400;">glucose</span></a><span style="font-weight: 400;"> metabolism. Other environmental and genetic factors play a more prominent role [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17077128/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17381351/"><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;">DIO2 enables the activation of thyroid hormones so they can play their crucial metabolic roles. One variant (rs225014-C) correlates with poor cognition, weight control, and glucose metabolism, which may indicate "hidden hypothyroidism."</span></p> <h3><span style="font-weight: 400;">Response to Thyroid Meds</span></h3> <p><span style="font-weight: 400;">Did you know that synthetic T4 (levothyroxine) for hypothyroidism is the second most prescribed drug in the US? We&rsquo;re witnessing a massive rise in thyroid disorders [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6025009/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The same DIO2 variant (rs225014) is associated with an inadequate response to thyroid meds in some people.</span></p> <p><span style="font-weight: 400;">Out of 45 patients, those who carried at least one &ldquo;C&rdquo; allele didn&rsquo;t respond as well to standard T4 treatment and were significantly more depressed. They preferred a combination of T4 and T3 (liothyronine) instead [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527224/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">A larger trial came to a similar conclusion, though the effects were significant only for patients who had both copies of the &ldquo;C&rdquo; allele [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19190113/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">A Dutch study with over 12,600 participants found no connection between DIO2 and thyroid treatment response. However, they didn&rsquo;t investigate the effects of the T4+T3 combination [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/27786042/"><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;">Some carriers of the &ldquo;C&rdquo; allele on rs225014 may not respond as well to standard T4 treatment for hypothyroidism. They may prefer a combination of T4 and T3 instead.</span></p> <h3><span style="font-weight: 400;">Joe&rsquo;s Experience</span></h3> <p><a href="https://selfhacked.com/blog/low-thyroid-hormones-low-t3-syndrome/"><span style="font-weight: 400;">According to Joe&rsquo;s experience</span></a><span style="font-weight: 400;"> with his clients: </span></p> <p><span style="font-weight: 400;">"Thyroid hormones aren&rsquo;t always beneficial for people with symptoms of hypothyroidism. They may even make things worse in some cases. </span><span style="font-weight: 400;">It seems like some doctors overprescribe thyroid meds, while others may underprescribe them. It might be worthwhile to get opinions from both 'conventional' and 'alternative' endocrinologists if your results are not 100% clear."</span></p> <p><span style="font-weight: 400;">NOTE: Always consult with your doctor before taking or discontinuing any drug or nutritional supplement.</span></p> <h2><span style="font-weight: 400;">How DIO2 Variants Affect Thyroid Hormones</span></h2> <p><span style="font-weight: 400;">The &ldquo;C&rdquo; allele on rs225014 reduces DIO2 activity and thus hinders the production of active T3 in the brain, muscle, and fat tissue [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15797963/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">This effect may prevent thyroid hormones from boosting cognition, energy production, and glucose metabolism [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/28324063"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/12788902/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Doctors give synthetic T4 to thyroid patients and count on the body to produce the active form, T3. Possibly, due to impaired conversion in muscles and other tissues, patients with rs225014-C may prefer a combination of T4 and T3.</span></p> <p><span style="font-weight: 400;">Given the expression of DIO2 in muscles, variations in this gene have a stronger correlation with thyroid hormones in young adults (and, presumably, those in better physical shape) compared with the elderly [</span><a href="https://www.physiology.org/doi/full/10.1152/ajpendo.00571.2004"><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;">The &ldquo;C&rdquo; allele on rs225014 reduces DIO2 activity and T3 production. It may thus prevent thyroid hormones from boosting cognition, fat burning, and glucose metabolism, but more clinical research is needed to verify this.&nbsp;</span></p> <h2><span style="font-weight: 400;">Your DIO2 Results for "Hidden Hypothyroidism"</span></h2> <p>*4992677039878852*</p> <p><strong>Primary SNP: </strong><a href="../../gene/dio2/"><strong>DIO2</strong></a> <a href="../../snp/rs225014/"><strong>rs225014</strong></a></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = associated with "hidden hypothyroidism"</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = not associated with "hidden hypothyroidism"</span></li> </ul> <p><span style="font-weight: 400;">Population frequency:</span></p> <p><span style="font-weight: 400;">Around 22% of the global and 14% of the European population have both copies of the "C" allele, so it's not rare and not something to be alarmed about.</span></p> <p>*2256697759289216*</p> <h2><span style="font-weight: 400;">Recommendations to Improve Thyroid Function</span></h2> <p><span style="font-weight: 400;">The below recommendations may help activate thyroid hormones and reduce the symptoms of "hidden hypothyroidism". Consult with your doctor b</span><span style="font-weight: 400;">efore trying any of these strategies.</span></p> <p><span style="font-weight: 400;">*3993837847836057*</span></p> <h3><span style="font-weight: 400;">Lifestyle</span></h3> <h4><span style="font-weight: 400;">Sunlight and Sleep Quality</span></h4> <p><span style="font-weight: 400;">Proper </span><a href="http://selfhacked.com/blog/what-it-means-to-keep-to-a-circadian-rhythm/"><span style="font-weight: 400;">circadian rhythm</span></a><span style="font-weight: 400;"> entrainment is essential for the DIO2 function. According to some animal trials, </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;"> (UV) exposure during the day and the lack of it during the night can boost DIO2 expression and activity [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/25449796/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/14614506"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/10067853"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><a href="https://selfhacked.com/blog/melatonin/"><span style="font-weight: 400;">Melatonin</span></a><span style="font-weight: 400;"> maintains sleep-wake cycles and improves </span><a href="https://selfhacked.com/blog/health-benefits-sleep/"><span style="font-weight: 400;">sleep quality</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15582288"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/23691095"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Try to increase melatonin and fine-tune your circadian rhythm by limiting blue light after sunset and getting enough sunlight during the day [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17364578"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020279/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/9374826/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">This may stimulate DIO2 and improve other aspects of thyroid health, too. Poor sleep quality and sleep deprivation initially increase thyroid hormones but exhaust them in the long run [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/2105332/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/8827131"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.sciencedirect.com/science/article/pii/B9781416066453000268"><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;">Proper circadian rhythm entrainment and sleep quality are essential for DIO2. Limiting blue light after sunset and getting enough sunlight during the day can help boost DIO2.</span></p> <h4><span style="font-weight: 400;">Cold Exposure</span></h4> <p><span style="font-weight: 400;">According to animal trials, </span><a href="http://selfhacked.com/blog/12-reasons-embrace-cold/"><span style="font-weight: 400;">cold exposure</span></a><span style="font-weight: 400;"> can boost DIO2 gene expression in brown fat/adipose tissue (BAT) by </span><strong>10-50 times</strong><span style="font-weight: 400;"> [</span><a href="http://www.ncbi.nlm.nih.gov/pubmed/6633638"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC209445/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Unlike white fat tissue, BAT stimulates fat burning and energy production. Cold exposure stimulates DIO2 to produce T3, which is essential for this effect to take place [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/14715917"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">,</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486781/"> <span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726172/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In one clinical trial, acute cold exposure also raised blood levels of T3 [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1331079/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Cold showers are the easiest way to practice cold exposure all year long and potentially enhance DIO2.</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Cold exposure boosts DIO2 in brown fat tissue, which may result in more T3, improved energy production, and fat loss. Cold showers are the easiest way to practice cold exposure year-round.</span></p> <h3><span style="font-weight: 400;">Diet</span></h3> <p><span style="font-weight: 400;">&ldquo;Eat your veggies&rdquo; may sound cliche, but it&rsquo;s one of the keys to improving DIO2. Kaempferol, found in different fruits and vegetables, enhanced DIO2 activity 10 times and boosted energy production in muscle cells [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17327447"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Some of the best sources of kaempferol include [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601579/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650511/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/21428901"><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;">Apples</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Grapes</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Broccoli</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Blackberries</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Spinach</span></li> </ul> <h3><span style="font-weight: 400;">Supplements</span></h3> <p><a href="https://www.selfhacked.com/blog/health-benefits-of-forskolin/"><span style="font-weight: 400;">Forskolin</span></a><span style="font-weight: 400;"> is a plant component cherished in Ayurvedic medicine. It increases cAMP, a messenger molecule that boosts DIO2 expression in human thyroid cells [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/10614643"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/6327383"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Forskolin may also stimulate the thyroid gland and T4 secretion [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/2052424"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/6286284"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Although melatonin is vital for circadian rhythm and sleep quality, higher amounts suppress thyroid hormones. For this reason, you may want to skip melatonin supplements [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5096296/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/9356225"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Well-designed clinical trials should verify the effects of the above strategies to stimulate DIO2. Forskolin is not approved by the FDA to prevent or treat any medical condition.</span></p> <h3><span style="font-weight: 400;">Drugs</span></h3> <p><span style="font-weight: 400;">If you've already been prescribed levothyroxine, and feel like your thyroid symptoms aren't fully resolved, it would be a good idea to show your doctor the cited research and ask them if you're better off trying a T4+T3 combination.</span></p>
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36 | content_learn_more_4992677039878852_text == Your DIO2 variant slightly correlates with the symptoms of "hidden hypothyroidism". If you experience the symptoms described in this post, consider applying natural hacks to boost your DIO2 activity and improve thyroid health.
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rsIDs = rs225014
rsStatus = rs225014,DIO2,chr14,80203237,T,C,,,11,17,HET
