tag:theconversation.com,2011:/id/topics/metabolic-diseases-2327/articlesMetabolic diseases – The Conversation2024-01-09T20:18:23Ztag:theconversation.com,2011:article/2207562024-01-09T20:18:23Z2024-01-09T20:18:23ZWhy don’t fruit bats get diabetes? New understanding of how they’ve adapted to a high-sugar diet could lead to treatments for people<figure><img src="https://images.theconversation.com/files/568452/original/file-20240109-23-jjo6l0.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2376%2C1442&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Fruit bats have honed their sweet tooth through adaptive evolution.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/fruit-bat-feeding-in-a-tree-royalty-free-image/1293525000">Keith Rose/iStock via Getty Images Plus</a></span></figcaption></figure><p>People around the world eat too much sugar. When the body is unable to process sugar effectively, leading to excess glucose in the blood, this can result in diabetes. According to the World Health Organization, diabetes became the <a href="https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death">ninth leading cause of death</a> in 2019.</p>
<p>Humans are not the only mammals that love sugar. Fruit bats do, too, eating up to <a href="https://dem.ri.gov/sites/g/files/xkgbur861/files/programs/bnatres/fishwild/outreach/critter-kits/bat-ex-benefits.pdf">twice their body weight</a> in sugary fruit a day. However, unlike humans, fruit bats thrive on a sugar-rich diet. They can <a href="https://doi.org/10.1007/s00360-019-01242-8">lower their blood sugar faster</a> than bats that rely on insects as their main food source.</p>
<p>We are a team of <a href="https://www.menlo.edu/about/find-an-expert/wei-gordon/">biologists</a> and <a href="https://scholar.google.com/citations?user=kkrPGvcAAAAJ&hl=en">bioengineers</a>. Determining how fruit bats evolved to specialize on a high-sugar diet sent us on a quest to approach diabetes therapy from an unusual angle – one that sent us all the way to Lamanai, Belize, for the <a href="https://www.batcon.org/belize-bat-a-thon/">Belize Bat-a-thon</a>, an annual gathering where researchers collect and study bats.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/568470/original/file-20240109-29-2hgb6j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Two people wearing face masks, one with a headlamp and one holding a small bat up to the camera" src="https://images.theconversation.com/files/568470/original/file-20240109-29-2hgb6j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/568470/original/file-20240109-29-2hgb6j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=800&fit=crop&dpr=1 600w, https://images.theconversation.com/files/568470/original/file-20240109-29-2hgb6j.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=800&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/568470/original/file-20240109-29-2hgb6j.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=800&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/568470/original/file-20240109-29-2hgb6j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1005&fit=crop&dpr=1 754w, https://images.theconversation.com/files/568470/original/file-20240109-29-2hgb6j.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1005&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/568470/original/file-20240109-29-2hgb6j.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1005&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Authors Nadav Ahituv, left, and Wei Gordon.</span>
<span class="attribution"><span class="source">Wei Gordon</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>In our <a href="https://doi.org/10.1038/s41467-023-44186-y">newly published research</a> in Nature Communications, we and colleagues <a href="https://netbiolab.org/w/People:SB_Baek">Seungbyn Baek</a> and <a href="https://scholar.google.com/citations?user=H4jO_DQAAAAJ&hl=en">Martin Hemberg</a> used a technology that analyzes the DNA of individual cells to compare the unique metabolic instructions encoded in the genome of the Jamaican fruit bat, <em>Artibeus jamaicensis</em>, with those in the genome of the insect-eating big brown bat, <em>Eptesicus fuscus</em>. </p>
<p><a href="https://doi.org/10.1038/nature11247">Approximately 2% of DNA</a> is composed of genes, which are segments of DNA that contain the instructions cells use to create certain traits, such as a <a href="https://doi.org/10.1016/j.acthis.2020.151503">longer tongue in fruit bats</a>. The other 98% are segments of DNA that regulate genes and determine the presence and absence of the traits they encode.</p>
<p>To understand how fruit bats evolved to consume so much sugar, we wanted to identify the genetic and cellular differences between bats that eat fruit and bats that eat insects. Specifically, we looked at the genes, regulatory DNA and cell types in two significant organs involved in metabolic disease: the pancreas and the kidney. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/568363/original/file-20240109-25-d0snov.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Four male *Artibeus jamaicensis* and four male *Eptesicus fuscus* bats were put in a fast then fed fruit or worms, respectively, or no meal before analyzing the cells and genes of their kidney and pancreas." src="https://images.theconversation.com/files/568363/original/file-20240109-25-d0snov.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/568363/original/file-20240109-25-d0snov.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=244&fit=crop&dpr=1 600w, https://images.theconversation.com/files/568363/original/file-20240109-25-d0snov.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=244&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/568363/original/file-20240109-25-d0snov.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=244&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/568363/original/file-20240109-25-d0snov.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=306&fit=crop&dpr=1 754w, https://images.theconversation.com/files/568363/original/file-20240109-25-d0snov.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=306&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/568363/original/file-20240109-25-d0snov.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=306&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This flowchart outlines the authors’ study methodology.</span>
<span class="attribution"><a class="source" href="https://doi.org/10.1038/s41467-023-44186-y">Wei Gordon, created with BioRender.com/Nature Communications</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p><a href="https://doi.org/10.1038/s41580-020-00317-7">The pancreas</a> regulates blood sugar and appetite by secreting hormones like insulin, which lowers your blood sugar, and glucagon, which raises your blood sugar. We found Jamaican fruit bats have <a href="https://doi.org/10.1038/s41467-023-44186-y">more insulin-producing and glucagon-producing cells</a> than big brown bats, along with regulatory DNA that primes fruit bat pancreatic cells to initiate production of insulin and glucagon. Together these two hormones work to keep blood sugar levels balanced even when the fruit bats are eating large amounts of sugar.</p>
<p><a href="https://doi.org/10.1093%2Fndt%2Fgfx027">The kidney</a> filters metabolic waste from the blood, maintains water and salt balance and regulates blood pressure. Fruit bat kidneys need to be equipped to remove from their bloodstreams the large amounts of water that come from fruit while retaining the low amounts of salt in fruit. We found Jamaican fruit bats have adjusted the compositions of their kidney cells in accordance with their diet, <a href="https://doi.org/10.1038/s41467-023-44186-y">reducing the number of urine-concentrating cells</a> so their urine is more diluted with water compared with big brown bats.</p>
<h2>Why it matters</h2>
<p>Diabetes is one of the most expensive chronic conditions in the world. The <a href="https://doi.org/10.2337/dci23-0085">U.S. spent US$412.9 billion</a> in 2022 on direct medical costs and indirect costs related to diabetes.</p>
<p>Most approaches to developing new treatments for diabetes are based on traditional laboratory animals such as mice because they are easy to reproduce and study in a lab. But outside the lab, there exist mammals like fruit bats that have actually evolved to withstand high sugar loads. Figuring out how these mammals deal with high sugar loads can help researchers identify new approaches to treat diabetes.</p>
<p>By applying new cell characterization technologies on these <a href="https://theconversation.com/e-coli-is-one-of-the-most-widely-studied-organisms-and-that-may-be-a-problem-for-both-science-and-medicine-206045">nonmodel organisms</a>, or organisms researchers don’t usually use for research in the lab, we and a growing body of researchers show that nature could be leveraged to develop novel treatment approaches for disease. </p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/QIBMyj8ebRU?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The authors disentangle a fruit bat from a net during the Belize Bat-a-thon.</span></figcaption>
</figure>
<h2>What still isn’t known</h2>
<p>While our study revealed many potential therapeutic targets for diabetes, more research needs to be done to demonstrate whether our fruit bat DNA sequences can help understand, manage or cure diabetes in humans.</p>
<p>Some of our fruit bat findings may be unrelated to metabolism or are specific only to Jamaican fruit bats. There are <a href="https://www.britannica.com/animal/Old-World-fruit-bat">close to 200 species</a> of fruit bats. Studying more bats will help researchers clarify which fruit bat DNA sequences are relevant for diabetes treatment. </p>
<p>Our study also focused only on bat pancreases and kidneys. Analyzing other organs involved in metabolism, such as the liver and small intestine, will help researchers more comprehensively understand fruit bat metabolism and design appropriate treatments.</p>
<h2>What’s next</h2>
<p>Our team is now testing the regulatory DNA sequences that allow fruit bats to eat so much sugar and checking whether we can use them to better regulate how people respond to glucose.</p>
<p>We are doing this by <a href="https://www.youtube.com/watch?v=Cv59sjupd1Y&t=77s">swapping the regulatory DNA sequences</a> in mice with those of fruit bats and testing their effects on how well these mice manage their glucose levels.</p>
<p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take about interesting academic work.</em></p><img src="https://counter.theconversation.com/content/220756/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Wei Gordon receives funding from NSF. </span></em></p><p class="fine-print"><em><span>Nadav Ahituv is a cofounder and on the scientific advisory board of Regel Therapeutics and also received funding from BioMarin Pharmaceutical Incorporate.
Funding for this research was supported by the National Human Genome Research Institute grant R01HG012396.
</span></em></p>Fruit bats can eat up to twice their body weight in fruit a day. But their genes and cells evolved to process all that sugar without any health consequences − a feat drug developers can learn from.Wei Gordon, Assistant Professor of Biology, Menlo CollegeNadav Ahituv, Professor, Department of Bioengineering and Therapeutic Sciences; Director, Institute for Human Genetics, University of California, San FranciscoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1971702023-01-05T10:43:05Z2023-01-05T10:43:05ZYes, intermittent fasting can boost your health, but how and when to restrict food consumption is crucial<figure><img src="https://images.theconversation.com/files/502968/original/file-20230103-16-ir16ze.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">file m k</span> </figcaption></figure><p>On top of kickstarting a new exercise regime, the new year is traditionally a period when many people reconsider their eating habits. In recent years, intermittent fasting has become a popular habit – and has been credited with some health benefits, be it to manage <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017674/">excess weight</a>, <a href="https://www.endocrine.org/news-and-advocacy/news-room/2021/intermittent-fasting-can-help-manage-metabolic-disease">chronic illnesses</a> or <a href="https://www.sciencedirect.com/science/article/abs/pii/S0899900719300462">flagging energy levels</a>. But what exactly is intermittent fasting? And does all the hype around it stand up to scientific scrutiny?</p>
<p>The term intermittent fasting covers several approaches, each based on different principles. It is important to note that no matter which method is used, the restrictions only affect food – never water – intake.</p>
<ul>
<li><p><strong>The “Eat Stop Eat” method</strong>. Put forward by Brad Pilon in his <a href="https://bradpilon.com/meet-brad/">book of the same name</a>, the principle is to alternate days of normal eating and fasting, including two non-consecutive fasting days in a week.</p></li>
<li><p><strong>The 5:2 method</strong>. Developed in the 2000s by the doctors Michelle Harvie and Tony Howell, this alternates between five days of normal eating and two days (which can be consecutive) of 70-75% calorie reduction during the week.</p></li>
<li><p><strong>Time-restricted eating (also called time-restricted feeding)</strong>. This is currently the most popular and most studied method. It consists of <a href="https://pubmed.ncbi.nlm.nih.gov/33921979/">narrowing the food intake window to between 6 and 10 hours per day, and therefore fasting between 14 and 18 hours during the day</a>.</p></li>
</ul>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/503050/original/file-20230104-129654-tn6tqf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Eat Stop Eat, 5:2 and Time Limit are the three most popular intermittent fasting methods" src="https://images.theconversation.com/files/503050/original/file-20230104-129654-tn6tqf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/503050/original/file-20230104-129654-tn6tqf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=331&fit=crop&dpr=1 600w, https://images.theconversation.com/files/503050/original/file-20230104-129654-tn6tqf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=331&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/503050/original/file-20230104-129654-tn6tqf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=331&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/503050/original/file-20230104-129654-tn6tqf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=416&fit=crop&dpr=1 754w, https://images.theconversation.com/files/503050/original/file-20230104-129654-tn6tqf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=416&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/503050/original/file-20230104-129654-tn6tqf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=416&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Summary of the different intermittent fasting methods.</span>
<span class="attribution"><span class="source">Anouk Charlot</span></span>
</figcaption>
</figure>
<h2>Science’s verdict?</h2>
<p>Outcomes vary depending on the adopted strategy.</p>
<p>With the “Eat Stop Eat” and 5:2 approaches, relatively few scientific studies have been conducted. The little data we have available has shown they can effectively <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766278/">help us lose weight</a> and <a href="https://www.annualreviews.org/doi/10.1146/annurev-nutr-071816-064634">improve certain metabolic parameters</a> such as fasting blood glucose. For example, the nutritionist Surabhi Bhutani showed the use of the 5:2 method for three months resulted in a <a href="https://onlinelibrary.wiley.com/doi/10.1002/oby.20353">weight loss of 3-6 kg in participants</a>.</p>
<p>However, both methods are very restrictive and can cause <a href="https://academic.oup.com/ajcn/article/81/1/69/4607679?login=false">side effects</a> on days of total fasting or severe caloric restriction – hunger, negative effects on mood, and risk of hypoglycaemia.</p>
<p>In the longer term, restriction also increases the risk of developing or worsening eating disorders, as well as <a href="https://theconversation.com/why-frequent-dieting-makes-you-put-on-weight-and-what-to-do-about-it-69329">yo-yo dieting</a>. These patterns often appear after the individual has attempted to lose weight by restricting themselves: despite initial progress, the deprivation is likely to generate frustrations that will encourage <a href="https://pubmed.ncbi.nlm.nih.gov/27773644/">the return of old eating habits</a>.</p>
<p>The most studied method is the one with a daily food intake but limited in time. Two “time slots” are often observed:</p>
<ul>
<li><p>When food intake starts with breakfast and ends in the late afternoon – known as “early time-restricted feeding”.</p></li>
<li><p>When food intake starts with lunch – known as “late time-restricted feeding”.</p></li>
</ul>
<p>This approach appears to improve metabolic regulation and slash the risk of metabolic diseases. However, these benefits vary according to the chosen time slot. When food intake starts in the morning, studies have observed <a href="https://www.sciencedirect.com/science/article/pii/S1550413118302535">weight loss</a> and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893547/">improvements in insulin sensitivity</a>.</p>
<p>Conversely, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387818/">there are fewer or no benefits</a> to starting meals at midday and ending them in the evening. Ram Babu Singh’s team (Halberg Hospital and Research Institute, India) also showed <a href="https://www.tandfonline.com/doi/full/10.1080/07420528.2019.1701817">positive results in participants who ate only in the morning</a>, and not in those who ate in the evening after 8 p.m.</p>
<h2>Why such a difference?</h2>
<p>Research suggests our internal clock and circadian rhythms may have something to do with it. Indeed, the benefits to only eating in the morning is that the periods of food intake and fasting coincide with our biological clock.</p>
<p>In our <a href="https://theconversation.com/mieux-respecter-son-horloge-interne-pour-une-meilleure-sante-194196">previous article</a>, we explained that in response to light cycles, our body produces hormones in a cyclical way to adapt our food intake to the body’s energy needs: the optimal period for eating is therefore from around 8 or 9 a.m. (when the sun rises) to 7 p.m. (when the sun starts to set, depending on the season).</p>
<p>Not eating breakfast and eating after 7 p.m. upsets circadian rhythms, and <a href="https://pubmed.ncbi.nlm.nih.gov/28877894/">increases the risk of developing metabolic diseases</a>.</p>
<p>However, while time-limited eating seems to be a good approach to metabolic health, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387818/">much remains to be understood about how it works</a> and how to optimise its effects. Work in 2022 showed <a href="https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00344-8">no difference in terms of weight loss</a> between opting for early- or late-morning eating. It did, however, have an effect on appetite during the day – this time to the advantage of the former.</p>
<p>And beyond the time of day when it seems preferable to eat, other factors may be at work that are not always measured in the studies carried out: quality and quantity of food absorbed, duration of the fasting period (which can extend from 12 to 20 hours per day), etc. It is also worth remembering every individual has his or her own metabolism and may respond differently to fasting. New, better controlled and more comprehensive studies are therefore needed to confirm the potential benefits of these methods and to understand the mechanisms involved in their effects.</p>
<h2>In practice, what to do?</h2>
<p>The most suitable method to avoid disrupting one’s circadian clock (and thereby limiting the risk of frustration or eating disorders) appears to be time-limited food intake by synchronising meals with circadian rhythms.</p>
<p>Thus, a typical day could be organised with a hearty breakfast in the morning taking place between 6 and 8 a.m., a lunch around midday and finally bringing dinner forward so that it takes place between 4 and 6 p.m., depending on the season.</p>
<p>This is not necessarily easy to reconcile with one’s social life. It can be complicated to practise intermittent fasting for a family, when one practises a sporting activity in the early evening or when one works in the evening until 7 or 8 p.m.</p>
<p>One solution would be to opt for a big breakfast and not too caloric a meal in the evening – preferably without carbs or sugars, so as not to risk shifting one’s biological clock.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/503052/original/file-20230104-18-l9wxew.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Reminder of practices to be favoured and avoided" src="https://images.theconversation.com/files/503052/original/file-20230104-18-l9wxew.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/503052/original/file-20230104-18-l9wxew.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=328&fit=crop&dpr=1 600w, https://images.theconversation.com/files/503052/original/file-20230104-18-l9wxew.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=328&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/503052/original/file-20230104-18-l9wxew.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=328&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/503052/original/file-20230104-18-l9wxew.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=412&fit=crop&dpr=1 754w, https://images.theconversation.com/files/503052/original/file-20230104-18-l9wxew.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=412&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/503052/original/file-20230104-18-l9wxew.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=412&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Typical day and foods to be favoured for practising time-limited eating.</span>
<span class="attribution"><span class="source">Anouk Charlot</span></span>
</figcaption>
</figure>
<h2>Chrono-nutrition</h2>
<p>Chrononutrition is increasingly popular and intermittent fasting appears to effectively boost metabolic health. That said, we have seen it is not a panacea. And we must ensure that the periods of fasting and food intake are consistent with our biological clock.</p>
<p>In the face of many existing methods, and potential risks, patients and health professionals still face a lack of information. Further research is essential to better understand their effects. Currently, there is not yet a general consensus on the ideal time to eat/fast, or on the optimal duration of each period. Moreover, these parameters may differ from one person to another, depending on their genetic make-up, history and lifestyle. It is therefore important to consider the use of this dietary strategy with qualified health professionals, with the view of setting up a healthy and balanced diet that will limit the risk of complications.</p><img src="https://counter.theconversation.com/content/197170/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Anouk Charlot's research is funded by a scholarship from Strasbourg University.</span></em></p><p class="fine-print"><em><span>Joffrey Zoll ne travaille pas, ne conseille pas, ne possède pas de parts, ne reçoit pas de fonds d'une organisation qui pourrait tirer profit de cet article, et n'a déclaré aucune autre affiliation que son organisme de recherche.</span></em></p>Nutritionists pick out the most effective intermittent fasting diets based on the latest science.Anouk Charlot, Doctorante, Université de StrasbourgJoffrey Zoll, MCU-PH en physiologie, faculté de médecine, Université de StrasbourgLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1517592021-02-05T03:50:52Z2021-02-05T03:50:52Z‘The disease of kings?’ 1 in 20 Australians get gout — here’s how to manage it<figure><img src="https://images.theconversation.com/files/375207/original/file-20201215-21-ygqadc.jpg?ixlib=rb-1.1.0&rect=0%2C1%2C952%2C703&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">"The Gout", by James Gillray.</span> <span class="attribution"><span class="source">Wikimedia Commons</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>I awoke one morning late last year to find a bright red bauble at the foot of my bed. It wouldn’t have looked amiss adorning a Christmas tree. But it felt ready to explode. It was my big toe, and this was my first encounter with gout.</p>
<h2>In good company</h2>
<p>With <a href="https://pubmed.ncbi.nlm.nih.gov/29393108/">a history</a> spanning more than 4,500 years, gout is among our earliest recorded diseases. Hippocrates, traditionally regarded as the father of medicine, called it “<a href="https://arthritis-research.biomedcentral.com/articles/10.1186/ar1906">the unwalkable disease</a>”, because it was very painful for people with gout to walk.</p>
<p>Many famous historical figures <a href="https://goutandyou.com/gout-and-famous-people/">suffered with gout</a>, including Christopher Columbus, Henry VIII, <a href="https://en.wikisource.org/wiki/Dialogue_Between_Franklin_and_the_Gout#:%7E:text=No%2C%20not%20your%20enemy.,the%20one%20nor%20the%20other.">Benjamin Franklin</a> and Beethoven. It became known as “the disease of kings”.</p>
<p>This moniker also reflects the fact gout has historically been <a href="https://pubmed.ncbi.nlm.nih.gov/16820040/">associated with</a> indulging in rich food and excessive alcohol. Scientific evidence today suggests this may have something to do with it, though the common belief drinking <a href="https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1780180704">port specifically causes gout</a> is unfounded.</p>
<p>Today, no longer just a disease of kings, the prevalence of gout is increasing <a href="https://www.nature.com/articles/nrrheum.2015.91">around the world</a>. Almost <a href="https://www.aihw.gov.au/reports/chronic-musculoskeletal-conditions/gout/contents/what-is-gout">one in 20 Australians</a> have had at least one attack of gout.</p>
<p>And some <a href="https://pubmed.ncbi.nlm.nih.gov/21169857/">stigma</a> still clings to the condition. Often gout is seen as being self-inflicted, a mark of overindulgence. But living with gout has <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/1756-185X.13979">far-reaching implications</a>, hampering a person’s ability to participate in everyday life.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/got-gout-heres-what-to-eat-and-avoid-50239">Got gout? Here's what to eat and avoid</a>
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</em>
</p>
<hr>
<h2>What is gout?</h2>
<p>Gout is <a href="https://pubmed.ncbi.nlm.nih.gov/29393108/">the most common form</a> of inflammatory arthritis. It’s caused by sodium urate crystals forming in the joints. While the big toe is particularly susceptible, gout can also affect the ankles, knees, elbows, wrists and fingers.</p>
<p><a href="https://pubmed.ncbi.nlm.nih.gov/25422986/">Urate</a>, or uric acid, is an end-product of the breakdown of biochemicals called purines, which are both components of your DNA and absorbed into the body through the foods you eat. Urate levels reflect how much is made in the liver and how much is flushed out when you go to the toilet. </p>
<p>If your urate levels become too high, the urate turns into crystals. When urate crystals form in the <a href="https://www.arthritis-health.com/types/joint-anatomy/how-do-synovial-joints-work">fluid</a> cushioning a joint, the body’s defence forces see them as foreign invaders. Inflammation and debilitating pain follow.</p>
<figure class="align-center ">
<img alt="A main, appearing in pain, clutches his inflamed foot." src="https://images.theconversation.com/files/382148/original/file-20210203-21-lbq8xf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/382148/original/file-20210203-21-lbq8xf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/382148/original/file-20210203-21-lbq8xf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/382148/original/file-20210203-21-lbq8xf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/382148/original/file-20210203-21-lbq8xf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/382148/original/file-20210203-21-lbq8xf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/382148/original/file-20210203-21-lbq8xf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Gout can be incredibly painful.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<h2>What causes gout?</h2>
<p>A high level of urate in the blood is the <a href="https://pubmed.ncbi.nlm.nih.gov/31558729/">greatest risk factor for gout</a>. But what causes high levels of urate? While we don’t know exactly, several factors certainly contribute.</p>
<p>A <a href="https://pubmed.ncbi.nlm.nih.gov/28844079/">tangled web</a> links urate, gout and other metabolic diseases, including type 2 diabetes and high blood pressure. <a href="https://pubmed.ncbi.nlm.nih.gov/33231639/">Being overweight</a> is a common factor. </p>
<p>Gout can run in families, with <a href="https://pubmed.ncbi.nlm.nih.gov/28566086/">genetics</a> playing a key role in determining urate levels. For example, genetic differences can impair <a href="https://pubmed.ncbi.nlm.nih.gov/32488095/">urate excretion</a>, thereby increasing blood urate levels.</p>
<p>Gout is also more common in males — almost 80% of people with gout are male. One reason for this is the female sex hormone oestrogen <a href="https://pubmed.ncbi.nlm.nih.gov/30415758/">lowers urate levels</a>, and is therefore protective against gout in pre-menopausal women.</p>
<p>And gout is more common <a href="https://pubmed.ncbi.nlm.nih.gov/32541923/">the older you get</a>. It affects 0.2% of Australian men in their 20s, increasing to <a href="https://pubmed.ncbi.nlm.nih.gov/26233513/">11% over the age of 85</a>.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/arthritis-isnt-just-a-condition-affecting-older-people-it-likely-starts-much-earlier-67698">Arthritis isn't just a condition affecting older people, it likely starts much earlier</a>
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</em>
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<h2>Management and prevention</h2>
<p>You should ice and raise the affected joint and minimise contact with it — even a light bedsheet can cause excruciating pain.</p>
<p>Attacks of gout can last for days or weeks. If you think you have gout, you should see your doctor. </p>
<p>Anti-inflammatory drugs can ease gout attacks. Your doctor might prescribe <a href="https://pubmed.ncbi.nlm.nih.gov/29359661/">colchicine</a>, or you can get <a href="https://www.healthdirect.gov.au/ibuprofen">ibuprofen</a> over the counter. </p>
<p>It’s <a href="https://pubmed.ncbi.nlm.nih.gov/32776706/">easy to stop exercising</a>, but <a href="https://www.healthgrades.com/right-care/gout/exercise-is-important-when-you-have-gout">swimming and cycling</a> are two ways you can comfortably continue moving during a gout flare.</p>
<p>Many people who have one gout attack will go on to have more. In one study, <a href="https://pubmed.ncbi.nlm.nih.gov/16267879/">70% of people</a> who had an attack of gout went on to have another within a year.</p>
<p>If you suffer two or more attacks, management of <a href="https://pubmed.ncbi.nlm.nih.gov/28549177/">chronic gout</a> involves taking a urate-lowering therapy such as <a href="https://rheumatology.org.au/patients/documents/Allopurinol_2016_002.pdf">allopurinol</a> or <a href="https://arthritisaustralia.com.au/medication-search/febuxostat/">febuxostat</a>.</p>
<figure class="align-center ">
<img alt="Two hands clinking beers." src="https://images.theconversation.com/files/382640/original/file-20210204-18-v168bl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/382640/original/file-20210204-18-v168bl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/382640/original/file-20210204-18-v168bl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/382640/original/file-20210204-18-v168bl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/382640/original/file-20210204-18-v168bl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/382640/original/file-20210204-18-v168bl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/382640/original/file-20210204-18-v168bl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Beer is often singled out as it’s relatively purine-rich. But it’s a good idea to cut back on all types of alcohol.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>If you’ve had gout once and want to prevent it coming back, it’s worth thinking about <a href="https://pubmed.ncbi.nlm.nih.gov/23024028/">lifestyle changes</a>. As with <a href="https://theconversation.com/losing-weight-is-hard-but-its-not-any-harder-if-you-have-type-2-diabetes-86773">other metabolic diseases</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/31468681/">losing weight</a> helps.</p>
<p>You might also consider minimising consumption of <a href="https://www.jstage.jst.go.jp/article/bpb/37/5/37_b13-00967/_pdf/-char/en">purine-rich foods</a>, which include meat, seafood and yeast products, like Vegemite.</p>
<p>But as with any diet, sticking to a low-purine diet can be challenging. Evidence for particular <a href="https://theconversation.com/got-gout-heres-what-to-eat-and-avoid-50239">foods to favour or avoid for gout</a> is <a href="https://pubmed.ncbi.nlm.nih.gov/30213692/">weak</a>, and overall, <a href="https://pubmed.ncbi.nlm.nih.gov/30305269/">diet contributes very little</a> to variation in urate levels. </p>
<p>So rather than purely focusing on purine-rich foods, <a href="https://pubmed.ncbi.nlm.nih.gov/33082244/">consuming less in total</a> can better control urate levels while improving your overall health. Limiting <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991555/">alcohol</a> is also a good idea.</p>
<h2>Epilogue</h2>
<p>With a red bauble stuck on the end of your foot, you learn to appreciate how important your big toe is for mobility.</p>
<p>Eventually, I managed to drop my <a href="https://pubmed.ncbi.nlm.nih.gov/32835125/">COVID kilos</a>, by watching portion sizes, not going back for seconds, replacing unhealthy snacks with fruit, and cutting back on alcohol.</p>
<p>And with that, I’m hoping my first encounter with gout might be my last. Although keeping off the kilos will require constant vigilance, the memory of that painful red bauble should be a powerful motivator.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/not-feeling-motivated-to-tackle-those-sneaky-covid-kilos-try-these-4-healthy-eating-tips-instead-152316">Not feeling motivated to tackle those sneaky COVID kilos? Try these 4 healthy eating tips instead</a>
</strong>
</em>
</p>
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<img src="https://counter.theconversation.com/content/151759/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>If you’ve ever had a bout of gout, you’ll know it’s truly awful. Here’s what causes it, and what you can do about it.Andrew Brown, Professor, School of Biotechnology and Biomolecular Sciences, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1470672020-10-01T13:47:03Z2020-10-01T13:47:03ZBelly fat linked to higher risk of premature death, regardless of your weight<figure><img src="https://images.theconversation.com/files/361040/original/file-20201001-24-5gjbr8.jpg?ixlib=rb-1.1.0&rect=35%2C0%2C5955%2C3997&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">'Apple shaped' people store more fat in their abdomen, while 'pear shaped' people store it in their lower body.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/fruits-black-african-american-womans-hands-1145346317">Red Confidential/ Shutterstock</a></span></figcaption></figure><p>It’s well known that carrying extra fat around your waist can be harmful to your health, bringing greater risk of developing illnesses such as <a href="https://www.nature.com/articles/ejcn200968/tables/1">type 2 diabetes and heart disease</a>. But a <a href="https://www.bmj.com/content/370/bmj.m3324">recent study</a> found that, regardless of weight, people who carry more fat around their abdomen had a higher risk of dying sooner – in fact, there was an 11% increase in death during follow up with every extra 10cm of waist circumference.</p>
<p>The researchers included 72 studies in their review, which contained data on 2.5 million people. They then analysed the combined data on body shape measures, looking at waist-to-hip ratio, waist-to-thigh ratio, and waist and thigh circumference – in other words, all the areas where a person naturally stores fat. </p>
<p>Beside the finding on belly fat, the researchers also found that people who tend to store more fat on the hips and thighs – instead of their abdomen – had a lower risk of dying sooner, with each extra 5cm thigh circumference associated with an 18% reduced risk of death during the follow-up period (between 3-24 years, depending on the study). But why might this be the case? The answer has to do with the type of fat tissue we tend to store in certain areas of our body.</p>
<p>Body fat (known as adipose tissue) plays an important role in our physiology. Its main purpose is to take glucose from the blood and safely <a href="https://www.nature.com/articles/nature05483">store this energy as lipid</a> inside our fat cells, which our body uses later for fuel. Our fat cells also produce <a href="https://www.nature.com/articles/s41574-019-0230-6">hormone signals</a> that influence many body processes, including appetite. Adipose tissue is therefore important for good metabolic health. </p>
<p>But having too little adipose tissue can affect how well blood sugar levels are regulated in the body. Insulin regulates healthy blood sugar levels, telling fat cells to take up glucose from the blood and store it for later. Without enough adipose tissue (a condition known as <a href="https://link.springer.com/article/10.1007/s11892-018-1099-9">lipodystrophy</a>), this process can’t work properly – resulting in <a href="https://link.springer.com/article/10.1007/s11892-018-1099-9">insulin resistance</a>, which can lead to diabetes.</p>
<p>Although fat is important for good metabolic health, where we store it (and the kind of fat tissue it is) can have different health consequences. Research shows that people with the same height and weight, but who store their fat in different places have <a href="https://academic.oup.com/ajcn/article/81/3/555/4648892">different risks</a> of developing certain <a href="https://www.ahajournals.org/doi/full/10.1161/jaha.117.008507">metabolic diseases</a>, such as <a href="https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001230">type 2 diabetes and cardiovascular disease</a>.</p>
<h2>Visceral versus subcutaneous</h2>
<p>Body shape is influenced by where fat is stored in our body. For example, “apple shaped” people store more fat around their waist and are likely to <a href="https://www.nature.com/articles/0800929">store more fat deeper</a> in the body surrounding their organs as <a href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/visceral-fat">visceral fat</a>. “Pear shaped” people have larger thighs, and store more fat more evenly around their body just under the skin as <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/subcutaneous-fat">subcutaneous fat</a>. </p>
<p>These <a href="https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1467-789X.2009.00623.x">different fat depots</a> have <a href="https://diabetes.diabetesjournals.org/content/63/11/3785">different physiological properties</a> and <a href="https://www.pnas.org/content/103/17/6676.long">express different genes</a>. It’s thought that different visceral and subcutaneous fat depots develop from <a href="https://elifesciences.org/articles/39636">different precursor cells</a> – cells that can become fat cells.</p>
<p>Visceral fat is considered more <a href="https://www.jci.org/articles/view/118083">insulin resistant</a>, and so carries a higher risk of type 2 diabetes. Body fat stored around the waist also releases more blood triglycerides in response to <a href="https://journals.physiology.org/doi/abs/10.1152/ajpendo.1996.270.2.E259?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org">stress hormone signals</a> compared to hip and thigh fat. High blood trigylceride levels are associated with greater risk of <a href="https://journals.sagepub.com/doi/abs/10.1177/174182679600300214?journalCode=cpra">heart disease</a>. This is partly why visceral fat is seen as as more harmful than subcutaneous fat.</p>
<figure class="align-center ">
<img alt="Overweight woman holds a tape measure around her waist." src="https://images.theconversation.com/files/361043/original/file-20201001-17-16arf36.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/361043/original/file-20201001-17-16arf36.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/361043/original/file-20201001-17-16arf36.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/361043/original/file-20201001-17-16arf36.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/361043/original/file-20201001-17-16arf36.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/361043/original/file-20201001-17-16arf36.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/361043/original/file-20201001-17-16arf36.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Visceral fat can be harmful.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/thick-woman-measuring-belly-pink-tape-1695163729">Yekatseryna Netuk/ Shutterstock</a></span>
</figcaption>
</figure>
<p>On the other hand, hip and thigh subcutaneous fat can better <a href="https://diabetes.diabetesjournals.org/content/59/10/2465.long">take up these triglycerides</a> from the blood and store them safely, preventing the body from incorrectly storing them in the muscles or liver, which can cause <a href="https://www.nature.com/articles/s41430-018-0323-7">liver disease</a>. Subcutaneous fat tissue can even develop specialised <a href="https://www.nature.com/articles/nrendo.2013.204">“beige” fat cells</a> that are able to burn fat. For these reasons, subcutaneous fat is thought of as safer – even protective against metabolic disease.</p>
<p>It’s thought that in some people subcutaneous fat stores run out of storage space (or the ability to make new fat cells) sooner than in others. This means more fat will be stored in the less safe visceral depots. Visceral fat can cause <a href="https://diabetes.diabetesjournals.org/content/56/4/1010">inflammation</a>, eventually leading to metabolic and cardiovascular disease. And if fat can no longer be stored in adipose tissue, eventually lipid can accumulate elsewhere – including the heart, muscles, and liver – which again can <a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.28821">lead to disease</a>.</p>
<p>As with height, your genes play a large part in weight and body shape. <a href="https://academic.oup.com/hmg/article/28/1/166/5098227">Large genetic studies</a> have identified over 400 of the tiniest <a href="https://www.nature.com/articles/nature14132">genome differences</a> that might contribute to body-fat distribution. For example, people who have a mutation in the LRP5 gene carry <a href="https://www.cell.com/cell-metabolism/fulltext/S1550-4131(15)00010-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1550413115000108%3Fshowall%3Dtrue">more fat in their abdomen</a> and less in their lower body. However, these tiny genetic differences are common in the population, affecting most of us in one way or another – and may explain why humans have such a range of different body shapes. </p>
<p>Unfortunately, this means that it might be more difficult for a person who naturally stores fat around their waist to maintain good health. But research also shows that weight loss can reduce visceral fat and improve <a href="https://journals.sagepub.com/doi/10.1177/1479164118825343?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed&">metabolic health</a>. So what is important to remember is that body shape is only a risk factor, and even with these differences you can still lower your risk of chronic disease if you maintain a healthy lifestyle.</p><img src="https://counter.theconversation.com/content/147067/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rebecca Dumbell has received funding from the British Society for Neuroendocrinology, The Physiological Society and The Genetics Society, and is a trustee of the British Society for Neuroendocrinology. </span></em></p>The type of fat tissue we store in certain parts of our body is partly behind this link.Rebecca Dumbell, Lecturer, Nottingham Trent UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1281482019-12-18T07:40:17Z2019-12-18T07:40:17ZNot all antipsychotics increase the risk of diabetes and raise cholesterol – some may be protective<figure><img src="https://images.theconversation.com/files/306666/original/file-20191212-85371-4vgo3s.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C7888%2C4056&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/pinkwhite-capsule-pills-spread-out-drug-1397095718">Fahroni/Shutterstock</a></span></figcaption></figure><p><a href="https://ps.psychiatryonline.org/doi/full/10.1176/ps.2006.57.12.1693">Millions of people</a> worldwide are prescribed antipsychotics every year. While these drugs are effective in treating the symptoms of schizophrenia, they can also have <a href="https://www.bap.org.uk/articles/antipsychotic-medication-and-weight-gain/">significant side-effects</a>, causing weight gain, diabetes and raised cholesterol. These are all risk factors for cardiovascular disease – the <a href="https://www.ncbi.nlm.nih.gov/pubmed/16338246">biggest killer</a> of people with schizophrenia. </p>
<p>However, our <a href="http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(19)30416-X/fulltext">latest study</a> found that not all antipsychotics cause the same degree of side-effects related to diabetes and cardiovascular disease. Indeed, some antipsychotics may improve sugar and cholesterol levels.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/schizophrenia-affects-your-body-not-just-your-brain-new-study-95452">Schizophrenia affects your body, not just your brain – new study</a>
</strong>
</em>
</p>
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<p>We pooled data from 100 randomised controlled trials (the gold standard for medical research) that examined antipsychotics in the short-term treatment of schizophrenia (six weeks, on average). We analysed the level of metabolic side-effects and their relationship to changes in the symptoms of schizophrenia. The side-effects that were studied were increases in weight and body mass index and increases in levels of glucose, cholesterol and other fats in the blood. The research compared 18 antipsychotics and the 100 trials included over 25,000 people.</p>
<p>We showed that different antipsychotics had marked differences in how they affected body weight and levels of sugar, cholesterol and other fats in the blood. Two antipsychotics in particular (clozapine and olanzapine) had a strong association with increases in body weight, glucose and cholesterol levels. </p>
<p>Those drugs with the worst side-effects produced, in only a few weeks, metabolic changes associated with an increased risk of cardiovascular disease of up to 76%. By contrast, some antipsychotics, such as lurasidone and cariprazine, were associated with improvements in glucose and cholesterol levels.</p>
<p>We also investigated which patient characteristics might predict a high level of these metabolic side-effects and found that non-white, older men were at higher risk of developing substantial metabolic side-effects when taking antipsychotics.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/307161/original/file-20191216-124031-1mkron4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/307161/original/file-20191216-124031-1mkron4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/307161/original/file-20191216-124031-1mkron4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/307161/original/file-20191216-124031-1mkron4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/307161/original/file-20191216-124031-1mkron4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/307161/original/file-20191216-124031-1mkron4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/307161/original/file-20191216-124031-1mkron4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Lurasidone is associated with improvements in blood glucose.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/test-blood-glucose-diabetes-pregnant-woman-532376782?src=ef788681-8a72-4ac3-82fa-50e652f1d17a-1-15&studio=1">Kwangmoozaa/Shutterstock</a></span>
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<h2>Side-effects linked to improvements</h2>
<p>We also showed that metabolic side-effects of antipsychotics are linked to improvement in symptoms of schizophrenia. The more weight people put on and the higher cholesterol levels go up, the greater the improvement in symptoms. One explanation for this is that the neurotransmitters that mediate metabolic side-effects might also contribute to an improvement in symptoms.</p>
<p>People with schizophrenia die up to 20 years earlier than the general public, mostly from heart attacks and stroke. Antipsychotics are widely used and some clearly play a role in increasing cardiovascular disease risk. So it’s important to understand their side-effects and how they vary between different types of medication and different people. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/is-schizophrenia-written-in-our-genes-53903">Is schizophrenia written in our genes?</a>
</strong>
</em>
</p>
<hr>
<p>This is the first time that research has compared antipsychotics on their metabolic side-effects and tried to identify which people might be more at risk of developing them. The findings that there are significant differences in side-effects between treatments have implications for the choice of antipsychotic, particularly for the at-risk groups we have identified.</p>
<p>We believe the results of the study should be reflected in treatment guidelines to help doctors and patients choose the best drug treatment for them. Drug choice should weigh up treatment benefits for symptoms against the risk of metabolic and other side-effects.</p><img src="https://counter.theconversation.com/content/128148/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Toby Pillinger does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Some antipsychotics with the worst side-effects are the best at treating symptoms.Toby Pillinger, Doctor and Clinical Researcher, King's College LondonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1271542019-12-05T16:02:06Z2019-12-05T16:02:06ZLimited eating times could be a new way to fight obesity and diabetes<figure><img src="https://images.theconversation.com/files/304824/original/file-20191202-67028-7oi1vv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Time limits on eating may help to keep diabetics' blood glucose in check.
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/glucometer-ripe-fruits-shape-clock-time-1557461105">ratmaner/Shutterstock.com</a></span></figcaption></figure><p>People with obesity, high blood sugar, high blood pressure or high cholesterol are often advised to eat less and move more, but <a href="https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30611-4">our new research suggests</a> there is now another simple tool to fight off these diseases: restricting your eating time to a daily 10-hour window.</p>
<p><a href="Http://doi.org/10.1016/j.cmet.2014.11.001">Studies done</a> <a href="Http://doi.org/10.1016/j.cmet.2012.04.019">in mice</a> and <a href="http://doi.org/10.1038/s41467-019-10563-9">fruit</a> <a href="https://doi.org/10.1126/science.1256682">flies</a> <a href="http://doi.org/10.1186/s12967-016-1044-0">suggest</a> that limiting when animals eat to a daily window of 10 hours can prevent, or even reverse, <a href="https://www.cdc.gov/pcd/issues/2017/16_0287.htm">metabolic diseases that affect millions in the U.S.</a> </p>
<p>We are scientists - <a href="https://panda.salk.edu">a cell biologist</a> and a <a href="https://profiles.ucsd.edu/pam.taub#narrative">cardiologist</a> - and are exploring the effects of the timing of nutrition on health. Results from flies and mice led us and others to test the idea of time-restricted eating in healthy people. <a href="https://doi.org/10.1016/j.cmet.2015.09.005">Studies lasting more than a year</a> showed that <a href="https://doi.org/10.1139/apnm-2018-0389">TRE was safe among healthy individuals</a>. Next, we tested time-restricted eating in patients with conditions known collectively as <a href="https://www.mayoclinic.org/diseases-conditions/metabolic-syndrome/symptoms-causes/syc-20351916">metabolic syndrome</a>. We were curious to see if this approach, which had a profound impact on obese and diabetic lab rats, can help millions of patients who suffer from early signs of diabetes, high blood pressure and unhealthy blood cholesterol. </p>
<h2>A leap from prevention to treatment</h2>
<p>It’s not easy to count calories or figure out how much fat, carbohydrates and protein are in every meal. That’s why using <a href="https://doi.org/10.1017/jns.2018.13">TRE provides</a> <a href="https://doi.org/10.1016/j.cmet.2015.09.005">a new strategy for fighting</a> <a href="http://doi.org/10.1002/oby.22449">obesity and</a> <a href="http://doi.org/10.1017/S0007114513001359">metabolic diseases</a> that affect millions of people worldwide. Several studies had suggested that TRE is a lifestyle choice that healthy people can adopt and that can <a href="http://doi.org/10.1016/j.cmet.2018.04.010">reduce their risk</a> for future metabolic diseases. </p>
<p>However, TRE is rarely tested on people already diagnosed with metabolic diseases. Furthermore, the vast majority of patients with metabolic diseases are often on medication, and it was not clear whether it was safe for these patients to go through daily fasting of more than 12 hours – as many experiments require – or whether TRE will offer any benefits in addition to those from their medications. </p>
<p>In a unique collaboration between our basic science and clinical science laboratories, we tested whether restricting eating to a 10-hour window improved the health of people with metabolic syndrome who were also taking medications that lower blood pressure and cholesterol to manage their disease.</p>
<p><a href="http://doi.org/10.1161/CIRCULATIONAHA.109.192644">We recruited patients</a> from UC San Diego clinics who met at least <a href="http://doi.org/10.1016/j.jacc.2015.06.1328">three out of five criteria</a> for <a href="https://www.nhlbi.nih.gov/health-topics/metabolic-syndrome">metabolic syndrome</a>: obesity, high blood sugar, high blood pressure, high level of bad cholesterol and low level of good cholesterol. The patients used a <a href="https://doi.org/10.1016/j.cmet.2015.09.005">research app called myCircadianClock</a>, developed in our lab, to log every calorie they consumed for two weeks. This helped us to find patients who were more likely to spread their eating out over the span of 14 hours or more and might benefit from 10-hour TRE. </p>
<p>We monitored their physical activity and sleep using a watch worn on the wrist. As some patients with bad blood glucose control may experience low blood glucose at night, we also placed a continuous glucose monitor on their arm to measure blood glucose every few minutes for two weeks. </p>
<p>Nineteen patients qualified for the study. Most of them had already tried standard lifestyle interventions of reducing calories and doing more physical activity. As part of this study, the only change they had to follow was to self-select a window of 10 hours that best suited their work-family life to eat and drink all of their calories, say from 9 a.m. to 7 p.m. Drinking water and taking medications outside this window were allowed. For the next 12 weeks they used the <a href="https://mycircadianclock.org/">myCircadianClock</a> app, and for the last two weeks of the study they also had the continuous glucose monitor and activity monitor. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/304982/original/file-20191203-66994-1n414zk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/304982/original/file-20191203-66994-1n414zk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/304982/original/file-20191203-66994-1n414zk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=629&fit=crop&dpr=1 600w, https://images.theconversation.com/files/304982/original/file-20191203-66994-1n414zk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=629&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/304982/original/file-20191203-66994-1n414zk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=629&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/304982/original/file-20191203-66994-1n414zk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=790&fit=crop&dpr=1 754w, https://images.theconversation.com/files/304982/original/file-20191203-66994-1n414zk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=790&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/304982/original/file-20191203-66994-1n414zk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=790&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Tens of millions of people in the U.S. have symptoms of metabolic syndrome.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/metabolic-syndrome-signs-symptoms-apple-pear-315847109">Designua/Shuttersock.com</a></span>
</figcaption>
</figure>
<h2>Timing is the medicine</h2>
<p>After 12 weeks, the volunteers returned to the clinic for a thorough medical examination and blood tests. We compared their final results with those from their initial visit. <a href="https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30611-4">The results, which we published in Cell Metabolism</a>, were pleasantly surprising. We found most of them lost a modest amount of body weight, particularly fat from their abdominal region. Those who had high blood glucose levels when fasting also reduced these blood sugar levels. Similarly, most patients further reduced their blood pressure and LDL cholesterol. All of these benefits happened without any change in physical activity. </p>
<p>Reducing the time window of eating also had several inadvertent benefits. On average, patients reduced their daily caloric intake by a modest 8%. However, statistical analyses did not find strong association between calorie reduction and health improvement. <a href="http://doi.org/10.1016/j.cmet.2018.04.010">Similar benefits of TRE on blood pressure and blood glucose</a> control were also found among healthy adults who did not change caloric intake. </p>
<p>Nearly two-thirds of patients also reported restful sleep at night and less hunger at bedtime – similar to what was reported in other TRE studies on <a href="https://doi.org/10.1016/j.cmet.2015.09.005">relatively healthier cohorts</a>. While restricting <a href="http://doi.org/10.1016/j.cmet.2018.04.010">all eating to just a six-hour window</a> was hard for participants and caused several adverse effects, patients reported they could easily adapt to eating within a 10-hour span. Although it was not necessary after completion of the study, nearly 70% of our patients continued with the TRE for at least a year. As their health improved, many of them reported having reduced their medication or stopped some medication. </p>
<p>Despite the success of this study, time-restricted eating is not currently a standard recommendation from doctors to their patients who have metabolic syndrome. This study was a small feasibility study; more rigorous randomized control trials and multiple location trials are necessary next steps. Toward that goal, we have started a <a href="https://clinicaltrials.gov/ct2/show/NCT04057339?term=Pam+taub&draw=2&rank=2">larger study</a> on metabolic syndrome patients. </p>
<p>Although we did not see any of our patients go through dangerously low levels of glucose during overnight fasting, it is important that time-restricted eating be practiced under medical supervision. As TRE can improve metabolic regulation, it is also necessary that a physician pays close attention to the health of the patient and adjusts medications accordingly. </p>
<p>We are cautiously hopeful that time-restricted eating can be a simple, yet powerful approach to treating people with metabolic diseases. </p>
<p>[ <em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>. ]</p><img src="https://counter.theconversation.com/content/127154/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Satchin Panda receives funding from the National Institute of Health, Department of Defense, Federal Emergency Management Agency, Helmsley Charitable trust, Robertwood Johnson Foundation, and Glenn Foundation for Medical Research. He is the author of the book "The Circadian Code" for which he receives author royalty. Satchin Panda is a founding member of the Center for Circadian Biology at UC San Diego. </span></em></p><p class="fine-print"><em><span>Pam Taub receives funding from NIDDK, American Heart Association, Department of Defense. </span></em></p>What if you could treat obesity, diabetes and high blood pressure just by limiting when you eat and drink all your calories? New research says it might work.Satchin Panda, Professor of Regulatory Biology at the Salk Institute for Biological Studies, Adjunct Professor of Cell and Developmental Biology at UCSD, University of California, San DiegoPam Taub, Associate Professor of Medicine, University of California, San DiegoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1262452019-11-04T12:17:10Z2019-11-04T12:17:10ZWhy it’s better to exercise before breakfast<figure><img src="https://images.theconversation.com/files/299853/original/file-20191101-88403-1nt4a5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">shutterstock</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/562427887?size=medium_jpg">Spectral-Design/Shutterstock</a></span></figcaption></figure><p>Exercise is recommended for people who are overweight or obese as a way to reduce their risk of developing type 2 diabetes and cardiovascular disease. But people don’t always have time to exercise as much as they would like, so finding ways to increase the health benefits of exercise is important. Our <a href="https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgz104/5599745">latest research</a> has found a way to do just that, and it’s to do with timing. This means you might be able to get away with doing less exercise if other commitments, such as family and work, always seem to get in the way.</p>
<p>To explain how this works, it helps to know a bit about insulin. Insulin is a hormone that helps control blood sugar levels. One of the main effects of insulin after a meal is to allow sugar in the blood to be transported into muscle, where it can then be stored or used as a fuel for energy. </p>
<p>When people don’t exercise enough and become overweight or obese, their bodies have to produce more insulin for the hormone to have this important effect. In other words, they become less sensitive to insulin. This is one of the reasons why being overweight increases the risk of getting type 2 diabetes and cardiovascular disease. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/should-you-eat-breakfast-53129">Should you eat breakfast?</a>
</strong>
</em>
</p>
<hr>
<p>One of the main health benefits of exercise is that it improves our response to insulin and we can better control our blood sugar levels – even if we don’t see this change happening. It is now becoming clear that when we eat in relation to exercise could be important for this insulin response.</p>
<p>Our study looked at the responses to six weeks of exercise, which was supervised cycling for 50 minutes, three times a week. In one group, overweight or obese men exercised before breakfast (fasted state) and showed an improved insulin response after the training. That is, they had to produce less insulin to control their blood sugar levels. This suggests that they had a lower risk of diseases such as type 2 diabetes after the training. But the men who performed the same exercise after eating breakfast did not show an improved blood insulin response. </p>
<p>The men who exercised before breakfast also burned about double the amount of fat during exercise than the group who exercised after breakfast. Current evidence suggests that this increased fat burning during exercise may explain why that group showed improved health benefits. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/299858/original/file-20191101-88419-15eiord.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/299858/original/file-20191101-88419-15eiord.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/299858/original/file-20191101-88419-15eiord.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/299858/original/file-20191101-88419-15eiord.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/299858/original/file-20191101-88419-15eiord.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/299858/original/file-20191101-88419-15eiord.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/299858/original/file-20191101-88419-15eiord.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Beta-cells in the pancreas release insulin in the blood vessel. Insulin stimulates the absorption of glucose in skeletal muscle.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/1334698616?src=ec3f1453-ded1-4958-8683-36d7e5c85b97-1-3&size=huge_jpg">Designua/Shutterstock</a></span>
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<h2>But don’t expect to lose more weight</h2>
<p>A common misconception about exercise in the fasted state is that the increased fat burning will lead to increased weight loss. But for weight loss, the important factor is energy balance. This is the amount of energy eaten as food and drinks minus the amount of energy that is expended by the body, partly through exercise. </p>
<p>There is <a href="https://academic.oup.com/jn/article/149/8/1326/5440571">some evidence</a>, that, over a short period (24 hours), skipping breakfast altogether and doing exercise may create a more negative energy balance, compared with eating breakfast and doing the same exercise. Yet <a href="https://www.ncbi.nlm.nih.gov/pubmed/25429252">evidence also suggests</a> that when it is only the timing of meals in relation to exercise that is changed (not skipping breakfast), the amount of weight lost will be similar even if fat burning is different. So increased fat burning during exercise does not lead to greater weight loss, unless the energy balance (for example, energy intake or energy expenditure) is different.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/skipping-breakfast-may-help-you-lose-weight-what-hunter-gatherers-can-teach-us-109840">Skipping breakfast may help you lose weight - what hunter-gatherers can teach us</a>
</strong>
</em>
</p>
<hr>
<p>It is now important to repeat the study in women, although it is likely that the same effect would be shown with exercise before versus after breakfast. This is because for men and women eating breakfast before exercise <a href="https://www.ncbi.nlm.nih.gov/pubmed/15702454">reduces fat burning during the exercise</a>. This research was also for moderate-intensity endurance exercise, such as cycling and jogging, and the results don’t necessarily apply for high-intensity exercise or weight lifting.</p>
<p>Finding ways to increase the health benefits from exercise may help to reduce the increasing prevalence of diseases such as type 2 diabetes. The new research suggests that for your health it could be better to move your feet before you eat.</p>
<hr>
<p><em>More on evidence-based articles about exercise:</em></p>
<ul>
<li><p><em><a href="https://theconversation.com/a-single-workout-could-save-your-life-88834?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=IsItTrue">A single workout could save your life</a></em></p></li>
<li><p><em><a href="https://theconversation.com/gym-membership-how-to-get-the-most-out-of-it-according-to-a-sports-scientist-107551?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=IsItTrue">Gym membership: how to get the most out of it, according to a sports scientist</a></em></p></li>
<li><p><em><a href="https://theconversation.com/keeping-fit-how-to-do-the-right-exercise-for-your-age-108851?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=IsItTrue">How to do the right exercise for your age</a></em></p></li>
</ul>
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<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/301912/original/file-20191115-66957-gxdqkd.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/301912/original/file-20191115-66957-gxdqkd.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=140&fit=crop&dpr=1 600w, https://images.theconversation.com/files/301912/original/file-20191115-66957-gxdqkd.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=140&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/301912/original/file-20191115-66957-gxdqkd.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=140&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/301912/original/file-20191115-66957-gxdqkd.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=176&fit=crop&dpr=1 754w, https://images.theconversation.com/files/301912/original/file-20191115-66957-gxdqkd.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=176&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/301912/original/file-20191115-66957-gxdqkd.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=176&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<p><em><a href="https://theconversation.com/uk/newsletters/the-daily-newsletter-2?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=GeneralBannerA126245">Click here to subscribe to our newsletter and stay healthy with guidance you can trust.</a></em></p><img src="https://counter.theconversation.com/content/126245/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rob Edinburgh does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Fasting exercise could help lower your risk of developing type 2 diabetes.Rob Edinburgh, PhD Candidate, Health, University of BathLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1023082018-08-30T15:10:56Z2018-08-30T15:10:56ZTime-restricted eating can overcome the bad effects of faulty genes and unhealthy diet<figure><img src="https://images.theconversation.com/files/233977/original/file-20180828-86132-e5wpie.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/food-clock-on-black-wood-laminate-577856071">sukrit3d/Shutterstock.com</a></span></figcaption></figure><p>Timing our meals can fend off diseases caused by bad genes or bad diet. Everything in our body is programmed to run on a 24-hour or circadian time table that repeats every day. Nearly a dozen different genes work together to produce this 24-hour circadian cycle. These clocks are present in all of our organs, tissues and even in every cell. These internal clocks tell us when to sleep, eat, be physically active and fight diseases. As long as this internal timing system work well and we obey them, we stay healthy. </p>
<p>But what happens when our clocks are broken or begin to malfunction?</p>
<p>Mice that lack critical clock genes are clueless about when to do their daily tasks; <a href="http://doi.org/10.1016/j.cell.2015.03.015">they eat randomly during day and night and succumb to obesity, metabolic disease, chronic inflammation and many more diseases</a>. </p>
<p>Even in humans, <a href="http://doi.org/10.1038/ng.3749">genetic studies</a> point to several gene mutations that compromise our circadian clocks and make us prone to an array of diseases from obesity to cancer. When these faulty clock genes are combined with an unhealthy diet, the risks and severity of these diseases skyrocket. </p>
<p>My lab studies how circadian clocks work and how they readjust when we fly from one time zone to another or when we switch between day and night shift. We knew that the first meal of the day synchronizes our circadian clock to our daily routine. So, we wanted to learn more about timing of meals and the implications for health. </p>
<h2>Time-restricted eating</h2>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/234087/original/file-20180829-195298-13f9qpf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/234087/original/file-20180829-195298-13f9qpf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/234087/original/file-20180829-195298-13f9qpf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/234087/original/file-20180829-195298-13f9qpf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/234087/original/file-20180829-195298-13f9qpf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/234087/original/file-20180829-195298-13f9qpf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/234087/original/file-20180829-195298-13f9qpf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Eating within an eight- to 12-hour window could diminish the impact of a bad diet and a broken body clock.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/red-alarm-clock-on-wood-table-580587166">amornchaijj/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>A few years ago <a href="https://doi.org/10.1016/j.cmet.2012.04.019">we made</a> a <a href="http://doi.org/10.1016/j.cmet.2014.11.001">surprising</a> <a href="https://doi.org/10.1016/j.cmet.2014.11.008">discovery</a> that when mice are allowed to eat within a consistent eight- to 12-hour period without reducing their daily caloric intake, they remain healthy and do not succumb to diseases even when they are fed unhealthy food rich in sugar or fat.</p>
<p>The benefit surpasses any modern medicine. Such an eating pattern – popularly called time restricted eating – also <a href="http://doi.org/10.1016/j.cmet.2015.09.005">helps overweight</a> <a href="http://doi.org/10.1016/j.cmet.2018.04.010">and obese humans</a> reduce body weight and <a href="http://doi.org/10.3233/NHA-170036">lower their risk for many chronic diseases</a>. </p>
<p>Decades of research had taught us what and how much we eat matters. But the new discovery about when we eat matters raised many questions. </p>
<p>How does simply restricting your eating times alter so many elements of personal health? The timing of eating is like an external time cue that signals the internal circadian clock to keep a balance between nourishment and repair. During the eating period, metabolism was geared toward nourishment. The gut and liver better absorbed nutrients from food, and used some for fueling the body while storing the rest. </p>
<p>During the fasting period, metabolism switched to rejuvenation. Unwanted chemicals were broken down, stored fat was burned and damaged cells were repaired. The next day, after the first bite, the switch flipped from rejuvenation to nourishment. This rhythm continued every day. <a href="http://doi.org/10.1126/science.aah4967">We thought that timing of eating and fasting was giving cues to the internal clock</a> and the clock was flipping the switch between nourishment and rejuvenation every day. However, it was not clear if a normal circadian clock was necessary to mediate the benefits of time restricted eating or whether just restricted eating times alone could flip the daily switch.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/234080/original/file-20180829-195304-pdiwzn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/234080/original/file-20180829-195304-pdiwzn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/234080/original/file-20180829-195304-pdiwzn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/234080/original/file-20180829-195304-pdiwzn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/234080/original/file-20180829-195304-pdiwzn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/234080/original/file-20180829-195304-pdiwzn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/234080/original/file-20180829-195304-pdiwzn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Eating late at night can disrupt circadian rhythms and raise the risk of chronic diseases including obesity.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/man-home-eating-slice-pizza-social-561470647?src=pP8uXJXhoBa_ETBrqX6seA-4-49">Ulza/Shutterstock.com</a></span>
</figcaption>
</figure>
<h2>What if you have a broken internal clock?</h2>
<p><a href="https://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30505-9">In a new study</a>, we took genetically engineered animals that lacked a functioning circadian clock either in the liver or in every cell of the body. </p>
<p>These mice, with faulty clocks don’t know when to eat and when to stay away from food. So, <a href="http://doi.org/10.1016/j.tem.2015.11.007">they eat randomly and develop multiple diseases</a>. The disease severity increases if they are fed an unhealthy diet. </p>
<p>To test if time restricted eating works with a damaged or dysfunctional clock, we simply divided these mutant mice into two different groups – one group got to eat whenever they wanted and the other group was only given access to food during restricted times. Both groups ate the identical number of calories, but the restricted eaters finished their daily ration within nine to 10 hours. </p>
<p>We thought that even though these mice had restricted eating times, having the bad clock gene would doom them to obesity and many metabolic diseases. But to our utter surprise the restricted eating times trumped the bad effects of faulty clock genes. The mice without a functioning clock that were destined to be morbidly sick, were as healthy as normal mice when they consumed food during a certain period. </p>
<p>The results have many implications for human health. </p>
<h2>The good news</h2>
<p>First of all, it raises a big question: What is the connection between our genetically encoded circadian clock timing system and external time of eating? Do these two different timing systems work together like co-pilots in a plane, so that even if one is incapacitated, the other one can still fly the plane? </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/234090/original/file-20180829-195316-piutyn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/234090/original/file-20180829-195316-piutyn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/234090/original/file-20180829-195316-piutyn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/234090/original/file-20180829-195316-piutyn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/234090/original/file-20180829-195316-piutyn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/234090/original/file-20180829-195316-piutyn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/234090/original/file-20180829-195316-piutyn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">As we age, our body clocks become less accurate, and we become more prone to chronic diseases. Keeping regular, restricted eating times can keep us healthy longer.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/group-multiethnic-senior-friends-embracing-bar-754624234?src=7YP9zkD5DaVpm8Ac9q5iJA-1-27">LightField Studios/Shutterstock.com</a></span>
</figcaption>
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<p>Deep analyses of mice in our experiment revealed that time restricted eating triggers many internal programs that improve our body’s resilience – enabling us to fight off any unhealthy consequences of bad nutrition or any other stress. This boost in internal resilience may be the key to these surprising health benefits. </p>
<p>For human health the message is simple, as I say in my new book “The Circadian Code.” Even if we have faulty circadian genes as in many congenital diseases, such as Prader-Willi syndrome or Smith-Magenis syndrome, or carry a malfunctioning copy of nearly a dozen different clock genes, as long as we have some discipline and restrict eating times, we can still fend off the bad effects of bad genes. </p>
<p>Similarly, <a href="http://doi.org/10.1172/JCI90328">other researchers have shown</a> as we get older our circadian clock system weakens. The genes don’t function correctly so our sleep-wake cycles are disrupted – just as if we had a faulty clock. So, lifestyle becomes more important for older people who are at higher risk for many chronic diseases such as diabetes, heart disease, high cholesterol, fatty liver disease and cancer. </p>
<p>As a potential translation to human health, we have created a <a href="http://mycircadianclock.org">website</a> where anyone from anywhere in the world can sign up for an academic study and download a free app called MyCircadianClock and start self-monitoring the timing of eating and sleeping. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/234075/original/file-20180829-195331-teatbc.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/234075/original/file-20180829-195331-teatbc.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=358&fit=crop&dpr=1 600w, https://images.theconversation.com/files/234075/original/file-20180829-195331-teatbc.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=358&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/234075/original/file-20180829-195331-teatbc.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=358&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/234075/original/file-20180829-195331-teatbc.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=450&fit=crop&dpr=1 754w, https://images.theconversation.com/files/234075/original/file-20180829-195331-teatbc.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=450&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/234075/original/file-20180829-195331-teatbc.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=450&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Research has shown that our daily eating, sleeping and activity patterns can affect health and determine our long-term risk for various diseases. This app is part of a research project that uses smartphones to advance research into biological rhythms in the real world, while also helping you understand your body’s rhythms.</span>
<span class="attribution"><a class="source" href="http://mycircadianclock.org/#about-study">http://mycircadianclock.org/#about-study</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>The app provides tips and guidance on how to adopt a time restricted eating lifestyle to improve health and prevent or manage chronic diseases. By collecting data from people with varying risk for disease, we can explore how eating times can help to increase our healthy lifespan. </p>
<p>We understand everyone’s lifestyle around home, work and other responsibilities is unique and one size may not fit all. So, we hope people can use the app and some tips to build their personalized circadian routine. By selecting their own time window of eight to 12 hours for eating that best fits their lifestyle, they may reap many health benefits.</p><img src="https://counter.theconversation.com/content/102308/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Satchin Panda receives funding from National Institute of Health, Department of Defense, Department of Homeland Security, American Federation of Aging Research, the Glenn Center for Aging; the Leona M. and Harry B. Helmsley Charitable Trust. He is affiliated with the Center for Circadian Biology at the University of California, San Diego. </span></em></p>You’ve heard the adage, you are what you eat. But a new study suggests that you are ‘when’ you eat may be more accurate. Restricting eating times can keep chronic diseases at bay and ward off obesity.Satchin Panda, Professor of Regulatory Biology at the Salk Institute for Biological Studies, Adjunct Professor of Cell and Developmental Biology at UCSD, University of California, San DiegoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/913272018-02-13T03:01:07Z2018-02-13T03:01:07ZWhat is your real ‘biological age’, and what does this mean for your health?<figure><img src="https://images.theconversation.com/files/206070/original/file-20180212-58344-9esozg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Biological age calculators are a crude measurement but can be a wake-up call to improve our lifestyle.</span> <span class="attribution"><a class="source" href="https://unsplash.com/photos/r4GMAtjuYj0">Lorene Farrugia</a></span></figcaption></figure><p>Age-based risk calculators that work out your “real biological age” are increasingly popular. We hear about body age on health shows like <a href="http://www.bbc.co.uk/programmes/b095gd8f">How to Stay Young</a>; gyms <a href="https://www.worldfitnesslevel.org/#/">promote</a> reductions in metabolic age and fitness age; games and apps <a href="https://www.nintendo.com/games/detail/Y9QLGBWxkmRRzsQEQtvqGqZ63_CjS_9F">claim to lower your brain age</a>; and researchers have developed specific organ measures like <a href="https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-018-0760-1">heart age</a>, <a href="https://www.ncbi.nlm.nih.gov/pubmed/18326503">lung age</a> and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955574/">bone age</a>.</p>
<p>It seems most people have a “biological age” that is older than it should be. Four out of five people, for instance, have an <a href="http://bmjopen.bmj.com/content/6/9/e011511?utm_source=trendmd&utm_medium=cpc&utm_campaign=bmjopen&trendmd-shared=1&utm_content=Journalcontent&utm_term=TrendMDPhase4">older heart age</a> than their current age. But what does this really mean?</p>
<p>All these age calculators compare your measurements for a range of health risk factors to an average or an ideal number to come up with your score. Having an older biological age on these calculators simply means you have at least one risk factor that is higher than the number set as “normal”. </p>
<p>But unless we know which specific risk factors are above normal, and how normal is defined, it’s hard to know whether you should really be worried, or what you should do about it.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/biological-vs-chronological-age-how-old-are-you-really-66962">Biological vs chronological age: how old are you really?</a>
</strong>
</em>
</p>
<hr>
<p>In the latest season of <a href="http://www.bbc.co.uk/programmes/b095gd8f">How to Stay Young</a>, researchers assess volunteers’ performance on 23 different tests and combine this into an overall body age. Individual test results are explained to each person, but the volunteers have little reaction to these numbers until they are converted into a body age. </p>
<p>Richard, an obese and inactive 49-year-old man, is reduced to tears when he sees his score: a body age of 92, more than 40 years older than his actual age. By the end of the program, he has <a href="http://www.dailymail.co.uk/health/article-4868500/How-body-20-years-older-think.html">lowered his body age by 13 years</a>, to 79. Each episode has a similar example.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/gwr_xZ9GmIg?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The last episode of the BBC/ABC show How to Stay Young featured Richard’s story (from 4.45 minutes in).</span></figcaption>
</figure>
<p>While a compelling story, it’s not entirely clear how these ages were calculated. Is it really plausible to reverse 13 years of ageing in just a few months? </p>
<p>What actually happened is Richard reduced specific risk factors to be closer to the level set as “normal” by the calculator. By standing up at work and starting cycling, he improved at least three risk factors: he increased physical activity and muscle strength, and lost 11kg to reduce his body mass index. This is not the same as reversing the ageing process at a biological level, known as “<a href="http://jcb.rupress.org/content/217/1/65">senescence</a>”.</p>
<p>Another example is heart age calculators, which are common online and have been <a href="https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-018-0760-1">used by millions of people</a> around the world. The principle is the same: if any risk factors are higher than what has been set for “normal”, then you will get an older heart age than your current age. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/206082/original/file-20180212-58331-ck8ysf.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/206082/original/file-20180212-58331-ck8ysf.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/206082/original/file-20180212-58331-ck8ysf.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=732&fit=crop&dpr=1 600w, https://images.theconversation.com/files/206082/original/file-20180212-58331-ck8ysf.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=732&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/206082/original/file-20180212-58331-ck8ysf.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=732&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/206082/original/file-20180212-58331-ck8ysf.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=920&fit=crop&dpr=1 754w, https://images.theconversation.com/files/206082/original/file-20180212-58331-ck8ysf.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=920&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/206082/original/file-20180212-58331-ck8ysf.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=920&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The NHS’s What’s your heart age? calculator (screenshot)</span>
<span class="attribution"><a class="source" href="https://www.nhs.uk/tools/pages/heartage.aspx">NHS Health Check</a></span>
</figcaption>
</figure>
<p>The problem is, the same person can get <a href="https://www.jmir.org/2014/5/e120/">an older heart age on one calculator</a> but a younger heart age on another calculator. This is because they all use <a href="https://www.ncbi.nlm.nih.gov/pubmed/25609227">different models</a> with different risk factors and different rules. Some include blood pressure and cholesterol, while others use body mass index to <a href="https://www.jmir.org/2014/9/e215/">estimate these clinical risk factors</a>. Some <a href="http://heart.bmj.com/content/96/9/708">won’t provide</a> a number for younger heart age, and set a maximum for older heart age.</p>
<p>You will also get a different heart age based on different definitions of “normal” for the same risk factor – is normal the average, or the ideal? </p>
<p>To add to the confusion, there is no universal agreement on what is ideal, as controversy over recent <a href="http://annals.org/aim/article-abstract/2670323/hypertension-limbo-balancing-benefits-harms-patient-preferences-before-we-lower">US guidelines to lower the blood pressure medication threshold</a> demonstrates. </p>
<p>If the ideal systolic blood pressure is set as 120mmHg, then what happens if you have 121mmHg? On a heart age calculator, this difference is <a href="https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-018-0760-1">enough to give you an older heart age result</a>. Clinically, this is probably not an important difference given the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278896/">variability in blood pressure readings</a>. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/health-check-what-do-my-blood-pressure-numbers-mean-29212">Health Check: what do my blood pressure numbers mean?</a>
</strong>
</em>
</p>
<hr>
<p>Since one-quarter of online heart disease risk calculators don’t explain how the calculations are done, it can be very hard to know what the result means, or <a href="http://www.jmir.org/2018/2/e29/">which one to believe</a>.</p>
<p>So is there any point to age-based risk calculators? There is <a href="https://www.ncbi.nlm.nih.gov/pubmed/20195154">some research</a> to suggest “biological age” formats like heart age have more emotional impact and may act as a wake-up call to motivate people like Richard to <a href="http://journals.sagepub.com/doi/full/10.1177/2047487313518479">change their lifestyle</a> and reduce their risk factors – which is a good thing. </p>
<p>But they can also <a href="https://www.ncbi.nlm.nih.gov/pubmed/26251465">mislead people by making them worry</a> that their risk of disease is higher than it actually is. As such, they shouldn’t be used to <a href="https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-018-0760-1">make decisions about preventive medication</a>, such as whether to take drugs to lower cholesterol levels or blood pressure. </p>
<p>If you get an older “biological age” on any of these calculators, don’t get too worried about the exact number – it’s not a direct measure of ageing or life expectancy. But it might mean you have a risk factor for chronic disease that could be reduced. Ask your doctor:</p>
<ol>
<li>Which specific risk factors are too high?</li>
<li>How is “normal” defined for those risk factors?</li>
<li>What is my absolute risk of disease (that is, my chance of having a heart attack or stroke in the next five years)?</li>
<li>How much can lifestyle and medication options reduce my risk of disease?</li>
<li>What are the risks and side effects of these options?</li>
</ol>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/ive-always-wondered-does-anyone-my-age-have-any-chance-of-living-for-centuries-83485">I've always wondered: does anyone my age have any chance of living for centuries?</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/91327/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Carissa Bonner receives funding from the National Health and Medical Research Council, the National Heart Foundation of Australia, The Royal Australian College of General Practitioners, and Therapeutic Guidelines Ltd.</span></em></p>Four in five of us have a “biological” age older than our real age, which means we have at least one risk factor that is higher than the number set as “normal”.Carissa Bonner, Research Fellow, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/690402017-01-18T19:07:49Z2017-01-18T19:07:49ZPhysical health ignored in people with mental illness<figure><img src="https://images.theconversation.com/files/150686/original/image-20161219-24303-b06w11.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The physical health of people with schizophrenia and bipolar disorder is often overshadowed by their mental health issues.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/pic-482066224.html">from www.shutterstock.com/igorstevanovic</a></span></figcaption></figure><p>Australians with serious mental illness are living on average for <a href="http://www.mentalhealthcommission.gov.au/media/39270/NMHC_ReportCard_Enhanced.pdf">10-32 years less</a> than the rest of the population, mainly due to preventable and treatable diseases like diabetes. No wonder, these early, preventable deaths have been described as a <a href="http://bjp.rcpsych.org/content/199/6/441">scandal</a>.</p>
<p>Clearly, people with mental health issues like depression, schizophrenia and bipolar disorder are not benefiting from advances in the treatment and prevention of physical disease the rest of society enjoys.</p>
<h2>A double whammy</h2>
<p>People living with serious mental health issues are significantly more likely to be obese, have impaired blood sugar levels (diabetes) and high cholesterol, risk factors collectively referred to as <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592657/">metabolic syndrome</a>. There are several reasons behind this high rate of physical disease, many of which can be modified. </p>
<p>Medications used to treat mental illness, although an essential part of treatment, can affect people’s physical health. Some medications can lead to significant weight gain, particularly in the first two years of treatment, (<a href="https://www.ncbi.nlm.nih.gov/pubmed/18547125">typically around 7kg within 12 weeks</a>). </p>
<p>Increased hunger and reduced physical activity associated with some medications are also major contributors to gaining weight. These medications have direct metabolic effects including changes in blood sugar levels, likely due to alterations in hormones such as glucagon. Understandably these serious physical side effects can lead to people not taking their medication. </p>
<p>People with mental illness are more likely to smoke, with <a href="http://psychcentral.com/news/2013/02/09/adults-with-mental-illness-smoke-one-third-of-cigarettes-in-u-s/51411.html">one third of all cigarettes smoked</a> in the US smoked by someone with a mental illness.</p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/150679/original/image-20161219-24299-1ifr8s2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/150679/original/image-20161219-24299-1ifr8s2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=420&fit=crop&dpr=1 600w, https://images.theconversation.com/files/150679/original/image-20161219-24299-1ifr8s2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=420&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/150679/original/image-20161219-24299-1ifr8s2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=420&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/150679/original/image-20161219-24299-1ifr8s2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=528&fit=crop&dpr=1 754w, https://images.theconversation.com/files/150679/original/image-20161219-24299-1ifr8s2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=528&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/150679/original/image-20161219-24299-1ifr8s2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=528&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">People with mental illness are more likely to smoke, have a poor diet and don’t tend to exercise, all of which can be addressed.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/537071362?src=vd2OKdRwYfg7_qeJ7lWTyw-1-33&id=537071362&size=medium_jpg">from www.shutterstock.com/jarareab</a></span>
</figcaption>
</figure>
<p>Having a mental illness is associated with <a href="http://www.sciencedirect.com/science/article/pii/S0022395612003172">unhealthy eating</a>, including excessive energy intake and a poor diet high in processed foods and sugary drinks. This contributes to obesity, heart disease and diabetes.</p>
<p>Mental illness is also associated with <a href="http://www.sciencedirect.com/science/article/pii/S0920996416302419">low levels of physical activity</a>, increased sitting time and <a href="http://link.springer.com/article/10.1007/s40279-016-0574-1?view=classic">poor fitness</a>. </p>
<p>It’s difficult enough to motivate the general population to take regular exercise and choose a healthy diet. But in people living with mental illness, where poor motivation can be an inherent part of the illness, these <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5080671/">barriers to a healthy lifestyle are compounded</a>.</p>
<p>Another key issue is the significant social disadvantage often associated with mental illness, which makes a healthy lifestyle even more challenging. This clearly requires a whole-of-government response, to ensure adequate support, infrastructure and funding to make a healthy lifestyle a reality.</p>
<h2>Integrating mind and body</h2>
<p>Mental health professionals usually focus on psychiatric symptoms, and often feel unqualified to deal with physical health issues. This may lead to <a href="https://www.ncbi.nlm.nih.gov/pubmed/18699951">physical health problems being overshadowed</a> and inadequately treated. Efforts are underway to ensure the mental health workforce is competent and confident in <a href="http://www.heti.nsw.gov.au/cmalgorithm/">screening for physical health issues</a> and routinely delivering evidence-based interventions.</p>
<p>Addressing the burden of poor physical health among people with mental illness is <a href="https://www.ncbi.nlm.nih.gov/pubmed/25553493">no longer a knowledge gap</a>, rather it is a failure of implementation.</p>
<p>In 2015 the <a href="https://www.ranzcp.org/">Royal Australian and New Zealand College of Psychiatrists</a> released a <a href="https://www.ranzcp.org/Files/Publications/RANZCP-Keeping-body-and-mind-together.aspx">report</a> outlining why psychiatrists and psychiatric services must</p>
<blockquote>
<p>think about the whole person, their overall health and the relationship between body and mind.</p>
</blockquote>
<p>This includes improving dietary habits, increasing physical activity and reducing smoking.</p>
<p>This cultural shift has seen the successful integration of lifestyle programs including <a href="https://www.ncbi.nlm.nih.gov/pubmed/26912471">exercise physiologists</a> and <a href="http://bjp.rcpsych.org/content/early/2016/10/20/bjp.bp.115.177139">dietitians</a> into mental health teams.</p>
<p>A <a href="https://www.theguardian.com/society/2014/jul/29/bondi-fitness-turns-tide-mental-illness">world first initiative</a> is Sydney’s <a href="https://www.youtube.com/watch?v=dFBfIq9yS_4&feature=youtu.be">Keeping the Body in Mind</a> program, where nurses, dietitians and exercise physiologists are part of mental health teams.</p>
<p>A critical next step to promoting long-term change is ensuring health professionals receive appropriate undergraduate and postgraduate training that prepares them to provide real world interventions for this vulnerable population. </p>
<p>For example, dietitians and exercise physiologists should receive training in psychopathology, while medical students need to be exposed to principles of lifestyle interventions and the interrelationship between mind and body.</p>
<p>Modern mental health treatment goals include a key focus on improving quality of life for people living with mental illness. Surely the first priority in achieving this goal must be achieving equality of life expectancy to start with.</p><img src="https://counter.theconversation.com/content/69040/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Simon Rosenbaum receives funding from Society For Mental Health Research. </span></em></p><p class="fine-print"><em><span>Katherine Samaras and Scott Teasdale do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>It’s time we saw past the mental illness in people living with schizophrenia and bipolar disorder to check their physical health too. Here’s why.Simon Rosenbaum, Society For Mental Health Research Early Career Fellow, UNSW SydneyKatherine Samaras, Professor of Medicine, endocrinologist and clinical researcher, UNSW SydneyScott Teasdale, PhD candidate, Dietitian, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/673562016-11-04T17:59:07Z2016-11-04T17:59:07ZUnderstanding the genes that make our circadian clocks tick<figure><img src="https://images.theconversation.com/files/144483/original/image-20161103-25346-xnq2es.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Time to get up.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/downloading_tips.mhtml?code=&id=334996769&size=huge&image_format=jpg&method=download&super_url=http%3A%2F%2Fdownload.shutterstock.com%2Fgatekeeper%2FW3siZSI6MTQ3ODIzMjI0NCwiYyI6Il9waG90b19zZXNzaW9uX2lkIiwiZGMiOiJpZGxfMzM0OTk2NzY5IiwiayI6InBob3RvLzMzNDk5Njc2OS9odWdlLmpwZyIsIm0iOiIxIiwiZCI6InNodXR0ZXJzdG9jay1tZWRpYSJ9LCJEdmQwYVFyemY1QXh1ZFdFUHhvcW8xczVRbGMiXQ%2Fshutterstock_334996769.jpg&racksite_id=ny&chosen_subscription=redownload_standard&license=standard&src=hOPPO2lXTzgMNTmHceZr-A-1-47">alarm clock image via www.shutterstock.com</a></span></figcaption></figure><p>Have you ever wondered why you don’t feel tired until late at night but your spouse is fast asleep at 10 p.m. and wakes spontaneously at 6 a.m.? </p>
<p>We each have an internal biological clock, called a circadian clock, that organizes the internal and external activities of our body around the 24-hour day. </p>
<p>While these clocks can be influenced by exposure to sunlight and electric light, for instance, our genes also play a role in how they function. That’s part of the reason that sleep and wake habits can vary from individual to individual. And that may also explain why certain chronotherapies, which help change the timing of the circadian clock, such as light boxes and taking the natural hormone melatonin as a supplement, vary in dose and effectiveness from person to person. </p>
<p>Circadian clocks are found in individual cells of our body. My <a href="http://www.ndbiology.com/duffield-lab/">research team</a> at the University of Notre Dame is teasing apart the molecular mechanisms of these cellular clocks, looking at how genes and the proteins they produce control the multitude of 24-hour rhythms in our bodily functions. </p>
<p>We think that an improved understanding of the circadian system, from genes through to physiology and behavior, will allow for the development of new and improved chronotherapies. </p>
<h2>How do circadian clocks work?</h2>
<p>At <a href="http://hmg.oxfordjournals.org/content/15/suppl_2/R271.full">least 15 genes</a> are thought to make up the cogs of the circadian clock mechanism. Natural genetic variations in these components can result in profound differences in circadian clocks from person to person. This is why some people have a short circadian clock cycle length or a long cycle length, and why some people are early birds and others are night owls.</p>
<p>Some of these genes and the proteins they produce form a series of interacting molecular pathways that then loop back on one another. The temporal pattern of genes being switched on and off starts afresh once every 24 hours, giving us a near perfect daily clock.</p>
<p>Circadian clocks do more than tell us when to feel sleepy and when to wake up. They are found in almost all organ systems of our body, such as in the brain, heart and liver. The clocks then modify cellular processes across the day that are specific to each tissue. When these organ systems are not in sync with one another, which can occur during shift work and jet lag, it can contribute to health problems. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/144484/original/image-20161103-25353-4eagxh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/144484/original/image-20161103-25353-4eagxh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=384&fit=crop&dpr=1 600w, https://images.theconversation.com/files/144484/original/image-20161103-25353-4eagxh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=384&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/144484/original/image-20161103-25353-4eagxh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=384&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/144484/original/image-20161103-25353-4eagxh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=482&fit=crop&dpr=1 754w, https://images.theconversation.com/files/144484/original/image-20161103-25353-4eagxh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=482&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/144484/original/image-20161103-25353-4eagxh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=482&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Out of sync.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-204951673/stock-photo-world-business-or-travel-concept.html?src=7efDO7sBpmaEfxs6v3GFXA-1-1">Clocks image via www.shutterstock.com.</a></span>
</figcaption>
</figure>
<h2>Coordinating the internal clocks is key</h2>
<p>The clock in the liver, for example, controls many of the biological
processes involved in the storage and release of energy molecules. The circadian rhythms in these cells are in tune with other organ systems in the body, such as fat cells and the brain.</p>
<p>Much of the function of the liver is given over to storing food molecules when they are in abundance, such as when we have just eaten a meal. The liver then mobilizes nutrients when we are fasting while we sleep.</p>
<p>If you eat in the middle of night, for example, that can throw off the body’s processes for storing these nutrients appropriately. Shift work and jet lag can result in metabolic problems because the timing of processes between organ systems is no longer correctly coordinated, and timing between those systems and the external environment is disrupted. The long-term ramifications of such poor coordination between our internal clocks and the external environment can result in the development of abnormal physiology, and ultimately disorders such as obesity and diabetes. </p>
<p>In fact, the incidence of cardiovascular and metabolic disease, obesity and diabetes is <a href="http://dx.doi.org/10.1186/s13098-015-0041-4">elevated in shift workers</a>, who account for about <a href="http://www.bls.gov/news.release/flex.nr0.htm">15 percent of the work force</a>. </p>
<p>Getting all of these processes on the same temporal track and in sync with the time zone you are functioning in is the key. So looking at the genes that play a role in how these clocks work can help us understand how they stay in sync. </p>
<p>Gaining a better sense of what genes are involved in regulating these circadian clocks could put us on a path to find better treatments and therapies to help people adjust to time shifts.</p>
<h2>Uncoupling the genetic brakes of the circadian clock</h2>
<p>Our lab in collaboration with the University of Oxford and Hoffmann-La Roche has identified a new biological pathway involved in resetting the circadian clock, which <a href="http://dx.doi.org/10.1016/j.cell.2013.08.004">was published in the journal Cell</a>. </p>
<p>We have found that preventing a gene called SIK1 from being expressed or inactivating the protein it produces can ease the effects of jet lag. </p>
<p>This is a remarkable finding because it reveals a new biological pathway that controls the clock resetting mechanism and because the protein that SIK1 expresses is a kinase enzyme. Protein kinases form one of the most common classes of drug targets, which makes the SIK1 protein an attractive target for pharmacological manipulation.</p>
<p>Our lab has also revealed a unique role for a gene called ID2 in regulating how <a href="http://dx.doi.org/10.1016/j.cub.2008.12.052">light resets the circadian clock</a> and how the clock can control downstream processes, including shaping the 24 hour rhythms of <a href="http://www.jbc.org/content/284/46/31735.long">fat and sugar metabolism</a> </p>
<p>In animals we have found that the absence of <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0073064">ID2 disrupts the normal cycle of feeding</a>, and makes the animals both <a href="https://www.hindawi.com/journals/jdr/2016/6785948/">lean</a> and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4262528/">super-sensitized to insulin</a>. This suggests that ID2 could be an important therapeutic target for resetting circadian clocks as well as controlling metabolic disorders, such as obesity and diabetes. </p>
<p>Animals that are missing the ID2 gene are also highly responsive to resetting of the clock by light. Instead of taking a week to adjust to a new time zone, they adapt in one to two days. Both ID2 and SIK1 appear to function as natural brakes on the resetting mechanism of the clock, and in principle could one day be drug targets for adjusting our biological rhythms.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/144485/original/image-20161103-25349-pow0th.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/144485/original/image-20161103-25349-pow0th.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/144485/original/image-20161103-25349-pow0th.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/144485/original/image-20161103-25349-pow0th.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/144485/original/image-20161103-25349-pow0th.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/144485/original/image-20161103-25349-pow0th.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/144485/original/image-20161103-25349-pow0th.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Bright light at night can shift our clocks in the wrong direction.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-391673578.html">Exhausted woman image via www.shutterstock.com.</a></span>
</figcaption>
</figure>
<h2>Bright light in the morning, and dark at night</h2>
<p>While this research is promising, treatments using this research are probably still some time off. </p>
<p>In the meantime, there are a few things you can do to help keep your internal clocks in sync and on track, and adjust to disruptions more quickly. Chronotherapies, like timed exposure to light and taking melatonin supplements, can help change the timing of the circadian clock. These methods can prevent or reduce the problems that jet lag or shift work can cause, and assist in the treatment of seasonal affective disorder.</p>
<p>Because the light of dawn resets our body clock and keeps us in sync with the outside world, getting a good dose of morning light is critical.</p>
<p>Waking in pitch darkness and driving to work in the dark does not help. Just because it says 7 a.m. on the alarm clock does not mean it is 7 a.m. in your body. Exposure to <a href="https://theconversation.com/a-dark-night-is-good-for-your-health-39161">bright light at night</a>, including that emitted from electronic gadgets, can shift your biological clock in the wrong direction, making it even harder to get up the next day. Some of us are fighting our physiology every day. </p>
<p>Keeping yourself on a fixed routine of going to sleep at the same time can also be beneficial.</p><img src="https://counter.theconversation.com/content/67356/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Giles E. Duffield receives funding from the National Institutes of Health and has received funding from the American Heart Association. </span></em></p>Gaining a better sense of what genes are involved in regulating circadian clocks could put us on a path to find better treatments and therapies to help people adjust to time shifts.Giles E. Duffield, Associate Professor in Biological Sciences, University of Notre DameLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/578542016-06-08T03:54:45Z2016-06-08T03:54:45ZSaturated fats make some cells lose track of time – and that’s bad<figure><img src="https://images.theconversation.com/files/124207/original/image-20160526-22068-i24ret.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Out of sync.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-98154296/stock-photo-three-wall-clocks-showing-time-in-different-parts-of-the-world-in-office.html?src=WgZzNTrKTL_nL1-uZOMLpQ-2-36">Clocks via www.shutterstock.com.</a></span></figcaption></figure><p>Foods high in fat, especially saturated fat, are bad for you. A high-fat diet is a risk factor for cardiovascular disease as well as metabolic disorders like <a href="http://www.ncbi.nlm.nih.gov/pubmed/9225171">obesity</a> and <a href="http://care.diabetesjournals.org/content/25/3/620.full">type 2 diabetes</a>. So why does saturated fat have these effects on the body? What’s going on in your body when you eat a fatty meal? </p>
<p>I’ve been studying circadian clocks – internal biological clocks – and how they affect human health and disease for about 30 years. </p>
<p>These clocks exist in all cells throughout the brain and body. They regulate the timing of processes, such as keeping important metabolic and inflammatory responses in check in fat and immune cells. And if the clocks in our cells can no longer tell accurate time, those cell processes won’t occur at the “right” time of day or night. </p>
<p>My previous research demonstrated that genetic and environmental alterations of internal body clocks produce <a href="http://dx.doi.org/10.1074/jbc.M113.539601">metabolic disease</a>, like diabetes and obesity. </p>
<p>What we didn’t know until recently is that not only can saturated fat actually cause “jet lag” in the internal circadian clocks in some types of cells in the body, but this effect is accompanied by strong inflammation. This suggests why consuming saturated fat can lead to metabolic disorders and heart disease. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/125585/original/image-20160607-15052-c3gb7f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/125585/original/image-20160607-15052-c3gb7f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/125585/original/image-20160607-15052-c3gb7f.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/125585/original/image-20160607-15052-c3gb7f.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/125585/original/image-20160607-15052-c3gb7f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/125585/original/image-20160607-15052-c3gb7f.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/125585/original/image-20160607-15052-c3gb7f.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Palmitate is often found in fast food.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-305776586/stock-photo-group-of-burgers-plate-and-fries-beef-isolated-on-white.html?src=pp-same_artist-305801747-AY6F4i7ApCOCTybUatpcMg-5">Burgers via www.shutterstock.com.</a></span>
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<h2>Testing ‘good’ fats and ‘bad’</h2>
<p>Our <a href="http://dx.doi.org/10.1016/j.ebiom.2016.03.037">study compared the effects</a> of a saturated fat, called palmitate, and an omega-3 polyunsaturated fat, called DHA, on body clocks and the induction of inflammation in cells. </p>
<p>We studied palmitate because it is commonly found in processed and fast foods and is known to trigger chronic inflammation, which is regarded as a causal factor in obesity and type 2 diabetes. DHA is a polyunsaturated fat (a “good” fat) and has anti-inflammatory properties, so we wanted to see if it could prevent or reduce the effect that palmitate had on cells.</p>
<p>We experimented on cultured mouse cells. Some cells were treated with either DHA or palmitate alone and other cells received palmitate and DHA at the same time so we could find out if healthy fat could protect cells from the effects of saturated fat.</p>
<p>After treating cells with palmitate and DHA at different times of the day, we analyzed the cells’ inflammatory markers. To read the cells’ “internal clocks” we measured how much their “molecular gears” luminesced or “glowed” in real time. This tells us where the cell is in its circadian cycle and if its processes are happening in sync with the cells around it.</p>
<h2>Saturated fat ‘jet lags’ circadian clocks</h2>
<p>We found that palmitate resets circadian clocks in some cells, but not all. If all clocks throughout the body were reset, then palmitate probably wouldn’t impose any noticeable changes. The time zone might shift, but all of the cells would in the same one, and would still work in sync.</p>
<p>Having some cells functioning in different “time zones” has consequences for our health.</p>
<p>For cells, functioning in a different time zone than the other cells around them is confusing. Think for a moment of how muddled you feel when you travel to a time zone that’s even just a few hours off from where you normally live. It takes a while to adjust, and until you do, you might get hungry, get sleepy or wake up at weird times. Now imagine the utter confusion for your body in trying to adjust internally to multiple time zones simultaneously so that many cells in your body feel that way, while other don’t.</p>
<p>“Jet lag” isn’t the only problem that palmitate causes for cells. It also induces inflammation in several different cell types. These two effects fluctuate in sync. For instance, in fat cells, both the inflammatory and jet lagging effects appear to peak at night. While there is no good time to eat saturated fat, it’s probably not a great idea to eat a meal rich in these “bad” fats late at night. </p>
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<img alt="" src="https://images.theconversation.com/files/122148/original/image-20160511-18140-mokrg5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/122148/original/image-20160511-18140-mokrg5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/122148/original/image-20160511-18140-mokrg5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/122148/original/image-20160511-18140-mokrg5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/122148/original/image-20160511-18140-mokrg5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/122148/original/image-20160511-18140-mokrg5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/122148/original/image-20160511-18140-mokrg5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">There’s no good time to eat saturated fat, but nighttime is especially bad.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-246715423/stock-photo-portrait-of-a-man-taking-food-from-refrigerator.html?src=pu3SEXznqbFkzAhAvKo3Pg-2-7">Man and fridge via www.shutterstock.com.</a></span>
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<p>We also tried to find out whether specific polyunsaturated “good” fats had protective effects on cells, and could counteract palmitate’s jet lagging and inflammatory effects.</p>
<p>We found that DHA, a common omega-3 polyunsaturated fatty acid, is anti-inflammatory. Besides inhibiting the inflammatory response to palmitate, this omega-3 also prevented cell clocks from being reset. </p>
<h2>Turning inflammatory responses on and off</h2>
<p>I think this work has significant implications in the management or prevention of metabolic and other inflammation-related disorders such as cardiovascular disease, stroke and arthritis. </p>
<p>Further studies with animal models will help us understand how saturated fats exacerbate inflammation. In terms of prevention, we can start looking at timed administration of omega-3 fatty acids or other anti-inflammatory treatments to prevent this jet lag and chronic inflammation.</p>
<p>There could be some benefit, for example, in figuring out how to use saturated fats like palmitate to turn on the body’s inflammatory responses. If we can figure out how to do that in specific tissues at specific times, we can use saturated fats to help the body respond to infection or injury. </p>
<p>Learning more about these cell-specific circadian clock changes and why they amplify inflammation will give us a better understanding of why high-fat diets, and saturated fat in particular, lead to metabolic disorders, like obesity.</p><img src="https://counter.theconversation.com/content/57854/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David J. Earnest receives funding from American Heart Association. </span></em></p>Saturated fats are linked to metabolic disorders and heart disease. That may be because thes fats make some cells lose track of time, causing inflammation.David J. Earnest, Professor of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center, Texas A&M UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/271802014-06-18T20:42:14Z2014-06-18T20:42:14ZWhy artificial sweetener can be dangerous<figure><img src="https://images.theconversation.com/files/51509/original/qvmq4989-1403070628.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">An excess of the one of the two amino acids in the artificial sweetener aspartame is a significant concern for people with phenylketonuria.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/wetterberg/3263493189">Hugo Wetterberg/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p>When you buy a diet coke, or any other consumables containing the artificial sweetener aspartame, you’ll see a warning against consuming the product if you have phenylketonuria, an inherited metabolic disorder. </p>
<p>“Artificial” sweeteners, such as NutraSweet and Equal, are not saccharides – the simple carbohydrates we call sugars. Instead, the sweetener aspartame is a <a href="http://upload.wikimedia.org/wikipedia/commons/thumb/d/df/Methylcarboxylate_General_Structure.png/200px-Methylcarboxylate_General_Structure.png">methyl ester</a> comprising two joined amino acids: aspartic acid and phenylalanine (Phe) – this is important for later so keep it in mind. </p>
<p>The safety of aspartame for general consumption has attracted attention since its discovery in 1965, but there’s <a href="http://theconversation.com/sweet-news-no-evidence-that-artificial-sweetener-aspartames-bad-for-you-12608">no evidence</a> of association with adverse effects. The warning on products containing aspartame is specifically for those with the severe disorder known as phenylketonuria.</p>
<h2>Genetic basis</h2>
<p>For someone to have phenylketonuria, they have to inherit an incorrect copy of a gene involved in Phe breakdown from each parent. Typically, the parents of an affected person (known as carriers) each have one correct and one incorrect copy of the gene, so are unaffected themselves. </p>
<p>The main feature of the condition is the body’s inability to break down excess Phe (recall that this one of the two amino acids in aspartame). Now, this part gets complicated but stay with me.</p>
<p><a href="http://www.nlm.nih.gov/medlineplus/ency/article/002222.htm">Amino acids</a> can join linearly and fold into three dimensional shapes to construct functional proteins that perform a wide range of roles in our bodies. We produce some amino acids ourselves, but others, including Phe, must be obtained directly from our diet. </p>
<p>Amino acids can’t be stored by the body if we consume them in excess (unlike fats, for instance, and carbohydrates), so we need a constant supply. They also can’t be directly eliminated from the body, which means when excess amino acids are ingested, each type has to be broken down in a specific sequence of steps before excretion.</p>
<p>The first step in the degradation of Phe is its conversion to tyrosine, an amino acid important in neurotransmission (when signalling molecules from one neuron bind to and activate another). </p>
<p>This reaction requires an enzyme as well as the assistance of a sidekick (enzyme co-factor). The enzyme is produced through expression of its corresponding gene, and a problem arises when there are mutations in this gene. </p>
<p>There are <a href="http://theconversation.com/variomics-seeks-to-understand-what-makes-us-unique-12957">548 separate mutations</a> recorded for this gene that lead to the production of a differing enzyme, which means the body may not be able to break Phe down. </p>
<p>This differing enzyme has a reduced ability of perform the initial step in the breakdown of Phe, so the level of the amino acid in the body rises. And this has a toxic effect on neurons. Early detection of high Phe levels and intervention is vital to avoid severe mental disability. </p>
<h2>Diagnosis and treatment</h2>
<p>Phenylketonuria was first identified by Asbjorn Folling, a biochemist and physician, who noticed an unusual odour in the urine of some individuals with developmental delays. This smell was due to a molecule produced by the body when Phe accumulates.</p>
<p>A diagnostic test that worked reliably from around eight weeks of age (a drop of ferric copper added to a wet nappy would turn green in a positive test) was developed in the late 1950s. The problem was that, by this age, untreated babies had often already suffered brain damage. </p>
<p>Only a few years later, a new, more sensitive method permitted detection from three days after birth. The Guthrie or heel-prick test requires only a drop of blood from an infant. This blood is spotted on a paper disk and placed on growth media featuring bacteria unable to synthesise Phe. </p>
<p>Growing bacteria – because the Phe present in the blood spot supplements what they are unable to produce themselves – represents a positive result.</p>
<p>The <a href="http://en.wikipedia.org/wiki/Neonatal_heel_prick">heel-prick test</a> is widely performed as part of neonatal screening programs. But the diagnostic test now uses a technique called tandem <a href="http://en.wikipedia.org/wiki/Mass_spectrometry">mass spectrometry</a> and screening includes a wide range of conditions.</p>
<p>In the 1950s, a low-Phe diet was introduced for people with this severe metabolic disorder and it continues to be the predominant treatment. Since Phe is found in most food sources, the diet involves getting most energy intake from a formula instead of meals, supplemented by a small amount of foods low in protein (such as fruit and vegetables). </p>
<p>The restrictive nature of this diet means researchers are still looking for better treatments avenues. A <a href="http://www.sciencedirect.com/science/article/pii/S1096719212001473">synthetic form of the enzyme co-factor</a> is one option, as it an <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3205297/">enzyme able to break down Phe</a> and <a href="http://theconversation.com/explainer-what-is-gene-therapy-19883">gene therapy</a>.</p>
<p>But the reason why people with phenylketonuria can’t have aspartame-sweetened food is because, during digestion, it can separate into its component amino acids (aspartic acid and Phe). And this is bad news for people with the disorder.</p><img src="https://counter.theconversation.com/content/27180/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rebecca LeBard does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>When you buy a diet coke, or any other consumables containing the artificial sweetener aspartame, you’ll see a warning against consuming the product if you have phenylketonuria, an inherited metabolic…Rebecca LeBard, Associate Lecturer, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/19042012-02-16T19:38:09Z2012-02-16T19:38:09ZAppearance vs. reality: the perfectly healthy obese<figure><img src="https://images.theconversation.com/files/7771/original/5fpb79pk-1329394797.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Evidence suggests that up to 30% of people who are obese are perfectly healthy.</span> <span class="attribution"><span class="source">Rudd Centre for Food Policy</span></span></figcaption></figure><p>No one can claim to be unaware of the risks of obesity in this day and age. Almost every day there are discussions in the media about the risks of carrying excess fat. But research shows the link between obesity and ill-health is not as simple as it’s often made out to be.</p>
<p>Obesity is all over the media – newspaper and magazine articles talk about high blood pressure, diabetes, heart disease and more unusual illnesses linked to obesity, such as sleep apnoea; there are suggested diets and exercise plans to help reduce fat at every turn and; popular, humiliating television shows enforce strict weight-loss regimens on the morbidly obese while providing entertainment.</p>
<p>But while <a href="http://www.cell.com/trends/endocrinology-metabolism/abstract/S1043-2760(11)00193-7">research shows</a> obese people often have metabolic conditions such as high blood pressure, diabetes and cardiovascular disease, this is not the whole picture. What’s rarely, if ever, mentioned in the popular press (although it’s receiving growing interest in scientific circles) is the phenomenon of the metabolically healthy obese. </p>
<p>In most obese people, we can find evidence of metabolic abnormalities that result from the excess fat they carry. We can measure that these people need more of a hormone called insulin from their pancreas when they eat, to help burn up glucose in their cells. We call this phenomenon “insulin resistance”. It’s insulin resistance that eventually causes obesity-related complications such as high blood pressure, high blood fat levels, diabetes and heart disease. </p>
<p>There has, of course, always been something of a paradox around fatness and the <a href="http://www.halls.md/ideal-weight/met.htm">Metropolitan Life Insurance Tables</a> survival curves, which show how long people live at different body weights. In the Life Insurance Tables, being overweight in itself is not actually a risk for early death – certainly not when compared with being underweight. This may, in part, relate to the fact that serious illnesses are often heralded by long-term insidious weight loss, particularly as we get older. It’s only at obese levels of weight that mortality is clearly higher.</p>
<p>Up to ⅔ of adults are now overweight or obese – why is obesity so common? Evolution gave many of us particularly good “thrifty” genes that help us to eat fast, store fat easily and not waste energy in futile exercise. Theses genes were very important in times of famine because they ensured people had enough energy (or fat) stored to raise their young and still be healthy. </p>
<p>Unfortunately, the environment has recently been giving us too many opportunities to grow that fat store, and, for some, the consequences of excess fat are – as we hear so often – dangerous for health.</p>
<p>But while being in the obese range (Body Mass Index or BMI – weight in kilogram² divided by height in centimetres – of 30 and over) increases mortality, there are some people in that category who are somehow protected from the risks of metabolic harm. The most fascinating part of this is evidence suggests that <a href="http://www.cell.com/trends/endocrinology-metabolism/abstract/S1043-2760(11)00193-7">up to a ⅓ of people who are obese are metabolically healthy</a>. But there’s not yet universal agreement on the percentage of people who are in this group so research to identify them is important.</p>
<p>Of course, being active and exercising even if your weight remains high is better than not being active at all. But exercise doesn’t appear to explain why some obese people are healthy, as many obese people are quite sedentary. </p>
<p>For metabolically healthy obese people, a strong lifelong focus on losing weight may be misplaced if there are no other disease risks attributed to their weight. But it’s also important to research whether these people are, in fact, permanently protected from insulin resistance and its metabolic consequences, particularly if they gain more weight as they age. </p>
<p>This is of great important because if some people are really protected from obesity-related health risks in the long term, obesity treatment could benefit from understanding how that protection works.</p>
<p>Our research group at the Garvan Institute <a href="http://www.ncbi.nlm.nih.gov/pubmed/20547978">studied the short-term effect of weight gain</a> by overfeeding healthy individuals (some of whom were overweight or obese) for one month. We studied them before and after they ate about 1,000 kJ extra every day – some of it in high-fat snacks. On average, there was a deterioration in our subjects’ insulin sensitivity and they gained extra liver fat as they gained weight. </p>
<p>But responses varied and some people remained insulin sensitive despite their weight gain. We are now planning a longer study to follow up subjects we tested five years ago to see what has happened to their metabolism as they gained (or possibly lost) weight over time. </p>
<p>If we can find out what protects some people from the common metabolic consequences of obesity such as high blood pressure, diabetes and heart disease, we’ll be better able to treat obese people with these problems. This fascinating puzzle will take time to resolve but what we do know is that not all obesity is unhealthy. </p><img src="https://counter.theconversation.com/content/1904/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Lesley Campbell does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>No one can claim to be unaware of the risks of obesity in this day and age. Almost every day there are discussions in the media about the risks of carrying excess fat. But research shows the link between…Lesley Campbell, Principal researcher at Garvan Institute & Conjoint Professor of Medicine, UNSW,, Garvan InstituteLicensed as Creative Commons – attribution, no derivatives.