tag:theconversation.com,2011:/us/topics/folic-acid-10910/articlesFolic acid – The Conversation2023-12-22T10:16:26Ztag:theconversation.com,2011:article/2200692023-12-22T10:16:26Z2023-12-22T10:16:26ZMost expectant mothers miss out on vitamins important for their health and their baby’s, study finds<figure><img src="https://images.theconversation.com/files/566580/original/file-20231219-23-vklpav.jpg?ixlib=rb-1.1.0&rect=11%2C11%2C7704%2C5151&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Certain micronutrients are important for the health of the mother and baby during pregnancy.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/pregnant-woman-reading-label-on-bottle-2117288603">Dragana Gordic/ Shutterstock</a></span></figcaption></figure><p>Our bodies require many important vitamins and minerals in order to function well. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662251/">B vitamins</a>, for example, are particularly important for many of our everyday functions – including energy levels, cell health and nerve function. </p>
<p>These vitamins become even more important when a mother is pregnant, as low levels of some vitamins (such as folic acid, also known as vitamin B9) are associated with <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218540/#:%7E:text=of%20the%20fetus.-,Folate%20deficiency%20has%20been%20associated%20with%20abnormalities%20in%20both%20mothers,(NTDs)%20in%20the%20offspring.">poor health outcomes</a> during pregnancy and for the infant after birth.</p>
<p>Since our body only makes many of these micronutrients in small amounts (if at all), we get the bulk of them from our diet. But <a href="https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004260">our recent study</a> showed that the majority of expectant mothers are missing out on many important vitamins – which could potentially have an affect on, not only their health, but their infant’s too.</p>
<p>We conducted a large study of over 1,700 women aged 18-38 in the UK, Singapore and New Zealand. We studied their health before, during and after pregnancy. </p>
<p>Before pregnancy, we found that nine in ten of the women had low blood levels of many important vitamins, including folic acid, riboflavin, vitamin B12 and vitamin D. <a href="https://www.mayoclinic.org/healthy-lifestyle/pregnancy-week-by-week/in-depth/prenatal-vitamins/art-20046945">These vitamins are needed</a> to support the mother’s health during pregnancy, and are important for the unborn baby’s development.</p>
<p>For the next part of the study, we randomly placed participants into two different groups. One group received a standard pregnancy vitamin supplement, which contained folic acid. The other group received an “enhanced” supplement, which contained folic acid, as well as riboflavin, vitamins B6, B12 and D. The amount of vitamins in the enhanced supplement was similar to what you can buy from pharmacies and supermarkets without a prescription.</p>
<p>Both groups took these supplements daily starting from when they were trying to get pregnant and throughout their pregnancy. They stopped taking them after delivering the baby.</p>
<p>We found that the enhanced supplement helped improve blood vitamin levels and reduced the prevalence of vitamin deficiency during pregnancy – especially when it came to riboflavin, vitamin B6 and vitamin D. The standard supplement increased levels of folic acid, but levels of other vitamins worsened during pregnancy. This was probably because of the increased needs during this time.</p>
<p>Riboflavin is important during pregnancy as low levels can mean a higher chance of having a <a href="https://doi.org/10.1017/S002966512100046X">low blood count and anaemia</a>.</p>
<p>For vitamin B6, the group taking the standard supplement had lower levels in the later part of pregnancy, meaning they might not have enough of this vitamin. Previous research has suggested vitamin B6 may <a href="https://pubmed.ncbi.nlm.nih.gov/27701665/">provide some relief</a> from pregnancy-related nausea and vomiting. </p>
<figure class="align-center ">
<img alt="A nauseous pregnant woman lays on a couch." src="https://images.theconversation.com/files/566581/original/file-20231219-21-8ht821.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/566581/original/file-20231219-21-8ht821.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/566581/original/file-20231219-21-8ht821.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/566581/original/file-20231219-21-8ht821.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/566581/original/file-20231219-21-8ht821.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/566581/original/file-20231219-21-8ht821.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/566581/original/file-20231219-21-8ht821.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">B6 may help with pregnancy nausea.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/depressed-pregnant-woman-resting-home-alone-2273536815">christinarosepix/ Shutterstock</a></span>
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<p>In both groups we saw a drop in homocysteine levels, with this being particularly marked in those taking the enhanced supplement. A lower homocysteine level is actually a good thing as it indicates a lower likelihood of vitamin deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/11641651/">High homocysteine levels</a> are linked with early pregnancy loss and a range of pregnancy complications, including preeclampsia. </p>
<p>The benefits of the enhanced supplement on the participants’ vitamin B12 levels lasted six months after having a baby. This is probably important for the mother’s ability to supply her baby with vitamin B12 if she breastfeeds. B12 helps children’s <a href="https://www.cdc.gov/breastfeeding/breastfeeding-special-circumstances/diet-and-micronutrients/vitamin-b12.html#:%7E:text=Vitamin%20B12%20is%20transferred%20through,will%20receive%20enough%20vitamin%20B12.">brain development and growth</a>.</p>
<h2>Important micronutrients</h2>
<p>Though our study included women from three different countries and various ethnic backgrounds, few black and American Indian women were included in the research. This means the results might not represent the experiences of women from these specific ethnic groups. It will be important for future studies to investigate vitamin levels in these groups.</p>
<p>The precise benefits of the improved vitamin levels will also need to be investigated further in future studies. But, we might speculate that the supplements will have additional benefits, based on what previous studies have shown.</p>
<p>For example, our <a href="https://pubmed.ncbi.nlm.nih.gov/33782086/">previous research</a> has shown that women taking the same enhanced supplement had lower rates of pre-term delivery, and also a lower risk of major haemorrhage after delivery of the baby.</p>
<p>It’s also well-known that <a href="https://pubmed.ncbi.nlm.nih.gov/1677062/">folic acid</a> is important during pregnancy, as it can help prevent major defects to the developing baby’s brain and spine. Taking a folic acid supplement before conception and in the first part of pregnancy is routinely recommended. </p>
<p>But many pregnancies are unplanned and a significant number of women do not take folic acid supplements in early pregnancy. This is why around 80 countries have introduced mandatory fortification of staple foods. But many experts feel that the level of fortification in foods <a href="https://jamanetwork.com/journals/jama/article-abstract/2807770">may not be enough</a> for pregnant women, which is why a supplement will still be important. </p>
<p>Taking vitamin D supplements before and during pregnancy may also have benefits, including reducing the chances of <a href="https://pubmed.ncbi.nlm.nih.gov/35763390/">infantile atopic eczema</a> (a condition which causes patches of itchy, cracked and sore skin) and <a href="https://pubmed.ncbi.nlm.nih.gov/35866154/">improving bone health</a> in children.</p>
<p>Overall, our study showed that most women living in high-income countries don’t get enough essential vitamins in their diet – even before they get pregnant. Several of these vitamins are <a href="https://pubmed.ncbi.nlm.nih.gov/30673669/">crucial for the infant’s development</a> in the womb. </p>
<p>Although some of these vitamins can be found in meat and dairy products, it’s clear that the majority of women still aren’t getting enough of them regardless of what sort of diet they follow. As more people choose to eat more plant-based foods, better advice about vitamin-rich foods will be needed. Many women may probably need to start taking supplements to ensure they get the vitamins they and their baby need.</p><img src="https://counter.theconversation.com/content/220069/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Keith Godfrey has received funding from the UK Medical Research Council, the National Institute for Health and Care Research and the European Union. He has received reimbursement for speaking at conferences sponsored by companies selling nutritional products, and is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, BenevolentAI Bio Ltd. and Danone. He is Co-Chair of the not-for-profit UK Preconception Partnership. </span></em></p><p class="fine-print"><em><span>Sarah El-Heis has received funding from the National Institute for Health and Care Research.</span></em></p>Our study found that before pregnancy, nine in ten women had low blood levels of many important vitamins.Keith Godfrey, Professor of Epidemiology and Human Development, University of SouthamptonSarah El-Heis, Associate Professor of Dermatology, University of SouthamptonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1301812020-01-23T18:46:54Z2020-01-23T18:46:54ZJoaquin Phoenix’s lips are not like Napoleon’s − here’s what everyone should know about cleft lip<figure><img src="https://images.theconversation.com/files/311185/original/file-20200121-117933-16v4fic.jpg?ixlib=rb-1.1.0&rect=122%2C47%2C3176%2C2227&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Joaquin Phoenix won the award for outstanding performance by a male actor in a leading role for 'Joker' at the 26th annual Screen Actors Guild Awards. </span> <span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/26thAnnualSAGAwards-PressRoom/6f4e297798694088b9f9603784f48604">Jordan Strauss/Invision via AP</a></span></figcaption></figure><p>Starring in the <a href="https://collider.com/napoleon-global-box-office-78-million/">November 2023 film “Napoleon,”</a> Joaquin Phoenix is back in the limelight, along with the prominent scar on his upper lip. You may recall in 2020, after discussing Phoenix’s appearance on her talk show, Wendy Williams received near universal <a href="https://www.today.com/health/wendy-williams-blasted-mocking-joaquin-phoenix-s-cleft-palate-scar-t171887">condemnation</a> for mocking those affected with cleft lip – a common birth defect in which the upper lip does not form completely while still an embryo. Note that it is also unclear whether Phoenix has a cleft lip or simply a scar. To her credit, Williams was quick to apologize. Regardless, this renewed attention to Phoenix’s scar offers another opportunity to highlight how people with facial differences (and their families) often feel stigmatized and can face discrimination and <a href="https://doi.org/10.4103/2231-0746.200336">social isolation</a>. </p>
<p>We have each devoted major portions of our professional lives to understanding what causes clefts and to the treatment and advocacy of those affected. <a href="https://scholar.google.com/citations?user=2Nq1fLsAAAAJ&hl=en">We are</a> <a href="https://scholar.google.com/citations?user=GYMrNdIAAAAJ&hl=en">geneticists</a> and a <a href="https://www.dental.pitt.edu/people/bernard-j-costello-dmd-md">pediatric craniomaxillofacial surgeon</a>. The three of us felt this was an opportunity to explain how clefts form and how clefts affect the people who live with them. And what, if anything, can be done to prevent them?</p>
<h2>The ABCs of clefting</h2>
<p>There are several different types of facial clefts. The most common are cleft lip, when the upper lip does not form properly, leaving a gap, and cleft palate, when the roof of the mouth does not close while a baby is developing in utero.</p>
<p>These birth defects arise very early during development when the embryo is about the size of a grain of rice. At this stage, the face is merely a collection of swellings rapidly growing toward one another in order to <a href="https://doi.org/10.1038/nrg2933">fuse together</a> and form the lips, nose and palate. Thus, in a way, everyone starts out with clefts of the lip and palate.</p>
<p>In most cases, these swellings fuse before the end of the first trimester of pregnancy, forming an intact lip and palate. When this fails to happen, a child is born with a cleft of the lip, the palate or both. Worldwide, facial clefts are estimated to occur in <a href="https://doi.org/10.4103/2231-0746.200336">1 in 700 births</a>, making it one of the most common birth defects. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/311628/original/file-20200123-162240-i0s4a3.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Illustration showing before and after depictions of cleft lip and cleft lip palate repair" src="https://images.theconversation.com/files/311628/original/file-20200123-162240-i0s4a3.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/311628/original/file-20200123-162240-i0s4a3.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=245&fit=crop&dpr=1 600w, https://images.theconversation.com/files/311628/original/file-20200123-162240-i0s4a3.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=245&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/311628/original/file-20200123-162240-i0s4a3.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=245&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/311628/original/file-20200123-162240-i0s4a3.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=308&fit=crop&dpr=1 754w, https://images.theconversation.com/files/311628/original/file-20200123-162240-i0s4a3.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=308&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/311628/original/file-20200123-162240-i0s4a3.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=308&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Cleft lip and palate are two of the most common birth defects worldwide.</span>
<span class="attribution"><a class="source" href="https://upload.wikimedia.org/wikipedia/commons/0/09/Cleft_Lip_%26_Cleft_Palate_Repair.png">BruceBlaus/Wikimedia</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<h2>How clefts harm quality of life</h2>
<p>People with cleft lip and palate, as well as their families, face many issues associated with these birth defects. Although clefts may seem like cosmetic problems, they adversely affect basic functions like eating and speaking. Children with clefts must endure multiple corrective surgeries, often beginning when they are only a few months old. However, the surgeries are often just the beginning. </p>
<p>Many years of intensive orthodontic treatment and speech therapy are routinely needed. The <a href="https://doi.org/10.1111/j.1601-0825.2009.01588.x">total lifetime treatment cost</a> is estimated to be at least US$200,000 per individual. Beyond immediate medical care, individuals born with a cleft also tend to <a href="https://doi.org/10.1136/archdischild-2017-313777">experience more learning difficulties</a>, <a href="https://doi.org/10.1136/archdischild-2017-313777">higher mortality rates</a> at all stages of life and <a href="https://doi.org/10.1093/aje/kwi132">higher risk for other disorders</a>, such as breast, brain and colon cancers. </p>
<p>Children born in the U.S. with these conditions are lucky to have these supports, given the myriad challenges cleft lips and palates present. There are superb teams dedicated to <a href="https://acpa-cpf.org/">advocacy</a>, to their <a href="https://acpacares.org">care</a> and <a href="https://www.smiletrain.org/">support</a>, and <a href="https://www.asha.org/advocacy/">who work</a> to address the needs of the children and their families.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/311207/original/file-20200121-117907-1ydz595.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Person holding baby with cleft lip next to another person holding a clipboard" src="https://images.theconversation.com/files/311207/original/file-20200121-117907-1ydz595.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/311207/original/file-20200121-117907-1ydz595.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/311207/original/file-20200121-117907-1ydz595.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/311207/original/file-20200121-117907-1ydz595.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/311207/original/file-20200121-117907-1ydz595.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/311207/original/file-20200121-117907-1ydz595.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/311207/original/file-20200121-117907-1ydz595.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"></a>
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<span class="caption">In China, orphanages mostly house children abandoned by their families because of serious medical issues, including cleft lip.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Emptying-The-Orphanages/badb3d4b1c0f4a89a3d7b8f16f3c3bb4/2/0">AP Photo/Ng Han Guan</a></span>
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<h2>Multiple factors cause clefts</h2>
<p>Facial clefts have likely been around for as long as people have. An early example is the pharaoh Tutankhamun, better known as King Tut, who suffered from a <a href="https://doi.org/10.1001/jama.2010.121">partial cleft palate</a>.</p>
<p>Because clefts are often externally visible features, many have tried to explain their occurrence. An early hypothesis suggested that the mother was pregnant during an <a href="https://doi.org/10.1597/06-113.1">eclipse</a>, while <a href="http://www.opensourceshakespeare.org/views/plays/play_view.php?WorkID=midsummer&Act=5&Scene=1&Scope=scene&LineHighlight=2252#2252">Shakespeare</a> attributed the feature to an intervention by mischievous sprites. Many cultures also believed that clefts were “<a href="https://doi.org/10.1146/annurev-genom-090711-163729">in the blood</a>,” or familial, which aligns with current understanding.</p>
<p>Our group at the University of Pittsburgh has spent many years trying to understand the causes of clefts, with some notable successes.</p>
<p>Clefts are considered “complex” by those who study birth defects, meaning that they result from a combination of environmental factors during pregnancy and family genetics. Some of the environmental causes include taking certain <a href="https://doi.org/10.1186/s12916-017-0845-1">prescription medications</a> and <a href="https://doi.org/10.1080/15459624.2018.1484127">exposure to some toxins</a> during pregnancy. </p>
<p>The completion of the <a href="https://doi.org/10.1080/15459624.2018.1484127">Human Genome Project</a> in the late 1990s and early 2000s provided important scientific tools for us to tease out the genetic factors leading to complex traits such as facial clefts. To date, scientists have identified at least <a href="https://doi.org/10.12688/f1000research.9503.1">30 possible genetic regions</a> increasing the risk of facial clefts, and we suspect that there are still many more regions to discover. </p>
<p>However, population-level studies such as the ones that identified those 30 genetic regions can tell us only so much. Researchers still face a major challenge identifying the specific genes that confer risk to specific individuals and families. There are other mysteries as well, such as why cleft palate alone is more common in girls, but when cleft palate is combined with cleft lip, it is <a href="https://doi.org/10.1016/S0140-6736(09)60695-4">more common in boys</a>.</p>
<h2>Are clefts preventable?</h2>
<p>Parents who have a child with a cleft sometimes blame themselves. This is unfortunate, because there are still no known measures parents can take that will definitively prevent a facial cleft.</p>
<p>Doctors do know that <a href="https://doi.org/10.1016/j.annepidem.2016.11.009">smoking</a> and <a href="https://doi.org/10.1001/archpediatrics.2011.185">poor nutrition</a> during pregnancy can increase the chances of having a baby with a cleft. There is also some evidence that <a href="https://doi.org/10.1097/SCS.0000000000004488">supplementation with folic acid</a> before and during pregnancy may provide some protection. </p>
<p>As scientists learn more about the genetic and environmental risk factors for clefting, new actionable evidence will hopefully emerge that will bolster prevention efforts. Our most important task, however, is to work toward improving the quality of life for those affected. That starts with understanding.</p>
<p><em>This article was updated on Nov. 27, 2023 to note Joaquin Phoenix’s role in the film “Napoleon.”</em></p><img src="https://counter.theconversation.com/content/130181/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mary L. Marazita receives funding from the National Institutes of Health, primarily the National Institute of Dental and Craniofaical Research. </span></em></p><p class="fine-print"><em><span>Bernard J Costello is affiliated with the AACMFS and ACPA. Past-president of the American Academy of Craniomaxillofacial Surgeons and Past-President of the American Cleft Palate-Craniofacial Association. </span></em></p><p class="fine-print"><em><span>Seth M. Weinberg receives funding from the National Institutes of Health. </span></em></p>Joaquin Phoenix has previously been mocked for a facial scar that some have assumed is a cleft lip. Two geneticists and a surgeon explain what causes this common birth defect.Mary L. Marazita, Director, Center for Craniofacial and Dental Genetics; Professor of Oral Biology and of Human Genetics, University of PittsburghBernard J. Costello, Associate Vice Chancellor and Professor, University of PittsburghSeth M. Weinberg, Professor of Oral and Craniofacial Sciences and Human Genetics, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/953022018-05-02T10:45:26Z2018-05-02T10:45:26ZFolic acid in pregnancy – MTHFR gene explains why the benefits may differ<figure><img src="https://images.theconversation.com/files/216250/original/file-20180425-175061-ym28c4.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/download/success?u=http%3A%2F%2Fdownload.shutterstock.com%2Fgatekeeper%2FW3siZSI6MTUyNDY3Mjc0NCwiYyI6Il9waG90b19zZXNzaW9uX2lkIiwiZGMiOiJpZGxfNzA3NzgwNjU2IiwiayI6InBob3RvLzcwNzc4MDY1Ni9odWdlLmpwZyIsIm0iOjEsImQiOiJzaHV0dGVyc3RvY2stbWVkaWEifSwiUkIvdzFuRldmNTE3eXZ0bi9ZNXhTZjBDY0xVIl0%2Fshutterstock_707780656.jpg&pi=33421636&m=707780656&src=7ltlrj4qNOP6w7AIm96RSg-1-0">Shutterstock</a></span></figcaption></figure><p>It’s generally recommended that <a href="https://www.nhs.uk/chq/pages/913.aspx?categoryid=54">all women should take folic acid</a>, both while they’re trying to get pregnant and during the <a href="https://theconversation.com/five-ways-to-boost-your-nutrition-before-pregnancy-76352">first 12 weeks of pregnancy</a>. This is because folic acid is considered to be very important for the development of a healthy foetus.</p>
<p>But recently, it has been claimed this “one-size-fits-all” approach may be wrong and that some pregnant women may benefit more from <a href="http://www.foxnews.com/health/2014/07/27/should-skip-prenatal-vitamins-with-folic-acid.html">alternatives to folic acid</a>. Specifically, it has been found that forms of a certain gene that vary among people, may affect how the body utilises folic acid.</p>
<p>The terms “folic acid” and “folate” are often used interchangeably to describe Vitamin B9, but they are not exactly the same. Folate is often called the natural form of vitamin B9, which is found in dark green vegetables, including broccoli and spinach and dried legumes. Folic acid is the synthetic form of vitamin B9, found in supplements and also added to processed, or “fortified,” foods. </p>
<p>By eating foods that are high in folate regularly, most people should be able to get the necessary amount (200 mcg a day). For some people though, more than this recommended amount of folate is necessary.</p>
<p>It is known that folate or folic acid is very important for the development of a healthy foetus. This is why all pregnant women and women trying for a baby are advised to take double this amount (400 mcg a day) – or even more in certain cases, to help prevent the risk of birth defects in unborn babies.</p>
<p>It would be almost impossible to get this much folate just from natural sources. That’s why folic acid is often prescribed to pregnant women in the form of supplements. </p>
<p>It is also the reason why <a href="https://www.theguardian.com/society/2018/jan/31/folic-acid-new-research-is-a-game-changer-in-push-to-fortify-british-foods">folic acid is added to grains</a> (this process is called fortification) <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257747/">in many countries</a>. Recently, there has been a push to make it <a href="https://theconversation.com/heres-why-the-uk-should-fortify-flour-with-folic-acid-88354">mandatory in the UK as well</a>.</p>
<h2>Understanding the science</h2>
<p>People differ in how much folate they need and receive in their diet, and this can be corrected with supplements. But people also differ in how much folate or folic acid they need for their health – based on the activity of “the MTHFR gene”. </p>
<p>To understand why this matters, first of all we need to know a bit more about the science of how our bodies work. There are 20,000 genes in the human genome. Each of these genes provides instructions in the form of a DNA sequence for making a specific protein. Proteins play various important roles in our body: from building our cells through to making our brain function.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/216251/original/file-20180425-175041-85ua1j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/216251/original/file-20180425-175041-85ua1j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/216251/original/file-20180425-175041-85ua1j.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/216251/original/file-20180425-175041-85ua1j.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/216251/original/file-20180425-175041-85ua1j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/216251/original/file-20180425-175041-85ua1j.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/216251/original/file-20180425-175041-85ua1j.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">Foods high in folate.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/success?u=http%3A%2F%2Fdownload.shutterstock.com%2Fgatekeeper%2FW3siZSI6MTUyNDY3Mjc0NywiYyI6Il9waG90b19zZXNzaW9uX2lkIiwiZGMiOiJpZGxfNTQzMTg0MzMzIiwiayI6InBob3RvLzU0MzE4NDMzMy9odWdlLmpwZyIsIm0iOjEsImQiOiJzaHV0dGVyc3RvY2stbWVkaWEifSwiQU8wNVB3eVl4MWFkQTRLN041L3U0TjhCYmpFIl0%2Fshutterstock_543184333.jpg&pi=33421636&m=543184333&src=vF120dw2_kj89W-uOelC6Q-1-16">Shutterstock</a></span>
</figcaption>
</figure>
<p>One of these genes – the MTHFR gene – provides the instructions for making the protein methylenetetrahydrofolate reductase. This protein is a key player in the complex process of converting folic acid (or folate) that we receive with foods into methylfolate, the form that our body can use. </p>
<p>The MTHFR gene is responsible for how much methylfolate is produced in the body. Our body needs methylfolate for a proper metabolism. If there is not enough methylfolate in the body, it leads to many serious health problems. </p>
<h2>MTHFR explained</h2>
<p>All people have two copies of the MTHFR gene – one copy is inherited from the mother and another copy is inherited from the father. Each copy of the gene can be normal or can have a defect – a change in DNA sequence that affects how much protein this gene can produce.</p>
<p>These defects are called mutations. The common mutation in the MTHFR gene is a single change in DNA sequence that reduces the activity of the protein produced. About 10-15% of people have both copies of the gene affected by this mutation.</p>
<p>These people have very low activity of the MTHFR protein in the body. This results into a highly reduced ability of the body to convert folic acid into a usable form and can lead to accumulation of the amino acid homocysteine – which is toxic to the body.</p>
<p>The MTHFR gene mutation has been found to be one of the factors that puts people at an <a href="https://link.springer.com/article/10.1007%2Fs10549-010-0783-5">increased risk of cancer</a>, <a href="https://www.sciencedirect.com/science/article/pii/S0378111913012869">cardiovascular disease</a>, <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0121147">infertility</a>, <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/j.1468-2982.2007.01400.x">migraine</a>, and <a href="https://academic.oup.com/qjmed/article/90/2/111/1612940">foetal development problems</a>. It has also been found to increase the risk of depression, <a href="https://www.sciencedirect.com/science/article/pii/S0889159110005799">schizophrenia</a> and <a href="https://link.springer.com/article/10.1007%2Fs12035-016-9722-8">dementia</a>. </p>
<h2>To supplement or not</h2>
<p>A diet rich in folate is said to be particularly important for those with the mutation in the MTHFR gene. People with a mutation in the gene may be affected more if they do not receive enough folate with foods. </p>
<p>It has been shown that <a href="https://www.sciencedirect.com/science/article/pii/S0140673611608726">people with this mutation</a> are affected more in Asia than in countries that use grain fortification with folic acid – such as the US, Australia, and New Zealand. But more studies are needed to prove whether alterations in diet and use of folate supplements can be sufficient to overcome negative health effects caused by the MTHFR gene mutations.</p>
<p>Caution is also needed with high-dose supplementation of folic acid in pregnant women with different forms of the MTHFR gene as very high intake of folate may have unintended negative effects on their offspring – particularly on early brain development, as demonstrated by <a href="https://jamanetwork.com/journals/jamapediatrics/fullarticle/1919923">recent human</a> and <a href="https://academic.oup.com/hmg/article/26/5/888/2856406">animal studies</a>. But ultimately, future studies are critical to determine a safe upper limit for all people – and pregnant women particularly – who have different genetic profiles.</p>
<hr>
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<img alt="" src="https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=112&fit=crop&dpr=1 600w, https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=112&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=112&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=140&fit=crop&dpr=1 754w, https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=140&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=140&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>This article is part of a series tied to Medicine made for you, a series by The Anthill podcast on the future of healthcare and how it could soon get a lot more personal. <a href="https://theconversation.com/uk/topics/medicine-made-for-you-82269">Read more here</a>.</em></p><img src="https://counter.theconversation.com/content/95302/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Darya Gaysina 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>Folic acid in pregnancy – and the gene which explains why the benefits may differ.Darya Gaysina, Senior Lecturer in Psychology, University of SussexLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/883542017-12-04T11:37:24Z2017-12-04T11:37:24ZHere’s why the UK should fortify flour with folic acid<figure><img src="https://images.theconversation.com/files/197339/original/file-20171201-17390-1tovt2v.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/download/confirm/546641992?size=medium_jpg">GagliardiImages/Shutterstock</a></span></figcaption></figure><p>The UK Health Secretary, Jeremy Hunt, <a href="https://www.gov.uk/government/news/new-maternity-strategy-to-reduce-the-number-of-stillbirths">announced plans</a> to halve the number of infant deaths, stillbirths and brain injuries by 2025. Yet successive UK governments have resisted expert advice to fortify flour with folic acid – including from the Food Standards Agency. This simple measure would prevent many serious birth defects, known as neural tube defects.</p>
<p>Neural tube defects are defects of the central nervous system that occur in the first month of an embryo’s life. They include conditions such as <a href="https://www.nhs.uk/conditions/spina-bifida/">spina bifida</a>, where the spinal column doesn’t close properly, and <a href="https://en.wikipedia.org/wiki/Anencephaly">anencephaly</a>, a condition where large parts of a baby’s brain and skull are missing. The incidence of neural-tube-defect pregnancies in the UK is around <a href="http://adc.bmj.com/content/archdischild/early/2015/11/13/archdischild-2015-309226.full.pdf">13 per 10,000 births</a>.</p>
<p>In 1991, supplements of folic acid given before conception and in early pregnancy were <a href="https://www.ncbi.nlm.nih.gov/pubmed/1677062?dopt=Abstract">shown to reduce the rate of neural tube defects</a>. This finding has since been supported by many other studies. A <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4160020/">meta-analysis of those studies</a>, conducted in 2010, found that if a woman takes 400 micrograms of folic acid daily before conception, she can reduce the risk of her baby having a neural tube defect by around 70%.</p>
<p>Since 1992, women in Britain and Europe have been <a href="https://www.food.gov.uk/sites/default/files/multimedia/pdfs/publication/eatingwhilepregnant1209.pdf">advised to take folic acid</a> supplements if they are trying to conceive. However, <a href="https://www.ncbi.nlm.nih.gov/pubmed/15722368">a study</a> conducted by the US Centers for Disease Control and Prevention, found that by 1998 this had made no difference to neural tube defect rates in Europe because over-the-counter supplements tend to be taken by those who least need them – because they’re getting enough folic acid in their diet. And the people who do need them, are the least likely to take them. </p>
<p>The US and Canada took a different route. Instead of advising supplementation with folic acid pills, they made it mandatory for <a href="https://www.fda.gov/aboutfda/whatwedo/history/productregulation/selectionsfromfdliupdateseriesonfdahistory/ucm091883.htm">flour to be fortified with folic acid</a>. Since then, more than 70 countries have followed their lead, and neural tube defects have fallen by 25-50%. </p>
<p>Canada implemented flour fortification in 1997. By 2000, neural tube defect rates had halved compared with the rate in 1996 (see graph below).</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/197332/original/file-20171201-17360-141owh8.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/197332/original/file-20171201-17360-141owh8.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=358&fit=crop&dpr=1 600w, https://images.theconversation.com/files/197332/original/file-20171201-17360-141owh8.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=358&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/197332/original/file-20171201-17360-141owh8.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=358&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/197332/original/file-20171201-17360-141owh8.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=450&fit=crop&dpr=1 754w, https://images.theconversation.com/files/197332/original/file-20171201-17360-141owh8.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=450&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/197332/original/file-20171201-17360-141owh8.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">
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<span class="attribution"><span class="source">NEJM/Laval University in Canada</span>, <span class="license">Author provided</span></span>
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<p>In 2014, a group of British scientists reported in <a href="http://adc.bmj.com/content/101/7/604.long">Archives of Disease in Childhood</a> that UK rates of neural tube defects had not changed much since 1998 (the year the US introduced mandatory fortification). The graph below shows how that played out.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/197333/original/file-20171201-17390-p96no.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/197333/original/file-20171201-17390-p96no.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=363&fit=crop&dpr=1 600w, https://images.theconversation.com/files/197333/original/file-20171201-17390-p96no.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=363&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/197333/original/file-20171201-17390-p96no.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=363&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/197333/original/file-20171201-17390-p96no.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=456&fit=crop&dpr=1 754w, https://images.theconversation.com/files/197333/original/file-20171201-17390-p96no.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=456&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/197333/original/file-20171201-17390-p96no.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=456&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="attribution"><span class="source">Geoff Webb</span>, <span class="license">Author provided</span></span>
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<p>If the UK government had introduced flour fortification at the same time and at the same level as the US, then almost 3,000 cases of neural tube defect would now have been prevented. Without terminations, this would equate to around 1,500 dead or miscarried babies and 1,500 babies with severe disabilities. </p>
<p>To be most effective, folic acid needs to be taken before or just after conception. However, in the UK, <a href="http://news.bbc.co.uk/1/hi/health/3515400.stm">40% of pregnancies are unplanned</a>, meaning the window of opportunity for taking the supplement is lost. A study led by Queen Mary University of London found that only <a href="http://adc.bmj.com/content/101/7/604.long">25% of British women</a> take folic acid supplements at the right time. And, as previously noted, people who take supplements tend to have the best diets and are the <a href="http://eu.wiley.com/WileyCDA/WileyTitle/productCd-1444332406.html">least likely to need them</a>.</p>
<h2>Objections don’t withstand scrutiny</h2>
<p>For every case of neural tube defect prevented, several thousand people eat the fortified food. This could be seen as “medication” without choice or consent, although, since World War II, flour has been <a href="http://www.legislation.gov.uk/">fortified with several vitamins and minerals</a>. Several other objections to fortifying food with folic acid have been suggested by those opposed to fortification:</p>
<ul>
<li>It might mask the symptoms of vitamin B12 deficiency in the elderly and so delay diagnosis and treatment.</li>
<li>It might promote the growth and malignancy of existing benign bowel tumours.</li>
<li>It might interfere with drugs like methotrexate, which is used to treat rheumatoid arthritis, that have an anti-folic-acid action.</li>
</ul>
<p>The US has been fortifying flour for 20 years with no indication that these represent <a href="http://eu.wiley.com/WileyCDA/WileyTitle/productCd-1444332406.html">real hazards</a>. The doses of folic acid involved are <a href="http://eu.wiley.com/WileyCDA/WileyTitle/productCd-1444332406.html">unlikely to seriously affect</a> diagnosis of B12 deficiency. </p>
<p>Rates of bowel cancer in the US <a href="http://www.sciencedirect.com/science/article/pii/S0140673612620017?via%3Dihub#bib18">have been dropping since 1970</a>, and this fall was not slowed by the introduction of fortified breakfast cereals in 1973 nor the mandatory fortification of flour in 1998. Most epidemiological evidence suggests that folic acid might be <a href="http://jn.nutrition.org/content/132/8/2350S.long">protective against bowel cancer</a> and a <a href="http://www.sciencedirect.com/science/article/pii/S0140673612620017?via%3Dihub">meta-analysis</a> of folic acid supplement trials published in The Lancet found no increase in bowel cancer after five years of use. </p>
<p>Folic acid alleviates the side effects of methotrexate and so some methotrexate treatment regimens for rheumatoid arthritis use folic acid for this purpose.</p>
<p>According to the <a href="https://www.ifglobal.org/en/37-temp-news/4768-uk-government-says-no-to-mandatory-fortification-of-flour-with-folic-acid-2">International Federation for Spina Bifida and Hydrocephalus</a>, the UK government has decided not to introduce fortification. More recently, the health ministers of Scotland and Wales wrote a <a href="http://www.bbc.co.uk/news/health-42199080">joint letter to Jeremy Hunt</a>, asking him to reconsider his position on fortification. According to Food Standards Scotland, 80% women of childbearing age in Scotland and Wales are deficient in folic acid.</p>
<p>I <a href="https://drgeoffnutrition.wordpress.com/2017/03/17/fortification-of-uk-flour-with-folic-acid-is-it-finally-time-to-decide/">recently advocated</a> flour fortification with 50% more folic acid than the US level. This could result in 300 fewer affected pregnancies each year. Unfortified flour could be permitted, but with a warning that it does not comply with government fortification advice.</p><img src="https://counter.theconversation.com/content/88354/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Geoff Webb 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>The US and Canada began fortifying flour with folic acid in the late 90s. More than 70 countries followed suit, but not the UK.Geoff Webb, Senior Lecturer, University of East LondonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/763522017-04-21T04:44:35Z2017-04-21T04:44:35ZFive ways to boost your nutrition before pregnancy<figure><img src="https://images.theconversation.com/files/166204/original/file-20170421-20068-11p72p7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Women (and their partners) can give their baby the best start in life by eating well even before they conceive.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/613852691?src=fbc33egthBZ5G0EgfU_9PA-2-27&size=medium_jpg">from www.shutterstock.com</a></span></figcaption></figure><p>Thinking about trying to have a baby? Then now is the time for <a href="https://www.ncbi.nlm.nih.gov/pubmed/22742616">future mums</a> (<a href="https://www.ncbi.nlm.nih.gov/pubmed/25523615">and dads</a>) to “spring clean” food and lifestyle habits. Here are our five nutrition tips <em>before</em> pregnancy. </p>
<h2>1. Aim for a healthy weight</h2>
<p>In your 20s and 30s it’s common to have “weight creep”, an extra kilogram or two gained each year, without realising. Carrying too much weight increases the risk of pregnancy complications, including <a href="https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/diabetes-gestational">gestational diabetes</a>, <a href="https://www.betterhealth.vic.gov.au/health/healthyliving/pregnancy-pre-eclampsia">pre-eclampsia</a> and <a href="https://www.ncbi.nlm.nih.gov/pubmed/19173021">delivery complications</a>. So, it’s worth trying to shift some of the “extra kilos” before trying to conceive.</p>
<p>A mother’s pre-pregnancy weight also has a direct <a href="https://www.ncbi.nlm.nih.gov/pubmed/23613888">effect on her baby’s birth weight</a>. Compared with mothers who are in the healthy weight range, mothers who are overweight or obese are 1.5-2 times more likely to have babies with a high birth weight, increasing the risk of birth complications. For these infants, there is an increased risk of developing <a href="https://www.ncbi.nlm.nih.gov/pubmed/19173021">obesity, heart disease</a> and <a href="https://www.ncbi.nlm.nih.gov/pubmed/25940642">type 1 diabetes</a> later in life. </p>
<p>But improving eating and physical activity helps you achieve <a href="https://theconversation.com/health-check-whats-the-best-diet-for-weight-loss-21557">a healthy weight right for you</a>. For women carrying excess weight, a <a href="https://www.ncbi.nlm.nih.gov/pubmed/25336072">loss of 5-10% of pre-pregnancy weight</a> is enough to improve fertility and reduce the risk of weight-related pregnancy complications.</p>
<h2>2. Improve your food and drink choices</h2>
<p>Increasing the variety of food you eat each week across the basic food groups – vegetables, fruit, wholegrains, vegetarian foods (including legumes like baked beans, kidney beans, lentils, eggs, nuts and seeds), lean meats/poultry/fish and dairy foods – also boosts the vitamins and minerals needed from the very beginning of pregnancy. </p>
<p>Start by assessing the quality of your diet using the free <a href="http://healthyeatingquiz.com.au/">Healthy Eating Quiz</a> and check how it suggests you boost your score. You can also use the <a href="https://www.eatforhealth.gov.au/node/add/calculator-servings">eat-for-health calculator</a> linked to the <a href="https://www.eatforhealth.gov.au/guidelines/australian-guide-healthy-eating">Australian Guide to Health Eating</a>. This calculates recommended daily serves from each of the five basic food groups, and gives an idea of daily serves to aim for to optimise your nutrients.</p>
<p>Getting your nutrients from food in the first instance is recommended, but some nutrients do need extra attention before conception and early in pregnancy.</p>
<h2>3. Take a folate supplement</h2>
<p><a href="https://en.wikipedia.org/wiki/Folate">Folate</a> is a B-group vitamin. It is needed to complete the development of the <a href="https://en.wikipedia.org/wiki/Neural_tube">neural tube</a>, which forms the baby’s brain and spinal cord in the first few weeks of pregnancy. This can be before you even know you’re pregnant. If the neural tube doesn’t close it can cause a neural tube defect like <a href="https://en.wikipedia.org/wiki/Spina_bifida">spina bifida</a>. </p>
<p>Taking a folate supplement (in the form of folic acid) from one month before pregnancy until the end of the first trimester is the best way to make sure you meet folate requirements during early pregnancy. </p>
<p>Choose a supplement with at least 400 micrograms of folic acid. Talk to your doctor if you have a family history of neural tube defects as you will need <a href="https://www.betterhealth.vic.gov.au/health/healthyliving/folate-for-pregnant-women">higher levels of folic acid</a>. </p>
<p>A folate supplement is in addition to eating good food sources of folate, like green leafy vegetables, fruits, lentils and <a href="http://www.foodstandards.gov.au/consumer/generalissues/pregnancy/folic/Pages/default.aspx">breadmaking flour, most of which is fortified with folic acid in Australia)</a>. Organic breadmaking flour and most regular flour is not fortified, so check the ingredient list on flour you buy for home cooking.</p>
<h2>4. Take an iodine supplement</h2>
<p>In pregnancy, <a href="https://en.wikipedia.org/wiki/Iodine">iodine</a> is needed to support the baby’s developing brain and nervous system. Good food sources of iodine include <a href="http://www.foodstandards.gov.au/consumer/generalissues/pregnancy/Pages/iodineandpregnancy.aspx">seafood, dairy foods, eggs and iodine fortified breadmaking flour (except for regular and organic flour)</a>.</p>
<p>Although seafood is high in iodine, some types such as <a href="http://www.foodstandards.gov.au/consumer/chemicals/mercury/Pages/default.aspx">shark and swordfish should be avoided before and during pregnancy</a> as they may contain large amounts of mercury. </p>
<p>In Australia it is recommended that women planning to become pregnant, take an iodine supplement containing <a href="https://www.nhmrc.gov.au/guidelines-publications/new45">150 micrograms of iodine daily</a> and to continue this while pregnant or breastfeeding.</p>
<p>Talk to your doctor or pharmacist about vitamin supplements to meet your needs. For more personal advice on nutrition consult <a href="https://daa.asn.au/what-dietitans-do/choosing-your-nutrition-expert/">an Accredited Practising Dietitian</a>. </p>
<h2>5. Avoid alcohol</h2>
<p>All health authorities agree it is best to avoid alcohol from the time you start thinking about having a baby. There is no known safe level of alcohol during pregnancy. Alcohol consumed in moderate-to-large quantities can cause <a href="http://www.nofasd.org.au/resources/what-is-fasd-1">foetal alcohol syndrome</a> and increase the risk of having a baby <a href="https://www.ncbi.nlm.nih.gov/pubmed/21729235">preterm birth and of low birth weight</a>, which increases the chance of the baby having medical problems. The <a href="https://www.ncbi.nlm.nih.gov/pubmed/17233797">risks to the baby at lower levels</a> are less clear. <a href="https://www.nhmrc.gov.au/health-topics/alcohol-guidelines">The safest option is drinking no alcohol</a> if you are pregnant, planning a pregnancy or breastfeeding.</p>
<h2>Putting it all together</h2>
<p>Now is the time to start make changes to improve the nutritional quality of your food. And it’s not all about mum.</p>
<p><a href="https://www.ncbi.nlm.nih.gov/pubmed/25523615">Dads-to-be can benefit</a> from eating a variety of nutritious foods, cutting down on alcohol, and <a href="https://theconversation.com/health-check-ten-ways-to-save-2-000-kilojoules-and-drop-a-clothes-size-37039">dropping a pants size</a>. One study found that overweight men were 1.2 times and obese men were 1.3 times <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521747/">more likely to be infertile</a>. But some good news in our study was that overweight and obese men who <a href="https://www.ncbi.nlm.nih.gov/pubmed/24459689">shed a few kilograms reported better erectile function</a>.</p>
<p>Any improvements you make to your food and lifestyle habits today will benefit you and your family in the future.</p><img src="https://counter.theconversation.com/content/76352/count.gif" alt="The Conversation" width="1" height="1" />
<h4 class="border">Disclosure</h4><p class="fine-print"><em><span>Clare Collins is affiliated with the Priority Research Centre for Physical Activity and Nutrition, the University of Newcastle, NSW. She is an NHMRC Senior Research fellow. She has received a range of research grants including NHMRC, ARC, Hunter Medical Research Institute, Meat and Livestock Australia, Diabetes Australia, the Heart Foundation. She has consulted to SHINE Australia, Novo Nordisk, Quality Bakers and the Sax Institute. She is a spokesperson for the Dietitians Association of Australia on some specific nutrition issues, including Australia's Healthy Weight Week.</span></em></p><p class="fine-print"><em><span>Jenna Hollis is affiliated with the Priority Research Centre for Physical Activity and Nutrition and the Priority Research Centre for Health Behaviour, at the University of Newcastle (Australia). She is a Project Officer at Hunter New England Population Health. She has received an Endeavour Postdoctoral Research Fellowship from the Department of Education and Training (Australian Government). She has also received funding from the Hunter Medical Research Institute (HMRI) and University of Newcastle, Australia. </span></em></p><p class="fine-print"><em><span>Siân Robinson is supported by the UK Medical Research Council and by the National Institute for Health Research through the NIHR Southampton Biomedical Research Centre.</span></em></p>Thinking about trying for a baby? Then now is the time for you and your partner to “spring clean” your food and lifestyle habits.Clare Collins, Professor in Nutrition and Dietetics, University of NewcastleJenna Hollis, Conjoint Lecturer, University of NewcastleSiân Robinson, Professor of Nutritional Epidemiology, University of SouthamptonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/603222016-06-08T06:56:05Z2016-06-08T06:56:05ZWeekly Dose: methotrexate, the anti-inflammatory drug that can kill if taken daily<figure><img src="https://images.theconversation.com/files/125468/original/image-20160607-31957-15rin20.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Methotrexate is used for arthritis, psoriasis, inflammatory bowel disease and cancer.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/neofedex/3447536476/in/photolist-6fDwu5-8P3fWH-aVhDDp-aVhDLc-aVhDGK-7pWQhW-aVhDPr-5rwZS-buU4UA-z5R6Uj-yqrh5Q">FedEx/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>Methotrexate, sold under the brand name <a href="http://rheumatology.org.au/downloads/MTX280509.pdf">Methoblastin</a>, is an antifolate drug, which means it inhibits the activation of folic acid in the body. </p>
<p>It is taken once per week to treat a range of conditions. These include rheumatoid arthritis, the skin disorder psoriasis and inflammatory bowel disease. This weekly therapy is known as “low-dose methotrexate”.</p>
<p>Methotrexate was first developed in the 1950s as a cancer treatment and is still used for this in higher doses.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/125655/original/image-20160608-3506-15u8yne.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/125655/original/image-20160608-3506-15u8yne.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/125655/original/image-20160608-3506-15u8yne.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=766&fit=crop&dpr=1 600w, https://images.theconversation.com/files/125655/original/image-20160608-3506-15u8yne.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=766&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/125655/original/image-20160608-3506-15u8yne.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=766&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/125655/original/image-20160608-3506-15u8yne.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=963&fit=crop&dpr=1 754w, https://images.theconversation.com/files/125655/original/image-20160608-3506-15u8yne.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=963&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/125655/original/image-20160608-3506-15u8yne.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=963&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="attribution"><a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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</figure>
<h2>How it works</h2>
<p>The methotrexate drug molecule is structurally similar to folic acid, which is important for making new cells. It inhibits the enzyme (dihydrofolate reductase) that turns folic acid into its active form. This reduces cell growth and is why methotrexate is used to treat some cancers.</p>
<p>The way methotrexate works for inflammatory conditions is less clear. But we know it has a <a href="https://www.ncbi.nlm.nih.gov/pubmed/17922664">range of effects</a> on DNA synthesis and immune signalling, which are thought to reduce the inflammation. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/125461/original/image-20160607-31962-1i1c9of.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/125461/original/image-20160607-31962-1i1c9of.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=896&fit=crop&dpr=1 600w, https://images.theconversation.com/files/125461/original/image-20160607-31962-1i1c9of.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=896&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/125461/original/image-20160607-31962-1i1c9of.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=896&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/125461/original/image-20160607-31962-1i1c9of.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1126&fit=crop&dpr=1 754w, https://images.theconversation.com/files/125461/original/image-20160607-31962-1i1c9of.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1126&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/125461/original/image-20160607-31962-1i1c9of.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1126&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Methotrexate can be used to treat autoimmune diseases such as psoriasis.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/mysiann/1638705074/in/photolist-3uNMVL-fCxFPs-fCg7wp-fCxGVY-fCg6mt-Kg165-nqGVx1-9aMqX4-3G3t78-3RtjQ9-6cNDrk-k8tv1T-57dTfe-fFMMaf-bzzU8S-bzzTZS-ohkePF-6cNDS2-gxHWXF-5pk8oV-5TP6yM-57FvDg-EHL7Bb-5ngmns-omBVEq-bTwp2k-dkaSyz-EUeBoZ-DWRzTB-58GiRZ-5TTDQY-bxcFC-5TTznf-dkaSKn-dkaSrr-e3dJ6L-dkaU4m-5TP9pV-5TTHQ5-dkaSNV-5TP1si-5TPiUV-5bkpSE-5h88GN-5TP8Xc-6if3u4-dkaTKm-dkaTT1-PmDER-oSG5j2">Mysi Ann/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>In rheumatoid arthritis, methotrexate reduces inflammation and damage to joints. Rather than just masking pain, methotrexate reduces it by reducing severity of the disease. For this reason, it’s known as a disease-modifying anti-rheumatic drug (DMARD).</p>
<h2>History</h2>
<p>Methotrexate was <a href="https://books.google.com.au/books/about/Methotrexate.html?id=VCAFHzHAotsC&redir_esc=y">developed in the 1950s</a> when researchers discovered that increased folic acid worsened leukaemia and that dietary deficiency of folic acid reduced the cancer cell count. </p>
<p>This inspired scientists to develop drugs structurally similar to folic acid that bound to its receptors in the body and inhibited its effects. </p>
<p>Methotrexate was synthesised in the 1950s and was shown to be effective for leukaemia and several types of solid tumours. Prior to this discovery, cancer treatments had been limited to surgery and radiotherapy. </p>
<h2>What it’s used for</h2>
<p>Methotrexate is still used intravenously in high doses to treat cancer. But its most common use now is in rheumatoid arthritis and other inflammatory conditions. Low-dose methotrexate (taken once a week) was shown to be effective in rheumatoid arthritis in <a href="http://www.nejm.org/doi/full/10.1056/NEJM198503283121303">1985</a>. It is now a drug of first choice for rheumatoid arthritis.</p>
<p>Methotrexate is also used as an intra-muscular injection to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285146/">terminate ectopic pregnancy</a>, as an <a href="http://www.kemh.health.wa.gov.au/development/manuals/O&G_guidelines/sectionc/9/c9.4.2.pdf">alternative to surgery</a>. </p>
<h2>Use and cost</h2>
<p>There were <a href="http://medicarestatistics.humanservices.gov.au/statistics/mbs_item.jsp">260,000 scripts</a> for methotrexate tablets dispensed on the Pharmaceutical Benefits Scheme (PBS) in 2015. </p>
<p>Methotrexate costs between A$0.73 and $1.87 per tablet on the <a href="http://www.pbs.gov.au/medicine/item/1622J-1623K-1818Q-2272N-2395C-2396D-4502Y-4512L-7250N-7251P">PBS</a>. Since it is taken only once per week, it is a very low-cost treatment. </p>
<h2>How it makes you feel</h2>
<p>The correct dose of methotrexate (commonly between 7.5mg to 25mg per week) will reduce inflammation and alleviate the condition it’s prescribed for, whether that’s rheumatoid arthritis, psoriasis, inflammatory bowel disease, and so on. But it can take one to two months to work.</p>
<p>The most common side effects include nausea and mouth ulcers, due to the drug’s inhibition of folate. This is because inhibiting folate targets rapidly dividing cells of the gastrointestinal tract.</p>
<p>Folic acid supplementation is used to <a href="http://www.cochranelibrary.com/editorial/10.1002/14651858.ED000063">prevent side effects</a> associated with low-dose methotrexate therapy. Preferably, folic acid is not taken on the same day methotrexate is taken. <a href="http://www.cochrane.org/CD000951/MUSKEL_folic-acid-or-folinic-acid-for-reducing-side-effects-of-methotrexate-for-people-with-rheumatoid-arthritis">Many studies</a> have shown that folic acid supplements do not hinder the effectiveness of methotrexate.</p>
<p>If methotrexate is taken too frequently – daily instead of weekly, for instance – it can suppress bone marrow, reducing blood cell production and impairing the immune system. This can make the body susceptible to infections and, in the worst-case scenario, <a href="https://www.mja.com.au/journal/2016/204/10/decade-australian-methotrexate-dosing-errors">result in death</a>.</p>
<p>In rare cases, this suppression of blood cell production can also occur at normal doses. This risk is higher in the elderly and in patients with reduced kidney function or dehydration. </p>
<p>Other severe (but rare) side effects include lung and liver damage with long-term usage. People prescribed methotrexate will be closely monitored by their doctor for these effects. </p>
<p>In addition to being an effective treatment for rheumatoid arthritis, methotrexate <a href="http://www.ncbi.nlm.nih.gov/pubmed/11955534">reduces the risk of death</a> from heart disease. This may be because it reduces inflammation, a risk factor for heart disease, and because it affects the cellular mechanisms that lead to the deposition of fat in arterial walls.</p>
<h2>Interactions</h2>
<p>Low-dose methotrexate interacts with drugs that inhibit the way the body uses folic acid, such as the antibiotics <a href="http://onlinelibrary.wiley.com/doi/10.1111/jcpt.12060/pdf">trimethoprim with sulfamethoxazole</a> (Bactrim, Resprim) and trimethoprim alone (Triprim, Alprim). Medicines that <a href="https://www.ncbi.nlm.nih.gov/pubmed/3913771">impair kidney function</a> can increase levels of methotrexate in the body. Taking these medicines in combination with methotrexate increases the risk of bone marrow suppression. </p>
<h2>The dangers of daily dosing</h2>
<p>A study published in the <a href="https://www.mja.com.au/journal/2016/204/10/decade-australian-methotrexate-dosing-errors">Medical Journal of Australia</a> detailed more than a decade’s worth of Australian data on methotrexate, looking at cases where people had accidentally taken methotrexate daily instead of weekly. </p>
<p>Taking methotrexate for as little as three days in a row is enough to cause serious consequences, including sepsis (infection of the blood) and death. Note that this is different to high-dose methotrexate in chemotherapy, where <a href="http://www.sciencedirect.com/science/article/pii/0002934380901059">“rescue therapy”</a> is used to prevent toxicity. </p>
<p>Since 2000, at least eight Australians have died and many more have been hospitalised after taking too much methotrexate. Methotrexate use is increasing, which has corresponded with an increase in accidental daily dosing reported to Australian Poisons Information Centres. </p>
<p>Given that most medicines are taken daily, these potentially fatal mistakes can be easy to make. Methotrexate is effective and safe if used correctly. Changes in packaging and labelling, and alerts in prescribing and dispensing software used by doctors and pharmacists, could help prevent overdosing. </p>
<p>If you have questions about your methotrexate treatment, speak with your doctor or pharmacist. For advice about dosing errors with methotrexate or any other medicine, contact the Poisons Information Centre, 13 11 26 (24 hours a day, 7 days a week), Australia-wide.</p><img src="https://counter.theconversation.com/content/60322/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rose Cairns 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>Methotrexate is a drug used for rheumatoid arthritis, psoriasis and inflammatory bowel disease. It is taken on just one day a week. Accidental daily dosing can cause life-threatening toxicity.Rose Cairns, Research Associate, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/371702015-10-12T03:51:41Z2015-10-12T03:51:41ZHealth Check: seven nutrients important for mental health – and where to find them<figure><img src="https://images.theconversation.com/files/98007/original/image-20151012-23288-t3ve32.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">While nutrient supplementation can have a role in treating certain psychiatric disorders, all kinds of nutrients should, in the first instance, be consumed as part of a balanced wholefood diet.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/nakrnsm/3815441846/">PROPatrick Feller/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Dietary nutrients are critical for brain structure and function, so they have a potentially profound impact on mental health. An increasingly <a href="http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(14)00051-0/abstract">robust body of research</a> points to the detrimental effect of unhealthy diets and nutrient deficiencies, and to the protective value of healthy diets – along with select nutritional supplements as required – for maintaining and promoting mental health. </p>
<p>Research literature suggests dietary improvement and nutritional interventions may help reduce the risk, or even arrest the progression, of certain psychiatric disorders. <a href="http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(14)00051-0/abstract">Clinical studies</a> support the use of certain nutrients, which influence a range of neurochemical activities beneficial for treating mental disorders, as medicinal supplements.</p>
<p>Evidence from clinical research supports the use of several nutritional medicines for certain psychiatric disorders: omega-3 fatty acids; N-acetyl cysteine (NAC); S-adenosyl methionine (SAMe); zinc; magnesium; vitamin D; and B vitamins (including folic acid). Other natural compounds such as amino acids, plant-based antioxidants and microbiotics (derived from fermented food or laboratory synthesis) are also known to influence brain health. </p>
<p>But while some evidence supports these natural compounds as having brain chemical-modulating effects, or having a role in treating certain mental disorders, we cannot currently name particular foods as being effective for the treatment of mental illness. The best nutritional advice at this point is to cultivate an unprocessed wholefood diet, with judicious prescriptive use of nutrients (if required) based on advice from a qualified health professional. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/98010/original/image-20151012-23309-1jxpwuh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/98010/original/image-20151012-23309-1jxpwuh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=353&fit=crop&dpr=1 600w, https://images.theconversation.com/files/98010/original/image-20151012-23309-1jxpwuh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=353&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/98010/original/image-20151012-23309-1jxpwuh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=353&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/98010/original/image-20151012-23309-1jxpwuh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=444&fit=crop&dpr=1 754w, https://images.theconversation.com/files/98010/original/image-20151012-23309-1jxpwuh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=444&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/98010/original/image-20151012-23309-1jxpwuh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=444&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Oily fish such as sardines are the best source of omega-3 fats.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/jmenj/9434507959/">Jeanne Menj/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>In the meanwhile, here are seven key nutrients that may positively influence brain health, and the foods they appear in.</p>
<p><strong>1. Omega-3</strong> </p>
<p>Polyunsaturated fats (in particular omega-3 fatty acids) <a href="http://www.ncbi.nlm.nih.gov/pubmed/23538073">have a vital role</a> in maintaining proper neuronal structure and function, as well as in modulating critical aspects of the inflammatory pathway in the body. Taking omega-3 supplements appears beneficial for addressing symptoms of depression, bipolar depression and post-traumatic stress disorder. And it may potentially help <a href="http://www.ncbi.nlm.nih.gov/pubmed/20124114">prevent psychosis</a>.</p>
<p>Omega-3 fats can be found in nuts, seeds and oysters, although the highest amounts exist in oily fish such as sardines, salmon (especially King salmon), anchovies and mackerel. Due to higher levels of mercury, larger fish, such as mackerel, should be consumed in moderation.</p>
<p><strong>2. B vitamins and folate</strong></p>
<p>We need B vitamins for a range of cellular and metabolic processes, and they have a critical role in the production of a range of brain chemicals. Folate (B9) deficiency <a href="http://www.psychiatrist.com/JCP/article/Pages/2009/v70s05/v70s0503.aspx">has been reported</a> in depressed populations and among people who respond poorly to antidepressants.</p>
<p>Several studies have assessed the antidepressant effect of folic acid (the synthetic form of folate) with antidepressant medication. <a href="http://www.psychiatrist.com/JCP/article/Pages/2009/v70s05/v70s0503.aspx">Some show positive results</a> in enhancing either antidepressant response rates or the onset of response to these medications. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/98012/original/image-20151012-23319-13i4uq6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/98012/original/image-20151012-23319-13i4uq6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/98012/original/image-20151012-23319-13i4uq6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/98012/original/image-20151012-23319-13i4uq6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/98012/original/image-20151012-23319-13i4uq6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/98012/original/image-20151012-23319-13i4uq6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/98012/original/image-20151012-23319-13i4uq6.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">Nuts are a good source of folate, amino acids and minerals.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/addiction/62824084/">Ahmed Al Masaood/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>Folate is found in abundance in leafy green vegetables, legumes, whole grains, brewer’s yeast and nuts. Unprocessed meats, eggs, cheese, dairy, whole grains and nuts are, in general, richest in B vitamins. If you’re going to take supplements, it’s advisable to take B vitamins together as <a href="http://www.ncbi.nlm.nih.gov/pubmed/23253391">they have a synergistic effect</a>.</p>
<p><strong>3. Amino acids</strong></p>
<p>Amino acids are the building blocks for creating proteins, from which brain circuitry and brain chemicals are formed. Some amino acids are precursors of mood-modulating chemicals; tryptophan, for instance, is needed to create serotonin. Another example is cysteine, a sulphur-based amino acid that can convert into glutathione – the body’s most powerful antioxidant. </p>
<p>When given as a supplement, an amino acid form known as N-acetyl cysteine (NAC) converts into <a href="https://en.wikipedia.org/wiki/Glutathione">glutathione</a> in the body. We have <a href="http://www.ncbi.nlm.nih.gov/pubmed/23369637">evidence that it’s helpful</a> in bipolar depression, schizophrenia, trichotillomania and other compulsive and addictive behaviours. Another amino acid-based nutrient known as S-adenosyl methionine (SAMe) <a href="http://www.ncbi.nlm.nih.gov/pubmed/24856557">has antidepressant qualities</a>. </p>
<p>Amino acids are found in any source of protein, most notably meats, seafood, eggs, nuts and legumes.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/98013/original/image-20151012-23319-wauedl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/98013/original/image-20151012-23319-wauedl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=398&fit=crop&dpr=1 600w, https://images.theconversation.com/files/98013/original/image-20151012-23319-wauedl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=398&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/98013/original/image-20151012-23319-wauedl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=398&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/98013/original/image-20151012-23319-wauedl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=500&fit=crop&dpr=1 754w, https://images.theconversation.com/files/98013/original/image-20151012-23319-wauedl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=500&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/98013/original/image-20151012-23319-wauedl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=500&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Amino acids are found in sources of protein such as meat.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/wurzeltod/357151207/">Suzanne Gerber/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<p><strong>4. Minerals</strong> </p>
<p>Minerals, especially zinc, magnesium and iron, have important roles in neurological function. </p>
<p>Zinc is an abundant trace element, being involved in many brain chemistry reactions. It’s also a key element supporting proper immune function. <a href="http://www.ncbi.nlm.nih.gov/pubmed/25012438">Deficiency has been linked</a> to increased depressive symptoms and there’s emerging evidence for zinc supplementation in <a href="http://www.ncbi.nlm.nih.gov/pubmed/21798601">improving depressed mood</a>, primarily alongside antidepressants. </p>
<p>Magnesium is also involved in many brain chemistry reactions and <a href="http://www.ncbi.nlm.nih.gov/pubmed/19085527">deficiency has been linked</a> to depressive and anxiety symptoms. Iron is involved in many neurological activities and <a href="http://www.biomedcentral.com/1471-244X/13/161">deficiency is associated with</a> anxiety and depressive symptoms as well as developmental problems. This is, in part, due to its role in transporting oxygen to the brain.</p>
<p>Zinc is abundant in lean meats, oysters, whole grains, pumpkin seeds and nuts, while magnesium is richest in nuts, legumes, whole grains, leafy greens and soy. Iron occurs in higher amounts in unprocessed meats and organ meats, such as liver, and in modest amounts in grains, nuts and leafy greens, such as spinach. </p>
<p><strong>5. Vitamin D</strong></p>
<p>Vitamin D is a fat-soluble compound that’s important as much for brain development as it is for bone development. Data suggests low maternal levels of vitamin D are <a href="http://www.ncbi.nlm.nih.gov/pubmed/22796576">implicated in schizophrenia risk</a>, and deficiency is linked to <a href="http://www.ncbi.nlm.nih.gov/pubmed/23377209">increased depressive symptoms</a>. But there’s little evidence to support the use of <a href="http://www.ncbi.nlm.nih.gov/pubmed/24423304">vitamin D supplements for preventing depression</a>.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/98015/original/image-20151012-23300-uz3k8j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/98015/original/image-20151012-23300-uz3k8j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=362&fit=crop&dpr=1 600w, https://images.theconversation.com/files/98015/original/image-20151012-23300-uz3k8j.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=362&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/98015/original/image-20151012-23300-uz3k8j.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=362&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/98015/original/image-20151012-23300-uz3k8j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=456&fit=crop&dpr=1 754w, https://images.theconversation.com/files/98015/original/image-20151012-23300-uz3k8j.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=456&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/98015/original/image-20151012-23300-uz3k8j.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=456&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Vitamin D can be synthesised via sunlight.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/naturesdawn/4299041739/">Dawn Ellner/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Vitamin D can be synthesised via sunlight: 15 minutes a day on the skin between 10am and 3pm during summer, although be sure to seek professional health advice regarding skin cancer concerns. Aside from sunlight, vitamin D can also be found in oily fish, UVB-exposed mushrooms and fortified milk.</p>
<p><strong>6. Plant-based antioxidants</strong></p>
<p>An increase in oxidative stress and damage to brain cells has been <a href="http://www.ncbi.nlm.nih.gov/pubmed/22271002">implicated in a range of mental disorders</a>, including depression and dementia. Antioxidant compounds (such as “polyphenols”, which are found in fruits and certain herbs) may “mop up” free radicals that damage cells to <a href="http://www.ncbi.nlm.nih.gov/pubmed/22334236">provide a natural way</a> to combat excessive oxidation.</p>
<p>Consuming natural antioxidant compounds through your diet is better than taking supplements of high doses of synthetic vitamin A, C or E, as the oxidative system is finely tuned and excess may actually be harmful. </p>
<p>Fruits and vegetables contain these antioxidant compounds in relative abundance, especially blackberries, blueberries, raspberries and goji berries; grapes; mangoes and mangosteen; onions; garlic; kale; as well as green and black tea; various herbal teas; and coffee.</p>
<p><strong>7. Microbiotics</strong></p>
<p><a href="http://www.ncbi.nlm.nih.gov/pubmed/23384445">Research</a> shows a connection between the bacteria in our guts and brain health, which may affect mental health. When the composition of the gut microbiota is less than optimal, it can result in inflammatory responses that <a href="http://www.ncbi.nlm.nih.gov/pubmed/21135322">may negatively affect</a> the nervous system and brain function. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/98009/original/image-20151012-23283-125i0an.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/98009/original/image-20151012-23283-125i0an.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/98009/original/image-20151012-23283-125i0an.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/98009/original/image-20151012-23283-125i0an.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/98009/original/image-20151012-23283-125i0an.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/98009/original/image-20151012-23283-125i0an.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/98009/original/image-20151012-23283-125i0an.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Diets high in sugary, fatty and processed foods are associated with depression and poor brain health.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/brizzlebornandbred/9375507295/">Paul Townsend/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>A balanced microfloral environment is supported by a diet rich in the foods that nourish beneficial bacteria and reduce harmful microbial species, such as <em>Helicobacter pylori</em>. Beneficial microflora can be supported by eating fermented foods such as tempeh, sauerkraut, kefir and yoghurt, and also by pectin-rich foods such as fruit skin. </p>
<h2>What now?</h2>
<p>Diets high in sugary, fatty and processed foods <a href="https://theconversation.com/you-are-what-you-eat-how-diet-affects-mental-well-being-27115">are associated</a> with depression and poor brain health. While nutrient supplementation can have a role in maintaining proper brain function and treating certain psychiatric disorders, nutrients should, in the first instance, be consumed as part of a balanced wholefood diet.</p>
<p>There is now enough research evidence to show the importance of nutrients for mental as well as physical well-being. A <a href="http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(14)00051-0/abstract">discussion about diet and nutrition</a> should be the starting point in conversations about mental health, just as it is for physical health.</p>
<p><em>If you’re interested in participating in a clinical trial prescribing nutrients for treating depression (SE Queensland and Victoria only), visit <a href="http://nutrientsdepressionstudy.com/">nutrientsdepressionstudy</a>.</em> </p>
<p><strong>Acknowledgement</strong>: Dr Drew Ramsey contributed to this article.</p><img src="https://counter.theconversation.com/content/37170/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jerome Sarris has received funding from Integria Health, Blackmores, Bioceuticals, Pepsico, HealthEd, Soho-Flordis, Pfizer, Elsevier, the Society for Medicinal Plant and Natural Product Research, CR Roper Fellowship, and The National Health and Medical Research Council. He is affiliated with The International Society for Nutritional Psychiatry Research. </span></em></p>A growing body of research points to the detrimental effect of unhealthy diets and the protective value of healthy diets – along with select nutritional supplements as required – for maintaining and promoting mental health.Jerome Sarris, Senior Research Fellow, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/275812014-06-13T04:35:34Z2014-06-13T04:35:34ZFive Australian medical stories everyone should know<figure><img src="https://images.theconversation.com/files/50220/original/z2tm3prx-1401859341.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The stories behind Australia's medical successes have often gone unreported. </span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/99329675@N02/11064892956/sizes/o/">Flickr: jpalinsad360</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>The history of Australian medical research is an unabashed good news story: it’s led to many astounding yet common medical treatments and to better understanding of disease. </p>
<p>In fact, as a society we benefit every single day from this innovation and growth in human knowledge. Yet so many of the stories behind the science remain hidden: we know so little about how we came to know what we know.</p>
<h2>1. Lithium as a treatment for mania</h2>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/50195/original/4ncvh4ty-1401856501.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/50195/original/4ncvh4ty-1401856501.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/50195/original/4ncvh4ty-1401856501.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/50195/original/4ncvh4ty-1401856501.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/50195/original/4ncvh4ty-1401856501.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/50195/original/4ncvh4ty-1401856501.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/50195/original/4ncvh4ty-1401856501.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The calming effects of lithium, which is a common treatment for mania, were first observed in guinea pigs.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/atomicbartbeans/73371424/sizes/o/">Hope for Gorilla</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<p>The first is about a young psychiatrist from Melbourne who had no research training whatsoever – John Cade. </p>
<p>Cade was particularly interested in bipolar disorder. He was convinced that the horrendous manic phase, where the person goes completely mad, must have been due to some toxin and he thought it would be secreted in the urine, particularly uric acid.</p>
<p>He was completely wrong. But his hypothesis led Cade to inject the urine from manic patients into guinea pigs. Because he knew lithium salts could help dissolve the uric acid crystals, Cade gave these salts to the guinea pigs. When he did that, he noticed they became calm and lethargic. </p>
<p>Not wanting to hurt anybody, Cade decided to take lithium himself. And then published an excellent clinical trial on ten patients in the manic phase of bipolar, six patients with schizophrenia and one with depression.</p>
<p>His results for mania were excellent, but there was no effect on schizophrenia or depression. In the best traditions of medical research, he published the paper in the Medical Journal of Australia. Sadly, the journal was not very widely read at the time and the findings lay silent.</p>
<p>But in the late 1960s, a Swedish group picked up the findings and and gave a young man by the name of Mogens Schou the job of investigating further. He did a double-blind trial and got regulatory approval for the drug in 1970.</p>
<p>Lithium remains one of the best treatments for bipolar disorder. In fact, what started as an experiment with a few guinea pigs and urine absolutely revolutionised treatment of the manic phase of bipolar.</p>
<h2>2. Analgesics and severe kidney disease</h2>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/50209/original/64b5xbzb-1401857960.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/50209/original/64b5xbzb-1401857960.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=360&fit=crop&dpr=1 600w, https://images.theconversation.com/files/50209/original/64b5xbzb-1401857960.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=360&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/50209/original/64b5xbzb-1401857960.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=360&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/50209/original/64b5xbzb-1401857960.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=452&fit=crop&dpr=1 754w, https://images.theconversation.com/files/50209/original/64b5xbzb-1401857960.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=452&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/50209/original/64b5xbzb-1401857960.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=452&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Priscilla Kincaid-Smith lobbied to stop harmful pain relief medication from being marketed as a useful stimulant.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/roadsidepictures/1862340173/sizes/o/">Flickr: roadsidepictures</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>For those of you not old enough to remember Bex and Vincent’s powders, they were painkillers that made a pleasant fizzy sound when put in a glass of water. You could go to the supermarket and there would be all these nice packets of the powders at the exit. And you would see people with four or five of these packets at the checkout to give them a bit of a pick-me-up.</p>
<p>Priscilla Kincaid-Smith began her studies in the Royal Melbourne Hospital in 1962. As a pathologist, she noted there were these tiny little black spots in the urine of some patients with chronic renal failure.</p>
<p>She put these samples under the microscope and saw they were the papillae (small nipple-like structures) of the kidneys that had been sliced off.</p>
<p>Early on, it was thought just one of the powders, or powders that contained aspirin, another painkiller called phenacetin, and caffeine, affected the kidneys and that phenacetin in particular was the problem.</p>
<p>Kincaid-Smith began testing with rats by giving them different painkillers. She found salicylates (an acid used for pain relief) alone could cause the kidney disease, but so could aspirin, panadol, paracetamol, a strong painkiller called indomethacin and other non-steroidal anti-inflammatory drugs.</p>
<p>But then she did her real work. With extensive activism and advocacy, gradually and over quite some time, Kincaid-Smith persuaded authorities that the sale of the painkillers should be restricted and that advertising should be abated.</p>
<p>A set of recommendations from the National Health And Medical Research Council (NHMRC) in 1970 achieved many of these goals. Advertising for these drugs as “pick-me-ups” disappeared and, with them, the disease essentially disappeared too.</p>
<h2>3. Colony stimulating factors</h2>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/50203/original/kdpd7qtb-1401857574.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/50203/original/kdpd7qtb-1401857574.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/50203/original/kdpd7qtb-1401857574.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/50203/original/kdpd7qtb-1401857574.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/50203/original/kdpd7qtb-1401857574.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/50203/original/kdpd7qtb-1401857574.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/50203/original/kdpd7qtb-1401857574.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Chemotherapy patients have benefitted from discoveries of the role that CSFs play in restoring white blood count.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/justonemorebook/4482602252/sizes/l">Flickr: justOneMoreBook</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span>
</figcaption>
</figure>
<p>Now we come to Don Metcalf and his large team of collaborators. This story begins in 1965 when Ray Bradley brought a little agar dish across the road from Melbourne University to the Walter and Eliza Hall Institute (WEHI).</p>
<p>In this dish, he had some large colonies of bone marrow cells that were growing: he had learnt how to grow them. Ray Bradley and Don Metcalf then published this discovery in 1966. They very quickly realised that the growth of these large colonies of cells depended on a variety of soluble hormonal factors, which were named colony stimulating factors (CSFs).</p>
<p>This story showed immense fortitude of the researchers involved because these CSFs are present in vanishingly small amounts. In one instance, all the workers at WEHI had to pee into a big bucket, and the urine was purified to get tiny amounts of CSF.</p>
<p>Later on, when the gene cloning era dawned, CSFs were made by genetic engineering in harmless bacteria. They have come to be amazing therapeutic substances, especially for people with cancer.</p>
<p>There are dose-limiting factors in cancer chemotherapy, usually either gut toxicity or bone marrow toxicity. If you have no white cells because the bone marrow is not making them you’ll die of an infection, it’s as simple as that.</p>
<p>So what these CSFs do is act as a bone marrow tonic to restore white blood count to normal. They’re an immensely important adjunct to cancer radiotherapy. Over 20 million cancer patients have received CSFs.</p>
<h2>4. Sleep apnoea</h2>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/50198/original/cf27zk4p-1401856788.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/50198/original/cf27zk4p-1401856788.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/50198/original/cf27zk4p-1401856788.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/50198/original/cf27zk4p-1401856788.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/50198/original/cf27zk4p-1401856788.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/50198/original/cf27zk4p-1401856788.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/50198/original/cf27zk4p-1401856788.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&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">Colin Sullivan designed the first CPAP, aiding sufferers of sleep apnoea</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/com_salud/7999032358/sizes/l">Flickr: COMSALUD</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>Now we come to Colin Sullivan from the University of Sydney and Royal Prince Alfred Hospital. He was a respiratory physician interested in sleep apnoea.</p>
<p>At least 4% of men and 2% of women suffer from obstructive sleep apnoea. It’s a serious problem that means when they fall asleep, they stop breathing. In the worst cases, there might be 500 such attacks a night. </p>
<p>Sleep apnoea causes daytime sleepiness, but more worryingly evidence now shows it leads to increased incidence of coronary artery disease, hypertension and stroke.</p>
<p>Colin Sullivan developed a “continuous automatic positive airways pressure kit” or CPAP to prevent the upper airway from closing. He then founded a firm called ResMed in 1989. </p>
<p>Since then, each model has been improved and they’re now mass-produced portable, home-use CPAP devices consisting of a small, light, comfortable nasal mask connected via light tubing to quiet, unobtrusive ventilator. This sits on your bedside table delivering ideal temperature and humidity-controlled pressurised air.</p>
<p>It’s such a good treatment that it brings in revenue of $1.6 billion per year.</p>
<h2>5. Spina bifida</h2>
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<img alt="" src="https://images.theconversation.com/files/50215/original/wrq8kmrz-1401858785.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/50215/original/wrq8kmrz-1401858785.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/50215/original/wrq8kmrz-1401858785.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/50215/original/wrq8kmrz-1401858785.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/50215/original/wrq8kmrz-1401858785.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/50215/original/wrq8kmrz-1401858785.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/50215/original/wrq8kmrz-1401858785.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">Fiona Stanley was the first to demonstrate that higher consumption of folate during pregnancy would lead to fewer cases of spina bifida.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/yourdon/9220312593/sizes/l">Flickr: Ed Yourdon</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span>
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<p>In 1981, UK scientists conducted a double-blind clinical trial showing folic acid supplementation in early pregnancy could lower the incidence of spina bifida. But it was Fiona Stanley who first showed, in a case-control study, that the more folate in your diet during pregnancy, the less spina bifida.</p>
<p>Since this discovery, Stanley has promoted mandatory fortification of flour with folic acid. This was finally enacted in 2009.</p>
<p>Stanley has another string to her bow. She is an epidemiologist and neonatologist and she’s responsible for showing that cerebral palsy is only very rarely due to birth trauma (5% to 10% of cases). The rest, and in the vast majority of cases it’s due to infections, blood incompatibilities, genetics or unknown causes.</p>
<p>That’s important because of the litigiousness of patients who are dealing with the terrible burden of having a cerebral palsy child against obstetricians. It’s legendary. And in fact, many people refrain from going into the field of obstetrics because they’re so frightened of this litigation.</p>
<p><br>
<em>This article is based on a speech delivered by Sir Gus Nossal at Celebrating Australian Science: Past, Present, Future, a symposium held by the Australian Academy of Science. You can <a href="https://www.youtube.com/watch?v=6M0bVzMiAjY&t=36m53s">watch his full presentation here</a>.</em></p><img src="https://counter.theconversation.com/content/27581/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gustav Nossal has previously worked with some of the researchers mentioned in this speech. </span></em></p>The history of Australian medical research is an unabashed good news story: it’s led to many astounding yet common medical treatments and to better understanding of disease. In fact, as a society we benefit…Gustav Nossal, Professor Emeritus , Walter and Eliza Hall InstituteLicensed as Creative Commons – attribution, no derivatives.