[Examine Newsletter] November 2022 Updates

See what's new on Examine for the past month!  ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ [Examine]( [View in browser](=) Hello! Here’s your recap of Examine's November 2022 updates. 📧 Reminder: If you would like to switch back to weekly emails instead of a monthly newsletter — just [click here](). --------------------------------------------------------------- Top 5 Study Summaries for November Nov. 17, 2022 Every month, we summarize 150+ recent studies for our [Examine+ Members](). You can read five of this month’s most favorited Study Summaries for free by clicking the links below. The two Study Summaries marked with are Editor’s Picks, which provide more details about the study, mention related studies, and include helpful graphics. [Evaluating the combination of a low carb diet and time-restricted eating]() In this 3-month randomized controlled trial, combining a low-carbohydrate diet with time-restricted eating (TRE) in an 8-hour eating window produced greater weight loss than a low-carbohydrate diet or TRE alone and improved cardiometabolic risk factors to a greater extent. = [Nonnutritive sweeteners and the gut microbiome]() Two weeks of saccharin or sucralose intake was correlated with higher blood glucose responses and alterations in gut microbiome function in adults without diabetes. A subsequent mouse study using fecal transplants from the study participants suggested that the increased glycemic responses may be linked to alterations in the participants’ gut microbiomes. [What’s the best form of creatine?]() This systematic review of 17 clinical trials compared 7 creatine formulations in terms of effects on body composition and exercise performance and concluded that creatine monohydrate is still the lowest-cost and best-studied form of creatine. [The effects of diet on sleep quality in trained athletes]() In this systematic review of 35 studies in trained athletes, caffeine intake in the evening decreased sleep quality, whereas evening consumption of protein rich in tryptophan and carbohydrates high in glycemic index improved sleep quality. [What type of exercise is best to improve sleep quality?]() This systematic review and network meta-analysis of 35 clinical trials found that any type of exercise can improve sleep quality in older adults, but moderate endurance training combined with walking showed the greatest benefits. You can also check out the [most-favorited summaries from previous months]().🔥 --------------------------------------------------------------- The daylight saving debate Nov. 10, 2022 The debate surrounding daylight saving time is more heated than ever before. There are three options available in the U.S., and other countries also have ongoing debates: - Continue switching times twice a year - Make it daylight saving time (DST) all year round - Make it standard time (ST) all year round Is DST a boon or a net negative? The first option is quite unpopular. A majority of the American public favors keeping DST all year, along with many legislators. Sleep scientists and circadian biologists tend to favor keeping ST all year round. Hawaii is close to the equator, so they stick to ST, as does Arizona, but for extreme-heat related issues. Every other state switches twice a year, giving you double the opportunity to forget to change one of your clocks. There are many issues at play here: energy consumption, public safety, and so on. When so many complex issues collide, countries usually conduct detailed analyses and consult leading experts in each of the involved fields. YEAH RIGHT! You may be aware of something called “politics”. No matter your expertise on relevant issues, your opinion isn’t as important as that of politicians and lobbyists. That may sound bitter, but politics comes up way too often when discussing science-related issues. After the spring time change this March, a former Examine researcher asked if I might want to help educate people about relevant daylight saving issues (Hi Kristen!). She happens to have completed a fellowship in sleep and circadian biology. We usually rely on our own independent analyses and don’t share outside links, but in this case, the topic is best addressed by outside experts. Here’s a succinct explanation of the science from a [piece by the American Academy of Sleep Medicine (AASM)](=): “The one-hour time shift during daylight saving time results in less exposure to light in the morning and greater exposure to evening light relative to typical sleep and work schedules. As a result, we tend to go to bed and fall asleep later, resulting in chronic sleep loss. Daylight saving time causes ongoing misalignment between our sleep/wake rhythm and the light/dark cycle, also called “social jet lag.” “The daylight saving time changes can be especially problematic for any populations that already experience chronic insufficient sleep or other sleep difficulties.” Of course, there are other issues at play as well, outside of circadian biology. But anyone with sleep issues knows that sleep is often the single most important factor influencing health and happiness. If you feel strongly about the issue, the AASM provides [a link]() for Americans to easily contact their representatives. --------------------------------------------------------------- Our first gene email: HFE and iron Nov. 3, 2022 Two weeks ago, I asked which of two genetics topics you preferred to learn about. Here are the results: - 54% of readers chose Which genes influence your response to different foods? - 46% of readers chose Do personalized diet plans work in clinical trials? That was a nail-biter! And speaking of nails, nails contain iron, which is the first of the food-related gene topics we’ll cover. Every few weeks, I’ll discuss another gene, but I won’t always use a cheesy transition to do so … Iron and the HFE gene can be a matter of life and death You already know that iron deficiency is worth keeping an eye on, and you’re fairly likely to know someone who’s been anemic. What you might not know is how dangerous iron overload can be, and how easily it can develop, especially if you’re genetically susceptible. Iron overload can sneakily contribute to chronic illness and even mortality. Hold up, what’s wrong with iron? Have you ever noticed multivitamin bottles with “IRON-FREE” displayed prominently on the label? If iron is the lone nutrient that isn’t included in a multivitamin+multimineral formulation, which is nearly always the case these days, there must be something up with iron. Now there’s nothing inherently wrong with iron, but there is something wrong with excess iron levels. Iron is important for so many health functions because of its ability to participate in electron exchange. But that same ability can also lead to the production of damaging free radicals, linking excess iron to a variety of harms, including inflammation, neurotoxicity, and insulin resistance. There’s also no easy way to get rid of excess iron, unless you’re a woman of childbearing age who has regular periods. Excess iron can either be an acute problem or a chronic one. Acute iron poisoning is typically seen in children, especially in cases of accidental ingestion of iron-containing supplements. The heart and liver are two of the organs most affected by chronic iron overload, as they’re both highly metabolically active organs. People with heart damage caused by excess iron survive, on average, less than a year if untreated. Luckily, most people don’t accumulate too much excess iron unless they have a genetic predisposition to do so. Hereditary hemochromatosis and the HFE gene One thing you may already be wondering: if iron is so dangerous, why would genes predisposing someone to iron overload have perpetuated in the first place? Although no one knows for sure, it’s possible that mutations may have helped boost iron levels in the context of the generally lower iron intake associated with the rise of agriculture and grains. Mutations could also ensure high iron levels in women who give birth or menstruate heavily. It’s estimated that 1 in 227 Caucasians in North America have the main mutation that’s associated with hereditary hemochromatosis, which is an umbrella classification that includes all the different genes that can predispose someone to iron overload. While there are several genes that can play a role, the HFE gene is the most commonly involved. HFE is short for High Fe (with Fe being the periodic table symbol for iron), making it a pretty easy gene to remember. The gene was only identified in 1996, so it’s quite likely that your family is not aware of it, or its effects on iron and health. If each of your parents has a mutated HFE gene, you’re designated as having hereditary hemochromatosis, but if only one parent has a mutation, you’re typically not at increased risk. People with hereditary hemochromatosis have increased dietary iron absorption along with dysregulated iron recycling, which can cause it to build up in tissues. The C282Y mutation is the most common mutation that causes severe overload, while the H63D mutation causes milder effects. Note that all of this is best discussed with a physician, and maybe a genetic counselor, too. Examine is neither of those things, so don’t take our word for anything without talking to a medical specialist! [Digging this research? Unlock more with a free two week trial of the Examine+ membership!]() Diagnosing iron overload Iron overload isn’t easy to diagnose on your own, since typical symptoms, such as fatigue, joint pain, worsening heart health, and hormonal issues, are also common maladies of aging. And iron overload tends to show symptoms in middle and older age, as iron accumulates in the body, which just happens to be the time period when these symptoms might start popping up anyway. If you’re of European origin, there’s around a 1 in 300 chance you have hereditary hemochromatosis, although the rate could be higher in some countries such as Ireland and Sweden. If you suspect you may have iron overload, your doctor will test for a few things, including how much iron is in your blood, how saturated your transferrin (short-term iron storage molecule) is with iron, and your ferritin (long-term storage) levels. Even if you aren’t homozygous for an HFE mutation, it may be worth paying attention to your iron intake, since even mild iron overload can exacerbate fatty liver disease and damage the kidneys. If you’re sure of having Northern European ancestry, it may be even more helpful to check your genetic data, as that region has much higher mutation rates than the rest of Europe and other regions. People of British stock should take particular heed, as the C282Y mutation is theorized to be of Celtic origin, first appearing somewhere between 1,000 to 3,000 years ago. The milder H63D mutation, on the other hand, is spread out across the globe, and emerged earlier than C282Y. Diets and supplements are preliminary ways of regulating iron status If you have excess iron, iron-containing food may not be the only culprit. While genes are the main determiners of iron load, supplementation can play a big role for some people. Athletes sometimes supplement with iron if they feel lethargic, and some consume multiple iron-containing supplements in combination with eating red meat regularly. The most direct way to reduce iron intake is by reducing meat consumption. Heme iron is easily absorbed and makes up nearly half of the iron in meat, but none of the iron in plants. Heme iron is absorbed more than twice as efficiently as non-heme iron, and this absorption is nearly four times higher in people with hemochromatosis. Red meat is richer in iron than most other meats, with over twice the levels of most fish, and around a quarter more than chicken. A variety of plant compounds can help reduce heme iron absorption from meat, such as quercetin, which is present in a wide variety of plants, including apples and bell peppers. Coffee and tea also impair iron absorption, and are easy to consume regularly. The mainstays of iron-deficiency anemia correction are supplementing with vitamin C to increase iron absorption, and avoiding calcium intake alongside iron. So doing the opposite of these could help with iron overload. An occasional, unsuspected culprit: cast iron pans While meat is the most common source of iron, an unlikely contributor to iron intake is cooking with cast iron. Cast iron cooking is actually used in some countries to reduce anemia rates, as pans can leach varying amounts of iron, depending on the food being cooked. Although the iron is in the less well-absorbed non-heme form, cooking acidic or vitamin C rich food can increase absorption rates substantially. In fact, a serving and a half of pasta sauce, despite being naturally low in iron, can end up containing enough iron to meet the recommended dietary allowance when cooked in a cast iron pan. Giving blood can directly treat excess iron If you have high iron levels, giving blood is the most reliable way to lower iron stores, plus it can provide a variety of benefits. The most obvious is that you’re helping someone you don’t know. Congratulations! Also, phlebotomy can improve insulin sensitivity by removing some iron from the body. Even more impressive is that phlebotomy may reduce cancer rates. If you’re dreading needles or the blood-drawing experience, don’t worry about having to undergo this process too frequently. Annual iron checks alongside selective use of phlebotomy have been shown to be about as effective as donating blood every 2–4 months. Conclusion The HFE gene is one of the few identified nutrition-related genes that has a major effect, by itself, in a fairly large number of people. Whether or not you should consider reducing iron intake, and perhaps even giving blood regularly, depends on getting your iron checked and genes tested. Since it’s difficult to pinpoint iron overload symptoms on your own, this is one of the few areas related to nutrients where gene testing can provide clear benefits (that is, if you’re known to be at risk of hereditary hemochromatosis). Thanks for reading all this way. It takes extra time to research and write these occasional long emails, so if you like or hate them, do let me know! --------------------------------------------------------------- So, did you find something of interest? If not, please reply to this email to let me know which topics you’d like us to tackle. And if you’re ready to stay on top of the latest research, consider becoming an [Examine+ Member](. Sincerely, Kamal PatelCo-founder, Examine Follow us on: [Facebook]( [Twitter]( [LinkedIn]( [Instagram](=) [About Examine]( | [Careers]() | [Member’s Area]() [Unlock Examine+]( PO Box 592, Station-P, Toronto, Ontario M5S 2T1 [Switch to weekly emails]() | [Opt out of all emails](