[Examine Newsletter] July 2023 Updates

See what’s new at Examine over the past month!  ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ [Examine]( [View in browser]() Hello! Here’s your recap of Examine’s July 2023 updates. We’re having a summer sale in early August! [Get on the early bird list]( by August 6 for an extra discount and a chance to win 1 of 5 Examine+ Yearly memberships. --------------------------------------------------------------- Lots of page updates, and more to come! July 27, 2023 Hi! It’s Nick (Lead Researcher at Examine) again. I’m here to give you an update on our page updates. It’s been a few weeks since I emailed you, and as promised, our team has been working hard to bring Examine’s pages up to date. Our new system for identifying and working on pages that need updates has been working great, and we’ve made a ton of progress. Here’s a list of what we’ve accomplished recently: Major Updates (Considerable updates to the FAQs, database, or both) Intervention Pages Health Topic Pages - [GABA](=) - [Ashwagandha](=) - [Magnesium](=) - [Tongkat Ali](=) - [Apigenin](=) - [Zinc](=) - [Maca](=) - [Shilajit](=) - [Bacopa Monnieri](=) - [Bitter Orange]() - [Melatonin]() - [Curcumin]() - [Isn’t Soy Protein Bad for Men?]() - [Focus & Attention]() - [Hyperemesis Gravidarum]() - [Anorexia Nervosa]() - [Healthy Aging & Longevity]() - [Menstrual Health]() - [Chronic Low Back Pain]() - [Human Immunodeficiency Virus (HIV)]() - [Egg Allergy]() - [Premenstrual Dysphoric Disorder]() - [Sickle Cell Disease]() - [Osteopenia]() - [Rosacea]() - [Body Dysmorphic Disorder]() - [Peripartum Depression]() - [Orthorexia]() - [Healthy Muscle Aging]() - [Gastroenteritis]() - [Bulimia Nervosa]() - [Acute Respiratory Infection]() - [Hemorrhoids]() - [Cataracts]() - [Fat Loss]() Minor Updates (Small additions, changes, or corrections) - [Taurine]() = - =[DHEA]() = - =[L-Tyrosine]() = - =[Alpha Lipoic Acid]() = - =[Anaerobic Exercise Performance]() = - =[Multiple Sclerosis]() = - =[Dry Eye]() We have a ton of intervention pages updates in the pipeline, too. In the next two months you can expect to see BIG updates to some of our most-requested pages, like: - N-Acetylcysteine (NAC) - Nicotinamide Mononucleotide (NMN) - Berberine - Inositol - Rhodiola Rosea - Creatine - Vitamin D We’ll be updating our popular Whey Protein, Fish Oil, and Theanine pages as well, plus many, many more. In addition to keeping our pages up to date, our goal is to keep our readers informed about what we’re doing. This is partially because I want you to appreciate the amazing work of our researchers (they rule), but it’s also because your feedback is tremendously important. I want you to know when we’ve finished an update so you can check it over and make sure we didn’t miss anything. I want you to know when we are working on an update so you can suggest studies and ask questions, and I want you to know when we are planning an update so you can tell us how we should prioritize it relative to other pages. We will also be launching our “update log” in the next few weeks, so you’ll be able to keep track of our content and site updates as they happen. Ultimately, the information we’re reviewing and pulling together is for you, and nobody knows what you need as well as you do. So let us know! You are always welcome to reply to this email with questions, concerns, and suggestions, or use our new Send Feedback buttons on every page of the site to contact us directly. --------------------------------------------------------------- Feedback of the week What do you think of the Research Snapshot? It’s the colorful box at the top right of our intervention and condition pages. Here’s [creatine](), for example: [Tell us if you love or hate the Research Snapshot]( --------------------------------------------------------------- 📅 Top 5 Study Summaries for July July 20, 2023 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 Study Summaries marked with are Editor’s Picks, which provide more details about the study, mention related studies, and include helpful graphics. [Can uneven protein distribution negatively affect muscle gain?]() In this randomized controlled trial in older adults, an even distribution of protein intake throughout the day resulted in greater net whole-body protein balance compared to an uneven distribution. = [Which antioxidant works best for prostate cancer prevention?]() This network meta-analysis reported that supplementation with green tea catechins shows promise for reducing the risk of prostate cancer. [Can eating walnuts improve children’s cognitive development?]() In this randomized controlled trial, walnut consumption improved attention, fluid intelligence, and ADHD symptoms in children with high adherence to the intervention. [Does mental fatigue impair exercise performance?]() In this randomized controlled trial, pre-exercise mental fatigue did not influence maximal power or force output during jumping and bench pressing tests, though it may affect other kinds of exercise. [Can N-acetylcysteine help with endometriosis?]() In this prospective cohort study, supplementation with N-acetylcysteine was associated with reductions in endometriosis-related pain and endometrioma size. You can also check out the [most-favorited summaries from previous months]().🔥 --------------------------------------------------------------- Two site improvements July 13, 2023 Just two quick things from me this week: 1. The Examine Database can now be filtered. Just start typing the name of the condition or outcome you’re looking for and it will start filtering. If you prefer the old style from before our Examine v2 launch, you can now also remove the condition row. And if you want to filter by grade and effect, just tap “More filters”. Scroll down [this page](), for example, to see it live. [Examine Database filtering demo] We’re working on bringing similar filtering features to our [Study Summaries]() soon! 2. You can now submit feedback more easily on Examine pages. There’s a feedback button on the right-hand side of every page. [Examine feedback submission demo] You can send us corrections, ideas, usability issues … anything, really! Even cat videos. I love cat videos. But seriously, more feedback will let us improve the site even faster. --------------------------------------------------------------- Does aspartame cause cancer? July 7, 2023 Word to the wise: This email is long because the topic is both complex and important — strap yourself in! I tried to limit it to 2,000 words, and even so I couldn’t cover everything. If you want more on this topic, let me know, and we could expand to covering a bunch of aspartame-specific studies in an article and video. Aspartame was all over the news last week because the World Health Organization (WHO) classified it as a possible carcinogen. If you drink a lot of Diet Coke or Coke Zero, you probably already know about this. Millions of people immediately Googled to find out if aspartame was actually dangerous, and millions of people came away (rightfully) confused. I mean, just check out the first sponsored search result when I googled “aspartame who”: [FDA and aspartame Google search] That’s not the WHO report! If you scroll all the way to the bottom of that website, you’ll see it was created by the good ol’ American Beverage Association. With literally billions of dollars at stake for megacorporations, and public health agencies not agreeing with each other, it’s hard to know who to trust. Whatever you do, don’t trust my opinions either (at least, don’t trust me blindly). I’m not a toxicologist or artificial sweetener researcher. Although I’ve been an author on a few peer-reviewed studies, none of them were on anything close to this topic. However, I do enjoy trying to connect research dots, and I’ll show you the path I took, so read the rest of this email to see if my dot-connecting makes sense. If not, move on to the next source! (Or reply and let me know.) Here’s a preview of this email if you’re curious about whether it’s worth your time: This isn’t a yes/no question about whether aspartame causes cancer. There are actually two much more important questions being asked: - How applicable are different lines of rodent evidence on aspartame safety regarding cancer and noncancer conditions? - What might you want to factor in to your specific decision regarding consuming aspartame never, sometimes, or often? Opinion 1: Nearly everyone is wrong Lots of health gurus shared strong opinions about the WHO’s decision without having read the actual studies! There are literally hundreds of published papers on aspartame, and most people have read zero of them. That’s led to a bifurcation of opinions. Some gurus say … “Aspartame was clearly linked to increased cancer risk in cohort studies, and artificial sweeteners [damage our gut microbiomes](), too. Just stop consuming them!” The other side says … “Everything possibly causes cancer. Aspartame has been proven safe in hundreds of studies. This is not news.” In my opinion, both sides are wrong, and cursory opinions like the above are masking the most important issues. The first quote is alarmist, absolutist, and based on limited evidence. It’s also ignoring a potential benefit of artificial sweeteners: some people have a very difficult time losing weight, and they find it helpful to substitute sugar calories with a sugar alternative’s zero calories. That may not apply to you, but what applies to you may not apply to others. The second quote is making a false equivalency — most substances classified as “possible carcinogens” aren’t consumed by as many people as frequently as diet soda is. For example, aloe vera and pickled vegetables are also possible carcinogens, but few people consume these in large amounts every day for decades (except for pickled vegetables in some Asian countries). Diet soda is guzzled by a higher percentage of people around the globe, since diet soda is a common partial water replacement, caffeinated pick-me-up, or caloric treat replacement. Basically, diet soda is a multitool, which is why it’s so astoundingly popular, with around 1 in 5 people regularly drinking it. And that’s also why this topic deserves a deep dive instead of a one-off Instagram post! It’s also important to keep in mind that the WHO classified aspartame in Group 2B, tagging it as a possible carcinogen with “far from conclusive” evidence. So anyone who says aspartame was classified as a carcinogen is wrong. ‘Possible’ is waaaaaay different from ‘probable’ or ‘definite’. Group 1A is labeled “Carcinogenic to humans” and contains substances with pretty strong evidence for one or more cancer types, like asbestos, aflatoxin from moldy peanuts and other plants, and processed meats. Group 2A are probable carcinogens, as opposed to Group 2B possible carcinogens, and includes the fire retardant vinyl bromide, the acrylamide formed from frying potatoes, and unprocessed red meats. [We covered]() the WHO’s red meat report back in 2015. If you don’t want to read that link, one of the main takeaways is that cumulative dose is most important. Do not be scared to eat a breakfast dish that contains bacon and fried potatoes. But if your combined exposure to Group 1A and 2A substances (and to a much lesser extent 2B) is high on most days, then it’s time to take a step back and reassess. Opinion 2: The first big issue involves rodent research When we discuss aspartame and cancer risk, we first need to determine how we can most accurately extrapolate data from rodent research to apply to humans. Here’s the issue: the bulk of “good” evidence about aspartame dangers comes from rodent studies. Sure, there’s also in vitro evidence, but the models used in this type of research are an approximation, at best, of what may occur in living animals or humans. And sure, there are some human studies that find increased cancer risk from aspartame. Notably, the French [NutriNet-Santé study](), which showed a 15% higher risk of cancer in aspartame consumers. But that’s fairly weak evidence. Simply put, these cohort studies are best for hypothesis generation, and cannot determine causality. That’s because cohort studies aren’t experiments. Groups aren’t given aspartame or a placebo. They’re not randomized to make sure the participants don’t differ in important characteristics. Rather, a group of people is tracked over time and asked about their aspartame consumption and other variables. This is about as good as human aspartame studies can get because it’s unethical to randomize a group to consume tons of aspartame every day for decades to see if they develop cancer. The biggest problem is that there are dozens of ways that aspartame consumers could be different from people who avoid aspartame. For example, aspartame consumers could have slightly higher chances of yo-yo dieting, slightly worse baseline mental health, and tons of other factors. These are all factors that could theoretically confound the relationship between aspartame and cancer. There are too many unknown factors to control for, so even the best controlled statistical model linking aspartame to cancer is incomplete. Rodent trials are different. Researchers can control way more variables. Rodents consume the same type of food every day and are housed under perfectly timed light/dark cycles. They don’t stay up late binging Netflix, get stressed out by their bosses, or take vacations. They also have 100% adherence rates and can’t choose to drop out of trials. Plus, due to their shorter lifespans (nine rodent days equates to about one human year), researchers can run trials up until the rodents develop diseases. That would be cost prohibitive and unethical in humans. Except that rodents aren’t human, so we have to be careful about how we interpret rodent data. Opinion 3: Rodent research should not to be ignored To learn more about rodent research and ethics, check out my [mini-interview with Examine rodent researcher Bill Willis, PhD](). This is such a tricky topic! Let me fill you in on just a tiny slice of the complexity involved. You might think it’s possible to extrapolate how well animal trials translate to human trials by looking at other health topics. That way, other topics can help us determine how important aspartame animal trials are. The problem is these are typically pharmaceutical efficacy trials. For example, one commonly cited statistic states that around 90% of drugs that succeed in animal trials fail in human trials. But that’s testing something that worked in animals to see if it works in humans, not testing something that harmed animals to see if it harms humans. The latter isn’t really done, because of ethical considerations. Not to mention that sweetener consumption is different than pharmaceutical use. For example, it’s not uncommon to drink 4–5 or more cans of diet soda a day, for decades. It’s much more rare for people to dose a single pharmaceutical 4–5 times or more a day for decades. As another example, some sweeteners are becoming ubiquitous, so that you’ll get dosed in your soda, dosed in your protein shake, and dosed in your dessert. That doesn’t happen with pharmaceuticals. These and other differences mean that there’s no great precedent for translating animal research on aspartame to humans. And there are myriad other issues — like the fact that animal trials can have as many or more methodological quality issues as human trials. Even with all that in mind, the rodent research should not be ignored! Aspartame animal studies typically involve rats, with a few being on mice and even fewer on other small animals. Aspartame doses of over 40 mg/kg of rat body weight are called “high dose”, while less than that is a “safer dose”. High dose studies often showed harm, while “safer dose” studies sometimes did. The harms included cancer (notably lymphoma and leukemia), oxidative stress, systemic inflammation, and a variety of other effects. (If you have any of these, they are mostly likely NOT due to your consumption of diet soda! Other lifestyle, environmental, and genetic factors are likely much more influential.) Interestingly, aspartame seemed to provide a protective effect from pancreatic cancer in rats when used as a substitute for sugar. Over on the human side, public health agencies and studies generally set safe upper aspartame limits at about 15–30 cans of soda a day, depending on your body weight. This may very well be accurate, but here’s the thing: science evolves. Many aspartame studies have come out in the past few years, and safety evaluation should be updated periodically. The safe upper dose may not stay the same in future years. If you’re an aspartame drinker and suspicious of all this fuss, consider the case of saccharin. Saccharin is the original artificial sweetener, accidentally discovered at Johns Hopkins (my alma mater!) in 1879. Come to think of it, sucralose was also accidentally discovered. What’s with artificial sweetener accidental discoveries? Maybe it’s because accidentally discovering a toxic substance is way more dangerous and we only hear from scientists who made something sweet. Anyway: A bunch of diet sodas used to use saccharin, but switched to other sweeteners in the 1980s because the FDA warned of animal research linking it to cancer. Here’s some visual evidence: [Saccharin Notice sign] Fast forward 20 years, and federal agencies concluded that the animal evidence wasn’t as applicable as previously thought, and the warnings disappeared. But saccharin lost the race, and now a variety of other sweeteners are used. So is the science on aspartame as definitive as some say it is? It might be, due to the massive amount of research already done. Or it might not be. We cannot predict the future. Opinion 4: This risk tolerance checklist could help your decision How you make risk-based decisions about what to consume matters as much as what the research says, because research is rarely definitive. You can ask your doctor, but chances are they’re not reading aspartame studies in their spare time. You can ask me, but I’ll just say “I’m not sure” and write you a 2,000-word reply on the pros and cons of aspartame research. So instead, here’s a handy checklist you can use: Do you consume any aspartame? If you don’t, this email is just for learning purposes. Continue not consuming aspartame! Is aspartame helping you maintain a healthier weight? If yes, extra weight is likely a much bigger risk factor for disease than artificial sweeteners are. If you’re very risk averse, consider reducing your aspartame-containing diet soda intake by even a little bit, or even progressively diluting it with carbonated water to help “reset” your sweetness tolerance. Do you have gut issues that you suspect might be linked to diet soda? Most people’s gut issues are probably not related to diet soda, since there are typically bigger gut-bacteria-affecting issues at play involving diet and stress levels, among other factors. But it doesn’t hurt to try a month of no diet soda. There is no dietary requirement for diet soda! If you only change that one variable (diet soda) and feel better, that’s a pretty decent clue. Are you consuming over five cans of aspartame-containing diet soda per day? Why five cans? I divided 15 cans (the bottom of the “safe upper limit” levels experts have put forth) by three, and got five. This calculation is completely arbitrary. But if you’re very risk averse, going from over five cans to under five cans might help psychologically, because you’d be at under a third of the limit. If you’re not risk averse at all or think I’m full of it, consume up to the FDA limit, which is 50 mg/kg of body weight per day, with Diet Coke containing around 180 mg per can, but try not to go over very often. Would you be willing to alternate other sweeteners or use fewer sweeteners? Modern humans have access to a wide variety of artificial and natural sweeteners. You could distribute and potentially minimize your risk by not using the same one every day if you’re going to be consuming sweeteners for decades. Ultimately, this is a complicated topic. It’s incorrect to say that aspartame has no causal link to cancer, but it’s also incorrect to heavily imply it does cause cancer. If you take one thing away from my novel, I hope it’s a respect for the complicated role of animal research in big questions of human health, and the power of individual choice over a lifetime. Health isn’t determined by what you do in a day or a week, but what you do consistently over years and years. Was this massive yet inevitably incomplete aspartame tome interesting or helpful for you? Let me know, and I may expand on it in an article and YouTube video. --------------------------------------------------------------- Sincerely, [Kamal Patel](), [Nick Milazzo](), and [Morgan Pfiffner](). P.S. If you’ve been thinking about checking out the Examine+ membership, [get on our early bird list by August 6]( for an extra discount and a chance to win 1 of 5 Examine+ Yearly memberships. 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](