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Email Facebook Twitter Pinterest Pocket Reddit Print By Cassandra Willyard 11 hours ago The internet is rife with advice for keeping the brain sharp as we age, and much of it is focused on the foods we eat. Headlines promise that oatmeal will fight off dementia. Blueberries improve memory. Coffee can slash your risk of Alzheimer’s disease. Take fish oil. Eat more fiber. Drink red wine. Forgo alcohol. Snack on nuts. Don’t skip breakfast. But definitely don’t eat bacon. One recent diet study got media attention, with one headline claiming, “Many people may be eating their way to dementia.” The study, published last December in Neurology, found that people who ate a diet rich in anti-inflammatory foods like fruits, vegetables, beans and tea or coffee had a lower risk of dementia than those who ate foods that boost inflammation, such as sugar, processed foods, unhealthy fats and red meat. Sign Up For the Latest from Science News Headlines and summaries of the latest Science News articles, delivered to your inbox E-mail Address* But the study, like most research on diet and dementia, couldn’t prove a causal link. And that’s not good enough to make recommendations that people should follow. Why has it proved such a challenge to pin down whether the foods we eat can help stave off dementia? First, dementia, like most chronic diseases, is the result of a complex interplay of genes, lifestyle and environment that researchers don’t fully understand. Diet is just one factor. Second, nutrition research is messy. People struggle to recall the foods they’ve eaten, their diets change over time, and modifying what people eat — even as part of a research study — is exceptionally difficult. For decades, researchers devoted little effort to trying to prevent or delay Alzheimer’s disease and other types of dementia because they thought there was no way to change the trajectory of these diseases. Dementia seemed to be the result of aging and an unlucky roll of the genetic dice. While scientists have identified genetic variants that boost risk for dementia, researchers now know that people can cut their risk by adopting a healthier lifestyle: avoiding smoking, keeping weight and blood sugar in check, exercising, managing blood pressure and avoiding too much alcohol — the same healthy behaviors that lower the risk of many chronic diseases. Diet is wrapped up in several of those healthy behaviors, and many studies suggest that diet may also directly play a role. But what makes for a brain-healthy diet? That’s where the research gets muddled. Despite loads of studies aimed at dissecting the influence of nutrition on dementia, researchers can’t say much with certainty. “I don’t think there’s any question that diet influences dementia risk or a variety of other age-related diseases,” says Matt Kaeberlein, who studies aging at the University of Washington in Seattle. But “are there specific components of diet or specific nutritional strategies that are causal in that connection?” He doubts it will be that simple. Worth trying In the United States, an estimated 6.5 million people, the vast majority of whom are over age 65, are living with Alzheimer’s disease and related dementias. Experts expect that by 2060, as the senior population grows, nearly 14 million residents over age 65 will have Alzheimer’s disease. Despite decades of research and more than 100 drug trials, scientists have yet to find a treatment for dementia that does more than curb symptoms temporarily (SN: 7/3/21 & 7/17/21, p. 8). “Really what we need to do is try and prevent it,” says Maria Fiatarone Singh, a geriatrician at the University of Sydney. Forty percent of dementia cases could be prevented or delayed by modifying a dozen risk factors, according to a 2020 report commissioned by the Lancet. The report doesn’t explicitly call out diet, but some researchers think it plays an important role. After years of fixating on specific foods and dietary components — things like fish oil and vitamin E supplements — many researchers in the field have started looking at dietary patterns. That shift makes sense. “We do not have vitamin E for breakfast, vitamin C for lunch. We eat foods in combination,” says Nikolaos Scarmeas, a neurologist at National and Kapodistrian University of Athens and Columbia University. He led the study on dementia and anti-inflammatory diets published in Neurology. But a shift from supplements to a whole diet of myriad foods complicates the research. A once-daily pill is easier to swallow than a new, healthier way of eating. Where diet fits Up to 40 percent of dementia cases could be prevented or delayed by modifying 12 risk factors. Targeting some of these risks reduces nerve cell loss in the brain; other interventions protect the brain’s ability to function and adapt even if some nerve loss has occurred, a concept called cognitive reserve. Diet plays a role in at least four of these risk factors. Twelve modifiable risk factors for dementia Reduce nerve cell damage Minimize diabetes Treat hypertension Prevent head injury Stop smoking Reduce air pollution Reduce midlife obesity Increase or maintain cognitive reserve Maintain frequent exercise Reduce depression Avoid excessive alcohol Treat hearing impairment Maintain frequent social contact Attain high level of education Source: G. Livingston et al/Lancet 2020 Earning points Suspecting that inflammation plays a role in dementia, many researchers posit that an anti-inflammatory diet might benefit the brain. In Scarmeas’ study, more than 1,000 older adults in Greece completed a food frequency questionnaire and earned a score based on how “inflammatory” their diet was. The lower the score, the better. For example, fatty fish, which is rich in omega-3 fatty acids, was considered an anti-inflammatory food and earned negative points. Cheese and many other dairy products, high in saturated fat, earned positive points. During the next three years, 62 people, or 6 percent of the study participants, developed dementia. People with the highest dietary inflammation scores were three times as likely to develop dementia as those with the lowest. Scores ranged from –5.83 to 6.01. Each point increase was linked to a 21 percent rise in dementia risk. Such epidemiological studies make connections, but they can’t prove cause and effect. Perhaps people who eat the most anti-inflammatory diets also are those least likely to develop dementia for some other reason. Maybe they have more social interactions. Or it could be, Scarmeas says, that people who eat more inflammatory diets do so because they’re already experiencing changes in their brain that lead them to consume these foods and “what we really see is the reverse causality.” To sort all this out, researchers rely on randomized controlled trials, the gold standard for providing proof of a causal effect. But in the arena of diet and dementia, these studies have challenges. Dementia is a disease of aging that takes decades to play out, Kaeberlein says. To show that a particular diet could reduce the risk of dementia, “it would take two-, three-, four-decade studies, which just aren’t feasible.” Many clinical trials last less than two years. As a work-around, researchers often rely on some intermediate outcome, like changes in cognition. But even that can be hard to observe. “If you’re already relatively healthy and don’t have many risks, you might not show much difference, especially if the duration of the study is relatively short,” says Sue Radd-Vagenas, a nutrition scientist at the University of Sydney. “The thinking is if you’re older and you have more risk factors, it’s more likely we might see something in a short period of time.” Yet older adults might already have some cognitive decline, so it might be more difficult to see an effect. Many researchers now suspect that intervening earlier will have a bigger impact. “We now know that the brain is stressed from midlife and there’s a tipping point at 65 when things go sour,” says Hussein Yassine, an Alzheimer’s researcher at the Keck School of Medicine of the University of Southern California in Los Angeles. But intervene too early, and a trial might not show any effect. Offering a healthier diet to a 50- or 60-year-old might pay off in the long run but fail to make a difference in cognition that can be measured during the relatively short length of a study. And it’s not only the timing of the intervention that matters, but also the duration. Do you have to eat a particular diet for two decades for it to have an impact? “We’ve got a problem of timescale,” says Kaarin Anstey, a dementia researcher at the University of New South Wales in Sydney. And then there are all the complexities that come with studying diet. “You can’t isolate it in the way you can isolate some of the other factors,” Anstey says. “It’s something that you’re exposed to all the time and over decades.” Food as medicine? In a clinical trial, researchers often test the effectiveness of a drug by offering half the study participants the medication and half a placebo pill. But when the treatment being tested is food, studies become much more difficult to control. First, food doesn’t come in a pill, so it’s tricky to hide whether participants are in the intervention group or the control group. Imagine a trial designed to test whether the Mediterranean diet can help slow cognitive decline. The participants aren’t told which group they’re in, but the control group sees that they aren’t getting nuts or fish or olive oil. “What ends up happening is a lot of participants will start actively increasing the consumption of the Mediterranean diet despite being on the control arm, because that’s why they signed up,” Yassine says. “So at the end of the trial, the two groups are not very dissimilar.” Second, we all need food to live, so a true placebo is out of the question. But what diet should the control group consume? Do you compare the diet intervention to people’s typical diets (which may differ from person to person and country to country)? Do you ask the comparison group to eat a healthy diet but avoid the food expected to provide brain benefits? (Offering them an unhealthy diet would be unethical.) And tracking what people eat during a clinical trial can be a challenge. Many of these studies rely on food frequency questionnaires to tally up all the foods in an individual’s diet. An ongoing study is assessing the impact of the MIND diet (which combines part of the Mediterranean diet with elements of the low-salt DASH diet) on cognitive decline. Researchers track adherence to the diet by asking participants to fill out a food frequency questionnaire every six to 12 months. But many of us struggle to remember what we ate a day or two ago. So some researchers also rely on more objective measures to assess compliance. For the MIND diet assessment, researchers are also tracking biomarkers in the blood and urine — vitamins such as folate, B12 and vitamin E, plus levels of certain antioxidants. Weighty survey Lengthy food frequency questionnaires (a snapshot of some questions below) are a common tool for assessing an individual’s eating habits over time. But the accuracy of results depends on how well participants can recall what they ate and how often. NIH Another difficulty is that these surveys often don’t account for variables that could be really important, like how the food was prepared and where it came from. Was the fish grilled? Fried? Slathered in butter? “Those things can matter,” says dementia researcher Nathaniel Chin of the University of Wisconsin–Madison. Plus there are the things researchers can’t control. For example, how does the food interact with an individual’s medications and microbiome? “We know all of those factors have an interplay,” Chin says. The few clinical trials looking at dementia and diet seem to measure different things, so it’s hard to make comparisons. In 2018, Radd-Vagenas and her colleagues looked at all the trials that had studied the impact of the Mediterranean diet on cognition. There were five at the time. “What struck me even then was how variable the interventions were,” she says. “Some of the studies didn’t even mention olive oil in their intervention. Now, how can you run a Mediterranean diet study and not mention olive oil?” Another tricky aspect is recruitment. The kind of people who sign up for clinical trials tend to be more educated, more motivated and have healthier lifestyles. That can make differences between the intervention group and the control group difficult to spot. And if the study shows an effect, whether it will apply to the broader, more diverse population comes into question. To sum up, these studies are difficult to design, difficult to conduct and often difficult to interpret. Kaeberlein studies aging, not dementia specifically, but he follows the research closely and acknowledges that the lack of clear answers can be frustrating. “I get the feeling of wanting to throw up your hands,” he says. But he points out that there may not be a single answer. Many diets can help people maintain a healthy weight and avoid diabetes, and thus reduce the risk of dementia. Beyond that obvious fact, he says, “it’s hard to get definitive answers.” A better way In July 2021, Yassine gathered with more than 30 other dementia and nutrition experts for a virtual symposium to discuss the myriad challenges and map out a path forward. The speakers noted several changes that might improve the research. One idea is to focus on populations at high risk. For example, one clinical trial is looking at the impact of low- and high-fat diets on short-term changes in the brain in people who carry the genetic variant APOE4, a risk factor for Alzheimer’s. One small study suggested that a high-fat Western diet actually improved cognition in some individuals. Researchers hope to get clarity on that surprising result. “I get the feeling of wanting to throw up your hands.” Matt Kaeberlein Another possible fix is redefining how researchers measure success. Hypertension and diabetes are both well-known risk factors for dementia. So rather than running a clinical trial that looks at whether a particular diet can affect dementia, researchers could look at the impact of diet on one of these risk factors. Plenty of studies have assessed the impact of diet on hypertension and diabetes, but Yassine knows of none launched with dementia prevention as the ultimate goal. Yassine envisions a study that recruits participants at risk of developing dementia because of genetics or cardiovascular disease and then looks at intermediate outcomes. “For example, a high-salt diet can be associated with hypertension, and hypertension can be associated with dementia,” he says. If the study shows that the diet lowers hypertension, “we achieved our aim.” Then the study could enter a legacy period during which researchers track these individuals for another decade to determine whether the intervention influences cognition and dementia. One way to amplify the signal in a clinical trial is to combine diet with other interventions likely to reduce the risk of dementia. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, or FINGER, trial, which began in 2009, did just that. Researchers enrolled more than 1,200 individuals ages 60 to 77 who were at an elevated risk of developing dementia and had average or slightly impaired performance on cognition tests. Half received nutritional guidance, worked out at a gym, engaged in online brain-training games and had routine visits with a nurse to talk about managing dementia risk factors like high blood pressure and diabetes. The other half received only general health advice. After two years, the control group had a 25 percent greater cognitive decline than the intervention group. It was the first trial, reported in the Lancet in 2015, to show that targeting multiple risk factors could slow the pace of cognitive decline. Now researchers are testing this approach in more than 30 countries. Christy Tangney, a nutrition researcher at Rush University in Chicago, is one of the investigators on the U.S. arm of the study, enrolling 2,000 people ages 60 to 79 who have at least one dementia risk factor. The study is called POINTER, or U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk. The COVID-19 pandemic has delayed the research — organizers had to pause the trial briefly — but Tangney expects to have results in the next few years. This kind of multi-intervention study makes sense, Chin says. “One of the reasons why things are so slow in our field is we’re trying to address a heterogeneous disease with one intervention at a time. And that’s just not going to work.” A trial that tests multiple interventions “allows for people to not be perfect,” he adds. Maybe they can’t follow the diet exactly, but they can stick to the workout program, which might have an effect on its own. The drawback in these kinds of studies, however, is that it’s impossible to tease out the contribution of each individual intervention. Embracing complexity To untangle the role of diet in dementia, researchers are designing trials that intervene earlier in life and last longer. Some studies combine multiple interventions, like diet, exercise and brain training, as well as measure a wider range of outcomes. Dementia and diet studies are due a makeover Then Now Target one risk factor at a time Target multiple risk factors and disease mechanisms simultaneously Enroll individuals with substantial cognitive impairment Enroll at-risk individuals who do not yet have symptoms of dementia Trials last 6–12 months Trials last 18–24 months Focus on cognitive and functional outcome measures Look at multiple outcome measures, including surrogate measures like biomarkers Source: R. Stephen et al/Frontiers in Neurology 2021 Preemptive guidelines Two major reports came out in recent years addressing dementia prevention. The first, from the World Health Organization in 2019, recommends a healthy, balanced diet for all adults, and notes that the Mediterranean diet may help people who have normal to mildly impaired cognition. The 2020 Lancet Commission report, however, does not include diet in its list of modifiable risk factors, at least not yet. “Nutrition and dietary components are challenging to research with controversies still raging around the role of many micronutrients and health outcomes in dementia,” the report notes. The authors point out that a Mediterranean or the similar Scandinavian diet might help prevent cognitive decline in people with intact cognition, but “how long the exposure has to be or during which ages is unclear.” Neither report recommends any supplements. Plenty of people are waiting for some kind of advice to follow. Improving how these studies are done might enable scientists to finally sort out what kinds of diets can help hold back the heartbreaking damage that comes with Alzheimer’s disease. For some people, that knowledge might be enough to create change. “One of the reasons why things are so slow in our field is we’re trying to address a heterogeneous disease with one intervention at a time. And that’s just not going to work.” Nathaniel Chin “Inevitably, if you’ve had Alzheimer’s in your family, you want to know, ‘What can I do today to potentially reduce my risk?’ ” says molecular biologist Heather Snyder, vice president of medical and scientific relations at the Alzheimer’s Association. But changing long-term dietary habits can be hard. The foods we eat aren’t just fuel; our diets represent culture and comfort and more. “Food means so much to us,” Chin says. “Even if you found the perfect diet,” he adds, “how do you get people to agree to and actually change their habits to follow that diet?” The MIND diet, for example, suggests people eat less than one serving of cheese a week. In Wisconsin, where Chin is based, that’s a nonstarter, he says. But it’s not just about changing individual behaviors. Radd-Vagenas and other researchers hope that if they can show the brain benefits of some of these diets in rigorous studies, policy changes might follow. For example, research shows that lifestyle changes can have a big impact on type 2 diabetes. As a result, many insurance providers now pay for coaching programs that help participants maintain healthy diet and exercise habits. “You need to establish policies. You need to change cities, change urban design. You need to do a lot of things to enable healthier choices to become easier choices,” Radd-Vagenas says. But that takes meatier data than exist now. Questions or comments on this article? E-mail us at feedback@sciencenews.org A version of this article appears in the July 2, 2022 issue of Science News. Citations S. Charisis et al. Diet inflammatory index and dementia incidence: A population-based study. Neurology. Vol. 97. December 2021. doi: 10.1212/WNL.0000000000012973. T. Ngandu et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. Vol 385. June 2015. doi: 10.1016/S0140-6736(15)60461-5. S. Radd-Vagenas et al. Effect of the Mediterranean diet on cognition and brain morphology and function: a systematic review of randomized controlled trials. The American Journal of Clinical Nutrition, Vol. 107. March 2018. doi: 10.1093/ajcn/nqx070.

All, I've been engaged in an off-forum Q&A dialog with a CR friend, and I figured some of you other crazies might appreciate reading about (and hopefully commenting on / criticizing) some of the details of my current diet & exercise regime, as well as tips & my motivation for them. If not, feel free it skip this post! I've only included my sided conversation, but I think from my answers it is pretty clear what the questions were. Feel free to ask for clarification on anything that's unclear. Regarding eating once per day. It's very hard, especially when just starting out on this regime, to eat once per day in the afternoon. It takes a lot of willpower. So I recommend, and always try myself, to wait a couple / few hours after waking before I eat, but then eat in the morning rather than waiting until afternoon, and definitely never try to grocery shop on a (very) empty stomach! For large scale chopped veggie storage, I use glass containers because I'm a bit paranoid about leeching from plastics. The glass jar I use is from Anchor Hocking. Turns out it is only 2gal. Here is a link. I believe both Target and Walmart have them as well, although I'm not sure about in-store availability. I chop my "chunky" veggies once per week, and store them in this glass jar, all mixed up, between layers of paper towels to absorb moisture and keep them fresh. I chop my "leafy green" veggies at the same time, throughly spin-dry them using salad spinner, and then store them in another containing between layers of paper towels to preserve freshness. Both go into my fridge, which I temperature control to maintain a very steady 34degF. Vegetable prep takes me just over one hour per week, but after many years I've got it down to an art/science. It used to take me about 2 hours. I find meditation and practices that cultivate mindfulness are helpful for fostering one's self-discipline. Other than that, I don't have much specific advice on that topic. I used to cook for my family when we were 4 rather than 3 . But now that it is just the three of us, and my daughter has an extremely busy schedule, my wife and daughter's eating schedule is pretty irregular. So they cook for themselves. I also found it hard to cook for them. Not because I was particularly tempted by the food I was making for them (although on occasion that too was the case), but more that I was conflicted by the opposing goals of cooking as healthy meals as possible for them, but also meals they would enjoy, and not waste by not eating. When practicing CR for a while, I've found you become extremely averse to wasting anything, but especially food. Plus I'm an ethical vegan. Both kids are (were) vegetarian, and my wife eats mostly vegetarian. But they enjoy quite a bit of dairy, which I had trouble buying/cooking for them for ethical reasons. Regarding exercise, I'll enumerate everything I do in a day, in order: [Get up at 2:45am - yes I'm kind of a early riser ] 4min - straight arm planking 2min - 100 body weight squats 10min - "10 minute abs" workout - Originally from YouTube video of that name, but after doing it several thousand times, I've got it memorized. . Video embedded at bottom. Warning - this will really hurt anyone not used to doing an ab workout, but her accent is strangely compelling... 20min - Jogging on treadmill at 4mph and 15% incline (very steep). 1.07miles, 200 kcal 120min - Stationary road bike. Modest intensity. HR around 95bpm. My Resting HR is about 45bpm. [breakfast - 1.5 hours] 10min - One mile run outdoors. Moderate pace . usually with my dog. 20min - Resistance training. 4day split to work all body parts on successive days, but giving each enough time to recover. Little rest between sets to keep it mildly aerobic. Pretty light weights. Pull-ups, pushups, light squats, triceps extensions, curls, shrugs, etc. All the standard exercises. Using dumbbells and body weight. 4min straight arm planking 2min - 100 body weight squats 2min - Ab Slide machine. Quite a good Ab exerciser 90min - Stationary road bike again. [Time now around 10:30am - Shower & 6min inversion therapy (to decompress spine and stretch back) & 20min power nap] [Puttering around for a while, light food prep, errands etc - 1-2 hours] 10min - One mile run outdoors. With dog. ~240min - pedalling at my bike desk while reading, surfing web, posting to CR forums [Off and on throughout afternoon evening - spend time with wife and daughter, especially when they eat dinner] 30min - brisk walk with my wife (and dog) [8:00pm - bedtime. 8:15 sound asleep] So in total I run for about 40min, do resistance training / calisthenics for about 45min, walk 30-45min, and then pedal for about 7h per day. On an average day, my Fitbit tells me I log about 45K steps (or step equivalents, including bike pedal revolutions), and about 23 miles. All of it at home, by myself (except if you count the mile walk with my wife and jogging with my dog ). I don't enjoy the hassle of working out with others at a gym. I don't seem to need the motivation of having other people around to exercise with. What motivates me to such extreme exercise? Hmmm... A few ideas: I like to eat, and to stay slim. Extreme exercise let's me do both. I'm exploring the possibility of getting CR benefits while eating lots of calories, but burning them off via lots of exercise and cold exposure. It makes me feel good. I like the endorphins, opiates, whatever makes exercise feel good. With my stationary bike and bike desk, I'm able to do other things while pedaling, like composing this message! I like being different from other people. I like pushing myself to extremes, to see what's possible. Pushing the envelope of human possibliity. I think exercising one's abilities and strengths is why we are here, and what makes life meaningful and significant. My biggest strength is probably self-discipline / conscientiousness. Exercising discipline strengthens the will. As Nietzsche said in Twilight of the Idols, "From life's school of war, what does not kill me makes me stronger." He was a big proponent of hormesis before it became fashionable. I hope being very different from others, and sharing my results, will enable people (like you!) to learn from my experiences and experiments, and figure out what might work best for them. Regarding sleep. I sleep for 6.5 hours per day (8:15pm - 2:45am) + a 20min power nap. Lately I've been sleeping like a baby, without my former problem of early waking (unless you count 2:45am as early ). I hope this is helpful. --Dean

I actually listened to the video, short and sweet. 24 November 2021|Fitness Identical twins Hugo and Ross Turner are adventure athletes that are always trying to find ways to improve their performance. https://www.bbc.com/reel/video/p0b5x2z7/is-a-vegan-diet-healthier-than-eating-meat-and-dairy-

All, One of the initial motivations for studying the possible benefits of the Omega-3s PUFAs DHA & EPA came from observations that the Inuits of Greenland, whose diet contains a very high proportion of polyunsaturated fat from cold-water fish and marine mammals, suffer from relatively low rates of cardiovascular disease. But randomized control trials of the benefits of DHA / EPA supplements for (primary or secondary) prevention of cardiovascular disease have generally been disappointing (e.g. [1]). This new study [2] in Science, might suggest at least part of the explanation for this apparent paradox. That paper used population-genetic analysis of Greenland Inuits to discover regions of two chromosomes that seem to have experienced strong selection in the recent past. Those regions also happen to contain genes involved in fatty acid metabolism; and the variants of the genes that have increased in frequency in Inuits are also associated with small stature and lower weight. From the abstract: By analyzing membrane lipids, we found that the selected alleles modulate fatty acid composition, which may affect the regulation of growth hormones. Thus, the Inuit have genetic and physiological adaptations to a diet rich in PUFAs. In an accompanying commentary, there is a fascinating map of relatively recent human genetic variations and where they occur around the world (click to enlarge): The one that isn't shown that I find very interesting is the salivary amylase gene (AMY1) for digesting starch. Several studies (e.g. [3]) have found that the number of duplicates of the AMY1 a person has can vary from 2 to about 15 from one individual to the next. The more AMY1 copies you have, the better you are at digesting starch / carbohydrates, and the less prone you are to obesity [3]. Study [4] looked at how the number of AMY1 copies varied between people of different ethnic groups and found a striking correlation between the amount of starch in their ancestral diet and the number of AMY1 copies their genome contained. Here is that result illustrated on a map (click to enlarge): In short, it appears that in cultures whose ancestral diet contained a large fraction of carbohydrates, more copies of the AMY1 gene were selected for since it helped them better process carbs. The bottom line appears to be that there is no "one size fits all" diet that is right for everyone. To some extent at least, the best diet for an individual depends on his/her genes. --Dean -------------------------------- [1] Arch Intern Med. 2012 May 14;172(9):686-94. doi: 10.1001/archinternmed.2012.262. Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials. Kwak SM(1), Myung SK, Lee YJ, Seo HG; Korean Meta-analysis Study Group. Collaborators: Myung SK, Ju W, Oh SW, Bae JH, Kim YK, Park CH, Jeon YJ, Lee EH, Chang YJ, Park SM, Eom CS, Lee YJ, Jung HS, Kwak SM. BACKGROUND: Although previous randomized, double-blind, placebo-controlled trials reported the efficacy of omega-3 fatty acid supplements in the secondary prevention of cardiovascular disease (CVD), the evidence remains inconclusive. Using a meta-analysis, we investigated the efficacy of eicosapentaenoic acid and docosahexaenoic acid in the secondary prevention of CVD. METHODS: We searched PubMed, EMBASE, and the Cochrane Library in April 2011. Two of us independently reviewed and selected eligible randomized controlled trials. RESULTS: Of 1007 articles retrieved, 14 randomized, double-blind, placebo-controlled trials (involving 20 485 patients with a history of CVD) were included in the final analyses. Supplementation with omega-3 fatty acids did not reduce the risk of overall cardiovascular events (relative risk, 0.99; 95% CI, 0.89-1.09), all-cause mortality, sudden cardiac death, myocardial infarction, congestive heart failure, or transient ischemic attack and stroke. There was a small reduction in cardiovascular death (relative risk, 0.91; 95% CI, 0.84-0.99), which disappeared when we excluded a study with major methodological problems. Furthermore, no significant preventive effect was observed in subgroup analyses by the following: country location, inland or coastal geographic area, history of CVD, concomitant medication use, type of placebo material in the trial, methodological quality of the trial, duration of treatment, dosage of eicosapentaenoic acid or docosahexaenoic acid, or use of fish oil supplementation only as treatment. CONCLUSION: Our meta-analysis showed insufficient evidence of a secondary preventive effect of omega-3 fatty acid supplements against overall cardiovascular events among patients with a history of cardiovascular disease. PMID: 22493407 ----------------- [2] Science. 2015 Sep 18;349(6254):1343-1347. Greenlandic Inuit show genetic signatures of diet and climate adaptation. Fumagalli M(1), Moltke I(2), Grarup N(3), Racimo F(4), Bjerregaard P(5), Jørgensen ME(6), Korneliussen TS(7), Gerbault P(8), Skotte L(2), Linneberg A(9), Christensen C(10), Brandslund I(11), Jørgensen T(12), Huerta-Sánchez E(13), Schmidt EB(14), Pedersen O(3), Hansen T(15), Albrechtsen A(16), Nielsen R(17). The indigenous people of Greenland, the Inuit, have lived for a long time in the extreme conditions of the Arctic, including low annual temperatures, and with a specialized diet rich in protein and fatty acids, particularly omega-3 polyunsaturated fatty acids (PUFAs). A scan of Inuit genomes for signatures of adaptation revealed signals at several loci, with the strongest signal located in a cluster of fatty acid desaturases that determine PUFA levels. The selected alleles are associated with multiple metabolic and anthropometric phenotypes and have large effect sizes for weight and height, with the effect on height replicated in Europeans. By analyzing membrane lipids, we found that the selected alleles modulate fatty acid composition, which may affect the regulation of growth hormones. Thus, the Inuit have genetic and physiological adaptations to a diet rich in PUFAs. Copyright © 2015, American Association for the Advancement of Science. PMID: 26383953 ----------------- [3] Nat Genet. 2014 May;46(5):492-7. doi: 10.1038/ng.2939. Epub 2014 Mar 30. Low copy number of the salivary amylase gene predisposes to obesity. Falchi M(1), El-Sayed Moustafa JS(2), Takousis P(3), Pesce F(4), Bonnefond A(5), Andersson-Assarsson JC(6), Sudmant PH(7), Dorajoo R(8), Al-Shafai MN(9), Bottolo L(10), Ozdemir E(3), So HC(11), Davies RW(12), Patrice A(13), Dent R(14), Mangino M(15), Hysi PG(15), Dechaume A(16), Huyvaert M(16), Skinner J(17), Pigeyre M(18), Caiazzo R(18), Raverdy V(13), Vaillant E(16), Field S(19), Balkau B(20), Marre M(21), Visvikis-Siest S(22), Weill J(23), Poulain-Godefroy O(16), Jacobson P(24), Sjostrom L(24), Hammond CJ(15), Deloukas P(25), Sham PC(11), McPherson R(26), Lee J(27), Tai ES(28), Sladek R(29), Carlsson LM(24), Walley A(30), Eichler EE(31), Pattou F(18), Spector TD(32), Froguel P(33). Comment in Nat Rev Endocrinol. 2014 Jun;10(6):312. Common multi-allelic copy number variants (CNVs) appear enriched for phenotypic associations compared to their biallelic counterparts. Here we investigated the influence of gene dosage effects on adiposity through a CNV association study of gene expression levels in adipose tissue. We identified significant association of a multi-allelic CNV encompassing the salivary amylase gene (AMY1) with body mass index (BMI) and obesity, and we replicated this finding in 6,200 subjects. Increased AMY1 copy number was positively associated with both amylase gene expression (P = 2.31 × 10(-14)) and serum enzyme levels (P < 2.20 × 10(-16)), whereas reduced AMY1 copy number was associated with increased BMI (change in BMI per estimated copy = -0.15 (0.02) kg/m(2); P = 6.93 × 10(-10)) and obesity risk (odds ratio (OR) per estimated copy = 1.19, 95% confidence interval (CI) = 1.13-1.26; P = 1.46 × 10(-10)). The OR value of 1.19 per copy of AMY1 translates into about an eightfold difference in risk of obesity between subjects in the top (copy number > 9) and bottom (copy number < 4) 10% of the copy number distribution. Our study provides a first genetic link between carbohydrate metabolism and BMI and demonstrates the power of integrated genomic approaches beyond genome-wide association studies. PMID: 24686848 ------------------------- [4] Perry, G. H., Dominy, N. J., Claw, K. G., Lee, A. S., Fiegler, H., Redon, R., et al. (2007). Diet and the evolution of human amylase gene copy number variation. [10.1038/ng2123]. Nat Genet, 39(10), 1256-1260.

All, I'm sometimes asked by friends and family who aren't quite as obsessive as I am about health & longevity for a few tips they might be able to adopt that might help them stay healthier longer but without "going overboard" like I do. Today I stumbled across an article that I think fits the bill really well, and that I'll point such people to in the future. It is titled 13 Habits Linked to a Long Life (Backed by Science) and it is from the website AuthorityNutrition.com, which I've never considered much of an authority on nutrition, but this article is quite good so I may have to reconsider... Here is the list: Avoid Overeating Eat Some Nuts Use The Spice Turmeric Eat Plenty of Healthy Plant Foods Exercise and Be Physically Active Don’t Smoke Keep Your Alcohol Intake Moderate Prioritize Your Happiness Avoid Chronic Stress and Anxiety Nurture Your Social Circle Increase Your Conscientiousness Drink Coffee or Tea Develop a Good Sleeping Pattern Each of the 13 is explained in clear, easy to understand language. The article describes the science to back up the recommendations, and has references for people who want to learn more. Finally, it's really brief for those with a short attention span. There are three additional items I can think of that I would add to the list: 14. Don't Sit Too Much (ref) 15. Practice Good Oral Hygiene (discussion, discussion) 16. Ask Your Doctor - Get regular medical checkups and recommended tests after age 50, or earlier if you've got risk factors (discussion) Anyone else have health and longevity "best practices" you would or do suggest to friends/family that aren't included on the list? --Dean

Someone asked me off-list what my current diet looks like, and I realized I haven't updated the on-line information about it in a long time, although I've alluded to it in scattered places on this forum. I figured I consolidate and expand on what I've shared, for others to criticize : These days I eat the following (by calories): ~30% vegetables ~15% starch, ~35% fruit, ~20% nuts/seeds by calories a few other miscellaneous things. Vegetables The vegetables are a huge variety, and prepared once per week into a big mix. Its a combination of 'chunky' vegetables (just about any veggie in the produce aisle), and greens - where the greens typical include a mix of Kale, collards, chard, spinach, and spring mix - mostly organic. I also eat about 80g of homegrown sprouts and microgreens per day, a mix of broccoli, fenugreek, radish, and arugula sprouts. Starches The starches are about 1/2 sweet potatoes, and the other half and even mix of lentils, black beans, chickpeas, wild & brown rice, quinoa, and barley, all cooked al dente. Fruit My fruit calories come from the following. Below the first two, which are the biggest calorie contributors, the others are probably similar in calorie contributions: Berries - Mix of strawberries, blueberries, wild blackberries, cranberries, sour cherries every day Bananas - I modulate these depending on my weight trajectory - I'm around 2-3 per day these days. Melon - Alternating between cantaloupe, honeydew, mango, papaya, pineapple Durian - I admit it, I'm addicted to durian... Orange - 1/2 an small orange per day, with a bit of the peal/pith Apples - One small-to-medium (crabapple-like) wild apple per day, picked in the fall from wild trees near my house Other Tree Fruit - Persimmons (one of my favorites), plums, peaches, nectarines, pears, pomegranate. Depending on the season. About 1/2 of one of these per day. Note - this does not include the non-standard fruits I eat, like avocado (1/2 per day), cucumber, zucchini, tomato (~100g / day), etc. Nuts / Seeds The nuts I eat include: Hazelnuts, Almonds and Walnuts, in equal parts. The seeds I eat are a mix of the following (in descending order of calories): Flax, chia, hemp, sunflower, pumpkin, sesame. Miscellaneous The miscellaneous category includes the following per day: 1/3 ear of corn - 'buttered' with avocado and 'salted' with curry powder, because its tasty. 12g of natto - for vitamin K2 and amyloid breaking. 1.5 tsp of fresh chopped mix of garlic, ginger, tumeric root & horseradish 2 tbsp of cider vinegar 2 tbsp of my ketchup - a homemade mix of cider vinegar, water, tomato paste, sriracha, hot mustard and psyllium as a thickener ~2 tbsp of wide mix of herbs and spices, heavy on the tumeric, but just about anything from the spice aisle you can think of, in a mixture I sprinkle into my "salad dressing" and on my starch mix. 1 Tbsp of fiber & resistant starch - Used as thickener for my salad dressing. Even mix of psyllium husks, plantain flour and potato starch. A small amount of sweetener in my salad dressing (see below) - erythritol & pure stevia. Other Notes: The dressing I make to put on my salad is taken from some of the items listed above, blended together until smooth in my Vitamix. It includes: About 150g of the salad greens - so I don't have to eat them all in leaf form :-) 60g of berry mix The 1/2 orange ~60g of cucumber 100g of tomato 2 tbsp of cider vinegar ~100ml of water 1 Tbsp fiber / resistant starch ~1 tbsp of spice mix A bit of sweetener - erythritol & pure stevia - to make it a little tastier. I eat the exact same thing every day - except for minor variations in fruits and veggies depending on seasonal availability The macronutrient ratio of my diet is about 70:15:15 C:P:F I eat one meal per day, from 6-7:30am. I also drink a lot of lemon water (distilled) before and after my meal from this stainless steel tumbler to avoid coffee/tea close to meal which impedes mineral absorption - ~40oz per day. I also drink a mix of cold & hot brewed, heavily filtered, coffee, black/green/rooibos/herb tea, & ground cacao - about 40-50oz per day. I haven't been counting calories - but it is probably shockingly high, given that I'm weight stable at a BMI of 17.3 (115lbs @ 5'8.5" tall) and my Fitbit tells me I'm exercising in one form or another for an average of about 8-9 hours per day, about 5 hours of that pedaling leisurely at my bike desk. That's it (I think). Criticize away! --Dean

I'm going to layout all my issues as i'm looking for hope/help starting a CR diet. I'm morbidly obese at 335 lbs and my body is falling apart. Recently I've had a cardiac stent inserted, I've got major back problems, fatigue, stomach problems, and now I have nerve damage (peripheral neuropathy) that's causing pain (pins needles) in my legs/arms. To say the least i'm not in great shape. Sometimes it's hard to find the will to go to work. It's a struggle just to do the basic things in my life like cooking, cleaning, and hanging out with kids and friends. Recently I've been reading a lot about following a CR diet to help repair the body in various ways, lose weight and extend your life. Mostly I just want to get healthy again, lose the weight and repair my nerve damage. I think a CR diet is the way to go because in my late 20's I went on a CR diet and lost 150 lbs.... for a period of time (about 2 years) I never felt better in my entire life. Unfortunately it didn't last and I put weight back on over the next several years. Fast forward 24 years and my body is a complete mess... I need to recapture my youth. Has anyone had experience rejuvenating their bodies using a CR diet?

Hey, I would be glad about all sorts of suggestions and questions about my diet. I do not have fixed times for meals. Most of the time I start eating around 10 in the morning and eat the last one at 10 in the evening.

Dear colleagues, A very interesting conference will be held July 26-27 at the George Washington University Medical Center: https://PCRM.org/ICNM Among the many presenters is Dr. Dean Ornish, the well-known vegan guru (who is often cited by our own mikeccolella). Looks interesting, and, IMO, worth attending. -- Saul

Hi all, I’m a researcher from MIT working on making a predictive model for skin, measuring what impact different environment, lifestyle and products used have on someone’s skin health. I thought this would be a great community to ask about what you’ve seen as the impact of diet on your skin. How might this relate to a tool that could help you track it? One initial thought is to look at information from people’s food tracking apps like MyFitnessPal and apply data science techniques to see how it affects the health of their skin. Would love to learn from this experience of you all and how different diet changes have shown up in your skin! Best, Meg mmaupin@mit.edu

The strategies are pretty standard but still pretty interesting for anyone who’s looked into ‘biohacking’. The guy is a CEO of a company that does half a billion dollars a year in revenue so he definitely has to be high performing. Funny enough he follows a ketogenic diet, fasts frequently and uses ssri’s for mood improvement. Here’s his whole protocol: https://hackernoon.com/im-32-and-spent-200k-on-biohacking-became-calmer-thinner-extroverted-healthier-happier-2a2e846ae113

Valter Longo's work has been discussed around here quite frequently as of late, particularly his work on the fasting mimicking diet. In typical Rich Roll fashion, he goes long form and tries to gain deep insight into Longo's understanding of nutrition, longevity, and health. Rich says that he considers it one of his most important conversations to date.