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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, Like we've seen for cardiovascular disease, eating fish can be a mixed blessing. The omega-3 fatty acids (DHA/EPA) are thought to be beneficial, particularly for brain function. But the mercury, PCBs and other contaminants that bioaccumulate in the fat of fish may also have harmful effects. This new study[1] (thanks to Al Pater!) looks at the association between consumption of fish, plant omega-3s, brain mercury levels and Alzheimer's disease and brain mini-strokes. What they found is a bit nuanced, but worth thinking about. They gave 550 quite elderly but initially dementia-free people in several US nursing homes a yearly dietary questionnaire to measure their weekly intake of fish, DHA/EPA and the plant-derived omega-3 Alpha Linolenic Acid (ALA) until they died. Over an average follow-up of 4.5 years, 286 of the participates died (average age 89!). These folks' brains were autopsied to measure mercury levels and to look for physical signs of Alzheimer's disease (plaques and tangles) as well as brain injuries associated with other forms of dementia, in particular macroinfarctions and microinfarctions (i.e. strokes of various sizes). Here are the highlights of what they found: The more fish meals per week a subject consumed, the higher their brain mercury level (P < 0.02). There was no correlation between intake of ALA or DHA/EPA supplements and brain mercury level. For the majority of people (77%) who weren't carriers of the APOE4 allele that increases one's susceptibility to Alzheimer's disease, neither eating fish, dietary DHA/EPA nor consuming ALA had a significant effect (one way or the other) on the risk of Alzheimer's disease. For the minority (23%) of subjects who were APOE4 carriers, eating more fish and more dietary DHA/EPA was associated with a decreased risk of Alzheimer's disease markers (P < 0.04). Neither DHA/EPA supplements nor dietary ALA impacted Alzheimer's risk in these folks. Dietary ALA, but not fish or DHA/EPA, was associated with reduced prevalence of macroinfarctions (P < 0.03) and microinfarctions (P < 0.04) associated with non-Alzheimer's cognitive impairment, independent of APOE4 status. Those were the major, statistically significant findings. There is one more thing I noticed looking at the table below that appears interesting/suggestive for the majority of us who are lucky enough not have the APOE4 gene. The cells I've highlighted below represent the level of various markers of Alzheimer's disease for APOE4-negative folks. The red cells represent the level of Alzheimer's markers for people who ate the most fish (top red row), or the most dietary DHA/EPA (bottom red row). From the confidence intervals, you can see that none of them are individually significant. But also notice that all of them are positive, meaning there was a trend towards increased markers of Alzheimer's disease in APOE4-negative people who ate the most fish, especially fatty fish. In contrast, now look at the green cells, representing markers for Alzheimer's disease in APOE4-negative people who consumed the most plant-derived ALA. Notice these too are not individually significant, but all of them are negative, pointing towards a reduced risk of Alzheimer's disease with increasing ALA intake. From all this, my summary takeaway message from this study would be the following: For people with the APOE4 gene and therefore increased risk of Alzheimer's disease, eating fish is likely to reduce one's risk of Alzheimer's disease, despite increasing brain mercury levels For people without the APOE4 gene, fish consumption doesn't seem to reduce, and may even increase, one's risk of Alzheimer's disease For people without the APOE4 gene, plant-derived omega-3 ALA (e.g. from walnuts, olive oil, flax, chia) consumption may reduce one's risk of Alzheimer's disease For everyone, dietary ALA appears to reduce one's risk of brain markers for non-Alzheimer's cognitive impairment. Or more succinctly, ALA is likely to be good for everyone's brain health, and fish is likely to be good for the brain health of only the minority of people who carry the APOE4 allele. This seems like an illustration of a benefit of getting one's DNA sequenced with a company like 23andMe to determine whether one is a carrier of the APOE4 allele. --Dean ------------ [1] JAMA. 2016 Feb 2;315(5):489-97. doi: 10.1001/jama.2015.19451. Association of Seafood Consumption, Brain Mercury Level, and APOE e4 Status With Brain Neuropathology in Older Adults. Morris MC, Brockman J, Schneider JA, Wang Y, Bennett DA, Tangney CC, van de Rest O. Full text: http://jama.jamanetwork.com.sci-hub.io/article.aspx?articleID=2484683 Abstract IMPORTANCE: Seafood consumption is promoted for its many health benefits even though its contamination by mercury, a known neurotoxin, is a growing concern. OBJECTIVE: To determine whether seafood consumption is correlated with increased brain mercury levels and also whether seafood consumption or brain mercury levels are correlated with brain neuropathologies. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analyses of deceased participants in the Memory and Aging Project clinical neuropathological cohort study, 2004-2013. Participants resided in Chicago retirement communities and subsidized housing. The study included 286 autopsied brains of 554 deceased participants (51.6%). The mean (SD) age at death was 89.9 (6.1) years, 67% (193) were women, and the mean (SD) educational attainment was 14.6 (2.7) years. EXPOSURES: Seafood intake was first measured by a food frequency questionnaire at a mean of 4.5 years before death. MAIN OUTCOMES AND MEASURES: Dementia-related pathologies assessed were Alzheimer disease, Lewy bodies, and the number of macroinfarcts and microinfarcts. Dietary consumption of seafood and n-3 fatty acids was annually assessed by a food frequency questionnaire in the years before death. Tissue concentrations of mercury and selenium were measured using instrumental neutron activation analyses. RESULTS: Among the 286 autopsied brains of 544 participants, brain mercury levels were positively correlated with the number of seafood meals consumed per week (??=?0.16; P?=?.02). In models adjusted for age, sex, education, and total energy intake, seafood consumption (=?1 meal/week) was significantly correlated with less Alzheimer disease pathology including lower density of neuritic plaques (ß?=?-0.69 score units [95% CI, -1.34 to -0.04]), less severe and widespread neurofibrillary tangles (ß?=?-0.77 score units [95% CI, -1.52 to -0.02]), and lower neuropathologically defined Alzheimer disease (ß?=?-0.53 score units [95% CI, -0.96 to -0.10]) but only among apolipoprotein E (APOE e4) carriers. Higher intake levels of a-linolenic acid (18:3 n-3) were correlated with lower odds of cerebral macroinfarctions (odds ratio for tertiles 3 vs 1, 0.51 [95% CI, 0.27 to 0.94]). Fish oil supplementation had no statistically significant correlation with any neuropathologic marker. Higher brain concentrations of mercury were not significantly correlated with increased levels of brain neuropathology. CONCLUSIONS AND RELEVANCE: In cross-sectional analyses, moderate seafood consumption was correlated with lesser Alzheimer disease neuropathology. Although seafood consumption was also correlated with higher brain levels of mercury, these levels were not correlated with brain neuropathology. PMID: 26836731

Does anyone else eat natto, the fermented soybean product which is quite popular in Japan? It is the richest food source of vitamin K2 (menaquinone-7 or MK-7) with 1 mg (1000 mcg) of K2 per 100g natto. That is about 20x higher than the next highest source, certain cheeses like Gouda. Unlike vitamin K1 which is found primarily in leafy greens, there is virtually no vitamin K2 in regular fruits and vegetables. Why should we care about vitamin K2 you ask? First and foremost because it has been shown to be protective against osteoporosis [1-2], a concern for CR practitioners. From [2], a study of 244 postmenopausal women supplemented with 180mcg/day of Vitamin K2 (MK-7) for three years: MK-7 intake significantly improved vitamin K status and decreased the age-related decline in BMC and BMD at the lumbar spine and femoral neck, but not at the total hip. Bone strength was also favorably affected by MK-7. MK-7 significantly decreased the loss in vertebral height of the lower thoracic region at the mid-site of the vertebrae. CONCLUSIONS: MK-7 supplements may help postmenopausal women to prevent bone loss. Another significant benefit of Vitamin K2 is for cardiovascular health. Vitamin K2 seems to prevent artery calcification (aka hardening of the arteries) [3-5], which happens when calcium circulating in the blood is turned into a crust in the arteries. In study [5] the same group of researchers from [2] measured arterial calcification in the same 244 postmenopausal women on 180mcg/day of K2 for three years, and found multiple markers of arterial stiffness improved with K2 supplementation, concluding: Long-term use of MK-7 supplements improves arterial stiffness in healthy postmenopausal women, especially in women having a high arterial stiffness. But those were studies of direct supplementation of vitamin K2 (MK-7), rather than getting it from food. Does eating natto actually raise serum MK-7 levels? Thankfully the answer is yes, according to [6]: erum MK-7 level with the frequency of dietary natto intake were examined in 134 healthy adults (85 men and 39 women) without and with occasional (a few times per month), and frequent (a few times per week) dietary intake of regular natto including MK-7 (775 micrograms/100 g). Serum MK-7 and gamma-carboxylated osteocalcin concentrations in men with the occasional or frequent dietary intake of natto were significantly higher than those without any intake. So where to get natto? I buy my natto in frozen form at my local asian market, for about $2.50 for four styrofoam containers each of which contains about 50g of natto. Here is what the package of four look like: I eat half of a container's worth of natto per day (cost ~ $0.30/day). That 25g of natto per day provides about 250mcg of Vitamin K2 (MK-7), which is about 30% more than the dose shown to improve bone health [2] and reduce arterial stiffness [5] in postmenopausal women. What's natto like you ask? There is no getting around the fact that it looks pretty gross, and has a very slimy texture. As a result, many people can't stomach it, but I actually enjoy the taste, especially when mixed into the serving of other legumes and starches I eat. Below is a photo of natto in the styrofoam container. Pretty appetizing, huh?! The chopsticks in the photo are helpful for scale: For those of you who would be too grossed out by natto to eat it, there are supplements available. In fact I take one of these* to increase my K2 beyond what I get from natto - adding an extra 100mcg MK-7 per day for $0.09. But I'm always in favor of getting nutrients from food sources when practical. This is one of the rare cases where the natural food source is price competitive with supplement sources. So for me natto is a good choice. Does anyone else eat natto? If not, you might consider giving it a try! [Note: This post does not address Natto's brain health benefits. For discussion of that, see this post further down this thread.] --Dean *Note - I've updated my supplement regime to this vegan NOW Foods brand K2 supplement, to make sure I'm getting K2 in MK-7 form, rather than (mostly) MK-4 per my previous supplement. --------- [1] J Bone Miner Metab. 2014 Mar;32(2):142-50. doi: 10.1007/s00774-013-0472-7. Epub 2013 May 24. Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women. Koitaya N(1), Sekiguchi M, Tousen Y, Nishide Y, Morita A, Yamauchi J, Gando Y, Miyachi M, Aoki M, Komatsu M, Watanabe F, Morishita K, Ishimi Y. Author information: (1)Department of Food Function and Labeling, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjyuku-ku, Tokyo, Japan. Menaquinone-4 (MK-4) administered at a pharmacological dosage of 45 mg/day has been used for the treatment of osteoporosis in Japan. However, it is not known whether a lower dose of MK-4 supplementation is beneficial for bone health in healthy postmenopausal women. The aim of this study was to examine the long-term effects of 1.5-mg daily supplementation of MK-4 on the various markers of bone turnover and bone mineral density (BMD). The study was performed as a randomized, double-blind, placebo-controlled trial. The participants (aged 50-65 years) were randomly assigned to one of two groups according to the MK-4 dose received: the placebo-control group (n = 24) and the 1.5-mg MK-4 group (n = 24). The baseline concentrations of undercarboxylated osteocalcin (ucOC) were high in both groups (>5.1 ng/ml). After 6 and 12 months, the serum ucOC concentrations were significantly lower in the MK-4 group than in the control group. In the control group, there was no significant change in serum pentosidine concentrations. However, in the MK-4 group, the concentration of pentosidine at 6 and 12 months was significantly lower than that at baseline. The forearm BMD was significantly lower after 12 months than at 6 months in the control group. However, there was no significant decrease in BMD in the MK-4 group during the study period. These results suggest that low-dose MK-4 supplementation for 6-12 months improved bone quality in the postmenopausal Japanese women by decreasing the serum ucOC and pentosidine concentrations, without any substantial adverse effects. PMID: 23702931 ------------ [2] Osteoporos Int. 2013 Sep;24(9):2499-507. doi: 10.1007/s00198-013-2325-6. Epub 2013 Mar 23. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Knapen MH(1), Drummen NE, Smit E, Vermeer C, Theuwissen E. Author information: (1)VitaK, Maastricht University, Oxfordlaan 70, 6229 EV, Maastricht, The Netherlands. We have investigated whether low-dose vitamin K2 supplements (menaquinone-7, MK-7) could beneficially affect bone health. Next to an improved vitamin K status, MK-7 supplementation significantly decreased the age-related decline in bone mineral density and bone strength. Low-dose MK-7 supplements may therefore help postmenopausal women prevent bone loss.INTRODUCTION: Despite contradictory data on vitamin K supplementation and bone health, the European Food Safety Authorities (EFSA) accepted the health claim on vitamin K's role in maintenance of normal bone. In line with EFSA's opinion, we showed that 3-year high-dose vitamin K1 (phylloquinone) and K2 (short-chain menaquinone-4) supplementation improved bone health after menopause. Because of the longer half-life and greater potency of the long-chain MK-7, we have extended these investigations by measuring the effect of low-dose MK-7 supplementation on bone health. METHODS: Healthy postmenopausal women (n = 244) received for 3 years placebo or MK-7 (180 μg MK-7/day) capsules. Bone mineral density of lumbar spine, total hip, and femoral neck was measured by DXA; bone strength indices of the femoral neck were calculated. Vertebral fracture assessment was performed by DXA and used as measure for vertebral fractures. Circulating uncarboxylated osteocalcin (ucOC) and carboxylated OC (cOC) were measured; the ucOC/cOC ratio served as marker of vitamin K status. Measurements occurred at baseline and after 1, 2, and 3 years of treatment. RESULTS: MK-7 intake significantly improved vitamin K status and decreased the age-related decline in BMC and BMD at the lumbar spine and femoral neck, but not at the total hip. Bone strength was also favorably affected by MK-7. MK-7 significantly decreased the loss in vertebral height of the lower thoracic region at the mid-site of the vertebrae. CONCLUSIONS: MK-7 supplements may help postmenopausal women to prevent bone loss. Whether these results can be extrapolated to other populations, e.g., children and men, needs further investigation. PMID: 23525894 ----------- [3] Acta Physiol Hung. 2010 Sep;97(3):256-66. doi: 10.1556/APhysiol.97.2010.3.2. Vitamin K and vascular calcifications. Fodor D(1), Albu A, Poantă L, Porojan M. Author information: (1)University of Medicine and Pharmacy, 2nd Internal Medicine, Clinic Iuliu Hatieganu, Cluj-Napoca, Romania. dfodor@umfcluj.ro The role of vitamin K in the synthesis of some coagulation factors is well known. The implication of vitamin K in vascular health was demonstrated in many surveys and studies conducted over the past years on the vitamin K-dependent proteins non-involved in coagulation processes. The vitamin K-dependent matrix Gla protein is a potent inhibitor of the arterial calcification, and may become a non-invasive biochemical marker for vascular calcification. Vitamin K(2) is considered to be more important for vascular system, if compared to vitamin K(1). This paper is reviewing the data from recent literature on the involvement of vitamin K and vitamin K-dependent proteins in cardiovascular health. PMID: 20843764 ---------------- [4] Nutrients. 2015 Aug 18;7(8):6991-7011. doi: 10.3390/nu7085318. High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification. Scheiber D(1), Veulemans V(2), Horn P(3), Chatrou ML(4), Potthoff SA(5), Kelm M(6,)(7), Schurgers LJ(8), Westenfeld R(9). Author information: (1)Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf 40225, Germany. daniel.scheiber@med.uni-duesseldorf.de. (2)Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf 40225, Germany. verena.veulemanns@med.uni-duesseldorf.de. (3)Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf 40225, Germany. patrick.horn@med.uni-duesseldorf.de. (4)Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht 6229 ER, The Netherlands. m.chatrou@maastrichtuniversity.nl. (5)Department of Nephrology, University Duesseldorf, Medical Faculty, Duesseldorf 40225, Germany. sebastian.potthoff@med.uni-duesseldorf.de. (6)Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf 40225, Germany. malte.kelm@med.uni-duesseldorf.de. (7)Cardiovascular Research Institute Duesseldorf, University Duesseldorf, Medical Faculty, Duesseldorf 40225, Germany. malte.kelm@med.uni-duesseldorf.de. (8)Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht 6229 ER, The Netherlands. l.schurgers@maastrichtuniversity.nl. (9)Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf 40225, Germany. ralf.westenfeld@med.uni-duesseldorf.de. Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures. PMCID: PMC4555157 PMID: 26295257 ------------- [5] Thromb Haemost. 2015 May;113(5):1135-44. doi: 10.1160/TH14-08-0675. Epub 2015 Feb 19. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Knapen MH, Braam LA, Drummen NE, Bekers O, Hoeks AP, Vermeer C(1). Author information: (1)Cees Vermeer, PhD, VitaK, Maastricht University, Biopartner Center Maastricht, Oxfordlaan 70, 6229 EV Maastricht, The Netherlands, Tel: +31 43 388 5865, Fax: +31 43 388 5889, E-mail: c.vermeer@vitak.com. Observational data suggest a link between menaquinone (MK, vitamin K2) intake and cardiovascular (CV) health. However, MK intervention trials with vascular endpoints are lacking. We investigated long-term effects of MK-7 (180 µg MenaQ7/day) supplementation on arterial stiffness in a double-blind, placebo-controlled trial. Healthy postmenopausal women (n=244) received either placebo (n=124) or MK-7 (n=120) for three years. Indices of local carotid stiffness (intima-media thickness IMT, Diameter end-diastole and Distension) were measured by echotracking. Regional aortic stiffness (carotid-femoral and carotid-radial Pulse Wave Velocity, cfPWV and crPWV, respectively) was measured using mechanotransducers. Circulating desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP) as well as acute phase markers Interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP), tumour necrosis factor-α (TNF-α) and markers for endothelial dysfunction Vascular Cell Adhesion Molecule (VCAM), E-selectin, and Advanced Glycation Endproducts (AGEs) were measured. At baseline dp-ucMGP was associated with IMT, Diameter, cfPWV and with the mean z-scores of acute phase markers (APMscore) and of markers for endothelial dysfunction (EDFscore). After three year MK-7 supplementation cfPWV and the Stiffness Index βsignificantly decreased in the total group, whereas distension, compliance, distensibility, Young's Modulus, and the local carotid PWV (cPWV) improved in women having a baseline Stiffness Index β above the median of 10.8. MK-7 decreased dp-ucMGP by 50 % compared to placebo, but did not influence the markers for acute phase and endothelial dysfunction. In conclusion, long-term use of MK-7 supplements improves arterial stiffness in healthy postmenopausal women, especially in women having a high arterial stiffness. PMID: 25694037 ---------- [6] J Bone Miner Metab. 2000;18(4):216-22. Intake of fermented soybean (natto) increases circulating vitamin K2 (menaquinone-7) and gamma-carboxylated osteocalcin concentration in normal individuals. Tsukamoto Y(1), Ichise H, Kakuda H, Yamaguchi M. Author information: (1)Central Research Institute, Mitsukan Group Co., Ltd., Aichi, Japan. Changes in circulating vitamin K2 (menaquinone-7, MK-7) and gamma-carboxylated osteocalcin concentrations in normal individuals with the intake of fermented soybeans (natto) were investigated. Eight male volunteers were given sequentially fermented soybeans (natto) containing three different contents of MK-7 at an interval of 7 days as follows: regular natto including 775 micrograms/100 g (MK-7 x 1) or reinforced natto containing 1298 micrograms/100 g (MK-7 x 1.5) or 1765 micrograms/100 g (MK-7 x 2). Subsequently, it was found that serum MK-7 and gamma-carboxylated osteocalcin concentrations were significantly elevated following the start of dietary intake of MK-7 (1298 or 1765 micrograms/100 g). Serum undercarboxylated osteocalcin concentrations were significantly decreased by dietary MK-7 (1765 micrograms/100 g) supplementation. Moreover, the changes in serum MK-7 level with the frequency of dietary natto intake were examined in 134 healthy adults (85 men and 39 women) without and with occasional (a few times per month), and frequent (a few times per week) dietary intake of regular natto including MK-7 (775 micrograms/100 g). Serum MK-7 and gamma-carboxylated osteocalcin concentrations in men with the occasional or frequent dietary intake of natto were significantly higher than those without any intake. The present study suggests that intake of fermented soybean (natto) increases serum levels of MK-7 and gamma-carboxylated osteocalcin in normal individuals. PMID: 10874601

All: Following up on a question from Vincent in another thread ... The long-running tofu-dementia connection remains a strong concern. To date, to the best of my knowledge, the ONLY prospective data on the long-term effects of soy products in the human diet are the White et al report (1), which is very rigorous prospective epidemiology in a very well-characterized long-term cohort study, and did indeed find that even what we might think of as pretty moderate increases in tofu consumption were associated with greater brain brain atrophy and poorer late-life cognitive scores. More recently, there are two reports from Hogervorst et al. (2,3) a weaker (cross-sectional) study which confirmed the finding of brain atrophy and cognitive decline: "weekly tofu intake had a negative association with memory in analyses controlled for age, sex, education and site. ... The analyses were not much altered when entering other foods. ... Analyses using median splits of soy product intake per week gave similar results to those concerning continuous consumption per week, showing a better memory performance in those who did not consume tofu daily or more than once daily." The effect was not seen in younger subjects ((3): indeed, oddly, such subjects seemed to have better cognitive function on a higher-tofu diet), but our proper concern is with longer-term effects, not what may be a short-term boost ((by analogy, not equivalence, cf. the effects of amphetamines). I have also come across (4), a prospective study in a cohort of Japanese Americans in King County, Washington. The results were all over the map (tho' perhaps suggestive, with the bidirectional relationships with HRT use), and it was an early report from only 2 y of followup in the cohort and after only 1 dietary assessment (dietary reporting instruments really need to be repeated, both because people are highly imperfect at reporting and because people's diets do actually change over time). I wrote to the authors to inquire about further followup: unfortunately, they won't be doing "a longer follow-up because of approximately 1200 women in the cohort, only 274 were in this sub-cohort. We likely do not have sufficient statistical power to conduct these newer analyses" (personal communication, Dr. Amy R. Borenstein). And, finally, there is (5), another cross-sectional study (this one in Hong Kong). It found that in women, and not men, higher consumption of an a posteriori-identified "vegetables-fruits" dietary pattern "rich in vegetables, fruits, soy products and legumes" was associated with reduced risk of cognitive impairment — but so was a "'snacks-drinks-milk products' pattern which was a mixture of healthy and unhealthy food groups including fast food, sweets and desserts, nuts, milk products and whole grains". Obviously, aside from being cross-sectional, there's no way to determine in that mix if soy products were playing a protective, deleterious, or neutral role in the overall protective association of the "vegetables-fruits" dietary pattern, even if we don't laugh the whole exercise out of the court of scientific opinion. Tofu, or Soy Generally? As Rodney says, so far this has only been found for tofu — but that's because very few soy foods have even been looked at. (1) found that miso was not associated with brain atrophy, but the serving size is very small and it is a complicatedly-processed food. Hogervorst et al actually found a protective effect of tempeh (2): this could be due to something about its processing neutralizing a toxic factor (formaldehyde was not found in market samples of tempeh, but again its presence in Indonesian tofu has only been intermittent, so that might be a sampling error), or enhancing a protective factor (eg., its higher levels of folate), or it could be a fluke (this is, again, a smaller and weaker study than White et al). We just don't know, and won't until we get (a) more studies confirming (or refuting) the link to tofu and a non-link to other soy foods. Isoflavones? White et al fingered isoflavones (soy phytoestrogens) as the most likely culprit for the tofu association, based on some animal data (and, presumably, the sheer fact that their presence is teh main thing to distinguish them from other similar foods). Phytoestrogens are found to improve cognitive function in some short-term studies in (usually menopausal or perimenopausal) women, but that doesn't mean that there isn't a long-term deleterious effect, or one specific to their hormonal status (cf. the HRT bidirectionality in (4) and maybe the inverse association of the "vegetables-fruits" dietary pattern of cognitive impairment in women but not men in (5)). Most soy foods, including most processed soy foods (soy burgers and hot dogs) and soy protein powders, have lots of isoflavones in them, and some are even "fortified" with extra isoflavones. So if those are the culprits, individual foods could be risky or harmless depending on how much isoflavone they contain. However, it could be something else entirely, in which case it would depend on whether the food contains "Contaminant X." Again, we just don't know, and won't until we get (a) more studies confirming (or refuting) the link to tofu, and (b) a non-link to other soy foods, and © a strong mechanistic explanation for any discrepancy. Thus, we shouldn't (yet) rule in or out any particular soy product on the basis of the presence or absence of phytoestrogens or any other factor. Again, more studies needed! Formaldehyde? Following up on a throwaway comment by an unreliable previous poster, Dean diligently found an interview by the lead author of (2) indicating the possible involvement of formaldehyde contamination as a factor in Indonesian tofu — which is, in fact, mentioned in the MS of (2). There is plenty of evidence that formaldehyde exposure is negatively associated with cognitive function, and in experimental studies it can hyperphosphorylate tau (leading to intraneuronal lesions that drive neuronal death and cognitive decline). So that's a plausible driver -- in the Indonesian study. It would not, however, explain the original finding in a cohort of Japanese men living in Hawai'i, which (again) was a stronger study design to begin with.(1) The one further complication is that the problem of formaldehyde contamination in Indonesia is not specific to tofu: aside from only being intermittently found in tofu, it's also been found in chicken and noodles, in use by restaurants and food stalls, and "scores of snacks and beverages containing formalin and rhodium-B were sold at a number of schools."! That might to some extent make its presence in tofu a bit of a wash relative to other foods, effectively taking it off the table as an explanation for the tofu-dementia link: we just don't know. Update: Aluminum? After I wrote this post, I realized that I hadn't addressed the question of aluminum contamination from processing with Al-based pots, or increased Al accessibility from the tofu-making process, which had both been invoked as potential causes of the association — a link that seems to have first been made in this post by Honolulu vegan advocate Dr. William Harris. I was inclined to dismiss this, as the last time I reviewed the evidence on this it seemed as if it had largely collapsed under the weight of negative studies. However, re-reviewing it now (see eg. these studies), the evident confusion about the bioavailability and body distribution of aluminum from different sources, and looking at cautious and responsible sources like the CDC's Agency for Toxic Substances and Disease Registry and the skeptical Steven Novella's blog on Alzheimer's and aluminum, my overall impression is that while there is no slam-dunk, there clearly seems to be a rational basis for concern. In light of this, people should not be making definitive statements either way about aluminum's link to AD specifically — and more importantly, to dementia more broadly. In the real world, no one gets pure AD, or vascular dementia, or dementia with Lewy bodies, or hippocampal sclerosis: one gets brain aging featuring elements of all of these, with (in most cases) features of one dominating neuropathologically and corresponding to a clinical dementia phenotype that is more or less characteristic of that neuropathological pattern. Age-related cognitive decline, dementia, and specific dementia phenotypes emerge from the aggregate loss of functional reserve. Aluminum could be neurotoxic in a way that is not specific to AD, and still increase the number of people who emerge with clinical dementia characterized as AD (or not). In turn, they should not be making definitive statements attributing the tofu-dementia association to aluminum toxicity. We only have the most tentative suggestion (via Dr. Williams) that tofu in one geographic location (Honolulu — which was the site of (1), but not of (2,3)), at one particular point in time (some years after the patients in (1) were eating the tofu that is somehow linked to their brain atrophy) had variable but potentially worrisome levels of aluminum. And, again, an uncertain if worrisome link between oral aluminum exposure and dementia or AD. A mixture of uncertain epidemiology, mixed animal data, and weak circumstantial evidence is not a basis for definitive statements. I'm not aware, unfortunately, of anyone marketing tofu or other products using methods that specifically minimize aluminum content, or that test and certify to the low levels in their product. And, as indicated, if such products exist, it's not clear whether that would be sufficient grounds to start liberally consuming soy again with no fear of dementia Bottom Line With the best available study (1) finding an association with brain atrophy and cognitive impairment; with supportive evidence from a weaker study (2,3); and absent even ONE equally-strong report of a lack of effect or of a protective one, it seems quite prudent to minimize or eliminate consumption of tofu per se (I see you rolling your eyes, Mary!), and likely soy products generally, especially in men. Reference 1. White LR, Petrovitch H, Ross GW, Masaki K, Hardman J, Nelson J, Davis D, Markesbery W. Brain aging and midlife tofu consumption. J Am Coll Nutr. 2000 Apr;19(2):242-55. PMID: 10763906 Free Full Text [www.jacn.org] 2. High tofu intake is associated with worse memory in elderly Indonesian men and women. Hogervorst E, Sadjimim T, Yesufu A, Kreager P, Rahardjo TB. Department of Human Sciences, Loughborough University, Loughborough, UK. Dement Geriatr Cogn Disord. 2008;26(1):50-7. Epub 2008 Jun 27. PMID 18583909 3: Hogervorst E, Mursjid F, Priandini D, Setyawan H, Ismael RI, Bandelow S, Rahardjo TB. Borobudur revisited: soy consumption may be associated with better recall in younger, but not in older, rural Indonesian elderly. Brain Res. 2011 Mar 16;1379:206-12. doi: 10.1016/j.brainres.2010.10.083. Epub 2010 Oct 28. PubMed PMID: 21035431. 4: Rice MM, Graves AN, McCurry SM, Gibbons L, Bowen J, McCormick W, Larson EB. Tofu consumption and cognition in older Japanese American men and women. J Nutr. 2000 Mar 1;130(3 Suppl):676S. http://jn.nutrition.org/content/130/3/666S.full 5: Chan R, Chan D, Woo J. A cross sectional study to examine the association between dietary patterns and cognitive impairment in older Chinese people in Hong Kong. J Nutr Health Aging. 2013 Sep;17(9):757-65. doi: 10.1007/s12603-013-0348-5. PubMed PMID: 24154648.

Dear ALL, The following fascinating article appeared in a University of Rochester publication this morning: https://www.urmc.rochester.edu/news/story/5508/not-all-sleep-is-equal-when-it-comes-to-cleaning-the-brain.aspx It describes the cleansing of the brain of debris by cerebral spinal fluid during slow wave sleep, discovered previously at UR; and notes that, during surgery, especially on older adults, it's important to use the appropriate anaesthetics, ketamine and xylazine, so that the glymphatic system should work as it usually works during deep slow wave sleep, to clear the brain. (The wrong anaesthetics can allow plaques to accumulate. Clinical examples are given. An obvious observation, not mentioned in the article (for obvious reasons): Might it be conceivably eventually a method of helping people having difficulty achieving slow wave sleep, to be take (orally take or inject ?) these two anaesthetics in (who knows what ?) quantity before bed to achieve better quality sleep? (I don't recommend experimenting with this on yourselves; but it would be fascinating if some qualified sleep researcher managed to start a clinical study of this possible method of improving sleep quality on patients at risk of Alzheimers. Probably would be VERY hard to get FDA approval). -- Saul