High Fat Diet Disrupts Brain Maturation

High Fat Diet Disrupts Brain Maturation

Summary: Consuming a high fat diet during adolescence could contribute to cognitive impairment as an adult, a new study reports.

Source: ETH Zurich.

Junk food is a burgeoning problem for modern society: we literally have too much on our plate. Fatty and unhealthy foods are especially popular with young children and adolescents. They are often the cheapest and most convenient eating option. Unfortunately, junk food can potentially damage the immature brain when consumed over an extended period as the young brain matures. High consumption of fatty foods during adolescence may in fact impair cognitive functions in adulthood, according to a recent study conducted by researchers from ETH Zurich and the University of Zurich, which has just been published in the medical journal Molecular Psychiatry.

The scientists arrived at this worrying conclusion after performing a study comparing the impact on the brains of juvenile and adult mice on being fed either an extremely high-fat diet or normal food. The fat-rich diet contained excessively high levels of saturated fats — the type most commonly found in fast foods, charcuterie products, butter and coconut oil.

Behavioural problems after only a few weeks

After a period of just four weeks, the researchers detected the first signs of impairment in the cognitive functions of young mice fed on a high-fat diet. These problems materialised even before the mice actually started to show any weight gain. One of the key factors in the development of these cognitive problems is a person’s age when the fatty foods are consumed: they tend to have a particularly negative impact on the maturation of the prefrontal cortex in the period from late childhood to early adulthood.

The prefrontal cortex is particularly vulnerable, as it takes longer to mature than other structures in the mammalian brain. In both mice and humans, this area of the brain is not fully developed until early adulthood. As it matures, the prefrontal cortex is therefore vulnerable to negative environmental experiences such as stress, infections and trauma, or even — as the study suggests — a poorly balanced diet.

The prefrontal cortex is responsible for the executive functions of the human brain: it looks after memory, planning, attention, impulse control and social behaviour. If this area of the brain is not functioning correctly, perhaps as the result of an accident or brain tumour, it can lead to cognitive deficits and personality changes. A person may have difficulty with complex learning processes, lose their inhibitions, or become aggressive, childish or compulsive.

No comparable effect on the adult brain

By contrast, the researchers failed to identify comparable changes in the behaviour of mature mice that had been fed a high-fat diet over an extended period. Obviously their metabolic systems were severely disrupted and they became obese. “Even so, this does not rule out the possibility that a high-fat diet may also be harmful for the brains of adult mice,” stresses Urs Meyer, former Group Leader of the Laboratory for Physiology and Behaviour at ETH Zurich and now professor at the University of Zurich.

Similarities between the mouse and human brain

According to Professor Meyer, the results of the mice study are readily translatable to humans: “As in humans, the prefrontal cortex in mice matures mainly during adolescence.” The executive functions attributed to this area of the brain are also similar for both mice and humans. The neuronal structures that are affected by fatty foods are also identical in both organisms.

Image shows a drawing of a brian made up of junk food.

The professor points out, however, that the very fatty diet – mice received over 60 percent of their calories in the form of fats — was not typical of the amount consumed by most people over an extended period. Such an exaggerated level of fat was deliberately chosen in order to be able to clearly demonstrate the effect of fatty foods on the maturation of the brain and to provide evidence for the underlying principle. “Only very few children and adolescents consume high-fat diets so excessively,” says Professor Meyer.

Nor is the study able to give any indication of the maximum amount of fat that a diet should contain so as to avoid subsequent damage to the maturing prefrontal cortex. This did not fall within the scope of the study. “Anyone eating fast food once a week is unlikely to be at risk.”

Nevertheless, Professor Meyer thinks that much more attention needs to be paid to nutrition as a child is growing up. “During adolescence, children and young adults should have a well-balanced diet based on nutritious foods.”

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Funding: This study was funded by the Swiss National Science Foundation, European Union Seventh Framework Program, Inserm, ETH Zurich, Mineco.

Source: Urs Meyer – ETH Zurich
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Hypervulnerability of the adolescent prefrontal cortex to nutritional stress via reelin deficiency” by M A Labouesse, O Lassalle, J Richetto, J Iafrati, U Weber-Stadlbauer, T Notter, T Gschwind, L Pujadas, E Soriano, A C Reichelt, C Labouesse, W Langhans, P Chavis and U Meyer in Molecular Psychiatry. Published online November 157 2016 doi:10.1038/mp.2016.193

CITE THIS NEUROSCIENCENEWS.COM ARTICLE
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Abstract

Hypervulnerability of the adolescent prefrontal cortex to nutritional stress via reelin deficiency

Overconsumption of high-fat diets (HFDs) can critically affect synaptic and cognitive functions within telencephalic structures such as the medial prefrontal cortex (mPFC). The underlying mechanisms, however, remain largely unknown. Here we show that adolescence is a sensitive period for the emergence of prefrontal cognitive deficits in response to HFD. We establish that the synaptic modulator reelin (RELN) is a critical mediator of this vulnerability because (1) periadolescent HFD (pHFD) selectively downregulates prefrontal RELN+ cells and (2) augmenting mPFC RELN levels using transgenesis or prefrontal pharmacology prevents the pHFD-induced prefrontal cognitive deficits. We further identify N-methyl-d-aspartate-dependent long-term depression (NMDA-LTD) at prefrontal excitatory synapses as a synaptic signature of this association because pHFD abolishes NMDA-LTD, a function that is restored by RELN overexpression. We believe this study provides the first mechanistic insight into the vulnerability of the adolescent mPFC towards nutritional stress, such as HFDs. Our findings have primary relevance to obese individuals who are at an increased risk of developing neurological cognitive comorbidities, and may extend to multiple neuropsychiatric and neurological disorders in which RELN deficiency is a common feature.

“Hypervulnerability of the adolescent prefrontal cortex to nutritional stress via reelin deficiency” by M A Labouesse, O Lassalle, J Richetto, J Iafrati, U Weber-Stadlbauer, T Notter, T Gschwind, L Pujadas, E Soriano, A C Reichelt, C Labouesse, W Langhans, P Chavis and U Meyer in Molecular Psychiatry. Published online November 157 2016 doi:10.1038/mp.2016.193

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Coconut Oil facts from Dr Mark Hyman

Coconut Oil – Are You Coco-Nuts to Eat It?

Did you know that 50 percent of media headlines about medical studies are dead wrong? And that many of these headlines don’t accurately match the conclusions of the studies they cover? That’s from a reviewpublished in the New England Journal of Medicine.

It makes me sad and furious at the same time that journalists don’t do their homework and create firestorms of confusion because of their negligent work.

That is exactly what happened when USA Today published their article, “Coconut Oil Isn’t Healthy. It’s Never Been Healthy.” Shame on you USA Today editors for doing such a sloppy job of journalism.

Why the American Heart Association Has Been and Still Is Wrong

First, there is not a single study showing that coconut oil causes heart disease. Not one. Second, the whole case against coconut oil is founded on a hypothesis that has been proven wrong. It’s the diet-heart hypothesis. Saturated fat raises LDL cholesterol. LDL cholesterol causes heart disease. Anything that raises LDL cholesterol is bad. Only problem is that the data does not support this hypothesis.

If you are geeky and want to read more where I cover the science in detail, read my blog “Fat: What I Got Wrong, What I Got Right.” But just like it took 150 years after Copernicus recognized the earth doesn’t revolve around the sun before it was finally accepted, it will take a while for the world to catch up with the false idea that low fat and low cholesterol diets won’t save us from heart disease. In fact, low fat diets cause heart disease. I have covered all this in my last book, Eat Fat, Get Thin with hundreds of references. Enjoy!

The USA Today article was based on a review by the American Heart Association (AHA). They published a review of fat and heart disease. The AHA has been at the vanguard of bad advice for decades since they first hooked onto the “fat is bad and will kill you” meme. They told us to eat very low fat, low cholesterol diets and to eat tons of starchy carbs (they get huge funding for cereal makers to put their seal of approval on sugary cereals because they are “fat free” but 75 percent sugar). Except now the overwhelming amount of research has proved that idea dead wrong. In fact, their recommendations have killed millions of people (no joke) from heart disease and diabetes. That’s why the very conservative 2015 USDA Dietary Guidelines removed any upper limits on dietary fat and eliminated any restrictions on dietary cholesterol. In fact, after decades of telling us to avoid eggs and shrimp they said, “Cholesterol is not a nutrient of concern for overconsumption”.

If you are interested in the corruption of the AHA, how’s its funding is supported by the Pharma industry, industrial food giants, including sugary cereal makers and industrial vegetable oil manufactures, then read this recent blog on Medium entitled, Is the American Heart Association a terrorist organization? I’m not calling the AHA a terrorist organization, I just want you to read the article and question who’s really pulling the strings.

How could this happen you might wonder? How could the scientists have gotten it so wrong? It all comes down to how we do the research. Most nutrition research is based on what we call observational studies. You follow a group of people for a long time, you ask them once a year what they ate last week and you see if patterns emerged. Good luck if they can remember. And also people aren’t honest – if they think butter is bad they will underreport it. Problem is those type of studies do not prove cause and effect, just correlation. If I did a study of women over 55-years old who have sex I could conclude that sex NEVER leads to pregnancy. Pretty meaningless. The populations studied that ate saturated fats were super unhealthy. Why? That’s because everyone who actually ate well, exercised, didn’t smoke also didn’t eat saturated fats because they were told not to. It was their healthy lifestyle that saved them, not less saturated fats.

Why Saturated Fats Are Not Bad and Are Essential for Health

This is exactly why study after study recently has shown no link between saturated fat and heart disease. You can read most of the important ones from the references, below, in my book and in the Fat What I Got Wrong, What I Got Right article. In fact, there have been very few cause and effect studies in nutrition – they are hard to do, take a long time and cost a lot. But two of the largest ones every published show that fat and saturated fat are not the problem. The first was the PREDIMED study where researchers gave 7000 participants olive oil or nuts vs. a low fat diet. By the way, olive oil contains 20 percent saturated fat. They had to stop the study because the people who didn’t eat the high fat diet were dying. 

The next study was completed over 40 years ago, but it wasn’t published because the results so contradicted the prevailing dogma that saturated fat was bad and that LDL cholesterol caused heart disease. This was a study that could not be conducted today because it would be considered unethical. They took 9000 people in mental hospitals and fed them butter and saturated fats or corn oil (polyunsaturated vegetable oil which the AHA report says we should eat more of). Guess what? The ones who ate the corn oil had more heart attacks and deaths despite lowering their LDL cholesterol. What? Really? Yes, it’s true. In fact, for every 30-point drop in LDL the risk of heart attack went up 22 percent. To top it off a recent review of all the science on big bad butter looking at 6.5 million patient years of butter eating, researchers found that butter eaters had no increased risk of heart disease, but they did have decreased risk of type 2 diabetes. You read that right. Butter = lower risk of type 2 diabetes. And if you still need to be convinced, here’s a review of 17 meta-analyses (review of all the best and relevant research) showing no link between saturated fat and heart disease.

The whole idea that LDL cholesterol causes heart disease is the reason we have a multi-billon dollar statin industry. One study of over 130,000 people who had heart attacks over 5 years showed that 75 percent had normal LDL and 50 percent had optimal LDL cholesterol. But only 10 percent had normal HDL or the protective cholesterol. Guess what raises HDL? Saturated fat. And coconut oil raises it the most of any saturated fat. And what lowers it? A low fat, high starch, and high sugar diet. We need cholesterol and saturated fat for the health of every cell membrane, for your brain cells and to make your sex hormones and more.

Cholesterol is not the cause of heart disease, it is the band-aid that tries to repair the arteries when damage occurs from a low fat, high starch sugar diet. This causes pre-diabetes and inflammation from a processed food diet, environmental toxins, a bad gut from a low fiber, processed diet or anything that causes inflammation.

Before we get off saturated fats, here’s one BIG warning. They ARE a problem if you eat them in the context of a high sugar, high starch, processed diet. It’s what I call sweet fat. Stay away. No bagels and butter. No donuts or French fries. Stick with butter and broccoli.

Why We Shouldn’t Be Main Lining Omega 6 Vegetable Oils

The other recommendation from the AHA other than dramatically lower saturated fat was to increase omega-6 refined vegetable oils. Bad idea. Yes, some studies show a lower risk of heart disease with a higher intake of omega-6 oils otherwise known as PUFA’s (soy, corn, safflower, canola, etc.). Again I cover this in detail in Eat Fat Get Thin, but the take home is this: If you eat saturated fat in the context of the typical American diet it will cause problems and people in those studies were eating exactly that. And to make it more confusing, the studies looking at PUFA’s included both omega-3 (super protective) and omega-6 fats. The omega-3’s made the omega-6 cousins look better. When you look at just the studies of omega-6 they actually increased the risk of heart attacks. And it is just common sense and evolutionary sense – our intake of these refined, heat processed, hexane treated, chemically deodorized oils (never consumed before in human history) have increase more than 1000 times (that’s 100,000 percent) in the last 100 years. Saturated fats make your cholesterol molecules stable and less likely to oxidize or go rancid. It is oxidized cholesterol that causes heart attacks. The PUFA’s are unstable and easily oxidized so when they are incorporated into cholesterol they make it unstable and go rancid – bad for your heart.

Is Coconut Oil Healthy?

We have had a coconut craze. What’s the deal? Broccoli is healthy but if that’s all you ate you would get sick. Coconut oil is healthy but only as part of an overall healthy diet not as the main course. Coconut oil has been consumed by populations in the South Pacific for thousands of years without ill effect. It has so many health benefits. You can read more in my article Is Coconut Oil Bad for My Cholesterol, or in my book Eat Fat Get Thin. But here’s the short list of benefits. It raises the good cholesterol, HDL. It improves the quality and size and type of cholesterol. It lowers the total cholesterol to HDL ratio – a far better predictor of heart disease than LDL. And cultures with 60+ percent of their diet as coconut oil have no heart disease. It also contains a unique type of saturated fat called MCT oil that boosts metabolism reverses, insulin resistance, and improves cognitive function. Coconut oil is also anti-fungal and anti-microbial and it contains lauric acid that is great for immune function. The only other good source of lauric acid is breast milk, which contains 24 percent saturated fat – far higher than the 6 percent the AHA recommends. Who would you trust, nature/God or the American Heart Association?

So, I am sorry you have to be buffeted about by bad conclusions from insufficient outdated science and bad journalism. But hopefully reading this helps, and if you are so inclined check out the references below, my other blogs on this topic, and my book and come to your own conclusions. 

Wishing you health and happiness,

Mark Hyman, MD


References

Appel, L.J., Sacks, F.M., Carey, V.J., Obarzanek, E. Swain, J.F., Miller, E.R. 3rd,OmniHeart Collaborative Research Group. (2005). Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial. Journal of the American Medical Association, 294(19):2455-2464.

Assunção, M.L., Ferreira, H.S., dos Santos, A.F., Cabral, C.R., & Florêncio, T.M.M.T. (2009). Effects of dietary coconut oil on the biochemical and anthropometric profiles of women presenting abdominal obesity. Lipids, 44(7), 593-601.

Barberger-Gateua, P., Samieri, C., Feart, C., & Plourde, M. (2012). Dietary omega 3 polyunsaturated fatty acids and Alzheimer’s disease: interaction with apolipoprotein E genotype. Current Alzheimer’s Research, 8(5), 479-491.

Calder, P.C. (1998). Dietary fatty acids and the immune system. Nutritional Reviews, II, S70-S83.

Cardoso et al. (2015). A coconut extra virgin oil-rich diet increases HDL cholesterol and decreases waist circumference and body mass in coronary artery disease patients. Nutrition Hospitals, 32(5), 2144-2152. doi: 10.3305/nh.2015.32.5.9642.

Crawford, M.A., Broadhurst, C.L., Guest, M., Nagar, A., Wang, Y., Ghebremeskel, K., & Schmidt, W. (2013). A quantum theory for the irreplaceable role of docosahexaenoic acid in neural cell signaling throughout evolution. Prostaglandins Leukotrienes and Essential Fatty Acids, 88(1), 5-13.

Daley, C. A., Abbott, A., Doyle, P. S., Nader, G. A., & Larson, S. (2010). A review of fatty acid profiles and antioxidant content in grass-fed and grain-fed beef. Nutrition Journal, 9(1), 10.

Das, U.N. (1994). Beneficial effect of eicosapentaenoic and docosahexaenoic acids in the management of systemic lupus erythematosus and its relationship to the cytokine network. Prostaglandins Leukotrienes and Essential Fatty Acids, 51(3), 207-213.

de Souza et al. (2015). Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: a systematic review and meta-anlaysis of observational studies. British Medical Journal, 351.

Estruch, R., Ros, E., Salas-Salvado, J., Covas, M.I., Corella, D., Aros, F.,…PREDIMED Study Investigators. (2013). Primary prevention of cardiovascular disease with a Mediterranean diet. New England Journal of Medicine, 368(14), 1279-1290. doi: 10.1056/NEJMoa1200303

FAO/WHO. (2009). Fats and fatty acids in human nutrition. Proceedings of the Joint FAO/WHO Expert Consultation. November 10-14, 2008. Geneva, Switzerland. Annals of Nutrition and Metabolism, 55, 1-3.

Fernando, W.M.A.D.B., Martins, I.J., Goozee, K.G., Brennan, C.S., Jayasena, V., & Martins, R.N. (2015). The role of dietary coconut for the prevention and treatment of Alzheimer’s disease: potential mechanisms of action. British Journal of Nutrition, 1-14.

Intahphuak, S., Khonsung, P., & Panthong, A. (2010). Anti-inflammatory, analgesic, and antipyretic activities of virgin coconut oil. Pharmacological Biology, 48(2), 151-157.

Kalmijn, S., Feskens, E.J.M., & Kromhout, D. (1997). Polyunsaturated fatty acids, antioxidants, and cognitive function in very old men. American journal of Epidemiology, 145, 33-41.

Liau, K.M., Lee, Y.Y., Chen, C.K., & Rasool, A.H.G. (2011). An open-label pilot study to assess the efficacy and safety of virgin coconut oil in reducing visceral adiposity. ISRN Pharmacology. doi: 10.5402/2011/949686

Mensink, R.P., Zock, P.L., Kester, A.D., & Katan, M.B. (2003). Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. American Journal of Clinical Nutrition, 77(5), 1146-1155.

Mielke, M.M., Zandi, P.P., Sjogren, M., Gustafson, D., Ostling, S., Steen, B., & Skoog, I. (2005). High total cholesterol levels in late life associated with a reduced risk of dementia. Neurology, 64(10), 1689-1695.

Mozaffarian, D., & Ludwig, D.S. (2015). The 2015 US Dietary Guidelines: Lifting the Ban on Total Dietary Fat. Journal of the American Medical Association, 313(24), 2421-2422.

Morin, C., Blier, P.U., & Fortin, S. (2015). Eicosapentaenoic acid and docosapentaenoic acid monoglycerides are more potent than docosahexaenoic acid monoglyceride to resolve inflammation in a rheumatoid arthritis model. Arthritis Research Therapies, 17, 142. doi: 10.1186/s13075-015-0653-y.

Morgan, R.E., Palinkas, L.A., Barrett-Connor, E.L., & Wingard, D.L. (1993). Plasma cholesterol and depressive symptoms in older men. The Lancet, 341(8837), 75-79. doi:10.1016/0140-6736(93)92556-9

Nafar, F., Clarke, J.P., & Mearow, K.M. (2017). Coconut oil protects cortical neurons from amyloid beta toxicity by enhancing signaling of cell survival pathways. Neurochemical International, 105, 64-79. doi: 10.1016/j.neuint.2017.01.008.

Narayanankutty, A., Mukesh, R.K., Ayoob, S.K., Ramavarma, S.K., Suseela, I.M., Manalil, J.J.,…Raghavamenon, A.C. (2016). Virgin coconut oil maintains redox status and improves glycemic conditions in high fructose fed rats. Journal of Food Science and Technology, 53(1), 895-901.

Nettleton, J. (1995). omega-3 fatty acids and health. New York Chapman & Hall. p. 67-73.

Nonaka, Y., Takagi, T., Inai, M., Nishimura, S., Urashima, S., Honda, K.,…Terada, S. (2016). Lauric acid stimulates ketone body production in the KT-5 astrocyte cell line. Journal of Oleo Science, 65(8), 693-699.

Ogbolu, D.O., Oni, A.A., Daini, O.A., & Oloko, A.P. (2007). In vitro antimicrobial properties of coconut oil on Candida species in Ibadan, Nigeria. Journal of Medical Foods, 10(2), 384-387.

Petrusson, H., Sigurdsson, J.A., Bengtsson, C., Nilsen, T.I., & Getz, L. (2012). Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study. Journal of the Evaluation of Clinical Practice, 18(1), 159-168.

Ramsden et al. (2016). Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-1973). British Medical Journal, 353.Simopoulos, A.P., & Salem Jr., N. (1992). Egg yolk as a source of long-chain polyunsaturated fatty acids in infant feeding. American Journal of Clinical Nutrition, 55, 411-414.

Rose, D.P. (1997). Dietary fatty acids and cancer. American Journal of Clinical Nutrition, 66(suppl), 998S-1003S.

Seaman, D.R. (2002). The diet-induced pro-inflammatory state: a cause of chronic pain and other degenerative diseases? Journal of Manipulative and Physiological Therapeutics, 25(3), 168-179.

Seneff, S., Wainwright, G., & Mascitelli, L. (2011). Nutrition and Alzheimer’s disease: The detrimental role of a high carbohydrate diet. European Journal of Internal Medicine, 1-7.

Simopoulos, A.P. (1991). Omega-3 fatty acids in health and disease and in growth and development. American Journal of Clinical Nutrition, 54, 483-463.

Sinclair, H. (1981). The relative importance of essential fatty acids of the linoleum and linolenic families: studies with an Eskimo diet. Progress in Lipid Research, 20, 897-899.

Siri-Tarino, P.W., Sun, Q., Hu, F.B., & Krauss, R.M. (2010). Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. American Journal of Clinical Nutrition, 91(3), 535-546.

Stillwell, W., & Wassall, S.R. (2003). Docosahexaenoic acid: membrane properties of a unique fatty acid. Chemistry and Physical Lipids, 126(1), 1-27.

Veum et al. (2016). Visceral adiposity and metabolic syndrome after very high-fat and low fat isocaloric diets: a randomized controlled trial. American Journal of Clinical Nutrition

Yang, H.Y., de la Rubia Orti, J.E., Sabater, P.S., Castillo, S.S., Rochina, M.J., Ramon, N.M., & Montoya-Castilla, I. (2015). Coconut oil: Non-alternative drug treatment against Alzheimer’s disease. Nutrition in Hospitals, 32(6), 2822-2877.

Mark Hyman MD is the Medical Director at Cleveland Clinic’s Center for Functional Medicine, the Founder of The UltraWellness Center, and a ten-time #1 New York

Breast milk, saw palmetto, bitter melon and virgin coconut oil for fat digestion

Fat Digestion

fat-digestion

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Action of Bile Salts
     Bile salts enhance the digestive action of lipases by breaking down fat globules into smaller droplets in a process called emulsification. This increases the surface area where lipases can act.

Bile salts are synthesized by hepatocytes and are secreted in bile which mixes with chyme. Bile salts are derived from cholesterol. Cholesterol is hydrophobic but when converted to bile salts possess a number of oxygen containing polar groups that are hydrophilic. Because all the polar groups are located on one side of the molecule, the molecule is amphipathic. The bile salts break up the fat globules into smaller hydrophilic coated droplets that more readily mix with water.
  Action of Pancreatic Lipase

     Pancreatic lipases work on the lipids on the surface of the lipid droplets by breaking the bonds of fatty acids on either end of the glycerol backbone. The fatty acids  and monoglycerides are released into solution. Of these end-products of digestion some are absorbed by the epithelial cells while others remain in aggregations called micelles.

Breast milk, saw palmetto, bitter melon and virgin coconut oil are saturated monoglycerides with antibacterial, anti-parasitic, antiviral, anti-fungal and anti-yeast properties.

fat-1

Anti-parasitic

To make it easier to take, dissolve a couple tablespoons in a hot tea of choice and drink. The first couple sips will be coconut oil, and then you will just taste the tea. Garlic– To help remove yeast and parasites, finely mince 1-2 cloves and drink in a cup of water before meals.

The rationale is that garlic and onion both have sulfur amino acids, which have good anti-parasitic properties. The recipe includes 6 tablespoons of raw virgin coconut oil, one clove of garlic and one large-sized red onion daily to efficiently kill and expel internal parasites.

Antiviral

Bitter melon contains high levels of anti-inflammatory, antibacterial, antiviral compounds.

Anti-inflammatory

Saw palmetto also seems to have an antiinflammatory effect on the prostate.

Fat digestion results in the mixture of sn2-monoglycerides and 2 fatty acids.

 

 

 

High rate of glial cell related brain tumor among the educated

Our brain detoxes during sleep (cleansing our brain from toxins during sleep). Our body also detoxifies in many ways as sum up by Dr Mercola.

While there are many different ways to rid your body of accumulated toxins, from detoxifying foods and chemical and/or natural detox agents to saunas, a biological process known as autophagy plays a key role.

The term autophagy means “self-eating,” and refers to the processes by which your body cleans out various debris, including toxins, and recycles damaged cell components.

The video above provides a more in-depth biochemical review of the autophagy processes involved in health and disease. As explained in layman’s terms by Greatist:1

“Your cells create membranes that hunt out scraps of dead, diseased, or worn-out cells; gobble them up; strip ’em for parts; and use the resulting molecules for energy or to make new cell parts.”

Dr. Colin Champ, a board-certified radiation oncologist and assistant professor at the University of Pittsburgh Medical Center explains it thus:

“Think of it as our body’s innate recycling program. Autophagy makes us more efficient machines to get rid of faulty parts, stop cancerous growths, and stop metabolic dysfunction like obesity and diabetes.”

By boosting your body’s autophagy process, you dampen inflammation, slow down the aging process, and optimize biological function. As noted by Fight Aging:2

“Greater autophagy taking place in tissue should mean fewer damaged and disarrayed cells at any given moment in time, which in turn should translate to a longer-lasting organism.”

Boosting Autophagy Through Exercise

Like the benefits of exercise, autophagy occurs in response to stress. And, in fact, exercise is one of the ways by which you boost autophagy. As you probably know, exercising creates mild damage to your muscles and tissues that your body then repairs, and by so doing makes your body stronger.

Exercise also helps flush out toxins by sweating, and is helpful for just about any detox program. In fact, many consider exercise a foundational aspect of effective detoxification.

Dr. George Yu, for example, who has been involved with clinical trials to help detoxify people from the Gulf War, recommends using a combination of exercise, sauna, and niacin supplementation to maximize elimination of toxins through your skin.

Exercise is an important component as it also causes vasodilation and increased blood flow. Beyond that, as noted in the featured article:

“One study looked at autophagosomes, structures that form around the pieces of cells that the body has decided to recycle.

After engineering mice to have glowing green autophagosomes … scientists found that the rate at which the mice were healthily demolishing their own cells drastically increased after they ran for 30 minutes on a treadmill.

The rate continued increasing until they’d been running for 80 minutes.”

How Much Exercise Do You Need to Optimize Autophagy?

The amount of exercise required to stimulate autophagy in humans is still unknown, however it is believed that intense exercise is more effective than mild exercise, which certainly makes logical sense.

That said, other research has shown that the “Goldilocks zone” in which exercise produces the greatest benefit for longevity is between 150 to 450 minutes of moderate exercise per week, lowering your risk of early death by 31 and 39 percent respectively.

Spending at least 30 percent of your workout on high-intensity exercises has also been shown to further boost longevity by about 13 percent, compared to exercising at a consistently moderate pace all the time.

Following these general guidelines will likely put you in the most advantageous position for maximizing autophagy as well.

How to Radically Inhibit Autophagy

One of the quickest ways to shut down autophagy is to eat large amounts of protein. What this will do is stimulate IGF-1 and mTOR, which are potent inhibitors of autophagy.

That is why it’s best to limit your protein to about 40 to 70 grams per day, depending on your lean body mass. The specific formula is one gram of protein for every kilogram of lean body mass, or one-half gram of protein per pound of lean body mass.

Substantial amounts of protein can be found in meat, fish, eggs, dairy products, legumes, nuts, and seeds. Some vegetables also contain generous amounts of protein — for example, broccoli. Forty grams of protein is not a large amount of food — it’s the equivalent of one six-ounce chicken breast.

To determine whether or not you’re getting too much protein, simply calculate your body’s requirement based on your lean body mass, and write down everything you eat for a few days. Then calculate the amount of daily protein you’ve consumed from all sources.

If you’re currently averaging a lot more than what is optimal, adjust downward accordingly. The following chart provides a quick overview of how much protein is in various foods.

Red meat, pork, poultry, and seafood average 6 to 9 grams of protein per ounce.

An ideal amount for most people would be a 3-ounce serving of meat or seafood (not 9- or 12-ounce steaks!), which will provide about 18 to 27 grams of protein

Eggs contain about 6 to 8 grams of protein per egg. So an omelet made from two eggs would give you about 12 to 16 grams of protein

If you add cheese, you need to calculate that protein in as well (check the label of your cheese)

Seeds and nuts contain on average 4 to 8 grams of protein per quarter cup Cooked beans average about 7 to 8 grams per half cup
Cooked grains average 5 to 7 grams per cup Most vegetables contain about 1 to 2 grams of protein per ounce

The Importance of Mitochondrial Biogenesis

Healthy mitochondria are at the core of staying healthy and preventing disease. Mitochondrial damage can trigger genetic mutations that can contribute to cancer, so optimizing the health of your mitochondria is a key component of cancer prevention. Autophagy is one way to remove damaged mitochondria, but biogenesis is the process by which new healthy mitochondria can be duplicated.

Interestingly, exercise plays a dual role as it not only stimulates autophagy but is also one of the most potent stimulators of mitochondrial biogenesis. It does this by increasing a signal in your body called AMPK, which in turn activates PGC-1 alpha.

By stimulating  your mitochondria — the organelles in nearly every cell that produce ATP — to work harder, your mitochondria start making reactive oxygen species (ROS), which act as signaling molecules. One of the functions they signal is to make more mitochondria.

In essence, the key to preventing disease — virtually  eliminating the risk of cancer, heart disease, diabetes, many other diseases — and  slowing down the aging process lies in  optimizing mitochondrial function and increasing mitochondrial numbers. Thankfully, exercise helps you do both.

Intermittent Fasting — Another Way to Boost Autophagy

Fasting is another biological stressor that produces many beneficial results, including autophagy. In fact, some of the benefits associated with fasting — such as a reduced risk of diabetes and heart disease — can at least in part be attributed to this process.

While there are many different kinds of intermittent fasting schedules, if you’re insulin resistant, my personal recommendation is to fast every day by scheduling all of your eating within a window of approximately 8 hours or less. For example, you could restrict your eating to the hours of 11am and 7pm. This equates to 16 hours of daily fasting.

I used to recommend skipping breakfast, but I’ve since realized that it probably doesn’t matter which meal you skip — breakfast or dinner — as long as you skip one of them. Some really struggle without breakfast, so play around with it and find out what works best for you.

Eating between the hours of 8 a.m. and 4 p.m. may work better for some people, and this schedule actually has an added advantage, because you’re now fasting for several hours before going to bed. I’m convinced that it’s best for most to avoid eating three hours prior to bed, as the last thing you need to be doing is producing energy when you don’t need it.

There’s compelling evidence showing that when you supply fuel to your mitochondria at a time when they don’t need it, they leak a large number of electrons that liberate reactive oxygen species as free radicals.

These free radicals damage your mitochondrial and eventually nuclear DNA. There’s also evidence indicating that cancer cells uniformly have damaged mitochondria, so eating too close to bedtime is not a good idea. I personally strive for six hours of fasting before bedtime, but at bare minimum, avoid eating at least three hours before going to bed.

To Boost Autophagy, Switch to a High-Fat, Low-Carb Diet

Nutritional ketogenesis is a third strategy that will help boost autophagy, and to accomplish that, you need to cut down on the non-fiber carbs and increase the amount of healthy fat in your diet, along with a moderate amount of protein. (Many Americans tend to eat far more protein than they need, which will counteract your efforts to get into nutritional ketosis.)  According to Champ:3

“Ketogenesis is like an autophagy hack. You get a lot of the same metabolic changes and benefits of fasting without actually fasting … Between 60 and 70 percent of one’s overall calories should come from [healthy] fat … Protein makes up 20 to 30 percent of calories, while carbs are kept below 50 grams per day …  Similar benefits have been noted in people following a diet in which carbs didn’t exceed 30 percent of their overall calories.”

Most Americans consume harmful fats like processed vegetable oils, which will invariably make your health worse. Not only is it processed, it’s very high in omega-6 oils, and excess omega-6 fats will integrate into the inner mitochondrial membrane and become highly susceptible to oxidative damage, causing your mitochondria to die prematurely.

It is best to keep omega-6 fats consumption to less than 4 to 5 percent of your total daily calories Replace the omega-6 fats with healthy fats-  such as natural, unprocessed fat- found in real foods such as seeds, nuts, real butter, olives, avocado, or coconut oil.

It’s also important to make the distinction about which carbs we’re talking about when we say “low-carb,” as vegetables are “carbs” too. However, fiber carbs (i.e. vegetables) will not push your metabolism in the wrong direction — only the non-fiber ones will (think sugars and anything that converts to sugar, such as soda, processed grains, pasta, bread and cookies, for example).

Even more importantly, the fiber is not broken down by sugar but travels down the digestion system, is consumed by bacteria in your intestine, and converted to short chain fats that actually improve your health.

If you look at the nutrition facts on a processed food package, it will list total carbs, and again, that’s not what we’re talking about. To calculate the dangerous non-fiber carbs, simply subtract the grams of fiber from the grams of total carbohydrate in the food in question. Remember, you do need carbs, but you need most all of them from vegetables, which are also high in fiber.

Autophagy Restores Function in Aging Muscle Stem Cells

It has long been known that mesenchymal stem cells (MSCs) in skeletal muscle are an important part of the muscle repair process. Previous research4 has shown that exercise affects the behavior of your muscle stem cells, and may help prevent or even restore age-related muscle loss. MSCs in muscle are very responsive to mechanical strain, and these stem cells accumulate in muscle post-exercise.

And, while the MSCs do not directly contribute to building new muscle fibers, they do release growth factors, which encourage other cells to generate new muscle. It’s also known that people’s muscles tend to become increasingly deficient in MSCs with age, and that autophagy efficiency declines as well. As a result, metabolic waste starts to build up in your cells and tissues.

A recent Spanish study5 reports that satellite cells — muscle stem cells responsible for tissue regeneration — rely on autophagy to prevent the arrest of the cell cycle, known as cellular senescence; a state in which stem cell activity significantly declines. In short, to improve the regeneration of muscle tissue, you need to augment autophagy.

With efficient autophagy — your body’s internal cleaning mechanism — your stem cells retain the ability to maintain and repair your tissues.

As reported by Fight Aging:6

“The researchers demonstrated that restoring youthful levels of autophagy in old satellite cell populations can restore them from senescence and return their regenerative capabilities … The paper … is one of the more compelling of recent arguments for putting more effort into treatments based on artificially increased levels of autophagy …

[M]any of the methods known to modestly slow aging in laboratory species are associated with increased levels of autophagy. It is a vital component in hormesis, wherein causing a little damage leads to a lasting increase in autophagy and a net gain. Stem cells spend much of their time in a state of quiescence, only springing into action when called upon.

This helps to preserve them for the long term. In older tissues with greater levels of molecular damage, ever more stem cells slip from quiescence into an irreversible senescent state. These senescent cells are no longer capable of generating new cells, and start to secrete all sorts of harmful signal molecules.”

Health and Longevity Are Rooted in Mitochondrial Function

The take-home message here is that your lifestyle determines your fate in terms of how long you’ll live and, ultimately, how healthy those years will be. For optimal health and disease prevention, you need healthy mitochondria and efficient autophagy (cellular cleaning and recycling), and three key lifestyle factors that have a beneficial effect on both are:

  1. What you eat: A diet high in quality fats, moderate in protein, and low in non-fiber carbs. Eating organic and grass-fed is also important, as commonly used pesticides like glyphosate cause mitochondrial damage
  2. When you eat: Daily intermittent fasting tends to be the easiest to adhere to, but any fasting schedule that you will consistently follow will work
  3. Exercise, with high intensity interval exercises being the most effective

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Damage to Blood–brain barrier (BBB) pathways leading to Alzheimer’s disease and Dementia

BBB.JPG Blood–brain barrier (BBB) pathways to neurodegeneration in dementia and Alzheimer’s disease (AD)

  • A: In the normal capillary, there is an intact BBB composed of tightly joined endothelial cells and supported by mural pericytes, as shown in this simplified schematic. The BBB normally selectively regulates the passage of molecules from blood to brain and vice versa, and restricts entry of blood-derived products and toxins into the brain. There are many transporters and receptors along the BBB that permit molecules to cross the BBB via substrate-specific transport systems, some of which are particularly relevant to AD pathophysiogenesis, as illustrated in the graphics above. For example, the normal BBB has high expression of the glucose transporter (GLUT1),moderate expression of low-density lipoprotein receptor-related protein-1 (LRP1), and minimal expression of receptor for advanced glycation end-products (RAGE).

Alzheimer’s Disease

  • B: In the AD capillary, there is a vicious cascade of events that can lead to neurodegeneration, as shown in this schematic and described as follows. 1. Pericytes degenerate and detach. 2. The BBB becomes leaky. 3. Blood-derived molecules like fibrinogen, thrombin, and plasminogen leak from vessels and are directly toxic to neurons and can further induce BBB damage. Erythrocyte extravasation induces accumulation of hemoglobin-derived iron which causes generation of reactive oxygen species (ROS) and oxidative stress to neurons, and albumin promotes local tissue edema. 4. BBB transporter expression is altered, e.g., LRP1 and GLUT1 expressions are significantly reduced, whereas RAGE expression is increased.

The alterations in LRP1 and RAGE (transportS Aβ from the blood into the brain ) reduce the clearance and increase the uptake of Aβ into the brain, respectively, leading to Aβ accumulation in the brain. Also, normal cerebrovascular functions are disrupted by vascular pathologies including 5. Cerebral amyloid angiopathy (CAA), 6. Damaged and thickening of the basement membrane, and 7. String vessels.

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 Genes

Patients with hereditary Dutch, Iowa, Arctic, Flemish, Italian, or Piedmont L34V vasculotropic mutations develop CAA followed by rupture of blood vessels and hemorrhagic strokes in midlife. CAA is known to worsen AD pathology and occurs in 80% of AD patients. CAA likely develops as a result of the ineffective transvascular and perivascular clearance of Aβ, as well as poor Aβ clearance by arterial VSMCs. It was recently reported that microvascular rather than arenchymal Aβ deposits are associated with early behavioral deficits in AD transgenic mice. Individuals with CAA carrying APOE4 allele(s) have accelerated vascular pathology that can modulate Aβ accumulation.

Reduced glucose utilization

Cognitively normal individuals with genetic risk for AD or positive AD family history and mild or no cognitive impairment that later develop AD all have reduced glucose utilization in the hippocampus, parietotemporal cortex, and/or posterior cingulate cortex measured by 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-PET, which occurs prior to brain atrophy and neuronal dysfunction. Brain glucose uptake correlateswith the level of GLUT1 on cerebralmicrovessels.

Other contributing factors: Diabetes, hypertension, pollution/nanoparticles

Pollution/nanoparticles

Air pollution has been shown to increase the risk of AD and AD-like brain pathologies. Young residents of the Mexico City Metropolitan Area (MCMA) exposed to air pollution display cognitive impairment, BBB disruption, Aβ42 plaques, and hyperphosphorylated tau accumulation,which are exacerbated in APOE4 carriers. Children from the MCMA have increased serum autoantibodies against neuronal proteins, likely due to compromised brain immunity and BBB breakdown. In mouse experimental studies, aerosolized nickel nanoparticles caused a rapid and drastic increase in Aβ40 and Aβ42. Also, APOE null mice exposed to mixed vehicle exhaust have accelerated BBB breakdown, decreased expression of tight junction proteins (e.g., occludin, claudin-5) and increased generation of reactive oxygen species activity.

Many types of nanomaterials are emerging in medical science and research for their potential as biosensors, biomaterials, tissue engineering, DNA modification, or drug delivery. The sources of nanoparticles that humans are exposed to are numerous and include nanoscaled debris from hip replacements, prostheses, cosmetics, sunscreen, and many others. Unfortunately, nanoparticles have proven to be toxic in a number of host systems. Highly active nanoparticles (e.g., silica coated to be hydrophilic, hydrophobic, or amphiphilic) can be taken up by cellular membranes, including the BBB, and cross the membrane passively or by carrier-mediated endocytosis.

Experimental studies in rodents have shown that silver, copper, or aluminum/aluminum oxide nanoparticles disrupt the BBB, reduce the expression of endothelial tight junctions, decrease CBF, and induce edema, synaptic

dysfunction, and neurodegeneration. Interestingly, silver and copper nanoparticle exposure exacerbated BBB dysfunction when accompanying sleep deprivation or diabetes.

Peripheral inflammation

Peripheral inflammation is being considered a possible risk factor for AD and dementia. Infectious agents including pneumonia, B. burgdorferi, Helicobacter pylori, and herpes simplex virus 1 (HSV-1) have been identified in AD post-mortembrain tissue. Interestingly,

HSV-1 infections are foundmore often in APOE4 carriers,which have increased BBB permeability. Additionally, dementia patients have a two-fold increased mortality rate from pneumonia, and pneumonia patients have elevated MMP-9 levels in their serum, which is known to be linked to BBB breakdown.

Poor oral hygiene, oral inflammation, and tooth loss worsen with age and are risk factors for AD. Recently, fungus was identified in post-mortem brain tissue from AD subjects and was found to localize around blood vessels in AD brain tissue. In AD, infectious agents likely enter the brain through a leaky, disrupted BBB and cause more detrimental effects than they would normally if the BBB were

intact.

Diet and AD

Recent studies report that diet can mediate the vasculoplastic reserve of the hippocampus. For example, consuming high levels of cocoa flavanols increased capillary density and enhanced dentate gyrus-associated cognitive function in cognitively normal healthy subjects

This suggests an interaction between vasculoplasticity and neuronal plasticity during normal aging and dementia, but how this relationship is affected by lifestyle and vascular risk factors is currently unclear and should be investigated in future studies.

Growing evidence supports the benefits of a Mediterranean diet in protecting against dementia and prolonging one’s cognitive reserve during aging. Age-related cognitive decline was attenuated in individuals consuming a Mediterranean diet, as found in a recent study of the Mediterranean-Dietary Approach to Systolic Hypertension (DASH) diet intervention for neurodegenerative delay (MIND).

In comparing Mediterranean and Western diets, the primary difference is the source and proportion of dietary fats, with olive oil specifically being the main fat consumed in the Mediterranean diet and high levels of saturated fatty acids and simple carbohydrates being consumed in Western diets. Microvascular dysfunction is evident in rodent models fed unhealthy diets, namely, those fed diets of Western culture, high fat, and high cholesterol.

An intact BBB is needed for proper cholesterol metabolism. In CSF, decreased cholesterol levels correlate with decreased Aβ42 and increased CSF APPα and APPβ (products of APP processing) levels, supporting an association between disrupted cholesterol metabolism and increased amyloidogenesis.

Resveratrol is a biologically active plant-derived phytoalexin. Resveratrol has been shown to cross BBB and regulate expression of MMPs, reduce pericyte loss, maintain integrity of BBB, and promote Aβ clearance [224–226]. Treatment with resveratrol completely reversed diabetes-induced vascular dysfunction by reducing capillary leakage, pericyte degeneration, and VEGF protein expression in the murine retina.

An earlier study has shown that resveratrol inhibits RAGE expression in vascular cells,which is implicated in Aβ transport into the brain and accelerated Aβ pathology in a mousemodel.

Furthermore, long-term consumption of resveratrol reduced oxidative stress and prevented behavioral deficits in a rat model with disrupted NVU.

Olive oil is high in essential omega-3 fatty acids, the major component of which is docosahexaenoic acid (DHA), and has long been reported to benefit cognition and overall brain health. DHA cannot be synthesized by the body and thus must be consumed, and the primary transporter of DHA from blood-to-brain is the major facilitator superfamily domain containing 2A (MFSD2A) at the BBB.

Individuals with AD have lower CSF DHA lipid levels, and those with mild dementia have lower CSF α-liolenic acid levels. Interestingly, reduced MFSD2A expression at the BBB can lead to a loss of its important functions, including maintenance of BBB integrity and omega-3 fatty acid transport into the brain.

Transgenic APOE4 mice also exhibit reduced uptake of DHA into the brain compared with transgenic APOE2 mice. But, whether this is related to reduced Mfsd2a expression is currently unknown. Additional studies are needed elucidate the underlying mechanisms of MFSD2A and fatty acids in relation to dementia and AD.

 

Exercise and environmental enrichment

Regular exercise and physical activity, particularly during midlife, are associated with improved cerebrovascular function and reduced rates of dementia and AD. Individuals that exercised regularly for 28 days exhibited reduced plasma homocysteine levels and increased endothelial progenitor cells in peripheral blood, factors that protect against vascular damage and cognitive impairment.

Experimental studies in diabetic rats have shown that treadmill exercise maintains claudin-5 expression at the BBB compared to rats not receiving exercise. Mechanistically, physical activity and cognitive stimulation in the form of enriched environment (e.g., tunnels, balls, ladders, and running wheel) accelerated Aβ enzymatic degradation and enhanced transvascular Aβ clearance, reducing Aβ accumulation in brains of AD transgenic mouse models.

Physical activity promoted Aβ clearance frombrain to blood via upregulation of LRP1 and downregulation of RAGE at the BBB. Mice without access to a running wheel had decreased occludin tight junction levels and disrupted BBB integrity. Although recent attention has been given to exercise, additional studies are needed to more completely understand the mechanism underlying its beneficial effects.

exercise

Source: Nelson et al, Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer’s disease, Department of Physiology and Biophysics and the Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90089, USA

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