New brain metabolism and ketone review article
"Brain fuel metabolism, aging, and Alzheimer’s disease",
Stephen Cunnane Ph.D., Scott Nugent B.Sc., Maggie Roy M.Sc., and others, Nutrition, January 2011
Here are some important excerpts from this article:
"The recent development of 11C-acetoacetate as a ketone tracer for PET studies opens a new window to compare brain metabolism of glucose and ketones in the same individual. If brain
ketone metabolism is not lower in AD or is less affected than glucose metabolism, one potential strategy to improve brain fuel availability and reduce the risk of AD that has already been targeted in clinical studies would be to develop a way to safely and reliably provide the brain with ketones as an alternative fuel to glucose..."
"Whether or not mitochondrial dysfunction reflects genetic or metabolic disturbances,
clinical trials attempting to redress the energy deficit in the AD brain suggest that cognitive function can be at least transiently improved if more fuel (glucose or ketones) can be
supplied to the brain."
"In carriers of apo E4, small areas of lower brain glucose metabolism are observed at an age
as young as 30 y old, e.g., 30-40 y before clinical onset. Indeed, we see an inverse relationship between CMRg in several brain regions and fasting plasma insulin, so brain metabolism
seems to be sensitive to even mild disturbances in systemic insulin control even if no clinical symptoms of cognitive decline are observed. Compared to non-carriers of apo E4, carriers have altered u3 [omega-3] fatty acid metabolism and higher measures of oxidative stress in the brain, both of which may contribute to a higher risk of early onset of brain hypometabolism. If brain hypometabolism can be present before clinical symptoms are apparent, this does not prove that hypometabolism is the earliest event in AD. However, to the best of our knowledge, hypometabolism is currently the earliest measurable abnormality in the brain that is connected to AD so its features and the reasons for it should shed light on the etiology of AD."
"The cerebral metabolic rate of ketones (CMRk) varies directlywith their blood concentration, starting at very low ketone concentrations...Hence, at a plasma b-hydroxybutyrate [one of the primary ketone bodies] concentration of 0.3-0.5 mM, such as can be achieved during 12-24 h fasting, b-hydroxybutyrate supplies 3-5% of whole brain energy requirements. As plasma ketones rise, CMRk also rises such that at a b-hydroxybutyrate of about 1.5mM, ketones provide about 18%, and at 6 mM, they provide about 60% of brain fuel." [Dr. Richard Veech's ketone ester can provide levels this high].
"Acute, controlled human experiments show that ketone infusion or ketogenesis inhibits the cognitive and behavioral sequelae of acute, experimental hypoglycemia, both in healthy
adults and in type 1 diabetes. It is generally assumed that the cognitive effects of hypoglycemia can be prevented by ketones because they seamlessly replace glucose to meet the brain’s energy requirements. However, acutely raising plasma ketones also increases cerebral blood flow in humans, an effect that may contribute to their beneficial impact on cognition during hypoglycemia. Studies in humans and animal models suggest further protective effects of ketones in the brain after ischemic insult [lack of oxygen/stroke] and other treatments damaging neuronal function."
"More recent controlled clinical trials confirm that short-term improvement can occur in cognitive tests when individuals with mild to moderate AD are provided with an exogenous source of glucose, ketones, insulin, or insulin sensitizers. These clinical studies show that the
affected brain regions in AD are at least partially viable and that cognition can improve when exogenous fuel supply to the brain is increased. In two of these studies, ketogenic supplements
based on medium chain triglycerides were used, thereby permitting a relatively normal choice of meals. Medium chain triglycerides have long been known to be ketogenic because they contain medium chain fatty acids (octanoic [8:0] and decanoic [10:0] acids), which do not require activation by CoA to enter mitochondria. The mild beneficial effects on cognition and relatively good tolerance to the doses of medium chain triglyceride used are promising, notwithstanding the possibility that carriers of apo E4 with AD derive little benefit from this treatment [Dr. Newport's comment: per one of the authors of the MCT oil studies, many of the ApoE4+ individuals did experience improvement, as a group when data was combined on the average they did not]. The explanation for the beneficial effect of mild, experimental ketonemia on cognition in AD may be as simple as exchanging one brain fuel for another as occurs in
fasting or starvation. It may also be due to the observation that although glycolysis may be impaired in the AD brain, CMRk and metabolic capacity to use a fuel other than glucose may
both be relatively normal in AD."
"...two observations in particular support the notion that the neurons affected in AD are still functional: (1) in AD, brain ketone uptake is apparently normal or at least less impaired than is glucose, and (2) there is a functional response to nutritional supplements that increase brain fuel
availability, particularly ketones. Hence, if brain fuel metabolism could be optimized or even partially returned toward normal, the risk of further cognitive decline may diminish. Raising plasma ketones to 0.4-0.5 mM would contribute to 5-10% of the brain’s energy requirements, which is equivalent to the early cortical glucose deficit in those genetically at risk AD. Such a mild, safe level of ketonemia is achievable with ketogenic supplements, so if implemented before symptoms develop, it seems plausible that they could diminish the risk of further metabolic deterioration and clinical onset of cognitive decline."
Regarding Omega-3 fatty acids:
"The u3 [omega-3] polyunsaturated fatty acid, DHA, is now widely understood to have an important role in mammalian brain development...Insufficient dietary intake of DHA and low levels of DHA in the hippocampus may have a role in cognitive decline in the elderly and/or AD. Hence, the low intake of DHA now widely but not universally reported in AD may contribute to the evolution of cognitive decline because of its role in brain glucose transport and in other aspects of brain function and structure. This emerging role of DHA in brain energy metabolism could be linked to the early presymptomatic onset of brain glucose hypometabolism in AD, at least in carriers of the e4 allele of apoE4. Nevertheless, such an effect probably involves relatively subtle changes in DHA metabolism because plasma DHA appears to be higher in the healthy elderly and is widely variable in AD."
Dr. Newport's comments:
The bottom line here, to try to prevent or stabilize AD, include medium chain fatty acids (coconut oil, palm kernel oil and MCT oil are the richest sources) in the diet to provide ketones as an alternative fuel to glucose AND eat fish (especially salmon) and/or take a supplement of marine based omega-3 oil (fish oil for most of us; algae based oil for vegans found in brands that are marketed to pregnant women).
Labels: AD, alzheimer's disease, alzheimers, brain metabolism, coconut oil, insulin deficiency, ketones, medium chain fatty acids, mitochondrial dysfunction, omega-3 fatty acids, prevention of alzheimer's
28 Comments:
Dr. Newport, could you post a link, maybe on the front page, to a post where you share the entire protocol (all supplements and also diet) you have your husband on? It would be very helpful.
Thanks.
By Anonymous, At February 6, 2011 at 7:47 PM
"Whether or not mitochondrial dysfunction reflects genetic or metabolic disturbances,
clinical trials attempting to redress the energy deficit in the AD brain suggest that cognitive function can be at least transiently improved if more fuel (glucose or ketones) can be
supplied to the brain."
Dr Newport, based on this point, I would understand the energy deficient AD brain performs better with a quick boost of energy. So why is Diabetes cited as a risk factor for AD? evidently I am missing some part of the puzzle, so please explain. I follow AD news and your website regularly since the incidence od AD in the menfolk of our family has been very-very high and am on the look out for any piece of understanding or information that will help.
By Anonymous, At February 27, 2011 at 1:31 PM
Mayo Clinic researchers reported a strong relationship between celiac disease and declining brain function.... they report,
cognitive impairment associated with celiac disease was never the initial clinical diagnosis. They further ask clinicians for
a reevaluation of the role of celiac disease in causing cognitive impairment [as it] has the potential of expanding the narrow spectrum of treatable dementia.
Also Hadsivasslliou has cured neurological problems with a gluten free diet .
By Anonymous, At March 13, 2011 at 5:59 AM
Dr Newport,
I understand that you are saying that some APOE4 patients do not benefit from the supplementation of keytones. Is this correct?
Jane
By Jane, At March 22, 2011 at 2:55 AM
I notice that there is a post asking regarding chewing gum. Some years ago when I had a very dry mouth, my doctor suggested chewing gum. I mentioned this to another doctor and he told me that when you chew gum the stomach is expecting to receive food to process and activates some form of acid and then nothing arrives for the acid to breakdown. From this I assume he implied that chewing gum is not a good idea. Just passing this on for consideration.
Also for those trying coconut oil, I have noticed a significant improvement in bowel function from oil pulling. Use 2 tsps of coconut oil in the morning on an empty stomach prior to brushing teeth, drinking or eating. Swirl around in you mouth like a mouthwash and then spit it out. I then brush my teeth and use a tongue cleaner. From the very first day I was no longer constipated. Yet I had for about 2 months been eating coconut oil and during this time did not notice any improvement in bowel function. Feel it is worth read Bruce Fife's book The New Arthritis Cure. Yet from eating the coconut oil my TSH blood test went from 11.2 down to 5.8 in 6-7 weeks and my cholesterol ratio went from 4.2 down to 3.9. So while when only eating coconut oil did not aid constipation, it definitely had a positive effect.
By Anonymous, At July 22, 2011 at 10:13 AM
Hi Dr. Newport,
I would like to add my deep appreciation to those of many others, for your efforts in fighting AD. Like you, I believe that CO/MCTs are probably good (and tasty) prophylactic measure vs. other neurodegenerative disorders. Even though there is no AD or other such conditions in my family, some degree of short term memory loss comes with aging to all. After reading you blog and watching your YouTube presentation I added virgin coconut oil to my fresh coconut daily (delight) consumption (I live on a tropical island). Adding CO to melted square of unsweetened 100% cocoa chocolate, let it solidify in the fridge for a short time - is my way of taking it (I don't cook with any oil/fat at all).
Best wishes for you and Steve.
Arbor
By Arbor, At December 25, 2011 at 11:55 AM
The full paper is at|:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844675/?tool=pubmed
Arbor
Am J Clin Nutr. 2010 Apr;91(4):875-82. Epub 2010 Feb 10.
Rapid cellular enrichment of eicosapentaenoate after a single intravenous injection of a novel medium-chain triacylglycerol:fish-oil emulsion in humans.
Carpentier YA, Hacquebard M, Portois L, Dupont IE, Deckelbaum RJ, Malaisse WJ.
Source
Laboratory of Experimental Surgery, Université Libre de Bruxelles, Brussels, Belgium.
Abstract
BACKGROUND:
Dietary deficiency in n-3 (omega-3) polyunsaturated fatty acids (PUFAs) prevails in Western populations and potentially results in adverse health outcomes. To circumvent the slow n-3 PUFA incorporation in phospholipids of key cells after oral supplementation, a new preparation for intravenous bolus injection was developed with 20 g triacylglycerols/100 mL of a mixture of 80% medium-chain triacylglycerols (MCTs) and 20% fish oil (FO) (wt:wt), and 0.4 g alpha-tocopherol/100 mL of the same mixture.
OBJECTIVE:
Our objective was to document the enrichment of n-3 PUFAs in leukocyte and platelet phospholipids after a bolus intravenous injection of MCT:FO in men.
DESIGN:
Twelve healthy male subjects received injections over a 5-min period of 50 mL of either MCT:FO or a control MCT:long-chain triacylglycerol (MCT:LCT) emulsion containing 20 g triacylglycerols/100 mL with equal amounts (wt:wt) of MCT and soybean triacylglycerols (LCT) and containing 0.02 g alpha-tocopherol/100 mL; after an 8-wk interval, the subjects received injections of the other preparation.
RESULTS:
Clinical and biological variables that assessed tolerance and safety remained unchanged. Plasma elimination was faster for MCT:FO than for MCT:LCT (half-life: 24.5 +/- 3.5 min compared with 32.9 +/- 3.0 min; P < 0.025). This was associated with a greater increase in the plasma nonesterified fatty acid concentration. The content of n-3 PUFAs, specifically eicosapentaenoic acid (20:5n-3), increased in leukocyte and platelet phospholipids within 60 min and > or =24 h after MCT:FO injection.
CONCLUSION:
Bolus intravenous injection of a novel MCT:FO emulsion allows rapid enrichment of cells with n-3 PUFAs.
PMID: 20147473
Free PMC Article
By Arbor, At December 25, 2011 at 12:03 PM
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شركة نقل اثاث
الاثاث من الاشياء التى نستطيع ان نبذل فية الكثير من الجهد والوقت من اجل ان يتم القيام باعمال النقل من مكان الى اخر سواء الى اى مكان فى المملكة او اى مكان خارج المملكة ، فاعمال النقل من الخدمات التى تبدو لنا انها سهلة وبسيطة الا انة فى نهاية الامر من الخدمات التى تؤدى الى التعرض الى مشاكل كثيرا من
الصعب ان يتم القيام بحلها من الكسر والخدش والتلفيات والضياع ،شركة قمم التميز من اهم وافضل الشركات التى تحقق اعلى مستوى من خدمات النقل للاثاث والقيام بالاتفاق مع مركز التعاون الخليجى من اجل ان يتم الحفاظ على الاثاث ضد اى مشكلة ، فاذا كنت فى حيرة من امر النقل فتاكد انك الان تمتلك افضل الشركات المميزة الخاصة باعمال النقل من خلال الاعتماد على توفير عدد من الخدمات المميزة . شركة شراء اثاث مستعمل بالدمام
شركة قمم التميز على وعى كبير باعمال النقل والتى تحقق افضل مستوى من خدمات النقل التى تؤكد ان الاثاث يتم الانتقال من مكان الى اخر دون ان يتم التعرض الى اى مشكلة من اهم الخدمات المقدمة الاتى :-
1- الاعتماد على افضل النجاريين المتخصصين فى اعمال الفك بطريقة حرفية لان الاثاث يحتاج الى القيام باعمال الفك الى قطع اصغر من الممكن حتى يتم حماية الاثاث من التعرض الى اى تلفيات او ظهور اى عيب فى الاثاث بعد التركيب .
2- تعتمد شركة نقل اثاث على افضل الطرق فى التعبئة والتغليف وتوفر النيلون والحبال والبلاستيك ذات الفقاقيع فى اعمال التغليف للزجاج والتغليف للاثاث والتغليف للمراتب وغيرها من الاشياء المتواجدة فى المكان .
3- التعبئة تتم من خلال صناديق مخصصة مغلقة حتى يتم انتقال بيه الى المكان المراد النقل الية .
4- اعمال النقل تتم من خلال الاعتماد على شاحنات متخصصة فى اعمال النقل والتى يتم تحميل الاثاث على السيارات من خلال اساليب وطرق النقل الحديثة المميزة .
الاهتمام باعمال النقل بكافة الوسائل المختلفة بالاضافة الى ان الشركة تهتم باعمال النقل من خلال توفير عدد من الوكلاء الخارجين لتسهيل اعمال النقل الان . شركة نقل عفش بالدمام
لا تكتفى شركة نقل اثاث بالقيام باعمال النقل فقط بل تهتم باعمال التركيب واعادة الاثاث الى ما كان علية بعد ان تتم اعمال النقل مباشرا .
شركة تخزين اثاث بالدمام
تخزين الاثاث من المهام التى نجتاج الية فى اوقات معينة اثناء الانتقال من شقة الى اخر او القيام بالسفر لفترات طويلة ، فالحرارة المرتفعة والرطوبة والاتربة الناعمة تؤدى الى ظهور التشققات و تؤدى الى التكسير المفاجىء للاخشاب ، فاذا كنت فى حيرة من اعمال النقل فتعاون مع شركة المتخصصة فى اعمال التخزين من الامور التى لابد من القيام بية بطريقة مميزة على ايدى متخصصين فى القيام بهذة الخدمة
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چاپ کارت ویزیت خانه طراحان سام نشانگر سلیقه، گرایشات، نظرات و دیدگاه های کاری یک شخص یا سازماناست. برای نیازهای فوری و تیراژهای زیر 1000، چاپ دیجیتال کارت ویزیت بهترین انتخاب است. چاپ دیجیتال کارت ویزیت به این صورت انجام می شود که ابتدا از فایل طراحی شده پرینت گرفته می شود و پس از آن از روکش های سلفون و لمینت برای پوشش روی کارت استفاده می شود .
در چاپ دیجیتال پارچه که به سابلیمیشن (sublimation)معروف است می توان بر روی انواع چاپ سابلیمیشن در ابعاد کوچک و بزرگ طرح ها و تصاویر مورد نظر را چاپ کرد.
در چاپ دیجیتال ، چاپ کاغذ دیواری براساس خواست مشتری درطرح, رنگ و اندازه دلخواه پذیرفته می شود و بر روی متریال خام کاغذ دیواری چاپ می گردد.
چاپ کاتالوگ خانه طراحان سام ابزار مهمی در معرفی و اطلاع رسانی در حوزه های تولید و خدمات است. کاتالوگ ها قبلا شبیه به تراکت و محدود به یک برگه پشت و رو با جلدی همانند پوستر بودند، اما امروزه کاتالوگ ها دارای صفحات و تنوع بیشتر در شکل و طرح هستند و انواع صحافی بر روی آنها اجرا می شود.
چاپ تراکت خانه طراحان سام برگه ای تبلیغاتی است که به طور معمول در سایز A5 ، برای معرفی محصول، شرح فعالیت ها وخدمات و اطلاع رسانی درباره رویدادی معین، چاپ می شود.
چاپ بروشور خانه طراحان سام (Brochure) دفترچه یا برگه ایست (معمولا به صورت تا شده از چند جا بر روی خود) برای ارائه توضیحات کاملی درباره یک محصول و نحوه استفاده از آن و بر این اساس به آن کالانما هم گفته می شود . یک کاربر پس از خواندن بروشور محصول، می تواند از آن محصول استفاده کند.
چاپ پوستر وسیله ای برای اعلان خبر در مورد رویدادها و موضوعات مختلف است که عموما به صورت عمودی طراحی شده و به نمایش در می آید. ابعاد طراحی پوستر باید مناسب برای مشاهده از فاصله نزدیک باشد. پوستر های قطع A3برای گردهمایی ها، همایش ها ، اجراهای تئاتر، انواع نمایشگاهها، روی داد های علمی و هنری، ارائه های دانشجویی و... به کار می رود.
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