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COCONUT OIL & ALZHEIMER’S DISEASE Ketones as Fuel for Neurons Dr. Mary Newport November COCONUT OIL & ALZHEIMER’S DISEASE Ketones as Fuel for Neurons Dr. Mary Newport November 2009 www. coconutketones. com

Steve Newport 2009 Steve Newport 2009

Steve Newport BSBA in Accounting from Xavier University, Cincinnati, Ohio Ø Worked for 9 Steve Newport BSBA in Accounting from Xavier University, Cincinnati, Ohio Ø Worked for 9 years as accountant/office manager for mental health centers until 1980 Ø 1980’s to 2003 - Worked from home for medical practice – accounting, management, billing, while caring for our children Ø Computer wiz Ø Loves landscaping, cooking, reading novels, kayaking Ø Can fix anything, invents tools Ø

Onset Of Alzheimer’s Disease Early clues (retrospective): Ø Grade School: l l Ø Early Onset Of Alzheimer’s Disease Early clues (retrospective): Ø Grade School: l l Ø Early adult: l l Ø Couldn’t remember rules of football “Fired” as altar boy – couldn’t remember flow of the service Couldn’t catch on to card games Did not feel he was functioning as well in accounting/ office manager position by late 20’s 30’s and 40’s l Hoarding – amasses garage full of “stuff”

Onset Of Alzheimer’s Disease Ø Age 50 -51: l l Ø Frequently forgets appointments Onset Of Alzheimer’s Disease Ø Age 50 -51: l l Ø Frequently forgets appointments even with 30 minute reminders Often loses wallet and keys Age 51 -52: l l l Payroll errors Procrastinates with tax reports Misses deadlines Can’t remember going to bank and post office Misplaces important mail Psychiatrist believes it is depression rather than dementia - starts anti-depressants and counseling

Mild to Moderate Alzheimer’s Disease Ø Age 56: l l l l Can no Mild to Moderate Alzheimer’s Disease Ø Age 56: l l l l Can no longer follow map – gets lost in New Port Richey Misses turn and ends up in Jacksonville Can’t remember how to turn on windshield wiper Confusion at tollbooth Gives up driving Stops reading – can’t explain why Often walks around house and yard with one shoe • No matching pairs of shoes in the house!

Moderate Alzheimer’s Disease Ø Age 57: l l l l l Doesn’t recognize some Moderate Alzheimer’s Disease Ø Age 57: l l l l l Doesn’t recognize some relatives at family reunion – lost and confused Loses 10 pounds in 3 weeks – no longer preparing meals for himself Develops intention tremor and problem with keeping food on fork Develops jaw tremor when talking Gait becomes slow, can no longer run Forgets that he “sired” older daughter Personality and sense of humor fading Takes lawn tractor and vacuum cleaner apart difficulty spelling simple written words, such as “out” and “put, ” and trouble recalling many common words when speaking

Clinical Trials Ø Age 58 (May 2008): l Participates in ADRC annual evaluation and Clinical Trials Ø Age 58 (May 2008): l Participates in ADRC annual evaluation and screens for vaccine trial at Johnnie Byrd • MRI: “Diffuse involutional change of frontal and parietal lobes and moderate left-sided and severe right-sided amygdala and hippocampal atrophy with no ischemic change, which would support a clinical diagnosis of Alzheimer’s disease. ” • Scores only 12 of 30 on MMSE l Doesn’t qualify for study – told to try again in a couple of weeks

Clinical Trials Scheduled for screenings for 2 different clinical trials May 20 and 21, Clinical Trials Scheduled for screenings for 2 different clinical trials May 20 and 21, 2008 Ø Late night internet research “risks and benefits” Ø Learn about Accera product, Ketasyn, now called Axona – read patent application Ø l l Active ingredient is medium chain triglyceride oil – derived from coconut oil 47% in pilot study had significant improvement in memory (ADAS-COG, ) the rest declined minimally

Glucose as Energy Ø Glucose is the usual source of energy for neurons (brain Glucose as Energy Ø Glucose is the usual source of energy for neurons (brain cells).

Glucose as Energy Ø In certain diseases, neurons and/or other brain and nerve cells Glucose as Energy Ø In certain diseases, neurons and/or other brain and nerve cells have a problem with transporting glucose into the cell and essentially starve and die.

“Diabetes of the Brain” “Diabetes of the Brain”

PET SCANS FOR GLUCOSE UPTAKE NORMAL BRAIN ALZHEIMER’S BRAIN PET SCANS FOR GLUCOSE UPTAKE NORMAL BRAIN ALZHEIMER’S BRAIN

ALZHEIMER’S VS. NORMAL BRAIN ALZHEIMER’S VS. NORMAL BRAIN

Medium chain triglycerides converted in liver to Ketones Medium chain triglycerides converted in liver to Ketones

Ketone Bodies Ketone Bodies

Ketones: Metabolism’s Ugly Duckling Theodore B. Van. Itallie, M. D. , and Thomas H. Ketones: Metabolism’s Ugly Duckling Theodore B. Van. Itallie, M. D. , and Thomas H. Nufert, B. A. Nutrition Reviews , Vol. 61, No. 10

KETONES AS FUEL Ketones can be taken up by neurons that cannot use glucose KETONES AS FUEL Ketones can be taken up by neurons that cannot use glucose

KETONES CONVERT TO ENERGY IN NEURON + = KETONES CONVERT TO ENERGY IN NEURON + =

Neuron Can Function And Stay Alive Neuron Can Function And Stay Alive

Diagram from: Parkinson disease: primacy of age as a risk factor for mitochondrial dysfunction Diagram from: Parkinson disease: primacy of age as a risk factor for mitochondrial dysfunction Theodore B. Van. Itallie, Metabolism Clinical and Experimental 57 (Suppl 2) (2008) S 50–S 55

Normal neurons can use glucose or ketones but usually use glucose if available Normal neurons can use glucose or ketones but usually use glucose if available

For neurons that cannot use glucose, Ketones can serve as an “alternate fuel. ” For neurons that cannot use glucose, Ketones can serve as an “alternate fuel. ”

DAY BEFORE COCONUT OIL INTERVENTION Ø Steve screens for clinical trial in St. Pete DAY BEFORE COCONUT OIL INTERVENTION Ø Steve screens for clinical trial in St. Pete l l Scores only 14 of 30 on MMSE, needs 16 to qualify Doctor asks him to draw a clock – consistent with moderately severe Alzheimer’s We pick up coconut oil on the way home More internet research, learn about medium chain triglycerides, ketones

HOW MUCH? Coconut Oil is 60% MCT oil 4 teaspoons MCT Oil or 7 HOW MUCH? Coconut Oil is 60% MCT oil 4 teaspoons MCT Oil or 7 teaspoons Coconut oil provide same amount of medium chain triglycerides

1 st DAY OF COCONUT OIL INTERVENTION Ø Receives at least 35 grams coconut 1 st DAY OF COCONUT OIL INTERVENTION Ø Receives at least 35 grams coconut oil with breakfast Ø Screens at Johnnie Byrd Center for vaccine clinical trial l l Scores 18 of 30 on MMSE Qualifies for study

First Days after Coconut Oil Intervention Ø Begins daily consumption of coconut l oil First Days after Coconut Oil Intervention Ø Begins daily consumption of coconut l oil Measured dose at breakfast, cooking and other coconut containing foods for dinner Ø More alert - Personality and sense of humor resurface Ø Steve says the “light switch came back on” and the “fog lifted” Ø Facial tremor disappears Ø Intention tremor infrequent

14 Days After Starting Coconut Oil 14 Days After Starting Coconut Oil

37 Days After Starting Coconut Oil 37 Days After Starting Coconut Oil

Steve’s Clocks DAY BEFORE COCONUT OIL 14 DAYS ON COCONUT OIL 37 DAYS ON Steve’s Clocks DAY BEFORE COCONUT OIL 14 DAYS ON COCONUT OIL 37 DAYS ON COCONUT OIL

More Research Ø Ketones, medium chain triglycerides, fatty acids, coconut oil Ø Dr. Richard More Research Ø Ketones, medium chain triglycerides, fatty acids, coconut oil Ø Dr. Richard Veech/NIH – Ketone expert l l Ketone ester (beta-hydroxybutyrate) Suggested ketone levels

Ketone Ester Dr. Richard Veech – NIH-Rockville, MD Became interested in studying ketones in Ketone Ester Dr. Richard Veech – NIH-Rockville, MD Became interested in studying ketones in early 1990’s Ø Developed an ester of ketone body betahydroxybutyrate – oral or IV Ø Can achieve levels comparable to starvation – 10 x coconut oil or MCT oil levels Ø No adverse effects in recent human toxicity testing Ø Needs funding to mass produce for testing in AD and other diseases Ø

35 grams (7 teaspoons) coconut oil with breakfast and with dinner 35 grams (7 teaspoons) coconut oil with breakfast and with dinner

20 grams (4 teaspoons) medium chain triglyceride oil (C: 8) 20 grams (4 teaspoons) medium chain triglyceride oil (C: 8)

Expanded Coconut Oil Intake Ø As a result of levels with coconut oil also Expanded Coconut Oil Intake Ø As a result of levels with coconut oil also used measured amounts at lunch and dinner Ø Mixing coconut oil and MCT oil Ø Substituting foods with MCTs for others: l l Goat’s milk and cheese for cow’s milk and cheese Coconut milk for other liquids in cooking

Between 2 - 4 months after Intervention Visual disturbance resolves Normalization of gait – Between 2 - 4 months after Intervention Visual disturbance resolves Normalization of gait – able to run again Completes household and gardening tasks with minimal to no supervision and without distraction Ø Wears both shoes and keeps pairs together Ø His ability to initiate and continue a course of conversation improves Ø Recognizes family members that he couldn’t recall one year earlier Ø Family says he no longer looks lost, conversation makes sense Ø Ø Ø

Between 4 -10 Months After Intervention Conversational skills continue to improve Ø Reading comprehension Between 4 -10 Months After Intervention Conversational skills continue to improve Ø Reading comprehension improves Ø Short term and recent memory improves Ø Stops having episodes of near syncope Ø No longer depressed – Says, “I have my life back. ” Ø Wants to do more with his life - volunteers in hospital warehouse Ø Vacuums, cuts grass and weeds gardens again (instead of taking equipment apart!) Ø

Getting the Message Out Ø Family confirms Steve has improved Ø Article: “What If Getting the Message Out Ø Family confirms Steve has improved Ø Article: “What If There Was a Cure for Alzheimer’s Disease and No One Knew? ” July 2008 l l l Sent letters to high profile persons to investigate MCT oil studies and make public aware Chicago ICAD conference Grass roots method/internet St Petersburg Times article October 2008 Website: www. coconutketones. com Legislators March 2009

Diseases With Decreased Glucose Uptake into Brain/Nerve Cells l l l Alzheimer’s disease Parkinson’s Diseases With Decreased Glucose Uptake into Brain/Nerve Cells l l l Alzheimer’s disease Parkinson’s disease Multiple sclerosis Huntington’s chorea ALS/Lou Gehrig’s disease Duchenne muscular dystrophy l l Some forms of autism Down’s syndrome – develop Alzheimer’s disease by ages 30 -40 Acute brain injury, accompanied by lack of oxygen Type I and Type II diabetes

Other Reported Improvements Ø Parkinson’s disease Ø Multiple sclerosis Ø Improved blood sugars in Other Reported Improvements Ø Parkinson’s disease Ø Multiple sclerosis Ø Improved blood sugars in type II diabetes Ø Down’s syndrome Ø Bipolar disorder Ø Glaucoma Ø Macular degeneration Ø Cognition in elderly dog

Foods with Short and Medium Chain Fatty Acids Ø Fats/Oils: l l l l Foods with Short and Medium Chain Fatty Acids Ø Fats/Oils: l l l l Coconut oil Palm Kernel Oil Babassu Oil Ucuhuba butter Butter Nutmeg Butter Sheanut Oil 59% 54% 55% (Amazon palm) 13% (Amazon tree seed) 11. 5% 3. 1% 1. 7%

Foods with Short and Medium Chain Fatty Acids Ø Per 8 ounces: l l Foods with Short and Medium Chain Fatty Acids Ø Per 8 ounces: l l l Goat Milk Whole Cow Milk Human breast milk Infant formula Cottage Cheese 1. 7 grams 0. 9 grams 0. 78 grams 1. 0 grams 0. 64 grams

Foods with Short and Medium Chain Fatty Acids Ø Per ounce: l l l Foods with Short and Medium Chain Fatty Acids Ø Per ounce: l l l Goat cheese Feta cheese Cream cheese American cheese Mozarella 2. 0 grams 1. 4 grams 0. 96 grams 0. 85 grams 0. 78 grams

Newborns and Ketones Ø Newborn develops “ketosis” at onset of breastfeeding Ø Ketones provide Newborns and Ketones Ø Newborn develops “ketosis” at onset of breastfeeding Ø Ketones provide 25% of energy requirements during first weeks of life Ø Even with equivalent amount MCTs in formula, same degree of “ketosis” doesn’t occur – missing factor?

Newborn MCFAs Equivalent in Adult Ø 10 pound breastfeeding baby gets about 3. 12 Newborn MCFAs Equivalent in Adult Ø 10 pound breastfeeding baby gets about 3. 12 grams MCFAs per quart breast milk = Ø 47 grams MCFAs for 150 pound adult = Ø 5. 5 tablespoons of coconut oil

Coconut Oil Equivalents Ø Coconut oil - 1 tablespoon = l l Coconut Milk Coconut Oil Equivalents Ø Coconut oil - 1 tablespoon = l l Coconut Milk (undiluted) – 4 ½ tablespoons Coconut meat – 2” x ½” piece Coconut grated – 1/3 cup Coconut oil capsules (1 gm) – 14 capsules

Use only NON-HYDROGENATED Coconut Oil Use only NON-HYDROGENATED Coconut Oil

START SLOW Ø Common effect – Diarrhea l Begin with 1 teaspoon and increase START SLOW Ø Common effect – Diarrhea l Begin with 1 teaspoon and increase slowly l Start on a day when you don’t have to go somewhere immediately! l Take with other food l Can take it slowly during meal over 20 -30 minutes l Some foods may help retain oil – cottage cheese l Try grated coconut or coconut milk as alternative for part of “dose”

Food Ideas Use coconut oil instead of butter on toast, English muffins, bagels, grits, Food Ideas Use coconut oil instead of butter on toast, English muffins, bagels, grits, corn on the cob, potatoes or sweet potatoes. Ø Add coconut oil or coconut milk to your favorite smoothie recipe. Ø Mix coconut oil into: Ø l l Oatmeal or other hot cereal. Rice, vegetables, noodles, pasta. Half and half with salad dressings. Soup, chili or spaghetti sauce.

Food Ideas Ø Use a measured amount of coconut oil to stir fry or Food Ideas Ø Use a measured amount of coconut oil to stir fry or sauté any of your favorite dishes. Ø Purchase or make coconut macaroons made from all natural products. Ø Make Coconut oil “fudge” Ø Eat a 2” x 2” square of raw coconut for a snack to provide 15 grams of oil. Ø Add flaked or grated coconut to hot or cold cereal, yogurt, fruit or vegetable salads

Mixing MCT and Coconut Oil Ø Reason: to achieve higher and continuous levels of Mixing MCT and Coconut Oil Ø Reason: to achieve higher and continuous levels of ketones Ø One combination: l l MCT Oil 16 ounces + Coconut oil 12 ounces Can emulsify with soy lethicin (about ½ teaspoon) Start low and increase as tolerated Take with each meal

Mixing MCT and Coconut Oil Ø Advantages: l l Stays liquid when mixed Mixes Mixing MCT and Coconut Oil Ø Advantages: l l Stays liquid when mixed Mixes more easily into many foods Takes advantage of properties of each oil More portable for eating away from home

Do Eat Foods with Omega-3 Fatty Acids Do Eat Foods with Omega-3 Fatty Acids

Eat Whole Foods Eat Whole Foods

Don’t Eat Foods with Transfats and Hydrogenated or Partially Hydrogenated Oils Don’t Eat Foods with Transfats and Hydrogenated or Partially Hydrogenated Oils

Why not use just MCT oil? Ø Many other fatty acids of all chain Why not use just MCT oil? Ø Many other fatty acids of all chain lengths in coconut oil that may serve special purpose: l l Supports thyroid Anti-microbial properties – kills certain viruses and bacteria that some research implicates in Alzheimer’s and Parkinson’s • Herpes viruses • Helicobacter pylori l May be other factors in the “whole” oil that benefit Alzheimer’s and other diseases

Why not use just Coconut Oil? Ø Ketone levels higher with MCT oil Ø Why not use just Coconut Oil? Ø Ketone levels higher with MCT oil Ø Recent evidence that medium chains cross blood brain barrier and appear to also be used by neurons as fuel

Cholesterol Issue Ø Proponents of each side of issue can find studies to support Cholesterol Issue Ø Proponents of each side of issue can find studies to support their beliefs Ø Large scale study with men and women of all ages needs be done to lay the issue to rest Ø Consider risks vs. benefits in making decision to try this intervention in Alzheimer’s and other diseases

Expectations Ø Most people will not have immediate or dramatic response and some “stabilize” Expectations Ø Most people will not have immediate or dramatic response and some “stabilize” l Keep a journal Ø Must be consistent and persistent Ø Cannot miss a day l If no fuel in the tank the car won’t run Ø Strongly suggest at least three month trial l l Monitor closely if stopping this intervention Some don’t realize how much it was helping until they stop it

Is there a relationship between lack of MCFAs AND AUTISM? Ø A Mother’s Observation: Is there a relationship between lack of MCFAs AND AUTISM? Ø A Mother’s Observation: Child developed neurologic symptoms of autism after discontinuing infant formula at 18 months l l l Lack of MCFAs the culprit? Do MCFAs delay onset of neuro symptoms? Onset of autism often during second year Ø Parental Survey: l Most autistic children not breastfed

www. coconutketones. com Ø Website for information only l l l l Copies of www. coconutketones. com Ø Website for information only l l l l Copies of article, “What If…? Diet guidelines and FAQs Complete articles - scientific references related to ketones that can be printed out Interviews Can email me with questions Updates Blog

Drs. George Cahill, Mary Newport & Richard Veech in Capitol Building – March 2009 Drs. George Cahill, Mary Newport & Richard Veech in Capitol Building – March 2009

KETOGENIC DIET Ø History l l l Fasting used as treatment for seizures and KETOGENIC DIET Ø History l l l Fasting used as treatment for seizures and epilepsy in biblical times and middle ages Early 1900’s - NY Pediatrician Rawle Geyelin successfully fasted children to control seizures (15 day fast) – 18% were helped 1921 – Wilder proposed that benefits of fasting (increase in ketone bodies) could be produced by diet rich in fats and low in carbohydrates - - “ketogenic diet”

KETOGENIC DIET Ø History (continued): l 1924 – Peterman reports effectiveness of diet from KETOGENIC DIET Ø History (continued): l 1924 – Peterman reports effectiveness of diet from Mayo Clinic – 51% seizure free after 2 ½ years on diet • • l 1 gram protein per kg body weight 10 -15 grams/day carbohydrate Remainder of calories as fat Total calories Basal Metabolic Rate + 50% Identical to ketogenic diet used today – some variations exist – including MCT oil version – half of calories are MCT oil

KETOGENIC DIET Ø Reported positive effects of ketogenic diet: l l l l Epilepsy KETOGENIC DIET Ø Reported positive effects of ketogenic diet: l l l l Epilepsy Alzheimer’s disease Parkinson’s disease Lou Gehrig’s disease (ALS) Traumatic brain injury and stroke Oxygen toxicity Glioblastoma and other cancerous tumors Weight loss

Brain Metabolism during Fasting 0. E. OWEN, A. P. MORGAN, H. G. KEMP, J. Brain Metabolism during Fasting 0. E. OWEN, A. P. MORGAN, H. G. KEMP, J. M. SULLIVAN, M. G. HERRERA, AND G. F. CAHILL, JR. The Journal of Clinical Investigation Vol. 46, No. 10, 1967 First report of ability of brain to use ketones as fuel

Overnight in normal people: glucose 100% of fuel Starvation: Ketones about 2/3 of fuel Overnight in normal people: glucose 100% of fuel Starvation: Ketones about 2/3 of fuel Diagram from: Ketone Bodies as a Fuel for the Brain during Starvation - Oliver E. Owen‡ BIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION Vol. 33, No. 4, pp. 246– 251, 2005

FIG. 3. Concentrations of ketone bodies and free fatty acids during starvation in humans. FIG. 3. Concentrations of ketone bodies and free fatty acids during starvation in humans. Values are shown as the means S. E. Ketone bodies undergo the greatest changes of all fuels during total starvation. Diagram from: Ketone Bodies as a Fuel for the Brain during Starvation Oliver E. Owen‡ BIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION Printed in U. S. A. Vol. 33, No. 4, pp. 246– 251, 2005

Ketone Effects Ø Presence of ketone in circulation, even at low levels increases cerebral Ketone Effects Ø Presence of ketone in circulation, even at low levels increases cerebral blood flow by as much as 40% Ø Ketones used within mitochondria to drive the chain reaction that produces ATP Ø Reduces generation of free radicals and at same time increases the scavengers of free radicals linked to the NADP system, such as glutathione. Ø Activates anti-inflammatory mechanisms

Ketone Effects l l l Presence of ketone in circulation, even at low levels Ketone Effects l l l Presence of ketone in circulation, even at low levels increases cerebral blood flow by as much as 40% Rectify cerebral energy metabolism (provide alternative fuel) Protect cerebral function Suppress cerebral edema and reduce extent of cerebral infarction in brain injury Treat diseases involving free radical damage such as occurs in coronary reperfusion, diabetic angiopathy, inflammatory bowel disease, pancreatitis

Ketone Effects Ø “Utilizing the nerve growth/ stimulatory effects of the ketone bodies…cells that Ketone Effects Ø “Utilizing the nerve growth/ stimulatory effects of the ketone bodies…cells that are still viable can be caused to improve beyond the state to which they have degenerated and accordingly some improvement of function will be seen in patients. ” l Veech has shown in mice receiving 30% ketone ester diet, significant increase in brain peptides BDNF and NGF, compared to high CHO or high fat diet.

Potential Effects of Ketones l l Would allow diabetics to maintain better control of Potential Effects of Ketones l l Would allow diabetics to maintain better control of blood sugars without fear of hypoglycemic consequences and thereby prevent the vascular changes in eye and kidney May treat refractory epilepsy and other seizure related disorders currently treatable with ketogenic diet

D, L-3 -hydroxybutyrate treatment of multiple acyl-Co. A dehydrogenase deficiency (MADD, ) Johan L D, L-3 -hydroxybutyrate treatment of multiple acyl-Co. A dehydrogenase deficiency (MADD, ) Johan L K Van Hove, et. al. , Lancet 2003; 361: 1433– 35 After a 150 mg/kg dose of D, L-3 hydroxybutyrate, plasma physiological ketone body concentrations peaked between 0· 19 mmol/L and 0· 36 mmol/L after 30 min to 1 h, and remained above pretreatment concentrations for 4 h. Brain MRI scans were obtained before (A and D), after 2 months (B and E), and after 9 months of treatment (C and F). There is diffuse involvement of the supratentorial white matter both centrally and peripherally and in the corpus callosum (A, D). On the posttreatment scans there is a progressive change in the central white matter with a decrease in signal intensity. Cavitation can occasionally be seen (F)

CELL BASICS – SIMPLE DIAGRAM CELL BASICS – SIMPLE DIAGRAM

CELL CELL

CELL MEMBRANE Ø Electron micrograph of cell membrane CELL MEMBRANE Ø Electron micrograph of cell membrane

CELL MEMBRANE CELL MEMBRANE

FATTY ACIDS FATTY ACIDS

FATTY ACIDS Hydrogenation produces abnormally shaped molecules called transfats FATTY ACIDS Hydrogenation produces abnormally shaped molecules called transfats

FUEL ANALOGY Different vehicles use different fuels FUEL ANALOGY Different vehicles use different fuels

NEURONS NEURONS

NEUROTRANSMITTERS NEUROTRANSMITTERS