Healthy Living, Healthy Mind: Ketones

The Aging Brain, Brain Health and Ketones

Mary T. Newport MD Key Biscayne Community Foundation January 24, 2018

Steve and Mary Newport December 2008

Accountant - Worked at home Physician – Neonatologist to care for our children Care of sick and premature newborns

Demen?a and Alzheimer’s Disease • Worldwide 46.5 million have demen?a now, expected to increase to 131.5 million by 2050: * – – – –

22.9 million people in Asia (includes Australia and New Zealand) 9.5 million in the Americas (5.2 million in the USA) 10.4 million in Europe 4 million in Africa

• In high-income countries only 20-50% of people with demen?a are recognized and documented in primary care.

• When someone has Alzheimer’s three other family members are affected on average.

• Caregivers oRen must give up their job to care for person with demen?a. Huge financial burden for family. hVps://www.alz.co.uk/research/WorldAlzheimerReport2015.pdf * Reported at Alzheimer’s Associa?on Interna?onal Conference, Boston 2013 **

ALZHEIMER’S DISEASE • 60-70% of demen?a pa?ents have Alzheimer’s.

• Exact cause or causes are unknown • No medica?on effec?vely treats other than slowing course of disease for 6 months in half who take them.

• If treatment could delay Alzheimer’s onset by five years, would reduce number of people affected by half!

– MCT Oil could be a treatment to prevent Alzheimer’s.

Early Symptoms of Alzheimer’s Stage 1: Preclinical – No symptoms yet. Disease begins 10 or 20 years before symptoms occur. Opportunity to prevent or delay disease.

Stage 2: The person is aware of memory lapses, but others don’t no?ce yet and tests are normal.

Stage 3: Signs of disease become more no?ceable to others and tes?ng is no longer normal.

• Problems may include: • • • • •

Losing or misplacing valuable objects.

Trouble finding the right word or name.

Trouble with planning or organizing.

Trouble retaining new informa?on.

Difficulty carrying out long-?me tasks.

Sleep Apnea and Demen?a • Sleep apnea is one of the known treatable causes of demen?a.

• Evalua?on with sleep study for people with suspected sleep apnea is recommended.

• Treatment with CPAP or oral device to keep airway open could help prevent demen?a.

• In some people, weight loss could help reduce or eliminate sleep apnea.

•

High Blood Pressure and Demen?a Demen?a, especially vascular demen?a, has many of

same risk factors as heart disease and stroke.

• Controlling blood pressure and inflamma?on in blood vessels could reduce risk of demen?a.

• News from Alzheimer Associa?on Interna?onal Conference 2017: Mediterranean plus DASH diets to control BP may help prevent or slow down demen?a.

• Foods that may help lower blood pressure:

• Foods low in sodium and rich in potassium, calcium or magnesium, dairy foods, flaxseed, dark chocolate or cocoa, olive oil, beets, pistachios, pomegranate.

• Medita?on can reduce blood pressure, reduce stress and increase blood flow to the brain.

Diabetes and Demen?a •

More than 100 million adults in USA have diabetes or prediabetes hVps://www.cdc.gov/media/releases/2017/ p0718-diabetes-report.html

•

¾ of people over 75 have diabetes or prediabetes

•

Diabetes is a major risk factor for demen?a – about 1/3 of diabe?cs will develop demen?a.

•

Rates of diabetes increase as sugar consump?on increases in a community.

•

Reducing sugar intake (including added sugar) could decrease rates of diabetes and demen?a.

Guyenet, S. By 2606 the US diet will be 100% sugar. Whole Health Source: Nutri1on and Health Science www.wholehealthsource.blogspot.com February 18, 2012

Alzheimer’s - Plaques and Tangles in Brain Billions $$ in research, but medica?ons that remove plaques have failed to improve memory in clinical trials.

Alzheimer’s is Type 3 Diabetes –

Problem with geYng glucose into brain Glucose!

X Type 3 Diabetes = • Insulin resistance • Insulin deficiency De la Monte SM, JR Wands. “Review of insulin and insulin-like growth factor expression, signaling, and malfunc?on in the central nervous system: Relevance to Alzheimer’s disease.” Journal of Alzheimer’s Disease Vol. 7 (2005): 45-61

Alzheimer’s is “Type 3 Diabetes” Abnormal glucose uptake may be present ten or twenty years before symptoms appear.

Study of people in their twen?es at risk for Alzheimer’s already had decreased glucose uptake in the brain.

Reiman EM, K Chena, GE Alexander, et al. Func?onal brain abnormali?es in young adults at gene?c risk for late-onset Alzheimer’s demen?a. PNAS Vol. 101 No. 1 (2004):284–289

Scan in Alzheimer’s brain shows decreased glucose uptake (blue areas)

NORMAL BRAIN

ALZHEIMER’S BRAIN

Alterna?ve Fuels in Starva?on • Glucose is the predominant fuel for most cells, including brain on typical higher carbohydrate (sugar) diet.

• During starva?on humans easily switch over to use alterna?ve fuels aRer glucose stores used up – Amino acids and lactate (Gluconeogenesis) “Brain Metabolism during Fas?ng ,” OE Owen, AP – FaVy acids

– Ketones

Morgan, HG Kemp, JM Sullivan, MG Herrera, GF Cahill, Jr, The Journal of Clinical Inves1ga1on, Vol. 46, No. 10, 1967

Alterna?ve Fuels in Starva?on

FATTY ACIDS

Alterna?ve Fuels in Starva?on

KETONES

Metabolic Flexibility Glucose!

Ketones!

Normal Diet!

(High Carb)!

Fasting!

MCTs!

!

Brain cells can burn " glucose or ketones for energy"

Could ketones bypass fundamental problem of geYng glucose into the brain by providing alterna?ve fuel in Alzheimer’s disease?

Ketones Protect Neurons In 2000, Dr. Richard Veech of the NIH in USA reported that ketones could protect brain cells from toxins that cause Alzheimer’s and Parkinson’s disease.

Kashiwaya Y, T Takeshima, N Mori, K Nakashima, K Clarke, and RL Veech, “D-b-Hydroxybutyrate protects neurons in models of Alzheimer’s and Parkinson’s disease,” PNAS May 9, 2000, 97(10): 5440-5444

Ketones use normal in mild Alzheimer’s brain

Stephen Cunnane, PhD and associates reported in people with mild Alzheimer’s: • Ketone uptake is normal throughout the brain, including the areas affected by Alzheimer’s – supports idea of ketones as alterna?ve fuel for the brain.

Cunnane SC, A Courschesne-Loyer, V St-Pierre, et al. Can ketones compensate for deteriora?ng brain glucose uptake during aging? Implica?ons for the risk and treatment of Alzheimer’s disease. Ann NY Acad Sci (2016).

TCA CYCLE

Could ketones from MCT Oil provide alterna?ve fuel for the brain in Alzheimer’s disease?

• By May 2008 - 58 years old • Former accountant: can’t use computer , calculator , or do simple math.

• Unable to read for 1 ½ years • Problems with spelling, finishing sentences.

• Doesn’t recognize many relatives.

• Walks slowly and cannot run.

Steve Newport Early Onset Alzheimer’s disease

First symptoms 2001

• Jaw and hand tremors.

• Easily distracted, takes things apart.

• Depressed and personality fading.

Internet search for risks and beneďŹ ts of two clinical trial drugs yielded unexpected result:

PRESS RELEASE New medical food improves memory and cogni?on in nearly half of Alzheimer’s pa?ents!

Found patent applica?on for AC-1202

AC-1202 -- MCT Oil for Alzheimer’s Samuel Henderson, Ph.D. filed patent applica?on in 2000 for medical food with MCT oil to treat Alzheimer’s disease:

Brilliant Insight: Could ketones from MCT oil improve memory and cogni?on in people with Alzheimer’s disease?

Reger MA, ST Henderson, et. al.“Effects of b-Hydroxybutyrate on cogni?on in memory-impaired adults,”, Neurobiology of Aging, 2004,Vol. 25, 311-314.

Constan?ni, et al. “Study of the ketogenic agent AC-1202 in mild to Moderate Alzheimer's disease: a randomized, double-blind, placebo-controlled, mul?center trial,” Nutr and Metab 2009 6(31): 1-25.

Medium chain triglycerides are converted to ketones in liver

*SS Bergen, Jr., Hashim SA, VanItallie TB “Hyperketonemia induced in man by medium-chain triglyceride,� Diabetes Vol. 15 No. 10 (1966): 723-725

Infant Formula

• MCTs (C8 and C10) are 3 to 5% of fats in human breast milk • Breasged newborn is in ketosis

• MCT oil added to feedings of very premature newborns in late 1970’s to early 1980’s

• Added to premature and some term infant formulas

MCT OIL COMES FROM PALM KERNEL OIL OR COCONUT OIL

Olive Oil

Canola Oil

Most margarine

No Medium Chain FaVy Acids

Peanut Oil Corn Oil

Fish and Cod Liver Oil

Soy Bean Oil

May 20, 2008

Steve screened for clinical trial

Scored only 14 of 30 on MMSE, needed 16 to qualify for study

Clock test– consistent with moderately severe Alzheimer’s

May 21, 2008:

Steve had 35 grams (35 ml)coconut oil in oatmeal for breakfast • Scored 18 of 30 on MMSE four hours later • Qualified for study!!

1 Day Before Starting Coconut Oil

14 Days ARer Star?ng Coconut Oil

37 Days After Starting Coconut Oil

Steve’s Improvements

DAY BEFORE COCONUT OIL

14 DAYS ON COCONUT OIL

• More anima?on in face • Personality and sense of humor returned • Recognized family members • No longer looked “lost” • Facial tremor resolved • Inten?on tremor occasional

37 DAYS ON COCONUT OIL

• Gait normalized and could run • Visual disturbance resolved and was able to read again • Resumed yard and house work • Ini?ated conversa?on and made sense

= 1 Teaspoon MCT (C8 & C10)= 7 Teaspoons Coconut Oil

Steve’s Regimen • Mixed MCT and Coconut Oil in 4:3 ra?o – Added soy lethicin to emulsify

• Increased gradually to limits of tolerance over several months.

• Ul?mately received 30 to 45 ml three ?mes a day with meals and 30 ml at bed?me • Ra?onale:

– Maximize the intake of the more ketogenic medium chain faVy acids, and provide lauric acid (50% of coconut oil) for an?microbial ac?vity, and other poten?al unknown benefits – Provide MCT for higher ketone levels, coconut oil for longer dura?on of mild ketogenic effect

• Reduced sugar and starches in his diet and ate healthy whole food diet.

MMSE tes?ng ďŹ rst 65 days

Nearly one year aker star?ng coconut/MCT oil: ADAS-Cog improved by 6 out of 75 points

Ac?vi?es of Daily Living score improved by 14 out of 78 points

Two years aker star?ng coconut/MCT oil:

MRI report No more shrinkage of brain between 2008 and 2010.

Steve’s Case Study Published in 2015

• Steve’s drama?c improvement with medium chain triglycerides from 2008 to 2010.

• Steve’s remarkable improvement in func?oning while taking beta-hydroxybutyrate ketone ester over a twenty month period beginning in mid-2010.

Doctor says an oil lessened Alzheimer's effects on her husband

Gezng the message out – 2008 to present

ARer two weeks of taking coconut oil, Steve Newport's results in an early onset Alzheimer's test gradually improved says his wife, Dr. Mary Newport. Before treatment, Steve could barely remember how to draw a clock. Two weeks aRer adding coconut oil to his diet, his drawing improved. ARer 37 days, Steve's drawing gained even more clarity. The oil seemed to "liR the fog," his wife says.

By Eve Hosley-Moore, Times Correspondent In print: Wednesday, October 29, 2008

The only thing that kept Dr. Mary Newport posi?ve in the face of her husband's early onset Alzheimer's disease was that he didn't seem aware of how much ground he was losing.

Reports From Other Caregivers Percent 100 90 80

91

RESPONSES OF PERSONS WITH DEMENTIA AND OTHER MEMORY IMPAIRMENT TO MEDIUM CHAIN TRIGLYCERIDES N = 184 Mary T. Newport MD - September 2012

70

59

60 50

42

40

35 24

30

21

20 10 0

6

3

4

7

3

1

Improvements were generally categorized as follows according to the wording used in reports by the caregivers: IMPROVED MEMORY/ COGNITION

IMPROVED SOCIAL INTERACTION, BEHAVIOR, MOOD

IMPROVED SPEECH,CONVERSATION

Higher scores on memory or cogni?ve test More interac?on with others Speaking again

RESUMPTION OF LOST ACTIVITIES

IMPROVED PHYSICAL SYMPTOMS

Showering again without help Less tremor

BeVer sense of direc?on Feels beVer Improved reading comprehension

More awareness of ?me and place

Able to do mental math again

IMPROVED SLEEP IMPROVED APPETITE Fewer nightmares Improved appe?te Sleeping beVer

No longer sleeping excessively

No longer twitching during sleep

Expressing thoughts

Gezng out of bed without Performing self-care again help Doing things around the house Able to walk again Doing household chores again Walking without assistance Preparing meals again Improved strength Resumed a hobby More ambulatory Reading again More energy More func?onal Less s?ness

Improved balance

Less dizziness Fewer episodes of faintness, clamminess, swea?ng

Improved gait Fewer episodes of seizure/ twitching

IMPROVED VISION Visual disturbance gone Able to see more clearly

Pain relief

Improved clock drawing

BeVer sense of humor

Clearer speech

BeVer cogni?on

Less agita?on

Less repe??veness

More alert Brighter Improved awareness Less foggy Less hazy Recognizing people or places Less distrac?ble

Improved behavior Less hos?le Less aggressive Happy Improved mood Less anxiety Less depression

Making sense More logical Improved conversa?on More talka?ve Improved verbal skills BeVer word recall

From my emails • 83 year old lady with Alzheimer’s. Her daughter said, “ARer 2 days on MCT oil we already no?ced she is speaking more clearly, almost finishes sentences that make sense, her face and eyes look younger, her appe?te has improved, and she is walking around the house like she used to...without a walker."

From my emails 41 years old man with Mul?ple Sclerosis for twelve years reports: “ARer 4 months… I’ve no?ced like a thick cloud has been liRed off, as I can use my short term memoriza?on and I can use my mind to figure tasks in my head before I can physically perform them (do them). My mathema?cal formulas (numbers, math) can now be performed in my mind first.”

From my emails Lady with fibromyalgia and coli?s who did not tolerate coconut oil but reacted well to MCT oil reports: "Although I didn't expect it and was astonished, my body reacted immediately and very posi?vely to the MCT oil…

Within five minutes of the first dose, I seemed to awaken as from a kind of walking sleep. I have long had Fibromyalgia, and all of a sudden, I had the sensa?on of pain liRing from my arms, shoulders, legs, neck, head....

In the same way, my mind and senses also awakened within moments of the first dose.... My body loves this MCT oil!! I have no more of the chronic brain fog that has plagued me for the last several years. I have so much more energy.... aRer only one week, I know I am gaining physical strength and, surprisingly, coordina?on... I am sleeping through the night."

Another Published Single-Case Report • 70 year old male with probable AD • Caprylic triglyceride (MCT C:8) increased over several days to 20 grams daily – total 109 days • MoCA score increased from 24 to 28/30 (now normal) • MMSE score increased from 23 to 28/30 (now normal).

• FDG-PET stable.

Farah BA. Effects of caprylic triglyceride on cogni?ve performance and cerebral glucose metabolism in mild Alzheimer’s disease: a single-case observa?on. Fron1ers in Aging Neuroscience Vol. 6 Ar?cle 133 July 2014: 1-5

Engineer from Taiwan Before MCTs

ARer MCTs

Lady from Care Home in Taiwan Before MCTs

ARer MCTs

Moun?ng Evidence • 80% of 55 people with AD taking medical food Axona (MCT oil) were stable or improved over 15 months in memory tes?ng and ac?vi?es of daily living as reported by caregivers.

Maynard SD and J Gelblum. Retrospec?ve cohort study of the efficacy of caprylic triglyceride in pa?ents with mild-to-moderate Alzheimer’s disease. Neuropsychiatric Disease and Treatment Vol. 9 (2013):1619–1627.

Other Reports – MCT Studies

Abe S, E Osamu, M Suzuki. Medium-chain triglycerides in combina?on with leucine and vitamin D benefit Cogni?on in frail elderly adults: A randomized controlled trial. J Nutr Sci Vitaminol Vol. 63 (2017): 133-140.

Farah BA. Effects of caprylic triglyceride on cogni?ve performance and cerebral glucose metabolism in mild Alzheimer’s disease: a single-case observa?on. Fron1ers in Aging Neuroscience Vol. 6 Ar?cle 133 July 2014: 1-5.

Maynard SD and J Gelblum. Retrospec?ve cohort study of the efficacy of caprylic triglyceride in pa?ents with mild-to-moderate Alzheimer’s disease. Neuropsychiatric Disease and Treatment Vol. 9 (2013):1619–1627.

Maynard SD and J Gelblum. Retrospec?ve case studies of the efficacy of caprylic triglyceride in mild-to-moderate Alzheimer’s disease. Neuropsychiatric Disease and Treatment Vol. 9 (2013): 1629–1635.

Ota M, J Matsuo, I Ishida, et al. Effect of a ketogenic meal on cogni?ve func?on in elderly adults: poten?al for cogni?ve enhancement. Psychopharmacology (Berl) Vol. 233 No. 21-22 (2016): 3797-3802.

Page KA, A Williamson, N Yu, et al. "Medium-chain faVy acids improve cogni?ve func?on in intensively treated type 1 diabe?c pa?ents and support in vitro synap?c transmission during acute hypoglycemia." Diabetes Vol. 58, No 5 (May 2009):1237–1244.

Rebello CJ, JN Kellera , AG Liua , et al. Pilot feasibility and safety study examining the effect of medium chain triglyceride supplementa?on in subjects with mild cogni?ve impairment: A randomized controlled trial. BBA Clinical Vol. 3 (2015): 123–125

Other Doctors who Recommend Ketosis with Coconut and/or MCT Oil Dale Bredesen, MD – Bredesen Protocol • The End of Alzheimer’s David PerlmuVer, MD • Grain Brain and Brainmaker Richard Isaacson, MD and Christopher Ochner, PhD • The Alzheimer’s Diet Terry Wahls, MD – Wahls Protocol Plus • The Wahls Protocol Bruce Fife, NP • Stop Alzheimer’s Now

Could MCT Oil Prevent Alzheimer’s?

• People at risk for Alzheimer’s have a 10-12% energy deficit in the brain related to inadequate glucose uptake.

• MCT oil can result in a high enough ketone level to provide the brain with 5 to 12% of its energy needs.

Cunnane SC, A Courschesne-Loyer, V St-Pierre, et al. Can ketones compensate for deteriora?ng brain glucose uptake during aging? Implica?ons for the risk and treatment of Alzheimer’s disease. Ann NY Acad Sci (2016).

Using MCTs to close the ‘brain energy gap’ in Mild Cogni?ve Impairment – from Dr. Stephen Cunnane

What about diabe?c ketoacidosis?

STRATEGY FOR

RAISING KETONES:

KETONE LEVELS:

Coconut Oil* Exercise

Overnight Fast

0.3 - 0.5 mmol/l 0.3 - 0.5 mmol/l 0.3 - 0.5 mmol/l

MCT Oil (30-45 gm per day)* 0.5 - 1 mmol/l Starva?on

2-5 mmol/l Classic Ketogenic Diet

2-5 mmol/l Diabe?c Ketoacidosis

25 mmol/l

*Increases ketone levels without restric?ng carbohydrate in diet and will also lower blood glucose level.

Ketones Provide Alterna?ve Fuel to the Brain

Ketones are An?-Inflammatory

Ketones and MCTs suppress appe?te and help burn fat • MCT oil increases body temperature to help burn fat.

• Ketones suppress the making of fat and increase breakdown of fat.

• Insulin deposits fat on body and tends to keep it there.

Ketones reduce glucose and insulin levels which: • Allows fat to be burned as fuel • Most effec?ve with a low carb diet • Ketones affect appe?te hormones to control hunger.

• Ketones help preserve muscle during weight loss.

Recommenda?ons for adding Coconut and/ or MCT oil to diet • Begin slowly and increase slowly to avoid diarrhea or other intes?nal upset • Start with 2 to 5 grams with food 2 to 3 ?mes a day • If no intes?nal problem, increase by 2 to 5 grams per meal every few days to 30 to 60 grams or more per day, depending on tolerance and what your goals are, and divide into 3 or 4 servings.

• To lose weight or avoid weight gain, subs?tute MCT oil for other fats in the diet and reduce carbohydrate intake.

• Include marine source of omega-3 faVy acids for DHA.

Coconut Equivalents Coconut oil – 57-60% medium chain faVy acids = about 8.5 grams MCFAs per 15 ml (1 tablespoon)

The following coconut foods contain the equivalent of 1 tablespoon of coconut oil: • Coconut milk (undiluted): 4½ tablespoons • Coconut meat: 2-inch x 2-inch x ½-inch piece • Coconut grated: 1/3 cup • Coconut oil capsules (1 gram): 14 capsules

Other Supplements that Increase Ketones • Ketone Salts – Consult your doctor – Pruvit – Ketone betahydroxybutyrate plus sodium, potassium, calcium and magnesium – Powder that can be mixed in water – Informa?on about how to use them in elderly and people with any medical condi?ons and gezng help from your doctor at www.coconutketones.com

Other Supplements that Increase Ketones • Ketone Ester – Consult your doctor – Extremely expensive – Tastes like jet fuel – Two companies launching in early 2018 • Ketoneaid hVps://igg.me/at/Ketoneaid/x/17858219 • Human www.hvmn.com

– May be able to take much less than dose they recommend for elite athletes.

Coconut Oil Availability My local grocery store 2008.

My local grocery store 2018.

What do you have to lose?

www.coconutketones.com Look for “Diet Guidelines”, blog and informa?on about using ketone salts

Facebook: Coconut Oil Helps Alzheimer’s, Demen?a, ALS, MS, Parkinson’s.

Email: preemiedoctor@aol.com

In memory of Steve Newport 1950 to 2016