MEDIUM CHAIN TRIGLYCERIDES,
KETONE ESTERS, AND KETOGENIC DIETS
FOR ALZHEIMER’S
AND OTHER DISORDERS
Mary T. Newport MD
December 12-14, 2012
Fellowship in Anti-Aging, Regenerative and
Functional Medicine – Module 15
Alzheimer’s Facts and Figures
According to the Alzheimer’s Association*:
• 5.4 million people in the USA alone have Alzheimer’s (AD) and
•
•
•
•
•
predicted to be 15 million in USA by 2050, and100 million
worldwide
1 in 8 older Americans has AD
More than 200,000 under age 65 have “early onset” AD
Nearly half of people over age 85 have AD
While deaths from stroke, heart disease, and certain cancers
declined between 2000 and 2006, deaths from AD increased
by 47.1%
Cost of care to government and businesses estimated $200
billion and equivalent of $210 billion unpaid caregiving
*2012 Alzheimer’s Disease Facts and Figures Report
from Alzheimer’s Association
Plaques and Tangles
100 billion nerve cells.
100 trillion synapses. Dozens of neurotransmitters.
Brain tour from Alzheimer’s Association, alz.org.
Blennow K, MJ de Leon, H Zetterberg. “Alzheimer's disease.” The Lancet,
Vol. 368 No. 9533 (2006): 387 - 403
PNAS 2008 105 (9): 3171-3172
4 – 8 month old WT
18 month old WT
11.9 month old APP23
18 month old APP23
12 month old APP23
18 month old APP23
Beta Amyloid
PET Scan
• Alzheimer's disease on
the horizon? PET scans
revealed beta-amyloid
plaque in the brains of
three Alzheimer's disease
patients (left) and three
normal controls (right).
The yellow indicates high
uptake of a label that
targets beta-amyloid
plaque, and the red
indicates medium uptake.
Dan Krotz. “New Clue in the Search to Predict Alzheimer’s Disease.” Berkley
Lab News Center, December 16, 2008
Brain metabolism and Alzheimer’s
In 1970, Dr. Siegfried Hoyer reported decreased glucose
levels & lower cerebral metabolic rate in brains of some
people with dementia.
By 2004, proposed decreased brain metabolism results in
diminished production of acetyl CoA and ATP, required for
synaptic activity and plasticity.
Siegfried Hoyer. “Brain metabolism and the incidence of cerebral
perfusion disorders in organic psychoses.” Deutsche Zeitschrift für
Nervenheilkunde 1970 ,197 (4): 285-92
Hoyer S: Causes and consequences of disturbances of cerebral
glucose metabolism in sporadic Alzheimer disease:
therapeutic implications. Adv Exp Med Biol 2004, 541:135-152
Brain metabolism and Alzheimer’s
In 1991, Hoyer reported that:
• There is a shift in the types of fuel used by the brain in
people as they age that is even more prominent in people
with AD
• Young normal people use fuel in the cerebrum in ratio of
100:1 of glucose to alternative fuels
• Elderly persons without Alzheimer’s, this ratio is 29:1
• Early stages of Alzheimer’s this ratio is 2:1
• Suggested fuel for brain cells must come from alternative
fuels, such as fatty acids and amino acids
Hoyer S. “Abnormalities of glucose metabolism in Alzheimer’s
disease.”
Annals New York Academy of Sciences Vol. 640 (1991): 53-58
Alzheimer’s is “Type 3 Diabetes”
Explosion of research into the relationship between AD and brain
glucose metabolism in 1990’s and beyond.
In 2005, De la Monte and Wands looked at brains of persons
with advanced AD who did not have type 1 or 2 diabetes:
• Levels of insulin and factors related to making and using insulin are
greatly reduced.
• All of the signalling pathways involved in the use of energy are
abnormal.
• The functioning of mitochondria is abnormal.
• Coined term “type 3 diabetes” to describe insulin deficiency and
insulin resistance in AD brain
De la Monte SM, JR Wands. “Review of insulin and insulin-like growth factor
expression, signaling, and malfunction 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”
In 2008, de la Monte and Wands looked at various stages of AD
brains in persons without type 1 or 2 diabetes:
• Loss of insulin and neurons with insulin growth factor receptors
begins early in the disease.
• This worsens with each stage of the disease until it is very severe and
occurs throughout the brain in most severe cases of AD.
• Suggest that therapies for type 1 or 2 diabetes may be beneficial.
• Intranasal Insulin
• Metformin or other medications for type 2 diabetes
De la Monte SM, JR Wands. “Alzheimer’s disease is type 3 diabetes –
evidence reviewed.” Journal of Diabetes Science and Technology, Vol. 2 No.
6 (November 2008): 1101-1113
FDG-PET scans show
decreased glucose uptake
NORMAL BRAIN
ALZHEIMER’S BRAIN
Alternative Fuels for AD
• Glucose is the primary and preferred fuel for most cells,
including brain.
• Humans are programmed by evolution to switch to use of
alternative fuels during starvation when glucose stores
have been used up
• Amino acids (Gluconeogenesis)
• Fatty acids
• Ketones
• Lactate
• Supplying an alternative fuel could bypass problem of
insulin deficiency and insulin resistance in AD brain
O. E. OWEN, A. P. MORGAN, H. G. KEMP, J. M.
SULLIVAN, M. G. HERRERA, AND G. F. CAHILL, JR.
“Brain Metabolism during Fasting”
The Journal of Clinical Investigation
Vol. 46, No. 10, 1967
First report of ability of brain to use ketones as fuel
• Obese nurse given only water, vitamins, and salt tablets for a
period of forty-one days.
• Sampled blood from catheters in arteries and veins around her
brain and liver.
• Her brain survived this lengthy period of starvation by using
ketones and by greatly reducing the use of glucose.
• 2/3 of fuel used by her brain was provided by the ketone
bodies beta-hydroxybutyrate and acetoacetate
Overnight in normal
people: glucose 100%
of fuel
Starvation:
Ketones about 2/3
of fuel
Diagram from: Oliver E. Owen. “Ketone Bodies as a Fuel for the Brain during Starvation,”
Biochemistry And Molecular Biology Education Vol. 33, No. 4, 2005:246–251
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: Oliver E. Owen. “Ketone Bodies as a Fuel for the Brain during Starvation,”
Biochemistry And Molecular Biology Education Vol. 33, No. 4, 2005:246–251
3 obese college
students starved
until β-OH B levels
increased
Given insulin to
drive blood glucose
into hypoglycemic
range
Developed none of
usual symptoms of
hypoglycemia:
Brain is protected
from hypoglycemia
by ketone bodies.
Diagram from: Chapter 26 - Alternative Fuel Utilization by Brain, George F. Cahill,
Jr. & Thomas T. Aoki from Cerebral Metabolism and Neural Function (1980)
Ketone Bodies
Dietary maneuvers can produce ketosis:
• Starvation or fasting
• Ketogenic diet
• Medium chain fatty acids (MCFAs) absorbed directly
into portal vein and converted in liver to ketone bodies
• Ketone esters, 1,3-D-Butanediol
SS Bergen, Jr., Hashim SA, VanItallie TB “Hyperketonemia induced in man
by medium-chain triglyceride,” Diabetes Vol. 15 No. 10 (1966): 723-725
ATP
Adapted by Joanna Newport
KETOGENIC DIET
• Reported positive effects of ketogenic diet:
• Epilepsy
• Alzheimer’s disease
• Parkinson’s disease
• Lou Gehrig’s disease (ALS)
• Traumatic brain injury and stroke
• Oxygen toxicity
• Glioblastoma
• Weight loss
Ketones Protect Neurons
Dr. Richard L. Veech
• “Addition of 4 mmol D-b-hydroxybutyrate protected cultured
mesencephalic neurons from MPP1 toxicity [Parkinson’s
model] and hippocampal neurons from Ab1–42 toxicity
[Alzheimer model].”
• “Ability of ketone bodies to protect neurons in culture suggests
that defects in mitochondrial energy generation contribute to
the pathophysiology of both brain diseases.”
• “Ketone bodies may play a therapeutic role in these most
common forms of human neurodegeneration.”
Y Kashiwaya, 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
Ketone Ester
• Richard L. Veech, MD, D Phil, NIH, Rockville, MD, began
developing ketone body product in late 1990’s
• Filed first patent application to develop therapeutic ketone body
in 1998.
• After at least a dozen variations, successfully synthesizes an
ester of (R)-3-hydroxybutyrate for oral or IV administration
around 2006
• Can achieve levels equivalent to those that occur in
ketogenic diet and in starvation without toxicity
• Series of hypothesis papers proposing use for treatment of AD,
other neurodegenerative diseases and traumatic brain injury
• Parkinson’s study imminent
“Hypothesis Paper: Ketone Bodies, Potential Therapeutic Uses,”
RL Veech, B Chance, Y Kashiwaya, HA Lardy, and GF Cahill, Jr.,
IUBMB Life, 51: 241–247, 2001
AC-1202 -- MCT Oil for AD
Samuel Henderson, Ph.D. files first patent
application for use of MCT oil to treat Alzheimer’s
disease in 2000:
• Insight: Mild ketosis produced by conversion of
medium chain fatty acids to ketones in liver may be
adequate to produce cognitive improvement in insulin
resistant Alzheimer’s brain
Medium Chain Triglycerides
Converted to Ketones in Liver
Medium Chain FAs also alternative fuel?
• Medium chain fatty acids cross the blood brain barrier
• MCFA feeding of lab rodents is associated with a substantial
increase in mitochondrial oxidative capacity, which is sufficient
to prevent lipid accumulation in this tissue.
• MCFAs are oxidized in mitochondria of neurons and contribute
to production of ATP (personal communication Dr. Henri Brunengraber).
Turner N, K Hariharan, J TidAng, et al. “Enhancement of muscle mitochondrial
oxidative capacity and alterations in insulin action are lipid species dependent:
potent tissue-specific effects of medium-chain fatty acids.” Diabetes Vol 48
(2009): 2547–2554.
AC-1202 Phase 2a Study - 2004
• 20 persons with mild to moderate AD given single dose
tricaprylic acid (40 gm) vs. placebo on another occasion
• On average, in nine ApoE4- persons ADAS-Cog improved by
average of 6 points (of 75)and improved Paragraph Recall
scores 90 minutes after just one dose; ApoE4+ as group did
not improve; some individuals did improve.
• β OHB levels increased to about 0.5 mmol/L
Reger MA, ST Henderson, et. al.“Effects of b-Hydroxybutyrate on cognition in
memory-impaired adults,”, Neurobiology of Aging, 2004,Vol. 25, 311-314
AC-1202 Phase 2b Study 2008
• 152 patients with mild to moderate AD received AC-1202
(containing 20 g MCT) or placebo for 90 days in a double-blind,
randomized design
• Mean change from Baseline in ADAS-Cog score on Day 45:
1.9 point difference, p = 0.0235 in ITT; 2.53 point difference, p
= 0.0324 in per protocol; 2.6 point difference, p = 0.0215 in
dosage compliant
• ApoE4- patients taking AC-1202 differed from placebo by 5.73
points at Day 45 (p = 0.0027) and by 4.39 points at Day 90 and
even more significant in dosage compliant patients.
Samuel T Henderson*, Janet L Vogel, Linda J Barr, Fiona Garvin, Julie J Jones
and Lauren C Costantini. “Study of the ketogenic agent AC-1202 in mild to
Moderate Alzheimer's disease: a randomized, double-blind, placebo-controlled,
multicenter trial,” Nutrition and Metabolism 2009 6(31): 1-25
AC-1202 Phase 2 trials
• Similar results in Phase 2 trials in Age-Related Memory
Impairment and in Elderly Dogs
• Main adverse effect – diarrhea
• Approved by FDA as “medical food” and marketed as
prescription Axona in spring 2009
•May 2008 - 58 years old
•Former accountant: can’t use computer ,
calculator , do simple math
•Unable to read due to visual disturbance for
1 ½ years
•Problems with word finding and spelling
simple words
•Doesn’t recognize certain relatives
Steve
Early Onset
Alzheimer’s disease
First symptoms 2001
ApoE4+
•Slow gait, unable to run
•Jaw tremor and intention tremor
•Distractible, takes things apart
•Personality/sense of humor fading
12 DAYS BEFORE INTERVENTION
 May 9, 2008
 Steve screened for bapineuzimab clinical trial in Tampa,
Florida
 Met criteria, except scores 12 of 30 on MMSE (Study required
score of 16)
 Scheduled appointment for May 21, 2008 to try again
1 DAY BEFORE COCONUT OIL
INTERVENTION
• May 20, 2008
• Steve screens for Eli Lilly
clinical trial in St. Petersburg,
FL
• Scored only 14 of 30 on
MMSE, needed 16 to qualify
for study
• Clock test– consistent with
moderately severe
Alzheimer’s
1st DAY OF COCONUT OIL
INTERVENTION
• May 21, 2008 - Steve receives 35 grams coconut oil with
breakfast = 20 grams medium chain fatty acids (AC1202 dose)
• Screened at Byrd Center for bapineuzimab clinical trial:
• Scored 18 of 30 on MMSE
• Qualified for study
1 Day Before Starting Coconut Oil
14 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
COCONUT OIL
First Days after Coconut Oil Intervention
• Begins daily consumption of coconut oil
• Measured dose at breakfast, cooking and other coconut containing
foods for lunch and dinner
• More alert - Personality and sense of humor resurface
• Steve says the “light switch came back on” and the “fog
lifted”
• Facial tremor no longer apparent
• Intention tremor less apparent
Between 0 - 2 months
after Intervention
 Visual disturbance resolves
 Normalization of gait – able to run again
 Completes household and gardening tasks with
minimal to no supervision and with less
distraction
 His ability to initiate and continue a course of
conversation improves
 Recognizes family members that he couldn’t
recall one year earlier
 Family says he no longer looks lost, conversation
makes sense
[bHB]
Plasma ketones & glucose vs time
0.3
[Glucose]
6
0.25
5
0.2
4
0.15
3
0.1
2
dinner
0.05
1
0
0
0
2
4
6
8
time (hr after breakfast)
10
DAY 51 – Levels after 35 Grams Coconut Oil
with Breakfast and with Dinner
12
[Glucose] (mM)
Plasma [ketone] (mM)
[AcAc]
Plasma [bHB] & [AcAc] after C-8 breakfast
Plasma [bHB] & [AcAc] (mM)
1 bHB
0.45
1 AcAc
0.4
2 bHB
0.35
2 AcAc
0.3
0.25
0.2
0.15
0.1
0.05
0
0
0.5
1
1.5
2
2.5
3
time (hr)
DAY 64 - Levels after 20 Grams Medium Chain Triglyceride Oil (C:8)
ADAS-Cog and ADLs
• On placebo for first 12 to 14 months of semagacestat trial
• Cognitive testing nearly one year after starting MCFAs:
• ADAS-Cog improved by 6 points on a 75 point scale from July 23,
2008 to May 9, 2009. Patients on place
• Activities of Daily Living score improved by 14 points on a 78 point
scale during that same interval.
Stable MRI at 2 Years
• 2004: “Normal” MRI
• 2008: “Diffuse involutional change of the frontal and
parietal lobes and moderate left-sided and severe rightsided amygdala and hippocampal atrophy with no
ischemic change, which would support a clinical diagnosis
of Alzheimer’s Disease
• April 28, 2010 nearly two years after starting MCFAs:
• “Stable MRI brain in comparison to prior examination dated
6/16/2008.”
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
30
24
21
20
10
6
3
4
7
3
1
0
COMMENTS: The graph depicts responses of persons with dementias to oils containing medium chain triglycerides as reported by
their caregivers. Reports were sent to MTN by email or letter and were spontaneous reports, not prompted with regard to specifics of
response. Specifics of the responses were then categorized for purpose of this graph. Of the 184 individuals there were 84 males,99
females, 1 unknown; 125 of 184 reported age with range of 44 to 95 years old (average 72.5.) The positive response is presumably
due to metabolism of medium chain triglycerides to ketone bodies for use by neurons as an alternative fuel in cells with decreased
Improvements were generally categorized as follows according to the wording used in reports by the caregivers:
IMPROVED
MEMORY/COGNITION
IMPROVED SOCIAL
INTERACTION,
BEHAVIOR, MOOD
Higher scores on memory More interaction with
or cognitive test
others
IMPROVED
RESUMPTION OF
IMPROVED PHYSICAL
SPEECH,CONVERSATI LOST ACTIVITIES
SYMPTOMS
ON
Showering again without
Speaking again
help
Less tremor
Improved clock drawing
Better sense of humor
Clearer speech
Better cognition
Less agitation
Less repetitiveness
More alert
Brighter
Improved awareness
Less foggy
Less hazy
Recognizing people or
places
Less distractible
Improved behavior
Less hostile
Less aggressive
Happy
Improved mood
Making sense
More logical
Improved conversation
More talkative
Improved verbal skills
Less anxiety
Less depression
Better word recall
Better sense of direction Feels better
Improved reading
comprehension
More awareness of time
and place
Able to do mental math
again
IMPROVED SLEEP
IMPROVED APPETITE
Fewer nightmares
Improved appetite
Sleeping better
No longer sleeping
excessively
No longer twitching during
Expressing thoughts
Performing self-care
again
Doing things around the
house
Doing household chores
again
Preparing meals again
Resumed a hobby
Reading again
More functional
Getting out of bed without
help
Able to walk again
Walking without
assistance
Improved strength
More ambulatory
More energy
Less stiffness
Improved balance
Less dizziness
Fewer episodes of
faintness, clamminess,
sweating
Improved gait
Fewer episodes of
seizure/twitching
Pain relief
IMPROVED VISION
Visual disturbance gone
Able to see more clearly
Ketone esters are
in development at NIH
and University of South Florida
Coconut Oil/MCT Oil
Exercise
Starvation
Classic Ketogenic Diet
Ketone Esters*
Diabetic Ketoacidosis
KETONE LEVELS:
0.3 - 0.5 mmol/l
0.3 - 0.5 mmol/l
2-5 mmol/l
2-5 mmol/l
2-5 mmol/l**
25 mmol/l
**Beta-hydroxybutyrate ester had no adverse effects in
human toxicity testing. FDA: Generally Regarded as Safe.
Ketone Ester at NIH
In Alzheimer mouse model:
• Reduced plaque
• Reduced tangle
• Improved memory and learning
Kashiwaya Y, Bergman C, Lee J-H, et al. “A ketone ester diet exhibits anxiolytic
and cognition-sparing properties, and lessens amyloid and tau pathologies in a
mouse model of Alzheimer’s disease.” Neurobiology of Aging (Online 2012)
Ketone Effects
• Presence of ketone in circulation, even at low levels
increases cerebral blood flow by as much as 39%
• Ketones used within mitochondria to drive the chain
reaction that produces ATP
• Reduces generation of free radicals and at same time
increases the scavengers of free radicals linked to the
NADP system, such as glutathione.
• Activates anti-inflammatory mechanisms
Ketone Effects
• Treat diseases involving free radical damage such as occurs in
coronary reperfusion, diabetic angiopathy, diabetic
nephropathy, inflammatory bowel disease, pancreatitis
• Suppress cerebral edema and reduce extent of cerebral
infarction in brain injury
Byrd Alzheimer’s Institute
Studying ketogenic diets and
ketone esters in:
• Oxygen Toxicity
• ALS
• Alzheimer’s
• Cancer
• Epilepsy
• Wound Healing
Diseases With Decreased Glucose
Uptake into Brain/Nerve Cells
• Alzheimer’s disease
• Some forms of autism
• Parkinson’s disease
• Down’s syndrome –
• Multiple sclerosis
develop Alzheimer’s in
middle age
• Acute brain injury,
accompanied by lack of
oxygen
• Type I and Type II
diabetes
• Huntington’s chorea
• ALS/Lou Gehrig’s
disease
• Duchenne muscular
dystrophy
Olive
Oil
Canola
Oil
Margarine
No
Medium Chain
Fatty Acids
Peanut
Oil
Corn Oil
Fish and
Cod
Liver Oil
Soy
Bean Oil
Foods with Medium
Chain Fatty Acids
Food
Coconut oil
Palm kernel oil
Grams
8.4 grams per 15 ml
8 gm per 15 ml
Goat butter
2.4 gm per 15 ml
Cow butter
1.6 gm per 15 ml
Goat milk
1.7 gm per 240 ml
Infant formula
1 gm per 240 ml
Cow milk (full fat)
0.9 gm per 240 ml
Human breast milk
0.78 gm per 240 ml
Goat cheese
2 gm per ounce
Feta cheese
1.4 gm per ounce
Heavy cream
1.3 gm per ounce
American cheese
0.78 gm per ounce
According to USDA National Nutrient Database (www.ars.usda.gov/nutrientdata
Foods with Medium Chain FAs
Coconut oil – 57-60% medium chain fatty 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
Steve’s Regimen
• Mix MCT and Coconut Oil in 1:1 ratio
• Add soy lethicin to emulsify
• Increased gradually to limits of tolerance
• Receives 45 ml three times a day with meals and 30 ml at
bedtime
• Rationale:
• Maximize the intake of the more ketogenic medium chain fatty
acids, and provide lauric acid (50% of coconut oil) for antimicrobial
activity, and other potential unknown benefits
• Provide MCT for higher ketone levels, coconut oil for longer
duration of mild ketogenic effect
Recommendations for adding
Coconut Oil and MCT oil to diet
• Begin slowly and increase slowly to avoid diarrhea or other
•
•
•
•
•
intestinal upset
Start with 1 teaspoon with food 2 to 3 times a day with meals
If no GI problem, increase by 1 teaspoon per meal every few
days to total 4-9 tablespoons per day as tolerated
If GI problem develops, revert to previous level
To avoid weight gain, substitute coconut oil/MCT oil for other
fats in the diet and/or reduce carbohydrate intake
Include marine source of omega-3 FAs (no omega-3 in coconut
oil); vegetable omega-3 may not convert readily to DHA and
EPA in persons with Alzheimer’s disease
Astarita G, J Kwang-Mook, NC Berchtold, et al. “Deficient Liver Biosynthesis of
Docosahexaenoic Acid Correlates with Cognitive Impairment in Alzheimer’s
Disease.” PloS One Vol 5 No 9 (Sept 2010): e12538
Other Ketone Studies: MADD Disease
Male with multiple acyl-CoA dehydrogenase deficiency
(includes problem with fatty acid beta oxidation):
• age 4 months with hypotonia, hepatomegaly, stridor,
swallowing dysfunction, labs characteristic of MADD;
normal brain MRI excluded malformations.
• Responded for a while to gastrostomy feedings of a fat
restricted diet every 4 h, L-carnitine, and glycine with
nearly age-appropriate development.
• At 2 years, over several weeks, lost ability to walk and
developed spastic quadriplegia with complete loss of the
use of all four limbs, and could no longer talk.
D,L-3-hydroxybutyrate treatment of multiple acyl-CoA dehydrogenase
deficiency (MADD,) Johan L K Van Hove, et.al., Lancet 2003; 361: 1433–35
SUMMARY
 Previous studies using 20-40 grams of MCT oil have
shown improved cognition in nearly half of people with
probable Alzheimer’s type dementia and mild cognitive
disorder.
 Similar improvement may occur using an equivalent
amount of medium chain fatty acids as coconut oil, more
widely available to world populations.
 Larger clinical trials should be conducted to confirm
whether coconut oil and/or MCT oil may be useful in the
prevention and treatment of Alzheimer’s disease and
other neurodegenerative disorders that involve
decreased glucose uptake.
What do you have to lose?
www.coconutketones.com
Look for “Diet Guidelines”
www.coconutketones.blogspot.com
Mary T. Newport MD - Blog
Other Ketone Studies: MCT Oil and
Diabetes Related Hypoglycemia
• Administration of MCT oil to people with “intensively treated”
type 1 diabetes who were prone to severe hypoglycemia.
• 10 of 11 using an insulin pump; 11th person required multiple
shots of insulin each day. Most of the people had between 6
and 30 episodes hypoglycemia per month.
• Deliberately caused hypoglycemic attacks using insulin in the
subjects. 9 were studied twice and served as their own control.
On one day they received MCT oil (40 grams) and, on another
day, placebo.
Page KA, A Williamson, N Yu, et al. "Medium-chain fatty acids improve
cognitive function in intensively treated type 1 diabetic patients and
support in vitro synaptic transmission during acute hypoglycemia."
Diabetes Vol. 58, No 5 (May 2009): 1237–1244.
Other Ketone Studies : MCT Oil and
Diabetes Related Hypoglycemia
• Measured plasma, glucose, insulin, free fatty acids, and
ketone levels (beta-hydroxybutyrate).
• Ketone levels increased to an average of 0.35 mmol/L
with MCT oil.
• When compared to the placebo, the researchers reported,
“MCT prevented the decline in cognitive performance
during hypoglycemia” in 5 of the 7 tests administered
(administrators blinded to MCT vs. placebo).
• Their findings “suggest that MCT could be used as
prophylactic therapy for such patients with the goal of
preserving brain function during hypoglycemic
episodes….”
Other Ketone Studies : MADD Disease
• Started on sodium-D,L-3-hydroxybutyrate every 4 hrs,
•
•
•
•
•
increasing over 1 month from 80 to 900 mg/kg per day to
obtain measurable concentrations of physiological ketone
bodies at all times (0.19 to 0.36 mmol/L).
After 9 days, he could move his arms, and after 1 month lift
both arms. After 4 months, he had head control and used his
arms to drink from a cup.
After 6 months, he could sit with support and spoke ten words.
After 16 months, he talked in short sentences, was crawling,
and rode a tricycle. He still had hyperreflexia, mild clonus, and
extensor right plantar response.
After 19 months, he walked independently.
MRI showed progressive improvement but with regions of
cavitation, that were probably results of the reparative
processes. Liver size and function tests returned to normal.
D,L-3-hydroxybutyrate treatment of multiple acyl-CoA dehydrogenase
deficiency (MADD,) Johan L K Van Hove, et.al., Lancet 2003; 361: 1433–35
After a 150 mg/kg dose
of D,L-3hydroxybutyrate, 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)
References
Bergen SS, SA Jr., Hashim, VanItallie TB. “Hyperketonemia induced in man
by medium-chain triglyceride,” Diabetes Vol. 15 No. 10 (1966): 723-725
Clarke K, K Tchabanenko, R Pawlosky, et al, including Veech. “Kinetics, safety
and tolerability of **(R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy
adult subjects.” Regulatory Toxicology and Pharmacology 63 (2012):401-408
De la Monte SM, JR Wands. “Review of insulin and insulin-like growth factor expression,
signaling, and malfunction in the central nervous system: Relevance to Alzheimer’s disease.”
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