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Innovative Solutions for
Fat Loss: New Perspectives
on Thyroid, Adrenal, and Hormones
Denis Wilson, MD
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• Diabetes
• Metabolic Syndrome
• Hypertension
• Stroke
• Heart disease
• Certain Cancers
• Dementia
• NAFLD
Why Obesity is a Problem
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How Obesity Leads to Metabolic Diseases
1. Obesity (especially central)
2. Inflammation
3. Insulin-resistance
4. Oxidative Stress
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The Prevalence of Obesity
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The Prevalence of Obesity
• In the United States today more than 35% of adults and
nearly 17% of children aged 2–19 years are obese
• Most of the world's population live in countries where
overweight and obesity kills more people than
underweight
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What Causes Obesity?
• Multi-factoral: Can’t leave a switch unflipped, but we’ll focus on common switches
• Hormones: Insulin, thyroid - low body temperatures, stress - cortisol
• Obesity, inflammation, insulin resistance, oxidative stress
• When people eat: fed state vs. non-fed state
• What kind of exercise and when?
• Environmental toxins
• What people eat: Increased consumption of added sugar and added oil
• Sleep time
• Screen time
• Microbiota
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Practical Approaches for Fat Loss
• Fat Loss? Easy Peasy!
• Diet and exercise per CALORIES versus
diet and exercise per HORMONES
• Direction and inertia
• At the bottom of many disease states is a vicious cycle.
Obesity > Inflammation > Insulin Resistance> Oxidative
Stress > Obesity. Find them and turn them around’
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First check body temperature
The core body temperature (blue line) of a mouse was recorded using an abdominal telemeter while oxygen consumption (pink lin
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The Utility of Body Temperature
• It’s easier to lose fat with a normal body temperature
• Dieting can cause a persistent lowering in the metabolic
rate
• People are more likely to keep their weight off after fat
loss if their body temperatures are normal
• There is a vast difference between losing fat with a
normal temperature and losing fat with a low temperature
• Temperature <=> Metabolic rate. Monitor during fat loss
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• Normalizing low body temperatures can be the key in
some, not all, patients
• I’ve had patients lose over 100 pounds when they could
never lose weight before
• One patient lost 35 pounds in one month without
changing anything else
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Normalizing the Body Temperature
• Anything that improves health and decreases stress
• Thyroid support dosed according to temperature: Zinc,
Iodine, Selenium, Kelp, Blue Flag, Guggul, Nettle,
Triphala. Not much support if it doesn’t improve Temp.
• Test dose for 2-3 days to rule out hidden toxic
nodule (^heart rate, palpitations) response to
iodine. If tolerated well, increase dose.
• Then, after 1 week, if temp still low, increase dose.
• Then, after 1 week, if temp still low, increase dose.
• Then, after 1 week, if temp still low, increase dose.
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Normalizing the Body Temperature
• Desiccated Thyroid titrated to body temperature: 30mg/day
to start. Consider adjusting the dose every 3 weeks.
Consider weaning if temperature goes down instead of up.
• Cyclic / sustained T3 Therapy - up regulate deiodinase
enzyme
• Sustained Release T3, increasing each day if pulse <100, then decrease every 2-3 days.
7.5 mcg BID
15 mcg BID
22.5 mcg BID
30 mcg BID
37.5 mcg BID
45 mcg BID
52.5 mcg BID
60 mcg BID
67.5 mcg BID
75 mcg BID
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Stress and Central Obesity
• Adrenal support for combatting stress,
helping thyroid
• Adrenal function can affect desire for food
• Eleutherococcus, Rhodiola, Holy Basil, Ashwagandha,
Hawthorne (anti-oxidant, anxiolytic)
• Dose Eleuthero especially in morning and early
afternoon
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Herbs and nutrients helpful for weight loss,
especially in insulin resistance
• Gymnema sylvestre: Reduces post-prandial glucose (PPG),
BMI, decreases HgA1c, improves lipid profile, anti-oxidant
• Vanadium (Bis-Glycinato Oxo Vanadium) (BGOV):
improves insulin sensitivity
• Chromium: improves insulin binding, lowers HgA1c
• Lipoic Acid: improves insulin sensitivity
• Devil’s club: reduces PPG and HgA1c
• Prickly Pear: Lowers glucose, leptin, optimizes metabolism,
pectin (stabilizes glucose and lipids and may help with toxins),
may improve insulin sensitivity
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Keeping it simple > focus on insulin• Leptin > decreases hunger
• Ghrelin > increases hunger
• Adiponectin > made by fat, modulates glucose and lipid metabolism; with
Leptin can completely reverse insulin resistance in mice.
• Hormone Sensitive Lipase > in fat, hydrolyzes stored triglycerides to free
fatty acids.
• Lipoprotein Lipase > hydrolyzes triglycerides in lipoproteins (e.g. VLDL).
Promotes cellular uptake of chylomicron remnants and free fatty acids
• Adipose Triglyceride Lipase > important in the catabolism of cellular fat
stores
• Peptide YY > produced by gut cells, reduces appetite
• Hundreds more > No, we don’t fully understand lipolysis
• Insulin > the switch between the fed and non-fed states
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• Insulin rises = fat-storing
mode
• Food used for fuel and for
storage
• Glygogen and fat storage
begin
• Hunger is a sign that it’s
coming to an end
Fed state Non-Fed state
• Insulin drops = switches to
fat-burning mode
• Stored glygogen and
stored fat used for fuel,
mostly glycogen first
• Hunger is not a demand. It’s
the body asking if you want
to keep burning fat. Answer
the question and the hunger
will go away.
• Autophagy and refurbishing
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• Autophagy is the is the natural,
regulated, destruction and
recycling of unnecessary or
dysfunctional cellular components.
Critical for good health and
prevention of chronic disease
• Autophagy is known to be
triggered by intermittent fasting
and is thought to be one reason
fasting appears to stave off aging.
There are currently no drugs that
target autophagy available on the
market.
Not only is it OK to be in the Non-fed
state, it’s hugely beneficial!
Yoshinori Ohsumi
Winner of the 2016
Nobel Prize in Medicine
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• 174 people with hypertension
• Almost 90% of the subjects achieved blood pressure less than
140/90 mm Hg
• Average reduction in blood pressure for all was 37/13 mm Hg
• Average reduction in blood pressure for severe was 60/17 mm
Hg
• All of the subjects who were taking antihypertensive
medication at entry (6.3% of the total sample) successfully
discontinued the use of medication.
Non-fed state for 10 days almost
completely reversed hypertension!
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• Unable to switch to stored fat as
fuel as long as insulin is up (fed-
state)…no matter how much
food is reduced. Body forced to
reduce energy expenditure
Not enough time in the non-fed state
12 pm
6 am6 pm
12 am
12 pm
6 am6 pm
12 am
Non-fed
Fed
Snack
• Switching fuels between
fed and non-fed states
Non-fed
• Balance. Awake/Asleep.
Exercise/Recovery. Work/Play.
Fed/Non-fed• First home refrigerator: 1913
First canned food: 1800’s
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• Insulin up in fed state, down in non-fed state
• Some lipolysis begins in the first hours of the non-fed state (though more
glucose is coming from glycogen at first)(Full transition to ketosis doesn’t
occur until 2 days into non-fed state)
• Just when lipolysis begins (1st sign of hunger), people tend to eat something
and shut it down, reaching non-fed state only while sleeping.
• Rephrase: “Why can’t I lose fat though I eat less?” to “Why can’t I eat all day
and not lose fat?” Remember insulin.
biology.stackexchange.com
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• Or, Just one meal/day,
same time every day
12 pm
6 am6 pm
12 am
• Eat within 6-8 hr window
• Perhaps skip breakfast,
or skip dinner
Non-fed
12 pm
6 am6 pm
12 am
Non-fed
Increasing time in the non-fed state
• Too much time in fed-state leaves
many over-fed. Staying in fed-state
and reducing food does not correct
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• Could skip an entire day, or more
Increasing time in the non-fed state
0 1 day 2 day 3 day
Dinner Breakfast
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• Insulin stays up> glycogenesis, lipogenesis, nearly
impossible to lose fat
• Insulin resistance> more insulin, more fat gain
Hypothyroid or just not enough
TIME in non-fed state?
In Over-Fed state:
“Over-Fed” is just as much about
time as calories, maybe more so
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• Many people have not gone 24 hours without a meal for
years, possibly their entire lives
• Think when was the last time you went 1 day without food? 2
days?
• It can be an enlightening experience. Where did we get the
idea that we need to be eating all the time?
• Feeding and Non-feeding are both great, in balance. Feasts,
celebrations, nutrition, recovery.
• Balance between fed/non-fed may be what determines body
set weight
Everyone has a
fed/non-fed time ratio
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Reducing Fuel Source versus
Switching Fuel Source
Determined by:
• What to eat, when to eat it
• How to exercise, when to do it
• Reducing Fuel Source (calories) => doomed to failure
• Switching Fuel Source (hormones) => successful,
restores natural balance
• Jason Fung, MD > Toronto
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• Minnesota Starvation
Experiment
• 36 men, 1560 cal/day
for 24 weeks followed by
20 weeks normal diet
• During LCD felt cold,
hungry, weak, tired,
dizzy
• RMR dropped 40%
Downsides of staying in fed-state and
Reducing Fuel Source
• Gained back weight
and fat and then some
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• Decreased metabolism persisted
for greater than a year on
reduced calorie diet (45%
carbohydrates).
7 trios of people measured
baseline, 8 weeks (circle) and
1 year (square)
Downsides of staying in fed-state and
Reducing Fuel Source
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• Reduced calorie intake in 50 obese people for 10
weeks. Measured weight, Ghrelin, Peptide YY at
baseline, 10 weeks, 62 weeks
• Gaining 1/2 the weight back in spite of maintenance
diet and exercise, increased Ghrelin/appetite,
decreased Peptide YY/satiety, even a year later.
Downsides of Reducing Fuel Source
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• 18 obese patients and 23 never-obese patients.
• Measured total energy expenditure at baseline, at 10% weight gain from over-feeding,
return to normal weight, at further 10% weight loss, at further 10% weight loss
• Energy expenditure increase with overfeeding (greater in obese than non-obese!),
energy decrease with underfeeding
Body “Set” Weight
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Body “Set” Weight
• 6 lean and 3 overweight volunteers
overfed by 50% for 6 weeks
• Fat went up with overfeeding tended
to come down off overfeeding
• Energy expenditure went up with
overfeeding, down off overfeeding
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By reducing caloric intake:
Summary of downsides of
Reducing Fuel Source
• People lose weight, for a time
• Energy expenditure goes down
• Ghrelin / hunger go up and stay up
• Peptide YY / satiety go down and stay down
• Unrelenting fatigue, weakness, preoccupation with food, trouble
concentrating until calories go back up
• People tend to gain the weight back and then some
• Sounds hopeless
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What can we do?• Thyroid > metabolism
Testosterone > male
Estrogen > female
Adrenal > stress
Insulin > fat
• As long as people have raised INSULIN in their
systems it will be hard for them to access their fat
stores
• When insulin up, eating less = reducing their fuel
sources (with all of its attendant downsides)
• Insulin quickly and strongly suppresses lipolysis
and lipases, preventing access to stored fat as fuel
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What brings insulin down?• Not eating.…anything. Only in the non-fed state does
insulin drop. Low carb diet reduces blood sugar level,
but only complete abstinence significantly reduces
insulin (protein and fat also raise insulin)
• When insulin drops, and glucagon and epinephrine
increase the body switches its fuel sources from
food to glycogen and fat
• This is not a reduction in fuel because there is ample
energy stored and accessible in glycogen and fat,
provided insulin stays low. One mouthful of a soft
drink will raise insulin.
• Insulin is the switch between fed and non-fed states
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• Water, broth, tea, coffee (even a little milk and sugar for
compliance). We can have all this during non-fed state! This
answers the question whether to burn fat or food.
• Vinegar
• Soluble Fiber - mechanoreceptors are main long-term satiety
• Avoid wheat, refined carbohydrates, starches
• High-intensity Interval Exercise
• Choose between benefits of fed or benefits of non-fed
• Cinnamon (delays gastric emptying)
The main challenge of
the non-fed state is hungerSolutions:
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Vinegar taken with a meal lowers resulting glucose and
insulin, and increases satiety, in a dose-dependent manner
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Vinegar lowers glucose high after
bread by as much as 34%.
Especially striking
in insulin resistant
Handy!
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Two teaspoons of vinegar is an effective dose.
Works better when taken with meal than when
taken 5 hours before a meal
Vinegar lowered the glycemic
index of white rice by almost 40%
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When our bodies ask if we would rather eat
or keep burning fat (hunger), we can answer
with High-Intensity Interval Exercise
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Epinephrine is the chief mobilizer of fat stores
HSL is
very
sensitive to
Insulin so
don’t drink
sugar
water while
you’re
trying to
mobilize fat
T3 increases the effects of epinephrine in stimulating lipolysis
J Appl Physiol Respir Environ Exerc Physiol. 1978 Jun;44(6):869-76.
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HIIE Increases epinephrine much
more than steady state exercise
Ten 6-second cycle ergometer sprints with a 30-second recovery between each sprint.
Epinephrine increased 6.3-fold, Norepinephrine increased 14.5-fold
People can walk or jog for hours without changing their catecholamines much
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Epinephrine (has been used to treat hypoglycemia)
• increases sympathetic tone
• increases blood sugar
• mobilizes fatty acids
• decreases brain fog
Non-fed state: body running on stored fuel
Epinephrine: encourages body to run on stored fuel
Hunger’s Q: Do you want to keep burning fat instead of food?
Our HIIE A: Yes! Keep burning fat! And step on it.
One minute of HIIE can put off hunger by 1-2 hours, or more.
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Visceral fat causes the most inflammation and
insulin resistance
• Visceral fat is the easiest and quickest fat to lose (days).
• It has the highest blood flow because it is warm and vascular.
• It has the most Beta-adrenergic receptors and is very
sensitive to epinephrine (choosing HIIE)
• HIIE increases GH significantly (just like non-fed state) within
30 seconds and it remains high for an hour
• GH fights muscle wasting
• HIIE is anti-Cushinoid
Cushing’s and metabolic syndrome reduce
Growth Hormone
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So let’s try this
Who’s hungry?
We can use our glycogen and fat stores,
instead of food, to address hunger
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HIIE Significantly reduced insulin resistance
(just like non-fed state) in this 15 week trial
HIIE reduces insulin resistance (23-58%) and is
great for fat loss and aerobic and anaerobic fitness
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HIIE burns fat much better than SSE (15wks)
Yes, people can exercise more and still gain weight,
when exercise focuses on calories instead of hormones
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HIIE significantly lowers oxidative stress
HIIE reduces inflammation
HIIE is perceived by participants as having lower
perceived exertion than steady state exercise
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Fat loss is under regulation (hormones)!
• Over-feeding increases TEE, Overfed-state calorie
reduction reduces it
• HIIE can burn fat, Steady state can slow it
• Therefore we want to eat and exercise in a ways
that address the regulation (hormones)
• Eating and exercising to win gold medals and
setting world records might be different than for fat
loss.
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Herman Pontzer; Scientific American, Feb 2017
• Double-labeled water technique shows that hunter gatherers
expend about the same energy as sedentary people in USA!
• Less energy on inflammation and immunity. Overfed state and
sedentary contributing to autoimmunity?
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The results of exercise alone for fat
loss are disappointing
HIIE is great for rolling on in Non-fed state!
We use it to address regulation and comfort
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Complex Resistance Exercise helpful for
building muscle and losing stubborn fat
• Visceral fat > prevalence of ß-adrenergic
receptors (increase lipolysis with Epi), comes
off first
• Stubborn fat > plenty of α-adrenergic receptors
(decrease lipolysis with Epi), comes off last
• Complex Resistance Exercise answers the
question, “Do you really want to trade the last
bit of fat for muscle?”
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Obesogenic toxins alone can
explain obesity epidemic
• Even animals are getting fatter (might
explain why so many thin people are
carrying more waist fat)
• Joe Pizzorno, ND explains we are all
toxic and that virtually all persistent
organic pollutants are fat-soluble and
concentrate in fat cells
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Obesogens target PPARγ so
much a test is being developed
• PPARγ is the target of certain drugs to
reduce blood sugar without increasing
insulin production.
• Agonists increase insulin sensitivity and
decrease blood sugar, but also increase
fat production.
• Obesogens can stimulate it to increase fat
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• Toxins do come out of the fat and increase
in the serum during fat loss
• The increased serum concentrations can
persist for over a year
• This may partly explain why so many people
tend to gain the weight back and more
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• Dr. Yu has treated 9/11 firefighters and
soldiers for toxic exposures
• He feels everyone should make active
detoxification part of a healthy lifestyle
• Also, that everyone losing weight
should be actively detoxing, for
example 2 bouts of exercise and sauna
(for 1 hour sweating) each week.
George C. Yu, MD
http://www.detoxacademy.org/pdfs/unexp.pdf
50-100 mg of Niacin (building up higher), followed by
exercise, followed by sauna (1 hour sweating).
Can also give polyunsaturated oil to facilitate exit
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Activated Charcoal Internally
• Coconut fiber / Hardwood activated charcoal
• Can use it during non-fed state to possibly absorb toxins,
reduce discomfort (headaches, brain fog, fatigue), aid fat
loss, prevent regain
• Normally used to treat ingested poisons, however, there
is huge surface area and blood flow in the gut and there
is huge adsorptive area in activated charcoal. If toxins
can cross into the gut, and likely they do (since that’s
how we usually get them) then likely very effective.
• Tasteless, turns stool black
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More thoughts• Microbiome can promote obesity and is transmissible.
Bariatric surgery changes microbiota. Non-fed state
changes microbiota
• Sleeping time has been steadily decreasing in the last 3
decades and contributes to obesity.
• Screen time increasing
• Keep fat warm to promote circulation and fat loss
• Obesity exploded after first national dietary
recommendations (higher carb, lower fat, higher insulin)
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Over-fed signs
1. Supraclavicular Fossa Fullness
2. Barrel chest
3. Blood rushing to face bending over
4. Bloated face and neck
5. Central obesity
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Summary
• Spend more time in non-fed state, let the fat roll off
• Manage hunger with HIIE, fiber, vinegar, cinnamon,
water, tea, coffee, broth
• Remove toxins with activated charcoal, sweating
(niacin/exercise/sauna)
• Eat for nutrition (good multi-vitamin and water can be
enough for months), and detox, and muscle.
• Exercise focus on regulating hormones and building
muscle and strength (not so much on burning calories)
• Non-fed “meal”> fiber, water, charcoal, vinegar