Innovative Solutions for

Fat Loss: New Perspectives

on Thyroid, Adrenal, and Hormones

Denis Wilson, MD

• Diabetes

• Metabolic Syndrome

• Hypertension

• Stroke

• Heart disease

• Certain Cancers

• Dementia

• NAFLD

Why Obesity is a Problem

How Obesity Leads to Metabolic Diseases

1. Obesity (especially central)

2. Inflammation

3. Insulin-resistance

4. Oxidative Stress

The Prevalence of Obesity

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

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

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’

First check body temperature

The core body temperature (blue line) of a mouse was recorded using an abdominal telemeter while oxygen consumption (pink lin

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

• 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

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.

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

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

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

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

• 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

• 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

• 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!

• 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

• 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

• 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

• Could skip an entire day, or more

Increasing time in the non-fed state

0 1 day 2 day 3 day

Dinner Breakfast

• 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

• 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

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

• 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

• 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

• 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

• 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

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

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

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

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

• 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:

Vinegar taken with a meal lowers resulting glucose and

insulin, and increases satiety, in a dose-dependent manner

Vinegar lowers glucose high after

bread by as much as 34%.

Especially striking

in insulin resistant

Handy!

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%

When our bodies ask if we would rather eat

or keep burning fat (hunger), we can answer

with High-Intensity Interval Exercise

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.

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

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.

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

So let’s try this

Who’s hungry?

We can use our glycogen and fat stores,

instead of food, to address hunger

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

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

HIIE significantly lowers oxidative stress

HIIE reduces inflammation

HIIE is perceived by participants as having lower

perceived exertion than steady state exercise

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.

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?

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

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?”

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

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

• 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

• 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

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

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)

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

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