Cortisol and Weight Gain:

The connection between

Debbie Rice ND MPH

January 2024

©2024 Precision Analytical Inc.

Remember

1. The information in this presentation is provided for informational and educational

purposes only and is not medical or treatment advice.

2. Any information and statements regarding dietary or herbal supplements have not
been evaluated by the Food and Drug Administration and are not intended to
diagnose, treat, cure, or prevent any disease.

3. The use of any information provided in this presentation is solely at your own risk.

©2024 Precision Analytical Inc.

Obesity Pandemic
• Multiple studies cite that obesity has become a pandemic
• United States: 2022
• Risk factors listed include:
• Education
• Poverty level
• Race/ethnicity
• Location
(does not include the world numbers)

©2024 Precision Analytical Inc. Adult Obesity Prevalence Maps | Overweight & Obesity | CDC
Obesity/Weight Changes
• The WHO states this as an epidemic across the world of
overweight and obesity – naming it
“Globesity” (WHO)

• There is differentiation that males have higher risk of being

overweight, while females have higher risk of obesity
• This is not just for Western and developed countries
• Includes developing countries as well

• Because of this, we see the risk for diseases which include

diabetes/metabolic syndrome, cardiovascular disease
including stroke, cancer, and more.

©2024 Precision Analytical Inc. https://www.who.int/activities/controlling-the-global-obesity-epidemic

Contributing Factors and Considerations:
• When evaluating HOW did we get here?
Consider:
• Increased stress of a connected society and economy – 24/7!
• Increased pressure to perform for work

Deprioritizes healthy habits

• Whole food nutrition (fast food instead)
• Physical activity (sedentary)
• Appropriate sleep habits (work deadlines, family dynamics)

©2024 Precision Analytical Inc. https://www.shutterstock.com/image-photo/young-businesswoman-tons-documents-calling-phone-130051355

Contributing Factors to Obesity and Overweight:
• When we think about
increased stress, we think
about

• CORTISOL
• Cortisol is our main stress
hormone

• So HOW does Cortisol tie in

to weight gain and obesity….

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Welcome to your Tour!
• Sit back and relax

• I will be your tour guide

through this awesomely
complex yet straightforward
discussion

©2024 Precision Analytical Inc. https://creazilla.com/nodes/7769288-tour-guide-clipart

Cortisol Production
• Adrenal Glands Produce:
(3 zones for hormone production in the adrenal cortex)

• Cortisol
• Adrenal Cortex: Zona Fasciculata

• DHEA/DHEA-s
• Adrenal Cortex: Zona Reticularis

• Aldosterone
• Adrenal Cortex: Zona Glomerulosa

• Catecholamines
• Adrenal Medulla: Epinephrine and
• Norepinephrine

©2024 Precision Analytical Inc.

Cortisol
• Cortisol
• Produced in the zona fasiculata in the adrenal cortex of
the adrenal glands
• It is a glucocorticoid
• steroid hormone that utilizes sugar and fats to mediate a
response; can influence immune response and reduce
inflammation

• Cortisol is released in response to stress. It is also

released in the presence of low blood sugar (which is a
stressor)

©2024 Precision Analytical Inc.

Cortisol: Glucocorticoid
• Cortisol
• Because cortisol is a glucocorticoid – it uses glucose for its actions:

• Cortisol blocks insulin to keep glucose in the blood stream

• Cortisol induces gluconeogenesis (break down of glucose from
fat cells/liver)
• Cortisol reduces protein uptake (diverts it to gluconeogenesis to
keep glucose in circulation)
• Cortisol suppresses the immune system to deal with the stress
• Cortisol increases blood pressure (vasoconstriction)
• Cortisol improves focus (mental and physical), eyesight, and
hearing

©2024 Precision Analytical Inc.

Cortisol: Glucocorticoid (GC)
Cortisol as a glucocorticoid (GC)
• Influences metabolism of glucose, fat, and protein

Properties include:
• Anti-inflammatory
• Anti-allergic
• Immuno-suppressive
• Metabolic optimization

©2024 Precision Analytical Inc.

Cortisol: Glucocorticoid
Goal of Cortisol
Maintain Homeostasis

• Cortisol creates a state of hyperglycemia

• Stress induced need for glucose to critical organs (brain, skeletal
muscle)
• Cortisol blocks insulin action on the cells to keep glucose in the
blood stream
• Increases enzymes responsible for glycogenolysis and
gluconeogenesis
• Induces catabolism in peripheral muscle to mobilize amino acids
for gluconeogenesis
• Activates Hormone Sensitive Lipase (HLP) to promote beta
oxidation of free fatty acids for glucose

©2024 Precision Analytical Inc.

Cortisol: Short Term effect
• Short Term Effect of Cortisol Release:
• Anti-inflammatory
• Ability to have energy to fight, deal with stress

• Increased focus
SYMPATHETIC NERVOUS
• Increased blood pressure (vasoconstriction) SYSTEM
• Increased HR and blood flow to muscles

• Decreased digestive effort

• Decreased sex hormone response PARASYMPATHETIC NERVOUS
SYSTEM
• Decreased immune response

©2024 Precision Analytical Inc.

 Cortisol’s short-term purpose:
TO KEEP YOU SAFE
To enable you to run from your saber-tooth tiger

• Your saber-tooth tiger may look like:

• Work stress
• Relationship stress
• Exercise
• Blood sugar dysregulation
• Not sleeping well
• Etc…

©2024 Precision Analytical Inc.

Cortisol: Long Term Effect
• Long Term Effect of Cortisol Release:
• Blood sugar irregularities/dysglycemia – diabetes and insulin
dysregulation
• Weight gain, specifically around the middle
• Immune suppression, immune dysregulation – get sick easier, more
difficult to recover
• Chronic Fatigue
• Gastrointestinal Issues – parasympathetic nervous system
suppression = constipation, diarrhea, heartburn, stomach upset, etc
• Cardiovascular Concerns – blood vessel constriction, over-
compensation of the cardiovascular system (high blood pressure)
• Sex Hormone Imbalances, infertility, irregular periods, heavy
periods, low libido/sex drive

©2024 Precision Analytical Inc.

Cortisol: Long Term Effect
• Long Term Effect of Cortisol Release:
• Blood sugar irregularities/dysglycemia – diabetes and insulin
dysregulation
• Weight gain, specifically around the middle
• Immune suppression, immune dysregulation – get sick easier, more
difficult to recover
• Chronic Fatigue
• Gastrointestinal Issues – parasympathetic nervous system
suppression = constipation, diarrhea, heartburn, stomach upset, etc
• Cardiovascular Concerns – blood vessel constriction, over-
compensation of the cardiovascular system (high blood pressure)
• Sex Hormone Imbalances, infertility, irregular periods, heavy
periods, low libido/sex drive

©2024 Precision Analytical Inc.

Cortisol Physiology
HPA = Hypothalamic – Pituitary – Adrenal Axis

Hypothalamus à CRH (In the paraventricular nucleus

PVN)

CRH à Pituitary Gland

Pituitary Gland à ACTH

ACTH à Adrenal Glands

Adrenal Glands à Cortisol

MORE ACTH = more cortisol LESS ACTH = less cortisol

©2024 Precision Analytical Inc.

©2024 Precision Analytical Inc.
Stress Response Hormones
• We all “know” that stress contributes to or exacerbates
disease states
• We know that cortisol is commonly or frequently referred to
as the “stress hormone”
• We also know that our stress response involves our
catecholamines:
Epinephrine and Norepinephrine, as well as Dopamine

• Therefore we can connect that cortisol and our

catecholamines influence disease states

©2024 Precision Analytical Inc.

Stress Response Begins in the Brain
• We need to understand that the stress
response begins in the BRAIN – not the
adrenal glands

• The brain signals the adrenal glands for a

cortisol response

• The brain signals the SNS for a catecholamine

response

©2024 Precision Analytical Inc.

HPA function and Stress Response
Stress and physiologic response:
Real vs perceived stress:
• Results in mental/emotional
dysregulation
Blood sugar imbalance:
• Ultimately insulin resistance
then obesity
Inflammation:
• Ultimately obesity
Day/Night disruption:
• HPA imbalance

©2024 Precision Analytical Inc.

HPA function and Stress Response: Obesity

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HPA Function and Stress Response: Obesity

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HPA Response and Sleep:

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Circadian Disruption:
• Cortisol responds to sunlight
• All our cells respond to sunlight
• Sunlight determines our wakefulness and sleepiness

We should be wakeful during the light

And sleepy during the night

©2024 Precision Analytical Inc.

Circadian Rhythm and Hormones

Hormones that regulate metabolism include:

• Growth Hormone
• Cortisol
• Leptin
• Ghrelin
• Thyroid
• Estradiol
• Testosterone
• DHEA
• Progesterone

©2024 Precision Analytical Inc.

Circadian Rhythm and Hormones
Hormones that regulate metabolism include:
• Growth Hormone These hormones need a healthy sleep
• Cortisol pattern to do their jobs correctly

• Leptin When there is sleep deprivation, these

• Ghrelin hormones are unable to work
• Thyroid optimally
• Estradiol
• Testosterone
• DHEA
• Progesterone

©2024 Precision Analytical Inc.

 We know that sleep is an important
Sleep and Metabolism contributor to overall health

Sleep is integral to our circadian

modulation

When sleep loss occurs, we are

susceptible to increased disease
states, disrupted metabolism, and
confused hormone signaling

©2024 Precision Analytical Inc.

Sleep and Sex
Differences
Here we can see the impact of sleep
disturbance on sex and inflammation:
KEY POINTS:
Females:
Are at higher risk for inflammatory
disease
More likely to have sleep issues
More likely to develop higher levels of
systemic inflammation associated with
sleep loss
Higher levels of CRP and IL-6
(inflammatory markers)

https://www.nature.com/articles/s41577-019-0190-z
©2024 Precision Analytical Inc.
Sleep deprivation and inflammatory markers

This is just good information to have

J

©2024 Precision Analytical Inc. https://www.nature.com/articles/s41577-019-0190-z

Sleep and Disease Risk
Sleep Needs:
• Appropriate sleep patterning (circadian rhythm)

When sleep deprivation is present, we see:

• Difficulty losing weight
• Easy to gain weight
• Imbalanced signaling for ghrelin and leptin
• Inappropriate cortisol signaling
• Cognitive Aging
• Biologic Aging
• Depression and mood shifts
• Poor metabolic resiliency

©2024 Precision Analytical Inc.

Hormones Involved in Weight Management
• Leptin
• Ghrelin
• Adiponectin
• Cortisol

….there are others, but these are our focus today

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 Hormones released
from Fat Cells
Fat Cells release hormones

Let’s take a look at how Fat Cells

communicate

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Fat Cells: Adipocytes

Previously thought to be
Adipocyte physiology
an inert, storage organ

This means it is capable

We now know adipose of secreting biologically
tissue is its own active components
endocrine organ which are called
adipokines

Biologically active = These are called

metabolically active Adipokines

©2024 Precision Analytical Inc.

Adipocytes

Adipokine = adipose tissue + Cytokine

• Adipokines affect metabolic signaling and manage hormones

affecting appetite, satiety, glucose metabolism, lipid (fatty
acid) metabolism, inflammation, and immune function

• Cytokines signal cellular activity

• These can include pro-inflammatory or anti-inflammatory
signals

©2024 Precision Analytical Inc.

Adipocytes

We have 2 major classes of adipose tissue:

White Adipose Tissue – WAT

Brown Adipose Tissue - BAT

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Adipocytes: Different Fat Cells in the Body
• WAT: White Adipose Tissue • BAT: Brown Adipose Tissue
• White Adipose Tissue: • Brown Adipose Tissue:

• Stores excess energy as • Stores energy as small lipid

triglycerides droplets
• metabolically active
• Adipokines released: • Thermogenic
• Adiponectin
• Leptin • Adipokines released:
• IL-6 • IL-6
• IL-8
• IL-10
©2024 Precision Analytical Inc.
Adipocytes: Adipokines
Adipokines released by WAT and BAT modulate:

• thermogenesis
• energy expenditure
• glucose homeostasis
• lipid metabolism
• insulin sensitivity
• angiogenesis
• anti-inflammation

©2024 Precision Analytical Inc.

Adipokine: Leptin
Leptin Function:
• Produced from WAT mass
• Suppresses hunger
• Stimulates satiety
(regulate appetite)
• Increases energy expenditure through fatty acid oxidation
• Results in decreased fat mass in the adipocyte

• Strong influence on immune cells (TH1)

©2024 Precision Analytical Inc.

Adipokine: Leptin

• Leptin is released in a diurnal and pulsatile fashion

• Levels are highest in the evening and early morning hours
• Circulating levels of leptin represent the amount of energy
stored in fat

Low levels of fat = low levels of leptin

©2024 Precision Analytical Inc. https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=20083828

Adipokine: Adiponectin
Adiponectin Function:

• Produced by WAT
• Increases fatty acid
oxidation (burn fats for
energy)
• Sensitizes insulin
• Anti-inflammatory
• High levels of Adiponectin
are better

©2024 Precision Analytical Inc. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554603/

Adipokine: Adiponectin
Adiponectin Function:

• Anti-atherosclerotic
• Anti-proliferative
• Suppressive of carcinogens
• Modulates immune function
by affecting both B and T
cells

©2024 Precision Analytical Inc. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554603/

Adipokine: Adiponectin
• Adiponectin levels are decreased in disease states like:
• Type 2 Diabetes
• Insulin Resistance
• Obesity
• Metabolic Syndrome
• Cardiovascular Disease(s)

©2024 Precision Analytical Inc.

Adipokine: Ghrelin
Ghrelin’s Gifts:
• Stimulates appetite
• Stimulates fat deposition
• Stimulates the release of growth hormone
• Inhibits insulin secretion
• Regulates hepatic glucose output
• Decreases energy expenditure
• Reduces thermogenesis
• Often called the “hunger hormone”
• Necessary for blood glucose balance
• *Gremlin Hormone J

©2024 Precision Analytical Inc. Curr Opin Clin Nutr Metab Care. 2013 Nov; 16(6): 619–624.
Adipokine: Ghrelin
Ghrelin’s Gifts:
• Reduces sympathetic nerve activity
• Prevents muscle atrophy
• Contributes to obesity and insulin resistance
• Involved in bone metabolism and formation
• May be indicated in cancer – it can have proliferative
properties

• *MI, VEGF

©2024 Precision Analytical Inc. Curr Opin Clin Nutr Metab Care. 2013 Nov; 16(6): 619–624.
Adipocytes: Effects in the body

https://www.mdpi.com/2227-9059/11/5/1290
©2024 Precision Analytical Inc.
Adipocytes and Adipokines: Effects in the body

©2024 Precision Analytical Inc. https://www.mdpi.com/2227-9059/11/5/1290

Adipokines Purpose:
• The main goal of Adipokines:

• Maintain Metabolic Integrity [homeostasis] through

sensitization or resistance to insulin (Suarez, Et Al, 2023)…or
regulating blood glucose levels

©2024 Precision Analytical Inc. https://doi.org/10.3390/biomedicines11051290

Adipokines and Inflammation

• “Adipose tissue inflammation is initiated and sustained over

time by aberrant adipocytes that secrete inflammatory
adipokines and by the invasion of immune cells formed in the
bone marrow that communicates via the production of cytokines
and chemokines.
• Low-grade inflammation of adipose tissue has a detrimental
effect on distant organ function and is believed to be the core
cause of obesity complications. Among them, visceral obesity
plays an essential role in the development of metabolic
syndrome.”-Suarez, Et. Al. 2023

©2024 Precision Analytical Inc. https://www.mdpi.com/2227-9059/11/5/1290

So….WHY
• Why is this all important?

• Let’s pull this all together now…

©2024 Precision Analytical Inc.

Putting It All Together
KEY POINTS – Cortisol
• Cortisol is released in response to a stress
• Cortisol is meant to be acutely protective
• It is not meant to maintain chronically high levels

When your body is in Fight or Flight mode:

• Appetite decreases
• Tissue repair stops
• Reproductive processes slow/hormones slow down
• Immune system pauses

©2024 Precision Analytical Inc.

Putting it All Together
• KEY POINTS – Cortisol

When your cortisol levels remain consistently high:

• Body craves carbohydrates/sugars for energy, and high fats

• Your sleep is not as optimal- even if you are sleeping the
same amount of time; quality is less
• Your energy expenditure becomes less
• Your appetite changes (timing of eating/type of food eaten)

©2024 Precision Analytical Inc.

Putting It All Together
• Sustained HIGH levels of Cortisol
à need for comfort foods: high fats, high glycemic index (your
brain runs better on glucose/sucrose for energy)
à with poor diurnal regulation, hormone signaling becomes
imbalanced (ghrelin, leptin, adiponectin) and timing of food
intake is different. Your body distributes these calories
differently
à this combination causes your WAT to redistribute to the
abdominal region of the body and you now have increased
(adipokine) activity from WAT
à this abdominal WAT decreases the activity of BAT

©2024 Precision Analytical Inc.

Putting It All Together
à Cortisol reduces the ability to focus and think clearly
When this occurs, we do not make smart food choices
Rather, we follow our cravings for high glycemic
carbohydrates and fats
And we may not consider the timing of when we eat

à When we are stressed, we don’t create space for physical

activity which also creates metabolic imbalance

Our bodies are thrown out of routine

And our bodies really like routine!

©2024 Precision Analytical Inc.

Putting It All Together
It’s not just about

CALORIES IN = CALORIES OUT

©2024 Precision Analytical Inc.

Putting It All Together

It’s not just about

CALORIES IN = CALORIES OUT

©2024 Precision Analytical Inc.

Putting It All Together

• Multiple studies show that sustained high levels of cortisol

correlate with a high BMI
• Elevated cortisol metabolites (THF/THE) correlate with high
BMI
• Still other studies have shown that sustained high levels of
cortisol predict obesity in multiple populations (children and
adults)

• Newman, M. Smeaton, J. Endocrine and Metabolic Science. Dec 2023.

• Rossum, E. Obesity. Feb 2017.

©2024 Precision Analytical Inc.

 The Vicious Cycle

Circle of Stress

Obesity

GC reactivity

*dependent on GC receptor activity:

over or under reactive
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958156/#:~:text=High%20levels%20of%20cortisol%
©2024 Precision Analytical Inc. 20can,to%20abdominal%20obesity%20%5B4%5D.
Cortisol and Weight Gain: Considerations
NOT all cases of weight gain have high cortisol levels

• Normocortisolistic obesity – normal cortisol levels

• There are likely other factors influencing metabolism

• Hypercortisolistic obesity – elevated cortisol levels

• Many times, this is also associated with abnormal body
composition, poor diurnal pattern, insulin dysregulation and
inflammatory states.

©2024 Precision Analytical Inc. https://onlinelibrary.wiley.com/doi/full/10.1002/oby.21774

Cortisol and Weight Gain: Considerations

• People who are overweight or obese and are mentally

stressed about weight discrimination show higher cortisol
levels

• This correlates to ongoing elevated cortisol levels that

perpetuate cortisol with weight gain

©2024 Precision Analytical Inc. https://onlinelibrary.wiley.com/doi/full/10.1002/oby.21774

Cortisol and Weight Gain: Treatment Considerations
When elevated cortisol is involved, it is important to consider:
• Stress Management
(yes! Even the studies say: mindfulness!)

• Adopting an appropriate sleep routine

• Stabilizing blood sugar:

• Timing and quality of nutrients is key
• Protein and balanced foods every 2-4 hrs when stressed can help to
maintain stable blood sugar and reduce cravings for high glycemic
foods

©2024 Precision Analytical Inc.

Cortisol and Weight Gain: Treatment Considerations
When elevated cortisol is involved, it is important to consider:
• Physical Activity:
• Walking for 20 min (especially post meal)
• Weight-lifting to support healthy muscle metabolism

• Food Planning:
• This reduces the stress of having to decide on foods in the moment
of stress
• This is proven to reduce snacking, poor food choices, craving
frenzies!

©2024 Precision Analytical Inc.

Cortisol and Weight Gain: Treatment Considerations
Addressing the root cause:
What is contributing to stress and elevated cortisol?
• Mood
• Immune function
• Virus
• Inflammation
• Environmental
• Food
• Exposures

©2024 Precision Analytical Inc.

Cortisol and Weight Gain: Treatment Considerations
AND…TEST, Don’t guess!

• It is important to have information to approach your

treatment appropriately

Serum testing:
• Leptin
• Adiponectin
• Inflammatory markers (cytokines)

©2024 Precision Analytical Inc.

Cortisol and Weight Gain: Treatment Considerations
AND…TEST, Don’t guess!

DUTCH testing:
• Metabolized Cortisol (cortisol metabolites: THF/THE)
• Diurnal pattern of free cortisol to evaluate appropriate
circadian rhythm
• 8-OH marker to evaluate oxidative stress (cellular stress)
• Inflammatory markers:
• Kynurenate
• Xanthurenate
• Quinolinate

©2024 Precision Analytical Inc.

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