Objectives - FxMed...•Converts inactive cortisone back into active cortisol (11bHSD2 converts it back to cortisone) •More cortisol = more fat storage esp. when 11bHSD1 is coming
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Carrie Jones, ND, MPH Medical Director– Precision Analytical, Inc.
• Zona Glomerulosa = Aldosterone • Sodium/potassium/H2O balance
• Zona Fasciculata = corticosterone and cortisol
• Zona Reticularis = DHEA, DHEA-s, Androstenedione (metabolites etiocholanolone and androsterone; precursor to testosterone)
Adrenal Medulla (inner layer)
• Norepinephrine (20%-25%)
• Epinephrine (75%-80%)
• Release triggered by Achmuch quicker than HPA cortisol response due to preformed concentrations
• **At high levels, cortisol goes from Cortex to Medulla and converts norepi epi
Let’s talk examples
What is so important about metabolized cortisol?
Metabolized cortisol represents 80% of total
cortisol production Free cortisol = 1%
(Stewart and Krozowski, 1999).
Typical Salivary “Adrenal Fatigue” result
Low free cortisol
levels all day
Which one is “Adrenal Fatigue” or insufficiency?
Which one is “Adrenal Fatigue” or insufficiency?
What does this mean? It means patient #2 has a lot of cortisol in total!
They are not in ‘adrenal fatigue’ They do have low levels of FREE cortisol so they likely feel fatigued! Must address both WHY the metabolized cortisol is high and help
that lower free cortisol.
Q: Why is the metabolized cortisol elevated?
(The ‘Why’ portion of your patient)
What causes elevated metabolized (total) cortisol or
an up-regulation in cortisol clearance? • Long term stress
• THIS IS NOT ‘ADRENAL FATIGUE!’ • But they are stressed and tired • Or stressed and wired • They are ‘fighting a fight’
Let’s talk about the obesity example
Obesity and 11bHSD1 (11-beta-hydroxysteroid dehydrogenase-1)
• 11b-HSD1 found in every cell in the body • Highest in fat, liver and brain • More at risk for adipose gain, diabetes/fatty liver, and memory
issues
• Converts inactive cortisone back into active cortisol (11bHSD2 converts it back to cortisone)
• More cortisol = more fat storage esp. when 11bHSD1 is coming from right within the fat cell
• Even with low controlled “systemic” cortisol, if 11bHSD1 is upregulated in the fat cell, it ‘sees’ higher cortisol = cortisol gets amplified = fat gain
Male, mid-forties, central obesity
If you just ran a free cortisol, and it was low, does that make sense?
Male, mid-forties, Central obesity: The full picture
Very high metabolized
cortisol
Suboptimal free cortisol
11bHSD1 upregulated
Relative Catabolic/Anabolic on DUTCH
Anabolic
Catabolic
This person is very catabolic!
So what’s happening?
• Inflammatory cytokines, insulin issues and stress are telling the brain to tell the Adrenals to make more cortisol
• 11bHSD1 is upregulated in fat tissue which causes more cortisonecortisol conversion creating more FAT GAIN
• With all this cortisol they are CATABOLIC (=↑glucose ↓muscle mass)
• To compensate, the liver upregulates cortisol clearance out of the body
• So free cortisol declines due to the clearance
• Result = higher metabolized cortisol, higher 11bHSD1, lower free cortisol and excess fat around the middle!
When cortisol clearance is abnormal, “free” cortisol
measurements can be misleading without
concurrent metabolite measurements
(without knowing the entire HPA picture, your diagnosis and treatment of your patients might be leading you down the wrong path )
Let’s talk Sex Hormones
Progesterone
DHEA metabolites
Estrogen Phase 1
Estrogen Phase 2
5a or 5b dominant?
Let’s talk estrogen! (Baseline test first, then re-test 3-6
months after treatment)
Common Estrogen Issues
• PMS
• Heavy periods
• Endometriosis
• Tender/fibrocystic breasts
• Weight gain
• Mood swings
• Fertility challenges
• Peri-menopause/menopause
• Estrogen cancer risks: breast, uterine, cervical
Men:
• Weight gain
• Breast development
• Fatigue
• Mood swings
• Erectile dysfunction
• Low libido
• Prostate cancer risk
Urine/Saliva/Serum shows Estrogen Dominance (male or female)
Whoa!
Sluggish clearance
Estrogen Dominant (male or female) DUTCH testing gives you the WHY
Whoa!
Sluggish clearance
Phase I detox
Before and After DIM (Phase 1)
Much better!
Let’s talk DIM… • E1 and E2 2, 4 or 16OH E1
• DIM: pushes E1 and E2 2OH E1
• 4OH E1 = more potent carcinogen because of the higher level of depurinating adducts (as opposed to stable adducts)
• When a quinone metabolites is formed reacts with DNA to form mostly depurinating adducts that break off from the DNA at N-3 and/or N-7 of Adenine or N-7 of Guanine leaving a DNA with a apurinic site (stable adducts stay attached to the DNA FYI)
• Poor repair of these sites mutations cancer
• NAC/glutathione – prevent damage to DNA by inhibiting formation of catechol quinones and/or reacting with them to stop problems via GST gene
• Resveratrol – non-competitive inhibitor of CYP1B1 to prevent E1/E24OH E1.