Some concepts I will be talking about require basic information on SOCS3. SOCS3 is elevated in mold illness and some types of chronic inflammation.
This introduction will come into play when talking about leptin resistance and other concepts. This is a technical post.
This post will be updated in the future regarding supplements that decrease SOCS3.
Introduction to SOCS3
Suppressor Of Cytokine Signaling 3 or SOCS3.
When a cytokine storm starts (such as IL6, IL10, and IFN-gamma) after infections, toxins, or injury, the body produces SOCS3 to try to dampen this response – hence the name suppressor of cytokine signaling.
In some immune cells such as dendritic cells (found in the gut and other places), SOCS3 causes them to be less tolerant and more reactive to foreign proteins (R).
In macrophages and dendritic cells, SOCS3 increases TNF, IL-12, and MHC-II/HLA expression, which are all inflammatory. SOCS3 also lowers IL-10 and Tregs, which are anti-inflammatory (R). All of these changes are bad.
SOCS3, Obesity and Th2 Dominance
Mechanism: Leptin-> STAT3->Weight loss.
SOCS3 blocks STAT3, which reduces Th1/Th17 inflammation, but increases leptin resistance and Th2 dominance.
Higher SOCS3 (The BAD):
- Causes leptin resistance (R)
- Causes Insulin resistance (R) (via decreasing IRS-1 (R)).
- Causes obesity (R).
- Is found in pregnancy, which can increase risks for developing obesity and type II diabetes during pregnancy (R) and may be a contributing cause of preterm labor (R). An increase in SOCS3 levels during pregnancy allows for the pregnant mother to increase food consumption in order to provide nutrients to her infant.
- Reduces the activity of pancreatic cells, which could cause type 2 diabetes by lowering insulin secretion (R).
Higher SOCS3 (The GOOD):
- Suppresses cancer growth by decreasing Th17 cytokines (R).
- Suppresses breast cancer (R) as well as many other cancers (R, R2), by decreasing STAT3 (R).
- Slows liver tumor growth (R).
- May prevent liver cell death, liver cancer, and liver failure (R).
- May prevent heart contractile dysfunctions and arrhythmias (R).
Do You Have High SOCS3?
You are more likely to have higher SOCS3 if you:
- Are Th2 dominant
- Gain weight easily
- Have chronic inflammation from mycobacteria, TGF-beta1, and MMP9.
What Inhibits SOCS3
- Butyrate – Butyrate -Calcium/Magnesium (R) – reverses a high-fat diet induced increase in SOCS3 in animals.
- Ecklonia cava (R)
- Bilberry (by preventing STAT3 activation) (R)
- Resveratrol effectively suppresses SOCS3 gene expression (R)
- Lycopene (R)
- PQQ (R)
- Probiotics (R)
- Chromium (nano-sized Cr tri-picolinate) (R)
So if you have good levels/high activity of SIRT1, you will have lower SOCS3 and lower leptin resistance.
Robust SIRT1 comes from circadian rhythm entrainment.
In the SIRT1 post, there are a number of SIRT1 activators, which you can use to inhibit SOCS3.
Resveratrol and Nicotinamide Riboside/Niagen NAD+ are two powerful supplements to increase SIRT1 and its activity.
SIRT1 is very important for DNMT1 to function and methylate better by taking its acetyl groups away (R).
SAM-e is the fuel for DNMT1 and SIRT1 is kind of like the steering wheel and motor.
This would suggest that breathing better and doing breathing exercises, exercising, and maybe even hyperbaric oxygen therapy may help lower SOCS3.
- IGF-1 lowers SOCS3 (when TNF-alpha is low) (R).
- Vitamin D deficiency (R), but this is not recommended.
What Increases SOCS3
- PPAR gamma (in mice) (R). There are a bunch of supplements that increase PPAR gamma.
- Forskolin – Increased SOCS3 expression by approximately 15-fold (R).
- DHA (via PPARgamma, in mice) (R)
- Melatonin (in rats) (R)
- EGCG (via reexpression of let-7) (R)
- Naringenin (strong) (R)
- Flavones (strong) (R)….flavones include Apigenin, Luteolin, Baicalin and Skullcap Root (contains the flavones baicalein, scutellarein, wogonin)
- TGF-beta (can be from autoimmunity, toxins, infections or injury) (R).
- Mycobacteria (R).
- TNF-alpha (in high doses) (R)
- Ionizing radiation, UV
- Endotoxin/LPS – maybe other toxins
- Homocysteine – lower methylation
- Interferon gamma, TNF-alpha – inflammation
- MMP – MMP-9 is elevated in mold.
- ROS/Oxidative stress
- THC, Anandamide (internal cannabinoid)
- 1,25 dihydroxy vitamin D
- Chemotherapy – toxins
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