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TGF-beta plays an important role in autoimmune diseases, food intolerances, cancer, cognitive function, wound healing and other diseases.

Intro to TGF-Beta

TGF-b is a cytokine that affects the growth and proliferation of many cell types, and it has pro- and anti-inflammatory effects.

TGF-beta is produced in cells such as platelets, macrophages, B- and T-lymphocytes, fibroblasts, ECs, osteoblasts and osteoclasts, astrocytes, and microglial cells.  The thymus, bone marrow and bone also produce TGF.

There are different types of TGF, but TGF-b1 is the main one involved in immunity.

TGF-beta is often very elevated in people with biotoxin/mold issues.

Blood TGF is highly significantly correlated with the platelet count, probably because most of the TGF is released by platelets. (R)

You want TGF to be balanced rather than too high or too low…

Summary of Activities of TGF-beta:

  • Causes collateral damage in infections
  • Causes the growth/changes in tissue
  • Decreases acetylcholine
  • Decreases slow wave or deep sleep
  • Decreases muscle regeneration
  • Decreases the action of the vitamin D receptor
  • Increases free radicals
  • Can decrease bone density
  • It inhibits the proliferation of most other cell types
  • Suppresses red blood cell formation and lymphocytes (T and B cells)
  • Suppresses antibody production
  • Suppresses Cytotoxic T Cell (CD8) and Natural Killer cell activity…this can cause viral infections to get out of control.
  • Deactivates macrophages
  • Promotes oral tolerance
  • Suppresses inflammation
  • Promotes wound healing and new blood vessel formation (angiogenesis)
  • Induces local inflammation and fibrosis
  • Stimulates extracellular matrix deposition
  • Promotes switch to IgA (R)
  • Can increase cancer growth
  • Cause negative changes in the airways
  • Can benefit cognitive function (when very mildly elevated)
  • Can activate EBV or Epstein Barr Virus (R)

The Good (Sometimes)

TGF increases serotonin transporters and serotonin uptake in the gut, which is low in IBS and IBD. (R)  So this suggests that TGF is protective against autoimmune gut disorders.

TGF is increased by helminthic therapy and this is one important mechanism by which it’s protective against colitis. (R)

Studies have shown that TGF-b in the gut area is necessary to create tolerance orally. (R)

The primary mechanisms of oral tolerance are the active suppression of immune responses through the induction of regulatory T cells in the gut-associated lymphoid tissue. These Th3 cells secrete TGF-b, IL-4, and IL-10, which decrease Th1 and other immune cells.

TGF-b also leads to the death of T cells that attack our tissue (clonal deletion). (R)

Due to its potent anti-proliferative effects, TGF-b normally functions as a tumor suppressor. However, cancer cells develop resistance to TGF-beta late in tumor progression by using multiple mechanisms.

TGF-b promotes wound healing due to its unique effect on the extracellular matrix by stimulating the synthesis of matrix proteins and decreased matrix degradation.

In infections, it protects against collateral damages caused by the immune system, but it also promotes immune evasion by pathogens and therefore can lead to chronic infections.

TGF-b suppresses the immune system at the systemic level but stimulates the immune and inflammatory responses at the local level.

TGF-b1 deficient mice develop an inflammatory response with massive white blood cell infiltration in numerous organs, accompanied by increased expression of TNF-aIFN-g, and class I and II MHC antigens, resulting in death at 3 to 5 weeks. These mice also have high levels of autoantibodies. Thus, TGF-b1 normally acts as an active suppressor of inflammation.

TGF-b can suppress the proliferation of T- and B-lymphocytes, monocytes, and macrophages. 

It suppresses immunoglobulin (Ig) secretion of mature B cells, but can increase IgA production (not a cause of autoimmunity).

TGF-b inhibits IFN-g, IL-2, IL-3, GM-CSF, and TNF-a in response to infections or other stimuli. TGF-b also decreases E-selectin and IL-8 on blood vessels.

TGF-b can deactivate macrophages by reducing their capacity to release superoxide and nitric oxide, suppressing their cytotoxic activity, decreasing their expression of MHC class II, inhibiting the production of TNF-a and IL-1, and antagonizing the effects of these cytokines.

TGF-beta inhibits mast cells (R).

TGF-b can also benefit cognitive function.  One study found TGF-beta was associated with increased cortical thickness, and this is thought in part to do with the reduction of cytokines. (R)

TGF is low in advanced atherosclerosis.

TGF-beta might play a role in protecting against depression (R).

The Bad

TGF-b can increase inflammation locally.

TGF-b inhibits acetylcholine formation (in muscle and spinal cells) (R).  Inhibition of acetylcholine formation elegantly explains many of the symptoms that CIRS people have (R).

In an inflammatory environment, it will produce proinflammatory Th17 and Th9 cells (instead of Tregs) and inhibit Th22 cells. (R)

TGF increases ROS, but Butyrate helps prevent this. (R)

If you have systemically high TGF, you might want to take a mitochondrial antioxidant such as MitoQ,  since much of the damage from TGF is by increasing ROS in your mitochondria.  (R, R2)

TGF-b suppresses red blood cells by inhibiting bone marrow stem-cell proliferation and decreasing the expression of receptors for IL-3, and GM-CSF on hematopoietic cells (R).

One thing that is interesting is that I have a client/friend with high TGF and low RBCs.  This makes sense because TGF decreases RBC formation.

In cancer, TGF-β is a potent inhibitor of cell proliferation and acts as a tumor suppressor at the beginning of tumor formation. However, once the cells become resistant to TGF-β, it mainly supports tumor growth and metastasis by promoting immune evasion and angiogenesis. (R)

TGF-beta decreases slow wave sleep (R, R2).

TGF-b decreases muscle regeneration (R), which is one reason why people with CIRS lose muscle.

TGF-b will increase VEGF, by increasing hypoxia inducible factor, which can make tumors spread. (R, R2)

Indeed, an elevated blood level of TGF-b significantly correlated with lymph node metastasis and poor prognosis in patients with gastric cancer. (R)

TGF-beta decreases the action of the vitamin D receptor (R).

In asthma, TGF-b is assumed to promote allergen tolerance but plays a detrimental role in irreversible tissue changes of the airways. (R)

TGF-beta suppresses natural killer cells and promotes Th17 cells (R).

TGF-b causes various cells to stick to the site of inflammation and tissue injury (chemotaxis).  These include neutrophils, monocytes, lymphocytes, mast cells, and fibroblasts; TGF-beta also activates these cells to produce inflammatory cytokines (IL-1, TNF, and IL-6); and causes white blood cells to stick to the vessel wall and Extracellular matrix.

TGF-b secretion is increased by male hormone treatment in certain hair cells.  Androgens increase ROS, which increases TGF. (R)

TGF-b has both positive and negative effects on bone mineral density.  It’s thought by scientists that in the short term in can help bone density, but chronically elevated TGF-b will decrease bone density. (R)

TGF-b has been proposed as a contributing factor in many chronic inflammatory diseases, which include rheumatoid arthritis, glomerulonephritis, pulmonary fibrosis, systemic sclerosis, and chronic hepatitis.

TGF-b is elevated in the blood of patients with invasive prostate cancer.

TGF-beta Inhibitors

These inhibit TGF in different places, but not necessarily systemically….

TGF-beta Increasers

  • Hypoxia (R) or low oxygen
  • Psychological stress in primates (R, R2) and in the rat hippocampus (R).  Psychological stress increases TGF-beta through catecholamines  (epinephrine, norepinephrine, and dopamine) (R).
  • Wounds and burns (R, R2),
  • SIRT1 (R) – maybe resveratrol is not a great idea
  • Pregnenolone (R),
  • Growth Hormone (R)
  • 5HT2A Receptors
  • Estrogen (R, R) – increased TGF in skin
  • T3 (R)
  • Cigarette smoke (R)
  • Progesterone (R, R2, R3) – increased TGF in epithelial cells…which are all over the body…
  • Somatostatin (R)
  • Mast cells release TGF-beta (R)
  • Interferon (R)
  • S Boulardii (R) – TGF increased in the blood in chicks.
  • Bacillus Subtilis (R) – TGF increased in the blood in chicks.
  • Artemisinin (R) – increased TGF in spleen cells,
  • AngiotensinII- increased TGF in heart (R),
  • Beta-2 Adrenoreceptor (R) agonist increased TGF in the hippocampus…
  • Endoplasmic reticulum stress (R)

How to Increase Intestinal TGF-beta

  • Ingesting TGF-beta itself (R)…Colostrum (R) and breast milk have TGF-beta.Cyplexinol is a source of TGF-beta as well.
  • IGF-1 (R) –Cyplexinol, Colostrum (R) and Antler velvet have this….Increased TGF in intestines.
  • LLLT (R, R2, R3), LLLT seems to increase TGF-beta in various places.  Put on your intestines for 5-10 minutes.  According to Dr. Hamblin, though, it probably won’t get through…
  • Pancreas/Ingesting insulin (R), – increases TGF in intestines…
  • Cinnamon (R) – by increasing regulatory Dendritic Cells
  • Curcumin (R), – in the intestines
  • Retinol (R), – in the intestines
  • Berberine (R) maybe…..GLP-2 (R) and DPP4 inhibitors (R)
  • Nucleotides (R) – in the intestines
  • Bile (R)...also Bile Acid Conjugates/TUDCA and Liver
  • ProbioticsLactobacillus rhamnosus (R)
  • Lactoferrin (R) – in mesenteric lymph node cells in intestines
  • Honokiol (R) – increased TGF-b in the lungs of animal models with chronic asthma.
  • 1,25 Vitamin D3 (Active form) (R) – increased TGF in blood….1,25 Vitamin D3 caused CD8+ T cells to secrete more TGFb (R, R2)
  • Shikonin (R) – increased TGF in intestines,
  • VEGF (R) – increased TGF in intestines.

TGF-beta and Mold

I’m not completely sure why TGF is elevated in people with mold issues.  It could be TGF is an attempt by the body to create oral tolerance, but it doesn’t have other necessary ingredients or the proper anti-inflammatory environment. It then gets out of control and can be quite damaging.

This will contribute to a state of low oxygen or hypoxia.

It also turns out that low oxygen can increase TGF, at least in some cells. (R)

This person does very well with hyperbaric oxygen therapy, which can help in part by decreasing TGF-beta.

The Genetics of TGFbeta1

You can find the TGFbeta1 gene on SelfDecode with 7 SNPs on the 23andme chip. SelfDecode is a program that allows you to analyze and deconstruct your genetics and uncover health information about yourself in order to make you more optimal.

If you upload your file you can see what your genetics are (I pasted my file here, so my SNPs show):

  1. RS1800469 (TGFB1) AA
  2. RS1800470 (TGFB1) —  Healthy controls carrying rs1800470 TT genotype had 191 pg/ml, while the CC genotype had 129.4 pg/mL (R).
  3. RS1800471 (TGFB1) CC
  4. RS1800472 (TGFB1) GG
  5. RS2241715 (TGFB1) AA
  6. RS4803455 (TGFB1) CC
  7. RS8110090 (TGFB1) AG

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  • Elad
  • sheri

    I had TGF beta tested for mold concerns–should I have had TGf Beta1 tested instead, or is that the same?

  • Pam

    Greetings Joseph,
    Thank you for this succinct information. I have breast cancer and my TGF beta 1 dropped from 18,000 to roughly 4,000 over the last month. Do you know any research of hyperbaric treatments with lowering the TGF beta 1?

  • Dar

    I have a situation; I was on Losartan for blood pressure and pharmacy changed the company which they bought from. I was highly allergic to the new company’s pill and was very sick all year. We didn’t catch this new company or allergy. I had so many things wrong and food intolerances came from blood work. However, after eliminating all this my symptoms were not resolved so Dr. went the mold route. 14 vials of blood for all the mold markers. ANY way. I show markers for mold sickness but my TGF Beta 1 scores were raised with the Losartan! I got off med after a year and the TGF Beta scores went below 2308. My symptoms went away. So HOw s it my scores were up on Losartan? The only symptoms I have now is fatigue and the vegas nerve going haywire.

  • Tam

    Do you know if TGF-beta Inhibitors would be effective in reducing the damage of Marfan’s Syndrome?

  • Barbie

    pregnenolone both increases and decreases?

  • Amanda

    This is so interesting! I’m doing a lot of research into Loeys-Dietz Syndrome (Type 4 to be exact with a mutation on the transforming growth factor beta-2 ligand “TGFΒ2”). I assume the increase of TGF in the beta-2 acts the same as an increase of beta-1 and that perhaps the same things used to decrease it cross both.

  • MollyMolly

    Shoemaker’s range (<2380) is a lot lower than LabCorp. According to LabCorp I'm normal at 4031 (ref 622-4625). Any thoughts?

  • Oliver Chalfant

    Are there any solid resources for high levels correlating with mold exposure? I’ve not found anything published other than the word of Shoemaker

    1. Joseph M. Cohen


  • Joe

    Wow, this is great. I admire your research skills, this is the only list of TGF beta inhibitors I was able to find. So this has saved me time crawling through pubmed(which I had already been doing for hours. Are you aware of any other TGF-Beta inhibitors, that you may not have included, such as pharmaceuticals like Perfenidone?

    Thank you.

    (Awesome website BTW)

  • alexgierczyk

    Another hypothesis is that TGFb is endogenously activated to counter chronic inflammatory conditions:

    This makes sense as Ritchie Shoemaker’s protocol works and addresses TGFb last.

    Unfortunately the etiology of chronic TGFb activation is not well understood:
    Wikipedia lists ROS, injury, MMP as activators.

    If you know someone with CIRS they might want to check for MARCoNs:
    That article explains how to do it correctly.

    1. Joseph M. Cohen

      I just interviewd Shoemaker today 🙂

      1. alexgierczyk


  • alexgierczyk
    1. Joseph M. Cohen


  • Lucas

    Seriously Brother, you’re very quickly becoming my hero. I don’t say that lightly. Experience keeps pointing me back to you (longecity was my first exposure). You’re at the intersection of everything I care about, biohacking, chronic disease, autonomy, and social justice (for the sake of health). Thank you for your service. Keep the healthy marketing up. The world needs you.

    1. Joseph M. Cohen

      Lol, thanks 🙂

  • Luigi

    interesting read if not highly technical for me. i have mild gastritis since 2006. also hep c which is being treated right now with DAA’s . im using ices on the area of pain in my side. i feel it def helps but i wander if this article links to me?

  • Dana

    This was an interesting perspective on tgf. I appreciate this post because when I read shoemaker research for instance, I only hear how it is affected in mold people, vs. the significance of it in general…and why it’s an important biomarker of health apart from mold. I know there’s a theory of why it is affected specifically, but I don’t remember. Usually it’s just part of the standard CIRS protocol. Would like to know your thoughts so I’ll post here when I find it. Anyway, this is all great stuff thank you for this 🙂

    1. Joseph M. Cohen

      Glad you liked 🙂 I’ll have a look when you post..

  • Judd Crane

    TGF beta and mold: could be mold causing rhinitis induced hypoxia.

    1. Joseph M. Cohen

      That def could be part of it

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