The human body is made up of billions of cells, and each one is able to communicate with one another. One of the primary ways our cells communicate with each other is through using special signaling molecules that they release and absorb to “talk” to each other. One of these signaling molecules is a tiny protein known as TGF beta-1.
Today we’re going to explore exactly what this protein does, what happens when it gets too high, and some underlying triggers that can cause TGF beta-1 to become elevated. Let’s dive in.
What Is TGF Beta-1?
TGF Beta-1 stands for transforming growth factor beta-1. It’s part of the transforming growth factor beta superfamily, which is a class of cytokines. Cytokines are a tiny type of protein secreted by cells that act as a signaling molecule that allows cells to communicate and interact with each other.1
The transforming growth factor beta class of proteins contains three variants, known as isoforms. Isoforms are simply two or more proteins that are functionally quite similar but have a slightly different sequence of amino acids or building blocks. The three known isoforms within the transforming growth factor beta class of proteins are:2
- Transforming growth factor beta-1
- Transforming growth factor beta-2
- Transforming growth factor beta-3
All of these isoforms use the same receptor signaling pathways – meaning they all bind to or fit into the same cellular receptors to trigger a response. All three transforming growth factor beta isoforms are present in humans. Virtually every cell in your body produces and contains receptors for TGF beta isoforms. But of the three isoforms, transforming growth factor beta-1 is by far the most abundant and ubiquitous form.
What Does TGF Beta-1 Do?
TGF beta-1 plays an important role in a number of cellular functions, including:3
- Proliferation: the growth and division of cells
- Differentiation: the maturation of cells to carry out specific functions
- Motility: cell movement
- Apoptosis: controlled cell death
Because it impacts so many cellular functions TGF beta-1 plays a particularly important role in things like:
- Embryo development
- Wound healing and tissue regeneration
- Angiogenesis – or the formation of new blood vessels
- Immunoregulation – the delicate balance of immune system upregulation and downregulation
But exactly what effect TGF beta-1 has is incredibly context-dependent – meaning that too much or too little of this protein can have detrimental effects. Let’s take a look at some of the effects of an upregulation of TGF beta-1.
TGF Beta-1 Upregulation: What Happens When TGF Beta-1 Levels Are Too High?
Before we look at what happens when TGF beta-1 upregulates, let’s first answer the question, what is upregulation? In simplest terms, upregulation is when a cell increases its response to certain stimuli – or becomes more sensitive to a certain signal by increasing the number of receptors available for a certain protein to bind to.4
When there’s an excessive upregulation of TGF beta-1 it can lead to:5,6,7,8,9
- Tumor promotion and cancer formation
- Fibrosis – excessive tissue formation in organs such as the lungs, heart, liver, kidneys, and other organs
- Central nervous system dysfunction and disease
- Inflammatory bowel disease
- Autoimmunity
- Chronic inflammatory response syndrome (CIRS)
- Endometriosis
- Hair loss
So what exactly causes an upregulation of TGF beta-1?
What Causes TGF Beta-1 Upregulation?
While elevated levels of TGF beta-1 have been closely linked to a number of conditions, it’s important to separate the difference between causation and correlation. TGF beta-1 levels may be upregulated in certain disease states, but that doesn’t necessarily mean that this cytokine is the cause of the condition.
With that being said, research has found that there are a few things that can cause an increase in TGF beta-1 and trigger inflammation.
TGF Beta-1 Upregulation and Mold
Exposure to toxic mold has been directly linked to an increase in TGF beta-1 and the development of chronic inflammatory response syndrome (CIRS). To learn more about CIRS and mold exposure, you can head over and check out the following articles:
- Five Essential Tips For Living With Mold Toxicity and CIRS
- Mold is a Major Trigger of Mast Activation Cell Syndrome
- Is Toxic Mold Exposure the Cause of Your Symptoms?
But mold exposure isn’t the only factor that can cause an upregulation of TGF beta-1.
TGF Beta-1 Upregulation and Low Oxygen Levels (Hypoxia)
Studies have found that low oxygen levels, also known as hypoxia, can trigger the secretion and synthesis of TGF beta-1.10 But what exactly causes hypoxia? There are countless things that can cause an issue with your oxygen supply and cause you to become hypoxic – but they all fall under one or more of the following three issues:
- Lack of adequate oxygen in inhaled air
- Dysfunction within the lungs – inhibiting their ability to properly transport air into your body
- A problem with blood flow – inhibiting your bloodstream from properly shuttle enough oxygen-rich blood to your cells
One lifestyle habit that can contribute to conditions that lead to hypoxia, as well as a spike in TGF beta-1, is smoking.
TGF Beta-1 Upregulation and Smoking
Studies have found a direct correlation between cigarette smoke and an upregulation in the TGF beta pathway. In fact, it’s believed that the oxidative stress and the spike in TGF beta-1 induced by cigarette smoking is a major contributor to some of the complications seen in long-term smokers – like fibrosing of the lungs and chronic airway diseases like emphysema and cystic fibrosis.11,12
TGF Beta-1 Upregulation and Psychological Stress
Psychological stress is an often overlooked aspect of health that can have a monumental impact on hormones, your immune system, and the regulation of important signaling molecules – including TGF beta signaling. Studies are finding more and more evidence that psychological stress can cause a direct spike in proinflammatory cytokines like TGF beta-1.13
So, How Worried Should I Be About TGF Beta-1?
So should you be worried about TGF beta-1? The answer is – not necessarily.
You see, because elevated TGF beta levels are typically in response to a deeper issue – this itty-bitty protein can actually be really helpful in cluing us in when something is wrong.
Bodies are complex and intricate. There’s rarely one single thing that throws your body off-balance enough to cause disease. So if TGF beta-1 is elevated, it likely means there’s a bigger lifestyle issue causing inflammation that needs to be addressed. And the good news is, you have a ton of power over all of the lifestyle factors that directly impact your inflammation and TGF beta-1 levels.
When It Comes to Your Health, You Are In the Driver’s Seat
Just like there’s not a singular trigger that throws your body into a state of disease, there’s not one singular thing that’s going to create true health and vibrance. True well-being and vitality require a big-picture, whole-life approach that encompasses how you eat, move, sleep, and think.
And that’s why I’m dedicated to bringing you the resources and knowledge to create a foundation of health in a way that’s unique to your individual body and life. So, if you enjoyed this article and are looking for ways to make your health a priority – without feeling overwhelmed – I encourage you to head over and browse through my blog. It’s full of hundreds of articles to keep you informed so you can live your healthiest life.
And if you want to take it to the next level, you can sign up for my email newsletter to get my best tip, tricks, and resources delivered straight to your inbox every week. All you have to do is enter your name and email address in the form below.
Now it’s time to hear from you. Were you surprised to learn about the underlying causes of elevated TGF beta-1? What are your favorite ways to prioritize your health right now? Leave your questions and thoughts in the comments below!
Dr. Jill Health® – MCAS Bundle MCAS treatment involves identifying and avoiding triggers that exacerbate symptoms and here is what I recommend to help support and stabilize mast cells to manage symptoms.
References:
- Cytokines, Inflammation and Pain (nih.gov)
- TGF-β – an excellent servant but a bad master | Journal of Translational Medicine | Full Text (biomedcentral.com)
- TGFB1 gene: MedlinePlus Genetics
- Upregulation of TGF-beta1 expression may be necessary but is not sufficient for excessive scarring – PubMed (nih.gov)
- Astroglial overproduction of TGF-β1 enhances inflammatory central nervous system disease in transgenic mice – Journal of Neuroimmunology (jni-journal.com)
- Pathobiology of transforming growth factor β in cancer, fibrosis and immunologic disease, and therapeutic considerations | Laboratory Investigation (nature.com)
- Transforming Growth Factor β in Tissue Fibrosis | NEJM
- TGF-β1 production in inflammatory bowel disease: differing production patterns in Crohn's disease and ulcerative colitis (nih.gov)
- TGF-b1 – Lab Results explained | HealthMatters.io
- Hypoxia upregulates the synthesis of TGF-beta 1 by human dermal fibroblasts – PubMed (nih.gov)
- Cigarette smoke-induced oxidative stress and TGF-beta1 increase p21waf1/cip1 expression in alveolar epithelial cells – PubMed (nih.gov)
- Transforming growth factor-β1 and cigarette smoke inhibit the ability of β2-agonists to enhance epithelial permeability – PubMed (nih.gov)
- Transforming growth factor-beta 1 and cortisol in differentially reared primates – PubMed (nih.gov)
26 Comments
I wish you had mentioned this connection! This was the missing link for me, after a decade of being incorrectly diagnosed with CIRS: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972366/
Thanks for sharing! There are many reasons besides CIRS that can cause elevation in TGF beta
I was diagnosed with toxic mold exposure in February, however even after 7 months of treatment my TGf b1 continues to climb. I’m doing the IV treatment, supplements and no mold is in my house (visible at past employer). I might have been re-exposed perhaps? What am I doing wrong 🤷♀️I’m sick of being sick
Robyn B
Hi Robyn
TGF beta may remain elevated for a long time after mold exposure and there are many other reasons besides mold for elevation. I would not rely on this marker as an indication of exposure alone, it should only be used in conjunction with history, VCS and all other CIRS markers to determine ongoing exposure. I suggest testing your environment to determine if there is mold
warmly
Dr Jill
I have a rash that has progressed onto most of my body. A Dr did a “mold” blood test and my TGF Beta 1 levels were 6x “normal”. My dr is convinced I am in contact with mold somewhere.
I had my house treated and retests are negative for mold.
How can I find the real cause of this elevated level? All other blood test show I am I. Normal range.
Thank you
Hi Liz,
I am sorry to hear it! I do not recommend treating the lab value of TGF beta, even if elevated. Much better to treat your symptoms and look for infectious burden or toxic exposures or other inflammatory triggers and then monitor TGF beta to go down. There are many causes of elevation besides mold.
warmly
Dr. Jill
Hi Dr. Jill,
We are practitioners and cannot find colleagues who know about TGF-beta to help interpret results for a patient. Her levels were “normal” this past 6/26/22 at 4,735, then increased significantly 4 months later to 10,688 on 10/26/22. No known mold exposure and she implements many mold cleaning tools throughout her living environment (works at home as well) such as Hepa filters in every room, and has tested several times for mold in her home and HVAC system. She doesn’t smoke. She did notice hair loss over the four month period when TGF-beta was increasing. She has had recent ultrasounds of her abdomen, pelvis, and thyroid as well as a mammogram to check for tumors a couple weeks ago. The only finding was 2 small thyroid nodules that the radiologist advised were still small enough that they did not need an FNA. Her thyroid blood markers are all normal, except she’s had elevated TPO antibodies for over 20 years. They have consistently remained in the 200-250 level. How do you recommend we proceed? What would you suggest that we test for? Other ideas to find the cause of this recent TGF-beta elevation? Appreciate any help or resources you can recommend.
I am considering taking Arthrogenx for hip stiffness. But it contains Growth Factor B.
Should I worry about that.
Where do they derive GF b from?
I had breast cancer 35 years ago. Will it cause a reoccurrance.
Thank you.
Hi Patti
I am unsure about this product but you may check serum IGF to see for sure on your labs
warmly
Dr. Jill
I would love to schedule an appointment with you to discuss my bloodwork work. Please let me know how I would do this. Thank you
Hi Susan
I am not currently accepting new patients except by referral from medical doctor or current patient. However, I am hiring a new doctor next March 2023 so feel free to call the office for more information 303-993-7910 or email info@flatironfunctionalmedicine.com
warmly
Dr. Jill
Thank you for your time in this matter. After being sick for few yrs a doctor tested me for mold which i tested high. Had house tested and remidiated. My growth hormone beta factor was 8300 when first tested and year later 9700. I also caregive for mom with dementia which is very stressfull. Having hard time with my healing as i am in stress mode alot. Been caring for mom for around 3 years now. Any advice would be appreciated.
My level is 19940 from moldy Marijuana. It’s going to be a long detoxing process.
This was very helpful. Have been struggling to make sense of TGF Beta 1!
What about low TGF Beta 1? My daughter is low and I can’t find much on how to treat this.
Low TGF beta is not generally pathological
My latest TGF-b1result was 21,720. My doctor says it’s the highest she has seen. I joked about my new record and she said that’s NOT a record I want. we are now looking for mold source in my home.
How to lower this to stop hair loss?
yes, you must treat the root cause of elevated TGF beta – decrease toxic load, avoid mold exposure, treat any active infections or viruses.
Hi Dr.Jill
I’m so happy I stumbled across your name googling my elevated TGF-b1 and the meaning ,causes and hopefully the controlling of this !
I’m 70 and have osteopenia, I ache as any 70 year old .
I’m active in the gym 3-4 times per week .
I do see a doctor who specializes in Health and Wellness ( for years) and I did tell him I ache and have a hard time with my left ankle and right hip ….. arthritic pain.
However June of this year I developed an elbow staph infection that landed me in the hospital for 5 days.
Have noooo idea where it came from ,however four years ago I fell and fractured my elbow and needed surgery to stabilize the fracture.
All has been well with it until my staph infection.
So when I saw this physician he did extensive blood work including this Human Transforming growth factor beta
(TGI-b1) the first was done in May when I was complaining about my achy joints .
After the first test of 7600 he put me on antibiotics plus vitamins: Monolaurin 600 mg …. 1 tab per day
Curcum-Eval 400 …. 1 tab per day
Andrographis Immune 2 tabs in AM and 2 tabs in PM
ArthroSoothe 2 tabs in AM and 2 tabs in PM
Plus my regular daily vitamins,fish oil ,vit D3-K2
Should I be very concerned about this rising count ?
I did feel much better after reading your article because prior articles had me believing I may have cancer,MS ,terrible lung diseases etc!
Thank you and I would love to receive your emails and newsletters!
Many things will drive up TGF beta so I would check for toxic exposure, VOC’s mold and other toxins. You may do toxic load testing through Vibrant labs who has a total toxic bundle which is urine testing. Keep an eye on the TGF beta number as well but it may take some time to come down
warmly
Dr Jill
I forgot to mention he repeated the TGF-b1 three month later and it’s now 9520 a 20,000 increase in three months!
What’s a normal range? I just got my tested at 8100, but I have no idea what to do with that number.
Labcorp raised the normal range recently because there were so many testing high. I still like to see < 2380 but depends on the lab
Hi Dr. Jill,
If the value is 2393 (flagged low by the labs I did which had standard range of 2537-22306) – would you be concerned? Or any tips to make it higher? Thanks!
Recently LabCorp changed their values on TGF beta due to new testing methods so we are still trying to figure out how the old values relate to the new as the reference range is much higher. Generally low TGF beta is less of an inflammatory issue than high TGF beta
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