Dr Deb Muth 00:03
Well, welcome back to Let’s Talk Wellness Now. I am your host, Dr. Deb. And what is the most talked-about peptides in functional medicine? aren’t actually FDA approved. Not because they don’t work, but because no one’s funded the research to prove it yet. The truth is, some of the compounds that dominate wellness forums, BPC-157, TB-500, thymosin beta-4, epitalin, occupy a fascinating space between breakthrough science and unregulated experimentation. In today’s episode, we’re stepping into that grey zone, the world of investigational peptides, to separate mechanism from marketing. I’m going to walk you through the science that actually shows and where it stops, how to evaluate claims when human data don’t yet exist, and the quality, purity, and safety red flags that you need to recognise.

Dr Deb Muth 01:06
I created it in a previous episode, so go check that one out. And why honesty is the most important prescription in peptide medicine. If you’ve ever wondered whether these research-only peptides are the frontier of healing or the next functional medicine fad, this episode is for you. So grab your cup of tea or coffee, get comfortable, and let’s talk about what it really means to use peptides that are promising but still under investigation. So we’re going to break just for a second here and have a word from our sponsor. It is because of them that we stay on the air. So thank you for this. And we will be right back. Did you know sweating can literally heal your cells? Infrared saunas don’t just relax you. They detox your body, balance hormones, and boost mitochondrial energy. I’m obsessed with my Health Tech sauna. And right now, you can save $500 with my code at healthtechhealth.com slash dr-muth-req-25.

Dr. Deb Muth 02:15
All right, guys, welcome back. Let’s dive into investigational peptides, the evidence gap. So the following peptides we’re about ready to discuss are extensively in integrative, functional, and regenerative medicine circles. They may have intriguing mechanisms and promising preclinical data. However, they lack FDA approval, and the evidence quality varies dramatically. from interesting preliminary research to essentially no human data at all. And this distinction is really critical for maintaining scientific integrity. So let’s talk about immune-modulating peptides. There’s thymus and alpha-1, and this is an international story on the thymic peptides. Thymusin alpha-1, known as TA1, is marketed internationally as zidaxin.

Dr. Deb Muth 03:16
It’s a 28-amino acid polypeptide originally isolated from thymusin fraction 5, which was extracted from bovine thymus tissue. Modern production uses synthetic peptide synthesis. The thymus gland is located behind the sternum and is the primary site for T cell maturation, and thymic peptides like TA1 play roles in human system development and regulation. Now, I love thymus peptides. I love thymus glandular products. I’ve used thymus glandular products for decades. Ground-up animal thymus gland is basically what it is. There are a couple of different supplement companies that I’ve used over the years that are amazing with this. And they do a fantastic job, and they really do help to support the immune system. So when thymus peptides came out, it was really exciting because it took the whole idea of thymus support to a new level.

Dr. Deb Muth 04:17
The mechanism actually behind the thymus in alpha-1 is complex and involves multiple aspects of immune function. At the cellular level, TA1 enhances T cell maturation and differentiation, particularly the development of helper T cells and cytotoxic T cells. It modulates T cell receptor expression and can influence the balance between Th1 cell-mediated immunity and Th2 humoral immunity responses. And it also enhances the natural killer cell activity and modulates dendritic cell function, which are critical for antigen presentation. and initiation of adaptive immune responses. And on the cytokine level, TA1 influences production of interleukin-2, IL-2, interferon gamma, IFN-γ, and interleukin-10, IL-10.

Dr. Deb Muth 05:19
These create immune modulatory rather than simple immune stimulatory effects. This is a very important distinction because TA1 appears to help balance the immune system rather than simply ramping this up, which theoretically makes it safer in conditions where immune overstimulation would be a problem, such as an autoimmune disease. Hashimoto’s, autoimmune, lupus, Sjogren’s, any of those autoimmune diseases, we don’t want to overstimulate their immune system. So you want to use a product like this that’s non-stimulating. Now, the regulatory status on TA1 is geographically variable and represents one of the challenges in discussing this peptide with patients. It is not FDA-approved in the United States. However, it is approved in several other countries for specific conditions.

Dr. Deb Muth 06:19
In Italy, it’s approved for the treatment of chronic hepatitis B and hepatitis C. In China, it’s approved for chronic hepatitis B and adjunct immune compromised patients receiving vaccinations or suffering from certain infections. It has an orphan drug designation in the United States for certain cancer indications, but its designation does not constitute approval. It simply provides regulatory incentives for further development. So the evidence base for thymosin alpha-1 is substantial in some areas but comes primarily from non-US populations and research groups, which creates challenges in evaluating quality and generalizable information. So in hepatitis B and C, multiple clinical trials, many conducted in China and Italy, have examined TA1 as an adjunct to antiviral therapy.

Dr. Deb Muth 07:21
A meta-analysis by Wu and colleagues published in the Journal of Viral Hepatitis in 2013 examined 23 randomized controlled trials, including over 2,000 patients with chronic hepatitis B. The analysis found that combining TA1 with nucleoside analogs like LAMVDUDE or an and TCAVAR improved the hepatitis antigen seroconversion rates by HBV DNA clearance compared to its nucleoside analogs alone. And the effect sizes were modest but statistically significant, with the HBE-AG seroconversion rates improving from about 24% with antivirals alone to 38% in combined therapy. Now in hepatitis C, early trials before the development of direct-acting antivirals showed that TA1 combined with interferon alpha improved sustained virological responses, and compared to interferon alpha,

Dr. Deb Muth 08:30
Furon alone, particularly in difficult-to-treat populations like those with a genotype one or a high viral load. However, the advent of highly effective direct acting antivirals that achieve SRV rates, sorry, SVR rates exceeding 95%, the role of TA1 in hepatitis C has become less clear. Now in sepsis and critical illness, more recent interest has focused on TA1 in severe cases of sepsis and septic shock. Ren and colleagues published a systematic review and meta-analysis in the Frontiers of Immunology in 2022, analyzing 18 randomized controlled trials, including 1787 patients with severe sepsis or septic shock the pooled analysis showed that ta1 administration was associated with reduced 28-day mortality relative risk at 0.70 meaning a 30 reduction in mortality compared to the standard care alone and the effect appeared

Dr. Deb Muth 09:39
most pronounced in patients with sepsis-induced immunosuppression measured by HLA-DR expression in monocytes. Now, this is amazing because going forward, we’re going to talk about something that’s commonly known as cytokine storm. Now, cytokine storm really became apparent since 2020 with the viral infection that we’re dealing with in the world today. But they were already looking at this kind of cytokine storm produced by sepsis or sepsis-induced immunosuppression. And it triggered this hyperinflammatory response called the cytokine storm. And many patients who survived the initial phase of the immune suppressed stata, characterized by a T cell exhaustion, reduced antigen presentation, and increased susceptibility to secondary infections. Thymusin alpha-1, TA1, may help restore this immune competence in this phase. However, it’s important to note that patient selection and timing are critical.

Dr. Deb Muth 10:43
Giving this immune stimulant during a hyperinflammatory phase could theoretically worsen outcomes. So you don’t want to give it to them while they’re in the flare up or the sepsis or the infection, but given to them during the immunosuppression phase afterwards might be beneficial. Now there is also some cancer immunotherapy that we see with TA1 and has been studied as an adjunct in cancer treatment with the hypothesis that it could enhance immune surveillance and response to tumors. And a comprehensive review of Garci and colleagues published in Expert Opinion on Biological Therapy in 2007 examined multiple trials in melanoma, lung cancer, hepatocellular carcinoma, and other malignancies. And the results were mixed. Some trials showed improvement in the immune parameters, increased CD4 in T-cells. improved lymphocyte proliferation responses and some actually showed trends toward improved progression free survival but overall survival benefits were inconsistent and the heterogeneity of the cancer types treatment protocols and...