Guggalsterones
Also known as: E-guggulsterone, Z-guggulsterone, guggulsterol, gugulipid, Guggulsterones
Overview
Guggulsterones are steroidal compounds, primarily E- and Z-guggulsterone, extracted from the gum resin of the Commiphora mukul tree, which has a long history of use in Ayurvedic medicine. These lipophilic phytosterols are recognized for their potential in lipid-lowering, anti-inflammatory, and purported anticancer effects. While traditionally used for various ailments, modern research has largely focused on their in vitro biological activities, particularly their ability to modulate nuclear receptors and signaling pathways. Extensive preclinical research, especially in vitro studies on cancer cell lines, has explored their mechanisms of action. However, despite promising laboratory findings, robust clinical evidence in humans for any of their purported benefits, including anticancer activity, remains limited. The quality of evidence is primarily based on systematic reviews and meta-analyses of in vitro studies, highlighting a significant gap in human clinical trials.
Benefits
Guggulsterones have demonstrated strong in vitro anticancer activity, primarily through the induction of apoptosis in various cancer cell lines. A meta-analysis of 23 in vitro studies showed that guggulsterone treatment significantly increased apoptosis in cancer cells, with odds ratios of 3.984 at 24 hours and 11.171 for treatment durations longer than 24 hours, indicating a time-dependent effect. Beyond apoptosis, guggulsterones have also been reported to inhibit cancer cell proliferation, suppress inflammatory markers like CDX2 and COX-2, reverse multidrug resistance by modulating P-glycoprotein, and inhibit angiogenesis. While these effects are significant in laboratory settings, their clinical relevance and efficacy in humans are yet to be established due to a lack of robust human clinical trials. Therefore, no specific population-specific benefits have been clinically proven.
How it works
Guggulsterones exert their biological effects by modulating multiple intracellular signaling pathways. Key pathways influenced include NF-κB, STAT3, β-Catenin, PI3K/Akt, and CHOP. This modulation leads to cellular responses such as apoptosis (programmed cell death) and inhibition of cell proliferation, particularly in cancer cell lines. Guggulsterones also interact with nuclear receptors, notably the farnesoid X receptor (FXR), and influence pathways involved in inflammation. While these mechanisms are well-documented in in vitro studies, their precise interactions with human body systems and systemic effects in vivo require further confirmation. As lipophilic compounds, their absorption and bioavailability in the human body may be variable.
Side effects
The safety profile of guggulsterones in humans is not well established due to a lack of comprehensive clinical trials. While traditional use of Commiphora mukul resin suggests some level of tolerability, formal toxicology and adverse effect profiles for isolated guggulsterones are largely undocumented. Common side effects are not well-reported in clinical settings. A significant concern is the potential for drug interactions, as guggulsterones can modulate nuclear receptors and drug transporters like P-glycoprotein. This suggests that concurrent use with other medications could alter their metabolism or efficacy, necessitating caution. Due to insufficient clinical data, specific contraindications and safety guidelines for special populations (e.g., pregnant or breastfeeding individuals, children, or those with pre-existing medical conditions) have not been established. Therefore, the use of guggulsterone supplements should be approached with caution.
Dosage
Optimal and safe dosage ranges for guggulsterones in humans have not been clinically established. In vitro studies have shown effective concentrations ranging from 5–75 μM for inducing biological effects, but these concentrations do not directly translate to human oral dosing. The minimum effective dose and maximum safe dose for human consumption remain undefined. In laboratory settings, apoptotic effects were observed to increase with longer exposure times, typically beyond 24 hours. However, this timing consideration is not applicable to human dosing without further research. Furthermore, there is no standardized clinical dosing, and the concentration of guggulsterones can vary significantly between pure guggulsterone supplements and whole Commiphora mukul resin extracts. Factors influencing absorption and bioavailability in humans are also largely unknown.
FAQs
Is guggulsterone effective for cancer treatment in humans?
Currently, evidence for guggulsterone's effectiveness in human cancer treatment is limited to promising in vitro (test tube) studies. Robust clinical trials in humans are needed to confirm these findings and establish efficacy.
Are there any proven benefits beyond anticancer effects?
Traditional uses of guggulsterone's source, Commiphora mukul, include lipid-lowering and anti-inflammatory effects. However, high-quality clinical evidence specifically for guggulsterones in these areas is lacking.
Is it safe to take guggulsterone supplements?
Safety data for guggulsterone supplements in humans are insufficient. Due to the lack of comprehensive clinical trials and potential drug interactions, caution is advised, and consultation with a healthcare professional is recommended.
How long does it take to see effects?
In laboratory studies, the pro-apoptotic effects of guggulsterones on cancer cells increased with treatment durations longer than 24 hours. However, this does not translate directly to a timeline for effects in humans.
Research Sources
- https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1155163/full – This systematic review and meta-analysis of 40 articles (23 included in meta-analysis) investigated the in vitro anticancer effects of guggulsterone. It found significant induction of apoptosis in various cancer cell lines, with odds ratios of approximately 4 at 24 hours and over 11 for longer exposures, demonstrating a time-dependent effect. The study highlighted guggulsterone's modulation of key signaling pathways (NF-κB, STAT3, PI3K/Akt) and its ability to reverse multidrug resistance. The authors emphasized the need for in vivo and clinical trials due to the current lack of human data.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC10185795/ – This article, also part of the systematic review, details the findings regarding guggulsterone's in vitro anticancer mechanisms. It confirms the significant apoptotic induction in cancer cells and the modulation of multiple signaling pathways. The research underscores the strong preclinical evidence for guggulsterone's potential as an anticancer agent, while simultaneously pointing out the critical gap in human clinical data, urging for further research to translate these findings into clinical applications.
- https://pubmed.ncbi.nlm.nih.gov/37201024/ – This PubMed entry corresponds to the same systematic review and meta-analysis, summarizing its key findings on guggulsterone's in vitro anticancer activity. It reiterates the significant apoptotic effects and the involvement of various cellular pathways. The abstract emphasizes the promising preclinical results but highlights the urgent need for well-designed clinical trials to evaluate the efficacy and safety of guggulsterone in human cancer treatment.