Nature’s most potent antioxidants - research-validated - defend your brain, heart & metabolic health
Exploring Geranylgeraniol's Therapeutic Potential
Research Aware
Our goal is to advance understanding of geranylgeraniol's mechanisms, including cell cycle regulation and anti-inflammatory pathways, to unlock its potential in treating various systemic diseases effectively and to share with people interested in their health.
Geranylgeraniol Activity in Systemic Disease
Geranylgeraniol (GG) demonstrates significant therapeutic potential across multiple disease states through diverse mechanisms including cell cycle regulation, anti-inflammatory pathways, mitochondrial protection, and metabolic modulation. Below is an extensively researched collection of evidence-based benefits organized by disease category, supported by peer-reviewed studies.
Index (Clickable)
Cancer
GG inhibits cancer cell proliferation by disrupting mevalonate pathway signalling:
Breast cancer:
Mitosis disruption: GG depletion suppresses kinetochore/centromere gene expression (BUB1, PLK1, CENPM, ZWINT), arresting mitosis and inducing apoptosis in MDA-MB-231 cells. Atorvastatin reduced expression of 32 key kinetochore genes by 85-95%, which was fully rescued by geranylgeraniol co-treatment.
YAP/TAZ pathway: Geranylgeranylation signaling promotes breast cancer cell proliferation through YAP-mediated activation of kinetochore/centromere genes, with GG depletion significantly impairing mitotic progression.
Melanoma:
Melanoma: GG suppresses B16 melanoma (IC<sub>50</sub> = 55 µmol/L) and DU145 prostate cancer cells (IC<sub>50</sub> = 80 µmol/L) via mevalonate depletion and HMG-CoA reductase downregulation, triggering G1-phase cell cycle arrest.
Prostate Cancer:
Geranylgeraniol suppresses the viability of human DU145 prostate carcinoma cells and the level of HMG CoA reductase. [2013].
Leukemia:
GG induces apoptosis in HL60 cells through intracellular acidification and calcium flux modulation.
.
Cardiovascular Disease
Heart Health and Circulation
CoQ10 synthesis: As a precursor to CoQ10, GG supports heart muscle function, improves circulation, and helps maintain healthy blood pressure. Wang, C., & Hekimi, S. (2016). Understanding Ubiquinone. Trends in Cell Biology, 26(5), 367-378.
Statin myopathy prevention: GG prevents statin-induced skeletal muscle fatigue without causing adverse effects in cardiac or vascular smooth muscle performance, completely abrogating force production reduction in fast-twitch glycolytic muscle
.
Nervous System Disease (Including Dementia & Alzheimer's)
Neuroinflammation and Neuroprotection
Microglial activation: GG dose-dependently suppresses LPS-induced inflammatory cytokines (Il-1β, Tnf-α, Il-6, Cox-2) in mouse-derived MG6 microglial cells through NF-κB pathway inhibition
Mitochondrial protection: In neuronal cell models, GG co-administration reduces inflammatory markers and prevents mitochondrial damage, maintaining cellular shape and components while reducing programmed cell death
Alzheimer's Disease Mechanisms
Amyloid-β production: GG and geranylgeranyl pyrophosphate preferentially increase Aβ42 production by stimulating γ-secretase activity, though this presents a complex relationship requiring further investigation
Brain isoprenoid levels: FPP and GGPP levels are elevated 36% and 56% respectively in Alzheimer's brain tissue compared to controls, suggesting dysregulated mevalonate pathway involvement.
.
Eye Disease (Schnyder Corneal Dystrophy)
UBIAD1 regulation: GG serves as the molecular target for HMG CoA reductase degradation through UBIAD1 protein interactions, with mutations in UBIAD1 causing cholesterol accumulation in corneas.
.
Glycemic Disease (Diabetes)
Glucose Homeostasis
Diabetes prevention: GG may prevent statin-induced diabetes without interfering with cholesterol-lowering effects, potentially through restoration of protein prenylation required for insulin secretion.
PPARγ activation: GG induces PPARγ expression and enhances thiazolidinedione medication effects in mouse adipocytes and human hepatocytes.
Metabolic improvement: Dietary GGOH supplementation alleviates obesity-associated glucose intolerance and improves bone microstructure in obese mice.
https://www.sciencedirect.com/science/article/abs/pii/S0271531721000439
.
Muscle Disease and Myopathy
Statin-Associated Muscle Symptoms (SAMS)
Comprehensive muscle protection: GG prevents statin-induced toxicity in myoblasts (400% improvement) and myotubes (100% improvement), while improving energy production and preventing ATP depletion.
Mitochondrial preservation: GG completely prevents statin-associated membrane toxicity, cellular respiration impairment, and reactive oxygen species production in muscle cells.
Force restoration: GG supplementation completely reversed statin-induced reduction in muscle force production and improved cardiac muscle contraction/relaxation.
Diabetic Muscle Atrophy
Mitochondrial quality improvement: GGOH supplementation mitigates soleus muscle atrophy in diabetic rats through decreased mitochondrial fragmentation (reduced DRP1) and improved autophagy (reduced LC3A/LC3B).
Cross-sectional area preservation: GG treatment significantly preserved muscle cross-sectional area compared to diabetic controls while reducing pro-inflammatory cytokine IL-1β.
.
Bone Disease
Bisphosphonate-Related Complications
Osteonecrosis prevention: Topical GG counteracts bisphosphonate-induced osteonecrosis of the jaw by promoting bone healing and reducing osteoclast activity.
Osteoblast/osteoclast restoration: GG supplementation restores viability in human osteoblasts and osteoclasts suppressed by nitrogen-containing bisphosphonates like zoledronate.
Vitamin K2 pathway: GG serves as a precursor for vitamin K2 (MK-4) synthesis, which inhibits osteoclast formation via RANKL expression suppression.
Liver Disease and Hepatic Protection
Anti-inflammatory Effects
LPS-induced inflammation: 10-day high-dose GGOH supplementation significantly inhibits LPS-induced liver inflammation and NF-κB activation in rats, reducing plasma inflammatory cytokines and liver damage markers (ALT/AST).
Signal transduction modulation: GG substantially decreases IRAK1 and TRAF6 protein levels, leading to reduced NF-κB signal transduction and liver protection.
Lung Disease
Acute Lung Injury
Anti-inflammatory protection: Related compound geraniol alleviates LPS-induced acute lung injury through TLR4-mediated NF-κB pathway inhibition, reducing pulmonary inflammation and apoptosis.
Macrophage modulation: GGPPS deficiency in macrophages aggravates lung injury, suggesting GG supplementation may provide protective effects in acute respiratory distress syndrome.
.
Rare Autoinflammatory Disease
Hyper-IgD Syndrome (HIDS)
Clinical pilot study: First reported clinical trial in 3 HIDS patients showed GG supplementation (150mg daily for 3 months) demonstrated safety with no liver toxicity, though plasma GGPP levels were not significantly increased.
https://www.medrxiv.org/content/10.1101/2024.07.17.24309492v1
Proteomic improvements: GG supplementation reversed some features of HIDS-specific plasma protein signatures, highlighting potential to modulate inflammation and protein prenylation pathways
https://www.medrxiv.org/content/medrxiv/early/2024/07/18/2024.07.17.24309492.full.pdf
.
Hormonal Health
Testosterone Enhancement
Steroidogenesis enhancement: GG enhances testosterone and progesterone production in testis-derived cells through cAMP/PKA signalling pathway activation.
Clinical trial evidence: Ongoing crossover clinical trial (NCT06747624) investigating GG effects on testosterone levels in middle-aged adults (40-65 years). Previous studies suggest benefits specifically in males with low baseline testosterone.
Safety profile: 8-week randomized trial demonstrated GG supplementation (150-300mg daily) does not significantly alter blood chemistry, hematology, or sex hormone profiles in healthy adults.
.
Inflammatory and Autoimmune Conditions
Rheumatoid Arthritis
Antiarthritic activity: Related compound geraniol significantly reduced paw edema, restored joint structure, and normalized inflammatory markers (RF, CRP, ESR) in complete Freund's adjuvant-induced arthritis models.
Molecular targets: Geraniol downregulates pro-inflammatory cytokines (TNF-α, IL-1β), COX-2, and matrix metalloproteinase-1 (MMP-1) through direct molecular interactions.
.
Key Mechanistic Pathways
Protein prenylation restoration: GG replenishes geranylgeranyl pyrophosphate for essential protein modifications
Mitochondrial protection: Prevents oxidative damage and maintains cellular energy production
NF-κB pathway inhibition: Reduces inflammatory signaling across multiple tissue types
Cell cycle regulation: Modulates kinetochore/centromere gene expression in cancer cells
Vitamin K2 synthesis: Serves as precursor for bone health and cardiovascular protection
Clinical Note: Multiple ongoing trials (NCT06747624, NCT Phase Wellness 2025) are evaluating GG's impact on testosterone, cardiovascular health, and broader therapeutic applications, with preliminary evidence suggesting significant potential across diverse disease states.