Geranylgeraniol for Health

Overseen By Michael Jurgelewicz, DC, CNS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Designs for Health

Must not be taking: NSAIDS, Statins, Blood thinners, others

Disqualifiers: Diabetes, Cancer, Heart disorders, others

Compensation: Varies

Number of Visits: 5

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications, including NSAIDs, statins, blood thinners, H2 blockers, PPIs, and blood sugar-lowering agents, to participate in this trial.

What data supports the effectiveness of the drug geranylgeraniol?

Research shows that geranylgeraniol can slow down the growth of certain cancer cells and help manage a jaw condition caused by some bone medications. It also has anti-inflammatory effects, which might help with blood clotting issues. ^{1 2 3 4 5}

How is the drug geranylgeraniol unique compared to other treatments?

Geranylgeraniol is unique because it works by depleting mevalonate, a key component in cell growth, which helps suppress tumor growth. Unlike many other treatments, it also has anti-inflammatory properties and can inhibit specific enzymes involved in inflammation and platelet aggregation. ^{1 3 6 7 8}

What is the purpose of this trial?

The primary purpose of this study is to investigate the effects of geranylgeraniol (GG) supplementation on testosterone levels in middle-aged (40 to 65 years) healthy men and women. The research team hypothesizes that geranylgeraniol (GG) supplementation will enhance testosterone levels and improve self-reported health outcomes in a healthy population.

Eligibility Criteria

This trial is for healthy men and women aged 40 to 65 who want to explore if taking Geranylgeraniol (GG) can boost their testosterone levels. Specific eligibility criteria are not provided, but typically participants must meet certain health standards.

Inclusion Criteria

I am between 40 and 65 years old.

I don't have a history of serious digestive, liver, or kidney diseases.

Negative pregnancy test confirmed with serum HCG on initial baseline testing and baseline testing at the start of the crossover (at 10 weeks)

Exclusion Criteria

I have taken CoQ10 or Ubiquinol supplements in the last 2 weeks.

I haven't taken hormone supplements like fenugreek or ashwagandha in the last 4 weeks.

Hemophilia

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Participants receive either geranylgeraniol (GG) supplementation or placebo for 8 weeks

8 weeks

3 visits (in-person) at baseline, 8 weeks, and 10 weeks

Washout

A 2-week washout period where no treatment is administered

2 weeks

Treatment Period 2

Participants receive the alternate treatment (either geranylgeraniol or placebo) for another 8 weeks

8 weeks

2 visits (in-person) at 10 weeks and 18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Geranylgeraniol

Trial Overview The study tests whether a supplement called Geranylgeraniol (GG) at a dose of 300 mg can increase testosterone levels over an 18-week period, compared with a placebo. Participants will switch between the GG supplement and the placebo at some point in the crossover design.

Participant Groups

Group I: Geranylgeraniol 300 mg Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Designs for Health

Lead Sponsor

Trials

3

Recruited

90+

Findings from Research

Geranylgeraniol effectively suppresses the growth of B16 melanoma cells in a dose-dependent manner, with an IC(50) of 55 µmol/L, by inducing cell cycle arrest and apoptosis.

The growth suppression is linked to the depletion of mevalonate, a crucial product of HMG-CoA reductase, suggesting that targeting this pathway could enhance the therapeutic potential of geranylgeraniol in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mevalonate depletion mediates the suppressive impact of geranylgeraniol on murine B16 melanoma cells. Katuru, R., Fernandes, NV., Elfakhani, M., et al.[2015]

Geranylgeraniol (GGO) induces apoptosis in human leukemia HL60 cells, and this process is linked to intracellular acidification, indicating a potential mechanism for its anti-cancer effects.

The induction of apoptosis by GGO is dependent on early changes in intracellular calcium levels and a decrease in pH, as shown by the inhibition of these effects when using specific inhibitors like TPA and BAPTA-AM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increase in intracellular Ca(2+) concentrations and the corresponding intracellular acidification are early steps for induction of apoptosis by geranylgeraniol in HL60 cells. Masuda, Y., Aiuchi, T., Mihara, S., et al.[2019]

Geranylgeraniol, a natural compound from Pterodon pubescens fruit oil, has been shown to inhibit platelet aggregation, particularly in the arachidonic acid pathway, indicating its potential as an anti-inflammatory agent.

The study reveals that geranylgeraniol works by inhibiting the cyclooxygenase enzyme, which is crucial in the metabolism of arachidonic acid, thus providing a new understanding of its mechanism of action in reducing platelet activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiplatelet activity of geranylgeraniol isolated from Pterodon pubescens fruit oil is mediated by inhibition of cyclooxygenase-1. Calixto, NO., da Costa e Silva, MC., Gayer, CR., et al.[2015]

Geranylgeraniol (GGOH) significantly improved the viability and migration ability of endothelial progenitor cells (EPC) that were negatively affected by nitrogen-containing bisphosphonates (N-BPs), suggesting its potential as a treatment for bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ).

The study demonstrated that GGOH treatment reduced apoptosis rates in EPC exposed to N-BPs, indicating that it may help counteract the harmful effects of these medications on bone healing and regeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isoprenoid geranylgeraniol: the influence on cell characteristics of endothelial progenitor cells after bisphosphonate therapy in vitro. Pabst, AM., Krüger, M., Ziebart, T., et al.[2018]

Medication-related osteonecrosis of the jaw (ONJ) is a serious side effect of bisphosphonates, which are commonly used to treat cancer and osteoporosis by inhibiting bone resorption.

Geranylgeraniol (GGOH) shows promise as a topical treatment to mitigate bisphosphonate-related ONJ by supporting the bone healing process, but further research is needed to establish effective delivery methods and validate its use in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Geranylgeraniol in Managing Bisphosphonate-Related Osteonecrosis of the Jaw. Chin, KY., Ekeuku, SO., Trias, A.[2022]

Geranylgeraniol effectively suppresses the growth of human prostate carcinoma cells, with an IC50 value of 80±18 µmol/L after 72 hours, indicating its potential as a therapeutic agent.

The mechanism of action involves inducing cell cycle arrest at the G1 phase and promoting apoptosis, which is linked to a decrease in the level of HMG CoA reductase protein, suggesting that targeting this enzyme could be a strategy for prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Geranylgeraniol suppresses the viability of human DU145 prostate carcinoma cells and the level of HMG CoA reductase. Fernandes, NV., Yeganehjoo, H., Katuru, R., et al.[2021]

A 10-day diet supplemented with geranylgeraniol (GGOH) in rats significantly reduced inflammation and liver damage by inhibiting the activation of NF-κB signaling, as evidenced by lower levels of inflammatory cytokines and liver enzymes.

GGOH supplementation led to decreased expression of key signaling molecules involved in NF-κB activation, such as IRAK1 and TRAF6, demonstrating its potential as a protective agent against liver inflammation and damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary supplementation with geranylgeraniol suppresses lipopolysaccharide-induced inflammation via inhibition of nuclear factor-κB activation in rats. Giriwono, PE., Shirakawa, H., Ohsaki, Y., et al.[2021]

Geranylgeraniol (GGOH), a safe food substance, promotes the differentiation of muscle cells (myoblasts) without harming their growth, suggesting potential benefits for muscle health.

GGOH reduces the expression of proteins associated with muscle atrophy, indicating its role in supporting muscle maintenance and development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Geranylgeraniol-induced Myogenic Differentiation of C2C12 Cells. Matsubara, T., Urata, M., Nakajima, T., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Mevalonate depletion mediates the suppressive impact of geranylgeraniol on murine B16 melanoma cells. [2015]

2. Japan pubmed.ncbi.nlm.nih.gov

Increase in intracellular Ca(2+) concentrations and the corresponding intracellular acidification are early steps for induction of apoptosis by geranylgeraniol in HL60 cells. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

Antiplatelet activity of geranylgeraniol isolated from Pterodon pubescens fruit oil is mediated by inhibition of cyclooxygenase-1. [2015]

4. Germany pubmed.ncbi.nlm.nih.gov

Isoprenoid geranylgeraniol: the influence on cell characteristics of endothelial progenitor cells after bisphosphonate therapy in vitro. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

The Role of Geranylgeraniol in Managing Bisphosphonate-Related Osteonecrosis of the Jaw. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Geranylgeraniol suppresses the viability of human DU145 prostate carcinoma cells and the level of HMG CoA reductase. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Dietary supplementation with geranylgeraniol suppresses lipopolysaccharide-induced inflammation via inhibition of nuclear factor-κB activation in rats. [2021]

8. Greece pubmed.ncbi.nlm.nih.gov

Geranylgeraniol-induced Myogenic Differentiation of C2C12 Cells. [2020]