The Active Ingredient in GG-PRIME™: What is Geranylgeraniol?

Geranylgeraniol (GG) supports muscle growth and repair through several mechanisms:

1. It induces myogenic differentiation of muscle stem cells (satellite cells) into mature muscle cells (myoblasts and myotubes), a crucial process for muscle growth and regeneration.[1][2] GG upregulates the expression of myogenic regulatory factors like MyoD and myogenin that drive this differentiation process.

Translation: Promotes muscle cell flourishing

2. GG suppresses the expression of muscle-specific ubiquitin ligases like Atrogin-1 that are involved in muscle protein degradation and atrophy.[1][2][4] By inhibiting these atrophy-promoting factors, GG prevents excessive muscle breakdown and wasting.

3. In vivo studies show that oral administration of GG rescues denervation-induced skeletal muscle atrophy by reducing the decrease in muscle fiber cross-sectional area and suppressing Atrogin-1 expression.[4] This demonstrates GG's ability to counteract muscle atrophy and promote muscle maintenance.

Translation: GG prevents the breakdown muscle by suppressing a protein involved in atrophy

4. GG improves muscle force production and prevents skeletal muscle fatigue, likely by supporting mitochondrial function and energy production within muscle cells.[1]

5. GG is a precursor for the synthesis of coenzyme Q10 (CoQ10), an essential nutrient for ATP generation and mitochondrial respiration in muscle cells, thereby enhancing muscle energy metabolism.[1][3]

Translation: Improves muscle stamina via mitochondrial health and coq10 production

In summary, GG facilitates muscle growth by stimulating the differentiation of muscle stem cells into mature muscle fibers, while also preventing muscle wasting by inhibiting atrophy pathways. It supports muscle repair and regeneration by maintaining muscle mass and function during atrophic conditions like denervation or disuse.[1][2][4]

Citations:
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691100/
[2] https://iv.iiarjournals.org/content/32/6/1427
[3] https://americanrivernutrition.com/geranylgeraniol-supplementation-may-benefit-males-with-low-testosterone-clinical-study/
[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652489/
[5] https://www.wholefoodsmagazine.com/articles/3268-a-new-supplement-brings-many-health-benefits-gg

COENZYME Q10

Supplementing with geranylgeraniol (GG) can increase CoQ10 levels and through several mechanisms, which in turn can enhance energy production. Here’s how GG supplementation works to boost CoQ10 levels:

1. Precursor Role: GG is a precursor in the biosynthesis of CoQ10. The mevalonate pathway, which produces cholesterol and other essential metabolites, also synthesizes CoQ10. GG is an essential building block in this pathway, contributing directly to the production of CoQ10[1][2].

2. Enhanced Absorption and Utilization: CoQ10, especially in its ubiquinone form, has poor gastrointestinal absorption and limited intracellular transport. GG, with a molecular weight one-third that of CoQ10, can easily penetrate cell membranes and enhance the endogenous production of CoQ10. This makes GG a more efficient way to increase intracellular CoQ10 levels compared to direct CoQ10 supplementation[1][2].

3. Synergistic Effects with CoQ10: GG works synergistically with CoQ10 by not only serving as a precursor but also by enhancing the metabolic pathways that synthesize CoQ10 and other essential cell-signaling molecules. This synergy can lead to improved cellular energy metabolism, increased ATP production, and better physical and mental performance[1][2].

4. Compensation for Age-Related Decline: As people age, the endogenous production of CoQ10 declines, which affects mitochondrial function and energy production. GG supplementation can compensate for this decline by boosting the body's natural CoQ10 synthesis, thereby improving mitochondrial respiration and ATP production[1][2].

In summary, GG supplementation increases CoQ10 levels by acting as a precursor in its biosynthesis, enhancing absorption and intracellular transport, compensating for age-related declines, mitigating statin side effects, and working synergistically with CoQ10. These mechanisms collectively support improved energy production and overall cellular function.

Citations:
[1] https://www.casi.org/node/1273
[2] https://www.townsendletter.com/article/453-geranylgeraniol-coq10-cell-essential-metabolites/
[3] https://www.healthline.com/nutrition/coenzyme-q10
[4] https://pubmed.ncbi.nlm.nih.gov/26526835/
[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691100/
[6] https://www.mountsinai.org/health-library/supplement/coenzyme-q10

STATINS EFFECT ON COQ10

Statin therapy significantly lowers CoQ10 levels in the blood. Here are the key findings:

- One study found that treatment with simvastatin (20 mg/day) for 4 weeks resulted in a 30% decrease in blood CoQ10 levels[3][4].
- Another study involving healthy volunteers treated with pravastatin (20 mg/day) or simvastatin (20 mg/day) for 4 weeks showed similar decreases of 50% and 54% in blood CoQ10 levels, respectively[4].
- A larger study with hypercholesterolemic patients treated with increasing doses of pravastatin (20, 40, and 80 mg/day) and lovastatin (10, 20, and 40 mg/day) over 18 weeks found that blood CoQ10 levels decreased to 80% of baseline with pravastatin and 71% of baseline with lovastatin[4].


- Based on the available studies, the average reduction in blood CoQ10 levels due to statin therapy ranges from approximately 30% to 54%, depending on the specific statin and dosage used[3][4].

In summary, statin therapy can lower CoQ10 levels in the blood by an estimated average of 30% to 54%, with variations depending on the type and dosage of the statin used[1][3][4].

Citations:
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230224/
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171566/
[3] https://jamanetwork.com/journals/jamaneurology/fullarticle/786017
[4] https://jamanetwork.com/journals/jamaneurology/article-abstract/786017
[5] https://www.mdpi.com/2076-3921/11/9/1698
[6] https://academic.oup.com/jcem/article/104/7/2501/5115827
[7] https://www.ccjm.org/content/ccjom/77/7/435.full.pdf
[8] https://www.ajconline.org/article/S0002-9149%2812%2901186-1/pdf

MITOCHONDRIAL HEALTH

Mitochondria are often referred to as the "powerhouses" of the cell due to their critical role in energy production. They produce over 90% of our body's energy through these mechanisms:

1. ATP Production:
- Mitochondria generate the majority of the cell's adenosine triphosphate (ATP), the primary energy currency of the cell, through a process called oxidative phosphorylation[4][5].
- This process occurs in the inner mitochondrial membrane, where enzymes of the electron transport chain (ETC) facilitate the transfer of electrons from nutrients to oxygen, creating a proton gradient that drives ATP synthesis[4][5].

2. Krebs Cycle:
- The Krebs cycle (or citric acid cycle) takes place in the mitochondrial matrix and produces NADH and FADH2, which are essential for the electron transport chain[4][5].
- These molecules donate electrons to the ETC, leading to the production of ATP[4][5].

GERANYLGERANIOL (GG) EFFECT ON MITOCHONDRIAL HEALTH

1. Mitochondrial Quality Control:
- GG supplementation has been shown to improve mitochondrial quality control by affecting processes such as mitochondrial fusion, fission, and autophagy[1][2][3].
- In diabetic rats, GG supplementation resulted in lower levels of mitochondrial fission protein DRP1 and higher levels of mitochondrial fusion protein MFN2, indicating a reduction in mitochondrial fragmentation and an improvement in mitochondrial integrity[1][2][3].

2. Reduction in Inflammation and Oxidative Stress:
- GG has been shown to reduce inflammation and oxidative stress, which are key factors in mitochondrial damage[1][2].
- In diabetic rats, GG supplementation led to lower levels of inflammatory markers such as IL-1β and higher levels of antioxidant enzymes like SOD2[2].

3. Autophagy and Mitophagy:
- GG supplementation enhances the clearance of damaged mitochondria through autophagy and mitophagy, processes that are crucial for maintaining mitochondrial health[1][2][3].
- The studies showed that GG-treated rats had lower levels of autophagy markers LC3A and LC3B, indicating increased degradation of damaged organelles[1][2][3].

4. Muscle Health and Atrophy Prevention:
- GG supplementation has been shown to mitigate muscle atrophy by improving mitochondrial function and muscle cross-sectional area (CSA)[1][2][3].
- In diabetic rats, GG supplementation resulted in a greater muscle CSA compared to untreated diabetic rats, suggesting a protective effect against muscle wasting[1][2][3].

Bottom Line:
Mitochondria are essential for energy production in cells, primarily through the generation of ATP. Geranylgeraniol (GG) has been shown to boost mitochondrial health by improving mitochondrial quality control, reducing inflammation and oxidative stress, enhancing autophagy and mitophagy, and preventing muscle atrophy. [1][2][3][4][5].

Translation: GG can improve overall mitochondrial health and increase coq10 - both essential for energy production

Citations:
[1] https://www.ttuhsc.edu/medicine/medical-education/documents/ACSM_2022__Nigel_Jiwan.pdf
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9677755/
[3] https://journals.lww.com/acsm-msse/fulltext/2022/09002/geranylgeraniol_supplementation_mitigates_muscle.2044.aspx
[4] https://www.medicalnewstoday.com/articles/320875
[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4321783/
[6] https://www.genome.gov/genetics-glossary/Mitochondria
[7] https://www.texaschildrens.org/content/media/insufficient-energy-production-mitochondria-causes-photoreceptor-neurons-degenerate
[8] https://digitalcommons.wku.edu/ijesab/vol2/iss13/28/
[9] https://www.britannica.com/science/mitochondrion
[10] https://www.casi.org/node/1060
[11] https://bscb.org/learning-resources/softcell-e-learning/mitochondrion-much-more-than-an-energy-converter/
[12] https://www.nature.com/scitable/topicpage/mitochondria-14053590/
[13] https://journals.lww.com/acsm-msse/fulltext/2021/08001/geranylgeraniol_increases_autophagy_and_mitophagy.876.aspx
[14] https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04369-z
[15] https://www.news-medical.net/health/Beyond-Energy-Mitochondrias-Role-in-Diet-and-Health.aspx
[16] https://www.researchgate.net/publication/363321679_Geranylgeraniol_Supplementation_Mitigates_Muscle_Atrophy_With_Mitochondrial_Quality_Improvement_In_Diabetic_Rats_2240

COGNITION

The research on geranylgeraniol and it's effect on the brain are in the nascent stages with most information coming from animal models. According to the preliminary data available, along with the knowledge of structure/function relationships, here is how GG may effect cognition:

Geranylgeranylation, a biochemical modification involving the attachment of geranylgeranyl groups (derived from geranylgeranyl pyrophosphate, GGPP) to specific proteins, could potentially impact cognition through several mechanisms:

1. Protein Function and Localization: Geranylgeranylation is a type of prenylation that typically involves the covalent attachment of geranylgeranyl groups to the cysteine residues in the C-terminal motifs of certain proteins. This modification can affect the protein's function, its localization within the cell, and its interactions with other proteins. Since many proteins involved in signaling pathways critical to brain function undergo prenylation, changes in geranylgeranylation patterns could influence neuronal signaling and brain health.

• Source: Staal, R. G. W., & Zwart, R. (2017). "Protein Prenylation: Enzymatic Mechanisms, Functional Implications, and Inhibitors." ChemBioChem, 18(24), 2468-2480. Link

2. Neuronal Signaling: Proteins modified by geranylgeranylation often include small GTPases, such as members of the Rab, Rho, and Rac families. These GTPases play crucial roles in various aspects of neuronal function, including axon guidance, dendrite morphology, and synaptic plasticity—all of which are essential for learning and memory. Disruptions in the proper functioning of these proteins could potentially impair cognitive processes.

• Source: Pereira-Leal, J. B., & Seabra, M. C. (2001). "Evolution of the Rab family of small GTP-binding proteins." Journal of Molecular Biology, 313(4), 889-901. Link

3. Neuroprotection and Neuroinflammation: Geranylgeranylated proteins are involved in cellular processes like apoptosis (programmed cell death) and inflammation. In the brain, dysregulated apoptosis and increased inflammation can lead to neurodegenerative changes that impact cognition. By influencing these pathways, geranylgeranylation could potentially modulate neuroprotective responses or contribute to neuroinflammatory conditions, thereby affecting cognitive function.

• Source: Lin, M. Y., & Beal, M. F. (2006). "Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases." Nature, 443(7113), 787-795. Link

4. Synaptic Function: The proper geranylgeranylation of proteins is critical for the maintenance of synaptic function. Synapses are the points of communication between neurons, and their function is essential for transmitting information throughout the nervous system. Any alteration in synaptic protein geranylgeranylation could disrupt synaptic stability or neurotransmitter release, thus affecting learning and memory.

• Source: Salaun, C., Greaves, J., & Chamberlain, L. H. (2010). "The intracellular dynamic of protein palmitoylation." Journal of Cell Biology, 191(7), 1229-1238. Link

5. Brain Plasticity: Brain plasticity, or neuroplasticity, refers to the brain's ability to change and adapt as a result of experience. This encompasses the strengthening or weakening of synapses in response to increases or decreases in activity. Proteins affected by geranylgeranylation are involved in the remodeling of the actin cytoskeleton within neurons, a process that is fundamental to the structural changes associated with long-term potentiation (LTP) and long-term depression (LTD). These are the primary mechanisms behind learning and memory.

• Source: Yoshihara, Y., & De Roo, M. (2009). "Postsynaptic signaling to chromatin." Nature Reviews Neuroscience, 10(6), 421-432. Link

Geranylgeranylation may affect cognition by influencing critical aspects of neuronal function and brain plasticity. However, as stated the research is limited and ongoing.  

• STUDIES:
  
  Effects on Cognitive Impairment
  
  - In a study using a D-galactose-induced aging mouse model, GG treatment was shown to reverse cognitive impairment, memory loss, and spatial learning deficits caused by D-galactose.[1] This suggests GG can improve cognitive function in age-related cognitive decline.
  
  - GG modulated behavioral changes induced by D-galactose, such as motor abnormalities and impaired novelty-induced exploratory behavior.[1] This indicates GG can mitigate cognitive and behavioral deficits associated with aging.
  
  - In a separate study on rats, GG improved memory impairment and neurotoxicity induced by zinc oxide nanoparticles, likely through its antioxidant effects.[1]
  
  Neuroprotective Mechanisms
  
  - GG reduced inflammatory markers and mitochondrial damage in neuronal cells, maintaining mitochondrial shape and function.[2] This suggests GG has neuroprotective effects by reducing inflammation and preserving mitochondrial integrity.
  
  
  - The antioxidant and anti-inflammatory properties of GG likely play a role in its neuroprotective and cognitive-enhancing effects by reducing oxidative stress and neuroinflammation, which are implicated in cognitive decline and neurodegenerative diseases.[1][2]
  
  While more research is needed, the available evidence suggests that geranylgeraniol has the potential to improve cognitive function, particularly in age-related cognitive impairment and neurodegenerative conditions, through its neuroprotective, anti-inflammatory, and antioxidant mechanisms.[1][2]
  
  Citations:
  [1] https://www.aging-us.com/article/205677/text
  [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813225/
  [3] https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/geranylgeraniol
  [4] https://www.mdbiowellness.com/blogs/doctors-desk/geranylgeraniol-benefits-pain-relief
  [5] https://www.sciencedirect.com/topics/medicine-and-dentistry/geranylgeraniol

Like cognition, the research on geranylgeraniol and it's effect on the blood sugar regulation are in the nascent stages with most information coming from animal models. According to the preliminary data available, along with the knowledge of structure/function relationships, here is how GG may effect blood sugar levels:

Geranylgeraniol (GG) and its derivative geranylgeranyl pyrophosphate (GGPP) play significant roles in the regulation of glucose transporter 4 (GLUT4) expression and function, particularly in the context of insulin-stimulated glucose uptake in skeletal muscle.

Geranylgeraniol and GLUT4 Expression

1. Statin-Induced Effects and GG Supplementation:
- Statins, commonly prescribed to manage cholesterol levels, can inhibit the synthesis of GGPP, which is crucial for the proper functioning of GLUT4. This inhibition can impair insulin-stimulated glucose uptake by reducing GLUT4 translocation to the plasma membrane.
- Supplementation with GG, which can be converted to GGPP, has been shown to counteract the negative effects of statins on glucose uptake. Specifically, GG administration improved both glucose tolerance and insulin tolerance in vivo, and largely reversed the decreased postprandial glucose uptake in skeletal muscle caused by statin treatment[2].

2. Mechanisms of GLUT4 Regulation:
- GGPP is essential for the translocation of GLUT4 to the plasma membrane, a critical step for insulin-stimulated glucose uptake. Inhibition of GGPP synthesis or function leads to decreased surface expression of GLUT4, thereby impairing glucose uptake.
- Studies have demonstrated that genetic inhibition of enzymes involved in GGPP synthesis, such as GGPS1, PGGT1B, and RABGGTA, results in reduced surface GLUT4 expression. Conversely, supplementation with GGPP restores the impaired GLUT4 translocation caused by statin treatment[2].



Summary

The relationship between geranylgeraniol levels and GLUT4 expression is primarily mediated through the role of GG in facilitating GLUT4 translocation to the plasma membrane. Statins can deplete GG levels, impairing GLUT4 function and glucose uptake. GG supplementation can mitigate these effects by restoring GG levels, thereby improving GLUT4 translocation and enhancing insulin-stimulated glucose uptake in skeletal muscle. This relationship underscores the importance of GG in maintaining proper glucose metabolism, particularly in the context of diabetes and statin use.

Translation: GG is essential for the proper construction of glucose transporters on the cell membrane. These transporters help move sugar from the blood into the cell for energy. Without enough GG, there are insufficient glucose transporters, which can lead to elevated blood sugar levels, increasing the risk and severity of type 2 diabetes.

Citations:
[1] https://iv.iiarjournals.org/content/36/6/2638
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9745480/
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9677755/
[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672939/
[5] https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0027854
[6] https://www.sciencedirect.com/science/article/pii/S1550413118307368
[7] https://www.sciencedirect.com/science/article/am/pii/S0271531721000439
[8] https://www.sciencedirect.com/science/article/pii/S0014579301030071
[9] https://www.researchgate.net/figure/Impaired-GLUT4-translocation-to-plasma-membrane-caused-by-simvastatin-is-restored-by_fig2_362670463
[10] https://www.researchgate.net/publication/328438543_Geranylgeraniol_Induces_PPARg_Expression_and_Enhances_the_Biological_Effects_of_a_PPARg_Agonist_in_Adipocyte_Lineage_Cells
[11] https://www.researchgate.net/figure/Effect-of-myr-Akt-on-HA-GLUT4-GFP-translocation-in-3T3-L1-adipocytes-treated-with_fig1_7995919
[12] https://journals.sagepub.com/doi/10.1177/1535370215620855
[13] https://www.cell.com/cell-reports/pdf/S2211-1247%2822%2901077-4.pdf

Geranylgeraniol (GG) may help improve insulin sensitivity and mitigate statin-induced insulin resistance through the following mechanisms:

1. Geranylgeranyl pyrophosphate (GGPP), which is synthesized from GG, regulates glucose uptake in skeletal muscle cells via two pathways:

a. GGTase I-mediated insulin signaling-dependent pathway: GGPP is required for proper insulin signaling through Akt phosphorylation, which facilitates GLUT4 translocation and glucose uptake into muscle cells.[2][3] Inhibition of this pathway contributes to statin-induced insulin resistance.

b. GGTase II-mediated insulin signaling-independent pathway: GGPP is necessary for the geranylgeranylation of Rab proteins like Rab8A, which directly regulate GLUT4 translocation and glucose uptake independent of insulin signaling.[2][3]

Translation: GG is involved with the expression of Sugar Transporters (GLUT4) on the outer cell membrane. These transporters facilitate the intake of sugar from the blood into the cell.

2. Supplementation with GG can prevent and reverse statin-induced skeletal muscle insulin resistance both in vitro (in muscle cells) and in vivo (in animal models).[2][3] This suggests that GG supplementation may help restore insulin sensitivity compromised by statin use.

3. Statins deplete GGPP levels by inhibiting the mevalonate pathway, leading to impaired protein geranylgeranylation and subsequent insulin resistance in skeletal muscle.[1][2][3] Providing exogenous GG can replenish GGPP levels and counteract this effect of statins.

Effect on PPARγ

PPARγ is a receptor located on the nucleus inside the cell. The nucleus is the inner core inside every cell that contains our DNA. When this receptor is activated it signals certain genes to turn on and take action.

Geranylgeraniol (GG) has a significant effect on the expression and activation of the peroxisome proliferator-activated receptor gamma (PPARγ), which plays a crucial role in glucose metabolism and insulin sensitivity. Here are the key details:

Induces PPARγ Expression

- GG increases the mRNA and protein expression levels of PPARγ in adipocyte lineage cells like 3T3-L1 pre-adipocytes and C3H10T1/2 mouse embryonic fibroblasts.[6][8][9]
- By upregulating PPARγ expression, GG promotes the differentiation of pre-adipocytes into mature adipocytes, a process known as adipogenesis.[6][8]

Enhances PPARγ Activation

- GG enhances the biological effects of rosiglitazone, a thiazolidinedione class PPARγ agonist, on adipocyte lineage cells.[6][8]
- When combined with rosiglitazone, GG further increases adipogenesis and lipid droplet formation in these cells, indicating enhanced PPARγ activation.[6][8]

Potential Mechanisms

- GG is a precursor for geranylgeranylpyrophosphate (GGPP), which is involved in the geranylgeranylation (prenylation) of intracellular proteins like small GTPases.[6][8]
- GGPP-induced protein prenylation may modulate signaling pathways that regulate PPARγ expression and activity.[6][8]
- Statins, which inhibit the mevalonate pathway and reduce GGPP levels, have been shown to decrease PPARγ expression and inhibit adipogenesis, further suggesting a link between GG and PPARγ regulation.[6][8][9]

Translation: GG may be involved in regulating a protein that signals activation of PPARy, a gene regulator that turns on genes to stimulate blood sugar control mechanisms.

In summary, geranylgeraniol supplementation may help statin users maintain proper insulin signaling and GLUT4 translocation in skeletal muscle, thereby improving insulin sensitivity and glucose uptake.[1][2][3] This could potentially mitigate the increased risk of type 2 diabetes associated with statin use.

Citations:
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691100/
[2] https://pubmed.ncbi.nlm.nih.gov/35961942/
[3] https://www.researchgate.net/publication/362670463_Geranylgeranyl_pyrophosphate_depletion_by_statins_compromises_skeletal_muscle_insulin_sensitivity
[4] https://onlinelibrary.wiley.com/doi/abs/10.1002/jcsm.13061
[5] https://americanrivernutrition.com/geranylgeraniol-supplementation-may-benefit-males-with-low-testosterone-clinical-study/

[6] https://www.researchgate.net/publication/328438543_Geranylgeraniol_Induces_PPARg_Expression_and_Enhances_the_Biological_Effects_of_a_PPARg_Agonist_in_Adipocyte_Lineage_Cells
[7] https://www.sigmaaldrich.com/AR/en/tech-docs/paper/1075308
[8] https://iv.iiarjournals.org/content/32/6/1339
[4] https://twu-ir.tdl.org/items/da03a0fe-2f25-4c5f-aa3c-80f182d0bc47
[9] https://pubmed.ncbi.nlm.nih.gov/30348686/

Geranylgeraniol (GG) plays a crucial role in supporting vitamin K function and bone health. Here's a detailed explanation of its effects and importance:

Geranylgeraniol (GG) and Vitamin K

GG is the isoprenoid side chain of menaquinone-4 (MK-4), one of the most bioactive forms of vitamin K2.[1][2] Vitamin K is essential for activating proteins involved in bone mineralization, such as osteocalcin and matrix Gla protein (MGP).[3] Without adequate vitamin K, these proteins remain inactive, leading to impaired bone formation and increased risk of fractures.

By providing the isoprenoid side chain for MK-4, GG supports the proper function of vitamin K2 in activating these bone-related proteins.[2] This synergistic relationship between GG and vitamin K2 is particularly important for maintaining bone health.

Importance for Bone Health

1. Supports Bone Formation and Mineralization: GG enhances the activity of vitamin K2, which in turn activates osteocalcin and MGP. Activated osteocalcin promotes bone mineralization, while activated MGP prevents calcium from depositing in soft tissues like blood vessels.[2][3] This dual action supports bone formation and prevents calcium depositing into the arterial walls.

2. Counteracts Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ)**: Bisphosphonates are commonly prescribed for osteoporosis, but they can lead to BRONJ, a severe side effect characterized by jaw bone necrosis. GG has been shown to reverse the cellular effects of bisphosphonates on oral fibroblasts, potentially mitigating the risk of BRONJ.[2]

3. Supports Bone Microstructure and Density: Studies in obese mice have demonstrated that dietary geranylgeraniol can improve bone microstructure and increase bone mineral density, potentially by suppressing inflammation and modulating the gut microbiome.[2]


By supporting vitamin K function and bone metabolism, GG plays a crucial role in maintaining bone health, promoting bone formation, and potentially mitigating the adverse effects of certain osteoporosis treatments.[1][2][3] Its inclusion in vitamin K supplements or bone health formulations can provide additional benefits for optimal bone health.

Citations:
[1] https://www.amazon.com/Designs-Health-Vitamin-Supreme-Capsules/dp/B003CF7TOA
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114760/
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040265/
[4] https://www.amazon.com/Designs-Health-Annatto-GG-300-Geranylgeraniol/dp/B0CM6NVRYX
[5] https://www.designsforhealth.com/products/vitamin-d-synergy

1 . Statin-induced muscle damage and atrogin-1 induction is the result of a geranylgeranylation defect

Cao P, Hanai J, Tanksale P, Imamura S, Sukhatme VP, Lecker SH. Statin-induced muscle damage and atrogin-1 induction is the result of a geranylgeranylation defect. FASEB J. 2009 Sep;23(9):2844-54. doi: 10.1096/fj.08-128843. Epub 2009 Apr 30. PMID: 19406843; PMCID: PMC2735363.

2. Geranylgeraniol Induces PPARγ Expression and Enhances the Biological Effects of a PPARγ Agonist in Adipocyte Lineage Cells

Matsubara T, Takakura N, Urata M, Muramatsu Y, Tsuboi M, Yasuda K, Addison WN, Zhang M, Matsuo K, Nakatomi C, Shigeyama-Tada Y, Kaneuji T, Nakamichi A, Kokabu S. Geranylgeraniol Induces PPARγ Expression and Enhances the Biological Effects of a PPARγ Agonist in Adipocyte Lineage Cells. In Vivo. 2018 Nov-Dec;32(6):1339-1344. doi: 10.21873/invivo.11384. PMID: 30348686; PMCID: PMC6365726.

3. Geranylgeraniol Induces PPARγ Expression and Enhances the Biological Effects of a PPARγ Agonist in Adipocyte Lineage Cells

Wang L, Zheng Z, Zhu L, Meng L, Liu H, Wang K, Chen J, Li P, Yang H. Geranylgeranyl pyrophosphate depletion by statins compromises skeletal muscle insulin sensitivity. J Cachexia Sarcopenia Muscle. 2022 Dec;13(6):2697-2711. doi: 10.1002/jcsm.13061. Epub 2022 Aug 12. PMID: 35961942; PMCID: PMC9745480.

4. Statin-Induced Geranylgeranyl Pyrophosphate Depletion Promotes PCSK9–Dependent Adipose Insulin Resistance

Shu X, Wu J, Zhang T, Ma X, Du Z, Xu J, You J, Wang L, Chen N, Luo M, Wu J. Statin-Induced Geranylgeranyl Pyrophosphate Depletion Promotes PCSK9-Dependent Adipose Insulin Resistance. Nutrients. 2022 Dec 14;14(24):5314. doi: 10.3390/nu14245314. PMID: 36558473; PMCID: PMC9853319.

5. Geranylgeraniol prevents the cytotoxic effects of mevastatin in THP-1 cells, without decreasing the beneficial effects on cholesterol synthesis

Campia I, Lussiana C, Pescarmona G, Ghigo D, Bosia A, Riganti C. Geranylgeraniol prevents the cytotoxic effects of mevastatin in THP-1 cells, without decreasing the beneficial effects on cholesterol synthesis. Br J Pharmacol. 2009 Dec;158(7):1777-86. doi: 10.1111/j.1476-5381.2009.00465.x. PMID: 19888963; PMCID: PMC2801219.

6. Effect of particle size on solubility, dissolution rate, and oral bioavailability: evaluation using coenzyme Q10 as naked nanocrystals

Sun J, Wang F, Sui Y, She Z, Zhai W, Wang C, Deng Y. Effect of particle size on solubility, dissolution rate, and oral bioavailability: evaluation using coenzyme Q₁₀ as naked nanocrystals. Int J Nanomedicine. 2012;7:5733-44. doi: 10.2147/IJN.S34365. Epub 2012 Nov 12. PMID: 23166438; PMCID: PMC3500035.

7. It Takes an Average of 17 Years for Evidence to Change Practice—the Burgeoning Field of Implementation Science Seeks to Speed Things Up

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8. Oral Administration of Geranylgeraniol Rescues Denervation-induced Muscle Atrophy via Suppression of Atrogin-1

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