The Science Behind Geranylgeraniol: Muscle and Bone Health Explained

Abstract: 

The article sheds light on the relation & importance of geranylgeraniol (GG) for our health. It will help us in understanding how our body responds to lower levels of Geranylgeraniol as we age or with the occurrence of any other health issue. The article provides a detailed analysis of geranylgeraniol’s role in three different health conditions like Muscle Atrophy, Statin-Related Muscle Issues & Jaw Osteonecrosis. 

The article effectively addresses the key findings from different preclinical trials which are given below: 

• Geranylgeraniol supports mitochondrial health and protects muscle mass.

• This natural ingredient could help manage Statin-Associated Muscle Symptoms (SAMS).

• It has the potential to positively manage Bisphosphonate-Related Osteonecrosis (BRONJ): 

• This natural compound is helpful for better bone health and the repair of natural tissue in the jaw.

• It can help relieve pain.

• Geranylgeraniol potentially contributes to Enhancing PPARγ Expression (regulates metabolism), which could possibly support insulin response and healthy cellular processes.

It is discussed in some preliminary findings that Geranylgeraniol could provide broad health benefits to humans, including reducing muscle damage and inflammation. Early research also indicates its potential advantages for bone health, especially in health conditions like obesity & osteoporosis. This review highlights what an individual can expect from this promising natural compound in the near future.

Introduction

Geranylgeraniol, is a Natural diterpene alcohol. Most commonly this diterpene alcohol is used for making perfume ingredients and is a starting point for synthesizing vitamins like A and E1.While widely utilized in perfume manufacturing, Geranylgeraniol  has gained attention for its therapeutic potential in health and wellness.

How GG Is Produced: In the human body, Geranylgeraniol (GG) is produced through an endogenous pathway (within the cell) known as the mevalonate pathway (produces molecules like cholesterol). The pathway is present in both single-celled microorganisms and multicellular organisms via evolutionary processes.

A primary natural source of Geranylgeraniol is: A tropical Annatto plant (Bixa orellana), which is native to South America is the main source of this natural potent ingredient. GG accounts for around 1% of the dry seeds and is present significantly as an oily component and coloring extracts of the food.

1.1 Key Geranylgeraniol Biological Functions

Geranylgeraniol exhibits multiple essential biological functions to help your body work in optimal levels. Its functions are given below:

• Synthesizing vitamins, such as vitamins A and E, to perform various essential body functions.

• It plays a role in preventing the inhibition of osteoclast (breaks down bone tissue) formation. This action is important for the maintenance and repair of the skeleton system.

• According to some studies, it has shown the potential to induce anticancer & antitumor activity. 

• Some findings have observed that GG helps in boosting essential male hormones, such as testosterone production in Leydig cells (cells in the testes that produce testosterone). 

• As per some reports, GG from the Annatto plant has relevance from long ago as it has been used in age-old medicine. 

• In ancient times, it was used as an antibiotic, cardiotonic, hypotensive, and as an anti-inflammatory agent. 

Interestingly, the current research discusses that  GG can exert the ability to positively affect glucose regulation (the process of maintaining a constant level of sugar in the blood), bone health, and healthy gut microbiota (support friendly biota and decrease disease-causing microbes). 

1.2  Age-Related Geranylgeraniol Decline

Research indicates that Geranylgeraniol production declines as a person ages.  Tabata Yuki et al., 2021 found an age-dependent decline in the liver’s Geranylgeraniol in male C3H/HeN mice in their study. However, they noted that a single administration of Geranylgeranoic acid at 11 months of age can potentially help in reducing the chances of spontaneous hepatoma (a cancer of the cells of the liver). Studies have also described that the use of statin for managing cholesterol levels is somehow linked to the inhibition of Geranylgeraniol synthesis. Due to which, individuals face muscle-related issues.

1.2.1 Geranylgeraniol’s Decline With Health Consequences  

The following are some of the  possible health-related concerns due to Geranylgeraniol decline: 

• Age-related loss of muscle mass & strength

• Increased Inflammation

• Insulin Resistance

• Muscle Damage from Statins

• Impair bone remodeling processes

Note: Geranylgeraniol is classified as a Generally Recognized as Safe (GRAS) compound as per The United States Food and Drug Administration 

1.3 Geranylgeraniol’s Positive Contributions Supported by Clinical Studies 

Various studies support the potential role of  Geranylgeraniol on different health-related conditions, including Soleus Muscle Atrophy, regulating testosterone production, managing statin-associated muscle symptoms, etc. Let's explore these one by one.

1.3.1  Mitigating Soleus Muscle Atrophy 

The study aimed to know if Geranylgeraniol could have the ability to improve muscle health & mitochondrial function and was designed to be examined on a diabetic rat model. 

The analysis was done on the muscle samples (soleus and gastrocnemius) of  the rat that were collected to investigate genes and proteins related to mitochondrial health, inflammation, and muscle structure of the Sprague-Dawley rats that  were divided into 3 groups:

• Control group (CON): Regular diet.

• Diabetic group (HFD): High-fat diet and induced diabetes with streptozotocin (STZ).

• Treatment group (Geranylgeraniol): High-fat diet, diabetes induced with streptozotocin, and Geranylgeraniol supplementation (800 mg/kg body weight) for 8 weeks.

It was discussed that the Geranylgeraniol showed its potential positive effect by the following mechanism : 

• Mitochondrial damage was reduced by Geranylgeraniol as it prevented mitochondrial fragmentation, reducing the demand for mitochondrial fusion & enhancing the removal of damaged organelles (autophagy).

• Supported mitochondrial quality control by regulating a key gene and protein like PINK1.

• Reduced inflammation by lowering levels of inflammatory markers like IL-1β.

• Improved muscle structure by increasing the cross-sectional area (CSA) of muscle fibers.

In this study, Geranylgeraniol supplementation has shown positive signs to improve mitochondrial quality, reduce inflammation, and support muscle health in diabetic rats. 

This shows that Geranylgeraniol carries a potential benefit for humans with diabetes; however, more research is required to assess the long-term effects of Geranylgeraniol as a supplement for this condition. Additionally, as per a 2018 study, Geranylgeraniol induces PPARγ expression (is a nuclear hormone receptor, playing an important role in the proper metabolism of cellular glucose). This expression is helpful in the management of diabetes, further strengthening Geranylgeraniol's role in diabetes. 

1.3.2 Managing Statin-Associated Muscle Symptoms (SAMS) 

Lets first quickly understand how statin causes muscle-related issues:

Statin is used to lower or manage the cholesterol in the body by inhibiting the pathway (mevalonate pathway) or inhibiting the enzyme HMG-CoA reductase responsible for the production of bad cholesterol. However, the same pathway is also responsible for the synthesis of CoQ10 (ubiquinone). When the mevalonate pathway is inhibited after using statin, it also hampers the synthesis of CoQ10.  This decline in CoQ10 could be associated with muscle-related problems and impair muscle energy metabolism during statin therapy. 

When used during statin therapy, Geranylgeraniol seems to have the ability to reverse the decrease of ubiquinone levels caused after using statins. It shows its effect without reducing statin’s inhibitory effect on cholesterol synthesis10. As per Tan  Barrie and Chin Kok-Yong 2023 article, geranylgeraniol might help manage statin-associated muscle symptoms (SAMS). 

Geranylgeraniol acts as an initiator for CoQ10 production and may support muscle protein synthesis.

This article discussed that Geranylgeraniol supplementation appears to be effective in reducing muscle-related side effects of statins. However, further studies are still needed for long-term safety and confirmation of Geranylgeraniol’s muscle-related beneficial effects.

1.3.3 Geranylgeraniol’s Positive Effect on Bisphosphonate-Related Osteonecrosis of the Jaw

For this, let's delve into a 2022 study by Chin Kok-Yong, Ekeuku Sophia Ogechi & Trias Anne12. Here, the researchers examined the potential use of Geranylgeraniol in tackling bisphosphonate-related osteonecrosis of the jaw (BRONJ). This is a rare but a serious side effect of bisphosphonate drugs, which are generally brought in use for the treatment of cancer and osteoporosis.

Existing in vitro and in vivo studies related to Geranylgeraniol’s effect on osteoclasts, osteoblasts, and other jaw-related cells were reviewed.  

The authors found out Geranylgeraniol’ working: 

Geranylgeraniol is involved in an essential process known as GTPase prenylation (disrupted by bisphosphonates).  An impaired prenylation of Rab GTPases can cause impairments in bone cell function13. By supplying this substance, this natural ingredient has the potential to fix bone remodeling, helping to reverse the harmful effects of bisphosphonates. Additionally, it can reduce damage to soft tissues, facilitate the growth of new blood vessels, decrease microbial infection and inflammation of the injured site & support bone healing.

Lastly, this study discusses that this natural ingredient from Annatto can have the ability to restore bone remodeling (replacing old and damaged bone with new bone) and can support tissue repair processes. It has positively shown the ability to be included as an adjunctive agent in managing bisphosphonate-related osteonecrosis of the jaw. However, more research is required to identify the best method for delivering Geranylgeraniol and its precise dosing for individuals.  

1.4 Geranylgeraniol’s Market Trend

The Global Geranylgeraniol Market Size up to 2026 is bright &  is possibly showing a promising growth. One of the major factors contributing to global geranylgeraniol market growth is the conscious shift in preference of individuals/consumers towards health supplements and other aging products. The Geranylgeraniol industry is vastly segmented into cosmetics, medicine, and food. Among them, medicinal applications will notice the highest growth in the forthcoming. 

Conclusion

According to various articles and research that showcased that Geranylgeraniol has the ability to contribute positively towards improving muscle health, managing muscle symptoms related to statin use, and addressing bone health issues like bisphosphonate-related osteonecrosis of the jaw. We conclude that it does indeed,  carry the possibility to be used as a therapeutic agent for low testosterone levels to address male sexual issues like late-onset hypogonadism. While these early studies are promising, more research on Geranylgeraniol is required to confirm its effectiveness and long-term safety. Additionally, the growing interest in Geranylgeraniol in the health supplement market indicates its potential for broader health applications.

Disclaimer:

There is limited long-term safety data that specifically addresses geranylgeraniol (GG) supplementation. Researchers suggest more studies to understand the complete impact of these ingredients on your overall wellness. We would like to inform you that these statements have not been reviewed by the FDA, and this compound is not meant to diagnose, treat, cure, or prevent any disease.