Coenzyme Q10 (CoQ10) is often considered a cornerstone nutrient in cardiovascular, metabolic, and mitochondrial health, as it may support cellular energy production and antioxidant status. Yet, despite its widespread use, an important biochemical reality is often overlooked: supplemental CoQ10 alone may not address all requirements for optimal CoQ10 status. Emerging research highlights a lesser-known but important compound biochemically upstream of CoQ10 synthesis, geranylgeraniol (GG), which may play a foundational role in the body’s ability to produce CoQ10. 

What is GG?

GG is an endogenously synthesized isoprenoid compound that may play a critical role in a wide range of biological processes affecting multiple organs and tissues throughout the body, such as protein geranylgeranylation, skeletal muscle protein synthesis, mitochondrial function, CoQ10 biosynthesis, vitamin K2 (MK-4) synthesis, and cell-signaling. GG is produced via the mevalonate pathway, the same metabolic pathway responsible for the synthesis of cholesterol, CoQ10, and other essential biomolecules. Importantly, endogenous GG production may decline with aging, which may have implications for cellular energy metabolism, mitochondrial function, and musculoskeletal health. Beyond human physiology, GG also serves as a fundamental biosynthetic precursor in plants, where it contributes to the formation of carotenoids such as lycopene, β-carotene, astaxanthin, lutein, and zeaxanthin. 

As mentioned, GG plays an important role in protein geranylgeranylation – a post-translational modification required for cellular signaling and for the proper localization and functions of many proteins. This process may be particularly important in skeletal muscle, where geranylgeranylation supports myogenesis and muscle cell differentiation. Preclinical evidence highlights GG’s importance in skeletal muscle health, especially under conditions that disrupt the mevalonate pathway. Statin therapy may reduce the availability of GG intermediates, potentially impairing protein geranylgeranylation and contributing to statin-associated muscle symptoms in susceptible individuals. Supporting geranylgeranylation with GG or related isoprenoids has been shown to mitigate these effects in preclinical models. In vitro studies further demonstrate that GG supplementation may mitigate the expression of muscle atrophy related genes, support myogenic differentiation, and protect against statin-induced muscle cell damage, while also reversing statin-associated inhibition of mitochondrial respiration and supporting mitochondrial function.

Animal models further support GG’s role in preserving skeletal muscle structure and function under both healthy and statin-challenged conditions. GG supplementation increased muscle force production and reduced fatigue in healthy rats, while co-supplementation with GG completely negated statin-induced fatigue and reductions in muscle strength. Additional preclinical models demonstrate reduced muscle fiber atrophy and suppression of the muscle atrophy marker Atrogin-1 in denervation-induced and glucocorticoid-induced muscle loss. In a streptozotocin-induced diabetes model, GG supplementation was associated with preservation of muscle mass, potentially related to favorable mitochondrial dynamics.

What role does GG play in supporting CoQ10 status?

CoQ10 is synthesized endogenously within peroxisomes and other cellular compartments via the mevalonate pathway, using downstream metabolites derived from GG and tyrosine (or phenylalanine), with vitamin B6 serving as a cofactor. Endogenous CoQ10 production may decline with age and can be further reduced by genetic variation, metabolic or cardiovascular conditions, or the use of medications such as statins. Research has identified certain limitations of CoQ10 supplementation related to its ability to reach intracellular and mitochondrial targets. 

GG may help address limitations of CoQ10 supplementation by supporting endogenous CoQ10 biosynthesis as an obligatory substrate within the mevalonate pathway. In vitro studies describe GG as “cell-permeable” and “readily diffusible” across cell membranes, consistent with its molecular weight being approximately one-third that of CoQ10. By providing an essential isoprenoid intermediate, supplemental GG may support metabolic pathways involved in CoQ10 production, complementing CoQ10 supplementation and potentially helping to offset age-related declines in endogenous CoQ10 synthesis that may impair mitochondrial respiration and metabolic rate. 

GG may be particularly relevant for individuals receiving statin therapy, which inhibits the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG‑CoA) reductase early in the mevalonate pathway, which may reduce intracellular levels of both CoQ10 and GG. Statin use has increased substantially in recent years and has been associated with muscle symptoms, mitochondrial dysfunction, and altered energy metabolism. CoQ10 supplementation alone may not consistently restore mitochondrial function or reverse statin-associated muscle symptoms. In a randomized controlled study (n = 28), CoQ10 supplementation increased plasma CoQ10 concentrations but only partially restored statin-induced mitochondrial dysfunction. In contrast, mechanistic in vitro research has suggested that GG supplementation may support mitochondrial structure and function and replenish downstream metabolites within the mevalonate pathway. A review of nine CoQ10 studies for statin-associated muscle symptoms (SAMS) reported inconsistent or absent benefit for SAMS even at high CoQ10 supplemental doses; the authors proposed GG as a key missing isoprenoid in understanding and potentially addressing SAMS.

In summary, CoQ10 supplementation increases circulating levels but may not reliably restore intracellular or mitochondrial CoQ10 stores. GG may support endogenous CoQ10 synthesis by replenishing key intermediates within the mevalonate pathway, offering a complementary approach, particularly in instances where endogenous CoQ10 production may be compromised.

Learn more about GG: 

Intro to Geranylgeraniol

Combination of Geranylgeraniol + Ubiquinol to Support Mitochondrial Function

Benefits of Geranylgeraniol

Bisphosphonates and Bone Health: Is There a Role for Geranylgeraniol?

By Antonia Toupet, PhD