Geranylgeraniol Background & Benefits
Geranylgeraniol (GG) is a substance that is made in the human body via a biochemical pathway called the mevalonate pathway. This is the same biochemical pathway that makes cholesterol, CoQ10, dolichol and Heme A.
The mevalonate pathway plays a critical role in numerous cellular processes throughout the body. For example, it keeps our mitochondria healthy and generates ATP - the energy that all cells use.
In the body, GG is converted to the 'activated' form called geranylgeranylpyrophosphate (GGPP). When taken orally, GG is activated and incorporated into the mevalonate pathway.
Unfortunately, as we age, our levels of GG decline. Certain medications also inhibit the mevalonate pathway, namely statins and bisphosphonates (the latter are prescribed to treat osteoporosis). By inhibiting the mevalonate pathway, these medicines also inhibit GG and CoQ10.
Scientific evidence shows that it is the reduction in GG that is responsible for many of the common side effects experienced by those taking statins, namely, muscle aches and pains and muscle weakness. Supplementation with GG may help mitigate the side effects of statins and may support healthy aging more broadly. Importantly, taking GG does not interfere with the effectiveness of statins in lowering cholesterol.
GG is ubiquitous in nature. It is a precursor to carotenoids, certain vitamins and chlorophyll. Hence, when you see a yellow/orange/red colour in plants, you know that GG is present! Notably, GG is also found in edible oils such as olive, linseed and sunflower oils. Xtend-Life' GG is extracted from the South American Annatto plant (Bixa orellana).
GG is used by the body for both protein synthesis and another process called post-translational modification of proteins. Post-translational modification means modification of the protein once it is synthesised in cells. This process affects what proteins can do.
When it comes to GG and its smaller sibling Farnesyl (a precursor to GG), their specific post-translational modification is a process called protein prenylation.
Numerous essential cellular proteins undergo prenylation and these proteins are involved in regulating a plethora of functions including signal transduction (how cells understand what's going on outside the cell), protein synthesis, the creation, growth and movement of cells, placement of proteins into membranes and structure of membranes, to name a few! As you can see, protein prenylation by GG is essential to the normal function of cells!
Researchers have pointed to GG as "the principal target of statin-dependent myotoxicity" and have concluded that statin-induced muscle damage "is the result of a geranylgeranylation defect". The loss of GG-dependent protein prenylation caused by statins affects muscle cells in particular and other cells in general. Multiple cell-based studies show that co-administration of GG with statins restores cell growth, DNA synthesis and cell division in muscle cells. Fortunately, supplementation with GG provides a simple means to restore protein generated from GG.
Statins reduce CoQ10 as well as GG. This is because CoQ10 requires GG for synthesis. Research shows that adding GG is more effective than adding CoQ10 at eliminating the ill-effects of the statin.
Statins also reduce Vitamin K2 by inhibiting GG through the mevalonate pathway. Lowered levels of Vitamin K2 accelerate calcification of arteries in those taking statins. In cell culture and animal studies, adding GG restores Vitamin K2 levels in the presence of statins.
Uses of Geranylgeraniol
The most common reason for taking GG is for the management of the side effects of statins. Others take GG to support healthy cellular function, particularly over the age of 40.
Muscle pain and weakness are the most frequent side effect among statin users. Research points to reduced GG as the primary cause, with lowered levels of CoQ10 likely as a contributing factor.
Signs You May Need Geranylgeraniol
If you are suffering side effects from statins or bisphosphonates then you may benefit from taking GG. In addition, older adults feeling sluggish or with lack of energy may benefit from GG.
Ivor Cummins, who is on our scientific board, recently interviewed Dr Barrie Tan to talk about GG. The video is quite technical but has a good explanation of how GG can benefit you.
CRICK, D. C. et al. Novel Salvage Pathway Utilizing Farnesol and Geranylgeraniol for Protein Isoprenylation. Biochemical and Biophysical Research Communications 237, 483–487 (1997) ARTICLE NO. RC977145.
CORSINI, A. et al. Relationship between mevalonate pathway and arterial myocyte proliferation: in vitro studies with inhibitors of HMG-CoA reductase. Atherosclerosis. Jun 1993;101(11):117-125.
VIGANO, T. et al. Mevalonate pathway and isoprenoids regulate human bronchial myocyte proliferation. European Journal of Pharmacology. Oct 15 1995:291(2):201-203.
VOGT, A. et al. Protein geranylgeranylation, not farnesylation, is required for the G1 to S phase transition in mouse fibroblasts. Oncogene Nov 7 1996;13(9):1991-1999.
CAMPIA, I. et al. Geranylgeraniol prevents the cytotoxic effects of mevastatin in THP-1 cells, without decreasing the beneficial effects on cholesterol synthesis. British Journal of Pharmacology. Dec 2009;158(7);1777-1786.
OKUYAMA, H. et al. Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms. Expert Review of Clinical Pharmacology. 2015 8:2, 189-199, DOI: 10.1586/17512433.2015.1011125
HIROTA, Y. et al. Functional Characterization of the Vitamin K2 Biosynthetic Enzyme UBIAD1. PLoS ONE 10(4): e0125737. doi:10.1371/journal.pone.0125737
HARSHMAN, S.G. et al. Atorvastatin Decreases Renal Menaquinone-4 Formation in C57BL/6 Male Mice. Journal of Nutrition 2019;149(3);416-421.