A previous article provided an introduction to geranylgeraniol (GG), a compound produced in the same biochemical pathway by which cholesterol, CoQ10 and other critical compounds are synthesized. This pathway—the mevalonate pathway—is perhaps familiar because cholesterol-lowering statin drugs work by inhibiting the enzyme HMG-CoA reductase, an early step in the process. As was discussed in that article, supplementing with GG may help mitigate some of the adverse side-effects of statins as well as those of bisphosphonates, which also target the mevalonate pathway. But the potential benefits of GG don’t end there. Here we’ll explore additional roles for this little-known compound.
Brazilian folk medicine has traditionally employed seeds from the plant Pterodon pubescens Benth (also called sucupira branca) for their medicinal properties. In modern times, these are still used for rheumatism, sore throat, and respiratory disorders such as bronchitis and tonsillitis. Modern laboratory assays have determined that this plant is a source of GG, and these extracts have been shown in animal models to be anti-inflammatory, analgesic, anti-rheumatic and muscle-relaxing.
Rodent models employing oral administration of GG show that GG is antinociceptive and may be beneficial for both acute and chronic inflammation. With more medical professionals and their patients looking for alternatives to NSAIDs and stronger pain relievers with addictive properties, perhaps GG will claim a place among other natural compounds used to mitigate inflammation, such as rosemary, ginger and curcumin.
Blood sugar control and metabolic health
The US FDA now warns physicians and patients about increased blood sugar and HbA1c among statin users. In fact, statin use is associated with increased risk for type 2 diabetes, attributed in part to decreased insulin secretion. One mechanism that might be at work here is statins inhibiting protein prenylation—a protein modification step that’s required for proper glucose-stimulated release of insulin from pancreatic beta cells.
Although much of the scientific literature on this issue is relatively silent on possible mechanisms behind “statin-associated diabetes,” one paper’s authors acknowledged that it may indeed be due to reduced synthesis of metabolites from the mevalonate pathway—such as GG. By providing an exogenous source of GG for protein prenylation, it’s possible that supplementing with GG may help reduce this risk, although this is theoretical and has yet to be studied. What has been studied, however—at least in cultured cells—is that that GG exerts its beneficial effects without interfering with the cholesterol-lowering properties of statins. In fact, researchers have written that GG “may be a potential drug for the prevention or treatment of statin-induced diabetes without interfering with the beneficial plasma cholesterol-lowering effects of statin.”
(It’s worth noting, however, that a great deal of controversy exists around whether elevated LDL-cholesterol, by itself and completely independent of other factors, is a risk for cardiovascular disease in the first place, and if so, the adverse effects of statins are so numerous and severe that for some patients they may not be the best course of action.)
Beyond the potential for GG to mitigate the effects of statins on blood glucose, GG may also aid in blood sugar regulation by inducing PPARγ expression and enhancing the biological effects of PPARγ agonist medications, such as the thiazolidinediones (TZDs) used to treat type 2 diabetes. This was shown in mouse adipocytes and human hepatocytes.
Type 2 diabetes, metabolic syndrome and other conditions associated with hyperinsulinemia are also associated with increased systemic inflammation and the buildup of fat in the liver. Dietary supplementation of GG in rats was shown to suppresses lipopolysaccharide-induced inflammation with significantly lower levels of inflammatory cytokines and the liver enzymes ALT and AST. Similar results were seen in human macrophage-like cells treated with GG: GG attenuated a lipopolysaccharide-induced inflammatory response via inhibition of nuclear factor κB (NF-κB). This anti-inflammatory effect may be an effect of GG increasing vitamin K2 synthesis, as menaquinone-4 was shown reduce activation of NF-κB in human macrophage-like cells.
It will be interesting to see more research emerge on the potential therapeutic benefits of GG in humans.