Free radicals are highly reactive and unstable molecules that are produced in the body naturally as a byproduct of metabolism. Free radicals are beneficial to the cell signalling and immune system, as well as maintenance of normal body functioning. However, excessive formation or insufficient removal of reactive oxygen species (ROS) and reactive nitrogen species (RNS) may modulate the blood vessel wall and damage DNA, creating an environment that facilitates the progression of atherosclerosis, and leading to various illnesses, such as heart disease, diabetes and cancer.

In vitro studies exhibited that several constituents of Ganoderma lucidum, in particular triterpenoids and polysaccharides, show antioxidant activity, reducing power, scavenging and chelating abilities. In contrast, polysaccharide extracts of Ganoderma lucidum have superoxide and hydroxyl radical scavenging activities but do not have antioxidative activity as measured by detecting malondialdehyde (MDA) contents of liver microsomes. It has been exhibited that the phenolic compounds from the fresh fruiting bodies of Ganoderma lucidum exhibit strong 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity but low superoxide dismutase (SOD) activity.

The study also showed that DPPH radical scavenging activity and SOD activity were positively correlated with phenolic compounds including caffeic acid, catechin, ferulic acid, gallic acid, myricetin, naringin, pyrogallol, protocatechuic acid, homogentisic acid, and quercetin, as well as total phenolic compounds. After comparing the antioxidant activities of four of the most widely known mushrooms, including Ganoderma lucidum, a study exhibited that polysaccharide extracts showed a strong correlation between the reducing power and the total amount of phenols and α-glucans, while a correlation between the reducing power and the amount of total polysaccharides and proteins was not found.

In vivo studies have shown that Ganoderma lucidum increases the activity of the antioxidant enzymes SOD and catalase (CAT), which are involved in removing harmful ROS. In an ischaemia and reperfusion isolated perfused rat heart model, administration of Ganoderma lucidum extract (400mg/kg for 15days) showed antioxidant properties and the author concluded that the cardioprotective properties of Ganoderma lucidum extract are related to its antioxidant effects.

A study in rats showed that Ganoderma lucidum ethanol extract (250mg/kg body weight) promoted the cardiotoxicity of adriamycin by reducing the increase in lipid peroxidation and reversing the decrease in the antioxidant enzymes, glutathione peroxidase (GPx), glutathione-S-transferase (GST), SOD and CAT in the heart tissue. The cardioprotective effect of Ganoderma lucidum may be attributed to the antioxidant chemicals triterpenes and polysaccharides. In a carotid-artery-ligation mouse model, daily oral Ganoderma lucidum (300mg/kg/day) prevented neointimal thickening 2weeks after ligation.

In Addition, subcutaneous injections of ganoderma triterpenoid (GT) extract (300mg/kg/day) abolished ligation-induced neointima formation. The authors concluded that GTs prevent atherogenesis by eliminating disturbed flow-induced oxidative stress through inhibiting the induction of a series of atherogenic factors, as well as inflammation.

A short-term supplementation study over 10days in healthy subjects showed an improvement in antioxidant status, but a longer double-blind, placebo-controlled, cross-over intervention study over 4weeks with a commercially available encapsulated Lingzhi preparation (1.44g Lingzhi/day; equivalent to 13.2g fresh mushroom/day) showed no significant effects in a range of biomarkers for antioxidant status, cardiovascular risk, DNA damage, immune status, and inflammation. A placebo-controlled cross-over study in 42 healthy subjects examined the antioxidation and hepatoprotective efficacy of triterpenoids and polysaccharide-enriched Ganoderma lucidum, which was taken as a 225mg capsule containing 7% triterpenoid-ganoderic acid (A, B, C, C5, C6, D, E and G), 6% polysaccharide peptides with a few essential amino acids and trace elements, once daily for 6 consecutive months.

The treatment showed an improvement in total antioxidant capacity, total thiols and glutathione content in plasma, significantly improved activities of antioxidant enzymes (SOD, CAT, GPx and glucose-6-phosphate dehydrogenase), and lowered the levels of thiobarbituric acid reactive substances, 8-hydroxy-deoxy-guanosine and hepatic marker enzymes, glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase. Mild fatty liver detected by abdominal ultrasonic examination was reversed to normal with Ganoderma lucidum treatment.