Superoxide Dismutase

By Dr Charlene DeHaven / 25 Sep 2017

Dr Charlene DeHaven provides an overview of the antioxidant superoxide dismutase

Superoxide dismutase (SOD) is a powerful antiageing ingredient and one of three intrinsic antioxidants that evolved naturally in the human body to lessen free radical damage. The processes used to manufacture these substances within the human body are the same metabolic processes used to produce other molecules composing body tissues and active molecules. In addition to SOD, the other molecules in this group of enzymatic antioxidants1 are catalase (CAT) and glutathione peroxidase (GPx). 

Each of these differs in its molecular structure but all are powerful antioxidants used by the human body to neutralise various forms of free radicals. SOD possesses the property of neutralising the superoxide free radical while CAT and GPx each neutralise other specific free radical types.2

SOD is a powerful antioxidant and animal evidence suggests that boosting levels of SOD may help prevent disease and increase life span.3 Due to such research data, SOD has been a desirable antiageing treatment but, prior to about 20 years ago, could only be given intravenously, due to the molecule being destroyed in the gastrointestinal tract.4 More recent research has suggested that SOD values within the body are higher in physiologically younger and healthier individuals.6 Administration of SOD may also improve diseases related to free radical damage and oxidative stress.5,7

Around 20 years ago, techniques were first developed that allowed for oral absorption3 but topical absorption remained elusive until recently. Because of formulating innovations, it is now possible to incorporate SOD into cosmeceuticals. Several formulating modifications have been investigated and improve topical absorption – including liposomal encapsulation, complexing with other molecules, or direct injection.8

SOD, CAT and GPx form a group of powerful antioxidants and are unique from other antioxidants that are classed as non-enzymatic in two important ways:

1) They are manufactured inside the body

2) Only very tiny amounts are required for powerful antioxidant effects9 SOD and free radicals

In skin, the production of free radicals occurs from solar exposure and energy production inside cells. The majority of the skin’s free radical damage – at least 85% – is from photo-exposure and most of the remainder is from excess free radical production during intracellular energy production. There may be other sources in certain individuals, such as pollution for city dwellers and smoking for tobacco users. Free radicals from all these sources will damage cells and tissues over the course of a lifetime and lead ageing. Visible ageing occurs after physiologic reserve declines and functional capacity diminishes during progressive and cumulative free radical damage.10,11,12 

A study with fruit flies (Drosophila melanogaster) by Shen et al. indicated that increasing SOD levels can improve ageing

Only tiny amounts of enzymes are required in chemical reactions and these compounds are not consumed – in other words they are not ‘used up’ in the process and remain to act again.9 Even after a chemical reaction involving SOD, this antioxidant remains intact and can again participate in further free radical neutralisation. This contrasts to other important antioxidants, such as vitamin C and vitamin E, which are consumed in the process of neutralising free radicals. Much larger amounts of non-enzymatic antioxidants are required to absorb free radicals.

SOD exists in two forms – SOD1 and SOD2. SOD2 is found in mitochondria, the energy production factored within all cells.13 Since energy generation is a free radical process, it is not surprising that large numbers of free radicals are formed within mitochondria. SOD1 is found in locations other than mitochondria, such as the cytoplasm of cells.14

The use of SOD in ageing

A study with fruit flies (Drosophila melanogaster) by Shen et al. indicated that increasing SOD levels can improve ageing. Lifespan in fruit flies increased by up to 26% when the substance curcumin, which causes higher SOD levels, was given.15

Caloric restriction is also thought to increase the average human lifespan. Animal groups, including mammals, have greater gene expression of SOD with caloric restriction.16 Mean animal lifespan has been increased by 10-20% with caloric restriction/energy restriction.17

Caloric restriction is a technique verified to cause increases in average lifespan for many organisms – including rodents, yeasts, fruit flies, worms and primates.18 With caloric restriction, sometimes called energy restriction, calories eaten are decreased by 30-50% while maintaining high nutritional value of foods.19 In other words, very little food is eaten and weight loss is severe, although the nutritional quality of food is kept high. And, even though average lifespan may increase, quality of life is difficult due to constant hunger.

Topical SOD has been shown to decrease MDA formation and protects cell membranes as well as protecting against fragmentation from free radical damage to Type I Collagen

Eating a healthy diet also improves parameters of oxidative stress and can improve health and lifespan. Supplementing the diet of fruit flies with apple polyphenols or curcumin increases their lifespan via upregulation of, in other words ‘turning on’, the genes coding for SOD.20 

Blueberry extract, soybean isoflavones, and black rice anthocyanins show similar effects. Many natural antioxidants and functional foods such as apple, blueberry, soybeans, green tea, black tea and black rice possess high antioxidant activity, upregulate genes for SOD production, and increases the amount of SOD produced. Measures to increase SOD have been found to play an important role in delaying ageing.21

Oxidative stress

Oxidative stress is a condition where more radical damage occurs within cells than is being neutralised by antioxidants within the body. Our cells are always in a state of oxidative stress because damage always exceeds the body’s protective abilities.22 There are never enough antioxidant mechanisms to fully neutralise free radical generation. With topical SOD, cell products associated with free radical damage and/ or protection can be measured. Improvements occur in these markers of oxidative stress23 – lactic dehydrogenase (LDH), malondialdehyde (MDA), and prostaglandin E2 (PGE2). The formation of PGE2, one of the key inflammatory molecules in the arachidonic acid cascade, is completely prevented. PGE2 has been implicated in all types of pro-inflammatory processes, ranging from sunburn to skin cancer development.24 Topical SOD has been shown to decrease MDA formation and protects cell membranes as well as protecting against fragmentation from free radical damage to Type I Collagen.25 MDA levels are good markers of ongoing free radical damage26 and these are decreased with topical SOD.

The use of SOD in cosmeceuticals

SOD can be incorporated into cosmeceuticals and is available in a topical form, which can be absorbed through the skin’s outer barrier.27 Studies on some topical forms of SOD indicate absorption and reduction of free radical damage/oxidative stress.28 SOD aims to protect against lipid peroxidation in delicate skin cell membranes, neutralise the superoxide radical, protect against damaging environmental conditions such as UV exposure,29 guard against pollution, combat photoageing, and reduce UV-induced erythema while enhancing protective effects of suncare products. 

Topical SOD has been indicated to be useful in the treatment of skin diseases involving inflammation and free radical generation.30 As with all antioxidants, these chemical events occur via the donation of an electron by SOD to the free radical, thus neutralising it.31 Unlike non-enzymatic antioxidants that are destroyed during redox activity, the enzymatic antioxidants like SOD persist longer.32

Conclusion

The association of excess free radical damage with solar exposure, environmental stress, pollution, and ageing is well known. Furthermore, ongoing oxidative stress and its associated inflammatory up-regulation is associated with even further downstream tissue injury. The reduction of inflammatory markers and oxidative parameters illustrates the skin benefits of topical SOD. 

References
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