Title: Antioxidants and sperm
Key words: vitamin C, sperm, lipids, oxidising, genetic abnormalities, metabolic processes, mitotis, ascorbic acid, genetic damage, vitamin E, beta-carotene
Date: April 2001
Action of ascorbic acid
Vitamin C (ascorbic acid) protects DNA in sperm, and so could reduce the risk of offspring inheriting genetic faults, according to a team of researchers in the US. Ascorbic acid also seems to protects biomolecules, such as the lipids which are associated with motility, and so helps to maintain sperm quality. The team's results extend what scientists already knew about the vitamin's role in protecting the cells in our bodies from the oxidising by-products of metabolism.
Bruce Ames at the University of California at Berkeley says that every cell in our bodies, including eggs and sperm, is 'hit' by about 10 000 oxidising reactions every day. Most of the oxidising agents - for example, peroxides and superoxide radicals - are by-products of normal metabolic processes, such as respiration and energy transfer.
Although antioxidants and reducing enzymes can neutralise most of these damaging species, unchecked radicals cause considerable damage to lipids, proteins and DNA. Ames believes this kind of oxidative action is the major culprit in damaging the DNA in sperm and eggs, and so causes birth defects, some genetic diseases and also childhood cancer.
Genetic abnormalities are more often associated with faults in paternal DNA than in maternal DNA. For example, the cancer, retinoblastoma, is more commonly linked to sperm defects. One explanation could be the large number of mitosis states involved in the formation of sperm; about 380 against 23 involved in egg production. Mutations are most likely to arise during mitosis because the repair activity of cells seems to stop during this stage.
Ames says that because ascorbic acid is about eight times more concentrated in seminal fluid than in blood plasma, it must play an important physiological role in helping to protect sperm from genetic damage. He adds that this is especially true during mitosis.
Ascorbic acid is a powerful water-soluble reducing agent, and so can act as an antioxidant. Ames and his colleagues reasoned that the level of ascorbic acid might be reflected in the degree of oxidative damage to sperm DNA (Proceedings of the National Academy of Sciences, vol 88, p 11003).
To demonstrate how varying amounts of ascorbic acid produce such damage, the researchers measured the amount of one particular oxidised DNA product - known as oxo8dG - from the sperm of 10 men. They then studied the men's dietary intake of ascorbic acid.
The men were kept on strictly controlled diets with a 250 milligram daily dose of ascorbic acid. The researchers measured the amount of oxo8dG in their sperm using a technique known as high-performance liquid chromatography. They found the level to be, on average, 34 x 10 -15 moles per microgram of DNA.
When the researchers reduced the dietary ascorbic acid to 5 milligrams per day, the level of oxo8dG doubled. Ames and his colleagues believe that this shows that the protective effect of ascorbic acid had been lost. Even when the scientists slightly increased the total intake of ascorbic acid from 5 to 10 milligrams per day, and then to 20 milligrams, the concentration in seminal fluid continued to fall, and the amount of oxo8dG rose to almost two and a half times the initial value.
The concentration of seminal ascorbic acid increased only once the dose was returned to 250 milligrams. This was accompanied by a fall in the amount of oxo8dG. Ames says: 'The US recommended daily amount of 60 milligrams a day is too low; the amount should be nearer 250 milligrams to be of real benefit.' He adds that 'two servings of fruit and three of vegetables a day is enough to obtain this amount.'
According to the researchers, the amount of oxo8dG is inversely related to ascorbic acid concentration in seminal fluid, which Ames believes closely reflects its level in the seminiferous tubules, where sperm are generated. A high level of ascorbic acid, which is diet dependent, plays a critical 'first defence' role, together with antioxidant enzymes, in protecting the human genome and thus in protecting offspring.
'Sufficient dietary ascorbic acid could be crucial to smokers,' says Ames. 'They have greatly reduced levels of the vitamin, mainly because of their huge intake of highly oxidising compounds, such as nitrogen oxide, from tobacco smoke.' Recent studies have linked fathers who smoke to an increased incidence of leukaemia and lymphoma in offspring (American Journal of Epidemiology, vol 33, p 123, 1991).
Ames says that his non-intrusive method for measuring the protective effect of ascorbic acid could help researchers to find the optimum amount of antioxidants, such as vitamin E and beta-carotene, needed for a healthy diet.
From New Scientist magazine, vol 133 issue 1812, 14/03/1992, page 20
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