In the study part funded by the supplement manufacturer Cambridge Nutraceuticals, Sheffield University researchers report an improvement of around 40% in semen quality in men receiving 14 milligrams (mg) of lactolycopene per day for 12 weeks.
The team, led by the University’s Dr Allan Pacey and Dr Liz Williams add that while the results are encouraging future studies would need to determine optimal dose and timing of lycopene.
“We didn't really expect that at the end of the study there would be any difference in the sperm from men who took the tablet versus those who took the placebo,” says Dr Pacey, a professor of andrology reproduction at Sheffield University. “When we decoded the results, I nearly fell off my chair."
"The improvement in morphology -- the size and shape of the sperm, was dramatic. We used a computer system to make these measurements, which takes a lot of the human error out of the results.
“Also, the person using the computer didn't know who had taken LactoLycopene and who had taken the dummy pills either.”
However, reaction to the study was mixed with some researchers pointing to the study’s choice of subjects and sample size as downsides to its findings.
“This is a small study where the volunteers were healthy, not infertile; with sperm parameters close to normal,” says Sheena Lewis, emeritus professor of reproductive medicine at Queen’s University Belfast.
“Hence it is difficult to extrapolate any lycopene benefits to infertile men with poor semen quality. There are no clinical outcomes to the study.”
Professor Ying Cheong, professor of reproductive medicine at the University of Southampton adds that the research team, “found no significant difference in the primary outcome, which was the overall motile sperm concentration or DNA fragmentation between the two groups”.
“But they observed in their sub-analysis, more fast progressive sperm and normal looking sperm in the lactolycopene arm, and a decrease in non-progressive sperm in the placebo arm.
“This study, undoubtedly, will add to our current knowledge of yet another antioxidant type supplement on sperm parameters, but what the study fails to tell us is if taking lactolycopene supplements improves fertility, that is the chance of actually having a successful pregnancy. It would be more impactful if the authors could use live birth as the end point.
“Hence, the tomato’s culinary history remains firmly in gastronomy rather than fertility.”
Evidence suggests dietary factors are associated with sperm quality, with data on average daily nutrient intake from food and supplements linking higher antioxidant intake and higher sperm concentration and motility.
However, over 25 randomised controlled trials to test oral antioxidant supplementation’s effect (single or combined) on semen quality yield mostly inconsistent and inconclusive results due to poor quality and high heterogeneity of design.
To date, there have been only a few trials to date that have directly considered the effect of lycopene on semen parameters.
A study of 30 infertile men given 4 mg lycopene daily for 12 weeks, saw improvements were seen in sperm concentration, motility and morphology in a high proportion of the men.
A more recent study reported a transient improvement in sperm motility after six weeks in infertile men randomised to a 12-week intervention of tomato juice, providing 30 mg lycopene each day, compared to a no-intervention control.
The team began this double-blind, placebo-controlled parallel study by enrolling sixty healthy male participants aged 19 to 30, all randomised to receive either 14 mg/d lactolycopene or a placebo for 12 weeks.
The primary endpoint was a change in motile sperm concentration. Secondary endpoints were all other aspects of sperm quality, including the level of sperm DNA damage.
Dietary Lycopene is known to be poorly absorbed by the human body, so the compound used for the trial was a commercially available formulation called LactoLycopene; designed by FutureYou Cambridge to improve bioavailability.
Out of the sixty men enrolled, fifty-six completed the procedure, where plasma lycopene levels were found to have significantly increased those randomised to receive lycopene supplementation.
There was no significant change in the primary endpoint (motile sperm concentration). However, the proportion of fast progressive sperm and sperm with normal morphology did improve significantly by around 40% in response to lactolycopene intervention.
"This was the first properly designed and controlled study of the effect of LactoLycopene on semen quality, and it has spurred us to want to do more work with this molecule," says Dr Williams, a specialist in Human Nutrition at the University of Sheffield.
"We were surprised by the improvement in sperm quality shown by the results," she adds.
"This was a small study and we do need to repeat the work in bigger trials, but the results are very encouraging.
“The next step is to repeat the exercise in men with fertility problems and see if LactoLycopene can increase sperm quality for those men and whether it helps couples conceive and avoid invasive fertility treatments."
Same as eating 2kg tomatoes
Discussing the results’ future implications, the team acknowledge the 14 mg/d of lactolycopene given to the men was the same as eating 2kg of cooked tomatoes or 2 tablespoons of concentrated tomato puree each day, representing a sizable increase in the lycopene intake of the study participants.
They also add that the underlying biological mechanism of action whereby lycopene exerts an effect on the sperm is currently unknown.
“The antioxidant properties of lycopene have been the focus of lycopene’s action on male infertility to date,” the team say.
“Oxidative stress may play a role in male infertility pathogenesis and while reactive oxygen species play a role in normal sperm function, disequilibrium of reactive oxygen species and antioxidant defence appears to be detrimental.
“While it is well known that sperm are very vulnerable to damage by free radicals, we cannot assume that the beneficial effects of lycopene we observed are because of its antioxidant properties,” the team add.
“We did not make any relevant measurements of oxidative stress in biological fluids such as seminal plasma. However, an antioxidant role for lycopene is a plausible hypothesis.”
Claims ‘slightly misleading’
Commenting on the study’s final figures, Dr Graham Wheeler, senior statistician at University College London (UCL) says that, “there was weak evidence to suggest that the primary outcome of this study, motile sperm concentration level, had improved after 12 weeks in participants receiving LactoLycopene.
“Therefore, the authors claim LactoLycopene improves sperm quality based on other measurements in this study instead, which is slightly misleading.
“Only 56 men were analysed in this study, and this number of participants was not statistically justified. This study may be too small to conclusively say whether the observed results are genuine effects, or simply due to chance.
“All participants were healthy volunteers. Given that we do not know how LactoLycopene may influence sperm quality, it is unclear whether such a supplement would benefit men with fertility issues.”
Source: Eur J Nutr
Published online: doi.org/10.1007/s00394-019-02091-5
“A randomized placebo-controlled trial to investigate the effect of lactolycopene on semen quality in healthy males.”
Authors: E Williams et al