Weight loss with TDR may help to improve fertility in men with obesity

Posted On: 4th July 2022

There is a downward global trend in sperm counts in men and, in 50% of couples seeking assisted reproduction there is male infertility.  There are no drug therapies for poor sperm quality and few clinical trials that address the role of obesity and effect of weight loss.

Emil Andersen working in Professor Signe Torekov’s group at the University of Copenhagen recently published evidence for increased sperm count following weight loss with Total Diet Replacement (TDR) in men with obesity.

In this sub-study of the ‘S-Lite’ project (Lundgren JR et al) 47 men with BMI 32-43 kg/m3 followed an 8 week 810kcal/day TDR diet followed by food reintroduction with an option to continue with use of one meal replacement product daily for a further 52 weeks.  In addition all were randomised after the TDR to either daily injections of the GLP-1 agonist Liraglutide with or without exercise or placebo injection with or without exercise.  Semen variables were measured before and after the TDR diet and after a further 52 weeks (Andersen E et al).

The men lost an average 16.5kg body weight during the 8 weeks TDR and at the same time sperm count increased by 40% and sperm concentration by 49%.  By 52 weeks weight loss maintained was an average 11.7kg. Dividing the 37 individuals included at 52 weeks into weight maintainers (those who maintained >11.7kg) and weight regainers (those who maintained <11.7kg) showed that sperm count and concentration were only significantly increased in the weight maintainer group.

In a preliminary report made at ENDO22, the meeting of the Endocrine Society in the USA, Aditi Sharma and colleagues from Imperial College London, showed that in 36 men with low sperm counts randomised to either usual dietary guidance or an 810kcal/d TDR diet for 16 weeks average weight loss was 1.5kg versus 14.3 kg respectively. They measured reactive oxygen species (ROS) in the semen finding that weight loss after TDR was associated with a 12-fold greater reduction of ROS than after the usual (control) diet (Sharma A et al). ROS react with many cellular components including DNA causing structural and functional damage and in semen have recently been shown to be strongly linked to DNA damage in sperm resulting in worse pregnancy outcomes. This first RCT of TDR weight loss in male infertility provides proof of concept that this simple and safe diet could be incorporated into infertility management programmes.

Anthony Leeds, chair of TDMR Europe, said ‘While more research work is needed including trials within fertility programmes, these two papers raise the prospect that a sufficient weight loss, perhaps more than 12kg, may so reduce oxidative stress in men that fertility outcomes may improve. Weight loss with TDR is known to result in larger and faster weight losses than some other methods and shows high compliance in clinical trials.  TDR is in use to achieve the initial weight loss in diabetes remission programmes in the UK and is known to be safe and cost effective.  It is highly likely that TDR will prove to be a useful intervention in male infertility.’

The  S-LITE study was funded by the Novo Nordisk Foundation and TDR products were provided by Cambridge Weight Plan Ltd UK.

The Imperial College study in men with obesity and oligospermia was funded by an

NIHR Post-Doctoral Fellowship, Imperial Biomedical Research Centre and the Imperial Health Charity and products were provided by LighterLife Ltd UK.

References:

Lundgren J R et al Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined     N Engl J Med 2021;384:1719-30. DOI: 10.1056/NEJMoa2028198

Andersen E et al Sperm count is increased by diet-induced weight loss and maintained by exercise or GLP-1 analogue treatment: a randomized controlled trial. Human Reproduction, pp. 1–9, 2022 https://doi.org/10.1093/humrep/deac096

Sharma A et al Weight loss using a formula low energy diet reduces seminal oxidative stress in men with obesity and oligospermia: a randomized controlled study. Abstracts of ENDO2022    J Endocrine Society  Volume 6 Issue Supplement 1 April-May 2022 page A*