Diet and Exercise for Obesity-related Sperm Changes

Overseen By Ronald Swerdloff, MD

Age: 18 - 65

Sex: Male

Trial Phase: Academic

Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Disqualifiers: Hypertension, Reproductive dysfunction, Cardiac disease, others

Compensation: Varies

Number of Visits: 8

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how changes in diet and exercise can improve sperm health in overweight, inactive Hispanic men. Researchers seek to determine if a healthier lifestyle can reverse certain epigenetic changes in sperm linked to weight and inactivity. Participants will be divided into groups to test diet changes, exercise routines, or a combination of both. Men who are overweight, inactive, and have risk factors for type 2 diabetes might be suitable candidates for this study. As an unphased trial, this study offers participants the opportunity to contribute to groundbreaking research on the impact of lifestyle on sperm health.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have a history of hypertension, reproductive dysfunction, or other serious health conditions, you may not be eligible to participate. It's best to discuss your specific medications with the trial investigators.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that lifestyle changes, such as improving diet and exercising, are generally safe and can enhance sperm health in men who are obese. Studies indicate that adopting a low-fat, low-calorie diet can reverse some negative effects of obesity on sperm. Exercise alone also reduces DNA damage in sperm cells.

One study found that combining diet and exercise leads to even better results for sperm health. This combination can increase sperm count and improve motility, which is their ability to move. Importantly, these lifestyle changes are usually well-tolerated and typically do not cause harmful side effects.

Overall, research suggests that eating healthier and exercising regularly is a safe and effective way to improve sperm health for men with obesity-related issues. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how lifestyle changes like diet and exercise can directly impact obesity-related sperm changes. Unlike typical treatments for obesity, which often focus on medications or surgeries, this trial looks at non-invasive methods like a low-fat, low-caloric diet and structured exercise sessions. The combination of diet and exercise might offer a more holistic approach, potentially improving not just weight and fitness but also sperm health. This could pave the way for a natural and less costly option, with fewer side effects than traditional treatments.

What evidence suggests that this trial's treatments could be effective for obesity-related sperm changes?

This trial will evaluate the effects of different lifestyle interventions on sperm quality in men who are obese. Participants will be assigned to one of several treatment arms. Research has shown that both diet and exercise can greatly improve sperm quality. Participants in the diet arm will follow a low-calorie diet, which studies have found can aid weight loss and increase sperm concentration, with some men experiencing a 1.49-fold increase. Those in the exercise training arm will engage in moderate exercise, which boosts semen quality by enhancing the body's natural defenses. The diet and exercise training arm combines both interventions, leading to even better results, with improvements in sperm concentration and count lasting up to a year after these changes. These lifestyle adjustments show promise in reversing the negative effects of obesity on sperm health. ^{4 6 7 8 9}

Who Is on the Research Team?

Christina Wang, MD

Principal Investigator

The Lundquist Institute

Are You a Good Fit for This Trial?

Hispanic men aged 18-40 with both parents from Mexico or Central America. Participants must be obese (BMI ≥ 30), inactive, and at risk for type 2 diabetes but in good health otherwise. They should not have serious diseases, reproductive dysfunctions, or a history of substance abuse. Men already on another trial or living far from the clinic are excluded.

Inclusion Criteria

Must have Hispanic Father and Mother from Mexico or Central America

I am a healthy male with normal blood and urine tests.

Consume < 30% of calories as fat/day

Exclusion Criteria

I live too far from the clinic to participate.

Sperm concentration below 15 million/mL in more than one of three screening samples

Known or suspected alcoholism or drug abuse or chronic infections

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Baseline Assessment

Initial assessment of sperm epigenome and other health metrics for all participants

1 week

1 visit (in-person)

Treatment

Participants undergo 12 weeks of diet and/or exercise interventions or no intervention

12 weeks

4 visits (in-person) at weeks 2, 4, 8, and 12

Follow-up

Participants are monitored for persistent effects of interventions on the sperm epigenome

36 weeks

2 visits (in-person) at 24 and 48 weeks after start of treatment

What Are the Treatments Tested in This Trial?

Interventions

• Diet
• Exercise
• Standard care

Trial Overview The study tests how diet and exercise affect sperm epigenetics in overweight, inactive Hispanic men. It's divided into three parts: comparing active to inactive men's sperm, then randomizing inactive men into control, diet-only, exercise-only, or combined intervention groups for a 12-week period; finally assessing if changes persist after stopping interventions.

How Is the Trial Designed?

Group I: Exercise Training Experimental Treatment 1 Intervention

≥3 sessions with fitness trainer per week, for ≥30 min, at moderate to high intensity

Group II: Diet and exercise training Experimental Treatment 2 Interventions

low fat/low caloric diet and ≥3 sessions with fitness trainer per week, for ≥30 min, at moderate to high intensity

Group III: Diet Experimental Treatment 1 Intervention

low fat/low caloric diet

Group IV: Normal/Active Active Control 1 Intervention

No intervention

Group V: Obese/Inactive Placebo Group 1 Intervention

Observational clinic visits

Who Is Running the Clinical Trial?

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Lead Sponsor

Trials

105

Recruited

46,600+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

Obesity negatively impacts testicular function in pubertal male rats, leading to increased body weight, abnormal spermatozoa, and higher levels of androgen receptors, which can affect reproductive capacity.

High-intensity intermittent resistance training, while generally beneficial for health, was found to further impair testicular function and sperm quality in obese rats, resulting in decreased sperm count and daily sperm production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent resistance exercise and obesity, considered separately or combined, impair spermatic parameters in adult male Wistar rats. Punhagui, APF., Teixeira, GR., de Freitas, MC., et al.[2021]

Aerobic exercise significantly improved sperm concentration and motility in both obese and nonobese male mice, indicating its positive impact on male fertility.

In obese mice, exercise also reduced sperm protamine deficiency, suggesting that physical activity may be more effective than dietary changes in enhancing sperm function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of aerobic exercise, low-fat and high-fat diet on the testis tissue and sperm parameters in obese and nonobese mice model. Nematollahi, A., Kazeminasab, F., Tavalaee, M., et al.[2020]

Combining diet and exercise is essential for effective obesity treatment, as neither alone is sufficient; however, very-low-calorie diets can help maintain physical function during significant weight loss.

Long-term success in maintaining weight loss is heavily dependent on adopting regular exercise habits after dieting, highlighting the importance of promoting lifelong exercise practices for sustained weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise during and after very-low-calorie dieting. Phinney, SD.[2018]

An active lifestyle, particularly through exercise, provides significant health benefits and protection against various conditions, regardless of weight changes in individuals.

Emerging research highlights the molecular mechanisms by which exercise improves metabolism and gene expression, suggesting that current exercise guidelines may need to be increased to maximize these benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise and the treatment of diabetes and obesity. O'Gorman, DJ., Krook, A.[2011]

A series of randomized controlled trials showed that sedentary men who started jogging lost body fat in direct relation to the distance they ran, indicating that exercise plays a crucial role in weight management.

Adding exercise to a prudent diet not only enhanced fat loss and reduced waist-to-hip ratios in overweight individuals but also significantly lowered the risk of coronary heart disease, highlighting the importance of regular physical activity for overall health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of experimental manipulation of energy intake and expenditure on body composition. Wood, PD.[2019]

A 16-week aerobic training program significantly improved semen quality in 90 sedentary obese adults, with increases in sperm count, motility, and normal morphology.

The exercise regimen also enhanced reproductive hormone levels, particularly increasing serum testosterone, which may explain the improvements in semen quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise improved semen quality and reproductive hormone levels in sedentary obese adults Rosety, MÁ., Díaz, AJ., Rosety, JM., et al.[2018]

A study on male mice showed that dietary interventions alone can enhance the reproductive health of their offspring by improving sperm motility and mitochondrial function, indicating a link between paternal health and offspring reproductive outcomes.

Combining diet and exercise interventions in obese male mice further improved sperm parameters and reproductive organ health, suggesting that lifestyle changes in fathers can positively influence the reproductive capabilities of their future male offspring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obese father's metabolic state, adiposity, and reproductive capacity indicate son's reproductive health. McPherson, NO., Fullston, T., Bakos, HW., et al.[2014]

This study demonstrated that male obesity negatively affects sperm quality, but these effects can be reversed through diet and exercise interventions, even if obesity persists.

In mice, a combination of diet and exercise improved sperm motility and morphology, reduced DNA damage, and correlated with better metabolic health, indicating that lifestyle changes can help improve fertility in overweight and obese men.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diet and exercise in an obese mouse fed a high-fat diet improve metabolic health and reverse perturbed sperm function. Palmer, NO., Bakos, HW., Owens, JA., et al.[2022]

In a study of 31,344 adults over an average of 6.8 years, increasing physical activity significantly reduced the odds of developing obesity, especially when combined with dietary improvements.

Participants who increased their physical activity and improved their diet experienced the greatest reductions in body fat percentage, body mass index, and waist circumference, highlighting the importance of both lifestyle factors in obesity prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations of changes in physical activity and diet with incident obesity and changes in adiposity: Longitudinal findings from the UK Biobank. Ahmadi, MN., Inan-Eroglu, E., Mishra, GD., et al.[2023]

Male obesity has significantly increased over the past 30 years and is linked to a decline in male fertility, affecting sperm quality and altering the structure of germ cells in the testes.

Obesity in men not only impacts their reproductive health but also has implications for the metabolic and reproductive health of their offspring, likely due to changes in the molecular profile of sperm, including epigenetic modifications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of obesity on male fertility, sperm function and molecular composition. Palmer, NO., Bakos, HW., Fullston, T., et al.[2023]

In a study of 522 men from the Trás-os-Montes and Alto Douro region, regular physical exercise was linked to improved sperm quality, particularly in non-smokers, suggesting that lifestyle choices can positively impact fertility.

Higher body mass index (BMI) was associated with poorer sperm quality, especially sperm concentration, indicating that maintaining a BMI under 30 kg/m² is important for male fertility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of lifestyle factors with semen quality: A pilot study conducted in men from the Portuguese Trás-os-Montes and Alto Douro region followed in fertility support consultations. Pinto-Pinho, P., Matos, J., Arantes-Rodrigues, R., et al.[2021]

Regular exercise significantly reduces body weight, total body fat, and visceral fat, with a clear dose-response relationship indicating that more exercise leads to greater benefits.

Sedentary lifestyles can lead to rapid weight gain and increased visceral fat, highlighting the importance of physical activity in preventing metabolic deterioration and improving insulin signaling through enhanced fatty acid oxidation in skeletal muscle.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise, abdominal obesity, skeletal muscle, and metabolic risk: evidence for a dose response. Slentz, CA., Houmard, JA., Kraus, WE.[2021]

Citations

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Diet and Nutritional Factors in Male (In)fertility ... According to some data, the quality of human semen has deteriorated by 50%–60% over the last 40 years. A high-fat diet and obesity, resulting from an unhealthy ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1521693423001013

Obesity and male infertility The men lost on average 16.5 kg (95% CI 15.2–17.8) weight while on the low-calorie diet, which increased sperm concentration 1.49 fold (95% CI 1.18–1.88, p < 0 ...

3. academic.oup.com academic.oup.com/humrep/article/37/7/1414/6587152

Sperm count is increased by diet-induced weight loss and ... This study shows that sperm concentration and sperm count were improved after a diet-induced weight loss in men with obesity. Our findings ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/20905998.2024.2421626

Can lifestyle changes significantly improve male fertility Lifestyle changes like diet, exercise, and stress reduction can improve male fertility, but more research is needed for solid guidelines.

5. mdpi.com mdpi.com/1422-0067/23/5/2542

Diet and Male Fertility: The Impact of Nutrients ... The aim of this review is to summarize the most recent evidence regarding the impact of nutrients and antioxidant molecules on sperm quality.

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The effect of obesity interventions on male fertility Infertility rates are ∼50% higher in men with obesity compared with men of normal weight (Campbell and McPherson, 2019), and overall, conception ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12467420/

Progress in Investigating the Impact of Obesity on Male ... Substantial evidence indicates that obesity adversely affects sperm quality, thereby impairing male fertility. Specifically, obesity is associated with ...

8. withpower.com withpower.com/trial/phase-1-2020-066be

Diet and Exercise for Obesity-related Sperm Changes This study demonstrated that male obesity negatively affects sperm quality, but these effects can be reversed through diet and exercise interventions, even if ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT03553927

Investigating the Physiological Effects of Weight Loss on ... The purpose of this study is to determine the physiological effects of weight loss on seminal parameters in male participants with reduced reproductive capacity ...