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: Unknown

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a rigorous, controlled clinical trial designed to show that diet, exercise training, and their combination in overweight, inactive men will alter epigenetic programming to create a "healthy" sperm epigenome. Our central hypotheses are: i) overweight and inactive lifestyle results in epimutations in the sperm epigenome relative to the normal epigenetic programming in lean and active men and ii) diet and exercise modulation leads to reversal of these epimutations resulting in both a healthier "phenotype" and "epigenotype" which may persist after stopping the interventions. The study is divided into three parts: 1. We will recruit 20 healthy, active men and 20 obese and inactive Hispanic men between 18 and 40 years to determine the differences in sperm epigenome (DNA methylation, histone modifications and non-coding RNAs) in a cross-sectional study in obese inactive vs. healthy active Hispanic men. Only Hispanic men will be studied because of the high prevalence of obesity and inactivity in Hispanic younger men and to reduce the genetic variability influencing the epigenome. 2. 80 obese and inactive men will be randomized to 4 groups of 20 men: 1) No intervention (control); 2) Low fat, low caloric diet; 3) Supervised, periodized endurance and resistance training without modification of diet; and 4) Both exercise and diet modification to characterize the plasticity of the sperm epigenome in response to 12-week diet and/or exercise training interventions in obese and inactive Hispanic men. Sperm epimutations will be compared before and after intervention within each group and between groups. 3. The sperm epigenome studies in 80 men randomized to no intervention or diet and/or exercise training will be repeated at 12 and 36 weeks after cessation of interventions to Identify the persistent effects of diet and exercise training on the sperm epigenome after stopping the interventions.

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.

What data supports the idea that Diet and Exercise for Obesity-related Sperm Changes is an effective treatment?

The available research shows that diet and exercise can improve sperm quality in obese individuals. For example, a study on mice found that diet and exercise reduced body fat and improved sperm function. Another study indicated that regular exercise improved semen quality in sedentary obese adults. These findings suggest that maintaining a healthy weight and engaging in regular physical activity can positively impact sperm health. ^{1 2 3 4 5}

What safety data exists for diet and exercise treatments for obesity-related sperm changes?

The research indicates that combining diet and exercise is generally safe and effective for obesity management. Studies show that increasing physical activity and improving diet can reduce obesity odds and improve body composition. Exercise, even without dieting, can lead to fat loss and improve metabolic health. There is a dose-response relationship, meaning more exercise leads to greater benefits. Properly managed very-low-calorie diets with exercise can preserve physical function during weight loss. Overall, regular exercise is a valuable addition to dietary changes for weight control and reducing chronic disease risk. ^{6 7 8 9 10}

Is diet and exercise a promising treatment for obesity-related sperm changes?

Yes, diet and exercise are promising treatments for obesity-related sperm changes. Studies show that they can improve sperm concentration and motility, reduce body fat, and improve overall sperm quality, especially in non-smokers. ^{1 2 3 11 12}

Research Team

Christina Wang, MD

Principal Investigator

The Lundquist Institute

Eligibility Criteria

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.

I have high blood pressure, but it's controlled with medication.

Known or suspected alcoholism or drug abuse or chronic infections

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Intermittent resistance exercise and obesity, considered separately or combined, impair spermatic parameters in adult male Wistar rats. [2021]

3. Germany 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. [2021]

4. Spain pubmed.ncbi.nlm.nih.gov

Exercise improved semen quality and reproductive hormone levels in sedentary obese adults [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Obese father's metabolic state, adiposity, and reproductive capacity indicate son's reproductive health. [2014]

6. United States pubmed.ncbi.nlm.nih.gov

Exercise and the treatment of diabetes and obesity. [2011]

7. United States pubmed.ncbi.nlm.nih.gov

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

8. United States 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. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Exercise, abdominal obesity, skeletal muscle, and metabolic risk: evidence for a dose response. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

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

11. Germany 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. [2020]

12. United States pubmed.ncbi.nlm.nih.gov

Impact of obesity on male fertility, sperm function and molecular composition. [2023]