Reference
Jensen TK, Priskorn L, Holmboe SA, et al. Associations of fish oil supplement use with testicular function in young men. JAMA Netw Open. 2020;3(1):e1919462.
Study Objective
To observe differences in parameters of testicular function in healthy, young men who had used fish oil supplements in the previous 3 months compared to those who had not
Design
A cross-sectional, observational study
Participants
The study included 1,679 men (average age 18.9 years) from Denmark, recruited at military conscription medical appointments.
Study Parameters Assessed
The study measured the following as parameters of testicular function:
- Testis size (measured by ultrasonography and physician palpation)
- Semen analysis (including total volume, sperm concentration, total sperm count, and sperm motility)
- Serum reproductive-hormone analysis (luteinizing hormone [LH], follicle-stimulating hormone [FSH], sex hormone–binding globulin [SHBG], free and total testosterone, estradiol, and inhibin B)
Participants received a comprehensive health, lifestyle, and diet questionnaire that evaluated their use of different dietary supplements, including the use of fish oil supplements within the last 3 months (this was further categorized by intake on 60 or more days or fewer than 60 days out of the total 3-month period prior).
Participants also underwent a physical exam, including body mass index (BMI) and hip-to-waist measurements.
Primary Outcome Measures
The primary outcome measure was any statistically significant differences in assessment of testicular function between men who had consumed fish oil supplements and those who had not.
Key Findings
There were 98 men (5.8%) who took fish oil supplementation in the prior 3 months. Just over half of these men (54.1%) had taken fish oil for more than 60 days.
Semen production
Those who took fish oil supplements but for fewer than 60 days in the previous 3 months had semen volume that was on average 0.38 mL higher than those who had not used fish oil supplements at all (95% CI, −0.03 to 0.80). Men who consumed fish oil supplements for 60 days or more in the previous 3 months had semen volume that was 0.64 mL higher than nonusers (95% CI, 0.15 to 1.12) (Ptrend<0.001).
Testicular size
Men who took fish oil supplements but for fewer than 60 days in the previous 3 months had testicular volume that was 0.8 mL larger than those who had not used fish oil supplements at all (95% CI, −0.02 to 1.90). Men who consumed fish oil supplements for 60 days or more in the previous 3 months had testicular volume that was 1.5 mL larger than nonusers (95% CI, 0.2 to 2.8) (Ptrend=0.007).
Total sperm count was also higher in those who took fish oil supplements versus nonusers (P=.007). FSH LH were 20% (P=0.003) and 16% (P<0.001) lower in men who used fish oil supplements compared to those who did not. Fish oil supplementation was also associated with an 8% higher ratio of free testosterone to LH (P=0.02).
Practice Implications
Deteriorating sperm quality has been reported for over the last half-century.1 Lifestyle factors and impacts from the environment present a number of potential detriments to testicular function that could potentially explain this continual decline. With infertility being an issue that many modern couples (and others seeking to conceive a child) may encounter—and with men contributing to 50% of these cases2—there is a clear need to improve semen count and quality. Supporting fertility may also be integral to supporting general population health and preventative medicine.
It should really be no surprise that healthy diets (which include fruits, vegetables, fish, and seafood) are associated with good semen quality, and diets high in processed, sweetened foods and saturated fats are associated with poor semen quality.3 In men with marked clinical fertility issues, clinical trials on supplementing with omega-3 fatty acids have shown supplementation to increase sperm count, concentration, and motility,4 as well as decrease DNA fragmentation and increase the number of morphologically normal spermatozoa.5 There are some clear mechanisms of action for why this is beneficial: The sperm cell membrane has a large concentration of fatty acids, with increases in polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), as it matures.2,6 The sperm membrane is integral in managing many aspects of fertilization. Higher DHA in the sperm membrane is associated with better sperm morphology and function.2 Unique to this study was that researchers tracked the fish oil supplementation in healthy, young males versus those with infertility, and supplementation was still associated with improved testicular function, specifically with regards to semen volume, testis size, and reproductive hormone levels.
Supporting fertility may also be integral to supporting general population health and preventative medicine.
As an observational study, the direct clinical application of this therapy may not be supported by this research on its own. But the study does raise a number of clinically relevant questions. The fact that the men who used fish oil and used it more frequently (more than 60 out of 90 days) had more significant differences than those who used fish oil less frequently suggests there is a dose-response relationship here, but the study did not record omega-3 dose and eicosapentaenoic acid (EPA)/DHA ratios for the individual participants, so it is very difficult to say just how much these men were taking. However, one could put forth the argument that most self-prescribers of fish oil in the general population are likely using a fairly low dose compared to what is prescribed therapeutically. This could mean that even a fairly small increase in dietary omega-3 could have significant impacts on testicular function, even in generally healthy young men.
Interestingly, the study did not adjust for dietary intake of fish, though the authors cite an average daily intake of 26 g of fish for this population demographic, an amount they describe as “low.” Since the participants were from a Scandinavian country, this fish intake may be quite high compared to the standard American diet. If these statistical differences were seen in a population that supplements with fish oil and also already consumes higher amounts of fish, could the impacts of fish oil supplementation on testicular function be even more profound in populations who do not consume as much fish in their natural diets?
While statistical differences in semen volume and testicle size are striking, how clinically significant are these differences? Do these differences actually mean increased ability of the sperm to fertilize an egg? And for men lured into this potential promise of enhancing their genitals with fish oil supplements, can they really expect to notice any difference? When one considers the medical reference ranges for healthy testicle size and the individual variability in ejaculation volume, even if a man who started to supplement with fish oil derived the maximum benefits reported in this study, it is likely that any physically noticeable difference would be very subtle, at best. However, the study did find that men who supplemented with fish oil were less likely to have semen quality that fell below the World Health Organization (WHO) reference limits, which does provide some further support for this having clinically relevant effects.
Of further clinical importance are the differences in reproductive hormones associated with fish oil supplementation reported in this study. The lower levels of FSH and LH, in combination with the other parameters of testicular function, suggest that fish oil supplementation may enhance the sensitivity of the gonadotropin-releasing system and the testicular cells. In other words, the impacts on semen quality from fish oil supplementation involve not just the structural nutrients provided to the sperm cells, but also affect hormones in a way that may favor sperm production. This may be an important long-term health target for men, as the levels of LH, FSH, testosterone, and their relative ratios have been implicated in the risk and the aggressiveness of prostate cancer,7,8 and also play a role in cardiovascular disease, insulin resistance, and obesity.9 This may provide further support for the theory of long-term fish oil supplementation in prevention of prostate cancer and other chronic health conditions in men that may be hormone-related.
The study is to be commended for the many measures it took to account for confounding variables when interpreting associations. For example, the questionnaire also evaluated the use of other supplements, including vitamin C, vitamin D, and multivitamins. When the results were stratified against those who used these individual supplements (with or without fish oil supplements) and those who did not use supplements at all, there was no effect of the other supplements that could account for the statistical differences. Researchers recorded a number of other relevant health history items for the participants that could affect testicular function, including: personal smoking history, maternal smoking history/in utero smoking exposure, alcohol use, history of sexually transmitted diseases (STDs), history of cryptorchidism/varicocele/other testicular defect or trauma, and recent history of fever. Researchers also accounted for general health status and perceived personal fitness level, as well as BMI and other basic health measurements, in the statistical comparison.
The investigators attempted to ensure consistency in sample collecting by standardizing the collection of serum hormones to generally the same morning time for all participants (or noting otherwise), as well as recording the time of previous ejaculation in relation to the time of semen sample collection. Many of the laboratory tests were performed a minimum of 2 times for confirmation. In summary, the research team eliminated many arguments that could be used to contest the inferred associations of the study results by including other factors that could have influenced the study end points.
Are there limitations to these findings? Primarily, this was an observational trial and did not involve a controlled clinical intervention. Part of the evaluation involved a questionnaire with self-reported answers, which does create opportunity for reporting bias. And while the study did account for many confounding factors, its participants were recruited from a very specific demographic—young army recruits in Denmark—which affects the generalizability of this to men of other ages and ethnic backgrounds. Also, there is still much debate about fish oil supplementation versus dietary fish consumption, the relative ratios of EPA/DHA, and how this affects total body levels of omega-3 (and how reliably this can be measured).
Lastly, the authors hypothesized that those who used dietary supplements would be generally “healthy” participants, and they were correct; participants who reported using supplements had lower smoking exposure and better self-reported health and physical fitness. The statistical analysis did adjust for these variables, but it is difficult to accommodate for whether there were other healthy lifestyle behaviors that may have contributed to the better semen quality among this group, though the differences in dose-response (≥60 days vs <60 days of fish oil use) do attenuate this slightly.
Research focused on enhancing testicular function will capture people’s attention, but to validate fish oil as a therapeutic tool in male infertility, we need clinical trials that not only control the intervention dose, but investigate clinically relevant outcomes to fertility, such as effects on conception rates, in vitro fertilization (IVF) outcomes, and live births—rather than looking only at sperm quantity or quality. Furthermore, the impacts of fish oil supplementation on reproductive hormone levels may affect other health conditions in men and deserves more exploration. Fish oil is likely to continue to be 1 of the most commonly self-prescribed and practitioner-recommended natural supplements for a variety of health benefits, and for those who choose to use it, finding products that are ethically sourced and environmentally responsible should be a priority.
