Can too many supplements harm male fertility?

While multiple studies have shown the benefit of antioxidant supplements in improving male fertility, what effect excessive supplementation has isn’t clear. This post combines a new study with older studies that show high levels of supplements can harm male fertility. However, these studies all have their limitations, and better quality research is needed to draw conclusions.

Note that this post refers to male, and not female, fertility. However, the same principles may apply. I’m not sure if there’s any data that relates to female fertility, but I’ll update this post in the future if I find some!

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A new study finds that excess male fertility supplements can cause harm

Moazamian et al. (2025) conducted a small animal study, where they treated mice with increasing doses of vitamin C, zinc, folate and carnitine, then evaluated sperm health and fertility.

They used a low/moderate/high dose of each supplement (the doses below are human doses, which were converted to the animal equivalents in the study):

• Vitamin C (30 mg, 300mg, 3000 mg).
• Zinc (5 mg, 15 mg, 45 mg).
• Folate (0.18 mg, 0.36 mg, 1.2 mg)
• Carnitines (150 mg, 750 mg, 3500 mg). This included blend#1: acetyl-L-carnitine and propionyl-L-carnitine; and blend#2: L-carnitine, acetyl-L-carnitine and propionyl-L-carnitine (#2 was to mimic a top-selling male fertility supplement).
• Control: no supplements.

Now let’s look at some of the results!

In terms of semen parameters, they found minimal differences in sperm concentration, motility, and acrosome integrity.

In terms of DNA fragmentation (these values were visually estimated from a graph):

• Vitamin C increased DNA fragmentation for the low, moderate and high dose (5%, 12.5%, 10%) compared to the control (2.5%).
• Zinc increased DNA fragmentation for the low dose (4%) compared to the control (2.5%). The moderate and high doses weren’t different from the control.
• Folate didn’t change DNA fragmentation levels compared to the control.
• Carnitines increased DNA fragmentation for the low, moderate and high dose (5%, 40%, 40%) compared to the control (2.5%). Because of this large increase, the researchers repeated the experiment with blend#2, which also increased DNA fragmentation (12% vs 5%).

They also mated the mice who received high doses of carnitine, and found no statistically significant difference in the pregnancy rate compared to control mice (62.5% vs 31.25%, p= 0.07).

The researchers also did an analysis on the composition of available supplements:

• From the ~40,000 supplements on the US market that contained vitamin C, zinc, folate or carnitines, more than 70% contained these ingredients at levels higher than the lowest dose from this study.
• When they focused on 34 commercially available male fertility supplements, 97.06% had at least one ingredient higher than the lowest dose in this study, while 32.35% had higher doses for all 4 ingredients. These commercially available supplements were previously assessed in a study by de Ligny et al. (2023), who found that 27 out of 34 had ingredients with dosages exceeding the recommended daily allowance.

Overall, this study found that higher doses of carnitines resulted in increased levels sperm DNA fragmentation, although this didn’t result in any significant difference in pregnancy rates. Obviously, this needs to be repeated in humans, so drawing conclusions here is difficult.

The authors warn against the “indiscriminate use of supplements” and conclude that “men with mild to no nutrient deficiencies or oxidative stress should avoid high-dose antioxidant supplements to circumvent the risk of reductive stress, which could negatively impact semen quality and fertility.” More on “reductive stress” below!

There were a number of limitations with this study:

• It’s a mouse study, and it’s unclear if the biology of their fertility as it relates to excessive supplementation matches humans.
• Antioxidants were administered via drinking water and variability in the amount of water each mouse drinks in a day could lead to inconsistencies in dosing.
• It’s unclear if the doses they used for mice accurately reflect the dose in humans.
• Small group sizes.
• Conflict of interest: The study discloses that several authors are employees or advisors of CellOxess Biotechnology, which has a commercial interest in measuring oxidative stress levels in humans.

So now let’s turn our attention to two things:

1. Why would excessive supplements cause harm? Next, we’ll look at the idea of “reductive stress” to explain this.
2. After this, we’ll look at some other evidence that considers excess supplements and its impact on male fertility.

Oxidative and reductive stress

Reactive Oxygen Species (ROS) are highly reactive molecules that are produced during normal cellular processes and can also originate from external sources like pollution or smoking. Diet can also influence ROS levels in the body. When present in high amounts, ROS can damage cells, proteins, and DNA. Antioxidants, like vitamins C and E, neutralize ROS and help prevent this damage.

In simple chemistry, oxidation means losing electrons while reduction means gaining electrons — together, these opposing processes create a balance called redox potential, which indicates how oxidized or reduced a system is.

There is a careful balance between ROS and antioxidants in the body, and an imbalance can cause cellular stress that can impair normal cellular functions. Excessive ROS can lead to oxidative stress, while having too many antioxidants can cause reductive stress (or antioxidative stress).

Both oxidative and reductive stress can cause problems for the cell, or in the context of the above study, for the sperm! This might explain why there was increased DNA fragmentation with carnitine in the above study. Additionally, key processes in sperm, such as capacitation and the acrosome reaction, depend on having just the right amount of ROS (de Lamirande and Gagnon 1995, Kowalczyk 2021). Therefore, maintaining a proper redox balance is crucial for healthy sperm function.

For more information on reductive stress and how it could cause damage, here’s a simplified (but very scientific) explanation from Dutta et al. 2022:

• Mitochondria naturally produce superoxide, a type of ROS, which is then converted into hydrogen peroxide (H₂O₂).
• Although H₂O₂ is itself a ROS and can be harmful to cells, mitochondria use specific enzymes — such as catalase and glutathione peroxidase — to break it down into water and oxygen. Common antioxidants do not target H₂O₂.
• When too many antioxidants are present, they remove free radicals like superoxide in the mitochondria too effectively.
• This disruption upsets the balance and leads to reductive stress, causing H₂O₂ to accumulate and spill out from the mitochondria. Excess H₂O₂ can damage proteins, lipids and DNA in the cell, potentially disrupting cell function, triggering inflammation, and even causing cell death.

Now let’s look at some of the evidence for excess supplements harming male fertility.

A brief review of studies examining excess supplement use and male fertility

So what evidence is there that excess supplements can harm male fertility? I checked a few reviews for this information (Henkel et al. 2019, Dutta et al. 2022 and Gomez et al. 2023), as well as references from the Moazamian et al. (2025) study I covered above. I checked these references out in a bit of detail, and left my comments in italics.

• Verma and Kanwar (1998) treated semen samples with increasing amounts of vitamin C, and found that higher concentration (> 1000 micromolar) can disrupt sperm motility and increased sperm membrane damage (lipid peroxidation). Levine et al. (1996) showed that supplementing up to 2500 mg of vitamin C a day only resulted in a serum concentration of about 80 micromolar — not anywhere close to the 1000 micromolar concentration in the Verma study. So this >1000 micromolar dose seems unrealistic. Looking over the Verma study, I found no rationalization for using such a high concentration.
• Bleau et al. (1984) measured selenium content in semen, finding that selenium levels between 50 and 69 ng/ml was ideal for sperm motility (higher and lower levels had lower motility). Lower levels were linked to male infertility, while higher levels were linked to higher miscarriage rates. This is a really old study, and there were only 36 patients with high selenium levels (with 24 pregnant and 12 not pregnant), so the sample size was pretty small.
• Zhang et al. (2023) found that excess selenium caused testicular damage in mice, and caused DNA damage. Again, the doses in this study appear to be very high. The lowest dose was 0.1 mg/kg, which for a 60 kg human would be 6 mg of selenium a day, which is very high. Turgut et al. (2003) and Yokota et al. (2019) also performed mouse studies using high levels of zinc and vitamin A, respectively, which I suspect are toxic and unrealistic doses for humans.
• Ménézo et al. 2007 also found that while vitamin C reduced sperm DNA fragmentation, it increased sperm DNA decondensation — meaning it unravelled sperm DNA, which might lead to issues with gene expression during embryo development. While this is interesting and concerning, the study didn’t show it affected fertility.
• An unpublished case report, mentioned by Henkel 2018, involved a couple who were taking a large number of supplements and then stopped for 3 months and became spontaneously pregnant. The couple had 7 failed IVF cycles before this, and high levels of sperm DNA fragmentation. This is just an anecdote, which is the lowest form of evidence available.
• Ran et al. (2025) found that while short term (14 day) L-carnitine exposure resulted in increased sperm motility, chronic (50 day) L-carnitine exposure resulted in nearly all sperm becoming non-motile. I can’t access this study, but they used the “clinical adult (human) dosage” of L-carnitine, and converted the dose to mouse units, so these results are concerning. They are done in mice, however, so it’s hard to be sure if the same results would be seen in humans.

In my view, the available data on antioxidant supplementation and male fertility is generally low quality, with some animal studies seemingly designed to show harmful effects by using toxic doses, which is misleading. More studies are needed that not only address excessive doses of a single supplement, but the effect of multiple supplements. Many patients take a large number of supplements, which may have very different effects compared to just a single supplement.

Henkel et al. (2019) and Dutta et al. (2022) argue that supplement studies are at a disadvantage because patients’ redox levels aren’t measured in advance, and there’s no clear definition or agreed-upon cutoff for normal levels. This could explain the inconsistent outcomes in supplement studies — patients with lower baseline antioxidant levels may benefit from supplementation, whereas those with already high levels might not. Without an initial measurement of these levels we just don’t know! Furthermore, I don’t think there are agreed upon dosages/treatment times for supplements, which only complicate the results of these studies.

Henkel et al. (2019) go as far as to say that it’s possible some cases of infertility might actually be caused (!) by excessive supplementation, and advises that clinicians carefully interview patients before prescribing supplements to prevent overdosing.

Additionally, Dutta et al. (2022) and Gomez et al. (2023) note that inflammation and oxidative stress are interconnected, and this can create a self-perpetuating cycle that damages male fertility. Although antioxidants can help reduce inflammation indirectly by lowering oxidative stress, they are not primarily anti-inflammatory and may need to be combined with targeted anti-inflammatory treatments.

Besides fertility, excess supplementation has been studies for other diseases, showing links to cancer, cardiomyopathy, Alzheimer’s disease, and defects in fetal organ development (Klein et al. 2011, Lloret et al. 2016, Rajasekaran et al. 2010, Ufer et al. 2010).

Too much of anything isn’t a good thing, and the same is likely true for supplements. However, without good quality evidence to back it up, it’s hard to know where to draw the line.

For related reading, check out these posts:

• The problem with supplements
• Study reviews 34 common male fertility sperm supplement brands for safety, efficacy
• Comprehensive review combines research on use of supplements for female infertility
• CoQ10 and other supplements improve IVF outcomes in women with ovarian aging

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About Embryoman

Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.

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