Fertility supplements: Growing research and credibility

Photo © AdobeStock.com/ParamePrizma

The fertility supplements market has been fraught with peril as of late. In March 2021, BBB National Programs announced that fertility supplement company FertilitySmart (Dover, DE) permanently discontinued seven advertising claims and several consumer testimonials in response to a challenge brought by dietary supplement association the Council for Responsible Nutrition (Washington, DC).¹ Two months later, in May, FDA and the FTC issued joint warning letters to five fertility supplement brands that had made illegal disease-treatment claims.²

When bad actors in a particular category make unsubstantiated or illegal product claims, it makes credibility and validation all the more important for other brands. Manufacturers and marketers who can substantiate product claims with clinical research stand to benefit from the gap in the market left by the pretenders. Here are some of the fertility ingredients that are demonstrating efficacy in clinical trials.

5-MTHF Glucosamine Salt

Folate has long been linked to fertility and is a common ingredient in fertility supplements and various fortified foods. Not all folate, however, is created equal.

Silvia Pisoni, market manager, reproduction and women’s health, for Gnosis by Lesaffre (Lille, France), says most of the folate found in dietary supplements and functional foods is folic acid, an inactive compound that is not readily absorbed in the body.

“The folate naturally contained in food tends to be unstable and susceptible to oxidation, losing activity during processing, manufacturing, and storage,” Pisoni says. “That’s why folate is often utilized in fertility supplements [rather than functional foods]. But to ensure the best results, it’s critical that the folate used is active folate.”

Recent research linked an impairment in the folate cycle through methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism to infertility in both women and men, Pisoni says. This impairment limits the body’s ability to convert folate into its bioactive form, methyltetrahydrofolate (5-MTHF).

One case series³ published in 2018 followed 33 couples with a history of fertility problems lasting at least four years. The couples had experienced several different fertility problems, including abnormal sperm, fetal loss, or premature ovarian insufficiency. Twenty of the couples had previously attempted and failed to conceive using assisted reproductive technology (ART). One or more of the partners in each couple carried an MTHFR isoform. A majority of the female participants had previously received a course of high-dose folic acid (5 mg/day) without success.

For this case series, 33 women and 29 men received one daily dose of a combination product containing Parthenogen’s (Lugano, Switzerland) branded Impryl B vitamin complex, Nurilia’s (Lyon, France) branded Tetrafolic chelated zinc, and 800 micrograms of Gnosis’s branded Quatrefolic ingredient. Quatrefolic is a 5-MTHF glucosamine salt, a folate derivative and structural analogue of 5-MTHF. The subjects followed this regimen for four months before attempting spontaneous conception for two months and then beginning a 74-day round of assisted reproductive technology treatment.

Thirteen couples, or 39%, reported spontaneous conception by the end of the four-month intervention period. Another 13 couples reported pregnancy attained after ART treatment. One couple was not followed up with, and two couples were still receiving ART treatment at time of follow-up. The study authors determined that 5-MTHF glucosamine salt may be able to eliminate the need for assisted reproductive technologies.

Pisoni says it’s critical that fertility brands have clinically validated data behind their products. It’s this data, she says, that will give consumers the confidence to select a fertility supplement that meets their needs.

Product Development, Research Protocols Advance

Research on natural fertility ingredients has become more advanced in recent years, which has opened up new avenues for brands. Nicole Avena, PhD, is a New York–based research neuroscientist who studies prenatal and early-life nutrition. Avena is also the author of What to Eat When You Want to Get Pregnant, a fertility nutrition book for consumers that was published in March 2021.

Avena says that a new push to include more women in clinical trials, especially pregnant women, has been a boon for fertility research. “This is huge,” Avena says. “When it comes to fertility, it’s essential to be able to work with pregnant women to understand how the baby is doing during pregnancy, not just when it’s born.”

Fertility ingredient formulations have also advanced in a way that gives formulators more flexibility with delivery systems, Avena notes. Fertility supplements now come in the form of pills, gummies, functional foods, and powdered drink mixes.

Several fertility ingredients are currently trending as a result of ongoing research. Avena points to cassava (Manihot esculenta), a South African tuber and a source ingredient for tapioca pudding, as an example of an emerging fertility ingredient that merits more in-depth research. “Cassava is believed to increase ovulation and increase the chance of having twins,” Avena says. “But the research is extremely limited in humans.”

Myo-inositol as another trending fertility ingredient for women. Research indicates it may help improve fertility in those undergoing in vitro fertilization. Avena says there is some evidence to suggest that ingredients like ashwagandha, maca root, zinc, and certain ingredients derived from the chaste tree (Vitex agnus-castus) may help improve male fertility.

Health Claims: Staying on FDA’s Good Side

Given that fertility supplements are an active area of ongoing FDA enforcement, brands in this space must devote special attention to regulatory requirements. In order to make a health claim on a supplement, a brand should be able to substantiate that claim, Avena says.

In some cases, a health claim can fall into the category of a qualified health claim, which has less evidentiary support than an FDA-authorized claim. However, Avena says the distinction between authorized and qualified claims isn’t as clear to consumers as it is to those in the industry. “Qualified health claims must come with a disclaimer that discloses the amount of evidence there is to substantiate the claim,” Avena explains. “Not providing such a disclaimer not only goes against the FDA dietary supplement guidelines but is also misleading to the consumer.”

Opportunities for Emerging Products

The fertility ingredients market is full of promise for clinically validated ingredients. Research and development are fueling interest in a diverse array of fertility supplements, both in terms of active ingredient and product format. Some brands are now launching synergistic fertility blends, expanding the market beyond single-ingredient products. As further clinical studies reveal which fertility ingredients are the best validated, expect the fertility market to offer more opportunities for credible brands.

References

1. BBB National Programs press release. “Certain Advertising Claims for FertilitySmart Conceive for Women Dietary Supplement Permanently Discontinued Following NAD Challenge.” Posted online March 23, 2021.
2. United States Food & Drug Administration press release. “FDA, FTC Warn Five Companies Illegally Selling Dietary Supplements Claiming to Treat Infertility.” Published online May 26, 2021.
3. Servy EJ et al. “MTHFR isoform carriers. 5-MTHF (5-methyl tetrahydrofolate) vs folic acid: A key to pregnancy outcome: A case series.” Journal of Assisted Reproduction and Genetics, vol. 35, no. 8 (August 2018): 1431-1435