Are artificial sweeteners affecting fertility?
Is there an association between artificial sweetener sonsumption and reproductive outcomes?
“The Danish National Birth Cohort also found that intake of > 1 artificially sweetened drink daily during pregnancy were 1.23 times more likely to report a child asthma diagnosis and child wheeze vs non-consumers and 1.74 times more likely to report a child with allergic rhinitis during the first 7 years. No association was found for sugar sweetened drinks. ”
The use of non-natural sweeteners, interchangeably known as artificial or intense sweeteners, is broad both geographically and in terms of the multitude of ingested substances they are incorporated in. Characterised as low caloric additives that act as sugar substitutes in predominantly ‘low-energy’ or ‘low sugar’ foods and drinks, their extensive and increasing use in recent decades is attributed to the increased prevalence of obesity and metabolic pathologies and consequent shift towards low carbohydrate/low sugar dietary patterns. However the widespread application of these substances is not without controversy, with ongoing debate regarding the short- and long-term health consequences associated with chronic intake. One area of concern is the potential impact of ingestion of artificial sweeteners on fertility, reproductive, pregnancy and offspring health outcomes.
Impact on Assisted Reproductive Outcomes
Consistent with data observed in preclinical research, a 2017 cross-sectional trial assessed the potential link between regular intake of artificially- or sugar- sweetened soft drinks (ASB, SSB) or coffee on fertility and pregnancy outcomes. In particular, the primary aims of the study where to determine whether daily ingestion of these substances by males and females influenced:
oocyte quality,
intracytoplasmic sperm injection (ICSI), specifically embryo quality on days 2 and 3,
chances of blastocyst formation,
pregnancy,
implantation and
miscarriage.
(Subjects were couples undergoing ICSI due to female-factor or unexplained infertility (n=524, mean age of f: 36.4 ± 5.0 years, m: 37.5 ± 5.8 years)).
Associations were found between regular consumption of ASB or coffee and oocyte morphology (ooplasm central granulation, vacuoles, smooth endoplasmic reticulum clusters [SERc], large perivitelline space, fragmented polar body, zona pellucida and shape abnormalities) and oocyte quality (>3 servings/day, granulation, vacuoles and SERc). They were also associated with dose-dependent negative effects on day 2 embryo quality and chances of blastocyst formation, implantations and pregnancy (2-3 servings/day). Interestingly, the ingestion of SSB had no effect on any measured parameter regardless of dose. Potential mechanisms suggested by the authors requiring further investigations were gene activation and obesity-induced metabolic effects.
This study is limited by the use of a non-validated food frequency questionnaire, lack of information on quantity of sweeteners consumed, and lack of data on glucose levels in blood serum or follicular fluid and so further investigation is warranted.
Two large separate cohort analyses also indicate a potential association between regular intake of artificial sweeteners and risk of preterm birth. They conducted a prospective cohort analyses of 59,334 women from the Danish National Birth Cohort (1996-2002) and examined the association between intakes of sugar-sweetened and artificially sweetened soft drinks and preterm delivery.
In female animal models these artificial sweeteners were shown to significantly increase the percentage of abnormal estrous cycles, serum progesterone levels and apoptosis in granulosa, oocyte and corpus luteum cells, and adversely influence the quality of human oocytes and embryo development. In pregnant animal models, artificial sweeteners resulted in significant decreases in circulating progesterone levels, placenta diameter and embryo glutathione concentrations, induced glucose-intolerance and a pro-oxidative environment in the endometrium. The adverse influence of artificial sweeteners on glucose is independent of their low-caloric status. Consequently, offspring exposed to artificial sweeteners in utero had reduced gestational lengths and foetal weights and increased chromosomal aberrations, foetal congenital malformations and embryo toxicity and decreased embryo development scores. The latter mechanism has been partly attributed to the impact of the aspartame metabolite formic acid and is one of the mechanism suggested to be a potential factor involved in the increased risk of preterm birth observed in human clinical trials.
Male animal models have also observed negative effects associated with exposure to artificial sweeteners on sperm parameters and an increased rate of sperm DNA fragmentation and apoptosis. The importance of local taste receptors in sperm maturation in the concentration of fertilisation-competent sperm is one recent area of investigation which may be a mechanism influencing the impact of artificial sweeteners on sperm health.
During Pregnancy
Clinical investigations into the influence of artificial sweeteners during pregnancy on offspring health parameters have found potential links between their ingestion and offspring body composition, metabolic health and risk of atopy (the genetic tendency to develop allergic diseases). The study findings illustrated positive associations between intrauterine exposure to artificially sweetened beverages and birth size and risk of overweight/obesity at 7 years. Data with longer follow-up are warranted.
In a sub-analysis of 918 women with gestational diabetes in the Danish National Birth Cohort, daily intake of >1 ASB during pregnancy was positively associated with large for gestational age offspring (adjusted RR 1.57; 95% CI: 1.05, 2.35 at birth), BMI scores (0.59 SD increase; 95% CI: 0.23, 0.96) and overweight/obesity (aRR 1.93; 95% CI; 1.24, 3.01) at 7 years of age, compared with non-consumers. Notably, maternal obesity status, offspring physical activity, beverage consumption and dietary patterns were not significantly associated with the observed impact of ASB on offspring body composition parameters.
Mechanisms of Action
For the nerds:
Potential mechanisms suggested by the research include ASB exacerbating glucose intolerance via dysregulation and activation of sweet taste receptors subsequently promoting excessive intake and increased intestinal glucose absorption (up-regulation of expression of Na+-dependent glucose transporter SGLT1 increase of intracellular Ca2+ concentrations translocation of GLUT2 in the brush border membrane of the enterocyte); gut microbiota alterations (reduction in the number of commensal bacteria i.e. Bifidobacterium, Lactobaccillus and Bacteroidetes correlated with insulin resistance and adiposity); and induction of oxidative stress (down regulation of glutathione/glutathione peroxidase antioxidant system).
The Danish National Birth Cohort also found that intake of > 1 ASB daily during pregnancy were 1.23 times more likely to report a child asthma diagnosis and child wheeze vs non-consumers, and 1.74 times more likely to report a child with allergic rhinitis during the first 7 years. No association was found for SSB.
It would seem to me that the absence of definitive evidence demonstrating the safety of regular ingestion of artificial sweeteners during pregnancy and the findings from both the mechanistic and clinical evidence clearly highlight the need for further investigations. Currently the research highlights concerns regarding the impact of artificial sweeteners on fertility, reproductive, pregnancy and offspring health outcomes and so it could be wise to re-think your choices when it comes to artificially sweetened drinks or sachets.