Alcohol, Smoking, and Caffeine in Relation to Fecundability, with Effect Modification by NAT2

Abstract

PURPOSE Common polymorphisms in the N-acetyltransferase-2 (NAT2) metabolic enzyme determine slow or rapid acetylator phenotypes. We investigated the effects of alcohol, smoking, and caffeine on fecundability, and determined whether the effects were modified by NAT2. METHODS Three NAT2 polymorphisms were genotyped in 319 women office workers participating in a prospective pregnancy study (1990–1994). Women were ages 20–41 and at risk for pregnancy. Discrete-time survival analysis was used to determine the effects of alcohol, smoking, and caffeine on fecundability and evaluate effect modification by NAT2. RESULTS 319 women (161 slow acetylators, 158 rapid) were followed for an average of 8 menstrual cycles, resulting in 124 pregnancies. There was no effect of caffeine on fecundability. Drinking 1+ alcoholic drink/day and current smoking were significantly associated with reduced fecundability, but only among slow acetylators (adjusted fecundability odds ratio (FOR) for smoking= 0.34: 95% CI, 0.22, 0.90; adjusted FOR for 1+ drink/day = 0.20: 0.05, 0.92). There was no effect among rapid acetylators. CONCLUSIONS NAT2 status significantly modified the effects of alcohol and smoking on fecundability, emphasizing the importance of incorporating genetic and metabolic information in studies of reproductive health. Replication of this study is warranted.

Coffee, tea and caffeine consumption and risk of primary infertility in women: a Danish cohort study

“…In contrast, a beneficial effect of coffee and caffeine consumption on female fertility has also been shown . In line with our results, however, a number of other studies have shown no association between coffee and total caffeine consumption and female fertility (). Thus, the results of a large cohort study of 18 555 women in North America followed from 1991 to 1999 showed no association between the consumption of coffee and total caffeine (from coffee, tea and caffeinated soft drinks) and the risk for ovulatory disorders .…”

“…Although other studies on this subject were published subsequently, the results are inconclusive. Many studies showed a detrimental effect of coffee, tea or total caffeine consumption on female fertility (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), whereas others showed no association (16)(17)(18)(19)(20)(21) or a beneficial effect (22)(23)(24)(25). One reason for the inconsistency of the results may be the limited statistical power of most studies.…”

Alcohol intake, reproductive hormones, and menstrual cycle function: a prospective cohort study

“…However, alcohol intakes in the current study are comparable with those seen in other healthy, American female populations, thereby increasing the generalizability of our results (26,47,48).Finally,becauseofrecentresearchthatindicated that common polymorphisms in the N-acetyltransferase-2 gene, which codes for the N-acetyltransferase-2 enzyme that is responsible for alcohol metabolism, may modify the effects of alcohol on fecundability (51), future studies looking at the association between alcohol and menstrual cycle function should consider further capturing genetic and metabolic information.…”

“…Results were similar but significantly attenuated for the daily dairy than for the 24HDR. The 24HDR, which we considered thegoldstandard,wasadministeredattheclinicvisitbytrainedstaff with the use of a multipass approach that captured precise alcohol quantitiesandtypes.Incontrast,thealcoholassessmentviathedaily diary in our study, which was comparable to that in other reproductive health studies (50,51), simply asked participants to reportthenumberofalcoholicdrinks,whichmayhavebeenproneto rounding and consequent misclassification. Indeed, we showed only a fair agreement between the 24HDR and daily diary for capturing alcoholic drink intake for the same day (weighted k = 0.23).…”

Nutrition in Human Fertility

“…However, many of the methodological issues that plague the literature on caffeine and reproductive hazards also apply to the literature on alcohol, starting with study design issues; only seven of the studies conducted to date have been prospective [ 31 , 34 -37 , 47 , 48 ]. Among the prospective studies, three report decreased fertility with increasing alcohol intake [ 31 , 37 , 48 ], two report no association between alcohol and fertility [ 34 , 36 ], one found decreased fertility with higher alcohol intake among women older than 30 years of age but a similarly strong association in the opposite direction among younger women [ 47 ], and one reported significantly decreased fertility among slow acetylators and no relation among rapid acetylators [ 35 ].While a careful review of the existing literature on the relations of alcohol and caffeine with fertility does not provide compelling evidence that they signifi cantly hamper fertility, the opposite belief is deeply ingrained in the general population and among healthcare providers. Despite much research, it is not possible to draw strong conclusions regarding the role of alcohol and caffeine on human fertility and further study is clearly needed.…”