Katariina Stumpf

Circulating enterolactone and prostate cancer risk: A Nordic nested case‐control study

Enterolactone, a phytoestrogen belonging to the class of lignans, is produced by the intestinal microflora from precursors in plant foods and has been implicated in protection against cancer. We study the effect of enterolactone on the risk of a subsequent diagnosis of prostate cancer. We conducted a longitudinal, nested case‐control study by linkage of 3 biobanks to the cancer registries in Finland, Norway and Sweden, respectively. Enterolactone concentrations were measured by time‐resolved fluoroimmunoassay in serum from 794 men who had a diagnosis of prostate cancer at a mean follow‐up time of 14.2 years after blood collection and among 2,550 control men matched within each cohort for age (±2 years), date of blood collection (±2 months) and county. The median enterolactone concentrations did not differ between case and control subjects in the full study group (8.4 nmol/L [25th–75th percentile = 4.5–15.0] vs. 8.5 nmol/L [25th–75th percentile = 4.3–15.9]), nor in the national groups. Odds ratios of prostate cancer risk estimated by conditional logistic regression for increasing concentrations of enterolactone in quartiles in the full study group were 1.00 (referent), 1.21 (95% confidence interval [CI] = 0.96–1.52), 1.16 (95% CI = 0.91–1.47) and 1.08 (95% CI = 0.83–1.39). The OR estimate for the highest vs. the lowest quartile of enterolactone in separate analyses of the Norwegian, Finnish and Swedish cohort was 1.21 (95% CI = 0.91–1.60), 1.02 (95% CI = 0.59–1.76) and 0.87 (95% CI = 0.45–1.67), respectively. No support for the hypothesis that high circulating enterolactone is protective against prostate cancer was found.

Whole grain food intake elevates serum enterolactone.

Both intake of whole grain and higher levels of serum enterolactone have been related to reduced risk for CHD and some cancers. Because lignans are prevalent in the outer layers of grains, these findings may be related. We carried out a crossover feeding study in which overweight, hyperinsulinaemic, non-diabetic men (n 5) and women (n 6) ate, in random order, wholegrain foods or refined-grain foods in a diet with 30 % energy from fat. The dominant whole grain was wheat, followed by oats and rice. All food was supplied by the investigators and each diet lasted for 6 weeks, with an intervening washout period of 6-9 weeks. Serum enterolactone concentrations were higher when eating the wholegrain than the refined-grain diet by 6.2 (within person SE 1.7) nmol/l (P=0.0008). Most of the increase in serum enterolactone when eating the wholegrain diet occurred within 2 weeks, though the serum enterolactone difference between wholegrain and refined-grain diets continued to increase through 6 weeks. Serum enterolactone concentrations can be raised by eating a diet rich in whole grains.

Short-Term Variations in Enterolactone in Serum, 24-Hour Urine, and Spot Urine and Relationship with Enterolactone Concentrations

Enterolactone, a mammalian lignan, is produced by colonic microflora from precursors present in food plants. Because intake of vegetables, fruits, berries, or whole grains is related to the enterolactone concentration in blood (1)(2) and excretion in urine (3)(4), enterolactone may function as a biomarker of fiber-rich foods. Important characteristics for a biomarker include convenient, low-risk collection of samples; specific, reliable laboratory measurement; and a high ratio of between-person to total variability \[intraclass correlation (ICC)\] (5). In epidemiologic studies, analytes with a low ICC often show weak associations with any disease (6). The present study describes the short-term variation in enterolactone in serum, 24-h urine, and spot-urine enterolactone:creatinine ratio and the relationship between enterolactone concentrations in serum, 24-h urine, and spot urine. The study protocol was approved by the Ethics Committee on Epidemiology and Public Health in the hospital district of Helsinki and Uusimaa. Twenty volunteers (13 females and 7 males) were recruited among university students. Exclusion criteria included age <18 years, antibacterial treatment during the preceding 3 months, and any major illness or regular medication, except contraceptive pills. The average age of the participants was 22.2 years [95% confidence interval (CI), 21.4–22.9 years], and the average body mass index was 22.3 (20.9–23.6) kg/m2. Of the female participants, seven took oral contraceptives. The female participant who regularly took an antidepressant reported this only at the end of the study. One participant dropped out because of antibacterial treatment for a urinary tract infection. One spot-urine sample was missing for one female participant, who was thus excluded from that analysis. The samples were collected on 5 successive days (Monday to Friday) for within-week variation and on the following 3 Mondays for within-month variation. Participants began collecting their urine 24 h before serum and spot-urine samples were …