Markers associated with genomic instability, immunogenicity and immune therapy responsiveness in Metaplastic carcinoma of the breast: Expression of γH2AX, pRPA2, P53, PD-L1 and tumor infiltrating lymphocytes in 76 cases.

BACKGROUND: Metaplastic breast cancer (MpBC) is an aggressive subtype of breast carcinoma that is often resistant to conventional chemotherapy. Therefore, novel treatment strategies are urgently needed. Immune check point inhibitors have shown activity in programmed death-ligand 1 (PD-L1) - positive metastatic triple negative breast carcinoma (TNBC), which raises the possibility that immunotherapy may also be effective in MpBC as most of the MpBCs are triple negative. The aim of the present study was to assess genomic instability and immunogenicity in tumor specimens of patients with MpBC. METHODS: A total of 76 patients diagnosed with MpBC over a 15-year period were included in the study. We performed immunohistochemical analyses for tumor cell PD-L1, immune cell PD-L1 and p53 on tissue microarrays (TMAs), analyzed stromal and intratumoral tumor infiltrating lymphocytes (TILs) from hematoxylin and eosin-stained (H&E) slides and scored gamma-H2AX (γH2AX) and phosphorylated-RPA2 (pRPA2) from whole tissue sections. We correlated marker expression with clinicopathologic features and clinical outcome. RESULTS: All tumors expressed γH2AX and pRPA2 with median expressions of 43% and 44%. P53- (68%), tumor cell PD-L1- (59%) and immune cell PD-L1-positivity (62%) were common in MpBCs. Median stromal TIL and intratumoral TIL counts were 5% and 0. The spindle and squamous cell carcinomas expressed the highest levels of PD-L1 and TILs, and carcinoma with mesenchymal differentiation the lowest. CONCLUSIONS: MpBC appears to be an immunogenic cancer with high genomic instability and frequent PD-L1-positivity, implying that check point inhibitors might be effective in MpBC. Expression levels of PD-L1 and TILs varied across different histologic subtypes, suggesting that immunotherapy might be less effective in carcinoma with mesenchymal differentiation.

Omega-6 polyunsaturated fatty acids, serum zinc, delta-5- and delta-6-desaturase activities and incident metabolic syndrome.

BACKGROUND: The associations of n-6 polyunsaturated fatty acids (PUFA) with metabolic syndrome have been poorly explored. We investigated the associations of the serum n-6 PUFA and the activities of enzymes involved in the PUFA metabolism, delta-5-desaturase (D5D) and delta-6-desaturase (D6D) with risk of incident metabolic syndrome. We also investigated whether zinc, a cofactor for these enzymes, modifies these associations. METHODS: A prospective follow-up study was conducted on 661 men who were aged 42-60 years old at baseline in 1984-1989 and who were re-examined in 1998-2001. RESULTS: Men in the highest versus the lowest serum total omega-6 PUFA tertile had a 70% lower multivariate-adjusted risk of incident metabolic syndrome [odds ratio (OR) = 0.30; 95% confidence interval (CI) = 0.18-0.51, Ptrend < 0.001]. Inverse associations were also observed for linoleic acid, arachidonic acid and D5D activity. By contrast, men in the highest tertile of D6D activity had an 84% higher risk (OR = 1.84; 95% CI = 1.15-2.94, Ptrend = 0.008). Similar associations were observed with many of the metabolic syndrome components at the re-examinations. Most associations were attenuated after adjustment for body mass index. Finally, the associations of D6D and LA were stronger among those with a higher serum zinc concentration. CONCLUSIONS: Higher serum total n-6 PUFA, linoleic acid and arachidonic acid concentrations and D5D activity were associated with a lower risk of developing metabolic syndrome and higher D6D activity was associated with a higher risk. The role of zinc also needs to be investigated in other populations.

How does lifestyle intervention affect depressive symptoms? Results from the Finnish Diabetes Prevention Study.

AIMS: To assess the effect of lifestyle intervention on depressive symptoms during a 36-month randomized clinical trial designed to prevent Type 2 diabetes. METHODS: A total of 522 middle-aged participants, who were overweight or obese and had impaired glucose tolerance, were randomized to the lifestyle intervention or control group in the Finnish Diabetes Prevention Study. The intervention group received individualized counselling aimed at reducing weight and increasing physical activity. Depressive symptoms were measured using the Beck Depression Inventory among a subgroup of 140 participants. RESULTS: On study entry, the mean Beck Depression Inventory scores ± sd were 6.8 ± 5.6 in the intervention group and 6.7 ± 5.5 in the control group. Beck Depression Inventory scores reduced during the intervention study: the mean ± sd (95% CI) reduction was 0.90 ± 4.54 (-1.99 to -0.19) scores in the intervention group and 0.75 ± 4.47 (-1.80 to 0.31) in the control group, with no difference between the groups. In a stepwise linear multivariate regression analysis, the variables with the strongest associations with the change in Beck Depression Inventory scores were baseline Beck Depression Inventory scores, marital status, weight change and change of total energy intake (R(2) = 0.209, P < 0.001). CONCLUSIONS: Participation in the study lowered depression scores, with no specific group effect. Among the lifestyle changes, particularly successful reduction of body weight was associated with the greater reduction of depressive symptoms. Thus, regardless of the intensity of the treatment, the success in executing alterations in one's lifestyle and behaviour is associated with beneficial changes in mood.

Glycemic index, glycemic load, and the risk of acute myocardial infarction in Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study.

BACKGROUND AND AIM: The role of dietary glycemic index (GI) and glycemic load (GL) in coronary heart disease (CHD) is unclear. Our aim was to study the association between the dietary GI and GL and the risk of acute myocardial infarction (AMI). METHODS AND RESULTS: The study population consisted of 1981 Finnish men from the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study, aged 42-60 years and free of CHD at baseline. During an average follow-up time of 16.1 years, 376 new AMI events occurred. In multivariable-adjusted Cox proportional hazards models, the relative risk (RR) for AMI in the highest quartile of GI was 1.25 (95% CI: 0.92-1.69; P for trend=0.08) and for GL 1.11 (95% CI: 0.79-1.57; P for trend=0.21) when compared with the lowest quartile. For overweight (BMI ≥ 27.5 kg/m²) men, the multivariable-adjusted RR for AMI in the highest compared to the lowest tertile of GI and GL were 1.58 (95% CI: 1.03-2.43; P for trend=0.04, P for interaction=0.01) and 2.05 (95% CI: 1.30-3.23; P for trend=0.002, P for interaction=0.002), respectively. For physically less active men; energy expenditure for leisure-time physical activity < 50 kcal/d, the RR for AMI was 1.72 (95% CI: 1.07-2.76; P for trend=0.04, P for interaction 0.80) with higher GL. CONCLUSIONS: Our results suggest that both high dietary GI and GL are associated with increased risk of AMI among overweight and GL possibly among less physically active men.

Serum Concentrations of 25-Hydroxyvitamin D and Depression in a General Middle-Aged to Elderly Population in Finland.

OBJECTIVES: Low concentrations of serum 25-hydroxyvitamin D [25(OH)D] have been postulated to associate with an increased prevalence of depression. As there are a limited number of publications on this issue, we examined the association between serum 25(OH)D and depression in a general middle-aged or older population. DESIGN: A population-based cross-sectional study. SETTING AND PARTICIPANTS: A total of 1602 men and women from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) in Eastern Finland, aged 53-73 y in 1998-2001, were analysed. MEASUREMENTS: Depressive symptoms were assessed with the DSM-III depression scale, and those individuals who had scores over 4 (range 0-12) or had reported undergoing current antidepressant therapy, were considered as suffering from depression. Associations were estimated in serum 25(OH)D tertiles using logistic regression. RESULTS: Among the participants, 183 subjects (11.4%) were considered to have depression. The mean age of the subjects was 62.6 years (SD 6.4, range 53.4-73.8 years). The mean serum 25(OH)D concentration was 43.8 nmol/L (SD 17.7, range 8.5-112.8 nmol/L), concentrations <50 nmol/L were observed in 65.0% of the subjects, and only 5.0% displayed concentrations ≥75 nmol/L. After multivariable adjustments, the odds ratios for having depression in the tertiles (from highest to the lowest) of serum 25(OH)D were 1, 1.35 (95 % CI: 0.87, 2.09) and 1.64 (95 % CI: 1.03, 2.59), P for trend=0.036. CONCLUSION: These findings indicate that a lower concentration of serum 25(OH)D is associated with a higher prevalence of depression in an elderly general population.

Association between serum long-chain omega-3 polyunsaturated fatty acids and cognitive performance in elderly men and women: The Kuopio Ischaemic Heart Disease Risk Factor Study.

BACKGROUND/OBJECTIVES: Fish intake and the long-chain omega-3 polyunsaturated fatty acids (PUFAs) in fish have been suggested to lower the risk of cognitive decline. We assessed whether serum long-chain omega-3 PUFAs eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) are associated with performance on neuropsychological tests in an older population and whether exposure to methylmercury, mainly from fish, or apolipoprotein-E4 (Apo-E4) phenotype can modify the associations. SUBJECTS/METHODS: A total of 768 participants from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study were included. Cognitive function was measured using five neuropsychological tests: the Trail Making Test, the Verbal Fluency Test, the Selective Reminding Test, the Visual Reproduction Test and the Mini Mental State Exam. Multivariate-adjusted analysis of covariance and linear regression were used to analyze the cross-sectional associations. RESULTS: We found statistically significant associations between serum EPA+DPA+DHA and better performance in the Trail Making Test and the Verbal Fluency Test. The individual associations with EPA and DHA were similar with the findings with EPA+DPA+DHA, although the associations with DHA were stronger. No associations were observed with serum DPA. Pubic hair mercury content was associated only with a worse performance in the Trail Making Test, and mercury had only little impact on the associations between the serum PUFAs and cognitive performance. Apo-E4 phenotype did not modify the associations with PUFAs or mercury. CONCLUSIONS: Higher serum long-chain omega-3 PUFA concentrations were associated with better performance on neuropsychological tests of frontal lobe functioning in older men and women. Mercury exposure or Apo-E4 phenotype had little impact on cognitive performance.

Fish oil-derived fatty acids, docosahexaenoic acid and docosapentaenoic acid, and the risk of acute coronary events: the Kuopio ischaemic heart disease risk factor study.

BACKGROUND: Previous findings concerning the serum levels of fish-derived (n-3) fatty acids and coronary heart disease are inconsistent. The purpose of this study was to investigate the association between the serum n-3 end-product fatty acids docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and eicosapentaenoic acid and the risk of acute coronary events in middle-aged men. METHODS AND RESULTS: We studied this association in the Kuopio Ischaemic Heart Disease Risk Factor Study, a prospective population study in Eastern Finland. Subjects were randomly selected and included 1871 men aged 42 to 60 years who had no clinical coronary heart disease at baseline examination. A total of 194 men had a fatal or nonfatal acute coronary event during follow-up. In a Cox proportional hazards' model adjusting for other risk factors, men in the highest fifth of the proportion of serum DHA+DPA in all fatty acids had a 44% reduced risk (P=0.014) of acute coronary events compared with men in the lowest fifth. Men in the highest fifth of DHA+DPA who had a low hair content of mercury (2.0 microgram/g). There was no association between proportion of eicosapentaenoic acid and the risk of acute coronary events. CONCLUSIONS: Our data provide further confirmation for the concept that fish oil-derived fatty acids reduce the risk of acute coronary events. However, a high mercury content in fish could attenuate this protective effect.

Low dietary folate intake is associated with an excess incidence of acute coronary events: The Kuopio Ischemic Heart Disease Risk Factor Study.

BACKGROUND: Although several prospective studies have shown that low folate intake and low circulating folate are associated with increased risk of coronary heart disease (CHD), the findings are inconsistent. METHODS AND RESULTS: We studied the associations of dietary intake of folate, vitamin B(6), and vitamin B(12) with the risk of acute coronary events in a prospective cohort study of 1980 Finnish men 42 to 60 years old examined in 1984 to 1989 in the Kuopio Ischemic Heart Disease Risk Factor Study. Nutrient intakes were assessed by 4-day food record. During an average follow-up time of 10 years, 199 acute coronary events occurred. In a Cox proportional hazards model adjusted for 21 conventional and nutritional CHD risk factors, men in the highest fifth of folate intake had a relative risk of acute coronary events of 0.45 (95% CI 0.25 to 0.81, P=0.008) compared with men in the lowest fifth. This association was stronger in nonsmokers and light alcohol users than in smokers and alcohol users. A high dietary intake of vitamin B(6) had no significant association and that of vitamin B(12) a weak association with a reduced risk of acute coronary events. CONCLUSIONS: The present work in CHD-free middle-aged men is the first prospective cohort study to observe a significant inverse association between quantitatively assessed moderate-to-high folate intakes and incidence of acute coronary events in men. Our findings provide further support in favor of a role of folate in the promotion of good cardiovascular health.

Low plasma lycopene concentration is associated with increased intima-media thickness of the carotid artery wall.

Although a number of epidemiological studies have evaluated the association between ss-carotene and the risk of cardiovascular diseases, there has been little research on the role of lycopene, an acyclic form of ss-carotene, with regard to the risk of cardiovascular disease. We investigated the relationship between plasma concentrations of lycopene and intima-media thickness of the common carotid artery wall (CCA-IMT) in 520 middle-aged men and women (aged 45 to 69 years) in eastern Finland. They were examined from 1994 to 1995 at the baseline of the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study, a randomized trial concerning the effect of vitamin E and C supplementation on atherosclerotic progression. The subjects were classified into 2 categories according to the median concentration of plasma lycopene (0.12 micromol/L in men and 0.15 micromol/L in women). Mean CCA-IMT of the right and left common carotid arteries was 1.18 mm in men and 0.95 mm in women with plasma lycopene levels lower than the median and 0.97 mm in men (P:<0.001 for difference) and 0.89 mm in women (P:=0.027 for difference) with higher levels of plasma lycopene. In ANCOVA adjusting for cardiovascular risk factors and intake of nutrients, in men, low levels of plasma lycopene were associated with a 17.8% increment in CCA-IMT (P:=0.003 for difference). In women, the difference did not remain significant after the adjustments. We conclude that low plasma lycopene concentrations are associated with early atherosclerosis, manifested as increased CCA-IMT, in middle-aged men living in eastern Finland.

Serum long-chain omega-3 polyunsaturated Fatty acids and future blood pressure in an ageing population.

OBJECTIVES: To investigate the associations of serum long-chain omega-3 polyunsaturated fatty acids (PUFA) and hair mercury with future blood pressure in an ageing population. DESIGN: Prospective study with baseline measurements in 1998-2001 and follow-up measurements in 2005-2008. The linear relationships (ß) of baseline serum fatty acids and hair mercury with future systolic and diastolic blood pressure and pulse pressure were analyzed with multiple linear regression models, using log-transformed values. PARTICIPANTS: 181 men and 200 women aged 53-73 y from the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD) population in Eastern Finland, who were free of cardiovascular disease, diabetes or hypertension at baseline. MEASUREMENTS: Total serum esterified and nonesterified fatty acids and pubic hair mercury were used as markers for exposure. Anthropometric and other lifestyle and health-related data were collected. RESULTS: The mean serum concentrations were 1.67% (SD 0.92) for eicosapentaenoic acid (EPA), 0.79% (SD 0.16) for docosapentaenoic acid (DPA) and 2.78 (SD 0.92) for docosahexaenoic acid (DHA), of all serum fatty acids. The mean hair mercury concentration was 1.5 µg/g (SD 1.6). We did not find statistically significant associations between the baseline serum long-chain omega-3 PUFA concentrations or hair mercury content and future blood pressure. Hair mercury did not modify the associations with the long-chain omega-3 PUFAs, either. CONCLUSIONS: Higher serum long-chain omega-3 PUFA concentration, a biomarker of fish or fish oil consumption, may not have an impact on future blood pressure in an ageing population.

Factors influencing Doppler indexes of left ventricular filling in healthy persons.

Ninety-three healthy persons aged 11 to 91 years were studied to assess the factors influencing Doppler indexes of left ventricular (LV) diastolic filling. The effects of physical activity, alcohol consumption and smoking were tested in addition to those of age, sex, heart rate, body mass index, blood pressure, left atrial diameter, and LV end-diastolic diameter, wall thickness, mass and fractional shortening. The data were fitted stepwise into multiple linear regression models both in the total population and in 3 groups aged less than 40, 40 to 60 and greater than 60 years. In the total population, age explained 45 to 68% of the variation in the peak early and late diastolic velocities, their ratio, deceleration of the early velocity, atrial filling fraction and peak filling rate normalized to mitral stroke volume. With advancing age--and with increases in either body mass index, heart rate, diastolic blood pressure or LV mass--the indexes of early filling decreased, whereas with regular modest use of alcohol or regular aerobic exercise they increased (p less than 0.05 for all). In the middle-aged subjects, gender explained 32 to 57% of the variation in the peak atrial velocity, early to atrial peak velocity ratio and atrial filling fraction; the peak velocity ratio measured 1.4 +/- 0.3 (mean +/- standard deviation) in men vs 1.0 +/- 0.2 in women (p less than 0.001). In conclusion, many constitutional and physiologic factors and even life-style can influence the Doppler indexes of LV filling. This demonstrates the exquisite sensitivity of the method but indicates also that individual measurements must be interpreted with caution.

Angiographic 5-year follow-up study of right gastroepiploic artery grafts.

BACKGROUND: The right gastroepiploic artery (RGEA) has been used from 1987 in coronary artery bypass grafting in several clinical studies. However, the published 1- to 5-year patency rates have been dependent on the selection of patients for angiography. METHODS: In our study, the RGEA was used from March 1987 to May 1990 for coronary artery bypass grafting in 31 consecutive patients, 25 male and 6 female. All but 1 patient had triple-vessel disease, and the mean number of distal anastomoses was 3.9 (range, 2 to 5). Internal thoracic artery grafts were used concomitantly in all patients. RESULTS: One early and two late deaths occurred. All but 1 of the 28 surviving patients underwent clinical and angiographic follow-up examinations 3 months and 5 years after the operation. The 5-year patency of RGEA grafts was 82.1%, with a 95% confidence interval of 63.1% to 93.9%. In 4 of the 5 nonvisualized cases, the recipient coronary artery showed proximal stenosis of up to 70%, allowing substantial competitive flow. The 5-year patency of the RGEA graft was near that of the left internal thoracic artery, at 90.3%, and the right internal thoracic artery, at 94.4%; and superior to the 66.7% patency of venous grafts. CONCLUSIONS: At 5-year follow-up, angiography of RGEA grafts showed good function and a smooth lumen, especially if the proximal stenosis was more than 70%.

Minimally invasive coronary artery bypass grafting using the right gastroepiploic artery.

BACKGROUND: Anastomosis of the left internal thoracic artery to the left anterior descending artery without sternotomy and without cardiopulmonary bypass is a standard approach in minimally invasive coronary artery bypass grafting. To expand the indications for minimally invasive coronary artery bypass grafting from one-vessel disease to two-vessel disease, we began to perform anastomosis of the right gastroepiploic artery (RGEA) to the right coronary artery (RCA). METHODS: From February to November 1996, an RGEA graft was used in 25 of the 100 patients who underwent minimally invasive coronary artery bypass grafting at our clinic. Eleven of the patients had only RCA disease and 14 had both RCA and left anterior descending artery disease. One of the operations was a redo coronary artery bypass grafting. The RGEA was anastomosed to the RCA through a laparotomy incision and the left internal thoracic artery was anastomosed to the left anterior descending artery through a left anterior thoracotomy. In 5 patients, the RGEA was lengthened by venous grafting. RESULTS: All patients underwent angiography after operation; 82.6% of the RGEA grafts and all the left internal thoracic artery grafts were functioning well. In three of the four nonvisualized RGEA grafts, the percentage of proximal stenosis of the RCA seen on postoperative angiography was not critical (40%, 50%, and 50%, respectively), allowing significant competitive flow through the native bypassed RCA. The patency of all the RGEA grafts without competitive flow was 95%, with a 95% confidence interval of 75.1% to 99.9%. CONCLUSIONS: The indications for minimally invasive coronary artery bypass grafting could be extended to primary operations in patients with left anterior descending artery and RCA lesions by using both the left internal thoracic artery and the RGEA.

Circadian variation of left ventricular diastolic function in healthy people.

AIM: To assess whether left ventricular function shows circadian variation in healthy people. SUBJECTS AND METHODS: 10 healthy men (7) and women (3) aged 35-50 underwent M mode echocardiography of the left ventricle and Doppler velocimetry of transmitral flow at 4 h intervals over 24 h. The participants were in hospital over the study period and their diet, meal times, and sleeping hours were standardised as far as possible. MEASUREMENTS: Heart rate, blood pressure, left ventricular and atrial diameters, fractional shortening, peak early and late transmitral velocities, time from the second heart sound to the early diastolic velocity peak (relaxation time), isovolumic relaxation period, acceleration and deceleration of the early transmitral flow, atrial filling fraction. RESULTS: A circadian rhythm was observed in heart rate and blood pressure, but neither the left ventricular diameters and systolic function nor the left atrial size showed statistically significant diurnal trends. The relaxation time (mean (SD)) measured 144 (16) ms at 2 pm, 144 (21) ms at 6 pm, 149 (22) ms at 10 pm, 168 (23) ms at 2 am, 174 (28) ms at 6 am, and 151 (21) ms at 10 am (P = 0.009). Diurnal rhythms were seen also in the isovolumic relaxation period (P = 0.003) and in the acceleration of the early diastolic transmitral flow (P = 0.037); the lowest and highest values of flow acceleration were observed during the nocturnal and daytime hours, respectively. CONCLUSIONS: The Doppler indices of left ventricular filling in healthy people show diurnal changes suggestive of a circadian rhythm in the rate of left ventricular relaxation. The most likely underlying mechanism is the day-night cycle in sympathoadrenal activity.

Low serum folate concentrations are associated with an excess incidence of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Study.

OBJECTIVE: To test the hypothesis that low serum folate concentrations are associated with an increased risk of acute coronary events in men free of prior coronary heart disease. SETTING: Research Institute of Public Health, University of Kuopio, Kuopio, Finland. DESIGN: Prospective study in a cohort of 734 men aged 46-64 y examined in 1991-1993 as part of the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) and followed for 5 y and 3 months. INTERVENTION: Acute coronary events during the follow-up period were obtained by national hospital discharge registry. Baseline serum folate concentrations were measured by radioimmunoassay. RESULTS: During the follow-up, six (2.5%) men with higher serum folate concentrations (highest third>11.3 nmol/1) and 28 (5.7%) men with lower serum folate (two lowest thirds) developed an acute coronary event (P=0.008). In a Cox model adjusting for age, examination years, and plasma lycopene concentration, in men with higher serum folate concentrations the relative risk for an acute coronary event was 0.31 (95% CI 0.11-0.90, P=0.031) when compared with men with lower serum folates. CONCLUSION: This prospective cohort study in middle-aged men from eastern Finland indicates that moderate-to-high levels of serum folate are associated with a greatly reduced incidence of acute coronary events.

Phloem fortification in rye bread elevates serum enterolactone level.

OBJECTIVE: To analyse the lignan content of phloem powder enriched rye bread and to study the dose-response relationship of the effect of dietary plant lignans derived from phloem on intestinal production of enterolactone by measuring enterolactone concentration in serum. DESIGN: A randomized double-blind supplementation trial. SUBJECTS: Seventy-five non-smoking men recruited by newspaper advertisements. INTERVENTION: Subjects were randomized to three study groups receiving either rye bread high in phloem (HP, 14% of rye flour substituted with phloem powder), rye bread low in phloem (LP, 7% of rye flour substituted with phloem powder) or placebo rye bread. Participants consumed 70 g of study bread daily for 4 weeks and provided serum samples for enterolactone analysis at baseline and at the end of the intervention. RESULTS: There was a significant increase in serum enterolactone concentration in the LP and HP groups compared with the placebo group (P=0.009 and P=0.003, respectively). Considerable interindividual differences were observed in the response to dietary lignans within the study groups. CONCLUSIONS: Our results indicate that plant lignans attached to insoluble fibre layer in phloem can be further metabolized and converted to enterolactone presumably by the bacteria present in the colon. Phloem powder is useful source of lignans for functional foods aimed to elevate serum enterolactone levels. SPONSORSHIP: Phloem powder and the study breads were provided by Finnpettu Oy and Linkosuo Oy, respectively. The clinical study work was sponsored in part by Oy Jurilab Ltd.