Jie-Xian Zhang

Rye Bran and Soy Protein Delay Growth and Increase Apoptosis of Human LNCaP Prostate Adenocarcinoma in Nude Mice

In this study, we investigated whether dietary intervention could inhibit tumor growth of an androgen‐sensitive human prostatic cancer.

Inhibitory effects of soy and rye diets on the development of Dunning R3327 prostate adenocarcinoma in rats

Dunning R3327 PAP prostate tumors were transplanted in 125 rats, the rats were divided into five groups, and tumor development was examined for 24 weeks during treatment with diets containing 33% of soy flour (SD), rye bran (RB), heat‐treated rye bran (HRB), or rye endosperm (RE).

Soy and rye diets inhibit the development of Dunning R3327 prostatic adenocarcinoma in rats

Two experiments were conducted to investigate the effect of soy and rye on the development of Dunning R3327 prostatic adenocarcinoma in rats.

Randomised controlled short-term intervention pilot study on rye bran bread in prostate cancer.

The short-term effects of rye bran bread intake in prostate cancer were investigated. Ten men with conservatively treated prostate cancer were randomised to a daily supplement of 295 g of rye bran bread and eight men to 275 g of wheat bread (control) with similar fibre content for three weeks. Blood samples, ultrasound-guided core biopsies of the prostate, and urine samples were taken. In the rye group, there was a significant increase in plasma enterolactone, and the apoptotic index increased significantly from 2.1% (SD 1.3) to 5.9% (SD 1.8), P<0.005 as measured by a TUNEL index in four cases in the rye group and seven cases in the control group. Besides a significant decrease in weight in both groups, only small changes were observed in plasma concentrations of prostate specific antigen (PSA), circulating sex hormones, excreted oestrogens, insulin-like growth factor (IGF)-I, and in the endothelial fibrinolytical system. High intake of rye bran bread is suggested to increase apoptosis in prostate tumours.

Rye Whole Grain and Bran Intake Compared with Refined Wheat Decreases Urinary C-Peptide, Plasma Insulin, and Prostate Specific Antigen in Men with Prostate Cancer

Rye whole grain and bran intake has shown beneficial effects on prostate cancer progression in animal models, including lower tumor take rates, smaller tumor volumes, and reduced prostate specific antigen (PSA) concentrations. A human pilot study showed increased apoptosis after consumption of rye bran bread. In this study, we investigated the effect of high intake of rye whole grain and bran on prostate cancer progression as assessed by PSA concentration in men diagnosed with prostate cancer. Seventeen participants were provided with 485 g rye whole grain and bran products (RP) or refined wheat products with added cellulose (WP), corresponding to ~50% of daily energy intake, in a randomized controlled, crossover design. Blood samples were taken from fasting men before and after 2, 4, and 6 wk of treatment and 24-h urine samples were collected before the first intervention period and after treatment. Plasma total PSA concentrations were lower after treatment with RP compared with WP, with a mean treatment effect of -14% (P = 0.04). Additionally, fasting plasma insulin and 24-h urinary C-peptide excretion were lower after treatment with RP compared with WP (P < 0.01 and P = 0.01, respectively). Daily excretion of 5 lignans was higher after the RP treatment than after the WP treatment (P < 0.001). We conclude that whole grain and bran from rye resulted in significantly lower plasma PSA compared with a cellulose-supplemented refined wheat diet in patients with prostate cancer. The effect may be related to inhibition of prostate cancer progression caused by decreased exposure to insulin, as indicated by plasma insulin and urinary C-peptide excretion.

Nuclear Magnetic Resonance–Based Metabolomics Enable Detection of the Effects of a Whole Grain Rye and Rye Bran Diet on the Metabolic Profile of Plasma in Prostate Cancer Patients

Prostate cancer (PC) is the most common cancer in the Western world and the second most important cancer causing male deaths, after lung cancer, in the United States and Britain. Lifestyle and dietary changes are recommended for men diagnosed with early-stage PC. It has been shown that a diet rich in whole grain (WG) rye reduces the progression of early-stage PC, but the underlying mechanism is not clear. This study sought to identify changes in the metabolic signature of plasma in patients with early-stage PC following intervention with a diet rich in WG rye and rye bran product (RP) compared with refined white wheat product (WP) as a tool for mechanistic investigation of the beneficial health effects of RP on PC progression. Seventeen PC patients received 485 g RP or WP in a randomized, controlled, crossover design during a period of 6 wk with a 2-wk washout period. At the end of each intervention period, plasma was collected after fasting and used for (1)H NMR-based metabolomics. Multilevel partial least squares discriminant analysis was used for paired comparisons of multivariate data. A metabolomics analysis of plasma showed an increase in 5 metabolites, including 3-hydroxybutyric acid, acetone, betaine, N,N-dimethylglycine, and dimethyl sulfone, after RP. To understand these metabolic changes, fasting plasma homocysteine, leptin, adiponectin, and glucagon were measured separately. The plasma homocysteine concentration was lower (P = 0.017) and that of leptin tended to be lower (P = 0.07) after RP intake compared to WP intake. The increase in plasma 3-hydroxybutyric acid and acetone after RP suggests a shift in energy metabolism from anabolic to catabolic status, which could explain some of the beneficial health effects of WG rye, i.e., reduction in prostate-specific antigen and reduced 24-h insulin secretion. In addition, the increase in betaine and N,N-dimethylglycine and the decrease in homocysteine show a favorable shift in homocysteine metabolism after RP intake.

Anticancer effects of a plant lignan 7-hydroxymatairesinol on a prostate cancer model in vivo

Clinical intervention studies and experimental studies with lignan-rich diets suggest that lignans may have inhibitory effects on prostate cancer, but no clinical or experimental studies with purified lignans have been published. The purpose of this study was to investigate the effect of a plant lignan 7-hydroxymatairesinol (HMR) on LNCaP human prostate cancer xenografts in athymic mice. Athymic nude male mice were injected subcutaneously with LNCaP cells. Starting 3 days after tumor cell injections, a control diet or a control diet supplemented with 0.15% or 0.30% of HMR was administered to mice and the tumor take rate and growth was observed for 9 weeks. HMR diet inhibited the growth of LNCaP tumors. Mice treated with HMR had smaller tumor volume, lower tumor take rate, increased proportion of nongrowing tumors, and higher tumor cell apoptotic index compared with controls. Furthermore, the cell proliferation index was reduced in mice receiving the 0.30% HMR diet compared with mice receiving the control diet. Our results suggest that dietary HMR started at the early phase of the tumor development inhibits the growth of the LNCaP human prostate cancer xenografts in athymic male mice.

Rye, lignans and human health

Rye bran contains a high content not only of dietary fibre, but also of plant lignans and other bioactive compounds in the so-called dietary fibre complex. Blood concentrations of lignans such as enterolactone have been used as biomarkers of intake of lignan-rich plant food. At present,evidence from studies in human subjects does not warrant the conclusion that rye, whole grains orphyto-oestrogens protect against cancer. Some studies, however, have pointed in that direction,especially in relation to cancers of the upper digestive tract. A number of prospective epidemiological studies have clearly shown a protective effect of wholegrain cereals against myocardial infarctions. A corresponding protective effect against diabetes and ischaemic stroke(brain infarct) has also been demonstrated. It seems reasonable to assume that these protective effects are associated with one or more factors in the dietary fibre complex.

Effects of meal frequency and high-fibre rye-bread diet on glucose and lipid metabolism and ileal excretion of energy and sterols in ileostomy subjects.

Objective: To investigate the effect of a rye, high-fibre diet (HFD) vs a wheat, low-fibre diet (LFD), meal frequency, nibbling (Nib, seven times a day) or ordinary (Ord, three times a day), and their combined effects on blood glucose, insulin, lipids, urinary C-peptide and ileal excretion of energy, cholesterol and bile acids in humans.Design: LFD period with Nib or Ord meal frequency followed by an HFD diet with Nib or Ord meal frequency in randomized, crossover design.Setting: Outpatients of ileostomy volunteers were called for an investigation in research word.Subjects: A total of 10 subjects (two female subjects, age 34 and 51 y; eight males, mean age 54.4 y, range 43–65 y) participated in the experiment. All subjects were proctocolectomized for ulcerative colitis (mean 16.0 y, range 8–29 y before the study).Intervention: In total, 10 ileostomy subjects started with LFD for 2 weeks, the first week on either Nib (five subjects) or Ord (five subjects) and the second week on the other meal frequencies, in a crossover design, followed by a wash-out week, and continued with HFD period for 2 weeks in the same meal frequency manner. All foods consumed in both Nib or Ord regimens were identical and a high-fibre rye bread was used in the HFD period and a low-fibre wheat bread in the LFD period.Main outcome measures: Day-profiles of blood glucose, insulin and lipids, blood lipids before and after dietary intervention, and excretion of steroids in the effluents and C-peptide in the urine.Results: During the Nib regimen, plasma glucose and insulin peaks were lower at the end of the day with HFD compared with LFD. Urinary C-peptide excretion was significantly higher in the day-time on LFD compared with HFD (LFD-Ord vs HFD-Ord, P<0.01; LFD-Nib vs HFD-Nib, P<0.01). Plasma free-cholesterol, total cholesterol, triglycerides and phospholipids were significantly higher (P<0.05) after LFD than after HFD with the Nib regimen. A higher excretion of energy (P<0.05) and chenodeoxycholic acid (P<0.05) were observed with HFD compared with LFD regardless of meal frequency. A higher daily excretion of cholic acid, total bile acids, cholesterol, net cholesterol and net sterols (P<0.05) was observed on HFD compared with LFD with the Nib regimen.Conclusions: An HFD decreased insulin secretion measured as a decreased excretion of C-peptide in urine and as decreased plasma insulin peaks at the end of the day during a Nib regimen. The smoother glycaemic responses at the end of the day during a Nib regimen may be a consequence of a second meal phenomenon, possibly related to the nature of dietary fibre complex.Sponsorship: This study was supported by grants from the Swedish Council of Forestry and Agricultural Research (SJFR).

Reproducibility of Plasma Alkylresorcinols during a 6-Week Rye Intervention Study in Men with Prostate Cancer

Alkylresorcinols (AR), phenolic lipids exclusively present in the outer parts of wheat and rye grains, have been proposed as concentration biomarkers of whole-grain wheat and rye intake. A key feature of a good biomarker is high reproducibility, which indicates how accurately a single sample reflects the true mean biomarker concentration caused by a certain intake. In this study, the short- to medium-term reproducibility of plasma AR was determined using samples from a crossover intervention study, where men with prostate cancer (n = 17) were fed rye whole-grain/bran or refined wheat products for 6-wk periods. AR homologs C17:0 and C21:0 differed between the treatments (P < 0.001). The reproducibility determined by the intraclass correlation coefficient (ICC) was high (intervention period 1: ICC = 0.90 [95% CI = 0.82-0.98], intervention period 2: ICC = 0.88 [95% CI = 0.78-0.98]). The results show that a single fasting plasma sample could be used to estimate the mean plasma AR concentration during a 6-wk intervention period with constant intake at a precision of +/- 20% (80% CI). This suggests that the plasma AR concentration can be used as a reliable short- to medium-term biomarker for whole-grain wheat and rye under intervention conditions where intake is kept constant.