Daniel D. Gallaher

Effects of lyophilized black raspberries on azoxymethane-induced colon cancer and 8-hydroxy-2'-deoxyguanosine levels in the Fischer 344 rat

This study examined the effects of lyophilized black raspberries (BRB) on azoxymethane (AOM)-induced aberrant crypt foci (ACF), colon tumors, and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels in male Fischer 344 rats. AOM was injected (15 mg/kg body wt ip) once per week for 2 wk. At 24 h after the final injection, AOM-treated rats began consuming diets containing 0%, 2.5%, 5%, or 10% (wt/wt) BRB. Vehicle controls received 5% BRB or diet only. Rats were sacrificed after 9 and 33 wk of BRB feeding for ACF enumeration and tumor analysis. ACF multiplicity decreased 36%, 24%, and 21% (P < 0.01 for all groups) in the 2.5%, 5%, and 10% BRB groups, respectively, relative to the AOM-only group. Total tumor multiplicity declined 42%, 45%, and 71% (P < 0.05 for all groups). Although not significant, a decrease in tumor burden (28%, 42%, and 75%) was observed in all BRB groups. Adenocarcinoma multiplicity decreased 28%, 35%, and 80% (P < 0.01) in the same treatment groups. Urinary 8-OHdG levels were reduced by 73%, 81%, and 83% (P < 0.01 for all groups). These results indicate that BRB inhibit several measures of AOM-induced colon carcinogenesis and modulate an important marker of oxidative stress in the Fischer 344 rat.

Effects of dietary inulin on serum lipids, blood glucose and the gastrointestinal environment in hypercholesterolemic men

Abstract Inulin is a complex carbohydrate that belongs to a class of compounds known as fructans. Inulin has been consumed in plant sources by mankind for centuries, and is most concentrated in chicory, Jerusalem artichoke, garlic, leek and onion. It can be extracted from purified concentrated sources such as chicory root, and used to enhance the technological and nutritional properties of foods. Inulin is thought to share many of the properties of soluble dietary fibers, such as the ability to lower blood lipids and stabilize blood glucose. Additionally, inulin has been shown to enhance the growth of bifidobacteria and lactobacilli and enhance the gut environment. The objective of this study was to examine the effect of a commercially available inulin from chicory root (degree of polymerization (DP) ranging between 2 and 60, modal DP=9) in men with hypercholesterolemia on serum parameters and fecal composition. The study was a randomized, double blind, crossover design with no washout period. Twelve men were randomly assigned to two controlled diets that differed only in that the control diet contained one pint of vanilla ice cream made with sucrose while the inulin containing diet was supplemented with one pint of vanilla ice cream made with 20 grams of inulin. Subjects consumed each controlled diet for three weeks. Daily intake of 20 g of inulin significantly reduced serum triglycerides by 40 mg/dL (p=0.05). A trend toward a reduction in serum cholesterol was observed. Trends toward short chain fatty acid (SCFA) profile changes were observed after inulin administration. Transit time did not differ significantly between treatments. These data suggest that dietary inulin supplementation may improve blood lipid profiles and alters the colonic environment in a manner that may be beneficial. Because inulin is easily incorporated into an acceptable food like low-fat vanilla ice cream, it shows promise as a functional ingredient in many processed foods.

A glucomannan and chitosan fiber supplement decreases plasma cholesterol and increases cholesterol excretion in overweight normocholesterolemic humans

Objective: Both chitosan and glucomannan have demonstrated hypocholesterolemic effects. A recent study in rats indicates that the combination of the two is also a potent hypocholesterolemic agent that increases fecal fat excretion. The objective of the present study was to determine the hypocholesterolemic effect of a supplement containing equal amounts of chitosan and glucomannan on blood lipid concentrations and fecal excretion of fat, neutral sterols and bile acids. Methods: Twenty-one overweight normocholesterolemic subjects (11 males and 10 females) were fed 2.4 g/day of a supplement containing equal amounts of chitosan and glucomannan. Prior to taking the supplement (initial period) and after 28 days (final period), blood was drawn for measurement of serum lipids and a three-day fecal sample collected for determination of fat, neutral sterol and bile acid excretion. Subjects maintained their normal dietary and activity patterns during the study. Results: Caloric intake and intake of fat and dietary fiber (excluding the supplement) did not differ between the initial and final periods. Serum total, HDL and LDL cholesterol concentrations were significantly lower (p < 0.05) in the final period compared to the initial period. Serum triacylglycerol concentration did not change between periods. There was a trend towards greater fecal excretion of neutral sterols and bile acids (p = 0.13 and 0.16, respectively) in the final period. However, fecal fat excretion did not differ between periods. Conclusions: Serum cholesterol reduction by a chitosan/glucomannan supplement is likely mediated by increased fecal steroid excretion and is not linked to fat excretion.

The effect of synbiotics on colon carcinogenesis in rats.

Evidence indicates that consumption of probiotic microorganisms such as bifidobacteria reduces the risk of colon cancer in animal models. Feeding certain fructans such as oligofructose and inulin, which are thought to selectively increase the growth of intestinal bifidobacteria (i.e., a prebiotic effect), also has been shown to reduce colon cancer risk. The objective of our study was twofold, i. e., to determine whether the combination of bifidobacteria and oligofructose would have an additive effect (i.e., synbiotic) in reducing colon cancer risk in rats, and to determine whether other oligosaccharides would also be effective as part of a synbiotic combination. The development of colonic preneoplastic lesions (aberrant crypts) was used as an index of colon cancer risk. In one series of experiments, rats were given the carcinogen 1, 2-dimethylhydrazine (DMH) and administered one of the following treatments: skim milk (control), bifidobacteria (bifido), oligofructose (OF) or bifido + OF. Neither bifido nor OF alone significantly reduced aberrant crypt number. Bifido + OF reduced aberrant crypt number in five of six experiments, although the reduction was significant in only one. However, a paired comparison of the six experiments indicated a significant overall reduction in aberrant crypts by bifido + OF (P = 0.039). Soybean oligosaccharide (SBO) and wheat bran oligosaccharide (WBO) were also fed in combination with bifidobacteria. In two other experiments, SBO did not alter the number of aberrant crypts compared with the control, whereas WBO reduced aberrant crypt number in one experiment but not in another. Of OF, SBO and WBO, only SBO reduced the colonic mucosa proliferation compared with the control. These results suggest that the combination of bifidobacteria and oligofructose reduces colon cancer risk in carcinogen-treated rats, but the effect of other oligosaccharides is uncertain.

Nutritional and Metabolic Response to Plant Inhibitors of Digestive Enzymes

Men’s food source derives predominantly from plants, from which only a relatively small proportion can be utilized nutritionally. Of these plants, many must be treated or processed in some way to improve the digestibility or remove naturally occurring toxicants. Considerable effort has been put forth in elucidating these factors in food that may constitute a hazard to man or his domesticated animals when consumed. One group of compounds that has received much attention are the digestive enzyme inhibitors. The distribution of these inhibitors among plants is widespread, and includes most agronomic crops (Liener and Kakade, 1980). The inhibitor is most often found within the edible portion. By far the most prominent of these enzyme inhibitors are the inhibitors of the proteolytic enzymes, particularly trypsin and chymotrypsin. Examples of amylase inhibitors are few, but potentially important. Although no inhibitors of pancreatic lipase have been definitely established, a compound to be discussed may fit this role. Finally, there are certain substances that inhibit all the digestive enzymes in a relatively nonspecific manner. Most notable among these are the tannins (Griffith and Mosley, 1980). The discussion to follow will consider only the more specific types of inhibitors.

Diabetes increases excretion of urinary malonaldehyde conjugates in rats

The effect of streptozotocin-induced diabetes on the urinary excretion of thiobarbituric acid test-positive materials was examined. In diabetic rats, urinary excretion of thiobarbituric acid reactive substances was increased 5-fold over that in nondiabetic animals. High-performance liquid chromatography of urine samples revealed that five of the six fractions previously found to be increased in vitamin E deficiency [Lee, H.-S., Shoeman, D.W., and Csallany, A.S. (1992)Lipids 27, 124–128] were also significantly increased in streptozotocin-induced diabetes. The data suggest that a high level of oxidative stress is induced by uncontrolled diabetes in rats.

Influence of whole grain barley, whole grain wheat, and refined rice-based foods on short-term satiety and energy intake

This study compared the effect of whole grain high-fiber barley, whole grain wheat and refined rice-based foods on energy intake and satiety. Forty-seven healthy subjects consumed a breakfast of hot cereal and a snack mix containing either barley, wheat, or refined rice, followed by an ad libitum smorgasbord lunch using a crossover design. Energy intake was measured at the lunch using plate waste. Hunger, fullness, desire to eat, amount of food consumed, and thirst were assessed using a modified Visual Analog Scale (VAS) before and after the breakfast, snack and lunch. Energy intake at lunch did not differ among products. There were no differences in the area under the time curve in modified VAS scores among products for any parameter. However, subjects reported significantly less hunger before lunch compared to their hunger before breakfast when consuming the barley, but there was no significant reduction in hunger before lunch after consumption of wheat or rice. In conclusion, intake of a whole grain high-fiber barley, whole grain wheat, or refined rice breakfast and snack did not decrease energy intake acutely, but consumption of whole grain high-fiber barley foods significantly decreased hunger whereas whole wheat and refined rice foods did not.

Lipophilic aldehydes and related carbonyl compounds in rat and human urine

Rat and human urine samples were analyzed for lipophilic aldehydes and other carbonyl products of lipid peroxidation. The following compounds were identified as their 2,4-dinitrophenyl hydrazones by cochromatography with pure standards using three solvent systems: butanal, butan-2-one, pentan-2-one, hex-2-enal, hexanal, hepta-2,4-dienal, hept-2-enal, octanal, non-2-enal, deca-2,4-dienal, 4-hydroxyhex-2-enal, and 4-hydroxynon-2-enal. In general, fasted rats excreted less of these compounds than fed rats, indicating they were partially of dietary origin or that the endogenous compounds were excreted in a form not susceptible to hydrazone formation. The compounds excreted in human urine were similar to those excreted in rat urine but were present in lower concentrations. Identification of the conjugated forms fo the lipophilic aldehydes and related carbonyl compounds excreted in urine may be a source of information about their reactions in vivo.

Vitamin E and probucol reduce urinary lipophilic aldehydes and renal enlargement in streptozotocin-induced diabetic rats.

Diabetes mellitus is characterized by complications affecting several organs, including the kidney. Lipid peroxidation increases in diabetes and has been implicated in the pathogenesis of diabetic complications. In this study, we examined the ability of two antioxidants, vitamin E and probucol, to reduce lipid peroxidation in vivo and renal hypertrophy, an early stage of diabetic nephropathy, in rats. Animals were divided into four groups: non-diabetic, diabetic, diabetic treated with vitamin E, and diabetic treated with probucol. Animals were given antioxidants by intraperitoneal injection after induction of diabetes by streptozotocin injection. After 7 wk, lipid peroxidation in vivo was measured by analyzing urinary excretion of lipophilic aldehydes and related carbonyl compounds (LACC) as 2,4-dinitrophenylhydrazones by high-performance liquid chromatography. A number of urinary lipophilic nonpolar and polar aldehydes and related carbonyl compounds were identified, almost all of which increased in diabetes. Antioxidant treatment resulted in significantly decreased excretion of urinary LACC excretion. Antioxidant treatment of diabetic rats reduced renal hypertrophy. There was a high correlation between kidney weight and urinary LACC. Since LACC are accepted markers of lipid peroxidation, these results indicate that antioxidants can reduce the elevated lipid peroxidation of diabetes and may slow the onset of diabetic nephropathy.

Effect of soluble and insoluble fiber on energy digestibility, nitrogen retention, and fiber digestibility of diets fed to gestating sows

Twenty-four sows (12 nulliparous, 12 multiparous) were used to determine soluble fiber (SF) and insoluble fiber (ISF) effects on energy digestibility, N balance, and SF and ISF digestibility. Experimental diets included a corn-soybean meal control (C; 1.20% SF, 9.78% ISF), a 34% oat bran diet high in SF (HS; 3.02% SF, 10.11% ISF), a 12% wheat straw diet high in ISF (HIS; 1.11% SF, 17.86% ISF), and a 16% sugar beet pulp diet (HS + HIS; 2.32% SF, 16.08% ISF). Sows were assigned randomly to diets within parity group and individually fed to meet their energy requirements according to the NRC model assuming 10 pigs per litter and 40 kg of gestation gain. Total feces and urine were collected in 5-d periods at wk 5, 10, and 14 of gestation. There were no interactions between dietary treatments and parity group for any of the response criteria evaluated. Dietary energy digestibility was greatest (P < 0.01) for females fed C (87.9%) and HS (89.3%) diets compared with females fed diets high in ISF (HIS, 82.9; HS + HIS, 86.8%). Energy digestibility was not affected by stage of gestation. Dietary N digestibility was similar between C and HS (86.1 and 86.2%) but greater (P < 0.01) than HIS and HS + HIS (82.8 and 82.8%, respectively). Nitrogen digestibility declined (P < 0.05) as gestation progressed for sows fed HS only. Nitrogen retention as a percentage of N intake was not affected by diet (C, 51.8; HS, 44.0; HIS, 42.0; HS + HIS, 48.6). Soluble fiber digestibility was different (P < 0.01) among experimental diets (C, 85.8; HS, 89.5; HIS, 77.7; HS + HIS, 80.3%). Sows fed HS + HIS (61.8%) and HS (58.4%) had greater (P < 0.05) ISF digestibility than sows fed C (53.5%), whereas sows fed HIS (38.3%) had lower (P < 0.01) ISF digestibility than sows fed the other experimental diets. Greater digestibility of dietary energy (87.1 vs. 86.2%; P < 0.05), N (85.7 vs. 83.2%; P < 0.01), and ISF (54.5 vs. 51.2%; P < 0.06) was observed in multiparous vs. nulliparous sows. In conclusion, increased intake of ISF decreased energy digestibility, whereas increasing SF intake improved energy digestibility. Diet had no effect on N retention. Insoluble fiber digestibility improved when SF intake increased, suggesting that knowledge of specific dietary fiber components is necessary to accurately predict effects of dietary fiber on digestibility. Multiparous sows demonstrated a greater ability to digest fibrous diets than nulliparous sows.