FUNCTIONAL INGREDIENTS

Carnitine Research Update
Placebo-controlled double-blind randomized trial on the use of L-carnitine, L-acetylcarnitine, or combined L-carnitine and L-acetylcarnitine in men with idiopathic asthenozoospermia.
SOURCE: Fertility & Sterility 2005 Sep;84(3):662-71.

Comparison of the effects of L-carnitine and acetyl-L-carnitine on carnitine levels, ambulatory activity, and oxidative stress biomarkers in the brain of old rats.
Ann N Y Acad Sci. 2004 Nov;1033:117-31.

L-carnitine inhibits hepatocarcinogenesis via protection of mitochondria.
Int J Cancer. 2004 Oct 21

Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood, and fatigue associated with male aging.
Urology. 2004 Apr;63(4):641-6.

The effect of l-carnitine on fat oxidation, protein turnover, and body composition in slightly overweight subjects.
Metabolism. 2004 Aug;53(8):1002-6.

Exploratory open label, randomized study of acetyl- and propionyl-carnitine in chronic fatigue syndrome.
Psychosom Med. 2004 Mar-Apr;66(2):276-82.

Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood, and fatigue associated with male aging.
Cavallini G, Caracciolo S, Vitali G et al. Urology. 2004;63:641-6.

L carnitine administration in elderly subjects with rapid muscle fatigue: effect on body composition, lipid profile and fatigue.
Drugs Aging. 2003;20(10):761-7.

The effects of L-carnitine L-tartrate supplementation on hormonal responses to resistance exercise and recovery.
Kraemer WJ. University of Connecticut, Storrs, CT 06269, USA.
J Strength Cond Res. 2003 Aug;17(3):455-62.

Antioxidant activity of mildronate and L-carnitine in the treatment of patients with cerebrovascular diseases
Klin Farmakol. 2003 May-Jun;66(3):32-5.

Caffeine, carnitine and choline supplementation of rats decreases body fat and serum leptin concentration as does exercise.
J Nutr 2000 Feb;130(2):152-7

Free and total carnitine concentrations in pig plasma after oral ingestion of various L carnitine compounds.
Int J Vitamin Nutrition Research. 2005 Jan;75(1):3-9.

Acetyl-L-Carnitine. Alternative Medecine Review 1999;4:438-440

Chuang WW, Lin WW, Lamb DJ, and Lipshultz LI. Effect of acetylcarnitine on sperm motility. J Urol. 2000; 163(4).

Lolic MM and Fiskum G. Neuroprotective effects of acetyl-L-carnitine after stroke in rats. Annot Emergency Medicine. 1997; 29:758-765.

Pettegrew JW, Klunke WE, Panchalingam K. Clinical and biochemical effects of acetyl-L-carnitine in Alzheimer's disease. Neurobiolical Aging. 1995; 16:1-4.

Sano M, Bell K, Cote L, et al. Double-blind parallel pilot study of acetyl levocarnitine in patients with Alzheimer's disease. Arch Neurol. 1992; 49:1137-1141.

Effects of docosahexaenoic acid supplementation on blood lipids, estrogen metabolism, and in vivo oxidative stress in postmenopausal vegetarian women.
Eur J Clin Nutr. 2005 Nov 9
Vegetarians are generally deficient in long-chain n-3 fatty acids. Long-chain n-3 fatty acids have a beneficial effect on plasma lipid levels, and some studies showed that they had breast cancer suppression effect. To investigate the effect of docosahexaenoic acid (DHA, 22:6n-3) supplementation on blood lipids, estrogen metabolism and oxidative stress in vegetarians. Design: Single-blind, randomized, placebo-controlled trial. Twenty-seven postmenopausal vegetarian women were recruited. After a 2-week run-in period with 6 g placebo corn oil, the subjects were subsequently randomized to receive either 6 g corn oil (n=13) or 6 g DHA-rich algae oil (2.14 g of DHA /day) (n=14) for 6 weeks. Two subjects in corn oil group withdrew before completion. Conclusion: DHA supplementation at a dose of 2.14 g/day for 42 days decreases plasma cholesterol but neither does it show beneficial effects on estrogen metabolism, nor does it induce deleterious effects on the observed in vivo antioxidant or oxidative stress marker in postmenopausal vegetarian women.

Consuming a diet rich in the omega-3 fatty acid docosahexanoic acid (DHA) may help prevent or treat Alzheimer's disease. In the study, which is reported in The Journal of Neuroscience, mice that ate DHA-enriched chow showed less beta-amyloid build-up in the brain than mice fed regular chow. Beta-amyloid is a protein that forms the characteristic brain plaques seen in patients with Alzheimer's disease." These results suggest that dietary DHA could be protective against beta-amyloid production, accumulation, and potential downstream toxicity," senior author Dr. Greg M. Cole, from the University of California at Los Angeles, and colleagues note. Research has linked high levels of DHA in the diet with a reduced risk of Alzheimer's disease. Still, the studies have shown an association, but don't prove that eating a diet high in DHA actually reduces amyloid levels and prevents Alzheimer's disease. To show this, animal studies are often needed. Cole's team used a mouse model of Alzheimer's disease and fed the animals low- or high-DHA chow or regular chow. The animals were fed the assigned diet until 22.5 months of age, at which point brain tissue was obtained and tested for amyloid build-up. The high-DHA diet reduced total amyloid level by 70 percent compared with the other diets, the investigators report. Moreover, brain plaques were reduced by 40.3 percent.

Docosahexaenoic acid concentrations are higher in women than in men because of estrogenic effects1,2,3
American Journal of Clinical Nutrition, Vol. 80, No. 5, 1167-1174, November 2004
During pregnancy there is a high demand for docosahexaenoic acid ( DHA ), which is needed for formation of the fetal brain. Women who do not consume marine foods must synthesize DHA from fatty acid precursors in vegetable foods. We studied sex differences in DHA status and the role of sex hormones. First, DHA status was compared between 72 male and 103 female healthy volunteers who ate the same rigidly controlled diets. Second, the effects of sex hormones were studied in 56 male-to-female transsexual subjects, who were treated with cyproterone acetate alone or randomly assigned to receive oral ethinyl estradiol or transdermal 17ß-estradiol combined with cyproterone acetate, and in 61 female-to-male transsexual subjects, who were treated with testosterone esters or randomly assigned for treatment with the aromatase inhibitor anastrozole or placebo in addition to the testosterone regimen. Results: The proportion of DHA was 15 ± 4% ( ± SEM) higher in the women than in the men. Among the women, those taking oral contraceptives had 10 ± 4% higher DHA concentrations than did those not taking oral contraceptives. Administration of oral ethinyl estradiol, but not transdermal 17ß-estradiol, increased DHA by 42, whereas the antiandrogen cyproterone acetate did not affect DHA. Parenteral testosterone decreased DHA by 22 in female-to-male transsexual subjects. Anastrozole decreased estradiol concentrations significantly and DHA concentrations nonsignificantly. Conclusion: Estrogens cause higher DHA concentrations in women than in men, probably by upregulating synthesis of DHA from vegetable precursors.

Omega-3 fatty acids from fish oils and cardiovascular disease.
Mol Cell Biochem. 2004 Aug;263(1-2):217-25.
Fish and fish oils contain the omega-3 fatty acids known as eicosapentaenoic acid (EPA) plus docosahexaenoic acid ( DHA ). Epidemiological studies have shown an inverse relation between the dietary consumption of fish containing EPA / DHA and mortality from coronary heart disease. These relationships have been substantiated from blood measures of omega-3 fatty acids including DHA as a physiological biomarker for omega-3 fatty acid status. Controlled intervention trials with fish oil supplements enriched in EPA / DHA have shown their potential to reduce mortality in post-myocardial infarction patients with a substantial reduction in the risk of sudden cardiac death. The cardioprotective effects of EPA / DHA are widespread, appear to act independently of blood cholesterol reduction, and are mediated by diverse mechanisms. Their overall effects include anti-arrhythmic, blood triglyceride-lowering, anti-thrombotic, anti-inflammatory, endothelial relaxation, plus others. Current dietary intakes of EPA / DHA from fish oils in North America and elsewhere are well below those recommended by the American Heart Association for the management of patients with coronary heart disease.

Docosahexaenoic acid promotes neurite growth in hippocampal neurons.
J Neurochem. 2004 Aug;90(4):979-88.
Docosahexanoic acid (22:6n-3; DHA) deficiency during development is associated with impairment in learning and memory, suggesting an important role of DHA in neuronal development. Here we provide evidence that DHA promotes neuronal differentiation in rat embryonic hippocampal primary cultures. DHA deficiency in vitro was spontaneously induced by culturing hippocampal cells in chemically defined medium. DHA supplementation improved DHA levels to values observed in freshly isolated hippocampus. We found that DHA supplementation in culture increased the population of neurons with longer neurite length per neuron and with higher number of branches. However, supplementation with arachidonic, oleic or docosapentaenoic acid did not have any effect, indicating specificity of the DHA action on neurite growth. Furthermore, hippocampal cultures obtained from n-3 fatty acid deficient animals contained a lower DHA level and a neuronal population with shorter neurite length per neuron in comparison to those obtained from animals with adequate n-3 fatty acids. DHA supplementation to the deficient group recovered the neurite length to the level similar to n-3 fatty acid adequate cultures. Our data demonstrates that DHA uniquely promotes neurite growth in hippocampal neurons. Inadequate neurite development due to DHA deficiency may contribute to the cognitive impairment associated with n-3 fatty acid deficiency.

Effect of fish and fish oil-derived omega-3 fatty acids on lipid oxidation.
Redox Rep. 2004;9(4):193-7.
There is evidence that omega-3 (omega3) fatty acids derived from fish and fish oils reduce the risk of cardiovascular disease via mechanisms underlying atherosclerosis, thrombosis and inflammation. Despite these benefits, there has been concern that these fatty acids may increase lipid peroxidation. However, the in vivo data to date are inconclusive, due in part to limitations in the methodologies. In this regard, our findings using the measurement of F(2)-isoprostanes, a reliable measure of in vivo lipid peroxidation and oxidant stress, do not support adverse effects of omega3 fatty acids on lipid peroxidation.

Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model.
Neuron. 2004 Sep 2;43(5):633-45.
Learning and memory depend on dendritic spine actin assembly and docosahexaenoic acid (DHA), an essential n-3 (omega-3) polyunsaturated fatty acid (PFA). High DHA consumption is associated with reduced Alzheimer's disease risk, yet mechanisms and therapeutic potential remain elusive. Here, we report that reduction of dietary n-3 PFA in an Alzheimer's disease mouse model resulted in 80%-90% losses of the p85alpha subunit of phosphatidylinositol 3-kinase and the postsynaptic actin-regulating protein drebrin, as in Alzheimer's disease brain. The loss of postsynaptic proteins was associated with increased oxidation, without concomitant neuron or presynaptic protein loss. n-3 PFA depletion increased caspase-cleaved actin, which was localized in dendrites ultrastructurally. Treatment of n-3 PFA-restricted mice with DHA protected against these effects and behavioral deficits and increased antiapoptotic BAD phosphorylation. Since n-3 PFAs are essential for p85-mediated CNS insulin signaling and selective protection of postsynaptic proteins, these findings have implications for neurodegenerative diseases where synaptic loss is critical, especially Alzheimer's disease.

Maturation of visual acuity is accelerated in breast-fed term infants fed baby food containing DHA-enriched egg yolk.
 J Nutr. 2004 Sep;134(9):2307-13.
Between 6 and 12 mo of age, blood levels of the (n-3) long-chain PUFA, docosahexaenoic acid (DHA), in breast-fed infants typically decrease due to diminished maternal DHA stores and the introduction of DHA-poor solid foods displacing human milk as the primary source of nutrition. Thus, we utilized a randomized, clinical trial format to evaluate the effect of supplemental DHA in solid foods on visual development of breast-fed infants with the primary outcome, sweep visual-evoked potential (VEP) acuity, as an index for maturation of the retina and visual cortex. At 6 mo of age, breast-fed infants were randomly assigned to receive 1 jar (113 g)/d of baby food containing egg yolk enriched with DHA (115 mg DHA/100 g food; n = 25) or control baby food (0 mg DHA; n = 26). Gravimetric measures were used to estimate the supplemental DHA intake which was 83 mg DHA/d in the supplemented group and 0 mg/d in controls. Although many infants in both groups continued to breast-feed for a mean of 9 mo, RBC DHA levels decreased significantly between 6 and 12 mo (from 3.8 to 3.0 g/100 g total fatty acids) in control infants, whereas RBC DHA levels increased by 34% from 4.1 to 5.5 g/100 g by 12 mo in supplemented infants. VEP acuity at 6 mo was 0.49 logMAR (minimum angle of resolution) and improved to 0.29 logMAR by 12 mo in controls. In DHA-supplemented infants, VEP acuity was 0.48 logMAR at 6 mo and matured to 0.14 logMAR at 12 mo (1.5 lines on the eye chart better than controls). At 12 mo, the difference corresponded to 1.5 lines on the eye chart. RBC DHA levels and VEP acuity at 12 mo were correlated, supporting the need of an adequate dietary supply of DHA throughout 1 y of life for neural development.

The fatty acids found in fish may slightly lower a man's risk of prostate cancer, but another type of fatty acid found in a range of foods may raise the risk, a large study suggests. Researchers found that among nearly 48,000 U.S. men followed for 14 years, those with the highest intakes of two fatty acids found in oily fish were 26 percent less likely than men with the lowest intakes to develop advanced prostate cancer. The opposite was true, however, when it came to alpha-linolenic acid, or ALA. Like the two fish-oil fats, ALA is an omega-3 unsaturated fatty acid that is thought to promote heart health; it is found in vegetable sources such as soybeans, canola oil, walnuts and flaxseed, and to a lesser extent in meat and dairy products. In this study, men with the highest intake of ALA were about twice as likely as those with the lowest intakes to develop advanced prostate cancer. And the risk was increased regardless of whether the ALA came from vegetable or animal sources, according to findings published in the American Journal of Clinical Nutrition.

The July/August 2004 edition of the journal Child Development reports a study found that infants whose mothers' had higher blood levels of docosahexaenoic acid (DHA) at birth showed more mature forms of attention during their first two years of development. These findings add to the evidence that DHA is an important factor in early development and that women who are pregnant, or intend to become pregnant, should consider supplementing their diets with DHA or fish oils. DHA supports an infant's brain and eye development. Reported studies have consistently shown that women's diets in the U.S. have one of the lowest levels of DHA in the world. Clinical studies have demonstrated that women who supplement their diets with DHA during pregnancy experience elevated DHA levels in their blood.

People who ate an average of 180 mg or more a day of DHA had about 40% less Alzheimer's disease and other dementia, compared with people who consumed less DHA, according to epidemiologic data collected in the Framingham Heart Study.

Fish oil interaction with warfarin.
Buckley MS, Goff AD,Shawnee Mission, KS of Arizona, Tucson, AZ 85724
Ann Pharmacother. 2004 Jan;38(1):50-2.
OBJECTIVE: To report a case of elevated international normalized ratio (INR) in a patient taking fish oil and warfarin. CASE SUMMARY: A 67-year-old white woman had been taking warfarin for 1(1/2) years due to recurrent transient ischemic attacks. Her medical history included hypothyroidism, hyperlipidemia, osteopenia, hypertension, and coronary artery disease. She also experienced an inferior myocardial infarction in 1995 requiring angioplasty, surgical repair of her femoral artery in 1995, and hernia repair in 1996. This patient has her INR checked in the anticoagulation clinic and is followed monthly by the clinical pharmacist. Prior to the interaction, her INR was therapeutic for 5 months while she was taking warfarin 1.5 mg/d. The patient admitted to doubling her fish oil dose from 1000 to 2000 mg/d. Without dietary, lifestyle, or medication changes, the INR increased from 2.8 to 4.3 within 1 month. The INR decreased to 1.6 one week after subsequent fish oil reduction, necessitating a return to the original warfarin dosing regimen. DISCUSSION: Fish oil supplementation could have provided additional anticoagulation with warfarin therapy. Fish oil, an omega-3 polyunsaturated fatty acid, consists of eicosapentaenoic acid and docosahexaenoic acid. This fatty acid may affect platelet aggregation and/or vitamin K-dependent coagulation factors. Omega-3 fatty acids may lower thromboxane A(2) supplies within the platelet as well as decrease factor VII levels. Although controversial, this case report illustrates that fish oil can provide additive anticoagulant effects when given with warfarin. CONCLUSIONS: This case reveals a significant rise in INR after the dose of concomitant fish oil was doubled. Patients undergoing anticoagulation therapy with warfarin should be educated about and monitored for possible drug-herb interactions. Pharmacists can play a crucial role in identifying possible drug interactions by asking patients taking warfarin about herbal and other alternative medicine product use.

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Review: Prebiotic effects of inulin and oligofructose, by Kolida, S., Tuohy, K. and Gibson, G. R. (Food Microbial Sciences Unit, School of Food Biosciences, The University of Reading, Whiteknights, UK.. afr99sk@reading.ac.uk). (BRITISH JOURNAL OF NUTRITION, 87 (2002) (Suppl 2): S193-S197).

Review: The bifidogenic nature of chicory inulin and its hydrolysis products, by Roberfroid, M. B.; Van, Loo. J. A.; Gibson, G. R. (Unite de Biochimie Toxicologique et Cancerologique, Department of Pharmaceutical Sciences, Universite Catholique de Louvain, B1200 Brussels, Belgium.). JOURNAL OF NUTRITION, 128 (1998) (1) 11-19.

Study: Effect of soluble or partly soluble dietary fibres supplementation on absorption and balance of calcium, magnesium, iron and zinc in healthy young men, by Coudray, C.; Bellanger, J.; Castiglia-Delavaud, C.; Remesy, C.; Vermorel, M.; Rayssignuier, Y. (Center de Recherche, en Nutrition Humaine, d'Auvergne, Unite des Maladies Métaboliques et Micronutriments, INRA de Thiex/Clermont-Ferrand, Saint Gen`es Champanelle, France. ). EUROPEAN JOURNAL OF CLINICAL NUTRITION, 51 (1997) (6) 375-380.

Study: Five-Week intake of short-chain fructo-oligosaccharides increases intestinal absorption and status of magnesium in postmenopausal women, by Tahiri, M.; Tressol, J. C.; Arnaud, J.; Bornet, F.; Bouteloup-Demange, C.; Feillet-Coudray, C.; Ducros, V.; Pepin, D.; Brouns, F.; Rayssignuier, A. M.; Coudray, C. (Unite Maladies Métaboliques et Micro-nutriments, Centre de Recherche INRA Clermont-Ferrand/Theix, Saint Genes Champanelle, France. ). JOURNAL OF BONE AND MINERAL RESEARCH, 16 (2001) (11) 2152-2160.

Study: Oligofructose stimulates calcium absorption in adolescents, by van, den. Heuvel. E. G.; Muys, T.; van, Dokkum. W.; Schaafsma, G. (TNO Nutrition and Food Research Institute, Department of Physiology, Zeist, Netherlands.. vandenheuvel@Voeding.TNO.NL). AMERICAN JOURNAL OF CLINICAL NUTRITION, 69 (1999) (3) 544-548.

Study: Non-digestible oligosaccharides and calcium absorption in girls with adequate calcium intakes, by Griffin, I. J.; Davila, P. M.; Abrams, S. A. (USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, 1100 Bates Street, Houston, TX 77030, USA.). British Journal of Nutrition, 87 (2002) (Suppl. 2) S187-S191.

Study: Effects of inulin-type fructans of different chain length and type of branching on intestinal absorption and balance of calcium and magnesium in rats, by Coudray, Charles.; Tressol, Jean. Claude.; Gueux, Elyett.; Rayssiguier, Yves. (Centre de Recherche en Nutrition Humaine d"Auvergne, Unite Maladies Metaboliques et Micronutriments, Centre de Recherche INRA, Clermont-Ferrand/Theix, 63122 Saint Genes Champanelle, France. coudray@clermont.inra.fr). EUROPEAN JOURNAL OF NUTRITION, 42 (2003) (2) 91-98.

Review: Caloric value of inulin and oligofructose by Roberfroid, M. (1999). Journal of Nutrition. 129: 1436S-1437S

Study: Digestion, excretion, and energy value of fructooligosaccharides in healthy humans, by Molis, C., Flourie, B., Ouarne, F., Gailing, M. F., Lartigue, S., Guibert, A., Bornet, F. and Galmiche, J. P. (1996). American Journal of Clinical Nutrition. 64: 324-328.

Study: Usable energy value of selected bulking agents, by Ranhotra, G. S., Gelroth, J. A. and Glaser, B. K. (1993), Journal of Food Science 58: 1176-1178.

Review1: Prebiotics and lipid metabolism, by Delzenne, N.M. & Williams, C.M. (2002). Curr. Opinion Lipidol. 13: 61-67 ¬

Study2: Role of non-digestible carbohydrates in colon cancer protection, by Niba, L.L. and Niba, S.N. (2003). Nutr. Food Science. 33:28-33.

Study3: Human studies with probiotics and prebiotics: clinical implications, by Saavedra, J. M. and Tschernia, A. (2002). British Journal of Nutrition. 87:S241-S246)

Anaphylactic Reaction to Inulin: First Identification of Specific IgEs to an Inulin Protein Compound.
Int Arch Allergy Immunol. 2005 Jan 12;136(2):155-158
Background: A woman with a past history of allergy to artichoke presented with two episodes of immediate allergic reactions, one of which was a severe anaphylactic shock after eating two types of health foods containing inulin. Results: Dot blot assay techniques identified specific IgEs to artichoke, to yoghurt F, and to a heated BSA + inulin product. Dot blot inhibition techniques confirmed the anti-inulin specificity of specific IgE. Conclusions: The absence of a positive reaction to an unheated milk-inulin mixture indicates the probability of protein-inulin binding. There is no cross-reactivity with the carbohydrates of the glycosylated allergens.

Addition of inulin fiber to a moderately high-carbohydrate diet reduces hepatic lipogenesis and plasma triacylglycerol concentrations in humans.
Am J Clin Nutr. 2003 Mar;77(3):559-64.
A high-carbohydrate, low-fat diet is recommended for the prevention of atherosclerosis, because it reduces plasma cholesterol concentrations. However, such a diet can increase plasma triacylglycerol concentrations--an undesirable side effect. The addition of nondigestible carbohydrate could reduce the risk of elevated triacylglycerol concentrations. OBJECTIVE: The objective was to determine whether the addition of a moderate dose of inulin to a moderately high-carbohydrate diet would decrease hepatic lipogenesis and plasma triacylglycerol concentrations and have a cholesterol-lowering action. DESIGN: Eight healthy subjects were studied twice in a double-blind, randomized, placebo-controlled crossover study after consuming for 3 wk a moderately high-carbohydrate, low-fat diet (55% of total energy) plus an oral placebo or 10 g high-performance inulin/d. Hepatic lipogenesis and cholesterol synthesis (deuterated water method), plasma lipid concentrations, fatty acid synthase, acetyl-CoA carboxylase 1, and sterol responsive element binding protein 1c messenger RNA concentrations were measured in adipose tissue at the end of the 2 diet periods. RESULTS: Plasma triacylglycerol concentrations and hepatic lipogenesis were lower after inulin than after placebo ingestion, but cholesterol synthesis and plasma cholesterol concentrations were not significantly different between the 2 groups. None of the adipose tissue messenger RNA concentrations changed significantly after inulin ingestion. CONCLUSIONS: The addition of high-performance inulin to a moderately high-carbohydrate, low-fat diet has a beneficial effect on plasma lipids by decreasing hepatic lipogenesis and plasma triacylglycerol concentrations. These results support the use of nondigestible carbohydrate for reducing risk factors for atherosclerosis.

Effect of dietary inulin supplementation on inflammation of pouch mucosa in patients with an ileal pouch-anal anastomosis.
Dis Colon Rectum. 2002 May;45(5):621-7.
Inflammation is a constant finding in the ileal reservoir of patients with an ileal pouch-anal anastomosis and is associated with decreased fecal concentrations of the short chain fatty acid butyrate, increased fecal pH, changes in fecal flora, and increased concentrations of secondary bile acids. In healthy subjects, inulin, a dietary fiber, is fermented to short chain fatty acids and leads to a lower pH and potentially beneficial changes in fecal flora. The aim of the present study was to investigate the effect of enteral supplementation of inulin on inflammation of the ileal reservoir. METHODS: Twenty patients received 24 g of inulin or placebo daily during three weeks in a randomized, double-blind, crossover design. Stools were analyzed after each test period for pH, short chain fatty acids, microflora, and bile acids. Inflammation was assessed endoscopically, histologically, and clinically. RESULTS: Compared with placebo, three weeks of dietary supplementation with 24 g of inulin increased butyrate concentrations, lowered pH, decreased numbers of Bacteroides fragilis, and diminished concentrations of secondary bile acids in feces. This was endoscopically and histologically accompanied by a reduction of inflammation of the mucosa of the ileal reservoir. CONCLUSION: Enteral inulin supplementation leads to a decrease of inflammation-associated factors and to a reduction of inflammation of pouch mucosa.

Applications of inulin and oligofructose in health and nutrition.
J Biosci. 2002 Dec;27(7):703-14.
Inulin and oligofructose belong to a class of carbohydrates known as fructans. The main sources of inulin and oligofructose that are used in the food industry are chicory and Jerusalem artichoke. Inulin and oligofructose are considered as functional food ingredients since they affect the physiological and biochemical processes in rats and human beings, resulting in better health and reduction in the risk of many diseases. Experimental studies have shown their use as bifidogenic agents, stimulating the immune system of the body, decreasing the pathogenic bacteria in the intestine, relieving constipation, decreasing the risk of osteoporosis by increasing mineral absorption, especially of calcium, reducing the risk of atherosclerosis by lowering the synthesis of triglycerides and fatty acids in the liver and decreasing their level in serum. These fructans modulate the hormonal level of insulin and glucagon, thereby regulating carbohydrate and lipid metabolism by lowering the blood glucose levels; they are also effective in lowering the blood urea and uric acid levels, thereby maintaining the nitrogen balance. Inulin and oligofructose also reduce the incidence of colon cancer. The biochemical basis of these beneficial effects of inulin and oligofructose have been discussed. Oligofructose are non cariogenic as they are not used by Streptococcus mutans to form acids and insoluble glucans that are the main culprits in dental caries. Because of the large number of health promoting functions of inulin and oligofructose, these have wide applications in various types of foods like confectionery, fruit preparations, milk desserts, yogurt and fresh cheese, baked goods, chocolate, ice cream and sauces. Inulin can also be used for the preparation of fructose syrups.

Effects of inulin on faecal bifidobacteria in human subjects.
Br J Nutr. 1999 Nov;82(5):375-82.
A controlled study with eight healthy free-living subjects was carried out, in which energy intake was adjusted to the individual energy requirements. On administration of inulin, blood lipids, the faecal microflora, short-chain fatty acids and accompanying gastrointestinal symptoms were characterized in order to investigate the long-term effect of inulin. During the run-in phase (8 d), subjects received a typical Western diet providing 45% energy as fat and 40% energy as carbohydrate. Subsequently, the subjects consumed a fat-reduced diet which provided 30% energy as fat and 55% energy as carbohydrate for a period of 64 d using inulin as a fat replacer. The amounts of inulin consumed by the subjects (up to 34 g/d) were based on individual energy requirements with the aim to keep the diet isoenergetic with that used in the run-in period. To assess the effects of inulin administration, a control study (run-in and intervention) was carried out in which subjects consumed the same diet but devoid of inulin during the whole course of the study. To investigate the effect of inulin on faecal flora composition total bacteria and bifidobacteria in the faeces were enumerated by in situ hybridization with 16S rRNA targeted oligonucleotide probes. Inulin significantly increased bifidobacteria from 9.8 to 11.0 log10/g dry faeces and caused a moderate increase in gastrointestinal symptoms such as flatulence and bloatedness, whereas blood lipids and short-chain fatty acids remained essentially unaffected.

Prebiotic carbohydrates modify the mucosa associated microflora of the human large bowel.
Gut. 2004 Nov;53(11):1610-6.
The mucosa associated flora of the large intestine is important in determining mucosal function although what controls its composition is unknown. This study has determined the effect of the prebiotic carbohydrates oligofructose and inulin on the mucosal flora. METHODS: An in vitro chemostat model of both planktonic and surface associated bacteria was used followed by an intervention study in 29 subjects undergoing colonoscopy. SUBJECTS: Fourteen subjects, recruited from colonoscopy waiting lists, supplemented their diet for two weeks with a mix of 7.5 g of oligofructose and 7.5 g inulin. Fifteen subjects were recruited at the time of colonoscopy and given no supplement. Multiple endoscopic biopsies were taken from the caecum, transverse and descending colon, and rectum. The mucosal flora was characterised by culture and to species level by cellular fatty acid profiles. Cell proliferation was assessed by immunohistochemical staining for minichromosome maintenance protein 2, Ki67, and proliferating cell nuclear antigen. RESULTS: In vitro prebiotics increased surface counts of bifidobacteria from 6.6 to 7.3 log(10) colony forming units (CFU) per slide with no significant changes in planktonic bacteria. In the feeding study, prebiotics increased mucosal bifidobacteria (log CFU/g mucosa (SEM)) in both the proximal (control 5.3 (0.4) v prebiotic 6.3 (0.3)) and distal (control 5.2 (0.3) v prebiotic 6.4 (0.3)) colon. Lactobacilli were also increased in the proximal and in the distal colon. There were significantly more eubacteria in fed subjects but no changes in total anaerobes clostridia, bacteroides, or coliforms, nor in proliferation indices. CONCLUSION: Prebiotic carbohydrates can change the composition of the mucosa associated flora significantly.

Symbiotic containing Bifidobacterium animalis and inulin increases stool frequency in elderly healthy people.
Asia Pac J Clin Nutr. 2004;13(Suppl):S112.
Background: the aim of the study was to investigate the effect of a symbiotic on gut microbiota and bowel habits. Methods: a double-blind, placebo-controlled, randomized crossover study was conducted in healthy elderly people (n= 49; mean age 70 +/- 4 years) over a total of sixteen weeks divided into periods of 4 weeks each, (1) run-in, (2) first intervention, (3) wash-out, and (4) second intervention. During the intervention periods study participants consumed daily sachets either containing the symbiotic or a placebo. The symbiotic contained bifidobacterium animalis and inulin. During the whole study subjects regularly completed questionnaires on bowel habits, well-being, gastrointestinal quality of life and underwent a medical examination. At the end of each intervention period the volunteers reported their dietary intake using a 4-day food record and provided a fresh faecal sample for the analysis of microbial and other parameters. Results: the habitual dietary intake remained constant over the entire period of investigation. The consumption of the symbiotic resulted in a significant increase of stool frequency compared to the placebo period (8.8 vs. 8.1 stools per week; p < 0.05). Among other gastrointestinal symptoms, e.g. Bloating, flatulence, no differences between the treatment and placebo periods could be found. For several parameters of well-being a significant positive influence of the symbiotic treatment could be demonstrated. The characterization of the microbial composition using fluorescence in-situ hybridization and enzymatic analyses are in progress. Conclusion: the administration of a symbiotic consisting of bifidobacterium animalis and inulin improves well-being and gastrointestinal quality of life in elderly subjects.

The effect of the daily intake of inulin on fasting lipid, insulin and glucose concentrations in middle-aged men and women.
Br J Nutr. 1999 Jul;82(1):23-30.
The present study was carried out to examine the effect of the daily intake of 10 g inulin on fasting blood lipid, glucose and insulin levels in healthy middle-aged men and women with moderately raised total plasma cholesterol (TC) and triacylglycerol (TAG) levels. This study was a double-blind randomized placebo-controlled parallel study in which fifty-four middle-aged subjects received either inulin or placebo for a period of 8 weeks. Fasting blood samples were collected before the supplementation period (baseline samples 1 and 2, separated by 1 week) and at weeks 4 and 8, with a follow-up at week 12. Compared with baseline values, insulin concentrations were significantly lower at 4 weeks (P < 0.01) in the inulin group. There was a trend for TAG values, compared with baseline, to be lower in the inulin group at 8 weeks (P < 0.08) returning to baseline concentrations at week 12. On comparison of the inulin and placebo groups, the fasting TAG responses over the 8-week test period were shown to be significantly different (P < 0.05, repeated measures ANOVA), which was largely due to lower plasma TAG levels in the inulin group at week 8. The percentage change in TAG levels in the inulin group during the 8-week study was shown to correlate with the initial TAG level of the subjects. We therefore conclude that the daily addition of 10 g inulin to the diet significantly reduced fasting insulin concentrations during the 8-week test period and resulted in lower plasma TAG levels, particularly in subjects in whom fasting TAG levels were greater than 1.5 mmol/l. These data support findings from animal studies that fructans influence the formation and/or degradation of TAG-rich lipoprotein particles, and the insulin data are also consistent with recent studies showing attenuation of insulin levels in fructan-treated rats.

Author(s): Scavariello EMS ; Arellano DB
Title: Gamma-Oryzanol: an important component in rice bran oil
Source: ARCHIVOS LATINOAMERICANOS DE NUTRICION 1998, Vol 48, Iss 1, pp 7-12
Language: Spanish
Abstract: gamma-Oryzanol, a mixture of ferulic acid esters of sterol and triterpene alcohols, it occurs in rice bran oil at a level of to 2%,where it serves as natural antioxidant. Recent research has shown that gamma-Oryzanol can lower the cholesterol levels in the blood, lowering the risk of coronary heart disease, besides that also has been used in Japan like natural antioxidant in foods, beverages and cosmetics. This review refers to aspects about gamma-Oryzanol, like its physiochemical properties, its presence in the rice bran oil, its antioxidant and hypocholesterolemic activity, as well as, identification, quantitation and extraction methods.

Author(s): Rong N; Ausman LM; Nicolosi RJ
Title: Oryzanol decreases cholesterol absorption and aortic fatty streaks in hamsters
Source: LIPIDS 1997, Vol 32, Iss 3, pp 303-309
Language: English
Abstract: Oryzanol is a class of nonsaponifiable lipids of rice bran oil (RBO). More specifically, oryzanol is a group of ferulic acid esters of triterpene alcohol and plant sterols. In experiment 1, the mechanisms of the cholesterol-lowering action of oryzanol were investigated in 32 hamsters made hypercholesterolemic by feeding chow based diets containing 5% coconut oil and 0.1% cholesterol with or without 1% oryzanol for 7 wk. Relative to the control animals, oryzanol treatment resulted in a significant reduction in plasma total cholesterol (TC) (28%, P < 0.01) and the sum of IDL-C, LDL-C, and VLDL-C (NON-HDL-C) (34%, P < 0.01). In addition, the oryzanol-treated animals also exhibited a 25% reduction in percent cholesterol absorption vs. control animals. Endogenous cholesterol synthesis, as measured by the liver and intestinal HMG-CoA reductase activities, showed no difference between the two groups. To determine whether a lower dose of oryzanol was also efficacious and to measure aortic fatty streaks, 19 hamsters in experiment 2 were divided into two groups and fed for 10 wk chow-based diets containing 0.05% cholesterol and10% coconut oil (w/w) (control) and the control diet plus 0.5% oryzanol (oryzanol). Relative to the control, oryzanol-treated hamsters had reduced plasma TC (44%, P < 0.001), NON-HDL-C (57%, P < 0.01), and triglyceride (TG) (46%, P < 0.05) concentrations. Despite a 12% decrease in high density lipoprotein cholesterol (HDL-C) (P < 0.01), the oryzanol-treated animals maintained a more optimum NON-HDL-C/HDL-C profile (1.1 +/-0.4) than the control (2.5 +/- 1.4; P < 0.0075). Aortic fatty streak formation, so defined by the degree of accumulation of Oil Red O-stained macrophage-derived foam cells, was reduced 67% (P < 0.01) in the oryzanol-treated animals. From these studies, it is concluded that a constituent of the nonsaponifiable lipids of RBO, oryzanol, is at least partially responsible for the cholesterol-lowering action of RBO. In addition, the cholesterol-lowering action of oryzanol was associated with significant reductions in aortic fatty streak formation.

Author(s): Sugano M; Tsuji E
Title: Rice bran oil and cholesterol metabolism
Source: JOURNAL OF NUTRITION 1997, Vol 127, Iss 3, p S521-S524
Language: English
Abstract: A range of human and animal studies have shown that rice bran oil (RBO) is an edible oil of preference for improving serum cholesterol levels and lipoprotein profiles with similarity to the more commonly used vegetable oils such as com oil and safflower oil. Of particular interest is the observation that blending RBO with safflower oil at a definite proportion (7:3, wt/wt) magnifies the hypo-cholesterolemic efficacy, compared with the effect of each oil alone. Although the mechanism underlying this effect is not apparent at present, the blending may have a practical significance. The blending effect was reproduced in rats fed a cholesterol-enriched diet, and there was also a decrease in liver cholesterol. The occurrence of peculiar components such as gamma-oryzanol and tocotrienols could be responsible for the hypocholesterolemic effect of RBO.

Author(s): Kahlon TS; Chow FI; Chiu MM; Hudson CA ; Sayre RN
Title: Cholesterol-lowering by rice bran and rice bran oil unsaponifiable matter in hamsters
Source: CEREAL CHEMISTRY 1996, Vol 73, Iss 1, pp 69-74
Language: English
Abstract: Unsaponfiable matter (U) was prepared from both raw and extrusion stabilized (130 degrees C) rice bran and tested for cholesterol-lowering activity in hamsters by addition to diets containing cellulose, raw rice bran, or stabilized rice bran at either the level found in the rice bran diet (0.4%,1X) or twice that level (2X). All diets contained 0.3% cholesterol,10% total dietary fiber,10.1% fat, and 3% N (same plant-to-animal N ratio). After 21 days, plasma cholesterol was significantly reduced by rice bran diets containing added U compared to the cellulose control diet, while the high density lipoprotein cholesterol -to-low density lipoprotein cholesterol ratio remained unchanged in all treatment groups. Liver cholesterol was significantly reduced by all rice bran-containing diets and with cellulose diets containing 2X added U when compared to the control diet. Rice bran diets plus added U resulted in cholesterol values lower than cellulose diets containing the same level of U. Stabilization of rice bran did not appear to affect the plasma and liver cholesterol responses to the unsaponifiable matter prepared from the extracted oil. There appears to be a dose response to rice bran unsaponifiable matter in plasma and liver cholesterol reductions. After 2 weeks, fecal fat and neutral sterol excretion were significantly greater with all treatment diets compared to the control diet. Fecal fat was negatively correlated with liver as well as plasma cholesterol (r = -0.97, P less than or equal to 0.0001 and -0.91, P less than or equal to 0.0006, respectively). Under the conditions of this study, cholesterol-lowering activity of rice bran is present in its unsaponifiable matter in addition to other components. Increased fecal excretion of fat and neutral sterols appears to be a possible mechanism for cholesterol-lowering by rice bran.

Author(s): Huang D, Ou B, Hampsch-Woodill M, Flanagan JA, Deemer EK.
Title: Development and validation of oxygen radical absorbance capacity assay for lipophilic antioxidants using randomly methylated beta-cyclodextrin as the solubility enhancer.
Source: Journal Agricultural and Chemistry, 2002, 50 (7), pp. 1815-1821
Language: English
Abstract: Brunswick Laboratories, 6 Thacher Lane, Wareham , Massachusetts 02571 , USA . We recently reported the improved oxygen radical absorbance capacity (ORAC) assay using fluorescein (FL) as the fluorescent probe. The current ORAC(FL) assay is limited in hydrophilic antioxidant due to the aqueous environment of the assay. Lipophilic antioxidants mainly include the vitamin E family and carotenoids, which play a critical role in biological defense systems. In this paper, we expanded the current ORAC(FL) assay to lipophilic antioxidants. Randomly methylated beta-cyclodextrin (RMCD) was introduced as the water solubility enhancer for lipophilic antioxidants. Seven percent RMCD (w/v) in a 50% acetone-H(2)O mixture was found to sufficiently solubilize vitamin E compounds and other lipophilic phenolic antioxidants in 75 mM phosphate buffer (pH 7.4). This newly developed ORAC assay (abbbreviated ORAC(FL-LIPO) was validated through linearity, precision, accuracy, and ruggedness. The validation results demonstrate that the ORAC(FL-LIPO) assay is reliable and robust. For the first time, by using 6-hydroxy-2,5,7,8-tetramethyl-2-carboxylic acid as a standard (1.0), the ORAC values of alpha-tocopherol, (+)-gamma-tocopherol, (+)-delta-tocopherol, alpha-tocopherol acetate, tocotrienols, 2,6-di-tert-butyl-4-methylphenol, and gamma-oryzanol were determined to be 0.5 +/- 0.02, 0.74 +/- 0.03, 1.36 +/- 0.14, 0.00, 0.91 +/- 0.04, 0.16 +/- 0.01, and 3.00 +/- 0.26, respectively. The structural information of oxidized alpha-tocopherol obtained by liquid chromatography/mass spectrometry reveals that the mechanism for the reaction between the vitamin E and the peroxyl radical follows the hydrogen atom transfer mechanism, which is in agreement with the notion that vitamin E is the chain-breaking antioxidant.

Author(s): Packer L, Weber SU,Rimbach G.
Title: Molecular aspects of alpha-tocotrienol antioxidant action and cell signalling.
Source: The Journal of Nutrition, Vol. 131, Iss. 2, p. 369-73.
Abstract: Packer L.et al. described antioxidant activity.Vitamin E was the most important lipid-soluble antioxidant. Although the antioxidant activity of tocotrienols is higher than that of tocopherols, tocotrienols have a lower bioavailability after oral ingestion. Tocotrienols penetrate rapidly through skin and efficiently combat oxidative stress induced by UV or ozone. Tocotrienols have beneficial effects in cardiovascular diseases both by inhibiting LDL oxidation and by down-regulating 3-hydroxyl-3-methylglutaryl-coenzyme A(HMG CoA) reductase, a key enzyme of the mevalonate pathway.

Author(s): Gen Y., Tsutomu K., Masohiko A., Makoto T., Tomio Y., Shuji T., Masahide I., Hiroshi H., Shigeaki B.
Title: Effects of gamma-oryzanol on hyperlipidemic subjects
Source: Current therapeutic, Vol. 4, No. 4, april, 1989
Abstract: Gen Y. et al. studied on the hypercholesterolemic effect of gamma-oryzanol which was investigated in 67 patients with hyperlipidemia. Three milligrams of gamma-oryzanol were administered daily, for 3 months. Plasma cholesterol and plasma triglyceride levels decreased significantly from the second month and after three months, respectively. High-density lipoprotein(HDL)-cholesterol was also significantly elevated after three months. The reduction in plasma-cholesterol was attributable to the decrease in low-density lipoprotein(LDL) cholesterol. Together with a long-term history of clinical use, this indicates the potential use of this drug as a treatment of first choice for mild hypercholesterolemic.

Author(s): Tong W., Kevin B.H., Robert M
Title: Antioxidant activity of phytosterols, oryzanol and other phytosterol conjugates
Source: JAOCS, Vol.79, No.12, 2002
Abstract: Tong W. et al. studied on antioxidant activity of phytosterols, oryzanol, ferulic acid ester of sterols, corn fiber oil and rice bran oil. At low concentration, these materials (phytosterols, oryzanol, ferrulic acid ester of sterols) did not improve the oxidative stability of the oil. The oxidative stability of oil was significantly affected by type of compounds tested and other concentration. Rice bran oil had significantly better antioxidant activity than the other. Viscosity of the oil was also significantly affected by type of the compounds. Rice bran oil was the most effective agent in preventing polymerization, and its activity increased dramatically with an initial increase in concentration but tended to level off an higher concentration. This experiment also suggest that the good antioxidant and antipolymerization of rice bran oil may not be due to is oryzanol content alone but to other minor lipid components, such as avenasterols. Rice bran oil showed very good antioxidant and antipolymerization ativity.

Author(s): Caudia Juliano, Massima Cossee, Maria Cristina, Luisella Pia
Title: Antioxidant activity of gamma-oryzanol mechanism of action and its effect on oxidative stability of pharmaceutical
Source: International Journal of pharmaceutics, Vol.299, Issue 1-2, 11August 2005, 146-154.
Abstract: Claudia et al. studied in antioxidant activity of gamma-oryzanol. In this research, gamma-oryzanol was extracted from rice bran oil. The molecular mechanism(s) of antioxidant activity of gamma-oryzanol by utilising different in vitro were investigated, such as scavenging at stable DPPH radical, OH radical and O2 radicals scavenging, and azocompound AMVN-initiated lipid peroxidation. The effect of scavenging on the oxidative stability of vegetable oils of pharmaceutical and cosmetic was evaluated in a oxidation accelerate test and compared with the effect of BHA and BHT. It was found that gamma-oryzanol is able to prevent AMVN-triggered lipoperoxidation. Moreover, when added to oil at concentration ranging between 2.5 and 10 mmol/kg, gamma-oryzanol shows a dose-dependant increase of induction time of oil, gamma-oryzanol improved the oxidative stability of oil.

Author(s): Mohammad Minhajuddin, Zafarul H. Beg, Jahangir Iqbal
Title: Hypolipidemic and antioxidant properties of tocotrienol rich fraction isolated from rice bran oil in experimentally induced hyperlipidemic rats
Source: Food and Chemical Toxicology, 43, 2005, 747-753
Abstract: Mohammad et al. studied on hypolipidemic and antioxidant effect of tocotrienol rich fraction (TRF) isolated from rice bran oil on experimentally induced hyperlipidemic rats. Hyperlipidemic rats were supplemented with different doses of TRF of one week. It was found that TRF supplementation decreased the lipid parameters with the optimum effect at a dose of 8 mg TRF /kg/day. HMG-CoA reductas activity, TBARS and conjugated dienes decreased significantly during the TRF treatment. These results suggest that TRF supplementation has health benefits through the modulation of physiological functions that include various atherogenic lipid profiles and antioxidants in hypercholesterolemic.

Author(s): Baliarsingh S, Beg ZN, Ahmad J
Title: The therapeutic impacts of tocotrienols in type 2 diabetic patients with hyperlipidemia
Source: Atherosclerosis, 2005, October; 182(2) : 867-74
Abstract: Baliarsingh S et al. investigated the theropeutic impacts of tocotrienols on serum and lipoprotein lipid levels in type 2 diabetic patients. Tocotrienol rich fraction(TRF) mediated decrease on elevated blood glucose and glucated hemoglobin A(1C)(HbA(1C)) in diabetic rats. They investigated effect of TRF on these parameters. After 60 days of TRF treatment, subjects showed an average decline of 20, 30 and 42% in serum total lipids, TC and LDL-C, respectively. In conclusion, daily intake of dietary TRF by type 2 diabetics will be useful in the prevention and treatment of hyperlipidemia and atherogenesis.

Author(s): Most MM., Tulley R., Morales S., Lefevre M.
Title: Rice bran oil, not fiber, lower cholesterol in humans
Source: American Journal of Clinical Nutrition, Vol. 81, No.1, 64-68, January 2005
Abstract: Most MM studied to assess the effects of defatted rice bran and rice bran oil in an average American diet on blood lipid in moderately hypercholesterolemic persons. It was found that defatted rice bran did not lower lipid concentrations. Total cholesterol was significantly lower with comsumption of the diet containing rice bran oil than with consumption of the control diet. The consumption of the rice bran oil diet, LDL cholesterol decreased by 7%, whereas HDL cholesterol was unchanged. In conclusion, rice bran oil, not fiber, lowers cholesterol in healthy, moderately hypercholesterolemic adults. There were no substantial differences in the fatty acid composition of the diets; therefore, the reduction of cholesterol was due to other components present in the rice bran oil, such as unsaponifiable compounds.

Author(s): Murase Y., Ishima H
Title: Clinical studies of oral administration of gamma-oryzanol on climacteric complaints and its syndrome
Source: Obstetrical and gynecological practice, 1963; 12: 147-9.
Abstract: Murase Y and Ishima H studies on effect of gamma-oryzanol for menopause. In this research gave 13 women who had hysterectomies, also called surgical menopouse, 100 mg gamma-oryzanol three daily for 38 days. It was found that it halved menopausal symptoms such as hot flashes in more than 67 percent of the women.