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Abstracts

Immune Enhancement

ABSTRACTS

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Depressed natural killer cell activity due to decreased natural killer cell population in a vitamin E-deficient patient with Shwachman syndrome: reversible natural killer cell abnormality by alpha-tocopherol supplementation

Adachi N; Migita M; Ohta T; Higashi A; Matsuda I Department of Paediatrics, Kumamoto University School of Medicine, Japan.

Eur J Pediatr (Germany) Jun 1997, 156 (6) p444-8

Natural Killer ( NK ) cell activity was examined in a 16-month-old Japanese boy with Shwachman syndrome associated with severe vitamin E deficiency. As evaluated by 51Cr-release assay from K562 cells, NK cell activity was constantly decreased. After 8 weeks of oral alpha-tocopherol (alpha-Toc) supplementation (100 mg/day), NK cell activity had normalised. When alpha-Toc supplementation was interrupted for 16 weeks. NK cell activity again decreased. Flow cytometry of peripheral lymphocytes revealed a lowered number of CD16+ CD 56- fraction, which has the most potent NK cell activity . Single cell-in-agarose assay, to investigate the binding and cytolytic activity of NK cell at the single cell level, revealed that the number of NK cells which bind to K562 cell was decreased, but that the cytolytic activity of the individual binding cell was relatively unaffected. A second supplementation of alpha-Toc for 8 weeks successfully restored NK cell activity, the number of cells expressing NK cell markers and the number of K562-binding cells as compared to the age-matched normal range. CONCLUSION: These results indicate that severe vitamin E deficiency caused impaired NK cell activity due to a decrease in the number of CD16+ CD56- NK cells and that this abnormality is reversible with alpha-Toc supplementation.

Enhancement of natural immune function by dietary consumption of Bifidobacterium lactis (HN019).

Arunachalam K, Gill HS, Chandra RK. Memorial University of Newfoundland, Janeway Child Health Centre, St Johns, Newfoundland, Canada.

Eur J Clin Nutr 2000 Mar;54(3):263-7

OBJECTIVE: To determine the effects of dietary consumption of Bifidobacterium lactis (strain HN019, DR10TM) on natural immunity. DESIGN: A randomized, double blind, placebo-controlled clinical trial. SETTING: Janeway Medical Centre, Memorial University, St Johns, Newfoundland. SUBJECTS: Twenty-five healthy elderly volunteers (median age 69 y; range 60-83 y). INTERVENTIONS: Twelve control subjects consumed 180 ml low-fat/low-lactose milk twice daily for a period of 6 weeks; 13 test subjects consumed milk supplemented with 1.5x1011 colony-forming units of B. lactis twice daily. Indices of natural immunity, including interferon production, phagocytic capacity and phagocyte-mediated bactericidal activity, were determined via peripheral blood at 0, 3, 6 and 12 weeks post-trial commencement. RESULTS: Subjects who consumed milk containing B. lactis for 6 weeks produced significantly enhanced levels of interferon-alpha, upon stimulation of their peripheral blood mononuclear cells in culture, in comparison to the placebo control group who received milk alone. There were also significant increases in polymorphonuclear cell phagocytic capacity among test group subjects, following consumption of milk supplemented with B. lactis, while individuals who consumed B. lactis-supplemented milk or milk alone showed enhanced phagocyte-mediated bactericidal activity. CONCLUSIONS: The results demonstrate that dietary consumption of B. lactis HN019 can enhance natural immunity in healthy elderly subjects, and that a relatively short-term dietary regime (6 weeks) is sufficient to impart measurable improvements in immunity that may offer significant health benefits to consumers. SPONSORS: Financial support for this project was provided by the New Zealand Dairy Board.

Recent progress in treatment and secondary prevention of breast cancer with supplements.

Austin, S.

Altern. Med. Rev. 1997; 2(1): 4-11.

No abstract available.

Protective effects of grape seed proanthocyanidins and selected antioxidants against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation, and peritoneal macrophage activation in mice.

Bagchi D, Garg A, Krohn RL, Bagchi M, Bagchi DJ, Balmoori J, Stohs SJ. Creighton University School of Pharmacy, Omaha, Nebraska, USA.

Gen Pharmacol 1998 May;30(5):771-6

1. The comparative protective abilities of a grape seed proanthocyanidin extract (GSPE) (25-100 mg/kg), vitamin C (100 mg/kg), vitamin E succinate (VES) (100 mg/kg) and beta-carotene (50 mg/kg) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced lipid peroxidation and DNA fragmentation in the hepatic and brain tissues, as well as production of reactive oxygen species by peritoneal macrophages, were assessed. 2. Treatment of mice with GSPE (100 mg/kg), vitamin C, VES and beta-carotene decreased TPA-induced production of reactive oxygen species, as evidenced by decreases in the chemiluminescence response in peritoneal macrophages by approximately 70%, 18%, 47% and 16%, respectively, and cytochrome c reduction by approximately 65%, 15%, 37% and 19%, respectively, compared with controls. 3. GSPE, vitamin C, VES and beta-carotene decreased TPA-induced DNA fragmentation by approximately 47%, 10%, 30% and 11%, respectively, in the hepatic tissues, and 50%, 14%, 31% and 11%, respectively, in the brain tissues, at the doses that were used. Similar results were observed with respect to lipid peroxidation in hepatic mitochondria and microsomes and in brain homogenates. 4. GSPE exhibited a dose-dependent inhibition of TPA-induced lipid peroxidation and DNA fragmentation in liver and brain, as well as a dose-dependent inhibition of TPA-induced reactive oxygen species production in peritoneal macrophages. 5. GSPE and other antioxidants provided significant protection against TPA-induced oxidative damage, with GSPE providing better protection than did other antioxidants at the doses that were employed.

Oxygen free radical scavenging abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro.

Bagchi D, Garg A, Krohn RL, Bagchi M, Tran MX, Stohs SJ. School of Pharmacy, Creighton University, Omaha, NE 68178, USA.

Res Commun Mol Pathol Pharmacol 1997 Feb;95(2):179-89

Proanthocyanidins, a group of polyphenolic bioflavonoids, have been reported to exhibit a wide range of biological, pharmacological and chemoprotective properties against oxygen free radicals. We have assessed the concentration-dependent oxygen free radical scavenging abilities of a grape seed proanthocyanidin extract (GSPE), vitamin C and vitamin E succinate (VES) as well as superoxide dismutase, catalase and mannitol against biochemically generated superoxide anion and hydroxyl radical using a chemiluminescence assay and cytochrome c reduction. A concentration-dependent inhibition was demonstrated by GSPE. At a 100 mg/l concentration, GSPE exhibited 78-81% inhibition of superoxide anion and hydroxyl radical. Under similar conditions, vitamin C inhibited these two oxygen free radicals by approximately 12-19%, while VES inhibited the two radicals by 36-44%. The combination of superoxide dismutase and catalase inhibited superoxide anion by approximately 83%, while mannitol resulted in an 87% inhibition of hydroxyl radical. The results demonstrate that GSPE is a more potent scavenger of oxygen free radicals as compared to vitamin C and VES.

Nutrition in pediatric HIV infection: setting the research agenda. Nutrition and immune function: overview.

Beisel WR. Department of Immunology and Infectious Diseases, Johns Hopkins University, School of Hygiene and Public Health, Baltimore, MD, USA.

J Nutr. 1996 Oct;126(10 Suppl):2611S-2615S.

Malnutrition can have adverse, even devastating effects on the antigen-specific arms of the immune system and on generalized host defensive mechanisms. Protein/energy malnutrition and/or deficiencies of single nutrients that assist in nucleic acid metabolism generally lead to atrophy of lymphoid tissues and dysfunctions of cell-mediated immunity. Deficiencies of single nutrients can impair production of key proteins. Trace element deficiencies are often multifactorial. Essential fatty acid deficiencies can reduce or perturb the synthesis of cytokine-induced eicosanoids. Arginine deficiency can diminish the production of nitric oxide, and deficiencies of antioxidant nutrients can allow increases in the damaging effects of free oxygen radicals. Humoral immunity continues to be maintained, although new primary responses to T-cell-dependent antigens are generally subnormal in both magnitude and quality. Immunological dysfunctions associated with malnutrition have been termed Nutritionally Acquired Immune Deficiency Syndromes (NAIDS). Infants and small children are at great risk because they possess only immature, inexperienced immune systems and very small protein reserves. The combination of NAIDS and common childhood infections is the leading cause of human mortality. NAIDS can generally be corrected by appropriate nutritional rehabilitation, but from a viewpoint highly important to this Workshop, AIDS and NAIDS are intensely synergistic. AIDS-induced malnutrition can lead to the secondary development of NAIDS, with its much broader array of additional immunological dysfunctions. The complex and far reaching insults to the immune system caused by NAIDS, and the synergistic combination of NAIDS and AIDS, thereby hasten the demise of many victims of AIDS. Aggressive nutritional support for children with HIV infections could delay, or lessen, the development of NAIDS and avoidance of NAIDS would improve both quality and length of life.

Whey proteins as a food supplement in HIV-seropositive individuals.

Bounous G, Baruchel S, Falutz J, Gold P. Department of Surgery, Montreal General Hospital, Quebec.

Clin Invest Med. 1993 Jun;16(3):204-9.

On the basis of numerous animal experiments, a pilot study was undertaken to evaluate the effect of undenatured, biologically active, dietary whey protein in 3 HIV-seropositive individuals over a period of 3 months. Whey protein concentrate was prepared so that the most thermosensitive proteins, such as serum albumin which contains 6 glutamylcysteine groups, would be in undenatured form. Whey protein powder dissolved in a drink of the patient's choice was drunk cold in quantities that were increased progressively from 8.4 to 39.2 g per day. Patients took whey proteins without adverse side effects. In the 3 patients whose body weight had been stable in the preceding 2 months, weight gain increased progressively between 2 and 7 kg, with 2 of the patients reaching ideal body weight. Serum proteins, including albumin, remained unchanged and within normal range, indicating that protein replenishment per se was not likely the cause of increased body weight. The glutathione content of the blood mononuclear cells was, as expected, below normal values in all patients at the beginning of the study. Over the 3-month period, glutathione levels increased in all 3 cases. In conclusion, these preliminary data indicate that, in patients who maintain an adequate total caloric intake, the addition of "bioactive" whey protein concentrate as a significant portion of total protein intake increases body weight and shows elevation of glutathione (GSH) content of mononuclear cells toward normal levels. This pilot study will serve as a basis for a much larger clinical trial.

Cover Story: Lactoferrin: the bioactive peptide that fights disease.

Brink, W.

Life Extension Magazine 2000 Oct; 6(10): 20-6. Ft. Lauderdale, FL: Life Extension Foundation.

http://www.lef.org/magazine/mag2000/oct2000_report_lactoferrin.html

In vitro effects of echinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency syndrome patients.

Broumand N; Sahl L; Tilles JG; See DM Department of Medicine, U.C. Irvine Medical Center, Orange 92668, USA.

Immunopharmacology (Netherlands) Jan 1997, 35 (3) p229-35

Extracts of Echinacea purpurea and Panax ginseng were evaluated for their capacity to stimulate cellular immune function by peripheral blood mononuclear cells (PBMC) from normal individuals and patients with either the chronic fatigue syndrome or the acquired immunodeficiency syndrome. PBMC isolated on a Ficoll-hypaque density gradient were tested in the presence or absence of varying concentrations of each extract for natural killer ( NK ) cell activity versus K562 cells and antibody-dependent cellular cytotoxicity (ADCC) against human herpesvirus 6 infected H9 cells. Both echinacea and ginseng, at concentrations > or = 0.1 or 10 micrograms/kg, respectively, significantly enhanced NK-function of all groups. Similarly, the addition of either herb significantly increased ADCC of PBMC from all subject groups. Thus, extracts of Echinacea purpurea and Panax ginseng enhance cellular immune function of PBMC both from normal individuals and patients with depressed cellular immunity.

Prospects of the clinical utilization of melatonin.

Bubenik GA; Blask DE; Brown GM; Maestroni GJ; Pang SF; Reiter RJ; Viswanathan M; Zisapel N Department of Zoology, University of Guelph, Ont., Canada. gbubenik@uoguelph.ca

Biol Signals Recept (Switzerland) Jul-Aug 1998, 7 (4) p195-219

This review summarizes the present knowledge on melatonin in several areas on physiology and discusses various prospects of its clinical utilization. Ever increasing evidence indicates that melatonin has an immuno-hematopoietic role. In animal studies, melatonin provided protection against gram-negative septic shock, prevented stress-induced immunodepression, and restored immune function after a hemorrhagic shock. In human studies, melatonin amplified the antitumoral activity of interleukin-2. Melatonin has been proven as a powerful cytostatic drug in vitro as well as in vivo. In the human clinical field, melatonin appears to be a promising agent either as a diagnostic or prognostic marker of neoplastic diseases or as a compound used either alone or in combination with the standard cancer treatment. Utilization of melatonin for treatment of rhythm disorders, such as those manifested in jet lag, shift work or blindness, is one of the oldest and the most successful clinical application of this chemical. Low doses of melatonin applied in controlled-release preparation were very effective in improving the sleep latency, increasing the sleep efficiency and rising sleep quality scores in elderly, melatonin-deficient insomniacs. In the cardiovascular system, melatonin seems to regulate the tone of cerebral arteries; melatonin receptors in vascular beds appear to participate in the regulation of body temperature. Heat loss may be the principal mechanism in the initiation of sleepiness caused by melatonin. The role of melatonin in the development of migraine headaches is at present uncertain but more research could result in new ways of treatment. Melatonin is the major messenger of light-dependent periodicity, implicated in the seasonal reproduction of animals and pubertal development in humans. Multiple receptor sites detected in brain and gonadal tissues of birds and mammals of both sexes indicate that melatonin exerts a direct effect on the vertebrate reproductive organs. In a clinical study, melatonin has been used successfully as an effective female contraceptive with little side effects. Melatonin is one of the most powerful scavengers of free radicals. Because it easily penetrates the blood-brain barrier, this antioxidant may, in the future, be used for the treatment of Alzheimer's and Parkinson's diseases, stroke, nitric oxide, neurotoxicity and hyperbaric oxygen exposure. In the digestive tract, melatonin reduced the incidence and severity of gastric ulcers and prevented severe symptoms of colitis, such as mucosal lesions and diarrhea. (227 Refs.)

Beta-carotene enhances natural killer cell activity in athymic mice.

Carlos TF; Riondel J; Mathieu J; Guiraud P; Mestries JC; Favier A Groupe de Recherches et d'Etudes des Pathologies Oxydatives (GREPO), Faculte de Pharmacie, La Tronche, France.

In Vivo (Greece) Jan-Feb 1997, 11 (1) p87-91

To study the effects of beta-carotene on Natural Killer (NK) cells, we chose athymic mice whose spleens have a higher percentage of NK cells than conventional mice. Preliminary studies conducted with beta-carotene given intraperitoneally to athymic mice xenografted with a small-cell lung carcinoma resulted in a slight but significant antiproliferative effect (unpublished observations). We speculated that such an activity of beta-carotene was related to its immunostimulating properties. NK cell activity in ungrafted athymic mice as influenced by beta-carotene was studied. Mice received beta-carotene intraperitoneally. Splenic NK cells were labelled with monoclonal antibody and numeration was completed by measurement of their functional activity against YAC-1 malignant cells with a 51Cr release assay. In addition, splenic lymphocytes were evaluated for their reduced glutathione (GSH) content. There was a non-significant increase in the number of NK cells in the spleen, however their killing capacity was significantly (p < 0.01) enhanced after beta-carotene treatment. Also the GSH content of splenic lymphocytes was significantly higher in beta-carotene treated mice. Comparison of the average body weights of treated animals and of their respective controls showed that treatment had no adverse effects.

Partners in defense, vitamin E and vitamin C.

Chan AC. Department of Biochemistry, Faculty of Medicine, University of Ottawa, ON, Canada.

Can J Physiol Pharmacol. 1993 Sep;71(9):725-31.

In addition to the enzymic mechanism of free-radical removal, essential nutrients that can scavenge free radicals, such as vitamins E and C, constitute a strong line of defense in retarding free radical induced cellular damage. Distinct pathways for the repair of oxidized vitamin E in human cells have been recently identified. Within 0.5 min after the addition of arachidonic acid to a human platelet homogenate, over half of the platelet vitamin E and added arachidonate were metabolized by platelet cyclooxygenase and lipoxygenase pathways. After adding nordihydroguaiaretic acid, a lipoxygenase inhibitor and a strong reductant, over 60% of the oxidized vitamin E was regenerated. To test other physiological, water-soluble reductants that may help regenerate vitamin E, eicosatetraynoic acid, a lipoxygenase inhibitor that is not an antioxidant, was used. In this system, both ascorbate and glutathione provided significant vitamin E regeneration. Kinetic analysis and studies of vitamin E regeneration in a protein-denaturing system revealed that ascorbate regenerates vitamin E by a nonenzymic mechanism, whereas glutathione regenerates vitamin E enzymatically. These studies suggest that significant interaction occurs between water- and lipid-soluble molecules at the membrane-cytosol interface and that vitamin C may function in vivo to repair the membrane-bound oxidized vitamin E.

Nutrition and immune responses.

Chandra RK

Can J Physiol Pharmacol 1983 Mar;61(3):290-4

Clinical and epidemiologic data suggest a causal relationship between nutritional deficiency and infection. Among other factors, impaired immune responses secondary to malnutrition increase susceptibility to infectious illness. Protein-energy undernutrition and deficiencies of iron, zinc, pyridoxine, and other nutrients depress a variety of immunity functions. Cell-mediated immunity, complement system, microbicidal activity of phagocytes, secretory antibody response, and antibody affinity are often decreased. Recent studies have revealed many metabolic and hormone alterations as well as changes in the number and function of lymphocyte subpopulations. Obesity also is associated with impaired cellular immune functions. Dietary factors may play a critical role in host resistance to disease.

Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects.

Chandra RK Memorial University of Newfoundland.

Lancet 1992 Nov 7;340(8828):1124-7

Ageing is associated with impaired immune responses and increased infection-related morbidity. This study assessed the effect of physiological amounts of vitamins and trace elements on immunocompetence and occurrence of infection-related illness. 96 independently living, healthy elderly individuals were randomly assigned to receive nutrient supplementation or placebo. Nutrient status and immunological variables were assessed at baseline and at 12 months, and the frequency of illness due to infection was ascertained. Subjects in the supplement group had higher numbers of certain T-cell subsets and natural killer cells, enhanced proliferation response to mitogen, increased interleukin-2 production, and higher antibody response and natural killer cell activity. These subjects were less likely than those in the placebo group to have illness due to infections (mean [SD] 23 [5] vs 48 [7] days per year, p = 0.002). Supplementation with a modest physiological amount of micronutrients improves immunity and decreases the risk of infection in old age.

Nutrition and immunology: from the clinic to cellular biology and back again.

Chandra RK Department of Pediatrics and Medicine, Memorial University of Newfoundland, Canada. rchandra@morgan.ucs.mun.ca

Proc Nutr Soc 1999 Aug;58(3):681-3

Diet and immunity have been known to be linked to each other for centuries. In the last 30 years systematic studies have confirmed that nutrient deficiencies impair immune response and lead to frequent severe infections resulting in increased mortality, especially in children. Protein-energy malnutrition results in reduced number and functions of T-cells, phagocytic cells and secretory immunoglobulin A antibody response. In addition, levels of many complement components are reduced. Similar findings have been reported for moderate deficiencies of individual nutrients such as trace minerals and vitamins, particularly Zn, Fe, Se, vitamins A, B6, C and E. For example, Zn deficiency is associated with profound impairment of cell-mediated immunity such as lymphocyte stimulation response, decreased CD4+:CD8+ cells, and decreased chemotaxis of phagocytes. In addition, the level of thymulin, which is a Zn-dependent hormone, is markedly decreased. The use of nutrient supplements, singly or in combination, stimulates immune response and may result in fewer infections, particularly in the elderly, low-birth-weight infants and malnourished critically-ill patients in hospitals. The interactions between nutrition and the immune system are of clinical, practical and public health importance.

Numerical and functional deficiency of suppressor T cells precedes development of atopic eczema.

Chandra RK, Baker M

Lancet 1983 Dec 17;2(8364):1393-4

Immunoregulatory T cells were studied quantitatively and functionally at age 1-2 months in 30 symptom-free infants with family history of atopic disease and in 30 infants with no such history. The infants were followed up for 24-37 months (mean 28.2 months) to see whether clinical atopic disease was expressed. In infants in whom atopic eczema subsequently developed, numbers of T8-positive cells were reduced, the T4/T8 ratio was raised, and functional suppressor activity was lower than normal. These findings indicate that a defect of T-cell regulation precedes clinical atopic disease and is of primary pathogenetic importance.

Nutrition, immune response, and outcome.

Chandra S, Chandra RK

Prog Food Nutr Sci 1986;10(1-2):1-65

The immune system plays a key role in the body's ability to fight infection and reduce the risk of developing tumors, autoimmune and degenerative disease. Nutritional deficiencies and excesses influence various components of the immune system. Early studies investigating the association between nutrition and immunity focused on generalized protein-energy malnutrition, particularly in children in developing countries. The extent of immunological impairment depends not only on the severity of malnutrition but on the presence of infection and on the age of onset of nutritional deprivation, among other factors. In industrialized nations, immune function has been shown to be compromised in many malnourished hospitalized patients, small-for-gestational age infants, and the elderly. Obesity also may adversely influence immune function. Imbalances of single nutrients are relatively uncommon in humans, and investigations of protein and amino acids and specific vitamins, minerals, and trace elements generally are carried out in experimental animals. Deficiencies of protein and some amino acids, as well as vitamins A, E, B6 and folate, are associated with reduced immunocompetence. In contrast, excessive intake of fat, in particular polyunsaturated fatty acids (e.g. linoleic and arachidonic acids), iron, and vitamin E are immunosuppressive. Trace elements modulate immune responses through their critical role in enzyme activity. Both deficiency and excess of trace elements have been recognized. Although dietary requirements of most of these elements are met by a balanced diet, there are certain population groups and specific disease states which are likely to be associated with deficiency of one or more of these essential elements. The role of trace elements in maintenance of immune function and their causal role in secondary immunodeficiency is increasingly being recognized. There is growing research concerning the role of zinc, copper, selenium, and other elements in immunity and the mechanisms that underlie such roles. The problem of interaction of trace elements and immunity is a complex one because of the frequently associated other nutritional deficiencies, the presence of clinical or subclinical infections which in themselves have a significant effect on immunity, and finally the altered metabolism due to the underlying disease. There are many practical applications of our recently acquired knowledge regarding nutritional regulation of immunity.

Serum thymic factor activity in deficiencies of calories, zinc, vitamin A and pyridoxine.

Chandra RK, Heresi G, Au B

Clin Exp Immunol 1980 Nov;42(2):332-5

Cell-mediated immunity is invariably impaired in protein-energy malnutrition. The effect of selected nutrient deficiencies on serum thymic factor activity was assessed in deprived rats and pair-fed controls. Deficits of calories, zinc or pyridoxine resulted in significant lowering of serum thymic factor activity whereas vitamin A deficiency did not have any effect. It is suggested that variants nutrients modulate different steps of cell-mediated immunity and that reduced thymic hormone activity may be the underlying mechanism of impaired immunity in some but not all nutritional deficiencies.

Nutrition of the elderly.

Chandra RK, Imbach A, Moore C, Skelton D, Woolcott D Department of Medicine, Memorial University of Newfoundland, St. John's.

Can. Med. Assoc. J. (CMAJ) 1991 Dec 1; 145(11): 1475-87.

The progressively increasing number of elderly people in the Canadian population and the disproportionate expenditure on their health care has stimulated interest in prevention of common illnesses observed in this age group. It is now recognized that nutrition plays an important role in health status, and both undernutrition and overnutrition are associated with greater risk of morbidity and mortality. Nutritional problems in the elderly can be suspected if there are several high-risk factors present--for example, living alone, physical or mental disability, recent loss of spouse or friend, weight loss, use of multiple medications, poverty, and high consumption of alcohol. Physical examination, anthropometry, and measurements of serum albumin levels and hemoglobin and lymphocyte counts are simple but helpful tools in confirming the presence of nutritional disorders. The prevention and correction of nutritional problems is likely to prove beneficial in the management of common geriatric illnesses. In these efforts, it is desirable to have a team approach in which the physician, the dietitian and the nurse each have a defined interactive role. Home care support services are important adjuncts in continuing care. Nutrition should receive a greater emphasis in the training of physicians and other health professionals.

Zinc and immunity.

Chandra, R.K., McBean, L.D.

Nutrition 1994 Jan-Feb; 10(1): 7-80.

No abstract available.

Enhancing immunity by dietary consumption of a probiotic lactic acid bacterium (Bifidobacterium lactis HN019): optimization and definition of cellular immune responses.

Chiang BL, Sheih YH, Wang LH, Liao CK, Gill HS. College of Medicine, National Taiwan University, Taipei, Taiwan.

Eur J Clin Nutr 2000 Nov;54(11):849-55

OBJECTIVE: To define the cellular basis for immune enhancement by a probiotic lactic acid bacteria strain (Bifidobacterium lactis HN019); and to determine whether immune enhancement can be optimized by delivery in oligosaccharide-enriched low-fat milk. DESIGN: A double-blind, three-stage before-and-after intervention trial. SETTING: Taipei Medical College Hospital, Taipei, Taiwan. SUBJECTS: Fifty healthy Taiwanese citizens (age range 41-81; median 60) randomly allocated to two groups. INTERVENTIONS: In stage 1 (run-in control stage) all subjects consumed reconstituted low-fat milk (LFM) for 3 weeks; in stage 2 (probiotic intervention) subjects consumed B. lactis in LFM (group A) or B. lactis in lactose-hydrolysed LFM (group B) for 3 weeks; in stage 3 all subjects returned to non-supplemented LFM for a further 3 weeks (washout stage). The innate immune functions of two different leucocyte types (polymorphonuclear (PMN) cells and natural killer (NK) cells) were assessed at four time points via in vitro analyses on peripheral blood samples. RESULTS: While consumption of LFM alone had no significant effect on immune responses, stage 2 results indicated significantly enhanced PMN cell phagocytosis and NK cell tumour killing activity following consumption of milk containing B. lactis. These increases levelled off following cessation of B. lactis consumption, but remained above the pre-treatment values. Increases in PMN and NK cell activity were greatest among subjects who consumed B. lactis in lactose-hydrolysed LFM. CONCLUSIONS: Dietary consumption of the probiotic bacterium B. lactis HN019 enhanced immune function of two different types of leucocytes; the degree of enhancement was increased by consuming B. lactis in an oligosaccharide-rich substrate. SPONSORSHIP: Financial support was provided by the New Zealand Dairy Board.

Biological and health implications of toxic heavy metal and essential trace element interactions.

Chowdhury BA, Chandra RK.

Prog Food Nutr Sci. 1987;11(1):55-113.

Human civilization and a concomitant increase in industrial activity has gradually redistributed many toxic metals from the earth's crust to the environment and increased the possibility of human exposure. Among the various toxic elements, heavy metals cadmium, lead, and mercury are specially prevalent in nature due to their high industrial use. These metals serve no biological function and their presence in tissues reflects contact of the organism with its environment. They are cumulative poison, and are toxic even at low dose. Studies of metabolism and toxicity of these elements have revealed important interactions between them and some essential dietary elements like calcium, zinc, iron, selenium, copper, chromium, and manganese. In general, a deficiency of these essential elements increases toxicity of heavy metals, whereas an excess appears to be protective. While most of the observations are on laboratory animals, limited human data are in agreement with the results of animal experiments. These suggest that the dietary presence of the essential elements may contribute to the protection of man and animal from the effects of heavy metal exposure, while their deficiency may increase toxicity. Appropriate dietary manipulation thus may be valuable in the prevention and treatment of heavy metal toxicity.

Natural killer cells from aging mice treated with extracts from Echinacea purpurea are quantitatively and functionally rejuvenated.

Currier NL, Miller SC. Department of Anatomy and Cell Biology, McGill University, H3A 2B2, Montreal, Canada.

Exp Gerontol. 2000 Aug;35(5):627-39.

A growing body of anecdotal evidence in young and adult humans suggests that certain phytochemicals have the capacity to ameliorate tumors and reduce infections, especially those mediated by virus, in vivo. These indications prompted us, therefore, to investigate the potentially immuno-stimulating effect of one such phytocompound, Echinacea purpurea, on natural killer (NK) cells since these cells are active in spontaneous, non-specific immunity against neoplasms and virus-mediated infections. We elected to study aging mice, since, at this stage of life, like humans, the above-mentioned afflictions increase in frequency. We had previously found that neither the cytokine, interleukin-2, nor the pharmacological agent, indomethacin, both potent stimulators of NK cell numbers/function in younger adult mice, was effective in stimulating NK cells in elderly mice. The present study was designed to assess the numbers/production of NK cells in the spleen and bone marrow of aging, normal mice, after in vivo dietary administration of E. purpurea (14 days), or, after injection of thyroxin, a stimulant of NK cell function (10 days). Immunoperoxidase labeling techniques, coupled with hematologic tetrachrome staining were used to identify NK cells in both the spleen (primary site of NK cell function) and the bone marrow (site of NK cell generation). Double immunofluorscence staining, employing propidium iodide, was used to assess NK cell lytic function. Our results revealed that E. purpurea, but not thyroxin, had the capacity to increase NK cell numbers, in aging mice, reflecting increased new NK cell production in their bone marrow generation site, leading to an increase in the absolute numbers of NK cells in the spleen, their primary destiny. The E. purpurea-mediated increase in NK cell numbers was indeed paralleled by an increase in their anti-tumor, lytic functional capacity. Collectively, the data indicate that E. purpurea, at least, and possibly other plant compounds, appear to contain phytochemicals capable of stimulating de novo production of NK cells, as well as augmenting their cytolytic function, in animals of advanced age.

Dehydroepiandrosterone (DHEA) treatment reverses the impaired immune response of old mice to influenza vaccination and protects from influenza infection.

Danenberg HD; Ben-Yehuda A; Zakay-Rones Z; Friedman G

Vaccine (England) 1995, 13 (15) p1445-8

Dehydroepiandrosterone (DHEA) is a native steroid with an immunomodulating activity. Recently it was suggested that its age-associated decline is related with immunosenescence. To examine whether DHEA administration could effectively reverse the age-associated decline of immunity against influenza vaccine, aged mice were simultaneously vaccinated and treated with DHEA. Reversal of the age-associated decline and a significant constant increase of humoral response was observed in treated mice. Increased resistance to post-vaccination intranasal challenge with live influenza virus was observed in DHEA-treated aged mice. Thus, DHEA treatment overcame the age-related defect in the immunity of old mice against influenza.

Nutrients and immune responses.

Delafuente JC. Department of Pharmacy Practice, College of Pharmacy, University of Florida, Gainesville.

Rheum Dis Clin North Am 1991 May;17(2):203-12

A wide spectrum of nutritional deficiencies, ranging from trace elements to protein, can impair normal immunologic functions. Repletion of deficient nutrients generally will restore the immune response. Under some experimental conditions, single nutrient supplementation boosts immunity; however, some mega-dose therapies have been shown to suppress the immune response. Adequate nutrition is essential for maintaining the integrity of the immune system.

Carnitine depletion in peripheral blood mononuclear cells from patients with AIDS: effect of oral L-carnitine.

De Simone C; Famularo G; Tzantzoglou S; Trinchieri V; Moretti S; Sorice F

AIDS (United States) May 1994, 8 (5) p655-60

OBJECTIVE: Reduced levels of serum carnitines (3-hydroxy-4-N-trimethyl-am monio-butanoate) are found in most patients treated with zidovudine. However, since serum carnitines do not strictly reflect cellular concentrations we examined whether a carnitine depletion could be found in peripheral blood mononuclear cells (PBMC) from AIDS patients with normal serum carnitine levels. In addition, we explored whether it was possible to relate the host's immunoreactivity to the content of carnitine in PBMC and whether carnitine levels can be corrected by oral supplementation of L-carnitine.

DESIGN: Immunopharmacologic study.

METHODS: Twenty male patients with advanced AIDS (Centers for Disease Control and Prevention stage IVCI) and normal serum levels of carnitines were enrolled. Patients were randomly assigned to receive either L-carnitine (6 g/day) or placebo for 2 weeks. At baseline and at the end of the trial, we measured carnitines in both sera and PBMC, serum triglycerides, CD4 cell counts, and the frequency of cells entering the S and G2-M phases of cell cycle following mitogen stimulation.

RESULTS: Concentrations of total carnitine in PBMC from AIDS patients was lower than in healthy controls. A significant trend towards the restoration of appropriate intracellular carnitine levels was found in patients treated with high-dose L-carnitine and was associated with an increased frequency of S and G2-M cells following mitogen stimulation. Furthermore, at the end of the trial we found a strong reduction in serum triglycerides in the L-carnitine group compared with baseline levels.

CONCLUSIONS: Our data indicate that carnitine deficiency occurs in PBMC from patients with advanced AIDS, despite normal serum concentrations. The increase in cellular carnitine content strongly improved lymphocyte proliferative responsiveness to mitogens. Because carnitine status is an important contributing factor to immune function in patients with advanced AIDS, we therefore believe that L-carnitine supplementation could have a role as a complementary therapy for HIV-infected individuals.

Vitamins and immunity: II. Influence of L-carnitine on the immune system.

De Simone C, Ferrari M, Lozzi A, Meli D, Ricca D, Sorice F.

Acta Vitaminol Enzymol. 1982;4(1-2):135-40.

Vitamin A affects the antibody responses and may affect phagocytic function and properdin levels. Pyridoxine deficiency impairs nucleic acid synthesis and depresses antibody formation, delayed hypersensitivity reactions and the ability of phagocytes to kill bacteria. Pantothenic acid deficiency impairs antibody formation. Vitamin C deficiency increases the incidence of infection, primary by a negative influence on reparative processes. Deficiencies of other vitamins either have not been sufficiently studied or have a variable effect. Moreover, even substances which for their biosynthesis require an adequate vitamin supplementation may exert immunomodulatory influences. With this respect the authors report their results on the influence of L-carnitine on the immune system. L-carnitine increases the proliferative responses of both murine and human lymphocyte following mitogenic stimulation and increase polymorphonuclear chemotaxis. Furthermore, L-carnitine, even at minimal concentrations, neutralizes the lipid induced immunosuppression.

High dose L-carnitine improves immunologic and metabolic parameters in AIDS patients.

De Simone C, Tzantzoglou S, Famularo G, Moretti S, Paoletti F, Vullo V, Delia S. Universita di L'Aquila, Italy.

Immunopharmacol Immunotoxicol. 1993 Jan;15(1):1-12.

Several reports indicate that systemic carnitine deficiency could occur in acquired immunodeficiency disease syndrome (AIDS), and that primary and secondary carnitine deficiency leads to critical metabolic dysfunctions. L-carnitine supplementation to peripheral blood mononuclear cells (PBMCs) of AIDS patients resulted in significant enhancement of the phytohemagglutinin (PHA)-driven proliferative response. High dose L-carnitine administration (6 gr per day for two weeks) to AIDS patients treated with zidovudine also led to increased PBMCs proliferation and reduced blood levels of triglycerides. In addition, a reduction of beta 2-microglobulin serum levels as well as circulating tumor necrosis factor (TNF)-alpha, mostly in patients exhibiting highly elevated levels, were found at the end of the treatment period. Our data suggest that in vivo L-carnitine could prove useful in ameliorating both the immune response and lipid metabolism in patients with AIDS, irrespective of initial serum carnitines levels. The mechanism(s) accounting for the observed results are currently not clear. Further studies are needed to confirm the hypothesis that L-carnitine affects the expression of HIV-induced cytokine.

Vitamins and immunity: II. Influenceof L-carnitine on the immune system.

De Simone C; Ferrari M; Lozzi A; Meli D; Ricca D; Sorice F

Acta Vitaminol Enzymol (Italy) 1982, 4 (1-2)

Vitamin A affects the antibody responses and may affect phagocytic function and properdin levels. Pyridoxine deficiency impairs nucleic acid synthesis and depresses antibody formation, delayed hypersensitivity reactions and the ability of phagocytes to kill bacteria. Pantothenic acid deficiency impairs antibody formation. Vitamin-C deficiency increases the incidence of infection, primary by a negative influence on reparative processes. Deficiencies of other vitamins either have not been sufficiently studied or have a variable effect. Moreover, even substances which for their biosynthesis require an adequate vitamin supplementation may exert immunomodulatory influences. With this respect the authors report their results on the influence of L-carnitine on the immune system. L-carnitine increases the proliferative responses of both murine and human lymphocyte following mitogenic stimulation and increase polymorphonuclear chemotaxis. Furthermore, L-carnitine, even at minimal concentrations, neutralizes the lipid induced immunosuppression.

Serum IL-6 level and the development of disability in older persons.

Ferrucci L, Harris TB, Guralnik JM, Tracy RP, Corti MC, Cohen HJ, Penninx B, Pahor M, Wallace R, Havlik RJ. Geriatric Department, I Fraticini, National Research Institute (INRCA), Florence, Italy.

J Am Geriatr Soc 1999 Jun;47(6):639-46

BACKGROUND: The serum concentration of interleukin 6 (IL-6), a cytokine that plays a central role in inflammation, increases with age. Because inflammation is a component of many age-associated chronic diseases, which often cause disability, high circulating levels of IL-6 may contribute to functional decline in old age. We tested the hypothesis that high levels of IL-6 predict future disability in older persons who are not disabled. METHODS: Participants at the sixth annual follow-up of the Iowa site of the Established Populations for Epidemiologic studies of the Elderly aged 71 years or older were considered eligible for this study if they had no disability in regard to mobility or in selected activities of daily living (ADL), and they were re-interviewed 4 years later. Incident cases of mobility-disability and of ADL-disability were identified based on responses at the follow-up interview. Measures of IL-6 were obtained from specimens collected at baseline from the 283 participants who developed any disability and from 350 participants selected randomly (46.9%) from those who continued to be non-disabled. FINDINGS: Participants in the highest IL-6 tertile were 1.76 (95% CI, 1.17-2.64) times more likely to develop at least mobility-disability and 1.62 (95% CI, 1.02-2.60) times more likely to develop mobility plus ADL-disability compared with to the lowest IL-6 tertile. The strength of this association was almost unchanged after adjusting for multiple confounders. The increased risk of mobility-disability over the full spectrum of IL-6 concentration was nonlinear, with the risk rising rapidly beyond plasma levels of 2.5 pg/mL. INTERPRETATION: Higher circulating levels of IL-6 predict disability onset in older persons. This may be attributable to a direct effect of IL-6 on muscle atrophy and/or to the pathophysiologic role played by IL-6 in specific diseases.

Immunological and clinical effect of long-term oral treatment with RU 41740 in patients with chronic bronchitis: double-blind trial long-term versus standard dose regimen.

Fietta AM, Merlini C, Uccelli M, Gialdroni Grassi G, Grassi C. Chair of Chemotherapy, University of Pavia, IRCCS, Policlinico S. Matteo, Italy.

Respiration. 1992;59(5):253-8.

The immunological and clinical effects of two oral treatment schedules of RU 41740 (standard for 3 months vs. long-term for 6 months) were assessed in 40 patients with chronic bronchitis by a controlled, double-blind, randomized trial. Both treatments significantly improved phagocytosis index of both neutrophils and monocytes, and the phagocytosis frequency and the candidacidal activity of neutrophils, showing the maximum stimulation at the end of the third course of treatment. Both treatment schedules reduced the number and the duration of infectious exacerbations of chronic bronchitis with respect to those observed in the corresponding period of the previous year. However, no significant difference between standard and long-term treatment with RU 41740 was found with respect to the immunological and clinical effect and tolerability.

The activities of coenzyme Q10 and vitamin B6 for immune responses.

Folkers K, Morita M, McRee J Jr Institute for Biomedical Research, University of Texas, Austin 78712.

Biochem Biophys Res Commun 1993 May 28;193(1):88-92

Coenzyme Q10 (CoQ10) and vitamin B6 (pyridoxine) have been administered together and separately to three groups of human subjects. The blood levels of CoQ10 increased (p < 0.001) when CoQ10 and pyridoxine were administered together and when CoQ10 was given alone. The blood levels of IgG increased when CoQ10 and pyridoxine were administered together (p < 0.01) and when CoQ10 was administered alone (p < 0.05). The blood levels of T4-lymphocytes increased when CoQ10 and pyridoxine were administered together (p < 0.01) and separately (p < 0.001). The ratio of T4/T8 lymphocytes increased when CoQ10 and pyridoxine were administered together (p < 0.001) and separately (p < 0.05). These increases in IgG and T4-lymphocytes with CoQ10 and vitamin B6 are clinically important for trials on AIDS, other infectious diseases, and on cancer.

Increase in levels of IgG in serum of patients treated with coenzyme Q10.

Folkers, K., Shizukuishi, S., Takemura, K., Drzewoski, J., Richardson, P., Ellis, J., Kuzell, W.C.

Res. Commun. Chem. Pathol. Pharmacol. 1982 Nov; 38(2): 335-8.

No abstract available.

Research on coenzyme Q10 in clinical medicine and in immunomodulation.

Folkers K; Wolaniuk A

Drugs Exp Clin Res (Switzerland) 1985, 11 (8) p539-45

Coenzyme Q10 (CoQ10) is a redox component in the respiratory chain. CoQ10 is necessary for human life to exist; and a deficiency can be contributory to ill health and disease. A deficiency of CoQ10 in myocardial disease has been found and controlled therapeutic trials have established CoQ10 as a major advance in the therapy of resistant myocardial failure. The cardiotoxicity of adriamycin, used in treatment modalities of cancer, is significantly reduced by CoQ10, apparently because the side-effects of adriamycin include inhibition of mitochondrial CoQ10 enzymes. Models of the immune system including phagocytic rate, circulating antibody level, neoplasia, viral and parasitic infections were used to demonstrate that CoQ10 is an immunomodulating agent. It was concluded that CoQ10, at the mitochondrial level, is essential for the optimal function of the immune system.

Immunological parameters in aging: studies on natural immunomodulatory and immunoprotective substances.

Franceschi C, Cossarizza A, Troiano L, Salati R, Monti D Institute of General Pathology, University of Modena, Italy.

Int J Clin Pharmacol Res 1990;10(1-2):53-7

Several immune parameters--particularly T-cell dependent immune responses--are altered in aged subjects. To test the hypothesis that they may be the consequence of more general age-related lymphocyte biochemical alterations, and particularly of the energy producing system, the effect of L-carnitine and acetyl-L-carnitine on cell proliferation was studied in peripheral blood lymphocytes from donors of different ages. The results showed that phytohaemagglutinin-induced peripheral blood lymphocyte proliferation was markedly increased in L-carnitine- or acetyl-L-carnitine-preloaded lymphocytes from young and especially from old subjects. Cells from aged subjects considerably improved their defective proliferative capability. Preliminary observations suggest that L-carnitine-preloading also protected peripheral blood lymphocytes from old donors when such cells were exposed to an oxidative stress.

Immunomodulatory and Anti-Cancer Properties of MGN-3, a Modified Xylose from Rice Bran, in 5 Patients with Breast Cancer (abstract).

Ghoneum, M.

Presented at the American Association for Cancer Research, Special Conference, Baltimore, MD, November 5-8, 1995.

Enhancement of human natural killer cell activity by modified arabinoxylane from rice bran (MGN-3)

Ghoneum M. M. Ghoneum, Drew University Medicine and Science, Department of Otolaryngology, 1621 East 120th Street, Los Angeles, CA 90059 United States International Journal of Immunotherapy ( Switzerland ) 1998 , 14/2 (89-99)

Arabinoxylane from rice bran (MGN-3) was examined for its augmentory effect on human NK (NK) cell activity in vivo and in vitro. Twenty-four individuals were given MGN-3 orally at three different concentrations: 15, 30 and 45 mg/kg/day for 2 months. Peripheral blood lymphocyte-NK cell activity was tested by sup 5sup 1Cr release assay against K562 and Raji tumor cells at 1 week, 1 month and 2 months posttreatment and results were compared with baseline NK activity. Treatment with MGN-3 enhanced NK activity against K562 tumor cells at all concentrations used. In a dose-dependent manner, MGN-3 at 15 mg/kg/day increased NK activity after 1 month posttreatment (twofold over control value), while significant induction of NK activity at 30 mg/kg/day was detected as early as 1 week posttreatment (three times control value). NK cell activity continued to increase with continuation of treatment and peaked (fivefold) at 2 months (end of treatment period). Increasing the concentration to 45 mg/kg/day showed similar trends in NK activity, however the magnitude in values was higher than for 30 mg/kg/day. After discontinuation of treatment, NK activity declined and returned to baseline value (14 lytic units) at 1 month. Enhanced NK activity was associated with an increase in the cytotoxic reactivity against the resistant Raji cell line. MGN-3 at 45 mg/kg/day showed a significant increase in NK activity after 1 week (eightfold) and peaked at 2 months posttreatment (27 times that of baseline). Culture of peripheral blood lymphocytes (PBL) with MGN-3 for 16 h demonstrated a 1.3 to 1.5 times increase in NK activity over control value. The mechanism by which MGN-3 increases NK activity was examined and showed no change in cluster of differentiation (CD) 16sup + and CD56sup + CD3sup - of MGN-3-activated NK cells as compared with baseline value; a fourfold increase in the binding capacity of NK to tumor cell targets as compared with baseline value; and a significant increase in the production of interferon-gamma (340-580 pg/ml) postculture of PBL with MGN-3 at concentrations of 25-100 mug/ml. Thus, MGN-3 seems to act as a potent immunomodulator causing augmentation of NK cell activity, and with the absence of notable side-effects, MGN-3 could be used as a new biological response modifier (BRM) having possible therapeutic effects against cancer.

NK Immunomodulatory Function in 27 Cancer Patients by MGN-3, a Modified Arabinoxylane from Rice Bran (abstract).

Ghoneum, M., Namatalla, G.

Presented at the 87th Annual Meeting of the American Association for Cancer Research, Washington, D.C., April 20-24, 1996.

Dietary probiotic supplementation enhances natural killer cell activity in the elderly: an investigation of age-related immunological changes.

Gill HS, Rutherfurd KJ, Cross ML. Milk & Health Research Centre, Institute of Food, Nutrition and Human Health, Massey University, Palmerston North, New Zealand. H.S.Gill@massey.ac.nz

J Clin Immunol 2001 Jul;21(4):264-71

Many elderly subjects are at increased risk of infectious and noninfectious diseases due to an age-related decline in lymphoid cell activity (immunosenescence). Noninvasive means of enhancing cellular immunity are therefore desirable in the elderly. Previous reports have suggested that dietary supplementation could represent an effective means of enhancing the activity of circulating natural killer (NK) cells in the elderly. In the present study, we have conducted a pre-post intervention trial to determine the impact of dietary supplementation with probiotic lactic acid bacteria (LAB) on peripheral blood NK cell activity in healthy elderly subjects. Twenty-seven volunteers consumed low-fat/low-lactose milk supplemented with known immunostimulatory LAB strains (Lactobacillus rhamnosus HN001 or Bifidobacterium lactis HN019) for a period of 3 weeks. A dietary run-in of milk alone was shown to have no significant effect on NK cells. In contrast, the proportion of CD56-positive lymphocytes in peripheral circulation was higher following consumption of either LAB strain, and ex vivo PBMC tumoricidal activity against K562 cells was also increased. Supplementation with HN001 or HN019 increased tumoricidal activity by an average of 101 and 62%, respectively; these increases were significantly correlated with age, with subjects older than 70 years experiencing significantly greater improvements than those under 70 years. These results demonstrate that dietary consumption of probiotic LAB in a milk-based diet may offer benefit to elderly consumers to combat some of the deleterious effects of immunosenescence on cellular immunity.

Enhancement of immunity in the elderly by dietary supplementation with the probiotic Bifidobacterium lactis HN019.

Gill HS, Rutherfurd KJ, Cross ML, Gopal PK. Milk & Health Research Centre, Massey University, New Zealand, and the New Zealand Dairy Research Institute, Palmerston North, New Zealand.

Am J Clin Nutr 2001 Dec;74(6):833-9

BACKGROUND: The aging process can lead to a decline in cellular immunity. Therefore, the elderly could benefit from safe and effective interventions that restore cellular immune functions. OBJECTIVE: We determined whether dietary supplementation with the known immunostimulating probiotic Bifidobacterium lactis HN019 could enhance aspects of cellular immunity in elderly subjects. DESIGN: Thirty healthy elderly volunteers (age range: 63-84 y; median: 69 y) participated in a 3-stage dietary supplementation trial lasting 9 wk. During stage 1 (run-in), subjects consumed low-fat milk (200 mL twice daily for 3 wk) as a base-diet control. During stage 2 (intervention), they consumed milk supplemented with B. lactis HN019 in a typical dose (5 x 10(10) organisms/d) or a low dose (5 x 10(9) organisms/d) for 3 wk. During stage 3 (washout), they consumed low-fat milk for 3 wk. Changes in the relative proportions of leukocyte subsets and ex vivo leukocyte phagocytic and tumor-cell-killing activity were determined longitudinally by assaying peripheral blood samples. RESULTS: Increases in the proportions of total, helper (CD4(+)), and activated (CD25(+)) T lymphocytes and natural killer cells were measured in the subjects' blood after consumption of B. lactis HN019. The ex vivo phagocytic capacity of mononuclear and polymorphonuclear phagocytes and the tumoricidal activity of natural killer cells were also elevated after B. lactis HN019 consumption. The greatest changes in immunity were found in subjects who had poor pretreatment immune responses. In general, the 2 doses of B. lactis HN019 had similar effectiveness. CONCLUSION:B. lactis HN019 could be an effective probiotic dietary supplement for enhancing some aspects of cellular immunity in the elderly.

Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients: a randomized controlled trial. MIN. VIT. AOX. geriatric network.

Girodon F, Galan P, Monget AL, Boutron-Ruault MC, Brunet-Lecomte P, Preziosi P, Arnaud J, Manuguerra JC, Herchberg S. Scientific and Technical Institute for Foods and Nutrition, Conservatiore National des Arts et Mettiers, Paris, France.

Arch Intern Med. 1999 Apr 12;159(7):748-54.

BACKGROUND: Antioxidant supplementation is thought to improve immunity and thereby reduce infectious morbidity. However, few large trials in elderly people have been conducted that include end points for clinical variables. OBJECTIVE: To determine the effects of long-term daily supplementation with trace elements (zinc sulfate and selenium sulfide) or vitamins (beta carotene, ascorbic acid, and vitamin E) on immunity and the incidence of infections in institutionalized elderly people. METHODS: This randomized, double-blind, placebo-controlled intervention study included 725 institutionalized elderly patients (>65 years) from 25 geriatric centers in France. Patients received an oral daily supplement of nutritional doses of trace elements (zinc and selenium sulfide) or vitamins (beta carotene, ascorbic acid, and vitamin E) or a placebo within a 2 x 2 factorial design for 2 years. MAIN OUTCOME MEASURES: Delayed-type hypersensitivity skin response, humoral response to influenza vaccine, and infectious morbidity and mortality. RESULTS: Correction of specific nutrient deficiencies was observed after 6 months of supplementation and was maintained for the first year, during which there was no effect of any treatment on delayed-type hypersensitivity skin response. Antibody titers after influenza vaccine were higher in groups that received trace elements alone or associated with vitamins, whereas the vitamin group had significantly lower antibody titers (P<.05). The number of patients without respiratory tract infections during the study was higher in groups that received trace elements (P = .06). Supplementation with neither trace elements nor vitamins significantly reduced the incidence of urogenital infections. Survival analysis for the 2 years did not show any differences between the 4 groups. CONCLUSIONS: Low-dose supplementation of zinc and selenium provides significant improvement in elderly patients by increasing the humoral response after vaccination and could have considerable public health importance by reducing morbidity from respiratory tract infections.

Effect of micronutrient supplementation on infection in institutionalized elderly subjects: a controlled trial.

Girodon F, Lombard M, Galan P, Brunet-Lecomte P, Monget AL, Arnaud J, Preziosi P, Hercberg S. Institut Scientifique et Technique de la Nutrition et de l'Alimentation, Paris, France.

Ann Nutr Metab. 1997;41(2):98-107.

To determine the impact of a trace element and vitamin supplementation on infectious morbidity, a double-blind controlled trial was performed on 81 elderly subjects in a geriatric center during a 2-year period. Subjects were randomly assigned to one of four treatment groups, and received daily: placebo; trace elements/zinc 20 mg; selenium 100 micrograms); vitamins (vitamin C 120 mg; beta-carotene 6 mg; alpha-tocopherol 15 mg); or a combination of trace elements and vitamins at equal doses. (1) Before supplementation, low serum values in vitamin C, folate, zinc and selenium were observed in more than two thirds of the patients. (2) After 6 months of supplementation, a significant increase in vitamin and trace element serum levels was obtained in the corresponding treatment groups: a plateau was then observed for the whole study. (3) Subjects who received trace elements (zinc and selenium) alone or associated with vitamins had significantly less infectious events during the 2 years of supplementation. These results indicate that supplementation with low doses of vitamins and trace elements is able to rapidly correct corresponding deficiencies in the institutionalized elderly. Moreover, zinc and selenium reduced infectious events.

Kuby Immunology, Fourth Edition 2000.

Goldsby, R.A., Kindt, T.J., Osborne, B.A.

New York: W.H. Freeman.

Effect of antioxidative vitamins on immune function with clinical applications.

Grimble RF Institute of Human Nutrition, University of Southampton, U.K.

Int J Vitam Nutr Res (Switzerland) 1997, 67 (5) p312-20

Infection and trauma cause inflammatory stress in patients. Tissue damage, enhanced inflammatory mediator production and suppressed lymphocyte function may occur as a consequence. The antioxidative vitamins, ascorbic acid and the tocopherols, are important not only for limiting tissue damage but also in preventing increased cytokine production which is a consequence of excessive activation of NF kappa B. Glutathione is a major endogenous antioxidant and is important for lymphocyte replication. Two vitamins, vitamin B6 and riboflavin participate in the maintainance of glutathione status. The former vitamin acts as a cofactor in the synthesis of cysteine (the rate limiting precursor for glutathione biosynthesis) and the latter vitamin is a cofactor for glutathione reductase. Deficiencies in tocopherol, vitamin B6 and riboflavin reduce cell numbers in lymphoid tissues of experimental animals and produce functional abnormalities in the cell mediated immune response. Ascorbic acid and tocopherols exert anti-inflammatory effects in studies in man and animals. In humans, dietary supplementation with ascorbic acid, tocopherols and vitamin B6 enhances a number of aspects of lymphocyte function. The effect is most apparent in the elderly. (69 Refs.)

Micronutrient supplementation and immune function in the elderly

High K.P. Dr. K.P. High, Dept. of Int. Med./Infectious Dis., Wake Forest Univ. School of Medicine, 100 Medical Center Boulevard, Winston-Salem, NC 27157-1042 United States khigh@wfubmc.edu

Clinical Infectious Diseases 1999, 28/4 (717-722)

Immunologic function, particularly cell-mediated immunity, declines with age, contributing to the increased incidence of infectious diseases in the elderly. Nutrition may play a pivotal role in maintaining immune competence in older adults. Most studies to date have focused on micronutrient deficiencies and supplementation, sometimes using 'mega-dose' formulations. Multivitamin/mineral supplements or specific micronutrients such as zinc and vitamin E may be of value; however, data suggest there is likely a therapeutic range for many micronutrients, and oversupplementation may be harmful. Specific alterations of dietary lipids may also be useful for modulating immune responses in the elderly. This review summarizes the prevalence of vitamin and mineral deficiencies in older adults and highlights the outcomes of trials of micronutrient supplementation to augment immune function in the elderly.

Modulation of secretory immunoglobulin A in saliva; response to manipulation of mood.

Hucklebridge F, Lambert S, Clow A, Warburton DM, Evans PD, Sherwood N. Psychophysiology and Stress Research Group, Department of Biomedical Sciences, University of Westminster, London, UK. hucklef@wmin.ac.uk

Biol Psychol. 2000 May;53(1):25-35.

Secretory immunoglobulin A (sIgA) measured in saliva, an index of mucosal immunity, has repeatedly been shown to be sensitive to psychological variables. Chronic stress is downregulatory whereas an acute psychological challenge induces mobilisation. We examined whether an acute manipulation of mood to induce negative hedonic tone would be downregulatory, as in the chronic stress paradigm and further, whether induction of positive mood might have opposite effects. Two separate experiments were conducted. In the first, mood manipulation was by mental recall and in the second by music. For both sIgA concentration and sIgA secretion rate there was a significant elevation in response to the mood manipulation by recall regardless of hedonic tone. There was some evidence that for sIgA secretion rate the response was more pronounced for positive mood. Mood induction by music also resulted in significant elevations in sIgA concentration and secretion rate and responses were not distinguished by mood valence. None of the mood induction procedures was associated with changes in free cortisol. In these studies, we found no evidence that transient lowering of mood was downregulatory for salivary sIgA. The predominant finding was of sIgA mobilisation. [Preventive action of an immunomodulator on respiratory infections in elderly subjects] [Article in French]

Hugonot R, Gutierrez LM, Hugonot L. Hopital Necker-Enfants malades, Paris.

Presse Med. 1988 Jul 27;17(28):1445-9.

Three hundred and fourteen elderly subjects admitted to chronic medical centers were given either RU 41740 (n = 155) or a placebo (n = 159) at the rate of one course per month during three months. RU 41740 was administered in doses of 2 mg per day during 8 days in the first course and 1 mg per day during 8 days in the second and third courses. The subjects were followed up and regularly examined every three months for one year. The incidence of acute infectious episodes was evaluated in both groups. Compared to those patients who received the placebo, the number of subjects without infection was significantly higher in the treated group during the 0-6 months and the 0-9 months periods and during the 12 months of observation. The number of infectious episodes was reduced during the 0-3 months and 0-9 months periods and throughout the 12 months of the trial. The mean duration of pulmonary infections that occurred during the 0-6 and 0-9 months periods was reduced. Finally, there was a significant decrease in the duration of antibiotic therapy during the 0-3, 0-6, 0-9 months periods and during the 12 months of observation. The drug was well tolerated. This study showed that RU 41740 is effective in protecting elderly and therefore fragile subjects against respiratory infections.

Food allergy-or enterometabolic disorder?

Hunter, J.O.

Lancet 1991 Aug 24; 338(8765): 495-6.

No abstract available.

Nutritional factors in inflammatory bowel disease.

Hunter JO. Addenbrooke's Hospital, Gastroenterology Research Unit, Cambridge, UK.

Eur J Gastroenterol Hepatol. 1998 Mar;10(3):235-7.

During the past 20 years there has been growing interest in the importance of nutritional factors in the pathogenesis of inflammatory bowel disease. There are so far no definite links between ulcerative colitis and diet, but links with Crohn's disease have been studied by both epidemiologists and clinicians. Epidemiological studies, although retrospective, have suggested that patients with Crohn's disease eat more sugar and sweets that control individuals; however, when dietary sugar is restricted, there is little clinical benefit. The clinical approach to nutrition in Crohn's disease has been by the use of elemental diets, which will produce symptomatic and objective remission in up to 90% of compliant patients. Those who return to normal eating soon relapse but, in some studies, have enjoyed prolonged remission on exclusion diets. The foods excluded have been not sugar, but predominantly cereals, dairy products and yeast. Attention has now switched to the possible harmful role of fat in Crohn's disease. The efficacy of elemental feeds appears to depend not on the presentation of nitrogen but on the amount of long chain triglyceride present. Increases in recent years in the frequency of Crohn's disease in Japan have been correlated with increased dietary fat intake, and a recent study suggested that W-3 fatty acids, which are metabolized by immunomodulatory leukotrienes and prostaglandins, may have a beneficial role to play. The links between nutrition and Crohn's disease have now become strong and the role of fat may be the most exciting of all.

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