Research Database -
International Updates

Nutrition

Issue 93

HAAG, Department of Physiology, University of Pretoria, PO Box 2034, Pretoria 0001, South Africa, mhaag@medic.up.ac.za, has reviewed (99 references) essential fatty acids and the brain.
Background: The aim of the paper is to review the role of essential fatty acids in brain function and in the genesis of psychiatric disease.
Methods: An extensive literature search was performed.
Results: The fatty acid composition of the cell membranes of nerve cells in the brain reflects dietary intake of various fatty acids. The degree of desaturation of the fatty acids (ie the number of double bonds) determines the fluidity of cell membranes and thus the function of nerve cells. In addition, it is thought that n-6 polyunsaturated fatty acids give rise to prostaglandins, substances involved in inflammatory processes. A higher intake of n-6 polyunsaturates can thus lead to a higher potential for inflammatory processes to occur in the nervous system. The ratio between n-3 and n-6 polyunsaturates may influence various aspects of serotoninergic and catecholaminergic neurotransmission (ie the transmission of nerve signals involving the neurotransmitters serotonin and noradrenalin or adrenalin). Clinical trials have shown that n-3 polyunsaturated fatty acids in the diet may have a beneficial effect in the treatment of various psychiatric disorders, but data are inconclusive at present.
Conclusions: The ratio of n-3 to n-6 polyunsaturated fatty acids can be modulated by diet. This ratio influences neurotransmission and prostaglandin formation, processes that are vital in the maintenance of normal brain function.
Haag M. Essential fatty acids and the brain. Canadian Journal of Psychiatry 48 (3): 195-203, Apr 2003.
Comment: The jump between basic membrane biochemistry and psychiatric disease is quite big, and some of the assumptions underlying this article would appear rather rash.

HIBBELN and co-workers, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rochville, Maryland 20852, USA,. have investigated the influences of smoking, gender, and diet on red blood cell fatty acid composition amongst patients with schizophrenia and schizoaffective disorder.
Background: It has been found that levels of essential fatty acids are decreased among schizophrenic patients. It has been speculated that this may be related to the disease itself, but it seems equally possible that it is due to other factors. The work aimed at elucidating this question.
Methods: 72 medicated schizophrenic or schizoaffective patients were given 3 grams per day of either eicosapentaenoic acid or placebo for 16 weeks. The fatty acid composition of their red blood cell membranes was measured before and after the intervention. Current smoking status, gender, dietary survey, and symptoms of psychiatric disease were assessed.
Results: Schizophrenic patients who smoked had significantly lower levels of both docosahexaenoic and eicosapentaenoic acids (p = 0.005 and 0.05 respectively), as compared to non-smokers. Women had higher levels of these compounds than men. Non-smoking women reported higher intake of eicosapentaenoic acid than either smoking women or men.
Conclusions: Smoking status, gender, and dietary intake significantly predicted the levels of essential fatty acids found in the study population. No evidence of relationship between polyunsaturated fatty acid composition and disease subgroups or severity of disease was found. It appears that earlier reports of associations between schizophrenia and polynsaturated fatty acid levels may have been due to patients smoking and differences in dietary intake of these substances.
Hibbeln JR, Makino KK< Martin CE, Dickerson F, Boronow J, Fenton WA. Smoking, gender, and dietary influences on erythrocyte essential fatty acid composition among patients with schizophrenia or schizoaffective disorder. Biological Psychiatry 53 (5): 431-441, Mar 1, 2003.

SORENSON and co-workers, Department of Nutrition and Food Sciences, Utah State University, Logan, Utah, USA, have investigated the impact of ‘Mad Cow Disease’ publicity on meat and total vitamin A consumption in Geneva.
Background: In March 1996, revelations about the possible risk for humans of eating meat contaminated with BSE had a sudden impact on the eating habits of the European population. This study aimed at quantifying the changes in meat and nutrient intakes in Geneva, Switzerland, between 1993 and 2000.
Methods: Independent annual cross-sectional surveys were conducted among 4047 women and 4092 men. Dietary habits were assessed and compared to baseline (January 1993 – April 1996) using a semi-quantitative food frequency questionnaire.
Results: Among women, beef abstainers increased from 8.9% to 14.9% in late 1996 and to 13.3% in 1997 (p = 0.05); amongst meat-consumers, meat and beef intakes declined by 10% and 12% respectively in late 1996. Between 1997 and 2000 most intake levels drifted back towards baseline but levels of chicken consumption remained significantly higher. Similar but less dramatic changes were found among the men surveyed. From late 1996 people ate significantly less liver. The only nutrients that decreased significantly each year from 1997 through 2000 were retinol and total vitamin A (women –22% and –11% respectively; men –16% and –10% respectively; p = 0.001 and 0.05 respectively).
Conclusions: The decrease in liver and beef consumption associated with BSE has lead to a significant long-term disparity in the retinol and total vitamin A levels in the European population.
Sorenson AW, Delhumeau C, Bernstein MS, Costanza MC, Morabia A. Impact of ‘Mad Cow Disease’ publicity on trends in meat and total vitamin A consumption in Geneva between 1993 and 2000. European Journal of Clinical Nutrition 57 (1): 177-185, Jan 2003.

Issue 92

BECHOUA and colleagues, Institut National de la Santé et de la Recherche Médicale U352, Laboratoire de Biochimie et Pharmacologie, INSA-Lyon, France, have researched the influence of low amounts of marine oil on some aspects of immune function in elderly people.
Background: Ageing involves, among other processes, a decrease in antioxidant defence and immune function. n-3 polyunsaturated fatty acids have been associated with health benefits, especially in autoimmune and inflammatory processes. These effects have usually been observed with high dosages known to increase lipid peroxidation. Low doses might affect the immune system differently if lipid peroxidation were prevented. In order to study this hypothesis, the trial investigated the immune function in elderly people supplemented with low doses of marine oil, a rich source of n-3 polyunsaturates.
Methods: In this randomized, double blinded design, 20 healthy subjects were either assigned to a placebo group or a trial group. The placebo group were given 600 mg of sunflower oil per day, and the trial group were given 600 mg of marine oil containing a total of 180 mg of n-3 polyunsaturates per day, for 6 weeks. At that point, the proliferation response of lymphocytes was measured along with other biochemical markers known to be sensitive to ageing.
Results: At day 42, the proliferation response of lymphocytes was
significantly decreased in the trial group compared to baseline values (p = 0.01). Also, the activity of an enzyme called PDE was slightly lowered in cytosolic but significantly increased in particulate fractions. This went with significantly increased levels of intracellular cyclic nucleotides (p = 0.05). The activity of glutathione peroxidase was markedly and significantly depressed in the marine oil group (p = 0.01). None of these changes were found in the placebo group.
Conclusions: Collectively, these results demonstrate that even low doses of n-3 fatty acids are sufficient to affect the immune response of elderly people.
Bechoua S, Dubois M, Vericel E, Chapuy P, Lagarde M, Prigent AF. Influence of very low dietary intake of marine oil on some functional aspects of immune cells in healthy elderly people. The British Journal of Nutrition 89 (4): 523-531, Apr 2003.

OH and colleagues, Department of Head Neck/Thoracic Medical Oncology, MD Anderson Cancer Center, Houston, TX 77030, USA, ywoh@mdanderson.edu, have found that folk yoghurt kills Helicobacter pylori.
Background: The aim of the study was to evaluate a traditional yoghurt that is used as folk medicine for its ability to inactivate Helicobacter pylori in vitro.
Methods: Micro-organisms from the yoghurt were identified and tested in different culture media for their effects on H. pylori in a co-culture well system.
Results: Two yeasts and several strains of lactobacillus were isolated from the yoghurt. Both the yeast and the lactobacilli showed bactericidal activity against H.pylori. They also retained their antibacterial activity when grown in corn meal and soy milk.
Conclusions: The organisms in this yoghurt secrete soluble factors capable of killing H.pylori, the bacterium associated with stomach ulcers. Therefore these yoghurt preparations could become simple and inexpensive therapies for H.pylori infections.
Oh Y, Osato MS, Han X, Bennett G, Hong WK. Folk yoghurt kills Helicobacter pylori. Journal of Applied Microbiology 93 (6): 1083-1088, 2002.

Issue 88

CHEN and co-workers, Department of Medi, Tulane Universiy School of Medicine, New Orleans, LA, USA, assess serum antioxidant vitamins and blood pressure in the United States population.
Background: Serum vitamin C has been inversely associated with blood pressure in several epidemiological studies, but little is known about the effects of other antioxidant vitamins.
Methods: The relation between serum levels of vitamins A, C, E, alpha-carotene, and beta-carotene, and blood pressure amongst 15,317 men and women aged 20 and over who participated in the Third National Health and Nutrition Examination Survey was examined. Blood pressure was characterized as the average of 6 measurements obtained over 2 visits by trained observers, and hypertension was defined as blood pressure of 140/90 mm Hg or over, and/or taking antihypertensive medication.
Results: In multivariate models, a 1 SD difference in vitamin A and vitamin E was associated with a 43% and 18% higher odds of hypertension, respectively. A 1 SD difference in aplpha-carotene and beta-carotene was associated with a 16% and 11% lower odds of hypertension. In addition, serum vitamins A and E were positively correlated with both systolic and diastolic blood pressure, whereas alpha- and beta-carotene were inversely associated with systolic blood pressure. Vitamin C was associated with diastolic blood pressure.
Conclusions: These findings indicate that antioxidant vitamins may be important in the prevention of hypertension.
Chen J< He J, Hamm L, Batuman V, Whelton PK. Serum antioxidant vitamins and blood pressure in the United States population. Hypertension 40 (6): 810-816, Dec 2002.

DIETRICH and colleagues, School of Public Health, University of California, Berkeley 94720-7360, USA, mdietrich@uclink.berkeley.edu, found that smoking and exposure to environmental smoke decrease some plasma antioxidants and increase gamma-tocopherol.
Background: Free radicals in cigarette smoke may cause oxidative damage to macromolecules and contribute to cardiovascular disease and cancer. Decreased plasma antioxidant concentrations may indicate smoke-related oxidative stress.
Methods: Plasma samples from 83 smokers, 40 passive smokers, and 36 nonsmokers were analyzed for total ascorbic acid, alpha- and gamma-tocopherol, 5 carotenoids, retinol, and cotinine. Groups were compared using analysis of variance with adjustment for sex, age, race, body mass index, alcohol intake, triacylglycerol concentration, fruit and vegetable intakes, and idetary antioxidants.
Results: After adjustment for dietary antioxidant intake and other co-variates, smokers and passive smokers had significantly lower plasma beta-carotene concentrations than nonsmokers, and significantly higher gamma-tocopherol concentrations. Smokers had significantly lower plasma ascorbic acid and beta-cryptoxanthin concentrations than passive smokers and nonsmokers, and significantly lower concentrations of lutein and zeaxanthin than nonsmokers (all p values 0.05).
Conclusions: These results suggest that cigarette smokers and passive smokers have a significantly lower plasma antioxidant status than do nonsmokers. Further research is needed to explain why gamma-tocopherol is elevates in smokers as compared to nonsmokers.
Dietrich M, Block G, Norkus EP, Hudes M, Traber MG, Cross CE, Packer L. Smoking and exposure to environmental tobacco smoke decrease some plasma antioxidants and increase gamma-tocopherol in vivo after adjustment for dietary antioxidant intakes. American Journal of Clinical Nutrition 77 (1): 160-166, Jan 2003.

ALAN R. GABY introduces the ‘Myers’ cocktail’, an intravenous nutrient therapy.
Abstract: Building on the work of the late John Myers MD, an intravenous vitamin and mineral formula has been used for the treatment of a wide range of clinical conditions. The modified ‘Myers’ cocktail’ which consists of magnesium, calcium, B vitamins, and vitamin C, has been found to be effective against acute asthma attacks, migraine, fatigue, CFS, fibromyalgia, muscle spasms, upper respiratory tract infections, chronic sinusitis, seasonal allergic rhinitis, cardiovascular disease, and other disorders. The paper presents a rationale for the use of intravenous nutrients, reviews relevant published clinical research, describes the author’s clinical experiences, and discusses potential side effects and precautions.
Gaby AR. Intravenous nutrient therapy: the ‘Myers’ cocktail’. Alternative Medicine Review 7 (5): 389-403, Oct 2002.

Comments: The above studies demonstrate the importance of nutritional supplements in the prevention and treatment of a wide range of chronic and acute complaints.

Issue 87

O’BYRNE and others, Center for Human Nutrition and the Division of Clinical Biochemistry and Human Metabolism, Department of Pathology, University of Texas Southwestern Medical Center, Dallas USA, compared the antioxidant effects of Concord grape juice flavonoids with alpha-tocopherol on markers of oxidative stress in healthy adults.
Background: Concord grape juice is a rich source of flavonoids, which have been shown to have greater antioxidant activity than alpha-tocopherol (a form of vitamin E) in vitro. However the activities have not been compared in vivo.
Methods: 32 subjects were randomly assigned to receive either 400 IU of alpha-tocopherol per day (17 subjects) or 10 ml of Concord grape juice per kilogram of body weight per day (15 subjects) for two weeks. Serum oxygen radical absorbance capacity, plasma protein carbonyls, urinary isoprostanes, and resistance of LDL to oxidation were measured before and after that time.
Results: After supplementation, plasma alpha-tocopherol increased by 92% in subjects who had received this supplement, and plasma total and conjugated phenols increased 17% and 22% in subjects who had received grape juice. Concord grape juice was associated with significantly higher triacylglycerols than alpha-tocopherol. Both supplements increased serum oxygen radical absorbance capacity significantly, and LDL oxidation rate was significantly decreased, with no difference in effectiveness. Protein carbonyl concentration decreased 20% after grape juice supplementation, which was a significantly different response to that after alpha-tocopherol supplementation.
Conclusions: In healthy adults, 10 ml of Concord grape juice per kg of body weight per day increased serum antioxidantcapacity and protected LDL against oxidation to an extent similar to that obtained with 400 IU of alpha-tocopherol, but decreased native plasma protein oxidation significantly more than alpha-tocopherol. Concord grape juice flavonoids are potent antioxidants that may protect against oxidative stress and reduce the risk of free radical damage and chronic disease.
O’Byrne DJ, Devaraj S, Grundy SM, Jialal I. Comparison of the antioxidant effects of Concord grape juice flavonoids and alpha-tocopherol on markers of oxidative stress in healthy adults. The American Journal of Clinical Nutrition 76 (6): 1367-1374, Dec 2002.

Issue 86

BATES and colleagues, Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge UK, chris,bates@mrc-hnr.cam.ac.uk, reported on the Selenium status and associated factors in a British National Diet and Nutrition Survey amongst young people aged 4 – 18 years.

Background: The objective of the study was to provide normative reference values, and to investigate socio-demographic factors influencing Selenium status in young people.

Methods: Selenium was measured in fasting blood samples in nearly 3000 young people aged 4 – 18 years living in mainland Britain.

Results: No evidence of severe selenium deficiency was uncovered, nor of selenium toxicity. Selenium concentration in red blood cells was significantly higher in older girls. Selenium concentrations were higher in more socially advantaged children and in black and Asian children. Selenium concentrations were lower in children whose parents were smokers although not in children who themselves smoked.

Conclusions: The observed associations between selenium status and age, gender, race, social class, and parental smoking suggest that selenium concentrations are determined by a variety of complex factors that need to be controlled for when assessing selenium status in young people.

Bates CJ, Thane CW, Prentice A, Delves HT, Gregory J, et al. Selenium status and associated factors in a British National Diet and Nutrition Survey: young people aged 4 – 18 y. European Journal of Clinical Nutrition 56 (9): 873-881, Sep 2002.

Issue 85

NEUMANN describes the metabolic effects and drug interactions of grapefruit, St John’s wort, and garlic.

Results: Grapefruit, largely drunk as juice, contains vitamin C and other antioxidants (lycopene, lemonoids and naringine). It is a metabolic inhibitor of medicinal substances that constitute a target for the enzyme CYP 3A4 and glycoprotein P in enterocytes. It affects drugs with a strong intestinal metabolic first pass effect and reduces their oral bioavailability.

Comments: Treating grapefruit juice and garlic as dangerous substances is as barmy as banning parents from photographing or filming their children in their nativity plays, a ruling recently enacted by an Edinburgh school council to supposedly prevent paedophiles getting hold of the photos of videos. Is this where we are really heading – to have health warnings on all our common foods?

Issue 84

BRIGELIUS-FLOHE and colleagues, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany, flohe@dife.de, review (157 references) the European perspective on vitamin E.

Background: Vitamin E was first described as an essential factor for female reproduction in rats. In humans, deficiencies in vitamin E lead primarily to neurological dysfunctions via molecular mechanisms that are unclear. Because of its antioxidative properties, it is believed that vitamin E could help prevent diseases associated with increased oxidative stress such as cardiovascular diseases, cancer, chronic inflammation, and neurological disorders. However clinical trials fail to demonstrate a consistent benefit. Given these findings, a group of scientists met to analyze the most recent knowledge of vitamin E function and metabolism.

Results: Mechanisms of absorption, distribution, and metabolism of different forms of vitamin E are discussed. Included are the mechanisms of tocopherol side-chain degradation and its putative interaction with drug metabolism, the usefulness of tocopherol metabolites as biomarkers, and novel mechanisms of the anti-atherosclerotic and anticarcinogenic properties of vitamin E. Clinical trials are analyzed on the basis of subject selection, disease stages, and the mode of intake, dosage, and chemical form of vitamin E.

Conclusions: The authors conclude that the functions of vitamin E are underestimated if only its antioxidative properties are considered. Future research should focus on what makes this component essential for humans, why the body apparently has a preference for utilizing alpha-tocopherol, and what functions others forms of vitamin E may have.

Brigelius-Flohe R, Kelly F, Salonon JT, Neuzil J, Zingg JM, Azzi A. The European perspective on vitamin E: current knowledge and future research. The American Journal of Clinical Nutrition 76 (4): 703-716, Oct 2002.

PLEINER and co-workers, Department of Clinical Pharmacology, University of Vienna, Austria, find that high doses of vitamin C reverse endotoxin-induced hyporeactivity to acetylcholine in the forearm.

Background: Acute inflammation causes endothelial vasodilator dysfunction that may be mediated by oxidative stress and thus susceptible to vitamin C.

Methods: Randomized, double-blinded crossover study on 8 healthy volunteers. Blood flow responses to acetylcholine (which is endothelium-dependent) and to glyceryl trinitrate (which is endothelium- independent) in the forearm were assessed before and after inducing acute inflammation by low doses of Escherichia coli endotoxin (LPS). The effect of intra-arterial vitamin C at a rate of 24 mg/min or placebo was studied 4 hours after LPS administration. In control experiments, vitamin C was administered without the previous LPS.

Results: LPS caused systemic vasodilation, increased white blood cell count, elevated body temperature, and reduced plasma vitamin C concentrations. The endotoxin decreased the responses of forearm blood flow to acetylcholine by 30% but not to glyceryl trinitride. Vitamin C completely restored the response to acetylcholine, bringing it back to levels comparable to baseline. There was no effect of vitamin C on baseline blood flow or acetylcholine- or glyceryl trinitrate-induced vasodilation in control subjects.

Conclusions: The data demonstrate that impaired endothelial vasodilation caused by E.coli endotoxemia can be counteracted by high doses of antioxidant in vivo. Oxidative stress may therefore play an important role in the pathogenesis of endothelial dysfunction during inflammation.

Pleiner J, Mittermayer F, Schaller G, MacAllister RJ, Wolzt M. High doses of vitamin C reverse E.coli endotoxin-induced hyporeactivity to acetylcholine in the human forearm. Circulation 106 (12): 1460-1464, Sep 2002.

Issue 83

THOMPSON et al., Department of Dport and Exercise Scicne at the University of Taths, UK, investigated prolonged vitamin C supplementation and recovery from demanding exercise.

Background: The aim of this study was to assess whether 2 weeks of vitamin C supplementation affects the recovery from bouts of unaccustomed exertion.

Methods: 16 male volunteers were allocated into placebo or vitamin C group (8 each). The treatment group consumed 2 x 200 mg of vitamin C daily for 2 weeks, and the placebo group consumed the same amount of lactose. Subjects performed a 90 minute shuttle-running test. Post-exercise serum creatine kinase activities, plasma malondialdehyde, plasma interleukin-6, and myoglobin concentrations were measured, as well as muscle soreness and muscle fatigue.

Results: Serum creatine kinase activity and myoglobin concentrations were unaffected, but malondialdehyde, muscle soreness and muscle fatigue were modestly improved by vitamin C. Moreover, although interleukin-6 levels increased in both groups immediately after exercise, the vitamin C group sustained a higher level two hours after exercise.

Conclusions: Vitamin C supplementation may have some modest beneficial effects on recovery from unaccustomed exercise.

Background: Anecdotal evidence of vitamin C as a cure and/or prevention for colds has been well-known to the general public since Linus Pauling popularized his own experience.

Methods: 168 volunteers were randomized to receive 2 daily vitamin C tablets of unspecified dose or 2 placebo tablets over the period from November to February. They filled in daily protocols of their health on a five-point scale and recorded incidences of colds.

Results: Subjects in the experimental group had fewer colds (p = 0.05), fewer days ‘challenged virally’ and shorter duration of symptoms (1.8 vs. 3.1 days, p = 0.03). Few side effects occurred with the active treatment.

Conclusions: The vitamin C preparation tested here (about which we are not informed) appears to be effective in the prevention and treatment of common colds and well received by the test subjects.

Issue 82

BECK, Department of Pediatrics, University of North Carolina at Chapel Hill, 27599-7220, USA, melinda_beck@unc.edu, reviewed (18 references) the effects of nutritional deficiency on immune system responses to infection and also discussed evidence for additional direct effects on viruses themselves.

Background: Malnutrition is associated with increased susceptibility to infection, thought to be a result of impaired immune function. However, the author and her fellow researchers have found that nutritional deficiency also affects the activity of infectious microorganisms invading malnourished individuals.

Discussion: The researchers looked at the specific case of selenium (Se) deficiency and found that mice deficient in Se were more susceptible to both coxackievirus and influenza virus. Those mice infected with a normally harmless strain of coxackievirus developed myocarditis. Similarly, Se-deficient mice infected with a mild strain of influenza virus developed severe pneumonitis. Glutathione peroxidase knockout mice also developed myocarditis after being infected with a normally harmless viral strain, indicating that the antioxidant selenoenzyme glutathione peroxidase-1 was critical in the normal (successful) battle against viral infection. The researchers sequenced viral samples isolated from Se-deficient mice and found mutations in the viral genomes of both coxackievirus and influenza virus that indicated increased virulence of the microorganisms.

Conclusion: The nutritional status of an individual is important not only for ensuring an optimal response of the immune system to an invading virus, but also in preventing viral mutations that can lead to increased pathogenicity of the virus itself.

Issue 81

TSOURELI-NIKITA and colleagues, Institute of Dermosciences, University of Siena, Siena, Italy, tlotti@unifi.it, examined the effects of vitamin E supplementation on symptoms and blood immunoglobulin E (IgE) levels in subjects with atopic dermatitis.
Background: The antioxidant vitamin alpha-tocopherol (vitamin E) can boost immune function and modify inflammatory and allergic immune responses. IgE levels are a characteristic marker of allergic activity and susceptibility in atopic individuals.
Methods: Subjects were 96 individuals suffering from atopic dermatitis. In a randomized, placebo-controlled, single-blind study, subjects received daily supplementation with either 400 IU vitamin E of natural origin (n=50) or placebo supplements (n=46) for 8 months. The researchers made the following measurements at baseline and every 15 days during the study: complete blood count, serum IgE levels, radioallergosorbent (RAST) score, antinuclear antibodies (ANA) and biochemical analyses. Effects on symptoms were evaluated from a questionnaire completed by the subjects at the end of the study.
Results: Of the 50 patients in the vitamin E group, 23 (46%) showed ‘great improvement’ in their symptoms and seven (14%) had almost complete remission of their dermatitis; this compared with only one of the 46 patients in the placebo group (2.2%) who showed ‘great improvement’ and none displaying complete remission. 10 (20%) patients in the vitamin E group versus four (8.7%) in the placebo group showed ‘slight improvement’, six versus five showed ‘no change’, and only four (8%) in the vitamin E group worsened compared with 36 (78.3%) in the placebo group. Less progression of atopic dermatitis occurred among females compared with males, and more females (five versus two) showed almost complete remission. Serum IgE levels varied greatly over the 8 months of the study, from 1005-490 IU/ml and 1239-812 IU/ml in the vitamin E and placebo groups respectively. In subjects in the vitamin E group who showed great improvement or near remission of atopic dermatitis, serum IgE levels decreased by 62% from baseline; in similar subjects in the placebo group, IgE levels decreased by 34.4%. No complications or adverse events were reported in either treatment group. Improvements in dermatitis included: remarkable improvements in facial redness and scaling, reduced itching (resulting in healing of lesions) and increased appearance of ‘normal’ skin.
Conclusion: The results demonstrated associations between vitamin E intake, IgE levels and signs and symptoms of atopic dermatitis and suggest that vitamin E may be an extremely beneficial treatment for the condition.
Tsoureli-Nikita E et al. Evaluation of dietary intake of vitamin E in the treatment of atopic dermatitis: a study of the clinical course and evaluation of the immunoglobulin E serum levels. International Journal of Dermatology 41 (3): 146-50. Mar 2002.
Comment: The results of the above research are extremely encouraging, especially since conditions such as dermatitis are both extremely distressing as well as intractable to many conventional and alternative treatment approaches. For a graphic description of the agonies of eczema, readers are urged to read the feature by Jennifer Worth on page 34.

THE MRC/BHF HEART PROTECTION STUDY COLLABORATIVE GROUP investigated possible long-term (5-year) effects of daily antioxidant vitamin supplementation on adults with cardiovascular disease or diabetes.
Background: Some have suggested that increased consumption of antioxidant vitamins may reduce the occurrence of cardiovascular disease, cancer and other serious illnesses or life-threatening clinical events.
Methods: This large, long-term, multicentre, randomized, placebo- controlled clinical trial involved 20,536 adults aged 40-80 years with coronary artery disease, other forms of occlusive artery disease or diabetes. Subjects were randomly assigned to receive: 1) dietary supplementation with antioxidant vitamins (600 mg vitamin E, 250 mg vitamin C and 20 mg beta-carotene daily); or 2) matching placebo over a period of 5 years. Outcome measures were the occurrence of major coronary events and fatal or non-fatal vascular events. Results were analysed on an intention-to-treat basis.
Results: 83% (average) of subjects in either group remained compliant with treatment during the study. In the vitamin-supplemented group, plasma concentrations of vitamin E (alpha-tocopherol) doubled, vitamin C levels increased by a third and those of beta-carotene increased four-fold. At the end of the study period, no significant differences between the vitamin-supplemented and placebo groups were detected with regard to all-cause mortality (14.1% in the vitamin group, 13.5% in the placebo group) or deaths due to vascular (8.6% versus 8.2%) or non-vascular (5.5% versus 5.3%) causes. Similar numbers of subjects in either group had a non-fatal myocardial infarction or died due to coronary occlusion (10.4% versus 10.2%), had a non-fatal or fatal stroke (5.0% in both groups) or underwent coronary or non-coronary revascularization (10.3% versus 10.6%). There were no differences between the two groups in the first occurrence of any of these “major vascular events” either overall (22.5% in both groups; event rate ratio 1.00) or according to subcategory analysis (fatal or non-fatal vascular events). No differences were detected between the two groups with regard to incidence of cancer or hospitalization for any other non-vascular event.
Conclusion: Supplementation with antioxidant vitamins in this large group of high-risk individuals appeared to be safe and substantially increased blood levels of the vitamins. However, long-term supplementation with antioxidant vitamins had no significant effects on 5-year mortality rates or incidence of vascular events, cancer or any other major outcome.
The Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360 (9326): 23-33. Jul 2002.

Comment: I for one would have been astonished if the dosages prescribed in this study, particularly 250 mg vitamin C, would have produced a significant difference in fatal or non-fatal vascular events for individuals already suffering serious coronary artery disease, other arterial diseases or diabetes. In order to treat serious illness such as cancer or heart disease with a vitamin such as vitamin C, dosages would usually have to be in the therapeutic range of possibly 3-10 g. See also detailed information in letters.

Issue 80

MUNOZ and colleagues, Center for Dental Research, Loma Linda University, School of Dentistry, Loma Linda, California, USA, investigated the effects of dietary supplementation with particular nutrients on gingivitis (inflammation of the gums) and other indicators of gingival/periodontal health in patients with periodontal disease.
Background: The benefits of nutritional supplements are frequently overlooked when recommendations are given for preserving healthy teeth and gums.
Methods: This was a 60-day, randomized, placebo-controlled, parallel-group clinical study involving 63 patients with Type II periodontal disease. Subjects received (as an adjunct to home care) either a twice-daily vitamin tablet containing seven active ingredients (comprising certain nutritional and plant-derived nutraceuticals) or a twice-daily placebo tablet. Gingival index (GI; an indicator of gingivitis), bleeding index (BI), periodontal pocket (probing) depth (PD) and attachment levels (AL) were measured at baseline and after 60 days of treatment.
Results: The vitamin-supplemented group showed clinically significant reductions in GI, BI and PD after 60 days of treatment (p<0.0001) compared with no such reductions in the placebo group. There were no significant changes in AL in either group. For patients in the vitamin-treated group with PD 4 mm, clinically significant improvements in PD and GI from baseline to 60 days were seen, but no changes in BI or AL. Data obtained for men and women were similar.
Conclusion: The findings suggest that the established periodontal treatment programme could be improved by including multivitamin/ nutrient supplementation.
Munoz CA et al. Effects of a nutritional supplement on periodontal status. Compendium of Continuing Education in Dentistry 22 (5): 425-8. May 2001.

MORCOS and CAMILO, Department of Medicine, Division of Cardiology, University of California, Irvine, California, USA, investigated possible toxic effects of long-term dietary intake of a combination of fish oil (omega-3 fatty acid) and garlic food supplements in rats.
Background: Dietary supplementation with fish oil and/or garlic are now well recognized as having beneficial effects on blood lipid levels. However, formal evaluation of any potential toxic effects of the combination on organ structures and functions have not been performed.
Methods: The study was a double-blind, placebo-controlled trial carried out on 28 Sprague-Dawley rats. Over a period of 12 months, the rats were fed 1) a ‘lab chow’ diet supplemented with the equivalent of 3x the maximum recommended human daily (body-weight-adjusted) dosage of fish oil and the usual recommended daily dosage of garlic (the US Food and Drug Administration [FDA] recommends a maximum daily dose of 3 g omega-3 fatty acids and a usual daily dose of 1200 mg of garlic for a 70-kg human); or 2) a placebo-supplemented lab chow diet. The animals were evaluated at baseline and at 2, 6 and 12 months.
Results: As would be expected, the fish oil/garlic-supplemented group exhibited lower blood levels of triglycerides, total cholesterol and low-density lipoprotein (LDL) during the acute phase (early time points) of the study. Over the course of the study, no differences were found between the supplemented and placebo groups with regard to external appearance, activity levels, daily food consumption, blood cell counts, kidney function, thyroid function, prothrombin time (PT) or activated partial prothrombin time (PPT), and no structural changes in organs were detected. At the end of the study, supplemented rats still showed lowered triglyceride and LDL levels, but total cholesterol and high- density lipoprotein (HDL) levels had become elevated.
Conclusion: No toxic effects on organ structure or function were seen due to chronic supplementation with fish oil and garlic, but some altered metabolic activities were apparent. The researchers report that the elevations in total cholesterol and HDL levels during the chronic toxicity period occur simultaneously with elevations in plasma levels of the liver enzymes ALT and AST, which are not involved in cholesterol synthesis. From this, they suggest that levels of liver enzymes that are involved in cholesterol synthesis (such as HMG-CoA reductase) may similarly become elevated (‘escape suppression’) during chronic toxicity.
Morcos NC, Camilo K. Acute and chronic toxicity study of fish oil and garlic combination. International Journal of Vitamin and Nutrition Research 71 (5): 306-12. Sep 2001.

RUHE and MCDONALD, Department of Nutrition, University of California, Davis 95616-8669, USA, reviewed (44 references) literature on the frequency, causal factors and treatment, including the possible role of dietary antioxidants, of type II diabetes (non-insulin-dependent diabetes mellitus, NIDDM).
Background: The incidence of NIDDM worldwide continues to increase. In 1997, there were 143 million cases of diabetes, and the World Health Organization (WHO) has predicted that this will double by 2025 to around 300 million. Economically developed nations have the highest incidence of NIDDM. In the USA, approximately 6.5% of the population (17 million individuals) are estimated to have diagnosed or undiagnosed diabetes. Obesity and physical inactivity are the most important contributory factors in the development of NIDDM. Cardiovascular disease, caused by degenerative processes occurring on macro- and microvascular levels, is the major cause of death and disability/disease severity in individuals with NIDDM. Evidence suggests that it should be possible to prevent 65-75% of cases of diabetes developing, at least among Caucasians, if such individuals stayed below their ideal weight, and current management of NIDDM is therefore mainly aimed at weight reduction. However, this approach has achieved, at best, only modest success. Some research suggests that dietary antioxidants may be able to help slow the progression of NIDDM, which may be an alternative or adjunctive approach to treatment until a definitive cure for the disease is uncovered. The findings of a number of experimental studies indicate that dietary supplementation with vitamin E and lipoic acid can reduce the effects of the oxidative damage that occurs in NIDDM as a result of disturbed glucose metabolism.
Discussion: The reviewers discuss the incidence and cause(s) of and therapeutic options for NIDDM and examine the possible benefit of dietary antioxidant supplementation in the management of the disease.
Ruhe RC, McDonald RB. Use of antioxidant nutrients in the prevention and treatment of type 2 diabetes. Journal of the American College of Nutrition 20 (5 Suppl): 363S-9S; discussion: 381S-3S. Oct 2001.

Comment: It seems incredible that these researchers can’t even imagine that diet, i.e. what individuals eat, rather than just weight control, could possibly play a role in the development of type II diabetes. Could it possibly be that people are consuming too much sugar, alcohol, trans fatty acids and other junk foods, which, over several decades, overload the exquisitely balanced insulin hormonal system, leading to insulin resistance, or Syndrome X? All that they seem to be able to postulate is that weight reduction and physical activity, and possibly antioxidant supplementation might do the trick until a cure is developed.

Issue 79

WAGNER and colleagues, Institute of Nutritional Sciences, University of Vienna, Austria, karl-heinz.wagner@univie.ac.at, investigated the effects of dietary supplementation with oil rich in polyunsaturated fatty acids (PUFAs) in comparison with dietary supplementation with an oil mixture rich in saturated (SFAs), monounsaturated (MUFAs) and polyunsaturated fatty acids on blood fatty acid levels.
Background: Results from previous studies comparing effects of SFAs, MUFAs and PUFAs and their combinations have been contradictory.
Methods: This was a double-blind, randomized, comparative, cross-over design study in 28 healthy male non-smokers aged 19-31 years. Dietary supplementation with two types of oils were compared: 1) an olive oil/sunflower oil mixture containing a high level of oleic acid and a moderate level of PUFAs (ratios of SFAs:MUFAs:PUFAs = 14:69:17) (‘M-rich’); 2) a single PUFA-rich corn oil (SFAs:MUFAs:PUFAs = 13:33:54) (‘P-rich’). The subjects entered a 2-week baseline period during which they consumed a mixed balanced diet (average calories 11.6 MJ, average fat 105 g/day). This was followed by a 2-week study period when they consumed a diet supplemented with either the P-rich oil (80 g corn oil/day) or the M-rich oil (68 g olive oil + 12 g sunflower oil/day) as the main fat source. Subjects were then crossed over to the opposite oil- supplemented diet for a further 2 weeks. Dietary compliance was confirmed by measuring fatty acid compositions of plasma low-density lipoproteins (LDLs) and levels of alpha- and gamma-tocopherol in plasma and plasma LDLs. The researchers investigated the effects of the dietary supplementations on plasma levels of LDL-cholesterol, high density lipoproteins (HDLs), HDL-cholesterol, very low-density lipoprotein (VLDL)-triglycerides, total triglycerides and total cholesterol.
Results: There were significant changes in plasma LDL and tocopherols and LDL-tocopherols and significant changes in the average ratio of oleic to linoleic acids in LDL, confirming that the dietary lipids were well incorporated. The P-rich diet significantly reduced LDL-cholesterol after the first 2-week study period and showed a similar but less pronounced (non-significant) trend after the cross-over study period. The P-rich diet reduced total triglyceride levels and VLDL-triglyceride levels to a significantly greater extent than the M-rich diet after the first 2-week study period and similarly reduced total cholesterol levels after the cross-over study period. Neither diet affected total HDL and HDL-cholesterol levels.
Conclusion: The PUFA-rich diet had a greater influence on lipoprotein metabolism than the MUFA-rich diet. The cholesterol-lowering effect of the PUFA-rich diet is likely to be related to its high content of unsaponifiable (non-hydrolysable) substances, mainly phytosterols in the corn oil.
Wagner KH et al. Impact of diets containing corn oil or olive/sunflower oil mixture on the human plasma and lipoprotein lipid metabolism. European Journal of Nutrition 40 (4): 161-7. Aug 2001.

VAN HOYDONCK and colleagues, Department of Public Health, Division of Nutritional Epidemiology, University of Leuven, 3000 Leuven, Belgium, Pascale.vanhoydonck@med.kuleuven.ac.be, investigated whether the oxidative balance of dietary constituents was related to risk of death in male Belgian smokers.
Methods: The researchers calculated an oxidative balance score that took into account dietary intakes of antioxidant vitamins (beta-carotene and vitamin C) and iron (a pro-oxidant). According to these scores, subjects were divided into two groups: 1) a low oxidative balance score group, which included subjects who consumed high levels of vitamin C and beta-carotene and/or low levels of iron; and 2) a high oxidative balance score group, which included subjects consuming low levels of vitamin C and beta-carotene and/or high levels of iron. Subjects were 2814 male smokers who had taken part in the Belgian Interuniversity Research on Nutrition and Health (BIRNH) Study. The investigators used the 10-year follow-up mortality data from this study to explore the association of the oxidative balance score with deaths due to any cause, deaths due to cardiovascular disease (CVD) and total deaths due to cancer.
Results: Male smokers with the highest oxidative balance scores had a higher relative risk (RR) of all-cause (1.44) and total cancer death (1.62;) compared with subjects with the lowest scores. There was a less pronounced, non-significant association for risk of CVD death (1.31). The data suggested a threshold risk for all-cause and total cancer death rather than a linear relationship.
Conclusion: The findings indicate that the oxidative balance of the diet is linked to subsequent death. For smokers who consume a diet with a high oxidative balance, it may be prudent to recommend consumption of higher levels of fresh fruit and vegetables and lower levels of meat.
Van Hoydonck PGA et al. A dietary oxidative balance score of vitamin C, beta-carotene and iron intakes and mortality risk in male smoking Belgians. The Journal of Nutrition 132 (4): 756-61. Apr 2002.

Comment: Surely smokers should stop smoking, which would reduce their risk of death to both heart disease and cancer.

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