Research Database -
International Updates

Nutrition

Issue 77

SCHUENEMANN and colleagues, Department of Medicine, School of Medicine and Biomedical Sciences, State University of New York, 207 Farber Hall, 3435 Main Street, Buffalo, NY 14214-3000, USA, HJS@buffalo.edu, studied the possible relationships of a number of dietary carotenoids and vitamins C and E with lung function and respiratory health.
Background: There is an increasing body of data to indicate a positive correlation between dietary antioxidant vitamins and lung function. However, dietary carotenoids other than beta-carotene have been little studied in this regard.
Methods: The study was carried out from 1995 to 1998. Subjects were a random sample of 1,616 men and women resident in western New York State, aged 35-79 years, who had no respiratory disease. Study measurements of lung function were forced expiratory volume in 1 second and forced vital capacity, both as the percentage of the predicted value (FEV1% and FVC% respectively). Intakes of a range of carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin and lycopene) and vitamins C and E were also recorded. Possible associations between lung function measures and antioxidant vitamin intakes were explored after adjusting the data for height, age, gender, race, total energy intake, smoking and other possible influences.
Results: There were significant correlations of lutein/zeaxanthin, vitamin C and vitamin E with FEV1% and FVC% (analysed by multiple linear regression). Analysis of all of the antioxidant vitamins simultaneously revealed that the strongest associations were between vitamin E and FEV1% and between lutein/zeaxanthin and FVC%. Decreases of 1 standard deviation (SD) of dietary vitamin E or lutein/zeaxanthin were associated with differences in FEV1 and FVC that were equivalent to about 1-2 years of ageing.
Conclusion: The results indicate that dietary carotenoids, including those other than beta-carotene, and vitamins C and E may contribute to respiratory health.
Schuenemann HJ et al. Lung function in relation to intake of carotenoids and other antioxidant vitamins in a population-based study. American Journal of Epidemiology 155 (5): 463-71. Mar 2002.

Comment: Another strong reason for resisting the EU Supplement Directive to water down antioxidant dosages.

Issue 76

MESSERER and colleagues, Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden, Maria.Messerer@mep.ki.se, investigated what subgroups of Swedish adults used dietary supplements and natural remedies.
Background: In 1996/1997, Statistics Sweden conducted a cross-sectional survey, in which participants, in face-to-face interviews, reported on their consumption of dietary supplements and natural remedies in the previous 2 weeks. The authors used findings from this survey for their analyses.
Methods: The study involved a nationally (Swedish) representative sample of 11,422 adults (5,596 men, 5,826 women) aged 16 to 84 years. 78% of people approached responded to the survey questions.
Results: Dietary supplements were reportedly used by 33% of women and 22% of men; natural remedies were used by 14% and 7% respectively. Use of dietary supplements and natural remedies was best predicted by age, sex and subjective health. Women and older people were more likely to be users. Obese men and women used dietary supplements less than underweight individuals. Subjective health was related to use among men: those reporting excellent health were less likely to use supplements/natural remedies than those reporting poor health; this association was weaker among women. Men who regularly carried out moderate/heavy exercise were significantly more frequent users of dietary supplements and natural remedies than those who reported little or no exercise; women moderate/heavy exercisers also used natural remedies, but not dietary supplements, significantly more frequently.
Conclusion: A third of women and more than a fifth of men use dietary supplements. Use of natural remedies is lower, at 7-14%. Use of dietary supplements and/or natural remedies is associated with several sociodemographic and health behaviour factors, such as female sex, older age, being underweight, having [subjectively] poor health, and taking regular moderate/heavy exercise.
Messerer M et al. Sociodemographic and health behaviour factors among dietary supplement and natural remedy users. European Journal of Clinical Nutrition 55 (12): 1104-10. Dec 2001.

HERRERA and BARBAS, Facultad de Ciencias Experimentales y Tecnicas, Universidad San Pablo-CEU, Madrid, Spain, eherrera@ceu.es, reviewed (91 references) the actions, biochemistry and metabolism of vitamin E.
Background: Naturally occurring vitamin E contains 4 tocopherols and 4 tocotrienols. The most common form found in nature is RRR-alpha-tocopherol, which has the highest biological activity. Vitamin E is the main lipid-soluble antioxidant found in the human body; however, not all its actions can be ascribed to its antioxidant effects.
Discussion: Vitamin E’s antioxidant properties prevent the propagation of free radical reactions in cells membranes. Vitamin E also has pro-oxidant activity. Reaction between the alpha-tocopherol radical and other free radicals results in the formation of non-radical oxidation products; these are conjugated to glucuronic acid and excreted in the bile or urine. In the blood stream, vitamin E is transported in plasma lipoproteins. After consumption, vitamin E is packaged into chylomicrons in the intestines and these are absorbed into the lymphatic system and eventually secreted into the systemic circulation. Some of the tocopherols transported in chylomicrons are taken up by extrahepatic tissues under the action of lipoprotein lipase (LPL). The remaining tocopherols in chylomicrons are transported to the liver, where ‘alpha-tocopherol transfer protein’ acts on them to incorporate a major proportion of alpha-tocopherol into nascent very low-density lipoproteins (VLDLs). After secretion into the blood stream, LPL converts VLDLs into intermediate-density lipoproteins (IDLs) and low-density lipoproteins (LDLs); excess surface components, including alpha- tocopherol, are transferred to high-density lipoproteins (HDLs). Some extrahepatic tissues take up alpha-tocopherol in the form of various lipoproteins via specific cell membrane receptors. Excess alpha- tocopherol and other forms of vitamin E are excreted in the bile.
Conclusions: We now know a great deal about the actions, effects and metabolism of vitamin E, although several questions still remain. For example, an understanding of how it interacts with other antioxidants may explain why foods that contain small amounts of vitamin E are more beneficial than large doses of vitamin E taken alone.
Herrera E, Barbas C. Vitamin E: action, metabolism and perspectives. Journal of Physiology and Biochemistry 57 (1): 43-56. Mar 2001.

PANDA and colleagues, Department of Biochemistry, Calcutta University College of Science, 700019, Calcutta, India, panda@ccf.org, analysed the stable oxidant components of cigarette smoke that are responsible for the breakdown of plasma, lung and heart proteins.
Background: The authors have previously reported that whole-phase cigarette smoke (CS) contains stable oxidants that cause oxidative damage and increased breakdown of protein (Free Radic. Biol. Med. 27: 1064. 1999). These effects have been shown to be completely prevented by ascorbic acid and partly prevented by glutathione.
Results: The results of the present study demonstrated that the stable oxidants in whole-phase CS are found exclusively in the tar phase. These oxidants could almost totally account for whole-phase CS-induced oxidation of human plasma proteins and also the oxidative breakdown of microsomal proteins in guinea pig lung and heart. Tar phase CS-induced breakdown of microsomal proteins involves: 1) oxidation of the proteins by oxidants in the tar extract; then 2) rapid breakdown of the oxidized proteins by microsomal proteases. The oxidation and proteolysis caused by the oxidants of the tar phase CS could be completely prevented by ascorbic acid and partially prevented by glutathione, as evidenced by the formation of protein carbonyl and bityrosine and loss of tryptophan residues and thiol groups. Other antioxidants, such as superoxide dismutase, catalase, vitamin E, beta-carotene and mannitol, could not prevent the protein damage.
Conclusions: Adequate intake of vitamin C may help smokers avoid CS-induced oxidative damage. The specific role of the tar phase in CS-induced oxidative damage emphasizes the need for more effective cigarette filters.
Panda K et al. Cigarette smoke-induced protein oxidation and proteolysis is exclusively caused by its tar phase: prevention by vitamin C. Toxicology Letters 123 (1): 21-32. Aug 2001.

Issue 75

NIETO and colleagues, Department of Biochemistry and Molecular Biology, University of Granada, 18071 Granada, Spain, investigated whether consumption of monounsaturated (MUFAs) and/or polyunsaturated fatty acids (PUFAs) of the n-3 and n-6 series could help repair intestinal damage and reduce inflammation in an experimental model of ulcerative colitis (UC).
Methods: 2,4,6-trinitrobenzenesulfonic acid-treated rats were fed diets enriched in olive oil (OO), fish oil (FO) or purified pig brain phospholipids (BPL) for 1 or 2 weeks. The investigators assessed colonic damage macroscopically and microscopically. They analysed ultrastructural and histological changes and also measured plasma and colonic mucosal fatty acid profiles and some biochemical markers of injury and inflammation.
Results: Plasma and mucosa fatty acid profiles were broadly similar to dietary profiles. OO-fed rats with UC had higher plasma MUFA proportions compared with those fed FO or BPL for 1 or 2 weeks. FO-fed rats with UC had higher [plasma] n-3 long-chain PUFA [proportions] than those fed OO or BPL. After 1 week, FO-fed rats with UC had lower MUFA mucosa levels and higher n-3 long-chain PUFA levels than those fed OO or BPL, had lower alkaline phosphatase (AP) and mieloperoxidase (MPO) activities and prostaglandin E(2) (PGE[2]) levels, and showed less macroscopic and microscopic colonic damage, fewer necrotic areas within the mucosa, more goblet cells with mature mucin granules, and enhanced histological repair.
Conclusion: The findings suggest that a balanced diet containing n-3 long-chain PUFAs could reduce inflammation and mucosal damage in UC.
Nieto N et al. Dietary polyunsaturated fatty acids improve histological and biochemical alterations in rats with experimental ulcerative colitis. The Journal of Nutrition 132 (1): 11-9. Jan 2002.
Comment: For sufferers of ulcerative colitis, the above research may be of inestimable benefit, i.e. that omega-3 PUFAs may help to reduce inflammation and damage.

SAURAT, Department of Dermatology, University Hospital and DHURDV, Geneva CH, Switzerland, analysed the effects of UV on epidermal stores of vitamin A and substances involved in its activity, storage, activation and protection.
Background: Significant amounts of vitamin A are stored in the human epidermis, along with enzymes involved in its storage or activation, protective binding proteins, transport molecules, and nuclear receptors involved in vitamin A-induced gene activity modulation. Vitamin A absorbs in the UV B range, so the vitamin A system may undergo marked alterations on exposure to UV light.
Methods: The investigators carried out studies to examine the effects of UV on epidermal stores of vitamin A (retinol and retinyl esters), its enzymes and binding proteins, and some relevant biological parameters (e.g. expression of apoptosis transcription factors (cJun) and thymine dimers).
Discussion: The available data indicate that the vitamin A system is a direct target of both UV A and UV B. The system seems to be involved in an adaptive response to UV exposure. Further studies are needed to uncover the details of the physiological role of this adaptive response in acute and chronic sun exposure. Targeting UV-induced vitamin A deficiency is a new concept for investigation in the prevention of skin cancer and ageing.
Saurat JH. Skin, sun, and vitamin A: from aging to cancer. The Journal of Dermatology 28 (11): 595-8. Nov 2001.

Issue 74

GRAHN and colleagues, Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada, Bruce.Grahn@usask.ca, reviewed (165 references) literature concerning the importance of zinc (Zn) and Zn deficiency in normal ocular function and chronic eye diseases respectively.
Background: The trace element zinc (Zn), which influences cell metabolism through a variety of mechanisms, appears to be vital for maintaining normal ocular function. Ocular tissues, particularly the retina and choroid, contain high concentrations of Zn. In a number of species, Zn deficiency has been shown to result in gross, ultrastructural and electrophysiological ocular manifestations. The physiological functions of Zn have been studied mainly in retina and retinal pigment epithelium, where Zn is believed to: interact with taurine and vitamin A; modify photoreceptor plasma membranes; regulate the light-rhodopsin reaction; modulate synaptic transmission; and serve as an antioxidant.
Discussion: Suboptimal Zn status in N. America may influence the development and progression of several chronic eye diseases; however, results of Zn supplementation trials and epidemiological studies have been conflicting with regard to Zn’s role in aged-related macular degeneration. Further well- controlled supplementation trials are needed to clarify the role of Zn in this disease. Research is also needed to further explore the mechanisms by which Zn regulates ocular morphology and function.
Grahn BH et al. Zinc and the eye. Journal of the American College of Nutrition 20 (2 Suppl): 106-18. Apr 2001.

Issue 73

TIDOW-KEBRITCHI and MOBARHAN, Loyola University Medical Center, Maywood, IL 60153, USA, reviewed (19 references) the possible relevance of adding vitamin E to polyunsaturated fatty acid supplementation in the treatment of patients with rheumatoid arthritis (RA).
Discussion: Animal, tissue culture and human studies have evaluated the effects of fish oil supplementation in patients with RA over the last two decades. These studies have clearly shown potentially beneficial changes in cytokine and eicosanoid metabolism. The overall clinical improvement, however, has been only moderate. European trials have shown significant pain reduction in patients with RA treated with vitamin E. A recent study in RA-prone mice evaluated the effects of vitamin E in addition to omega-3 and omega-6 fatty acids on cytokine and eicosanoid production; the authors [of this study] suggested that vitamin E might have an additional positive effect on autoimmune disease by decreasing proinflammatory cytokines and lipid mediators. The authors of the present article pose the questions: Is this information ultimately important in terms of dietary advice for patients with RA? Are further clinical trials indicated? This article presents a brief critical review.
Tidow-Kebritchi S, Mobarhan S. Effects of diets containing fish oil and vitamin E on rheumatoid arthritis. Nutrition Reviews 59 (10): 335-8. Oct 2001.

JOLLY and colleagues, Division of Clinical Immunology, Department of Medicine, The University of Texas Health Center at San Antonio, San Antonio, TX 78229-3900, USA, examined the influence of food restriction combined with substitution of fish oil for corn oil in autoimmune-prone mice.
Background: Multiple animal studies have shown that moderate food and/or energy (calorie) restriction delays age-related immune dysfunction and prolongs life span. The amount and type of dietary fatty acids can also profoundly affect life span. Marine-derived fish oils contain (n-3) fatty acids, which have potent anti-inflammatory properties.
Methods: Autoimmune-prone (NZB x NZW)F(1) (B/W) mice, which develop fatal autoimmune renal disease, were used. Food restriction involved a 40% overall reduction in intake of all dietary components. Mice were fed one of three experimental diets: a food-restricted/fish oil (FRFO) diet; a food-restricted/corn oil (FRCO) diet; an ad libitum/fish oil (ALFO) diet; or an ad libitum/corn oil (ALCO) diet.
Results: The FRFO diet maximally extended life span to 645 days, compared with 494 days in mice fed the FRCO diet. The ALFO diet prolonged life span to 345 days, compared with 242 days in mice fed the ALCO diet. Increased life span was partly associated with decreased body weight, blunting of renal proinflammatory cytokine (interferon-gamma, interleukins-10 and -12 and tumour necrosis factor-alpha) levels and lower nuclear factor-kappaB (NF-kappaB). Reductions in NF-kappaB were preceded by enhanced superoxide dismutase, catalase and glutathione peroxidase activities.
Conclusions: The results demonstrate the profound additive effects of food restriction and (n-3) fatty acids in prolonging life span in B/W mice and may have additional implications in the management of obesity, diabetes, cancer and/or the ageing process.
Jolly CA et al. Life span is prolonged in food-enriched auto-immune-prone (NZB x NZW)F(1) mice fed a diet enriched with (n-3) fatty acids. The Journal of Nutrition 131 (10): 2753-60. Oct 2001.

Issue 70

SKIBA-KING, Podell Medical Center, 571 Central Avenue, Suite 106, New Providence, NJ 07974, USA, reviewed (16 references) literature on consumer use of natural products, including the reasons why people are choosing to use such products and the consequences for mainstream health care practice.
Discussion: The author concludes that consumers who elect to use natural products are electing to do more than simply use a product – their choice is an act of self-empowerment. Most often, such products are not obtained in a professional consultative setting, but in chain stores and supermarkets. Education is therefore important. Ideally, consumers should consult with a health care practitioner who shares this shift in perspective and who follows the relevant literature. A paradigm shift could be on the health care horizon, which, when complete, would make herbs and other natural products part of mainstream health care practice.
Skiba-King EW. Vitamins, herbs, and supplements: tools of empowerment. Journal of Psychosocial Nursing and Mental Health Services 39 (4): 34-41. Apr 2001.

MESSERER and colleagues, Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden, maria.messerer@mep.ki.se, used meta-analysis to estimate the prevalence and trends in dietary supplement and natural remedy use in Sweden during the 1980s and 1990s.
Methods: The authors analysed three nationally representative, cross- sectional surveys conducted in Sweden in 1980-81, 1988-89 and 1996-97. In face-to-face interviews, 38,954 participants aged 16-84 years (14,642 in 1980-81, 12,391 in 1988-89 and 11,561 in 1996-97) reported consumption of dietary supplements and natural remedies during the previous 2 weeks. The main outcome measures were changes in prevalence of dietary supplement and natural remedy users between 1980 and 1997.
Results: A 70% increase in the prevalence of dietary supplement users was found, occurring mainly between 1988-89 and 1996-97 (men: odds ratio (OR), 1.7; women: OR, 1.7). The increase in the prevalence of natural remedy users was even more dramatic: more than 3 fold in men (OR, 3.3) and almost 3 fold in women (OR, 2.6); and the systematic increase started in the 1980s. The increase occurred in all age groups and all socioeconomic groups except farmers. In 1996-97, the prevalence of dietary supplement users was 22% for men and 33% for women, and of natural supplement users, was 7% and 14% respectively.
Conclusion: The use of dietary supplements and natural remedies by the adult Swedish population has increased dramatically over the last 2 decades.
Messerer M et al. Use of dietary supplements and natural remedies increased dramatically during the 1990s. Journal of Internal Medicine 250 (2): 160-6. Aug 2001.
Comment: It is very encouraging to read that Swedish consumers, as well as most other consumers, I suspect, are intelligent enough to take supplements to ensure that they are not deficient in nutrients, rather than listening to the scaremongering negative rants – that supplements are a total waster of money – from the pharmaceutical industry and medical profession.

ERLINGER and colleagues, Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, 2024 E. Monument Street, Suite 2-600, Baltimore, MD 21205, USA, terlinge@jhmi.edu, assessed the relationship between serum beta-carotene and markers of inflammation in a very large number of adult subjects who were current smokers, ex-smokers or never smokers.
Background: Low serum levels of beta-carotene have been associated with increased risk of cancer and cardiovascular disease. However, in clinical trials, dietary supplementation with beta-carotene either had no benefit or caused harm. These findings raise the possibility that confounding by other factors might explain the association between serum beta-carotene level and disease risk.
Methods: The investigators analysed data from 14,470 subjects aged 18 years or older who participated in the Third National Health and Nutrition Examination Survey. C-reactive protein (CRF) and white blood cell (WBC) count were the markers of inflammation examined.
Results: After adjusting for beta-carotene intake and other factors, geometric mean levels of serum beta-carotene for subjects with undetectable (0.22 mg/dL), mildly elevated (0.22-0.99 mg/dL) and clinically elevated (1.0 mg/dL) CRP were 18.0, 16.1 and 13.6 ug/dL respectively in never smokers; 18.1, 15.7 and 13.9 ug/dL in ex-smokers; and 11.3, 10.2 and 9.4 ug/dL in current smokers (p<0.001 in all cases). In corresponding analyses, WBC count was also inversely related to serum beta-carotene levels (p<0.05 in all cases).
Conclusion: The strong and inverse associations of serum beta-carotene level with CRP and WBC count suggest that the relationship between serum beta-carotene level and disease risk might be confounded by inflammation. More broadly, for beta-carotene, and probably other nutrients, it seems unwise to interpret biomarker data as prima facie evidence of dietary intake without a more complete understanding of the physiological processes that affect nutrient levels.
Erlinger TP et al. Relationship between systemic markers of inflammation and serum beta-carotene levels. Archives of Internal Medicine 161 (15): 1903-8. Aug 2001.

Issue 68

PETERSEN and colleagues, Department of Infectious Diseases, Rigshospitalet, Blegsamsvej 9, 2100 Copenhagen, Denmark, investigated whether antioxidant vitamin supplementation could modulate cytokine and lymphocyte responses and reduce muscle damage after strenuous eccentric exercise.
Methods: 20 male recreational runners were randomized to receive either antioxidants (500 mg vitamin C and 400 mg vitamin E) or placebo for 14 days before and 7 days after a 5% downhill 90-minute treadmill run at 75% of VO2 max).
Results: Plasma vitamin concentrations measured before and after exercise differed significantly between the supplemented and control groups. However, exercise-induced changes in cytokines, muscle enzymes and lymphocyte subpopulations were identical in the two groups. The plasma level of interleukin (IL)-6 and IL-1 receptor antagonist increased 20-30 fold after exercise. Creatine kinase plasma levels were increased six-fold the day after exercise. Concentrations of CD4+ memory T cells, CD+8 memory and naive T cells, and natural killer cells increased at the end of exercise. In the post-exercise period, total lymphocyte counts were below pre-exercise levels.
Discussion: The results do not support the theory that exercise-induced inflammatory responses are induced by oxygen free radicals.
Petersen EW et al. Effect of vitamin supplementation on cytokine response and on muscle damage after strenuous exercise. American Journal of Physiology. Cell Physiology 280 (6): C1570-5. Jun 2001.

WANG and JIAO, Fruit Laboratory, Beltsville Agriculture Research Center, Agricultural Research Service, US Department of Agriculture, Beltsville, MD 20705-2350, USA, analysed biochemical characteristics of oxidation during maturation and ripening in blackberries (Rubus sp.).
Results: Maturation and ripening was accompanied by decreased activities of oxygen-scavenging enzymes (superoxide dismutase, EC 1.15.1.1; glutathione peroxidase, EC 1.11.1.9; catalase, EC 1.11.1.6) and enzymes in the ascorbate-glutathione cycle (ascorbate peroxidase, EC 1.11.1.11; monodehydroascorbate reductase, EC 1.6.5.4; dehydroascorbate reductase, EC 1.8.5.1; and glutathione reductase, EC 1.6.4.2). Non-enzyme components in the ascorbate-glutathione cycle, such as ascorbate (AsA), dehydroascorbate (DHAsA), glutathione (GSH) and oxidised glutathione (GSSG), and the ratios of AsA/DHAsA and GSH/GSSG were also decreased. The decreases in antioxidant capacity were correlated with increases in the ratios of saturated to unsaturated fatty acids of polar lipids and of free sterols to phospholipids.
Discussion: The observed decreases in antioxidant capacity may contribute to decreased fluidity, enhanced lipid peroxidation and membrane deterioration, which may be associated with ripening and senescence of the blackberry.
Wang SY, Jiao H. Changes in oxygen-scavenging systems and membrane lipid peroxidation during maturation and ripening in blackberry. Journal of Agricultural and Food Chemistry 49 (3): 1612-9. Mar 2001.

RODRIGUEZ-PALMERO and colleagues, University of Barcelona, Department of Human Physiological Sciences and Nutrition, Av. Joan XXIII s/n 08028 Barcelona, Spain, assessed the extent to which n-3 polyunsaturated fatty acids (PUFAs) became incorporated into plasma and erythrocyte lipids of elderly subjects after ingestion of very low doses of fish oil. They also studied effects on plasma alpha-tocopherol and retinol levels.
Methods: 45 subjects aged 60-92 years who were residents of a Municipal nursing home in Barcelona received a non-commercialized milk formula containing 1% fish oil (providing 0.4 g/day of n-3 PUFAs) for 15 months. Plasma and erythrocyte fatty acid profiles and plasma antioxidant levels were measured before and after the end of treatment.
Results: Total n-3 PUFAs in plasma and erythrocytes increased significantly by 32% and 18% respectively. Eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) levels in plasma and erythrocytes also increased significantly. Linoleic and arachidonic acids levels remained unchanged. The n-6/n-3 ratio decreased by 21% in plasma and by 16% in erythrocytes. Younger subjects showed greater incorporation of EPA and DHA than older subjects. Erythrocyte alpha-tocopherol increased significantly. Retinol and plasma alpha-tocopherol levels did not change significantly.
Discussion: The results showed that low doses of n-3 PUFAs supplemented with adequate alpha-tocopherol could be incorporated into blood lipids in elderly subjects without lowering antioxidant levels.
Rodriquez-Palmero M et al. Administration of low doses of fish oil derived N-3 fatty acids to elderly subjects. European Journal of Clinical Nutrition 51 (8): 554-60. Aug 1997.

Issue 67

BROWN and HU, Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA reviewed (141 references) clinical and experimental evidence regarding the role of dietary nutrients (in particular, n-3 fatty acids, antioxidant vitamins E and C, folic acid and L-arginine) in modulating endothelial function and their potential to prevent cardiovascular (CV) disease.
Background: The vascular endothelium is the primary site of dysfunction in many diseases, particular CV disease. Risk factors such as smoking, hypercholesterolaemia, hyperhomocysteinaemia, hypertension and diabetes mellitus adversely affect endothelial function. Evidence is emerging to suggest an important role of dietary factors in modulating endothelial function. N-3 fatty acids, antioxidant vitamins (particularly E and C), folic acid and L-arginine appear to have beneficial effects on vascular endothelial function, either by decreasing endothelial activation or by improving endothelium-dependent vasodilation. These may be some of the mechanisms by which these nutrients reportedly reduce the risk of CV disease.
Brown AA, Hu FB. Dietary modulation of endothelial function: implications for cardiovascular disease. The American Journal of Clinical Nutrition 73 (4): 673-86. Apr 2001.

MEHENDALE and colleagues, National AIDS Research Institute, Pune, India. sanjaymehendale@yahoo.com studied the association between low carotenoid concentration and risk of HIV seroconversion.
Background: Low vitamin A and carotenoid levels could increase the risk of sexual HIV acquisition by altering the epithelium of the genitals or through immune dysfunction(s).
Methods: The authors measured serum vitamin A and carotenoid levels in patients at risk of subsequent HIV infection. They conducted a nested case-control study with individuals attending two sexually transmitted disease (STD) clinics in Pune India. Serum micronutrient levels were measured in 44 cases (11 women and 33 men) with documented HIV seroconversion and in STD patients matched for gender and length of follow-up, with no subsequent HIV seroconversion (controls).
Results: STD patients in Pune had low vitamin A and carotenoid levels, and low serum beta-carotene levels were independently associated with an increased risk of subsequent HIV seroconversion. STD patients with beta-carotene levels less than 0.075 micromol/L were 21 times more likely to acquire HIV infection than those with higher levels (adjusted odds ratio (OR) = 21.2; p = 0.01). There was no such association observed in case of other non-provitamin A carotenoids.
Conclusions: There appears to be an association between low vitamin A and beta-carotene levels and subsequent HIV seroconversion. This study reports the first evidence of such an association and an increased risk for heterosexual HIV acquisition in STD patients in Pune, India.
Mehendale SM et al. Low carotenoid concentration and the risk of HIV seroconversion in Pune, India. Journal of Acquired Immune Deficiency Syndromes 26 (4): 352-9. 1 Apr 2001.
Comments: There are possibly tens of millions of people currently as risk of contracting or dying from AIDS in Africa and many developing nations. The scandal of the lack of effective treatments other than retroviral pharmaceuticals will be a deep stain when the history of the late twentieth century is told, as many research projects attempting to develop potential natural treatments – homeopathy, electromagnetic, herbal, gem, nutritional – which were being explored during the late 1980s were either starved of funding or closed down outright. The above study shows clearly and simply that people with low vitamin A and beta-carotene levels are at 21-fold (2100%) greater risk of acquiring HIV infection! Surely this result can lead to nutritional programmes which may be a start to saving lives.

Issue 66

DARLINGTON and STONE, Epsom General Hospital, Dorking Road, Epsom, Surrey KT18 7EG, UK, gdarlington@sthelier.sghms.ac.uk reviewed (224 references) the role of reactive oxygen species (free radicals) in inflammatory disorders such as rheumatoid arthritis and osteoarthritis, and evidence supporting the use of dietary supplements (antioxidants and n-3 polyunsaturated fatty acids [PUFAs]) as adjunctive treatment.
Discussion: Reactive oxygen species (free radicals) are important in the development and maintenance of rheumatoid arthritis in humans and animals. Synoviocytes and chondrocytes produce nitric oxide (NO), which gives rise to the highly toxic radical peroxynitrite. Several cytokines, such as tumour necrosis factor-alpha (TNFalpha), are involved in free radical formation, partly by increasing the activity of nitric oxide synthase (NOS). NO may mediate some of the deleterious effects of cytokines on bone resorption. Aspirin, tetracyclines, steroids and methotrexate can suppress NOS. Beneficial effects of high doses of dietary antioxidants such as ascorbate and the tocopherols have been reported, especially in osteoarthritis. Beta-carotene and selenium (the latter a component of the antioxidant enzyme glutathione peroxidase) may also be beneficial. Some n-3 PUFAs are precursors of eicosanoid synthesis, while n-6 PUFAs can increase formation of the proinflammatory cytokines TNFalpha and interleukin-6 and of reactive oxygen species. However, some prostaglandins (PGs) suppress cytokine formation; thus, n-3 PUFAs often oppose the inflammatory effects of some n-6 PUFAs. Gamma-linolenic acid (GLA) is a precursor of PGE1, possibly accounting for its reported ability to ameliorate arthritic symptoms. Some have claimed that fish oil supplements rich in n-3 PUFAs such as eicosapentaenoic acid are beneficial in rheumatoid arthritis, possibly by suppressing the immune system and its cytokines. Some other marine-derived (e.g. from the green-lipped mussel) and vegetable oils (eg. olive oil and evening primrose oil) have indirect anti-inflammatory actions, probably mediated by PGE1.
Conclusions: There is a growing scientific rationale for using dietary supplements as adjunctive treatments of inflammatory disorders such as rheumatoid arthritis and osteoarthritis.
Darlington LG, Stone TW. Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders. The British Journal of Nutrition 85 (3): 251-69. Mar 2001.
Comment: The above substantive review of the literature recommends using dietary supplements as adjunctive treatment for rheumatoid and osteoarthritis. We all await the fast-track implementation of this research into clinical practice.

GARDNER and colleagues, Stanford Center for Research in Disease Prevention and the Department of Medicine, Stanford University Medical School, Stanford, CA, USA, cgardner@stanford.edu investigated the effects of soy protein and isoflavones on plasma lipid concentrations in postmenopausal moderately hypercholesterolaemic women.
Background: Evidence exists that soy protein may have a hypocholesterolaemic effect. Isoflavones in soy may be partly responsible for this effect, but few studies have looked at the separate effects of soy protein and isoflavones.
Methods: This randomized, double-blind, placebo-controlled clinical trial involved 94 postmenopausal women with moderate hypercholesterolaemia. The women completed a 4-week run-in phase when they consumed a milk protein supplement. Subjects were then randomly assigned to 12 weeks of dietary protein supplementation (42 grams/day) with: 1) a milk protein (Milk group); 2) a soy protein containing trace amounts of isoflavones (Soy- group); or 3) a soy protein containing 80 mg aglycone isoflavones (Soy+ group).
Results: LDL-cholesterol levels decreased more in the Soy+ than in the Soy- group (0.38 versus 0.09 mmol/l; p=0.005), but neither of these changes was significantly different from the 0.26 mmol/l decrease seen in the Milk group. Similar findings were obtained for total cholesterol levels. There were no significant differences in HDL-cholesterol or triacylglycerol levels between the 3 treatment groups.
Conclusion: The results suggest total and LDL-cholesterol lowering effects attributable to the isoflavone-containing fraction. However, the lowered LDL-cholesterol in the Milk group and the lack of significant difference between either Soy group and the Milk group suggest that the observed changes may have been due to other factors related to participation in the study.
Gardner CD et al. The effect of soy protein with or without isoflavones relative to milk protein on plasma lipids in hypercholesterolemic postmenopausal women. The American Journal of Clinical Nutrition 73 (4): 728-35. Apr 2001.
Comment: Readers following the ongoing soy debate will be especially interested in the above results, which appear to raise yet more questions about what are the factor(s) responsible for the total and LDL-cholesterol lowering effects.

Issue 64

GIL, FERRERES and TOMAS-BARBERAN, Departmento de Ciencia y Tecnologia de Alimentos, CEBAS (CSIC), Murcia, Spain evaluated the effect of modified atmosphere packaging (MAP) and cooking on the flavonoid and vitamin C content (ascorbic acid [AA] and dehydroascorbic acid [DHAA]) of fresh-cut spinach.
Results: Total flavonoid content remained quite constant at approximately 1,000 mg/kg f.w. during storage in air and MAP atmospheres. Vitamin C (750 mg/kg f.w.) was better preserved in MAP storage. AA was transformed to DHAA during storage, and its concentration was higher in MAP-stored tissues. Only flavonoids with either a dihydroxyl grouping or acylated with ferulic acid showed significant free-radical scavenging (antioxidant) activity. Total antioxidant activity decreased during storage, particularly in MAP storage, possibly due to the higher contents of DHAA and lower contents of AA and antioxidant flavonoids in MAP-stored spinach. Boiling extracted 50% of total flavonoids and 60% of vitamin C into the cooking water. Flavonoid
glucuronides were extracted more than other glycosides. Vitamin C
content of cooked spinach was higher in MAP- than air-stored samples.
Gil MI et al. Effect of postharvest storage and processing on the antioxidant constituents (flavonoids and vitamin C) of fresh-cut spinach. Journal of Agricultural and Food Chemistry 47 (6): 2213-7. Jun 1999.

KLEIN and colleagues, Surgical Metabolism and Nutritional Laboratory, SUNY Health Science Center, University Hospital, Syracuse, NY 13210, USA review the ‘rediscovery’ and increasing scientific validation of the traditional use of ‘nutraceuticals’ such as honey, green tea, ginseng and vitamin supplements to enhance dietary nutrition.
Background: Hospital patients who are unable to eat receive parenteral or enteral nutrition. This is now also given to patients at home. Prior to the advent of nutritional support, the value of food was recognised for its medicinal (‘nutraceutical’) benefits. Owing to a growing database of evidence, conventional Western medicine is now starting to rediscover and accept the validity of using traditional ‘alternative’ nutraceutical remedies to enhance dietary intake. This review focuses on the effects of honey, green tea, ginseng and vitamin supplementation on the immune system.
Discussion: Honey has proven antimicrobial activity. Green tea enhances humoral and cell-mediated immunity and decreases the risk of certain cancers and of cardiovascular disease. Ginseng enhances the production of macrophages, B and T lymphocytes, natural killer cells and the colony-forming activity of bone marrow. Vitamin supplementation is associated with an increased antibody titre response to both hepatitis B and tetanus vaccines, due to stimulation of macrophages and T cells.
Conclusion: Due to a growing database of evidence, nutraceuticals are becoming more widely accepted as an adjunct to conventional therapies for enhancing wellbeing.
Klein C et al. From food to nutritional support to specific nutraceuticals: a journey across time in the treatment of disease. Journal of Gastroenterology 35 (suppl 12): 1-6. 2000.

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