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Complementary therapies are often employed to stimulate the immune system and Dr Ginni Mansberg looks at the evidence for some of the most popular agents and practices.

Immune modulation Ginni Mansberg, BMed, is a medical journalist and practising GP The Editor thanks José Vlaun Andros Humphries, MD, PG (Immunology), MSc Allergy Candidate, UK, Medical Director of Optimum Health Clinic, Antigua, and Member, European Academy of Allergology and Clinical Immunology, for his kind assistance in the peer review of this article

A summary of immune function Innate (or natural) immunity refers to nonspecific defence mechanisms that constitute the first lines of defence. These include physical barriers such as skin, the ciliary escalatory movement (e.g. respiratory mucosa) and inflammation, which is the response to tissue injury and involves both cellular and humoral mediators.1 Adaptive (or acquired) immunity involves an antigenspecific immune response and can be passive or active, natural or artificial. Depending on the antigen and route of presentation, the response can be either cellular (e.g. cytotoxic T-cells), humoral (e.g. antibodies) or both. Foreign molecules (antigens) are processed to induce a specific immune response that takes days to develop. Protein antigens can lead to different classes of specific antibodies or immunoglobulins (e.g. IgM, IgA and IgG) with distinct roles in defence e.g. toxin neutralisation, opsonisation and immune lysis. Certain complex antigens (e.g. viruses) can induce cytotoxic cells as well as antibodies. In contrast, the tuberculosis bacterium (lipoprotein complex) induces mainly cytotoxic cells without antibodies. Polysaccharide antigens (e.g. bacterial capsules) give mainly short-lived antibody responses (IgM). During the induction of the ‘primary’ response, a form of immune memory develops so that upon subsequent exposure to the same antigen, a greater, more efficient and usually longer-term ‘secondary’ immune response ensues in addition to some specific protection.1

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Summary

• The human immune system is complex and involves a combination of innate (natural) and adaptive (acquired) immunity, each involving both cellular and humoral components • Lifestyle intervention, including adequate sleep and reducing obesity and excessive alcohol consumption, has positive effects on the immune system • While a balanced diet is associated with normal immune function, there is limited evidence to support specific diets stimulating immune-system biomarkers • Deficiencies in certain micronutrients can weaken immunity. However, supplementation above that of a normal balanced diet appears not to give further benefit. There is some evidence that zinc and selenium supplements help to maintain the integrity of immune responsiveness • Of herbal products, echinacea, Korean ginseng and polysaccharide K have the most evidence to support their positive effects on the immune system, however may still be equivocal. Ashwagandha, cat's claw, ginger, garlic and milk thistle have not had their results from in-vitro and animal studies reproduced in clinical trials, however Siberian ginseng has • Psychological stressors, such as anxiety and depression, can affect certain cellular and humoral mediators of immune responsiveness • There is some evidence that meditation involving eyes being closed, for at least 20 minutes, helps fight infections • There are positive results from trials of relaxation, hypnosis and massage, however further controlled studies are needed to determine whether such practices undertaken in subdued light activate melatonin, which is known to stimulate the immune system

The chief leukocyte cells of the innate immune system are the phagocytes, including polymorphonucleoleucocytes and macrophages, as well as other cells. These can be ‘activated’ by various mediators. Certain classes of antibodies (e.g. IgG) can attach to their surfaces to confer specificity.1 Phagocytes can kill most bacteria and digest specific antigens and display important components in their outer membranes.1 In the adaptive immune system, there are two types of lymphocytes, activated by antigen-presenting phagocytes.1 All lymphocytes start in the bone marrow, B lymphocytes maturing there while T-cells mature in the thymus.1 B cells (plasma cells) produce antibodies.1 Once produced, memory cells ‘remember’ their antigens and can mount a rapid response to repeat exposures. Some T-cells have specialised functions, such as attacking enemy or foreign cells and regulating the immune process. There is also the non-adaptive component of the immune system, which includes cytokines (e.g. interleukin) and interferon production and natural killer (NK) cells.2

Ageing We know the elderly tend to get more infections than younger people.1 This seems to be linked to changes in endocrine function and a decrease in T-cells, probably as a result of the thymus atrophying with age and the total numbers of T-cells declining.1 Another possibility is that both B and T-cells lose their ‘memory’ with age.1

Lifestyle factors Obesity3 and alcohol abuse4 are both linked, directly or indirectly, to reduced functioning of some immune cells and susceptibility to some infections, as well as to wound healing, especially if diabetes or cirrhosis is present. Diabetes can impact on both innate and adaptive immunity. Similarly, chronic alcoholism can affect liver function and result in a whole cascade of metabolic dysfunctions. Sleep Lack of sleep is thought to disrupt immune function.5 Epidemiologic data suggest sleep-deprived shift workers have reduced immune function and more upper respiratory tract infections.6 Shiftworking nurses are known to be more susceptible to certain diseases, including breast and colorectal cancer.7,8 ‘There is compelling evidence that shift workers have disturbed circadian rhythms and that diminished levels of melatonin affect immune competence, as the hormone stimulates antibody responses,’ says Assoc Prof Ray Kearney, of the Department of Infectious Diseases and Immunology at The University of Sydney. ‘Some beta-blockers, such as propranolol, can inhibit melatonin production and suppress immunity’, he adds. Experimentally, a small study of healthy women shows that sleep deprivation decreases NK cell function.5 An earlier study of 42 healthy males found a reduction of immune responses and T-cell production with even minor sleep deprivation.6

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Exercise Exercise causes an acute-phase response, with increased C-reactive protein, interleukin-6 (IL-6) and activation of lymphocyte subsets.9 Studies in breast-cancer survivors have also found that exercise increases cytotoxic NK cells.10 However, those with a sedentary lifestyle who do unaccustomed exercise have a delayed increase in creatine kinase and activation of macrophages and some lymphocyte subsets.9 Resting immune function is not very different in athletes compared with non-athletes.11 However, athletes who undertake intensified training have some markers of the immune response depressed in the resting state, which may be due to the cumulative effects of elevation of hormones such as cortisol and IL-6 and IL-10.11 Prof Kearney points out, however, that cortisol is not wholly immune-suppressive: ‘Effects of cortisol are dose-dependent. Moderate pharmacological doses are anti-inflammatory while even higher doses are immune-suppressive. Furthermore, absorbed endotoxin can trigger platelet activating factor (PAF) that can precipitate shock in marathon runners. Cortisol is a potent inhibitor of PAF at physiological concentrations,’ he told the JCM.

Nutritional medicine Most of the evidence concerning the effects of diet and nutrition on the immune system is from population studies and historical observations, often in developing countries, rather than clinical trials.2 In one small clinical trial, Kenyan children were randomised to several different food-based supplements: meat-based, milk-based, vegetable oil-based or none.12 Antibody titres to Helicobacter pylori, rotavirus, tetanus toxoid and malaria surface proteins showed very little change.12 The epidemiological evidence to date shows relationships between cancer prevalence and food consumption in different populations around the world.13 ‘In contrast, records show that cancer incidence during periods of war is less when the population is on food rationing,’ says Prof Kearney, ‘The most effective and documented way to reduce cancer risk as well as increase longevity, experimentally, is by calorie restriction.’ However, Prof Mark Wahlqvist, Director of the Asia Pacific Health and Nutrition Centre at Monash University’s Department of Medicine, says it is important to consider the sources of calories one is considering restricting, since fatty acids are needed for more than energy, while amino acids provide energy for leukocytes.2 Thus calorie restriction may increase the risk of immune dysfunction or other conditions if the foods restricted are rich in important nutrients.2 Prof Wahlqvist says studies in the 1990s began to reveal that micronutrient malnutrition — often coupled with excess energy intake — adversely affected immunity and increased the risk of developing chronic diseases: ‘It has been shown that the course of these chronic diseases can be altered by nutritional interventions that improve immune function.’2 Deficiencies in some nutrients can impair immune function

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[see the ‘Which immunomodulatory nutrient is that?’ table], as can nutrient imbalances, such as excess leucine or iron and changes in omega–3:omega–6 fatty-acid ratios.2 However, protein energy malnutrition (PEM) is a major cause of immune deficiency, manifesting as lymphoid tissue atrophy, decreased lymphocyte counts and low cellular and humoral responses. PEM is associated with a high incidence of morbidity and mortality from infections that usually accompany other nutrient deficiencies.2 Specific diets Varying fruit-and-vegetable intakes have been studied in a randomised controlled trial (RCT). A low (defined as two serves per day), medium (five serves/day) and high (eight serves/day) intake of fruits and vegetables resulted in no difference on markers of immune function such as number and activity of NK cells, secretion of cytokines and lymphocyte proliferation in normal healthy men.14 However, in people with a low-carotenoid diet, another RCT showed that supplemental juices high in carotenoids stimulated NK cell cytotoxicity, cytokine secretion and lymphocyte proliferation.15 Soya isoflavones have been shown in vivo to modulate enzymes involved in xenobiotic biotransformation, namely, the activation or detoxification of ‘foreign’ carcinogenic chemicals.13 Several compounds in cruciferous vegetables, such as broccoli and cauliflower, have also been shown in vivo to augment these enzymes.13 Polyunsaturated fatty acids, in particular omega–3 fatty acids, have been used successfully in the management and prevention of several inflammatory and allergic diseases.16–18 Micronutrients Human intervention trials involving immunomodulatory micronutrients [see ‘Which immunomodulatory nutrient is that?’ table, p 19], with immunity biomarkers as endpoints, are scarce and inconclusive.1 Vitamin C — conflicting results from a variety of poorly des-igned trials makes it difficult to make firm conclusions about the role of vitamin C on the immune system.1 At this stage, it seems that it works synergistically with other vitamins in healthy immune functioning rather than alone.1 Different immunostimulatory effects demonstrated include enhancing lymphoproliferative response to mitogens and lymphotrophic activity, increasing interferon levels, antibody responses, immunoglobulin levels and the secretion of thymic hormones.19 Vitamin A — various in-vitro studies have found strong links between vitamin A and certain subcategories of T- and B cells and cytokines.1 Vitamin A deficiency is also associated with impaired immune function and infectious diseases.1 However, a clinical study of vitamin A supplementation without a pre-existing deficiency didn’t affect T-cell immunity in a group of healthy older people.1

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Studies have focused on the role of vitamin A supplementation and vaccinations in developing nations. In a study of young children, antibody responses to tetanus toxoid were increased in those given oral vitamin A supplements (60,000 mcg).20 However, a further study reported that responses to measles vaccines were decreased in children with high maternal antibodies and supplemented with 100,000 IU oral vitamin A compared to controls.21 The most likely explanation, as well known in immunology, is that the pre-existing maternal antibodies neutralised the antigens in the measles vaccine to diminish a greater immune response. The significance, if any, in the reported effect of vitamin A is unknown, as concomitant infections can also suppress immune responsiveness. But the role of vitamin A supplementation might be extended further in populations where deficiency is common. A Mozambique trial of 200,000 IU/day oral supplementation to vitamin A-deficient children found supplemented children were less likely to be admitted to hospital with lower respiratorytract infection than those receiving placebo.22 Vitamin E — a study of 88 older healthy people randomised to take placebo or 60, 200, or 800 mg/d of vitamin E for 235 days found that vitamin E increased antibody responses to hepatitis B and tetanus vaccination, but not to diphtheria and pneumococcal vaccine.23 Another interesting large RCT of elderly nursing-home residents found that 200 IU/day of vitamin E had no effect on the rate of lower respiratory-tract infections or number of antibiotics prescribed compared to placebo, but did protect against upper respiratory-tract infections.24 The authors called for further studies to confirm their findings. Vitamin B group — a Taiwanese RCT of vitamin B6 supplementation in critically ill intensive-care patients found that the supplementary injections increased T-lymphocyte and T-helper cell numbers after 14 days compared to the group receiving a placebo.25 In-vitro studies show that pyridoxine, folic acid and vitamin B12 deficiencies have effects on the immune system.26 However, intervention trials of these nutrients have not confirmed these. Zinc is vital for immune functioning. It is effective in prevention of infectious diseases, as a recent review27 of nine trials showed, with significant reductions in the incidence of diarrhoea as well as pneumonia and malaria, although fewer trials are available for analysis for these diseases.27 People with inherited acrodermatitis enteropathica, which causes zinc deficiency through reduced zinc absorption, have reduced numbers of T-cells, reduced thymic hormones and impaired polymorphonuclear phagocytosis.28 All are reversible upon zinc supplementation.28 Another study in Indian children with diarrhoea found that zinc supplementation increased numbers of circulating CD3 and CD4 cells, but not CD8 cells, B cells or NK cells.29 Daily doses of zinc over 150 mg can paradoxically impair

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Which immunomodulatory nutrient is that?2 Innate Nutrient

Adaptive immunity Humoral

Cellular

4

4

Amino acids essential

4

non-essential 4

arginine 4

4

4

4

4

4

zinc

4

4

4

copper

4

glutamine Essential fatty acids (n–3 and n–6) Elements

4 4

iron selenium

4

4

magnesium

4

4

4

4

4

4

4

4

Vitamins B2 B6

4

4

B12

4

4

biotin

4

4

4

4

4

4

folic acid

4

C

4

A

4

D

4

E

4

Non-nutrients flavonoids

4

4

pepides (glutathione)

4

4

immune function, so care must be taken when selecting a product30 — see also JCM 2006;5(3):69. Coenzyme Q10 — Breast cancer and myeloma rates have been found to be higher in people with low levels of serum coenzyme Q10.31 End-stage AIDS has been associated with a significant deficiency in coQ10.32 Despite limited studies, there are some encouraging preliminary data from the study of seven AIDS patients.32 Another small study by the same Texan research groups found raised IgG and T4 counts in well subjects when coenzyme Q10 was administered with pyridoxine (vitamin B6).33 Further studies are required. Selenium deficiency causes reduced functioning of many immune cells and supplementation has been found to stimulate white-cell and thymus function.34 Selenium supplementation (200 mcg/day) has been shown to improve T-cell function in vivo in patients with normal serum selenium levels at baseline.35 A recent RCT in 262 HIV-positive people also found that

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supplementation with 200 mcg/day selenium (Selenomax, Nutrition 21 Inc., New York, New York) over nine months indirectly improved CD4 cell counts, probably by reducing progression of the viral load.93 L–carnitine (3-hydroxy-4-N,N,N-trimethylaminobutyrate) is an essential nutrient with a major role in cellular energy production. There is evidence that, at high doses, L–carnitine might mimic some of the biological activity of glucocorticoids, especially immunomodulation.36 At this stage, evidence comes from in-vitro and animal studies. Glutamine is a nonessential amino acid. There is little evidence for beneficial clinical effects of supplementary glutamine in reducing infections or shortening hospital stay.37 A large study of critically ill intensive-care patients supplemented with glutamine showed no net benefit or harm.38 However, in a small RCT of patients with severe burns, glutamine supplements markedly reduced infections and mortality compared to controls.39 Arginine, a dibasic amino acid, is under normal conditions a nonessential amino acid, because it can be synthesised in humans in the urea cycle.37 However, in critically ill septic patients, arginine synthesis can be exceeded by its catabolism to nitric oxide and urea, rendering arginine conditionally essential.37 In a study where such patients supplemented with an immunomodulatory formula including arginine, they experienced less infectious complications, were mechanically ventilated for shorter periods of time and their hospitalisation period was shorter. Mortality rates were generally not improved.40 Probiotics Probiotics appear to augment the maturation of the visceral immune system, as well as having some general effects. They appear to enhance immunity when it is weakened as well as buffer exaggerated reactions (e.g. allergies and inflammatory bowel disease). Probiotics appear to bolster the intestinal mucosa so the integrity of the gut wall is retained and pathogenic microbes that could otherwise colonise the gut are excluded.41,42 They may also restore normal intestinal permeability43 and reduce pro-inflammatory cytokines.44,45 Some researchers suggest probiotics may buffer heavy metals.46–48 Probiotics may also promote the production of enzymes that help decrease the severity of certain food intolerances.49 However, these actions have not been fully documented. Green tea Epidemiological studies indicate that high intake of green tea is associated with a lower risk of some cancers.50 Whether this is through immune modulation remains unclear. One of the principle active ingredients in green tea, catechins, have been shown to enhance in-vitro resistance of alveolar macrophages to Legionella pneumophila, as well as upregulate IL-6 and TNF–α production by macrophages in response to infection.50,51

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Herbal medicine

Garlic In-vitro studies show positive effects of some compounds in garlic, such as enhanced macrophage activity52 and T-cell proliferation.53 Ginger An interesting in-vitro study of mouse immune cells found that volatile oil of ginger (0.001–10 ng/mL) significantly inhibited T-lymphocyte proliferation, decreased the number of the total Tlymphocytes and T-helper cells.54 This is supported by separate US research showing immunosuppression in vitro.55 Echinacea Echinacea spp. have been extensively studied for their effects on upper respiratory tract infections.56 In-vitro and in-vivo studies suggest echinacea stimulates phagocytosis, enhances mobility of leukocytes, stimulates TNF and IL-1 secretion from macrophages and lymphocytes.57 The binding of the polyacetylene fraction of echinacea to T-cell surface receptors is thought to cause its antiviral and immunostimulant activity.58 In a small German double-blind, placebo-controlled crossover study, 40 healthy males received either a commercially available pressed juice of E. purpurea herbs or placebo juice for a total of two weeks.59 The study found only minor effects on two out of 12 lymphocyte subsets tested, so further studies are required. Another Cochrane review found that although there was significant benefit from taking echinacea in several trials, these were counterbalanced by negative results in other trials. Different preparations and poor study design made analysis difficult, and the jury is still out about the role of this herb in immune functioning.60 Cat’s claw In-vitro studies show that cat’s claw (Uncaria tomentosa) alkaloids enhance phagocytosis and modulate NFκB and TNF–α, and alleviate inflammation.61,62 Clinical trials have yet to be done. Korean ginseng Animal and in-vitro studies indicate that Panax ginseng enhances phagocytosis, NK cell activity and the production of interferon63 — see also pp 60–64. Human trials have also shown promise. A study of 227 healthy volunteers found that 100 mg/day of P. ginseng for 12 weeks enhanced efficacy of the influenza vaccine.64 In another study of 60 healthy volunteers, enhanced chemotaxis, phagocytosis, increased total Thelper cell numbers was found in those who took 100 mg bid for eight weeks.65 Another study randomised 75 patients with acute exacerbation of chronic bronchitis to receive either antibiotics or antibiotics plus P. ginseng.63 Those in the ginseng group showed faster bacterial clearance.63

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Case study: chronic FLU Karen, 32, attended her GP complaining of having a flu for the past three months. She could hardly remember a day that had passed in that time when she hadn’t had a sore throat, headache, cough or running nose in some combination. She had returned to work four months previously when her twins had turned three months’ old and, with both in day care, they were always bringing home the latest viral illness. The twins were still both up at night at different times. Karen was struggling to put dinner on the table and most nights she’d eat either eggs on toast, breakfast cereal or take-aways. The stress of juggling the babies and work were taking their toll on her marriage too, with her husband spending more time at work. On examination, Karen had a sniffle but was afebrile, had no cervical adenopathy and her chest was clear. She thought her immune system seriously needed a boost and although

Siberian ginseng Eleutherococcus senticosus has been shown in a Russian in-vivo study to stimulate Tlymphocyte and NK cell production.66 In a clinical trial in athletes, subjects were randomised to take Korean ginseng, 4 g/day of Siberian ginseng or a placebo for four weeks. There were no changes in circulating numbers of total T-cells, T-helper cells (CD4), T-suppressor cells (CD8), CD4: CD8 ratio, NK cells or B lymphocytes.67 There was a slight increase in cortisol levels relative to testosterone levels in the athletes taking Siberian ginseng, prompting the authors to suggest there is a threshold of ‘stress’, below which Siberian ginseng increases the ‘stress’ response and above which it decreases the stress response.67 However, in an earlier study of

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she had never previously been to a complementary therapist, she raised the idea with her GP. Her GP realised Karen’s immune system was probably performing below par due to lack of sleep, poor nutrition and stress. He suggested working on the babies’ bedtime routine to get them sleeping through the night. He referred her to a dietitian at the local hospital to examine her diet and practical ways of improving it, but suggested she consult a naturopath about the possibility of zinc and selenium supplements and to explore herbal therapies and supplements, such as Korean ginseng. Three months later, Karen had reduced her work commitments to three days a week. Her babies were both sleeping through the night most nights and her diet had improved. She’d had one further cold, but was feeling healthier and better able to resist infections.

36 healthy individuals randomised to either take Siberian ginseng or placebo68, Siberian ginseng increased the numbers of circulating T-lymphocytes, especially T-helper and NK cells. There was also increased T lymphocyte activity.68 Ashwagandha Withania somnifera (ashwagandha) is widely used in Ayurvedic medicine, the traditional medical system of India, often as a general health tonic and immune booster.69 A study in mice found that ashwagandha prolongs life and increases cytotoxic Tlymphocyte production.70 Human studies have yet to be done. Milk thistle Silybum marianum and its key compon-

ents, including the flavonoid silymarin, has been shown to be immunostimulating in in-vitro studies, stimulating lymphocyte function and numbers55 and macrophage function, and suppressing the effects of TNF–α on inflammatory cells.71 However, clinical trials are yet to be done.

Traditional Chinese medicine

Acupuncture A pilot crossover study randomised 10 healthy young men to receive either acupuncture or sham acupuncture. Blood samples were taken before the session, 10 minutes after and 30 minutes after removing the needles. After the third session, the acupuncture group was found to have significantly lower serum levels of leukocytes and lymphocytes.72 Another small Korean clinical trial of a single session of acupuncture for chronic headache found that acupuncture lowered levels of serum TNF–α.73 Levels of IL-1 and IL-6 were not affected.73 Chinese herbalism In traditional Chinese herbalism, differing combinations of various herbs are combined to modulate the immune system, usually on a bespoke basis. Many individual herbs from this tradition, such as the fungi Ganoderma lucidum and Cordyceps sinensis, are thought to be immunomodulatory, however it is difficult to verify this in humans as much of the scientific evidence for them is derived from case reports and preclinical studies, many of which are untranslated. The herb dong quai (Angelica sinensis) has been shown to be immunostimulatory in in-vitro studies, stimulating both lymphocyte numbers and activity4 and macrophages.74,75 Clinical trials have not yet been undertaken. Codonopsis pilosula reduced the immunosuppressive effect of radiotherapy in cancer patients receiving it but had no effect on most humoral immune parameters, except IgM was slightly increased.76 In-vitro, animal, and anecdotal human data show Astragalus membranaceus reduces immune suppression following

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chemotherapy77, improving the responses of lymphocytes, enhancing NK cell activity and potentiating the activity of monocytes.78 Polysaccharide K, an extract from the mushroom Coriolus versicolor, has accumulated good evidence for its efficacy as an immunostimulant, with human trials showing it improves survival in patients with GI, lung and breast cancers undergoing chemotherapy and/or radiotherapy.79–82 It is thought to sensitise peripheral blood lymphocytes, leading to the activation and proliferation of cytotoxic effector cells.80 Qi therapy A small Chinese study saw healthy subjects randomised to a session of qi gong or a placebo (no intervention).83 Blood was taken immediately prior to and after the intervention, and the qi gong group had an increase in lymphocyte and monocyte numbers but had no effect on macrophages.83 Further studies are warranted.

Mind–body medicine The link between psychological wellbeing and the immune system is still being unravelled [see JCM 2004;3(6):46–58]. The persistent activation of the hypothalamic– pituitary–adrenal axis in the chronic stress response [see JCM 2006;5(6):12–25] and in depression probably impairs the immune response and contributes to the development and progression of some types of cancer.84 Both stress and depression are associated with the decreased cytotoxic T-cell and NK cell activities, as well as reduced monocyte production of IL-10.84,85 People who feel stressed also report more infections, such as the re-activation of cold sores (herpes simplex) and shingles (herpes zoster) indicating that stress may inhibit the immune system.85 On the flipside, the effects of happiness and a positive attitude on health and the immune system specifically are only just being studied now.86 New research suggests that people with a positive outlook have higher salivary IgA and cortisol output, which might explain why positive people

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tend to get sick less.86 ‘It is worth noting that physiological levels of cortisol are required for optimum immune responsiveness,’ adds Prof Kearney, ‘Higher levels are anti-inflammatory, however high pharmacological doses are even immune-suppressive.’

Massage therapy A clinical trial of Dominican children with HIV found that those receiving a 12-week massage-therapy course had less decline in CD4 counts than those in the control group.87 A further small clinical trial of 34 breastcancer patients who were randomised to receive either thrice-weekly massage or nothing found that the massage group had higher numbers of certain lymphocyte subsets.88 However, only 15 patients had blood collected for immune cell assays, so interpretation is difficult.

Relaxation/hypnosis An interesting study of 35 stressed medical students who were randomised to either try self-hypnosis or a control group uncovered some interesting results.89 When the subjects perceived stress during exam time, there was an increase in B and activated T-lymphocyte numbers, as well as NK cell cytotoxicity. The hypnosis did not affect immune function in any way in this study, although it did help with perceived stress.89

Meditation Interesting results were found from a small RCT of 25 patients either undergoing an eight-week meditation course or a ‘waiting list’. The test group underwent a single class that met weekly for 2.5–3 hours per class, along with a silent seven-hour retreat that was held during the sixth week of the course. In addition, subjects were assigned home practice that consisted of formal and informal meditative practices that they were instructed to perform for one hour per day, six days per week, with the aid of guided audio.Those who meditated had a stronger antibody response

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to influenza vaccine than non-meditators.90 ‘Some forms of meditation require the eyes to be closed,’ Prof Kearney says, ‘Such meditation, if continued for longer than 20 minutes, activates the pineal gland to produce melatonin which is a potent immune enhancer. Hence persons with underlying auto-immune diseases such as rheumatoid arthritis (RA) can worsen RA by augmenting levels of auto-antibodies, when supplementing with melatonin or practising long periods of meditation.’

Homeopathy Unfortunately, only a few small groups are working on studies for homeopathy for immune modulation.91 Positive results came from a human study of histamine dilutions on basophil activity.91 However, the study had problems with statistical analysis and has not been replicated. The homeopathic anti-inflammatory complex Zeel comp. N (Biologische Heilmittel Heel GmbH, Baden Baden, Germany) is thought to inhibit synthesis of leukotriene B4 and prostaglandin by 5–lipoxygenase (5– LOX) and COX 1 and 2, respectively.92 In an in-vitro study, Zeel comp, as well as tinctures of Arnica montana, Sanguinaria canadensis and Rhus tox (Toxicodendron quercifolium), showed inhibitory effects on the 5–LOX and on the COX 1 and COX 2 enzymes.92 ◗ References 1 Stambach M. The Truth about your immune system: what you need to know. Stamford: Harvard Medical School, 2004. 2 Wahlqvist ML, Kouris-Blazos A. Immune function, infection and diseases of affluence. In: Wahlqvist ML (ed). Food and Nutrition (2nd edn). Sydney: Allen & Unwin, 2002. 3 Palmbad J, et al. Scand J Haematol 1977;19:293–303. 4 Frank J, et al. Alcohol Alcohol 2004;39:386–92. 5 Wright CE, et al. Brain Behav Immun 2006 Oct 5. 6 Irwin M, et al. FASEB J 1996;10(5):643–53. 7 Schernhammer ES, et al. J Ntl Cancer Instit 2001;93(20):1563–8. 8 Schernhammer ES, et al. J Natl Cancer Inst 2003;95(11):825–87. 9 Sorichter S, et al. Med Sci Sports Exerc 2006;38(10):1739–45.

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