Immunity: natural strategies for health and performance

Andrew Hamilton investigates natural strategies to boost your natural immunity and keep infection and the effects of exercise stress at bay

Athletes constantly live on a knife-edge between overreaching and overtraining. That new programme might shed valuable seconds off your PB, but if it proves too much and you come down with a viral infection you stand to lose fitness, not gain it. Building and maintaining immunity should be thought of as a vital part of any athlete’s programme, particularly as the existence of post-exercise immunosuppression is now well- established^(1,2,3). But what can athletes do to maximise their immunity and reduce the risk of infection and illness?

The human immune system consists of a complex array of different elements, whose job is to work synergistically to recognise, attack and destroy foreign invaders. In very simple terms, there are two lines of defence. The first is the innate immune system, consisting of barriers designed to prevent foreign agents from infecting the body. These include:

• physical barriers, such as the skin and epithelial tissues of the lungs, nose and intestinal tract;
• chemical barriers, such as the high acidity of the stomach;
• cellular barriers, such as phagocytic cells whose job is to engulf invaders.

If the first line of defence is breached, an infection occurs and then the ‘acquired’ immune system kicks in to fight the infection and destroy it. The acquired system employs a number of different cell types working in cooperation to help the body recognise and defeat the invaders. For example, cells known as monocytes or macrophages ingest any foreign material and then present it to other cells known as lymphocytes. When this material is presented to a B-lymphocyte immune cell, the lymphocyte is signalled to proliferate and produce antibodies that will specifically bind to the foreign invader. These antibodies attach themselves to the surface of the invader (usually bacteria or a virus-infected cell) and act as ‘labels’, effectively telling the other cells of the immune system that these invaders are foreign and need to be destroyed. This destruction can be by means of macrophages engulfing the invader, by an attack from other immune cells known as ‘natural killer cells’, or by immune proteins collectively called ‘complement’, which can punch holes in the bacterial wall. If the foreign material is presented to a T-lymphocyte immune cell, it too proliferates; some T-lymphocytes (CD8+) become activated to kill any cells carrying this foreign material, while others (the CD4+ T-cells) secrete biochemical substances (such as interleukins and cytokines) which boost the activity of killer cells.

The point is that your immune system contains a large number of functionally different cells and a wide array of defence mechanisms. Because of this, it’s actually quite difficult to accurately assess the impact of nutrition on immunity, especially as there are no instruments that can predict the cumulative effect of several small positive changes in different immune system parameters⁽⁴⁾.

The phenomenon of post-exercise immunosuppression (PEIS), in which certain elements of the immune system become temporarily depressed after heavy bouts of exercise, is now well-documented in athletes^(5,6), linked with an increased incidence of infection, particularly of the upper respiratory tract. In particular, it appears that during recovery from prolonged, intense exercise the number of lymphocytes in the blood is reduced below resting levels and the function of natural killer and B cells is impaired^(7,8). Strenuous exercise also seems to inhibit innate immunity by reducing mucosal protection⁽⁹⁾. And there is evidence that this drop in immunity may worsen the disease outcome when exercise is performed during the incubation period of an infection⁽¹⁰⁾. The consensus of scientific opinion is that PEIS occurs mainly as a consequence of the increased secretion of stress hormones, such as adrenaline and cortisol, during vigorous and prolonged exercise, particularly as these types of hormones are known to suppress immune function.

The role of glutamine

In recent years, the role of an amino acid called glutamine has come under intense scrutiny. Several studies have demonstrated a fall in plasma glutamine levels following vigorous exercise, and doctors had long been aware that this also occurs as a consequence of other stressful events, such as trauma and burns, which lead to immunosuppression. When it was subsequently shown that many immune cells have an unusually high capacity to utilise glutamine⁽¹¹⁾ and that (unlike most cells in the body) these immune cells were unable to synthesise glutamine in situ and therefore required a constant supply from blood plasma⁽¹²⁾, glutamine depletion was considered by many to be an obvious trigger for the PEIS commonly observed after acute, exhaustive exercise. This theory was supported by in-vitro studies showing that glutamine stimulates the activity of certain immune cells, such as lymphokine-activated killer cells⁽¹³⁾.

Given these findings, scientists quickly began to speculate that PEIS might be prevented if extra glutamine could be administered after exercise – hence the proliferation of glutamine supplements. However, more recent research has thrown this idea into doubt. While a study on glutamine-supplemented marathon runners found they experienced only half the rate of respiratory tract infections of unsupplemented controls⁽¹⁴⁾, the same scientists also found that that glutamine supplementation after a marathon did not influence the lymphocyte distribution or the concentration of other immune proteins. Meanwhile, glutamine-supplemented cyclists who performed 60, 45, and 30 minutes of exercise at 75% of maximal oxygen consumption, separated by two-hour rest periods, showed no increase in immune activity by comparison with unsupplemented controls⁽¹⁵⁾.

In a nutshell, boosting plasma glutamine concentration did not prevent post-exercise immunodepression, a finding which has since been confirmed by a further study on glutamine-supplemented marathon runners⁽¹⁶⁾. Scientists now believe this is because the post-exercise drop in plasma glutamine is relatively small, to around 80-90% of resting values, by comparison with the drop in severe burns patients, whose glutamine levels can fall to below 40% of normal. Although there is a reduction in circulating glutamine after exercise, there still seems to be enough of the stuff for the immune cells to function normally. Moreover, while plasma glutamine levels undoubtedly fall, there is evidence that the intra-cellular levels of glutamine in important immune cells in the blood actually rise⁽¹⁷⁾. Glutamine, it seems, is not the magic immune bullet that athletes had hoped it would be.

The carbohydrate connection

In recent months, carbohydrate-bashing has become more fashionable than ever, and it seems like everyone and his dog is now flourishing on a low-carbohydrate diet! But, quite apart from the weight-loss myths pedalled in the press, athletes would seem to have even more reason to ignore this fashion than most because there is strong evidence that intense training coupled with a low-carb diet is the perfect recipe for immunosuppression! The PEIS observed after intense training appears to occur mainly as a result of the secretion of stress hormones into the body, and scientists have proposed that any nutritional manipulation capable of reducing this stress hormone release should limit this immune suppression⁽¹⁸⁾. The latest research suggests not only that limiting carbohydrate intake induces a greater release of stress hormones during exercise, but also that athletes can manipulate their carbohydrate intake to ameliorate PEIS.

Studies have shown that when athletes train in a glycogen-depleted state after spending several days on low-carbohydrate diets (less than 10% of dietary intake from carbohydrate), the release of stress hormones, such as adrenaline and cortisol, is exaggerated by comparison with normal or high-carbohydrate dietary conditions^(19,20). Moreover, this enhanced stress hormone release is linked to a decrease in immune function; for example, just one hour’s exercise at 75% VO2max in a glycogen-depleted state resulted in a significantly bigger fall in circulating immune lymphocytes than the same amount of exercise on a high-carb diet⁽²¹⁾. The good news for athletes is not just that high-carbohydrate diets can reduce the stress hormone response but also that taking in carbs during exercise reduces stress hormone production which, in turn, seems to ameliorate PEIS.

In a landmark study carried out last year, cyclists were fed differing amounts of carbohydrates during 2.5 hours of strenuous cycling⁽²²⁾. Taking in 30-60g of carbohydrate per hour in the form of a 6% carbohydrate drink was found to prevent the decrease in an important type of immune cell, known as interferon-g-positive T-lymphocytes, experienced by a placebo control group. The researchers also discovered that the carbohydrate-supplemented group showed no measurable drop in production of an active chemical (known as interferon-g) that these T-cells secrete when stimulated. Interferon-g production is critical to anti-viral defence, and scientists now believe that suppressed production after strenuous exercise may be an important factor in the increased risk of infection.

These results are supported by another recent study from the US, where two groups of runners were asked to perform a three-hour treadmill run at 70% VO2max, one ingesting a carbohydrate drink and the other a placebo⁽²³⁾. By comparison with the control condition, carbohydrate ingestion reduced the rise in plasma concentrations of a number of cytokines – very small protein molecules secreted by cells of the immune system, which regulate the intensity and duration of the immune response. The lower levels of cytokines measured in the carbohydrate-fed runners appeared to indicate reduced ‘immune stress’. However, it remains to be established whether carbohydrate ingestion during training and competition can reduce the incidence of upper respiratory tract infection (URTI). The American researchers mentioned above have noted a beneficial trend in a study of 98 marathon runners, but their results did not reach statistical significance, indicating the need for further, larger studies⁽²⁴⁾.

The role of essential vitamins and minerals in maintaining immunity has long been recognised; deficiencies of the any of the vitamins A, E, folic acid, B6, B12 and C can impair immunity, as can deficiencies of the minerals iron, copper, selenium, zinc, magnesium and manganese⁽²⁵⁾. But are there any nutrients that can offer extra immune support when taken in higher quantities than their current UK Reference Nutrient Intake (RNI) values? The obvious candidate is vitamin C; ever since Dr Linus Pauling carried out his original studies into vitamin C, the notion that it might be beneficial for combating URTIs, such as the common cold, has become widely accepted. But while vitamin C is found in high concentrations in immune cells such as leucocytes and has also been implicated in a number of immune functions, such as the promotion of T-cell proliferation and inhibition of virus replication, the research on athletes and immunity has produced very mixed results.

Two studies carried out in the 1990s initially provided strong support for a protective effect of high doses of vitamin C in athletes. In the first study, two groups of ultra-marathon runners were supplemented for three weeks leading up to a 90k race, one group taking 600mgs of vitamin C per day (15 times the current RNI of 40mgs) and the other taking placebo⁽²⁶⁾. In the fortnight after the race, the incidence of URTIs in the supplemented groups was half that of the controls. A follow-up study carried out three years later supported these results⁽²⁷⁾; ultra-marathon runners were split into four groups, one given 500mgs per day of vitamin C, the second receiving the same plus 270mgs of vitamin E, the third 300mgs of vitamin C, 200mgs of vitamin E and 18mgs of beta-carotene, and the fourth receiving just placebo. After the 90k race, the runners receiving the highest doses of vitamin C showed the lowest incidence of URTIs, regardless of whether they were also receiving the antioxidant nutrients (vitamin E and beta-carotene), clearly pointing to vitamin C as the protective nutrient.

The problem is that other studies have not been able to replicate these findings. For example, no immunity benefits were found in an American study when runners were supplemented with 1,000mgs of vitamin C per day for eight days before completing a 2.5-hour run⁽²⁸⁾. And in a very recent placebo-controlled study conducted by the same researchers, 1,500mgs of vitamin taken daily for seven days before and during an ultra-marathon did not positively affect any aspect of immune function.

A number of herbs are reputed to stimulate immunity, but in recent years it is echinacea purpurea that has become particularly popular among athletes, despite a lack of evidence of its effectiveness against PEIS. There’s no doubt that in the laboratory echinacea does demonstrate a significant effect on a number of immune cells, especially on macrophage activity⁽³⁰⁾, as well as on the activation of some leucocytes and natural killer cells⁽³¹⁾. But how, if at all, does this translate into immune protection for athletes?

The evidence, unfortunately, is rather disappointing. While some small-scale studies have indicated that, in those already infected, the severity and duration of acute URTIs may be modestly reduced with echinacea, three recent double-blind placebo-controlled studies found no evidence of immunostimulation^(32,33,34).

Some researchers have suggested that the problem with echinacea studies is that many commercially available echinacea products do not possess enough active constituents to exert a definitive clinical effect. To get around this problem, a very recent double-blind, placebo-controlled study used a formulation prepared from freshly harvested echinacea plants, which contained the suspected active constituents (alkamides, cichoric acid, and polysaccharides) at known and high concentrations⁽³⁵⁾. A group of 282 healthy adults with a history of two or more colds in the previous year were randomised to be treated with either echinacea or placebo at the first onset of cold symptoms. During the study period, 128 subjects contracted a common cold (59 on echinacea and 69 on placebo). But the echinacea group reported less troublesome symptoms and responded faster to ‘treatment’ than the controls. The researchers concluded that their results pointed to the need for more, larger scale studies using standardised extracts.

A role for probiotics

It was almost a century ago that the Nobel prize winner Elie Metchnikoff carried out his research into fermented milk products, such as live yoghurt, and suggested that, far from being inevitably detrimental to health, bacteria could play an important role in maintaining it. Since then, a wealth of research has accumulated, confirming that certain types of bacteria are beneficial to human health when ingested. These so-called probiotics can be defined as ‘live microbial feed supplements, which beneficially affect the host by improving its intestinal microbial balance’. Although probiotics have been shown to produce a number of gastrointestinal health benefits, they’ve never been perceived as ‘sexy’ by the athletic community. But that might be about to change!

Over the last decade there has been an explosion of research into the immunostimulatory properties of probiotics – and the results are impressive. A recent meta-analysis of relevant studies examined the scientific literature on probiotics and immunity in-vitro, in animals and in humans⁽³⁶⁾. Of these, 48 reported positive immunostimulatory effects, 17 in-vitro, 21 in animals and 10 in humans. To date, there are no published studies on the possible benefits of probiotics for athletes, but things are moving quickly and two studies on this very topic are due for publication later this spring. In the first, 118 German sports performers were screened for levels of an immune protein called secretory immunoglobulin A (sIgA), with 52 found to have below-average levels⁽³⁷⁾. These 52 were then split into three groups for four weeks, the first treated with a probiotic food supplement containing a proprietary blend of beneficial bacteria (Lactobact omni FOS, manufactured by Winclove Bio Industries), the second a zinc and magnesium supplement and the third both together. When their faeces were analysed, only those taking the probiotic were found to have significantly increased levels of sIgA.

The second study, also carried out in Germany, examined the effects of probiotics on post-exercise immunosuppression⁽³⁸⁾. A total of 44 endurance athletes were split into two groups, one to receive probiotics, the others to act as controls. After four weeks of supplementation with a probiotic blend (Lactobact omni FOS), the athletes were tested after a 60-minute endurance session. As expected, faecal microflora was improved in the probiotic group, but the researchers also discovered that this group experienced a lesser post-exercise decrease in the level of circulating natural immune killer (NK) cells than the controls, with a faster return to pre-exercise NK cell levels – an indication that probiotics may be able to reduce PEIS. As with all unpublished studies, these results should be interpreted with caution, but if they are confirmed the role of probiotics in the health of athletes looks promising.

In summary, here is the best advice for athletes wishing to maintain maximum immunity:

• Carbohydrate intake – The normal diet should provide ample carbohydrate at all times, accounting for 60% or more of total calories. Low-carb diets such as Atkins or Zone should be avoided. For longer (90-plus minutes) or very intense sessions, 500-1,000mls of carbohydrate drink containing 60g of carbohydrate per litre should be ingested every hour;
• Diet quality – Immunity can be adversely affected by any number of nutrient deficiencies. Athletes should ensure that their diet is rich in whole unprocessed foods, fruits and vegetables, contains adequate high-quality sources of protein and is low in fatty, sugary, fast or processed food. A broad-spectrum multi-vitamin/mineral supplement may be beneficial in preventing a nutrient shortfall, but large doses of any single nutrient should be avoided as this could create imbalances leading to impaired immunity;
• Vitamin C – The evidence is too mixed for a firm recommendation but, given its low toxicity and cost, athletes wishing to take a modest supplement (200-1,000mgs per day) have little to lose;
• Glutamine – Although beneficial in the clinical setting, there’s little hard evidence that it offers immune protection to athletes;
• Echinacea – Athletes who contract a URTI may find that taking a standardised echinacea preparation shortens its duration. However, while echinacea does not appear on the IOC’s banned substances list for 2004, those subject to drug-testing should be aware that all herbs contain a number of biologically active ingredients which, under certain circumstances, may inadvertently produce a positive result;
• Probiotics – Although the early indications are promising, very little data exists on the benefits of probiotics for athletes. Foods like live yoghurt and other fermented products can be included in the diet if desired, especially as they are also rich in other nutrients; indeed, they are recommended after antibiotic treatment. To date there’s insufficient evidence of the benefits of supplementing the diet with probiotics, although this may change in the near future;
• Lifestyle – Athletes should ensure they get plenty of sleep and relaxation, minimising fatigue and emotional stress where possible. Good hygiene is also important, with regular hand washing recommended to reduce the risk of transferring virus particles to the mucous membranes of the eyes, nose and throat.

Andrew Hamilton

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