. 2018 Mar 14;52(7):439–455. doi: 10.1136/bjsports-2018-099027

Table 4.

Nutritional supplements for immune health in athletes: proposed mechanism of action and evidence for efficacy

Supplement	Proposed mechanism of action	Evidence for efficacy
Vitamin D	This is an essential fat-soluble vitamin known to influence several aspects of immunity, particularly innate immunity (eg, expression of antimicrobial proteins). Skin exposure to sunlight accounts for 90% of the source of vitamin D.	Moderate support Evidence for deficiency in some athletes and soldiers, particularly in the winter (decreased skin sunlight exposure) Deficiency has been associated with increased URS. Recommend 1000 IU/day D₃ autumn-spring to maintain sufficiency Further support required⁹⁸
Probiotics	Probiotics are live micro-organisms that when administered orally for several weeks can increase the numbers of beneficial bacteria in the gut. These have been associated with a range of potential benefits to gut health, as well as modulation of immune function.	Moderate support in athletes with daily dose of ~10¹⁰ live bacteria Cochrane review of 12 studies (n=3720) shows ~50% decrease in URS incidence and ~2 day shortening of URS; minor side effects. More evidence is required supporting efficacy to reduce gastrointestinal distress and infection, for example, in a travelling athlete.^{23 99}
Vitamin C	This is an essential water-soluble antioxidant vitamin that quenches ROS and augments immunity. It reduces interleukin-6 and cortisol responses to exercise in humans.	Moderate support for ‘preventing URS’ Cochrane review of 5 studies in heavy exercisers (n=598) shows ~50% decrease in URS taking vitamin C (0.25–1.0 g/day). Further support required Unclear if antioxidants blunt adaptation in well-trained Relatively small effects on cortisol compared with carbohydrate; immune measures no different from placebo No support for ‘treating URS’ Cochrane reviews show no benefit of initiating vitamin C supplementation (>200 mg/day) after onset of URS.^{100 101}
Carbohydrate (drinks, gels)	It maintains blood glucose during exercise, lowers stress hormones, and thus counters immune dysfunction.	Low-moderate support Ingestion of carbohydrate (30–60 g/hour) attenuates stress hormone and some, but not all, immune perturbations during exercise. Very limited evidence that this modifies infection risk in athletes^{19 102}
Bovine colostrum	First milk of the cow that contains antibodies, growth factors and cytokines Claimed to improve mucosal immunity and increase resistance to infection	Low-moderate support that bovine colostrum blunts the decrease in saliva antimicrobial proteins after heavy exercise Some evidence in small numbers of participants that bovine colostrum decreases URS Further support required^{103 104}
Polyphenols, for example, Quercetin	These are plant flavonoids. In vitro studies show strong anti-inflammatory, antioxidant and antipathogenic effects. Animal data indicate an increase in mitochondrial biogenesis and endurance performance.	Low-moderate support Human studies show some reduction in URS during short periods of intensified training and mild stimulation of mitochondrial biogenesis and endurance performance, although in small numbers of untrained subjects. Limited influence on markers of immunity Putative antiviral effect for Quercetin Further support required^{105 106}
Zinc	This is an essential mineral that is claimed to reduce incidence and duration of colds. Zinc is required for DNA synthesis and as an enzyme cofactor for immune cells. Zinc deficiency results in impaired immunity (eg, lymphoid atrophy) and zinc deficiency is not uncommon in athletes.	No support for ‘preventing URS’ High doses of zinc can decrease immune function and should be avoided. Moderate support for ‘treating URS’ Cochrane review shows benefit of zinc acetate lozenges (75 mg) to decrease duration of URS; however, zinc must be taken <24 hours after onset of URS for duration of cold only. Side effects include bad taste and nausea.²⁴
Glutamine	This is a non-essential amino acid that is an important energy substrate for immune cells, particularly lymphocytes. Circulating glutamine is lowered after prolonged exercise and very heavy training.	Limited support Supplementation before and after exercise does not alter immune perturbations. Some evidence of a reduction in URS after endurance events in competitors receiving glutamine supplementation (2×5 g) Mechanism for therapeutic effect requires investigation.^{107 108}
Caffeine	This is a stimulant found in a variety of foods and drinks (eg, coffee and sports drinks). Caffeine is an adenosine receptor antagonist and immune cells express adenosine receptors.	Limited support Evidence that caffeine supplementation activates lymphocytes and attenuates the fall in neutrophil function after exercise Efficacy for altering URS in athletes remains unknown.^{109 110}
Echinacea	This is a herbal extract claimed to enhance immunity via stimulatory effects on macrophages. There is some in vitro evidence for this.	Limited support Early human studies indicated possible beneficial effects, but more recent, larger scale and better controlled studies indicate no effect of Echinacea on infection incidence or cold symptom severity.^{111 112}
Omega-3 PUFAs	Found in fish oil May influence immune function by acting as a fuel, in their role as membrane constituents or by regulating eicosanoid formation, for example, prostaglandin Prostaglandin is immunosuppressive. Claimed to exert anti-inflammatory effects postexercise	Limited support for blunting inflammation and functional changes after muscle-damaging eccentric exercise in humans and no evidence of reducing URS in athletes^{113 114}
Vitamin E	An essential fat-soluble antioxidant vitamin that quenches exercise-induced ROS and augments immunity	No support Immune-enhancing effects in the frail elderly but no benefit in young, healthy humans One study actually showed that vitamin E supplementation increased URS in those under heavy exertion. High doses may be pro-oxidative.^{115 116}
β-glucans	Polysaccharides derived from the cell walls of yeast, fungi, algae and oats that stimulate innate immunity	No support in humans Effective in mice inoculated with influenza virus; however, human studies with athletes show no benefits.^{117 118}

PUFA, polyunsaturated fatty acids; ROS, reactive oxygen species; URS, upper respiratory symptoms.