One possible way to boost the immune response to the flu shot is by supplementing with probiotics or prebiotics. There’s evidence to suggest^[8] that both can positively influence the immune response. It also seems that the way both prebiotics^[9][10] and probiotics^[11] influence the immune system could improve the immune response to vaccination. This implies that supplementation could help make flu shots stick. This hypothesis has been examined in multiple clinical trials. However, some of these trials have come up^[12] positive^[13], while others have found no evidence^[14][15] of an effect.

Colds and the flu are caused by viruses that travel from person to person. Although you fend off infections year round, you may be more vulnerable during the colder months: the ambient cold may weaken your immune system, according to preliminary human^[26] and animal^[27] evidence, and if it makes you spend more time inside with other people, it also gives you more opportunities to trade viruses and microbes.

Unfortunately, even if you follow these best practices, you can still get unlucky and catch a cold or contract the flu. This is why, once winter hits, one of the most popular questions we get is: among the many supplements used to ward off an infection or lessen its symptoms, are there any that work?

The answer is a tentative yes. In this article, we’ll review four supplements whose benefits are backed by moderate evidence and four whose benefits are backed by only preliminary evidence.

Supplements with moderate evidence

The evidence regarding the benefits of vitamin C, vitamin D, and zinc is often mixed, but it suggests a positive effect.

Vitamin C

Vitamin C is marketed as the go-to supplement for preventing and treating colds.

Mechanistically, it makes sense: vitamin C helps immune cells form and function, and it supports the physical barriers (such as the epithelial cells of your skin) that protect you from pathogens.^[28] Moreover, at least 148 animal studies have found that vitamin C administration helps prevent infections caused by microorganisms.^[29]

Those animal studies, however, don’t answer the question that most matters to us: can vitamin C supplementation help humans ward off colds? A 2013 Cochrane meta-analysis of human studies tried to answer this question,^[30] and here are the takeaways:

• People who start taking vitamin C when they already have a cold don’t appear to see much of a benefit. Some studies suggest that very high doses (several grams) might reduce the duration of colds, but more studies are needed for confirmation.
• People who take vitamin C regularly can expect shorter colds (by 8% in adults and 14% in children) with slightly less severe symptoms.
• Athletes who take vitamin C regularly are half as likely to catch a cold as athletes who don’t. Only people who “perform regular or acute bouts of intense exercise” seem to enjoy this benefit.

A 2018 meta-analysis also supports the idea that vitamin C can shorten colds and lessen symptoms.^[31] It included only 9 trials, however, all of which were among the 29 trials included in the 2013 Cochrane meta-analysis.

Vitamin C can reduce the duration of colds (and even help ward them off, if you’re an athlete), but only if you’ve been supplementing regularly. If you start when you’re sick, it’s probably too late.

Vitamin D

Vitamin D receptors are found throughout the body, and vitamin D is involved in many cellular processes, including the regulation of immune cells during infections,^[32][33] so it should come as no surprise that a deficiency can impair immunity.

Epidemiological studies show an association between low vitamin D levels and a higher risk of viral infections of the upper respiratory tract (URT). ^[34][35] According to a 2017 systematic review and meta-analysis of individual participant data from randomised controlled trials, taking vitamin D could help prevent asthma symptoms as well as URT infections.^[36] More may not be better, however: a randomized trial published the same year found no statistically significant difference in incidence and duration of URT viral infections between children taking 400 IU/day and children taking 2,000 IU/day.^[37]

Vitamin D serves many functions in the body, and a deficiency may impair immunity. A large systematic review suggests that supplementation may help prevent upper respiratory infections.

Zinc

Zinc plays many roles in the body — including several in the immune system alone. If you easily catch colds, make sure your diet provides you with enough zinc. Athletes and other people who sweat a lot are at greater risk of zinc insufficiency, but taking too much zinc is aso a risk, so be careful.

Zinc lozenges can limit virus replication at the nasal epithelium and may reduce respiratory tract inflammation. Sucked throughout the day (75–95 milligrams of zinc per day, starting within 24 hours of symptom onset), they can reduce the duration of a cold by 2–4 days, though symptoms may persist for a few days thereafter.^[38][39] Lozenges with zinc acetate may be more effective than lozenges with zinc gluconate (a more common form), but the trials are few, and a recent meta-analysis failed to find a significant difference.^[40]

Zinc lozenges can cause nausea and dysgeusia (a change in taste perception), but those symptoms stop when supplementation stops.^[38][39] In addition to nausea and dysgeusia, zinc nasal sprays can cause anosmia,^[41] and this loss of smell perception may persist after supplementation has stopped. For that reason, and because the sprays have not been shown to be more effective than the lozenges, the sprays are not recommended.

The zinc dose shown to reduce the duration of colds (75–95 mg/day^[38][39]) is above the safe upper limit (40 mg/day). You should suffer no harm if you take up to 100 mg/day for up to two weeks, but if you start suffering from nausea, vomiting, loss of appetite, stomach cramps, diarrhea, or headaches, all signs that you may be taking more zinc than your body can stand, just stop supplementing with zinc. Also, remember that zinc is present in foods and in many supplements, notably multivitamins: make sure that you don’t end up taking more zinc than you planned to.

Taking zinc lozenges throughout the day, starting from the very first symptoms of a cold, may reduce the duration of the illness, but supplementation should not exceed 100 mg of zinc per day for up to two weeks. Since zinc nasal sprays might cause a lingering loss of smell perception, they’re better avoided.

Supplements with preliminary evidence

Many other supplements might help reduce the duration and severity of colds and the flu, but the evidence tends to be mixed, scarce, or low in quality. Among the most promising supplements are echinacea, elderberries, Pelargonium sidoides, and probiotics.

Echinacea

Taken daily, echinacea might reduce the risk and duration of upper respiratory infections,^[42] yet trial effects are so small as to lack statistical or clinical significance.^[43] Moreover, many of the trials were low in quality, or their quality was difficult to determine.

Echinacea can interact with medications, particularly immunosuppressive drugs. If you take any medication, you may want to consult a physician before trying this supplement.

Echinacea might reduce the risk and duration of upper respiratory infections, but many of the studies are of low quality and the effects are very small at best.

Elderberries

Elderberries (the fruits of the elderberry shrub) are known for their antioxidant properties, and in one randomized controlled trial, an elderberry extract reduced the duration and severity of colds more than placebo.^[44] Also, a few human trials have shown elderberries to reduce symptoms of the flu,^[45] but here the evidence is weakened by small sample sizes and, in some cases, low methodological quality.

Due to the small number of studies, both the efficacy and safety of elderberries are still in doubt.^[46] Should you choose to prepare elderberry juice yourself, rather than to purchase a supplement, remember that the berries must be properly cooked, since they can otherwise cause nausea or, worse, cyanide toxicity. Only ever use the berries — the rest of the plant is poisonous and should not be consumed in any form.

Elderberries are a promising but understudied supplement: they may reduce the symptoms of colds and the flu, but the evidence is still preliminary. Beware: the plant is poisonous, and even the berries can be dangerous if not prepared properly.

Pelargonium sidoides

Pelargonium sidoides contains prodelphinidins — tannins that can help prevent bacteria from attaching to the lining of the throat and lungs. Pelargonium sidoides may reduce the duration and severity of colds,^[47][48] but the studies are few and haven’t been critically appraised in systematic reviews. In addition, none of the studies were designed to see if Pelargonium sidoides could ward off colds.

Pelargonium sidoides seems to reduce the duration and severity of colds, but the evidence is still preliminary.

Probiotics

Various probiotics have been shown to interact with immune system cells,^[49] but a 2015 report summarizing 17 Cochrane systematic reviews found no high-quality evidence that probiotics could prevent illnesses.^[50]

Since then, a different systematic review and meta-analysis of 23 randomized controlled trials (RCTs) has found that probiotics appear to decrease the incidence of respiratory tract infections (RTIs) in children,^[51] and two RCTs reported that specific probiotics might help prevent upper RTIs in athletes^[52] and the elderly,^[53] but the Cochrane reviews are still the most reliable evidence we have.

Truth is, systematic reviews of probiotics studies are difficult to perform, for two reasons:

• Different studies used different bacterial strains, so their comparability is low.
• Some studies combined strains, making it impossible to determine which strain or strains caused the effects noted.

With regards to the flu, a 2017 meta-analysis of 9 RCTs found that taking probiotics and/or prebiotics helped improve the efficacy of the flu vaccine in healthy adults when supplemented around the time of vaccination. However, many of the trial participants were healthy older adults, often above the age of 70, and we can’t be sure the benefits extend to a younger population.

Probiotics might help prevent respiratory tract infections, but the evidence is of low quality. Several studies suggest that probiotics may increase the efficacy of the flu vaccine in healthy, older adults.

Recommendations

Reaching for a supplement or two can seem like a quick, simple way to defend yourself against colds and the flu. Be it for prevention or treatment, however, even taking the best supplements won’t help as much as following these best practices:

So, as always, choose efficacious supplements to complement your healthy habits — not to make up for a lifestyle that predisposes you to getting sick.

If you’re looking for information on optimal dosages and combinations, then you may be interested in our Allergies & Immunity Supplement Guide.

It is sometimes recommended that you “feed a fever”, but there are no human studies examining whether eating more or less improves recovery from an influenza infection (a common cause of fever). Nonetheless, a small amount of research on mice suggests being adequately-fed is worthwhile when dealing with a flu.

A 2017 study looked at whether increasing the food intake of mice would be protective against infection with a strain of influenza A (H1N1). Following infection, the animals naturally ate less (as is common during illness) and many died within 30 days. However, mice who were force-fed an extra 1/5th of their usual calorie intake were more likely to survive the virus.^[16] Conversely, research on mice who were energy restricted (e.g., fed a diet with similar amounts of micronutrient but 40% fewer calories) found these animals were more prone to dying following influenza infection.^[17] Furthermore, increasing the food intake of these calorie restricted mice leading up to when they were infected partially reversed their viral susceptibility.^[17] That being said, all of these studies involved mice infected with very high doses of influenza virus. As a result, the effect of food intake on flu recovery in humans remains uncertain.

In non-tropical countries of the Northern hemisphere (e.g., the United States), flu rates are almost always highest during the winter;^[18] there are various proposed theories for why this is.

One explanation involves humidity and temperature. During the winter, the air is colder and less humid. This is notable, because various experiments have found that aerosol and droplet transmission of the influenza virus (two major routes of infection)^[19] occurs much more readily in colder and dryer (less humid) environments.^[20][21]

Another factor could be a reduction in vitamin D synthesis during the winter as a result of reduced exposure to ultraviolet light.^[22] Vitamin D has a well-established role in the immune system,^[23] meaning a wintertime drop could increase susceptibility to influenza. In support of this, a 2022 meta-analysis of 10 clinical trials found vitamin D supplementation reduced the risk of getting the flu by 22%.^[4]

Finally, other explanations exist, including changes in social behavior (e.g., large groups gathering inside more during the winter)^[24] and an alteration to the circadian rhythm due to longer nights.^[25] Ultimately, it’s likely a combination of factors working in tandem which make the flu a seasonal virus.