Colds and flu: Keeping well in the winter season

Most of the magic bullets to treat colds and flu – from antibiotics to zinc lozenges – are shots in the dark and not as effective as tried-and-tested traditional remedies.

Virtually everyone has a theory about colds and flu and, given the glut of information, it may be hard to separate the facts from plain fiction. Yet, there are data that show what makes us vulnerable to these infections, and how to stay well when the weather turns cold.

Susceptibility and stress
Catching the flu is not a random event. Bugs may be getting nastier (see box below), and our poorly ventilated, sometimes crowded, environments may encourage the spread of virulent viruses. But if exposure were the only factor, all of us would get sick every time we were exposed.

In truth, many people in a room may be exposed to a cold or flu virus, but only some become infected. Susceptibility, not exposure, is the key and is likely to be influenced by a number of things.

People who have heart complaints, asthma, chronic kidney disease or diabetes, or who are taking medications (for instance, steroids) are more susceptible to colds and flu. Smokers are also more susceptible to upper respiratory tract infection (URTI; Am J Public Health, 1993; 83: 1277-83).

But predicting susceptibility in an otherwise healthy population is less straightforward. Nutritional status and exercise play a role (see boxes, pp 2 and 3) but, recently, a great deal of study has focused on the role of stress.

The ability of stress to alter immune function, and precipitate and aggravate infectious diseases has long been recognised (J Fla Med Assoc, 1993; 80: 409-11). Today, there is strong evidence that the single biggest risk factor that puts otherwise healthy people at risk of catching a cold may be stress.

In one study, after determining their stress levels by questionnaire, 394 subjects were exposed to common rhinoviruses (the virus causing the common cold). Only 27 per cent of the low-stress group showed clinical symptoms compared with 47 per cent of those at the high end of the scale (N Engl J Med, 1991; 325: 606-12).

In another study, 276 subjects, who had been carefully evaluated for their level of involvement in one or more of a dozen types of social ties – for example, with a spouse or partner, sibling, parent, close friend or fellow worker – were given nasal drops containing rhinoviruses.

Susceptibility to colds was reduced as social support increased. Of those with three or less relationships, 62 per cent came down with a cold compared with only 35 per cent in those with six or more types of social support (J Am Med Assoc, 1997; 277: 1940-4).

A repeat of that study (Health Psychol, 1998; 17: 214-23) evaluated stress more precisely (long term vs short term) as well as the severity of illness, and also measured blood levels of natural-killer (NK) cells, the immune system cells that combat infectious agents. Those stressed for more than a month had lower NK-cell activity and were 2.2 times more likely to develop colds. The biggest risk came with increased job stress.

Stressed children have a greater susceptibility to URTI and show measurable decreases in mucosal immunity (J Psychosom Res, 1997; 43: 271-8). Depression is also strongly related to catching a cold (Epidemiology, 2001; 12: 345-9).

Prescription drugs, like antibiotics, can also increase colds/ flu susceptibility. A substantial number of GPs still prescribe antibiotics for colds/flu, even though these drugs don’t work against viruses (J Am Med Assoc, 1997; 278: 901-4; J Am Med Assoc, 1998; 279: 875-7).

Australian doctors report that flucloxacillin, a semisynthetic penicillin, can cause cholestatic jaundice (Med J Aust, 1989; 151: 701-5), though its relation to the drug may go unrecognised because of a delayed onset (Lancet, 1992; 339: 679). Older patients and those receiving flucloxacillin for more than two weeks are particularly at risk (BMJ, 1993; 306: 233-5).

Newer combination antibiotics such as Septrin – trimethoprim and sulphamethoxazole, or co-trimoxazole – have been linked with skin rashes and blisters (Ind J Derm, 1982; 48: 207-8; Br J Dermatol, 1987; 116: 241-2; Dermatology, 1986; 172: 230-1), and a host of HIV-like symptoms, including anaemia, loss of appetite, nausea, vomiting, numbness, convulsions, chills, fever, swollen glands, and ulcers in the mouth, eyes and urethra.

Overuse of antibiotics also contributes to the emergence of ‘superbugs’, and can deplete the friendly gut bacteria needed to maintain good health and immunity. Clearly, when you take antibiotics, you are risking a trade-off of symptoms which may leave you more unhealthy than you were before.

Over-the-counter madness
If you do succumb to a cold or flu, there are literally hundreds of over-the-counter (OTC) remedies that claim to relieve cold symptoms, but most have been proven useless (J Am Med Assoc, 1993; 269: 2258-63). The most popular varieties use a scattergun approach, mixing several different types of ingredients, often resulting in a variety of side-effects.

For instance:
*Nasal sprays containing phenylephrine hydrochloride, oxymetazoline hydrochloride or xylometazoline hydrochloride may clear the nose initially but, after a few days, their continued use can cause a rebound effect, producing worse nasal congestion than before.

* Oral decongestants stimulate the sympathetic nervous system and can increase blood pressure and pulse – risky for those with hypertension. They can cause heart rhythm disturbances, anxiety and a rebound effect. Perhaps the worst offender is phenylpropanolamine (PPA). In one study, this chemical increased the risk of stroke in women more than threefold (N Engl J Med, 2000; 343: 1826-32). This was the last straw in more than a decade of studies of PPA. The US Food and Drug Administration (FDA) has asked drug companies to stop marketing products containing PPA but, in the UK, it is still widely found in cold remedies.

* Antihistamines may reduce a runny nose and sneezing, but have a minimal effect on other symptoms. They can have a sedating effect and are often added to multisymptom cold remedies because of their ability to counteract the stimulant effect of decongestants.

* Cough suppressants such as guaifenesin (Robitussin) and dextromethorphan (NyQuil or Night Nurse) show no efficacy in suppressing coughs. The latter has been associated with liver damage and is used by teenagers to get a ‘poor man’s high’. Codeine also doesn’t suppress coughs, but can result in constipation.

* Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, paracetamol (acetaminophen) and ibuprofen may in fact increase nasal symptoms. There is also evidence that aspirin decreases the antibody response in rhinovirus infections (J Am Med Assoc, 1975; 231: 1248-51; J Infect Dis, 1990; 162: 1277-82). Furthermore, the influenza virus grows best at 34-35º C, but poorly – if at all – at temperatures greater than 37º C. So reducing fever with NSAIDs may simply prolong the agony of a cold or flu.

To jab or not to jab?
Predicting a flu epidemic is not an exact science, as was elegantly illustrated in 1976 when US officials, spurred on by illness among soldiers at Fort Dix, New Jersey, predicted a swine flu epidemic as lethal as the great flu pandemic of 1918. In the event, rates of flu and pneumonia-related deaths in 1976 were at their lowest in years (MMWR, 1976; 25: 391-2), much to the chagrin of the government, which had spent millions preparing a vaccine.

As flu can be caused by any of hundreds of strains of myxovirus, which mutate more or less constantly, vaccination amounts to a kind of biological Russian roulette. Even if the vaccine is for the right strain of myxovirus, for reasons not yet fully understood, you may not respond by producing anti-bodies to it. One study found that 30-40 per cent of elderly people do not respond to vaccination (Hum Immunol, 1994; 40: 202-9), and even if an immune response occurs, there is doubt as to whether this reduces the incidence of influenza (Vaccine, 1994; 12: 1185-9).

Studies into the efficacy of the flu vaccine show mixed results (Gerontology, 1995; 41: 3-10), and questions remain as to whether the inactivated virus used in the vaccine can truly provide complete protection (Int Arch Allergy Immunol, 1995; 108: 318-20).

Then there are the side-effects. While authorities say these are rare, this is cold comfort if you are among those affected. The ill-fated swine flu vaccine resulted in a rise of Guillain-Barré syndrome, a type of paralysis (Am J Epidemiol, 1979; 110: 105-23). In one UK study, around one in 12 patients said the flu vaccine was a trigger for asthma attacks (Lancet, 1998; 351: 326-31). Optic neuritis and permanent blindness, vasculitis and joint problems, reversible paralysis and myelopathy have also been reported (Am J Ophthalmol, 1997; 124: 703-4; J Rheumatol, 1997; 24: 1198-202; Ned Tijd Geneeskunde, 1995; 139: 2152-4; Muscle Nerve, 1995; 18: 1199-201).

Reviews of the benefits of vaccines in healthy adults have shown that these are negligible, sucessfully reducing the number of virus carriers (as shown by blood tests), but not of those who actually develop the flu (Cochrane Database Syst Rev, 2000; [2]: CD001269; Vaccine, 2000; 18: 957-1030).

Vitamin C, zinc and Echinacea
Research shows that most of us treat colds and flu at home (J Fam Pract, 1998; 47: 366-9). Decades of research have gone into vitamin supplementation and immunity, and many nutrients have proved to be important in shoring up our immune defences (see box below).

The most popular of these are vitamin C and zinc, although opinion varies regarding their true effectiveness. In the 1970s, Linus Pauling’s review of the evidence concluded that large doses of vitamin C prevented colds and alleviated symptoms (Proc Natl Acad Sci USA, 1971; 68: 2678-81).

Since that time, however, the efficacy of vitamin C has been hotly debated. A 1975 analysis by Thomas Chalmers concluded that the case for vitamin C had “questionable validity” (Am J Med, 1975; 58: 532-6), but a recent analysis of the report suggests that his analysis was seriously flawed (J Am Coll Nutr, 1995; 14; 116-23).

It is now generally accepted that a dose of 1-8 g of vitamin C daily can decrease the severity of cold symptoms by an average of 23 per cent and reduce the duration of illness by nearly half (Scand J Infect Dis, 1994; 26: 1-6; Br J Nutr, 1992; 67: 3-16).

More recent reviews of the evidence say that, while vitamin C can alleviate cold symptoms, taking large doses is not preventative (Cochrane Database Syst Rev, 2000; [2]: CD000980). However, some groups may benefit from regular supplementation, such as athletes under heavy physical stress (Int J Sport Med, 1996; 17: 379-83). One review suggests a reduction in cold incidence of up to 50 per cent with regular vitamin C use (Int J Tuberc Lung Dis, 1999; 3: 756-61).

Zinc has long been promoted as a remedy and preventative for colds and flu. In one study, a nasal gel containing zinc significantly shortened the duration of a cold if taken within 24 hours of the onset of symptoms (Ear Nose Throat J, 2000; 79: 778-80, 782).

However, taken as a whole, the evidence for the efficacy of zinc lozenges is inconclusive (Cochrane Database Syst Rev, 2000 [2]: CD001364; J Nutr, 2000; 130 [5S Suppl]: 1512S-5S). The first study of zinc lozenges found a seven-day reduction in colds duration with zinc (Antimicrob Agents Chemother, 1984; 25: 20-4). Such results piqued drug company interest and, by the end of the1980s, five more studies had been carried out. However, only one of these showed zinc to have any effect. But then, in 1996, another study suggested that zinc lozenges were effective against cold symptoms (Ann Intern Med, 1996; 125: 81-8), thus launching zinc back on the road to popularity.

One trial of zinc lozenges (12.8 mg) found that patients taking one every two to three hours early in the course of a cold reduced the duration and severity of their symptoms, especially cough (Ann Intern Med, 2000; 133: 245-52).

But another randomised double-blind trial of 249 children (total daily dose of 50-60 mg) found no difference between zinc lozenges and placebo (J Am Med Assoc, 1998; 279: 1962-7). More recently, a trial of both zinc gluconate and zinc acetate concluded that neither had much effect on cold symptoms (Clin Infect Dis, 2000; 31: 1202-8).

So far, at least 10 double-blind trials have evaluated zinc lozenges for treating the common cold. Half have shown efficacy and half have not, results which may be due to methodological differences. Trials that began therapy shortly after onset of symptoms, used zinc gluconate or glycine-sweetened zinc gluconate and gave multiple daily zinc doses of 13-23 mg per dose found zinc to be effective. Most of the negative trials, on the other hand, varied from this protocol in one way or another.

Echinacea, one of the best-selling OTC herbals, has also shown mixed efficacy. German researchers gave the liquid root extract of either E. purpurea or E. angustifolia, two of the most popular types, or placebo to 302 healthy volunteers in a double-blind randomised trial. Results showed that both types of Echinacea were only slightly more effective than the placebo in preventing colds over a 12-week period, although participants taking the herb reported feeling better than those taking placebo. The authors concluded that, at best, Echinacea may reduce the risk of catching a cold by about 10-20 per cent (Arch Fam Med, 1998; 7: 541-5).

Other studies, however, have shown that Echinacea can relieve symptoms, reducing both the severity and duration of a cold (Arzneim Forsch, 2001; 51: 563-8; Arch Fam Med, 1998; 7: 541-5). One trial in Sweden looked at 246 healthy adults who caught a cold and took an E. purpurea preparation or placebo. The subjects took two tablets three times a day for seven days or until they felt better. The Echinacea preparations were significantly more effective than the placebo (Phytomedicine, 1999; 6: 1-6).

The key to these and other remedies may be to treat at the first signs of cold or flu. A recent review of 13 trials of Echinacea in the treatment and prevention of colds concluded that, while it may not prevent colds, early treatment could be beneficial for relieving symptoms (J Fam Pract, 1999; 48: 628-35). It also noted that Echinacea preparations vary widely in composition.

When colds or flu strikes, we all hope for a magic bullet to make things right, but most of the methods we use are still shots in the dark. Traditional approaches – usually involving rest, liquids and keeping warm – may not be glamorous but, in the end, appear to be effective, less prone to adverse effects and less expensive.

Pat Thomas

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What Doctors Don't Tell You Written by What Doctors Don't Tell You

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