Cold-fX: More Hype than Hope for Colds and the Flu

Cold and flu season is in full swing here in Canada, and we’re all trying to avoid catching something, and recover faster if we’re already sick. Supported by endorsements from Canadian celebrities, and a recently announced tie-in with the 2010 Vancouver Olympics, the biggest selling cold product in Canada is Cold-fX, manufactured by Edmonton-based Afexa Life Sciences. If it’s not already in a pharmacy near you, it will be soon.

What is Cold-fX?

American ginseng (Panax quinquefolium) has been used medicinally for centuries, most commonly as an “adaptogen” where it was and is still believed to be effective for everything from anemia to AIDS to impotence and even cancer. [1] Few uses have been evaluated scientifically, and when studied, ginseng has not been demonstrated to be conclusively effective for any medicinal use. [1] [2]

Colds can be caused by one of hundreds of viruses. In general, adults get 4-6 colds per year.  There are few effective treatments for colds, with most products simply relieving symptoms, without affecting the duration of the cold. Influenza (the flu) is caused by one of three influenza viruses (A, B, or C). Influenza can cause much more serious infections than colds, especially in the very young, the very old, and other high-risk individuals.  Both colds and flu are easily transmitted by hand contact or by inhalation. Both cause a cascade of immune reactions in response to an infection.  Headache, fever, fatigue, congestion, cough, and sore throat are all common symptoms.

How ginseng might prevent colds or flu is not known with certainty.  Research suggests American ginseng does seem to have an effect on elements of the immune system. Monocytes, tumor necrosis factor, natural killer cells and other factors involved in cell-based immunity seem to be stimulated by ginseng. However, how this might relate to viral infections, like colds and the flu, is not clear. In fact stimulation of interleukin and tumor necrosis factor might actually increase the severity of cold or flu symptoms. [1]

CV Technologies has developed a formulation of ginseng root which is claimed to be consistent (“standardized”) with respect to the content of polysaccharides and ginsenosides, using the company’s proprietary, patented process, ChemBioPrint.  It is these components of the ginseng root that are believed to be the active components for the prevention and treatment of colds and influenza infections.  The rationale for standardization of herbal medicines is a good one: if the active ingredients are known, the manufacturer can ensure a consistent product.

How has Cold-fX been studied to treat or prevent colds or the flu?

For the purposes of this review, let’s consider the available evidence that has been published. There are only three relevant trials, all funded by the manufacturer:

McElhaney et al. Journal of the American Geriatric Society, 2004. [3]

This study examined whether Cold-fX could prevent respiratory illness (i.e., the common cold or influenza) in 198 healthy nursing home residents over an eight or twelve week period. (Two separate studies were combined in the results.) Patients took Cold-fX 200mg twice a day, or a placebo. Patients and physicians were not aware (i.e., double-blind) of the treatment assigned.

Results: Cold-fX was as well tolerated as the placebo. In each study, there was no significant difference between the groups in the number of patients that reported cold or flu symptoms. In addition, there was no significant difference in the number of laboratory-confirmed flu cases. However, when the studies were combined, the difference in lab-confirmed flu cases was statistically significantly less in the Cold-fX group (1%) than the placebo group (9%).  The act of combining the two trials has been criticized as means to make the results appear statistically meaningful.

Bottom line: If we accept the combining of the two trials, we can conclude the following: In nursing home residents, when taken for 8 to 12 weeks, Cold-fX appeared to reduce laboratory-confirmed cases of colds and flu, but had no effect when considering what patients actually reported.

Predy et al. Canadian Medical Association Journal, 2005. [4]

This study examined the effectiveness of Cold-fX to prevent colds and flu in 323 healthy adults, ranging in age from 18 to 65 (average age 42). Anyone with any significant illness (e.g., diabetes, heart or lung disease) was not permitted to participate. Also double-blinded, participants were instructed to take Cold-fX 400mg once daily (two, 200mg capsules) or a placebo, for four months. A daily journal was used to record cold symptoms. No laboratory verification of colds was performed.

Results: Patients taking Cold-fX had 0.68 colds/person and those taking placebo had 0.93 colds/person – a reduction of 0.25 colds over the study period. Patients taking Cold-fX had fewer cold symptoms, and for fewer days, but the duration of each cold was not different between groups. Cold-fx was well tolerated.

Bottom line: A healthy adult taking Cold-fX might expect to have 0.25 less colds over a 16 week period. This has led some to question whether this result is clinically relevant.)

McElhaney et al. Journal of Alternative and Complementary Medicine, 2006. [5]

This paper is the most recent, but is actually the oldest study, being conducted in 1998. The journal’s quality is questionable, with an Editor-in-Chief who is homeopath and an acupuncturist, and journal content that includes “research” on implausible, non-science based treatments such as therapeutic touch, acupuncture, reiki, and, not surprisingly, homeopathy. Setting this aside, let’s consider the paper itself.

This very small study (43 people) examined the effectiveness of Cold-fX to prevent colds or the flu in community-dwelling (i.e., not in nursing homes) seniors, over the age of 65. Anyone with a “medical condition” (not well defined) was not permitted to participate, nor was anyone on medications (again, not well defined). Also double-blind, participants were told to take Cold-fX 400mg (two, 200mg capsules), or a placebo, once daily for 16 weeks. Almost no information is provided to help the reader determine if two groups were similar with respect to background and medical history. Patients were asked to record any cold symptoms in a daily journal, and, if the product they were taking helped reduce their symptoms. After four weeks of taking Cold-fX, all participants received the flu vaccine. Patients were then assessed at week 8 and week 16.

Results: The number of patients reporting colds or flu symptoms did not differ significantly over the 16 weeks. However, the authors conducted a post-hoc analysis and looked at different time periods. They observed that in the second eight week period, there were fewer colds (7 vs. 13) and they were of a shorter duration (5.6 days vs. 12.6 days), in the Cold-fX group. There were no significant differences in the adverse events reported by the two groups.

Bottom line: Over a 16 week period Cold-fx failed to demonstrate an improvement over placebo. Given the high number of study design flaws, data omissions, the poor quality journal, and long publication delay, it is difficult to draw conclusions from the results. At best, it is suggestive that Cold-fX needs to be taken for at least eight weeks, with a flu shot after four weeks, before it may have any noticeable effect.

What does the science tell us, then?

The most persuasive evidence comes from the Predy study. In addition, it’s from the most reputable journal of the three cited. The effect, while statistically significant, is not all that meaningful. The 2004 trial didn’t show any meaningful impact of Cold-fX, and the 2006 trial’s data analysis is questionable: In any case it doesn’t reveal any impact until the drug is taken for eight weeks. Based on the three trials, it seems reasonable to reserve final judgement on Cold-fX. If Cold-fX was really as effective as the advertising implies (“Stop colds. Start now”), the effect would be obvious across all three trials. If it does have any effect at all at preventing colds, the effect very, very modest.

What if I feel like I’m coming down with a cold? Will starting Cold-fX now have any effect?

There is no published evidence to demonstrate the effectiveness of Cold-fX if started at the onset of a cold.

CV Technologies offers a 300mg form of their product (“Extra-Strength Cold-fX“) with the directions to start “at the first sign of colds of flu symptoms”. There are no published trials documenting the effectiveness of the 300mg dosage strength, or evaluating the dosing instructions of 12 capsules over the first 3 days, in reducing the duration of colds or the flu.

How safe is Cold-fX?

There’s no published evidence with Cold-fX suggesting it can be used safely for longer than 4 months.  American ginseng has been associated with gastrointestinal, nervous, and cardiovascular effects,but this does not appear to be different than placebo. [1] It is not considered safe for use in pregnant or breast-feeding women. [1] As the clinical trials did not allow most people with medical conditions to participate, its safety in these groups is unclear. Ginseng interacts with several prescription drugs, especially warfarin (Coumadin), so anyone considering Cold-fX should consult their pharmacist, to ensure that Cold-fX is safe to take with their prescription or non-prescription medications. [1]

Conclusion

Cold-fX is a undeniable Canadian sales success, but this seems to be due more to marketing, rather than science. The data published to date suggests that it may have some sort of a biological effect- but it’s a small one, and for many people that take it, the data suggests it will not be effective in preventing colds or the flu.

It’s important to point out the positive aspects of this product: the manufacturer has taken some steps to address standardization problems inherent with natural health products, there is a plausible (though not well established) mechanism of action, and several clinical trials have been performed (albeit each with flaws), with additional trials underway.

Cold-fX is priced at around CAD$0.45 per capsule, which works out to about $0.90 per day. Using the data above, four months of treatment will cost about $100. You need to take it for 16 months (say, four winters in a row) to prevent a single cold, according to the Predy trial. So the cost of preventing a single cold episode works out to be roughly $400. Is this worth it? That’s for you to decide.

If the cost looks excessive compared to the benefit, consider the following: One of the best thing you can do to avoid getting a cold is easy, costs next to nothing, and has been demonstrated to be convincingly effective: wash your hands frequently.

For More Information:

For more information about the treatment of colds and the flu, I recommend the excellent Natural Medicines Comprehensive Database, which provides a thorough overview of the efficacy of different products.

As I completed this review I came across an excellent (and more detailed) analysis by Ottawa Skeptics that delves a little deeper into the Cold-fX phenomenon. It does a thorough job of contrasting the marketing claims with what the science actually demonstrates.

References

[1] American Ginseng. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2009 [cited 10 February 2009] Available from: http://www.naturaldatabase.com. Subscription required to view.

[2]Vogler B K, Pittler M H, Ernst E. The efficacy of ginseng: a systematic review of randomised clinical trials. European Journal of Clinical Pharmacology 1999; 55(8): 567-575. (Summary here)

[3] Janet E. Mcelhaney, Stefan Gravenstein, Sharon K. Cole, Edward Davidson, Dennis O’Neill, Sharon Petitjean, Barry Rumble, Jacqueline J. Shan (2004). A Placebo-Controlled Trial of a Proprietary Extract of North American Ginseng (CVT-E002) to Prevent Acute Respiratory Illness in Institutionalized Older Adults Journal of the American Geriatrics Society, 52 (1), 13-19 DOI: 10.1111/j.1532-5415.2004.52004.x

[4] Gerald N. Predy, Vinti Goel, Ray Lovlin, Allan Donner, Larry Stitt, Tapan K. Basu (2005). Efficacy of an extract of North American ginseng containing poly-furanosyl-pyranosyl-saccharides for preventing upper respiratory tract infections: a randomized controlled trial Canadian Medical Association Journal, 173 (9), 1043-1048 DOI: 10.1503/cmaj.1041470

[5] Janet E. McElhaney, Vinti Goel, Benjamin Toane, Johnathan Hooten, Jacqueline J. Shan (2006). Efficacy of COLD-fX in the Prevention of Respiratory Symptoms in Community-Dwelling Adults: A Randomized, Double-Blinded, Placebo Controlled Trial Journal of Alternative and Complementary Medicine, 12 (2), 153-157 DOI: 10.1089/acm.2006.12.153

Update: 2009-09-25: Updated manufacturer’s name to Afexa Life Sciences from CV Technologies, to reflect the organization’s name change.