Ginseng Cuts Respiratory Infections in Elderly, but Not in Leukemia Patients

NEW YORK – A standardized extract of American ginseng (Panax quinquefolium) has been shown to be safe and effective in reducing the incidence and severity of acute respiratory infections among both community-dwelling and institutionalized elderly people.

However, the same product was not effective in decreasing respiratory infections among people with chronic lymphocytic leukemia (CLL), a condition that leaves patients particularly vulnerable to influenza and other acute respiratory infections (ARIs), reported Dr. Edward G. Shaw at an international conference sponsored by the Society for Integrative Oncology.

The promising findings from three studies among otherwise healthy elderly individuals led to the hope that this particular extract, known as CVT-E002 and marketed as an over-the-counter product called COLD-FX, might be similarly effective in patients with CLL, said Dr. Shaw of the Comprehensive Cancer Center, Wake Forest University, Winston-Salem, N.C.

CLL is the most common adult form of leukemia, affecting roughly 20/100,000 Americans. Because of the associated anemia, thrombocytopenia, and compromised immune system function, CLL survivors are at substantially increased risk of infections, especially respiratory infections. Common drug therapies like chlorambucil and fluorouracil increase this risk.

"There is a pressing need for effective, relatively low-cost interventions to reduce infection risk in CCL patients," Dr. Shaw said.

Panax ginseng is a reasonable botanical candidate for that job. Although it is indigenous to the United States and Canada, it is commonly used in traditional Chinese medicine and other Asian healing traditions. It is widely promoted as an immune system booster, and a number of preclinical and clinical studies support this claim.

The CVT-E002 extract, marketed by Afexa Life Sciences, is standardized to provide consistent doses of immunologically active compounds poly-furanosyl-pyranosyl-saccharides, which enhance natural killer cell activity, Dr. Shaw said. It is the only American ginseng extract that has been granted investigational new drug clearance by the U.S. Food and Drug Administration.

In 2004, Dr. Janet McElhaney of Eastern Virginia Medical School, Norfolk, published data from two studies of 89 and 109 people (mean age, 81 and 83.5 years, respectively) in nursing home and assisted living settings. The subjects were randomized to the ginseng extract (200 mg twice daily) or to placebo. The first trial lasted 8 weeks, and the second ran for 12. In both study cohorts, upward of 90% of the subjects had been vaccinated against influenza infections.

An episode of ARI was defined as two or more concurrent respiratory symptoms or one respiratory plus one constitutional symptom. Infectious diagnoses were confirmed by culture and serology.

Using an intent-to-treat analysis, Dr. McElhaney and her colleagues pooled the data from the two distinct trials. They found that lab-confirmed influenza was more common among the placebo group (seven cases in 101 subjects), compared with the ginseng-treated group (one case in 97 subjects). Incidence of influenza and respiratory syncytial virus infections combined was also higher in the placebo vs. the ginseng group (nine cases vs. one case). These differences were statistically significant (J. Am. Geriatr. Soc. 2004;52:13-9).

Interestingly, the investigators found no difference between the active treatment and placebo groups in terms of subjective reporting of ARI symptoms; roughly one-third of the people in each group reported ARI episodes, though the incidence of actual lab-confirmed infections was far lower.

Approximately 90% of the subjects in both groups reported adverse effects, the most common being gastrointestinal related. A total of 8% of the placebo group and 4% of the ginseng group required hospitalization, but none of these admissions was related to the study medications.

In 2006, Dr. McElhaney – now at the Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut, Farmington – published a trial of the same COLD-FX ginseng formula vs. placebo in a cohort of 43 community-dwelling adults aged 65 years and older. As in the previous trial, the ginseng dose was two 200-mg extract capsules daily, for a period of 4 months. After the first month of the trial, all subjects in both groups were immunized against influenza.

The investigators observed a significant reduction in episodes of ARI during November and December, the closing months of the trial. Of the placebo-treated group, 62% had an ARI episode, compared with 32% among those taking the CV-E002 extract. Duration of symptoms was also considerably longer in the placebo group (12.6 days vs. 5.6 days). Lab confirmation of infection was not done in this study (J. Altern. Complement. Med. 2006;12:153-7).

Adverse effects were few in both groups, and there was no significant difference between them. All of these studies were funded in part by CV Technologies, the company that manufactures the CVT-E002 extract.

These data, along with positive results from a Canadian study (CMAJ 2005;173:1043-8), prompted the Wake Forest group to look at the potential of the ginseng extract to reduce infection risk in CLL patients.

A total of 293 untreated CLL patients were randomized to take COLD-FX, 200 mg twice daily, or matching placebo for 3 months. The patients were instructed to keep a daily record of ARI symptoms in written diaries and to rate their symptoms on a 0-3 scale of severity. Subjects also recorded activity limitations, episodes of fever, and antibiotic use.

The patients had a mean age in the mid-60s; 75% of the active treatment group and 78% of the placebo group had been vaccinated against influenza. The investigators excluded people with HIV, cirrhosis, cardiovascular disease, multiple sclerosis, other malignancies, and liver enzyme abnormalities. They also excluded people on immunomodulatory drugs, hematopoietic stem cell recipients, and those on corticosteroids, antibiotics, or warfarin.

Of all subjects, 53% had an ARI during the study period from January to March. On average, ARI days occurred at a rate of 0.1/patient-day. Put another way, 1 of every 10 days is an ARI day for these patients, Dr. Shaw explained. Since only about half of the subjects actually had ARIs, this means that for them 1 out of every 5 days is an ARI symptom day.

Overall, there were no major differences between the treatment and placebo groups in terms of the primary study end points. In the ginseng-treated group, 50% had at least one ARI episode, compared with 55% in the placebo group, but this difference was not statistically significant.

In terms of symptom duration, the ginseng group had a mean total of 8.9 ARI days vs. 6.9 days, but this difference was also deemed not statistically significant.

There were no differences in use of antibiotics or other secondary end points. While there was a trend toward lower incidence of moderate to severe ARIs in patients taking the ginseng supplement (31% vs. 39%), it did not reach significance.

In terms of adverse events, there were 13 "serious" episodes in the ginseng group versus 27 in the placebo group. Diarrhea, dizziness, hyperglycemia, and joint pain were among the most common reported adverse effects, but these were rare, and only 2 of the 40 episodes were considered "possibly related to the treatment."

Both the ginseng-treated and placebo-treated groups showed a mean increase in total white blood cells, with the increase being slightly higher in the placebo group. However, both groups showed a decrease in absolute neutrophil counts. Peripheral blood CD4 cell counts decreased in the active treatment group but increased in the placebo group. None of these differences were statistically or clinically significant.

The study was funded by the National Cancer Institute and Afexa Life Sciences.

The researchers said they did not know why the ginseng extract failed to produce the expected reductions in ARI among these CLL patients, but suggested that it may be a dosing issue. "We went with the dose used in the previous studies of healthy elderly, noncancer patients. It might not have been enough for CLL patients with impaired immune function." Dr. Shaw added that dose-escalation studies are in the works.

NEW YORK – A standardized extract of American ginseng (Panax quinquefolium) has been shown to be safe and effective in reducing the incidence and severity of acute respiratory infections among both community-dwelling and institutionalized elderly people.

However, the same product was not effective in decreasing respiratory infections among people with chronic lymphocytic leukemia (CLL), a condition that leaves patients particularly vulnerable to influenza and other acute respiratory infections (ARIs), reported Dr. Edward G. Shaw at an international conference sponsored by the Society for Integrative Oncology.

The promising findings from three studies among otherwise healthy elderly individuals led to the hope that this particular extract, known as CVT-E002 and marketed as an over-the-counter product called COLD-FX, might be similarly effective in patients with CLL, said Dr. Shaw of the Comprehensive Cancer Center, Wake Forest University, Winston-Salem, N.C.

CLL is the most common adult form of leukemia, affecting roughly 20/100,000 Americans. Because of the associated anemia, thrombocytopenia, and compromised immune system function, CLL survivors are at substantially increased risk of infections, especially respiratory infections. Common drug therapies like chlorambucil and fluorouracil increase this risk.

"There is a pressing need for effective, relatively low-cost interventions to reduce infection risk in CCL patients," Dr. Shaw said.

Panax ginseng is a reasonable botanical candidate for that job. Although it is indigenous to the United States and Canada, it is commonly used in traditional Chinese medicine and other Asian healing traditions. It is widely promoted as an immune system booster, and a number of preclinical and clinical studies support this claim.

The CVT-E002 extract, marketed by Afexa Life Sciences, is standardized to provide consistent doses of immunologically active compounds poly-furanosyl-pyranosyl-saccharides, which enhance natural killer cell activity, Dr. Shaw said. It is the only American ginseng extract that has been granted investigational new drug clearance by the U.S. Food and Drug Administration.

In 2004, Dr. Janet McElhaney of Eastern Virginia Medical School, Norfolk, published data from two studies of 89 and 109 people (mean age, 81 and 83.5 years, respectively) in nursing home and assisted living settings. The subjects were randomized to the ginseng extract (200 mg twice daily) or to placebo. The first trial lasted 8 weeks, and the second ran for 12. In both study cohorts, upward of 90% of the subjects had been vaccinated against influenza infections.

An episode of ARI was defined as two or more concurrent respiratory symptoms or one respiratory plus one constitutional symptom. Infectious diagnoses were confirmed by culture and serology.

Using an intent-to-treat analysis, Dr. McElhaney and her colleagues pooled the data from the two distinct trials. They found that lab-confirmed influenza was more common among the placebo group (seven cases in 101 subjects), compared with the ginseng-treated group (one case in 97 subjects). Incidence of influenza and respiratory syncytial virus infections combined was also higher in the placebo vs. the ginseng group (nine cases vs. one case). These differences were statistically significant (J. Am. Geriatr. Soc. 2004;52:13-9).

Interestingly, the investigators found no difference between the active treatment and placebo groups in terms of subjective reporting of ARI symptoms; roughly one-third of the people in each group reported ARI episodes, though the incidence of actual lab-confirmed infections was far lower.

Approximately 90% of the subjects in both groups reported adverse effects, the most common being gastrointestinal related. A total of 8% of the placebo group and 4% of the ginseng group required hospitalization, but none of these admissions was related to the study medications.

In 2006, Dr. McElhaney – now at the Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut, Farmington – published a trial of the same COLD-FX ginseng formula vs. placebo in a cohort of 43 community-dwelling adults aged 65 years and older. As in the previous trial, the ginseng dose was two 200-mg extract capsules daily, for a period of 4 months. After the first month of the trial, all subjects in both groups were immunized against influenza.

The investigators observed a significant reduction in episodes of ARI during November and December, the closing months of the trial. Of the placebo-treated group, 62% had an ARI episode, compared with 32% among those taking the CV-E002 extract. Duration of symptoms was also considerably longer in the placebo group (12.6 days vs. 5.6 days). Lab confirmation of infection was not done in this study (J. Altern. Complement. Med. 2006;12:153-7).

Adverse effects were few in both groups, and there was no significant difference between them. All of these studies were funded in part by CV Technologies, the company that manufactures the CVT-E002 extract.

These data, along with positive results from a Canadian study (CMAJ 2005;173:1043-8), prompted the Wake Forest group to look at the potential of the ginseng extract to reduce infection risk in CLL patients.

A total of 293 untreated CLL patients were randomized to take COLD-FX, 200 mg twice daily, or matching placebo for 3 months. The patients were instructed to keep a daily record of ARI symptoms in written diaries and to rate their symptoms on a 0-3 scale of severity. Subjects also recorded activity limitations, episodes of fever, and antibiotic use.

The patients had a mean age in the mid-60s; 75% of the active treatment group and 78% of the placebo group had been vaccinated against influenza. The investigators excluded people with HIV, cirrhosis, cardiovascular disease, multiple sclerosis, other malignancies, and liver enzyme abnormalities. They also excluded people on immunomodulatory drugs, hematopoietic stem cell recipients, and those on corticosteroids, antibiotics, or warfarin.

Of all subjects, 53% had an ARI during the study period from January to March. On average, ARI days occurred at a rate of 0.1/patient-day. Put another way, 1 of every 10 days is an ARI day for these patients, Dr. Shaw explained. Since only about half of the subjects actually had ARIs, this means that for them 1 out of every 5 days is an ARI symptom day.

Overall, there were no major differences between the treatment and placebo groups in terms of the primary study end points. In the ginseng-treated group, 50% had at least one ARI episode, compared with 55% in the placebo group, but this difference was not statistically significant.

In terms of symptom duration, the ginseng group had a mean total of 8.9 ARI days vs. 6.9 days, but this difference was also deemed not statistically significant.

There were no differences in use of antibiotics or other secondary end points. While there was a trend toward lower incidence of moderate to severe ARIs in patients taking the ginseng supplement (31% vs. 39%), it did not reach significance.

In terms of adverse events, there were 13 "serious" episodes in the ginseng group versus 27 in the placebo group. Diarrhea, dizziness, hyperglycemia, and joint pain were among the most common reported adverse effects, but these were rare, and only 2 of the 40 episodes were considered "possibly related to the treatment."

Both the ginseng-treated and placebo-treated groups showed a mean increase in total white blood cells, with the increase being slightly higher in the placebo group. However, both groups showed a decrease in absolute neutrophil counts. Peripheral blood CD4 cell counts decreased in the active treatment group but increased in the placebo group. None of these differences were statistically or clinically significant.

The study was funded by the National Cancer Institute and Afexa Life Sciences.

The researchers said they did not know why the ginseng extract failed to produce the expected reductions in ARI among these CLL patients, but suggested that it may be a dosing issue. "We went with the dose used in the previous studies of healthy elderly, noncancer patients. It might not have been enough for CLL patients with impaired immune function." Dr. Shaw added that dose-escalation studies are in the works.

NEW YORK – A standardized extract of American ginseng (Panax quinquefolium) has been shown to be safe and effective in reducing the incidence and severity of acute respiratory infections among both community-dwelling and institutionalized elderly people.

However, the same product was not effective in decreasing respiratory infections among people with chronic lymphocytic leukemia (CLL), a condition that leaves patients particularly vulnerable to influenza and other acute respiratory infections (ARIs), reported Dr. Edward G. Shaw at an international conference sponsored by the Society for Integrative Oncology.

The promising findings from three studies among otherwise healthy elderly individuals led to the hope that this particular extract, known as CVT-E002 and marketed as an over-the-counter product called COLD-FX, might be similarly effective in patients with CLL, said Dr. Shaw of the Comprehensive Cancer Center, Wake Forest University, Winston-Salem, N.C.

CLL is the most common adult form of leukemia, affecting roughly 20/100,000 Americans. Because of the associated anemia, thrombocytopenia, and compromised immune system function, CLL survivors are at substantially increased risk of infections, especially respiratory infections. Common drug therapies like chlorambucil and fluorouracil increase this risk.

"There is a pressing need for effective, relatively low-cost interventions to reduce infection risk in CCL patients," Dr. Shaw said.

Panax ginseng is a reasonable botanical candidate for that job. Although it is indigenous to the United States and Canada, it is commonly used in traditional Chinese medicine and other Asian healing traditions. It is widely promoted as an immune system booster, and a number of preclinical and clinical studies support this claim.

The CVT-E002 extract, marketed by Afexa Life Sciences, is standardized to provide consistent doses of immunologically active compounds poly-furanosyl-pyranosyl-saccharides, which enhance natural killer cell activity, Dr. Shaw said. It is the only American ginseng extract that has been granted investigational new drug clearance by the U.S. Food and Drug Administration.

In 2004, Dr. Janet McElhaney of Eastern Virginia Medical School, Norfolk, published data from two studies of 89 and 109 people (mean age, 81 and 83.5 years, respectively) in nursing home and assisted living settings. The subjects were randomized to the ginseng extract (200 mg twice daily) or to placebo. The first trial lasted 8 weeks, and the second ran for 12. In both study cohorts, upward of 90% of the subjects had been vaccinated against influenza infections.

An episode of ARI was defined as two or more concurrent respiratory symptoms or one respiratory plus one constitutional symptom. Infectious diagnoses were confirmed by culture and serology.

Using an intent-to-treat analysis, Dr. McElhaney and her colleagues pooled the data from the two distinct trials. They found that lab-confirmed influenza was more common among the placebo group (seven cases in 101 subjects), compared with the ginseng-treated group (one case in 97 subjects). Incidence of influenza and respiratory syncytial virus infections combined was also higher in the placebo vs. the ginseng group (nine cases vs. one case). These differences were statistically significant (J. Am. Geriatr. Soc. 2004;52:13-9).

Interestingly, the investigators found no difference between the active treatment and placebo groups in terms of subjective reporting of ARI symptoms; roughly one-third of the people in each group reported ARI episodes, though the incidence of actual lab-confirmed infections was far lower.

Approximately 90% of the subjects in both groups reported adverse effects, the most common being gastrointestinal related. A total of 8% of the placebo group and 4% of the ginseng group required hospitalization, but none of these admissions was related to the study medications.

In 2006, Dr. McElhaney – now at the Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut, Farmington – published a trial of the same COLD-FX ginseng formula vs. placebo in a cohort of 43 community-dwelling adults aged 65 years and older. As in the previous trial, the ginseng dose was two 200-mg extract capsules daily, for a period of 4 months. After the first month of the trial, all subjects in both groups were immunized against influenza.

The investigators observed a significant reduction in episodes of ARI during November and December, the closing months of the trial. Of the placebo-treated group, 62% had an ARI episode, compared with 32% among those taking the CV-E002 extract. Duration of symptoms was also considerably longer in the placebo group (12.6 days vs. 5.6 days). Lab confirmation of infection was not done in this study (J. Altern. Complement. Med. 2006;12:153-7).

Adverse effects were few in both groups, and there was no significant difference between them. All of these studies were funded in part by CV Technologies, the company that manufactures the CVT-E002 extract.

These data, along with positive results from a Canadian study (CMAJ 2005;173:1043-8), prompted the Wake Forest group to look at the potential of the ginseng extract to reduce infection risk in CLL patients.

A total of 293 untreated CLL patients were randomized to take COLD-FX, 200 mg twice daily, or matching placebo for 3 months. The patients were instructed to keep a daily record of ARI symptoms in written diaries and to rate their symptoms on a 0-3 scale of severity. Subjects also recorded activity limitations, episodes of fever, and antibiotic use.

The patients had a mean age in the mid-60s; 75% of the active treatment group and 78% of the placebo group had been vaccinated against influenza. The investigators excluded people with HIV, cirrhosis, cardiovascular disease, multiple sclerosis, other malignancies, and liver enzyme abnormalities. They also excluded people on immunomodulatory drugs, hematopoietic stem cell recipients, and those on corticosteroids, antibiotics, or warfarin.

Of all subjects, 53% had an ARI during the study period from January to March. On average, ARI days occurred at a rate of 0.1/patient-day. Put another way, 1 of every 10 days is an ARI day for these patients, Dr. Shaw explained. Since only about half of the subjects actually had ARIs, this means that for them 1 out of every 5 days is an ARI symptom day.

Overall, there were no major differences between the treatment and placebo groups in terms of the primary study end points. In the ginseng-treated group, 50% had at least one ARI episode, compared with 55% in the placebo group, but this difference was not statistically significant.

In terms of symptom duration, the ginseng group had a mean total of 8.9 ARI days vs. 6.9 days, but this difference was also deemed not statistically significant.

There were no differences in use of antibiotics or other secondary end points. While there was a trend toward lower incidence of moderate to severe ARIs in patients taking the ginseng supplement (31% vs. 39%), it did not reach significance.

In terms of adverse events, there were 13 "serious" episodes in the ginseng group versus 27 in the placebo group. Diarrhea, dizziness, hyperglycemia, and joint pain were among the most common reported adverse effects, but these were rare, and only 2 of the 40 episodes were considered "possibly related to the treatment."

Both the ginseng-treated and placebo-treated groups showed a mean increase in total white blood cells, with the increase being slightly higher in the placebo group. However, both groups showed a decrease in absolute neutrophil counts. Peripheral blood CD4 cell counts decreased in the active treatment group but increased in the placebo group. None of these differences were statistically or clinically significant.

The study was funded by the National Cancer Institute and Afexa Life Sciences.

The researchers said they did not know why the ginseng extract failed to produce the expected reductions in ARI among these CLL patients, but suggested that it may be a dosing issue. "We went with the dose used in the previous studies of healthy elderly, noncancer patients. It might not have been enough for CLL patients with impaired immune function." Dr. Shaw added that dose-escalation studies are in the works.