Immune Ingredients Clinical Evidence

AHCC:
Note: Multiple studies show a benefit of AHCC for immunity at 3 grams or more a day. Animal research has shown a benefit for immunity at an equivalent human dosage of 500 mg. That, in combination with the fact that 1 gram was shown effective in humans for liver function, suggests AHCC is likely effective for immunity in humans at lower dosages than used so far in the current studies.

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Liver Function at 1 gram

Presented at the 18th International Congress on Nutrition and Integrative Medicine (ICNIM), July 2010. Kim J. The effect of AHCC in nonviral, chronic, and abnormal liver function condition: A randomized, double-blind, placebo-control study.

Topic:
Does AHCC improve liver function in patients with nonviral, chronic, and abnormal liver function condition?

Background:
AHCC has shown promise as a cancer therapy and as an immune modulator. Can it help those with nonviral, chronic, and abnormal liver function condition?

Study Type:
Human clinical intervention trial

Study Design:
Randomized, double-blind, placebo-controlled. At 4, 8, and 12 weeks, researchers measured levels of aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transferase (γ-GT). These are all enzymes that serve as markers of inflammation or damage in the liver.

Dosage:
1 g or 3 g daily for 12 weeks

Subjects:
30 men with nonviral, chronic, and abnormal liver function condition

Results:
Levels of all three enzymes decreased significantly in the 1-g group at all three testing periods. In the 3-g group, levels of the enzymes fell significantly as well, except for γ-GT at the 4-week mark.

Conclusions:
“It was shown that consumption of AHCC possessed beneficial effects on nonviral, chronic, and abnormal liver function condition.”

Immune Function at 3–6 grams

 

Human Immunology
Yin Z, H Fujii, T Walshe. Effects of active hexose correlated compound
(AHCC) on the frequency of CD4+ and CD8+ T cells producing IFN-γ and/or TNF-α in healthy adults. 2010 Dec; 71(12): 1187–90.

Topic:
Does AHCC have an effect on immune function of healthy adults ages 50 or greater?

Background:
AHCC has been shown to have an enhancing effect on immune function of humans and rodents, including an increase of natural killer (NK) cell activity, interleukin-12 production, and resistance to bacterial infection. Animal studies have shown that the effects of AHCC are more evident in hosts with impaired immune function, which is measured as the ability to enhance immune function parameters specifically in a murine tumor model, such as interferon (IFN)–g production by CD8+T cells and the numbers of NK and gdT cells. However, it is largely unknown whether AHCC could enhance immune parameters such as (IFN)–g and tumor necrosis factor (TNF-a) production by CD4+ and CD8+T cells in humans, particularly elderly adults with increased risk of infection and malignancy.

Study Type:
Human clinical intervention trial.

Study Design
Open-label trial:  Subjects were treated with AHCC for 60 days.  Peripheral blood was collected at base line, 30, and 60 days during supplementation, and another 30 days after supplementation was discontinued.  The production of interferon (IFN)-g and TNF-a by CD4+ and CD8+T cells was measured by flow cytometry.
 

Dosage:
3 grams AHCC per day (3 500-mg capsules twice daily)

Subjects:
30 healthy adults over the age of 50

Results:
AHCC supplementation resulted in the following significant changes compared to base line:

  • The frequency of CD4+ and CD8+T cells producing IFN-g alone, TNF-a alone, or both increased during AHCC intake
  • The f r e quency of such cells remained high even 30 days after discontinuing AHCC

Conclusions:
“Our results suggest that AHCC can enhance CD4+ and CD8+T cell immune responses in healthy persons via increasing production of cytokines IFN-g and TNF-a from T cells. Effects were seen after 30 days, and remained up to 30 days after discontinuing the compound. AHCC may improve immune response against pathogens through this mechanism.”

 Nutrition and Cancer
Terakawa N et al. Immunological effect of active hexose correlated compound (AHCC) in healthy volunteers: a double-blind, placebo-controlled trial. 2008. 60(5):643–51.

 Topic:
Does AHCC have an effect on immune responses in healthy volunteers?

Background:
Biological response modifiers (BRMs) are substances that stimulate the body's response to infection and disease. Attempts have been made to treat cancer with BRMs, but their clinical efficacy has not been clearly confirmed. AHCC has had numerous positive clinical results on cancer patients without any adverse effects, but has not been investigated for its effect on immune response in humans. The immune response can be measured by dendritic cells (DCs), the most potent antigen-presenting cells capable of priming tumor-specific T cells. DCs use in cancer immunotherapy appears to be a promising way to elicit and expand efficient antitumor immune responses.

Study Type:
Human clinical intervention trial

Study Design:
Double-blind, randomized, placebo-controlled: Subjects were treated with AHCC daily for 4 weeks. Blood samples were taken at base line and again after 4 weeks. The number of circulating DC1 and DC2 cells, natural killer cells and CD4+/CD8+ T lymphocytes was measured by flow cytometry. In addition, other immune function parameters were measured.

Dosage:
3 grams of AHCC per day (n=10) or placebo (n=11)

Subjects:
21 healthy volunteers

Results:
Volunteers supplemented with AHCC had the following significant changes:

  • Greater number of total DCs than at base line and compared with control
  • The number of DC1 cells was greater after AHCC intake than at base line, and the AHCC group had a tendency to have higher DC1s than control
  • DC2s were significantly increased after 4 weeks compared with control
  • The allo-stimulatory activity of DC1s was also increased after intake compared with control as measured by the mixed lymphocyte reaction (MLR)

Conclusions:
“These results suggest that AHCC could be an effective modulator of immunological function in patients with cancer.  AHCC acts as a promising BRM.”

 Biotherapy
Won JS. The hematoimmunologic effect of AHCC for Korean patients with various cancers. 2002 Nov; 16(6): 560–64.

Topic:
Does AHCC have a hematoimmunologic effect on cancer patients?

Background:
AHCC has immunomodulatory properties and is usually used as one of the complementary treatment agents for cancer patients. However, the mechanism of its anti-tumor effect is not clear. Therefore, an assessment of AHCC’s hematologic and cellular immunity effect was conducted in various cancer patients.

Study Type:
Human Clinical Intervention Trial.

Study Design:
Open-label trial: Patients were administered AHCC for 9 months. A peripheral blood examination, including total leukocytes, peripheral lymphocytes, hemoglobin, and hematocrit was performed before AHCC administration and then every 3 months for a total of 3 times. Assessment of immune parameters was also performed before intake and then every 3 months after for a total of 2 times.

Dosage:
3–6 grams of AHCC per day

Subjects:
12 cancer patients

Results:
AHCC supplementation resulted in the following changes compared with base line:

  • The ratio of natural killer cells to total lymphocytes increased from 21.67% before taking AHCC to 26.21% and 26.0% 3 to 6 months after
  • Numbers of white blood cells, hemoglobin, hematocrit, and thrombocyte did not change after taking AHCC, even though patients were undergoing radiotherapy or chemotherapy
  • No adverse effects were observed

Conclusions:
“This study suggests that AHCC can be used for the prevention of bone marrow depression and chemotherapy. Also from the hematoimmunologic point of view, AHCC treatment seems to be safe and good for cancer patients, acting as a biological response modifier.”

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Biotherapy
Uno K et al. Active hexose correlated compound (AHCC) improves immunological parameters and performance status of patients with solid tumors.  2000 March; 14(3): 303–9.

 Topic:
Does AHCC have a biological response modifier (BRM)-like effect in advanced-stage cancer patients?

Background:
Several medicinal compounds obtained from polysaccharide-rich plants are known to have BRM effects that enhance the immune system’s antitumor effects. BRMs are substances that stimulate the body’s response to infection and disease, including tumors. Because interleukin 12 (IL-12) and interferon-γ (IFN-γ) negatively modulate tumor growth the possible effect of AHCC on the production of IL-12 and IFN-γ as well as natural killer (NK) cell activity (which also plays a critical role in cancer immunity) was investigated.

Study Type:
Human clinical intervention trial

Study Design:
Open-label controlled trial: Subjects were administered AHCC for 6 months. NK cell activity in the peripheral monocytes and TH1 cytokine production (IFN-g, IL-12) were the immunological parameters investigated. Performance status (PS) as an indicator of quality of life was also measured. Each parameter was measured and evaluated 4 times, before AHCC and after administration of AHCC at 2 months, 4 months, and 6 months.

Dosage:
6 grams of AHCC per day (in 3 doses after meals)

Subjects:
38 cancer patients and 117 healthy patients

Results:
AHCC supplementation to cancer patients resulted in the following changes compared with the status before intake:

  • Significant improvement in NK cell activity
  • Significant improvement in INF-g and IL-12 production
  • Significant improvement in PS evaluation

Conclusions:
“The basal levels of 2 cytokines and NK activity in patients with tumors were lower than those in healthy people.  All of 3 immunological parameters of patients increased to the normal levels after the intake of AHCC. These results demonstrate that AHCC improves both immunological abnormalities and clinical conditions.”

International Journal of Immunotherapy
Ghoneum M et al. Immunomodulatory and anticancer effects of active AHCC. 1995; XI(1):
23–8.

Topic:
Does AHCC have immunomodulatory and anticancer effects in cancer patients?

Background:
The increased incidence of spontaneous tumors in immune-suppressed individuals, as well as those with congenital or acquired immunodeficiencies, indicates that the immune system can provide a major mechanism for host resistance against cancer and infectious diseases.  Several biological response modifiers (BRMs) have been developed to stimulate the immune system for tumor fighting, but their use is limited because of their severe side effects.  AHCC possesses BMR activity but without side effects and is therefore investigated in cancer patients.

Study Type:
Human clinical intervention trial.

Study Design:
Open-label trial:  Subjects were treated with AHCC for up to 17 months. Tumor-associated antigens (TAAs) for each type of malignancy were measured prior to AHCC treatment and at 3- to 40-week intervals. Natural killer (NK) cell activity was also monitored.

Dosage:
3 grams of AHCC per day

Subjects:
11 cancer patients with advanced malignancies

Results:
Supplementation with AHCC had the following results:

  • A significant decline in TAA occurred in 8 out of the 11 patients with different types of malignancies
  • PSA levels in prostate cancer patients and CA 125 levels in ovarian cancer patients decreased as early as 1 to 2 months and reached normal levels within 1–4 months
  • 9 out of 11 patients demonstrated marked increase in NK activity as early as 2 weeks after treatment
  • The percentages of patients with complete remission were as follows: prostatic (66%); ovarian (66%); multiple myeloma (50%); breast, 33% complete remission and 2 partial
  • In vitro studies showed that AHCC possesses suppressive effects on tumor cell growth

Conclusions:
“The high augmentory effect of AHCC and the absence of notable side effects make AHCC a promising immunotherapeutic agent for the treatment of cancer patients.”

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Presented at Experimental Biology Meeting. April 2010.
Gardner E et al. Active hexose correlated compound (AHCC) improves immune cell populations after influenza vaccination of healthy subjects.

Topic:
Does AHCC have an effect on immune response of healthy adults after influenza vaccinations?

Background:
AHCC has been shown to have an enhancing effect on immune function of humans and rodents, including an increase of natural killer (NK) cell activity, interleukin-12 production, and resistance to bacterial infection.

Study Type:
Human clinical intervention trial

Study Design:

Randomized, double-blind, placebo-controlled trial: Subjects were treated with AHCC or a placebo on the day of vaccination and for 3 weeks following vaccination. Blood was drawn at immunization and 2 weeks later for phenotypic analysis of lymphocytes using flow cytometry. 

Dosage:
3 grams of AHCC per day (n=14) or placebo (n=15)

Subjects:
29 healthy adults

Results:
AHCC supplementation resulted in the following changes compared with control:

  • The fold increases in percentages of T cells, CD8+ T (cytotoxic) cells, and CD56+ (NK) cells (but not CD4/CD8 ratios) were significantly higher than at vaccination for AHCC-supplemented subjects 
  • CD56 bright cytotoxic NK cells were higher in AHCC group
  • AHCC supplementation had a more dramatic effect on immune cell phenotypes after vaccination of subjects over 60 years old

Conclusions:
“This study suggests that short-term AHCC supplementation may be a good therapeutic intervention to sustain, or increase, the immune response to influenza vaccination in healthy subjects.”

Presented at 2nd Meeting of the Society for Natural Immunity. May 1994.
Ghoneum M. NK-immunomodulation by AHCC in 17 cancer patients. 

Topic:
Does AHCC have an immunomodulating effect on cancer patients?

Background:
Active hexose correlated compound (AHCC) is an enzyme-fermented extract of the basidiomycetes mushroom. The complex compound contains a mixture of polysaccharides, amino acids, lipids, and minerals. The predominant components are oligosaccharides, totaling approximately 74% of the total dry weight. Of these, nearly 20% are partially acetylated α-1,4-glucans, which are believed to constitute the active compounds in AHCC. 

Study Type:
Human clinical intervention trial

Study Design:
Open-label trial: Cancer patients with different advanced malignancies participated in the study. Patients received AHCC for 2–6 months. Natural killer cell activity was examined by 4-hour Cr release assay against sensitive K562 and resistant Raji tumor cells.

Dosage:
3 grams of AHCC per day

Subjects:
17 cancer patients

Results:
AHCC supplementation resulted in the following changes:

  • Significant enhancement of NK activity against K562 as early as 2 weeks, two- to threefold increase compared with base line.
  • Activity was further increased at subsequent periods up to 6 months post-treatment with AHCC.
  • NK activation was also detected against Raji cells, but at later stages (1–2 months) with two- to tenfol d increase compared to base line.

 Conclusions:
"We conclude that AHCC is a potent immunomodulator and may be useful in immunotherapy of cancer.”

 


 Mechanism of Action
AHCC prompts an early activation of the immune system by increasing the activity of immune cells known as natural killer cell (NK cells) and the immune system messengers known as cytokines. These cells trigger the immune response against infectious or abnormal cells. AHCC can enhance CD4+ and CD8+T cell immune responses in healthy people through increasing the production of the cytokines gamma interferon and tumor necrosis factor alpha from T cells.

VITAMIN C

 British Journal of Nutrition

Hemilä H. Vitamin C intake and susceptibility to the common cold. 1997 Jan;77(1):59–72.

Topic:
Under what circumstances does vitamin C affect susceptibility to the common cold?

Background:
The role of vitamin C in preventing the common cold has been widely studied but vitamin C has not been definitively shown to reduce the incidence of colds. Are there special circumstances when vitamin C helps prevent colds?

Study Type:
Review paper

Dosage:
Varied by study

Summary:
The researchers pooled results from the 6 largest studies of vitamin C supplementation. Overall, cold incidence was not reduced in the groups taking vitamin C as compared to the placebo groups. However, theorizing that vitamin C supplementation might make more difference in populations with lower-than-average levels of the nutrient, the researchers focused on 4 studies with British male school children and students. They found that those taking vitamin C did enjoy a highly significant reduction in the number of infections.

Conclusions:
“Thus these studies with British males indicate that vitamin C intake has physiological effects on susceptibility to common cold infections, although the effect seems quantitatively meaningful only in limited groups of people.”

 Cochrane Database of Systematic Reviews

 Douglas RM et al. Vitamin C for preventing and treating the common cold. 2004 Oct 18; (4):CD000980. Updated 2007 Jul 18; (3):CD000980.

Topic:
Does vitamin C reduce the incidence, duration or severity of the common cold?

Background:
Vitamin C is widely used by the public to prevent and treat the common cold, even though its efficacy for this purpose has been debated since the 1940s or earlier.

Study Type:
Review paper

Dosage:
200 mg/day or higher

Summary:
The researchers performed a meta analysis (a study that compiles and analyzes the results of previous studies) of 30 placebo-controlled studies with a total of 11,350 participants. They found:

  • While taking vitamin C did not prevent colds in the general population, it did reduce the incidence of colds in people involved engages in vigorous exercise (such as skiing or running a marathon) or in those exposed to extremely cold environments.
  • There was an 8% reduction in the duration of colds for adults and a 13.6% reduction for children.
  • Participants taking vitamin C took fewer days off school and work.
  • Participants who caught their colds naturally showed more benefit in reduced severity of cold symptoms from taking vitamin C than those who were infected in the laboratory.

Conclusions:
“[T]he consistent and statistically significant small benefits of duration and severity for those using regular vitamin C prophylaxis indicates that vitamin C plays some role in respiratory defence mechanisms…[R]outine mega-dose prophylaxis is not rationally justified for community use. But evidence suggests that it could be justified in people exposed to brief periods of severe exercise or cold environments.”

 International Journal of Sports Medicine

Hemilä H. Vitamin C and common cold incidence: a review of studies with subjects under heavy physical stress. 1996 Jul; 17(5): 379–83.

Topic:
Can vitamin C reduce the incidence of the common cold in subjects engaged in strenuous physical exercise?

Background:
Research has found that subjects performing heavy physical exercise are at increased risk of contracting upper respiratory infections. Can vitamin C reduce this risk?

Study Type:
Review paper of 3 placebo-controlled studies

Dosage:
600-1,000 mg/day

Summary:
Researchers analyzed 3 studies: one of children at a skiing camp in the Alps, one of soldiers training in Northern Canada and one of runners in a 90-km race. All 3 studies showed that those subjects who supplemented with vitamin C suffered fewer colds than those who took placebo.

Conclusions:
“Accordingly, the results of the three studies suggest that vitamin C supplementation may be beneficial for some of the subjects doing heavy exercise who have problems with frequent upper respiratory infections.”

Annals of Nutrition and Metabolism
Wintergerst ES, S Maggini, and DH Hornig. Immune-enhancing role of vitamin C and zinc and effect on clinical conditions. 2006; 50(2): 85–94.

Topic:
Can vitamin C and zinc improve immune function?

Background:
Levels of vitamin C in plasma and leukocytes (white blood cells) fall rapidly when the body is fighting infection or under stress. Can vitamin C and zinc help the immune system respond more effectively to infections?

Study Type:
Review paper

Dosage:
Up to 1 gram/day

Summary:
Supplementation with vitamin C was found to enhance the function of various components of the immune system, such as antimicrobial cells, natural killer cells, the proliferation of lymphocytes (a kind of white blood cell), chemotaxis (the movement of cells toward or away from a chemical stimulant), and delayed-type hypersensitivity (a kind of immune response in which T cells and T helper cells recognize an antigen and destroy it on contact). Vitamin C also protects cells from free radicals and inflammation.

Conclusions:
“These trials document that adequate intakes of vitamin C and zinc ameliorate symptoms and shorten the duration of respiratory tract infections including the common cold. Furthermore, vitamin C and zinc reduce the incidence and improve the outcome of pneumonia, malaria, and diarrhea infections, especially in children in developing countries.”

 


Mechanism of Action
Supplementation with vitamin C enhances the function of various components of the immune system, such as antimicrobial cells, natural killer cells, the proliferation of lymphocytes (a kind of white blood cell), chemotaxis (the movement of cells toward or away from a chemical stimulant), and delayed-type hypersensitivity (a kind of immune response in which T cells and T helper cells recognize an antigen and destroy it on contact). Vitamin C also protects cells from free radicals and inflammation.

VITAMIN D

 Archives of Internal Medicine

 Ginde AA, JM Mansbach and CA Camargo Jr. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. 2009 Feb 23; 169(4):384–90.

Topic:
Can vitamin D help prevent upper respiratory tract infections?

Background:
Previous research suggests vitamin D may enhance immunity.  What is the relationship between vitamin D levels and upper respiratory tract infections (URTIs)?

Study Type:
Human observational trial

Study Design:
Researchers analyzed data from the Third National Health and Nutrition Examination Study, conducted from 1988-1994.

Dosage:
No intervention given; blood levels of vitamin D were simply measured

Subjects:
18, 883 subjects, ages 12 and older

Results:
Researchers divided subjects into those with vitamin D levels lower than 10 ng/mL, those with levels between 10 and 30 ng/mL, and those with levels over 30 ng/mL. They found that 24% of respondents in the group with the lowest vitamin D levels reported having a recent URTI, compared with 20% of those in the middle group and 17% of those with the highest levels of vitamin D. The protective effect was even stronger in subjects with asthma or chronic obstructive pulmonary disease.

Conclusions:
“Serum 25(OH)D levels are inversely associated with recent URTI. This association may be stronger in those with respiratory tract diseases.”

 Current Opinion in Allergy and Clinical Immunology

 Abuzeid WM, NA Akbar NA, and MA Zacharek. Vitamin D and chronic rhinitis. 2011 Dec 26. [Epub ahead of print]

Topic:
Does vitamin D play a role in chronic rhinitis and chronic rhinosinusitis (CRS)?

Background:
Vitamin D has been found to enhance immune function. What is its effect on rhinitis?

Study Type:
Review paper

Dosage:
Varied by study

Summary:
Researchers found that vitamin D:

  • Helps suppress inflammation.
  • Helps immune cells differentiate.
  • Has been shown to play an important role in asthma, and according to the theory of the unified airway—which states that the lining of the nose and sinuses will have the same reaction to environmental challenges as the lining of the trachea and lungs—may also play a ro le in chronic rhinitis and rhinosinusitis.

Conclusions:
“Recent findings on the function of vitamin D may explain aspects of the pathopsysiology of chronic rhinitis and CRS, and may help direct the future treatment of these diseases.”

Current Opinion in Clinical Nutrition and Metabolic Care
Amrein K and B Venkatesh. Vitamin D and the critically ill patient. 2011 Dec 18. [Epub ahead of print]

Topic:
Can vitamin D help improve outcomes for critically ill patients?

Background:
Vitamin D’s immune-supporting effects are well known. What is the relationship between vitamin D and serious illness?

Study Type:
Review paper

Dosage:
Varied by study

Summary:
Researchers found that vitamin D deficiency is associated with increased risk of cardiovascular disease and morbidity and mortality in the general population. They note it is not yet clear whether vitamin D deficiency is a marker for other causes of death or if large doses of vitamin D can improve outcomes for patients in intensive care units.

Conclusions:
“In critically ill patients, the pleotropic [multiple] effects of vitamin D including its role in immune function are of great interest.”

Annals of Nutrition and Metabolism

 Biesalski HK. Vitamin D recommendations — beyond deficiency. 2011; 59(1): 10–6.

Topic:
What should recommendations for vitamin D be?

Background:
Vitamin D aids in bone growth, enhances the immune system, and, when maternal stores are adequate, protects nursing infants from infectious diseases. What are the ideal levels of the nutrient, specifically to prevent respiratory infections?

Study Type:
Review paper

Summary:
The author finds that levels below 50 nmol/L may be insufficient for all of the non-bone-related functions of vitamin D and that sufficient stores of vitamin A are needed for vitamin D to work.

Conclusions:
“Studies combining both vitamins [A and D] in sufficient amounts…demonstrated a beneficial effect on the prevention of respiratory tract infections. Consequently, it should be strongly recommended to increase the intake of vitamin D and to ensure a daily intake of vitamin A as counseled.”

 Expert Review of Clinical Pharmacology
Chun RF, JS Adams, and M Hewison. Immunomodulation by vitamin D: Implications for TB. 2011 Sep; 4(5): 583–91.

Topic:
What is the role of vitamin D in tuberculosis prevention?

Background:
Tuberculosis is a major cause of death worldwide, and low levels of vitamin D are associated with TB.

Study Type:
Research summary

Summary:
The authors find that vitamin D regulates the immune system on a cellular and molecular level and speculate that vitamin D deficiency may lead to immune dysfunction. They note the importance of bioavailability of vitamin D in relation to its immune-modulatory actions and its impact on TB, and they offer a hypothesis that vitamin D supplementation may prevent and treat TB.

Clinical Endocrinology

Hewiston M. An update on vitamin D and human immunity. 2012 Mar; 76(3):315–25.
 

Topic:
What is the current scientific understanding of the importance of vitamin D?

Background:
The benefits of vitamin D on bone health are well known, but in the past five years, many other benefits (especially related to immunity) have been studied.

Study Type:
Review paper

Summary:
The authors note that insufficient vitamin D is common in many populations worldwide and that low levels of the nutrient are associated with autoimmune and cardiovascular disease, hypertension, and cancer.


Mechanism of Action
Vitamin D plays many roles in the body, including modulating cell growth and neuromuscular and immune function. Vitamin D’s immune-supportive action is due to several factors: It helps mucous membranes serve as more effective barriers against infectious agents, it helps suppress the inflammatory response, and it helps immune cells differentiate.

AP-BIO ANDROGRAPHIS EXTRACT

Phytomedicine

Saxena RC et al. A randomized double blind placebo controlled clinical evaluation of extract of Andrographis paniculata (KalmCold) in patients with uncomplicated upper respiratory tract infection. 2010 Mar; 17(3–4):178–85.

Topic:
Can a proprietary extract of Andrographis (previously KalmCold, now AP-Bio) help relieve symptoms of upper respiratory tract infections?

Background:
Andrographis has long been used in Ayurvedic medicine to stimulate the immune system and to reduce inflammation. 

Study Type:
Human clinical intervention trial

Study Design:
Randomized, double-blind, placebo-controlled. Subjects took either AP-Bio Andrographis extract or placebo and rated the following symptoms: cough, expectoration, nasal discharge, headache, fever, sore throat, earache, malaise/fatigue, and sleep disturbance.

Dosage:
200 mg/day for 5 days

Subjects:
223 subjects

Results:
In both the treatment and the placebo groups, symptoms declined from days 1 to 3 of treatment. However, from days 3 to 5, symptoms of subjects in the placebo group stayed the same or worsened, while symptoms of those in the treatment group improved. Overall, AP-Bio was found to be significantly more effective (52.7%) than placebo at reducing symptoms of upper respiratory tract infections.

Conclusions:
“The findings of this study revealed that KalmCold [AP-Bio] was effective in reducing symptoms of upper respiratory tract infection.”

 

Mechanism of Action
Andrographis paniculata (AP-Bio) stimulates the production of protective antibodies and prompts delayed-type hypersensitivity response (a kind of immune response in which T cells and T helper cells recognize an antigen and destroy it on contact). It also spurs the body’s innate (or nonspecific) immune response, as measured by increases in proliferation of lymphocytes (a kind of white blood cell) and phagocytosis (a process in which immune cells engulf infectious agents).


COPPER AND ZINC

American Journal of Clinical Nutrition

Berger MM et al. Trace element supplementation modulates pulmonary infection rates after major burns: a double-blind, placebo-controlled trial. 1998 Aug; 68(2):365–71.

Topic:
Can increased supplementation with trace elements (including copper and zinc) help reduce pulmonary infections in patients with major burns?

Background:
The number one reason people die after major burns is infection. Patients often suffer short-term depletion of trace elements that support the immune system after being badly burned. Would supplementation help?

Study Type:
Human clinical intervention trial

Study Design:
Randomized, placebo-controlled. Subjects consumed either standard trace element intakes plus placebo, or standard trace element intakes plus supplements of trace elements.

Dosage:
For the control group: 20 micromoles of copper, 0.4 micromoles of selenium, and 100 micromoles of zinc. For the treatment group: 40.4 micromoles of copper, 2.9 micromoles of selenium, and 406 micromoles of zinc, for 8 days.

Subjects:
20 subjects, ages 40 ± 16 years, with burns on 48% ± 17% of their bodies

Results:
Plasma levels of zinc and copper remained below normal in both groups until day 15 for zinc and day 20 for copper. Plasma levels of selenium remained normal in the treatment group, while they fell in the control group. Leukocyte (white blood cell) counts were higher in the treatment group. The number of infections per patient in the treatment group (1.9 ± 0.9) was significantly lower than in the control group (3.1 ± 1.1).

Conclusions:
“Early trace element supplementation appears beneficial after major burns; it was associated with a significant decrease in the number of bronchopneumonia infections and with a shorter hospital stay when data were normalized for burn size.”

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American Journal of Clinical Nutrition

Kelley DS et al. Effects of low-copper diets on human immune response. 1995 Aug; 62(2): 412–6.

Topic:
What are the effects of a diet low in copper on the immune system?

Background:
Copper is known to support immune function. What happens when copper intake is low, and how quickly can these effects be reversed?

Study Type:
Human clinical intervention trial

Study Design:
Subject consumed a diet with varying levels of copper in three phases.

Dosage:
0.66 mg for 24 days, followed by 0.38 mg for 42 days, followed by 2.89 mg for 24 days

Subjects:
11 healthy men, ages 21–32 years

Results:
During the middle (low-copper) phase of the study, there was a significant decrease in peripheral blood mononuclear cells (including lymphocytes, monocytes,+ and macrophages) and an increase in the percentage of circulating B cells (a kind of lymphocyte that makes antibodies). In the final (high-copper) phase, blood levels of copper were restored to normal, but indices affected by the low-copper diet persisted.

Nihon Rinsho (Japanese Journal of Clinical Medicine)
Kodama H. Essential trace elements and immunity. 1996 Jan; 54(1): 46–51.

Topic:
What are the effects of trace minerals on the immune system?

Background:
Historically, the immune system has been divided into two parts: humoral and cell-mediated. Humoral immunity was so named because its protective effects were found in the body humor (serum), whereas cell-mediated immunity referred to the protective effects of white blood cells. Trace minerals are known to support immunity—but which kind?

Study Type:
Review paper

Dosage:
Varied by study

Summary:
The author finds that deficiencies in zinc, iron, copper, and selenium can all cause dysfunction of cell-mediated immunity. However, these deficiencies do not affect B cell (lymphocyte) function. Additionally, excess supplementation also can impair the immune system.

Conclusions:
“Among essential trace elements in humans, zinc, iron, copper, and selenium are essential for the integrity and optimum function of the immunity.… A proper balance of these elements is essential for maintenance of immunocompetence.”

Current Opinion in Clinical Nutrition and Metabolic Care
Prasad AS. Zinc: role in immunity, oxidative stress and chronic inflammation. 2009 Nov; 12(6): 646–52.

Topic:
Which conditions can zinc be used to treat?

Background:
Zinc serves as a signal molecule for immune cells and can thus be expected to affect a wide variety of immune-related conditions.

Study Type:
Review paper

Dosage:
Varied by study

Summary:
The authors found that zinc has been successfully used to treat:

  • Diarrhea in children
  • Chronic hepatitis C
  • Shigellosis
  • Leprosy
  • Tuberculosis
  • Pneumonia
  • Acute lower respiratory tract infection
  • Common cold
  • Leishmaniasis (a disease caused by parasites)

 Zinc has also been successfully used to decrease the incidence of:

  • Respiratory tract infections in children
  • Infections, oxidative stress, and inflammation in the elderly and in patients with sickle cell disease
  • Blindness in elderly individuals with dry-type age-related macular degeneration

Conclusions:
“Zinc supplementation has been successfully used as a therapeutic and preventive agent for many conditions.”

 

BMC: Public Health

Yakoob MY et al. Preventative zinc supplementation in developing countries: impact on mortality and morbidity due to diarrhea, pneumonia and malaria. 2011 Apr 13; 11 Suppl 3: S23.

Topic:
Can preventive zinc supplementation among children under age 5 in developing countries prevent deaths from diarrhea, pneumonia, and malaria?

Background:
Zinc deficiency is widespread among children in the developing world and places them at increased risk of infection due to decreased immune response.

Study Type:
Review paper

Dosage:
Varied by study

Results:
The authors found zinc supplementation reduced deaths from diarrhea and pneumonia but not from malaria.

Conclusions:
“We, therefore, conclude that zinc supplementation in children is associated with a reduction in diarrhea mortality of 13% and pneumonia mortality of 15%.”

Biogerontology
Kahmann L et al. Effect of improved zinc status on T helper cell activation and TH1/TH2 ratio in healthy elderly individuals. 2006 Oct-Dec; 7(5–6): 429–35.

 Topic:
Can supplementation with zinc help strengthen immunity in the elderly?

Background:
Mild zinc deficiency is common among the elderly and can lead to decreased cell-mediated immunity.

Study Type:
Human clinical intervention trial

Study Design:
Subjects took zinc supplements for 7 weeks.

Dosage:
Not stated in abstract

Subjects:
19 healthy subjects, ages 69.8 ± 5.1 years

Results:
Subjects were mildly deficient in zinc at the beginning of the study. Over the course of the study, their blood levels of zinc rose and their levels of activated T-helper cells (white blood cells that direct the activities of other immune cells) were significantly reduced, indicating that the immune system was less threatened. The ratio of TH1 to TH2 (different kinds of T-helper cells) was unchanged.

Conclusions:
“These findings suggest that elderly individuals may benefit from moderate zinc supplementation due to improved immune response leading to reduced incidences of autoimmune diseases and infections.”

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 Journal of Translational Medicine

John E et al. Zinc in innate and adaptive tumor immunity. 2010; 8:118

Topic:
How does zinc impact immunity?

Background:
Zinc affects both innate and adaptive immunity. In other words, it affects the body’s ability to respond to new and previously encountered threats.

Study Type:
Review paper

Dosage:
Varied by study

Summary:
The authors find that zinc deficiency:

  • Increases rates and duration of infection
  • Plays a role in weakened immune systems in the elderly
  • Plac es stress on the immune system

 Meanwhile, supplementation with zinc:

  • Improves immunity
  • Decreases inflammation

Conclusions:
“These general findings suggest that zinc is critical for normal immune cell function, whereby zinc depletion causes immune cell dysfunction, and zinc supplementation can either restore function in the setting of dysfunction or improve normal immune cell function.”

 

Mechanism of Action

Copper deficiency causes dysfunction in both the humoral and cell-mediated branches of the immune system. When copper stores are low, numbers of CD4+ (helper) cells and total T cell counts fall. This is due to reduced production of interleukin-2, a cytokine that helps T cells divide and differentiate. Long-term copper deficiency also damages enzymes that serve as antioxidants and can even cause changes to the phenotype (structure and chemistry) of immune cells.

Zinc deficiency damages both innate and adaptive (learned) immunity, and can lead to atrophy of the thymus (a gland where T cells develop and differentiate), changes in thymic hormones, and lymphopenia (a condition characterized by low levels of lymphocytes in the blood). These changes lead directly to increased rates of infection and longer-lasting infections. When zinc stores are low, DNA-repair enzymes and signaling molecules also suffer. Supplementation with zinc improves immune response and downregulates mechanisms that lead to chronic inflammation.