THE MEDICAL SCIENCE BEHIND THIS PROGRAM: SUMMARY AND RECOMMENDED PROTOCOL.

By Dr. Edison de Mello

Strengthen your defenses against disease, from the common cold to cancer.

Your immune system is your body's "surveillance task force", fighting off infectious organism such as bacteria, viruses, parasites and fungi and keeping you feeling healthy. When the immune system doesn't do its job properly, disease ranging from your everyday common cold to more serious infections and even cancer can result. The successful treatment of every disease requires a fully functioning immune system and a healthy mind and body.

This system is both complex and ingenious, but the basics of how it works to protect us is quit simple to understand. The immune system's role is to recognize what belongs within our bodies, such as our own cells or the beneficial organisms that reside in our intestines and on our skin, verses what is a foreign invader. There are several organ systems that comprise the immune system and provide a protective barrier against foreign organisms such as the skin and the mucus membranes that line the nasal cavity. The major component of this system includes the white blood cells that are involved in recognizing and destroying virally infected and abnormally growing cells, secreting antibodies that are used in the clearing of pathogenic organisms, and producing compounds that are involved in the regulation of the inflammatory response.

Your immune system can be weakened by stress, sleep deprivation, nutritional imbalances, and aging (which impacts production of hormones that regulate the immune response).

Our Immune Support Program contains natural herbs and nutrients which are known to activate and support the immune system. Two key goals are to prevent the occurrence of the common cold and flu during times of increased exposure to people with these conditions; and to decrease the duration in which an infection may persist.

Supplements:

Akasha Naturals Vitamin D supplement ( at least 2000 IU per day) along with the Active Immunity formula provides nutrients such as, Vitamin C, Zinc, and Selenium, that are needed for optimal functioning of the immune system in addition to the high potency mushroom blend that it provides. Medicinal Mushrooms contain polysaccharide compounds called beta-glucans that can activate white blood cells and facilitate the clearing of foreign invaders.

Immune Support is a comprehensive herbal formula that will help shorten the duration of common infections by both activating the immune response and reducing the negative effects that stress has on the immune system through its combination of Ayurvedic herbs plus Andrographis.

Flora Plus is highly effective probiotic supplement that will help with the assimilation of nutrients and elimination of toxins and provide an overall healthier digestive and immune system by enhancing the integrity of the mucosal lining in the intestines, which acts as a protective barrier against foreign organisms.

Doctor-recommended health practices during supplement program.

As integrative physicians, we at Akasha are committed to healing the patient rather than simply treating the disease. In addition to taking the Akasha Naturals supplements designed for immune support, we recommend healthful practices that support the immune system and an overall feeling of well being.
Your diet and lifestyle should include:

• Fresh fruits, vegetables and essential fatty acids including both Omega 3 and Omega 6. (sources include Chia Seeds, Flax Seeds and Fish Oil)
• 8 hours of good sleep every night - most Americans don't get enough sleep even though new studies are showing that 8 hours is the optimum in most cases.
• Practicing that which gives you an overall feeling of mental and spiritual well-being: exercise you enjoy, a walk with a friend, a quiet moment to relax and recharge.
• Stress management is also important to overall health. We recommend a daily practice of some sort that helps you to lower the impact stress has on the body.

RELEVANT RESEARCH STUDIES: Immunity

Active Immunity

1. Hsu TL, Cheng SC, Yang WB, Chin SW, Chen BH, Huang MT, Hsieh SL, Wong CH. Profiling carbohydrate-receptor interaction with recombinant innate immunity receptor-Fc fusion proteins. J Biol Chem. 2009 Dec 11; 284(50): 34479-89.

http://www.ncbi.nlm.nih.gov/pubmed/19837675

*Quick Summary of Study: This study aims to find the mechanism in which Medicinal Mushrooms elucidate a positive effect on the immune system by studying several polysaccharide receptors found on different white blood cells of the innate immune system. Potential binding of these compounds to certain cell receptors may activate these white blood cells.

Abstract

The recognition of bacteria, viruses, fungi, and other microbes is controlled by host immune cells, which are equipped with many innate immunity receptors, such as Toll-like receptors, C-type lectin receptors, and immunoglobulin-like receptors. Our studies indicate that the immune modulating properties of many herbal drugs, for instance, the medicinal fungus Reishi (Ganoderma lucidum) and Cordyceps sinensis, could be attributed to their polysaccharide components. These polysaccharides specifically interact with and activate surface receptors involved in innate immunity. However, due to the complexity of polysaccharides and their various sources from medicinal fungi, quantitative analysis of medicinal polysaccharide extracts with regard to their functions represents a major challenge. To profile carbohydrate-immune receptor interactions, the extracellular domains of 17 receptors were cloned as Fc-fusion proteins, such that their interactions with immobilized polysaccharides could be probed in an enzyme-linked immunosorbent assay. The results show that several innate immune receptors, including Dectin-1, DC-SIGN, Langerin, Kupffer cell receptor, macrophage mannose receptor, TLR2, and TLR4, interact with the polysaccharide extracts from G. lucidum (GLPS). This analysis revealed distinct polysaccharide profiles from different sources of medicinal fungi, and the innate immune receptor-based enzyme-linked immunosorbent assay described here can serve as a high-throughput profiling method for the characterization and quality control of medicinal polysaccharides. It also provides a means to dissect the molecular mechanism of medicinal polysaccharide-induced immunomodulation events.

2. Bhaskaram P. Micronutrient malnutrition, infection, and immunity: an overview. Nut Rev. 2002 May; 60(5 Pt2): s40-45.

http://www.ncbi.nlm.nih.gov/pubmed/12035857

*Quick Summary of Study: This review article explores the role that vitamins and minerals have on maintaining a healthy immune system and preventing infections among underprivileged populations.

Abstract

Micronutrient deficiencies and infectious diseases often coexist and exhibit complex interactions leading to the vicious cycle of malnutrition and infections among underprivileged populations of the developing countries, particularly in preschool children. Several micronutrients such as vitamin A, beta-carotene, folic acid, vitamin B12 vitamin C, riboflavin, iron, zinc, and selenium, have immunomodulating functions and thus influence the susceptibility of a host to infectious diseases and the course and outcome of such diseases. Certain of these micronutrients also possess antioxidant functions that not only regulate immune homeostasis of the host, but also alter the genome of the microbes, particularly in viruses, resulting in grave consequences like resurgence of old infectious diseases or the emergence of new infections. These micronutrient infection and immune function interactions and their clinical and public health relevance in developing countries are briefly reviewed in this article.

3. Kiremidjian-Schumacher L, Roy M, Wishe HI, Cohen MW, Stotzky G. Supplementation with selenium and human immune cell functions. II. Effect on cytotoxic lymphocytes and natural killer cells. Biol Trace Elem Res. 1994 Apr-May; 41(1-2): 115-127.

http://www.ncbi.nlm.nih.gov/pubmed/7946899

*Quick Summary of Study: Selenium supplementation was found to increase the activity of certain white blood cells compared to baseline values.

Abstract

This study examined the effect of dietary (200 micrograms/d for 8 wk) supplementation with selenium (as sodium selenite) on the ability of human peripheral blood lymphocytes to respond to stimulation with alloantigen, develop into cytotoxic lymphocytes, and to destroy tumor cells, and on the activity of natural killer cells. The participants in the study were randomized for age, sex, weight, height, and nutritional habits and given selenite or placebo tablets; all participants had a selenium replete status as indicated by their plasma Se levels prior to supplementation. The data indicated that the supplementation regimen resulted in 118% increase in cytotoxic lymphocyte-mediated tumor cytotoxicity and 82.3% increase in natural killer cell activity as compared to baseline values. This apparently was related to the ability of the nutrient to enhance the expression of receptors for the growth regulatory lymphokine interleukin-2, and consequently, the rate of cell proliferation and differentiation into cytotoxic cells. The supplementation regimen did not produce significant changes in the plasma Se levels of the participants. The results indicated that the immunoenhancing effects of selenium in humans require supplementation above the replete levels produced by normal dietary intake.

4. Kodama N, Komuta K, Nanba H. Effect of Maitake (Grifola frondosa) D-Fraction on the activation of NK cells in cancer patients. J Med Food. 2003 Winter; 6(4): 371-377.

http://www.ncbi.nlm.nih.gov/pubmed/14977447

*Quick Summary of Study: This study investigated the role that Maitake Mushroom extract had on disease progression in cancer patients.

Abstract

Maitake D-Fraction, extracted from maitake mushroom, has been reported to exert its antitumor effect in tumor-bearing mice by enhancing the immune system through activation of macrophages, T cells, and natural killer (NK) cells. In a previous study, the combination of immunotherapy with the maitake D-Fraction and chemotherapy suggested that the D-Fraction may have the potential to decrease the size of lung, liver, and breast tumors in cancer patients. In the present study, we administered maitake D-Fraction to cancer patients without anticancer drugs, and at the same time NK cell activity was monitored to investigate whether the activity is closely related with disease progression. The numbers of CD4(+) and CD8(+) cells in the peripheral blood were measured in 10 patients, and NK cell activity was assessed using K-562 cells as target cells. Serum soluble interleukin-2 receptor (sIL-2R) levels in three patients and the expression of tumor markers in four patients were determined by enzyme-linked immunosorbent assay. The slight changes observed in the CD4(+) and CD8(+) cell numbers were independent of disease severity or stage as well as serum sIL-2R levels. In contrast, maitake D-Fraction hindered metastatic progress, lessened the expression of tumor markers, and increased NK cell activity in all patients examined. Thus maitake D-Fraction appears to repress cancer progression and primarily exerts its effect through stimulation of NK activity. In addition, we conclude that measurement of NK cell activity may be a useful clinical parameter in monitoring disease progression during and following immunotherapy with maitake D-Fraction.

Andrographis Immunity

1. Panossian A, Davtyan T, Gukassyan N, Gukasova G, Mamikonyan G, Gabrielian E, Wikman G. Effect of andrographolide and Kan Jang--fixed combination of extract SHA-10 and extract SHE-3--on proliferation of human lymphocytes, production of cytokines and immune activation markers in the whole blood cells culture. Phytomedicine. 2002 Oct; 9(7): 598-605

http://www.ncbi.nlm.nih.gov/pubmed?term=12487323

*Quick Summary of Study: Tissue culture study examining the effects of the herbal combination of Andrographis and Eleuthero Root on the activation and proliferation of certain white blood cells.

Abstract

The immunomodulatory properties of a diterpene lactone andrographolide and Kan Jang--a standardized fixed combination of Andrographis paniculata extract SHA-10 and Eleutherococcus senticosus extract SHE-3 were investigated. Their role on spontaneous and phytohemagglutinin (PHA)-induced proliferation of human peripheral blood lymphocytes (PBL) and on production of interferon-gamma (INF-gamma) and tumor necrosis factor-alpha (TNF-alpha) were determined in vitro. Proliferation of PBL induced by PHA was enhanced by co stimulation with andrographolide and Kan Jang. At the same time andrographolide and Kan Jang inhibit spontaneous proliferation of PBL in vitro. These preparations also have effect on the formation of INF-gamma, TNF-alpha and some immune activation markers such as neopterin (Neo), beta-2-microglobulin (beta2MG), and soluble receptor for interleukin-2 (sIL-2R or sCD25) in blood cells culture. Andrographolide and Kan Jang stimulate the INF-gamma, Neopterin and beta2MG formation, but do not have any significant effect on the production of INF-gamma and Neopterin in PHA stimulated blood cells. An opposite effect on these immune makers was observed in the PHA-stimulated blood cells: both andrographolide and Kan Jang increase the formation of TNF-alpha and beta2MG in cultivated whole blood cells. Thus, andrographolide and Kan Jang can have an in vitro effect on the activation and proliferation of immunocompetent cells as well on the production of key cytokines and immune activation markers. The results show an overall higher effect of the fixed combination as compared with the equivalent amount of the pure substance andrographolide. The data are consistent with results from clinical studies of Kan Jang and contributed to a better understanding of these results.

2. Kulichenko LL, Kireyeva LV, Malyshkina EN, Wikman G. A randomized, controlled study of Kan Jang versus amantadine in the treatment of influenza in Volgograd. J Herb Pharmacother. 2003; 3(1):77-93.

http://www.ncbi.nlm.nih.gov/pubmed/15277072?dopt=Citatio
*Quick Summary of Study: Clinical study found that the combination of Andrographis and Eleuthero Root was able to reduce the duration of illness and reduce the frequency of post-influenza complications.

Abstract

Two randomized, parallel-group clinical studies with a verum and a control group were performed to investigate the effect of a standardized extract (SHA-10) of Andrographis panaiculata (N.) fixed combination Kan Jang in the treatment of diagnosed influenza viral infection. The pilot study was performed on 540 patients with 71 Kan Jang-treated patients with the second phase conducted enrolling 66 patients. The differences in the duration of sick leave and frequency of post-influenza complications indicate that the Kan Jang phytopreparation not only contributes to quicker recovery, but also reduces the risk of post-influenza complications. Kan Jang was well tolerated by patients.

3. Saxena RC, Singh R, Kumar P, Yadav SC, Negi MP, Saxena VS, Joshua AJ, Vijayabalaji V, Goudar KS, Venkateshwarlu K, Amit A. A randomized double blind placebo controlled clinical evaluation of extract of Andrographis paniculata (KalmCold) in patients with uncomplicated upper respiratory tract infection. Phytomedicine. 2010 Mar; 17(3-4):178-85.

http://www.ncbi.nlm.nih.gov/pubmed/20092985?dopt=Citation

*Quick Summary of Study: Controlled clinical trial shows that Andrographis extract was able to reduce symptoms in patients with uncomplicated upper respiratory tract infection compared to control.

Abstract

A randomized, double blind placebo controlled clinical study was conducted to evaluate the efficacy of KalmCold, an extract of Andrographis paniculata, in patients with uncomplicated upper respiratory tract infection (URTI). The assessment involved quantification of symptom scores by Visual Analogue Scale. Nine self evaluated symptoms of cough, expectoration, nasal discharge, headache, fever, sore throat, earache, malaise/fatigue and sleep disturbance were scored. A total of 223 patients of both sexes were randomized in two groups which received either KalmCold (200 mg/day) or placebo in a double blind manner. In both the treatments, mean scores of all symptoms showed a decreasing trend from day 1 to day 3 but from day 3 to day 5 most of the symptoms in placebo treated group either remained unchanged (cough, headache and earache) or got aggravated (sore throat and sleep disturbance) whereas in KalmCold treated group all symptoms showed a decreasing trend. Within groups, mean scores of symptoms in both the groups decreased significantly (p < or = 0.05) from day 1 to day 3 and day 5 while from day 3 to day 5 all symptoms except expectoration in placebo group did not improve significantly whereas in KalmCold treated group all symptoms improved significantly (p < or = 0.05) except earache. Comparing mean between both groups, all symptoms at day 1 and day 3 were found to be the same while at day 5 all symptoms except earache in KalmCold treated group improved significantly (p < or = 0.05) than placebo group. Similarly, within groups, overall scores of all symptoms in both the groups decreased significantly (p < or = 0.05) from day 1 to day 3 and day 5 while from day 3 to day 5 placebo group did not improve significantly whereas KalmCold treated group showed significant improvement (p < or = 0.05). On between groups analysis, KalmCold group showed significant reduction (p < or = 0.05) in overall symptom scores as compared to placebo group. In both placebo and KalmCold treated groups, there were only a few minor adverse effects with no significant difference in occurrence (Z = 0.63; p > 0.05). The comparison of overall efficacy of KalmCold over placebo was found to be significant (p < or = 0.05) and it was 2.1 times (52.7%) higher than placebo. The findings of this study revealed that KalmCold was effective in reducing symptoms of upper respiratory tract infection.

4. Puri A, Saxena R, Saxena RP, Saxena KC, Srivastava V, Tandon JS. Immunostimulant agents from Andrographis paniculata. J Nat Prod. 1993 Jul; 56(7):995-9.

http://www.ncbi.nlm.nih.gov/pubmed/8377022

*Quick Summary of Study: Animal study investigated the differenence between full spectrum Andrographis extract verses isolated extract of andrographolides in their ability to stimulate the immune system.

Abstract

EtOH extract and purified diterpene andrographolides of Andrographis paniculata (Acanthaceae) induced significant stimulation of antibody and delayed type hypersensitivity (DTH) response to sheep red blood cells (SRBC) in mice. The plant preparations also stimulated nonspecific immune response of the animals measured in terms of macrophage migration index (MMI) phagocytosis of 14C-leucine labelled Escherichia coli and proliferation of splenic lymphocytes. The stimulation of both antigen specific and nonspecific immune response was, however, of lower order with andrographolide than with the EtOH extract, suggesting thereby that substance(s) other than andrographolide present in the extract may also be contributing towards immunostimulation.

5. Xia YF, Ye BQ, Li YD, Wang JG, He XJ, Lin X, Yao X, Ma D, Slungaard A, Hebbel RP, Key NS, Geng JG. Andrographolide attenuates inflammation by inhibition of NF-kappa B activation through covalent modification of reduced cysteine 62 of p50. J Immunol. 2004 Sep 15; 173(6):4207-17.

http://www.ncbi.nlm.nih.gov/pubmed?term=15356172

*Quick Summary of Study: Tissue culture study investigated the mechanism in which Andrographis extract induced an anti-inflammatory effect on cell lines that were stimulated with antigenic compounds.

Abstract

NF-kappaB is a central transcriptional factor and a pleiotropic regulator of many genes involved in immunological responses. During the screening of a plant extract library of traditional Chinese herbal medicines, we found that NF-kappaB activity was potently inhibited by andrographolide (Andro), an abundant component of the plant Andrographis that has been commonly used as a folk remedy for alleviation of inflammatory disorders in Asia for millennia. Mechanistically, it formed a covalent adduct with reduced cysteine (62) of p50, thus blocking the binding of NF-kappaB oligonucleotide to nuclear proteins. Andro suppressed the activation of NF-kappaB in stimulated endothelial cells, which reduced the expression of cell adhesion molecule E-selectin and prevented E-selectin-mediated leukocyte adhesion under flow. It also abrogated the cytokine- and endotoxin-induced peritoneal deposition of neutrophils, attenuated septic shock, and prevented allergic lung inflammation in vivo. Notably, it had no suppressive effect on IkappaBalpha degradation, p50 and p65 nuclear translocation, or cell growth rates. Our results thus reveal a unique pharmacological mechanism of Andro's protective anti-inflammatory actions.

6. Akramiene D, Kondrotas A, Didziapetriene J, Kevelaitis E. Effects of beta-glucans on the immune system. Medicina (Kaunas). 2007; 43(8):597-606.

http://medicina.kmu.lt/0708/0708-01e.pdf

*Quick Summary of Study: Review article discusses the immunostimulating properties of beta-glucans, a polysaccharide found in medicinal mushroom, such as Maitake and Reishi.

Abstract

Beta-glucans are naturally occurring polysaccharides. These glucose polymers are constituents of the cell wall of certain pathogenic bacteria and fungi. The healing and immunostimulating properties of mushrooms have been known for thousands of years in the Eastern countries. These mushrooms contain biologically active polysaccharides that mostly belong to group of beta-glucans. These substances increase host immune defense by activating complement system, enhancing macrophages and natural killer cell function. The induction of cellular responses by mushroom and other beta-glucans is likely to involve their specific interaction with several cell surface receptors, as complement receptor 3 (CR3; CD11b/CD18), lactosylceramide, selected scavenger receptors, and dectin-1 (betaGR). beta-Glucans also show anticarcinogenic activity. They can prevent oncogenesis due to the protective effect against potent genotoxic carcinogens. As immunostimulating agent, which acts through the activation of macrophages and NK cell cytotoxicity, beta-glucan can inhibit tumor growth in promotion stage too. Anti-angiogenesis can be one of the pathways through which beta-glucans can reduce tumor proliferation, prevent tumor metastasis. beta-Glucan as adjuvant to cancer chemotherapy and radiotherapy demonstrated the positive role in the restoration of hematopiesis following by bone marrow injury. Immunotherapy using monoclonal antibodies is a novel strategy of cancer treatment. These antibodies activate complement system and opsonize tumor cells with iC3b fragment. In contrast to microorganisms, tumor cells, as well as other host cells, lack beta-glucan as a surface component and cannot trigger complement receptor 3-dependent cellular cytotoxicity and initiate tumor-killing activity. This mechanism could be induced in the presence of beta-glucans.

Krawitz C, Mraheil MA, Stein M, Imirzalioglu C, Domann E, Pleschka S, Hain T.Inhibitory activity of a standardized elderberry liquid extract against clinically-relevant human respiratory bacterial pathogens and influenza A and B viruses. BMC Complement Altern Med. 2011 Feb 25;11:16.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056848/?tool=pubmed

*Quick Summary of Study: This study investigated the potential benefits of Elderberry extract in treating bacterial super infection during a flu virus infection.

Abstract

BACKGROUND:

Black elderberries (Sambucus nigra L.) are well known as supportive agents against common cold and influenza. It is further known that bacterial super-infection during an influenza virus (IV) infection can lead to severe pneumonia. We have analyzed a standardized elderberry extract (Rubini, BerryPharma AG) for its antimicrobial and antiviral activity using the microtitre broth micro-dilution assay against three Gram-positive bacteria and one Gram-negative bacteria responsible for infections of the upper respiratory tract, as well as cell culture experiments for two different strains of influenza virus.

METHODS:

The antimicrobial activity of the elderberry extract was determined by bacterial growth experiments in liquid cultures using the extract at concentrations of 5%, 10%, 15% and 20%. The inhibitory effects were determined by plating the bacteria on agar plates. In addition, the inhibitory potential of the extract on the propagation of human pathogenic H5N1-type influenza A virus isolated from a patient and an influenza B virus strain was investigated using MTT and focus assays.

RESULTS:

For the first time, it was shown that a standardized elderberry liquid extract possesses antimicrobial activity against both Gram-positive bacteria of Streptococcus pyogenes and group C and G Streptococci, and the Gram-negative bacterium Branhamella catarrhalis in liquid cultures. The liquid extract also displays an inhibitory effect on the propagation of human pathogenic influenza viruses.

CONCLUSION:

Rubini elderberry liquid extract is active against human pathogenic bacteria as well as influenza viruses. The activities shown suggest that additional and alternative approaches to combat infections might be provided by this natural product.

Flora Plus

1. Putaala H, Barrangou R, Leyer GJ, Ouwehand AC, Hansen EB, Romero DA, Rautonen N. Analysis of the human intestinal epithelial cell transcriptional response to Lactobacillus acidophilus, Lactobacillus salivarius, Bifidobacterium lactis and Escherichia coli. Benef Microbes. 2010 Sep 1; 1(3):283-95.

http://www.ncbi.nlm.nih.gov/pubmed/21831765

*Quick Summary of Study: A tissue culture study examining the effects that probiotic and pathogenic strains of bacteria have on human epithelial cells.

Abstract

The complex microbial population residing in the human gastrointestinal tract consists of commensal, potential pathogenic and beneficial species, which are probably perceived differently by the host and consequently could be expected to trigger specific transcriptional responses. Here, we provide a comparative analysis of the global in vitro transcriptional response of human intestinal epithelial cells to Lactobacillus acidophilus NCFM™, Lactobacillus salivarius Ls-33, Bifidobacterium animalis subsp. lactis 420, and enterohaemorrhagic Escherichia coli O157:H7 (EHEC). Interestingly, L. salivarius Ls-33 DCE-induced changes were overall more similar to those of B. lactis 420 than to L. acidophilus NCFM™, which is consistent with previously observed in vivo immunomodulation properties. In the gene ontology and pathway analyses both specific and unspecific changes were observed. Common to all was the regulation of apoptosis and adipogenesis, and lipid-metabolism related regulation by the probiotics. Specific changes such as regulation of cell-cell adhesion by B. lactis 420, superoxide metabolism by L. salivarius Ls-33, and regulation of MAPK pathway by L. acidophilus NCFM™ were noted. Furthermore, fundamental differences were observed between the pathogenic and probiotic treatments in the Toll-like receptor pathway, especially for adapter molecules with a lowered level of transcriptional activation of MyD88, TRIF, IRAK1 and TRAF6 by probiotics compared to EHEC. The results in this study provide insights into the relationship between probiotics and human intestinal epithelial cells, notably with regard to strain-specific responses, and highlight the differences between transcriptional responses to pathogenic and probiotic bacteria

2. Prakash S, Tomaro-Duchesneau C, Saha S, Cantor A. The gut microbiota and human health with an emphasis on the use of microencapsulated bacterial cells. J Biomed Biotechnol. 2011; 2011:981214.

http://www.ncbi.nlm.nih.gov/pubmed/21772792

*Quick Summary of Study: This review article talks about the vast diversity of microorganisms that reside in the lower gastrointestinal tract and discusses their role in human health and disease prevention. The article also explains the various benefits and limitations that encapsulated probiotic supplements have on human health.

Abstract

The gut microbiota plays a crucial role in maintaining health. Alterations of the gut bacterial population have been associated with a number of diseases. Past and recent studies suggest that one can positively modify the contents of the gut microbiota by introducing prebiotics, probiotics, synbiotics, and other therapeutics. This paper focuses on probiotic modulation of the gut microbiota by their delivery to the lower gastrointestinal tract (GIT). There are numerous obstacles to overcome before microorganisms can be utilized as therapeutics. One important limitation is the delivery of viable cells to the lower GIT without a significant loss of cell viability and metabolic features through the harsh conditions of the upper GIT. Microencapsulation has been shown to overcome this, with various types of microcapsules available for resolving this limitation. This paper discusses the gut microbiota and its role in disease, with a focus on microencapsulated probiotics and their potentials and limitations.

3. Gourbeyre P, Denery S, Bodinier M. Probiotics, prebiotics, and synbiotics: impact on the gut immune system and allergic reactions. J Leukoc Biol. 2011 May; 89(5):685-95.

http://www.ncbi.nlm.nih.gov/pubmed/21233408

*Quick Summary of Study: A review article that explains what parameters are used to defined a probiotic organism. The article goes on to further explain about the roles that these organisms have on intestinal immunity and allergy treatment.

Abstract

Probiotics and prebiotics, alone or together (synbiotics), can influence the intestinal microbiota and modulate the immune response. They may therefore be tools that can prevent or alleviate certain pathologies involving the gut immune system, such as allergies for which no treatment is yet available. This review focuses first on the definitions of probiotics, prebiotics, and synbiotics and key cells in the gut immune system. It then discusses their effects on mucosal immune stimulation. Experimental findings suggest that different probiotic species have similar effects on innate immunity by improving the mechanisms of pathogen destruction. On the contrary, their impacts seem to be variable on the adaptive immune system. Prebiotics can also exert an influence on the gut immune system via the stimulation of the autochthonous bacteria metabolism. Finally, this review focuses on the effects of food supplements on allergy. Different studies performed in humans or rodents have supported a potential role for selected probiotics and prebiotics in reducing some allergic parameters. Probiotic effects on allergy treatment are unclear, especially in human studies. However, they are potentially effective at short-term for prevention when they are administered in perinatal conditions. A clinical study performed with an infant cohort revealed a beneficial effect of prebiotics in preventing allergic manifestations at long-term. Further studies are nonetheless essential to confirm these findings. Food supplements offer potential tools for the prevention or treatment of allergy, but insufficient evidence is available at present to recommend their use in clinical practice.

4. Madsen K, Cornish A, Soper P, McKaigney C, Jijon H, Yachimec C, Doyle J, Jewell L, De Simone C. Probiotic bacteria enhance murine and human intestinal epithelial barrier function. Gastroenterology. 2001 Sep;121(3):580-91.

http://www.ncbi.nlm.nih.gov/pubmed/11522742

*Quick Summary of Study: This review article discusses the role that probiotics have on intestinal immunity and explains the potential mechanism in which probiotics aid in pathogenic bacteria destruction.

Abstract

Probiotics and prebiotics, alone or together (synbiotics), can influence the intestinal microbiota and modulate the immune response. They may therefore be tools that can prevent or alleviate certain pathologies involving the gut immune system, such as allergies for which no treatment is yet available. This review focuses first on the definitions of probiotics, prebiotics, and synbiotics and key cells in the gut immune system. It then discusses their effects on mucosal immune stimulation. Experimental findings suggest that different probiotic species have similar effects on innate immunity by improving the mechanisms of pathogen destruction. On the contrary, their impacts seem to be variable on the adaptive immune system. Prebiotics can also exert an influence on the gut immune system via the stimulation of the autochthonous bacteria metabolism. Finally, this review focuses on the effects of food supplements on allergy. Different studies performed in humans or rodents have supported a potential role for selected probiotics and prebiotics in reducing some allergic parameters. Probiotic effects on allergy treatment are unclear, especially in human studies. However, they are potentially effective at short-term for prevention when they are administered in perinatal conditions. A clinical study performed with an infant cohort revealed a beneficial effect of prebiotics in preventing allergic manifestations at long-term. Further studies are nonetheless essential to confirm these findings. Food supplements offer potential tools for the prevention or treatment of allergy, but insufficient evidence is available at present to recommend their use in clinical practice

5. O'Mahony L, Feeney M, O'Halloran S, Murphy L, Kiely B, Fitzgibbon J, Lee G, O'Sullivan G, Shanahan F, Collins JK. Probiotic impact on microbial flora, inflammation and tumour development in IL-10 knockout mice. Aliment Pharmacol Ther. 2001 Aug; 15(8):1219-25.

http://www.ncbi.nlm.nih.gov/pubmed/11472326

*Quick Summary of Study: Animal study that explored the beneficial role that probiotic supplementation had on intestinal health in mice compared to the control group.

Abstract

BACKGROUND:

The enteric bacterial flora has been implicated in the pathogenesis of enterocolitis and colon cancer in C57BL/6 IL-10 knockout mice. Probiotic Lactobacilli modify the enteric flora and are thought to have a beneficial effect on enterocolitis. We conducted a controlled feeding trial in IL-10 knockout mice using the probiotic Lactobacillus salivarius ssp. salivarius UCC118.

AIM:

To determine the effect of probiotic consumption on the gastrointestinal microflora, tumour development and colitis in IL-10 knockout mice.

METHODS:

Twenty IL-10 knockout mice were studied (10 consumed probiotic organisms in milk and 10 consumed unmodified milk) for 16 weeks. Faecal microbial analysis was performed weekly to enumerate excretion of the probiotic UCC118, total lactobacilli, Clostridium perfringens, bacteroides, coliforms, bifidobacteria and enterococci. At sacrifice, the small and large bowel were microbiologically and histologically assessed.

RESULTS:

L. salivarius UCC118 was detected in feces from all mice in the probiotic fed group, but not the control group. Faecal coliform and enterococci levels were significantly reduced in probiotic fed animals compared to the controls (P < 0.05). At sacrifice, a significant reduction in C. perfringens numbers was observed in the test mice (P < 0.05). There were no fatalities in the test group compared to two deaths from fulminant colitis in the control group. Only one test mouse developed colonic adenocarcinoma compared to five in the control group. Test animal mucosal inflammation consistently scored lower than that of the control mice.

CONCLUSION:

In this placebo controlled trial, modification of enteric flora in IL-10 knockout mice by probiotic lactobacilli was associated with reduced prevalence of colon cancer and mucosal inflammatory activity

6. Pool-Zobel BL, Neudecker C, Domizlaff I, Ji S, Schillinger U, Rumney C, Moretti M, Vilarini I, Scassellati-Sforzolini R, Rowland I. Lactobacillus- and bifidobacterium-mediated antigenotoxicity in the colon of rats. Nutr Cancer. 1996; 26(3):365-80.

http://www.ncbi.nlm.nih.gov/pubmed/8910918

*Quick Summary of Study: Animal study investigates the preventive anti-genotoxic role that probiotic organisms have on colonic cells derived from rats that were treated with mutagenic toxins.

Abstract

Lactic acid bacteria (LAB) are proposed to have several beneficial effects, including the inactivation of carcinogens. We have studied the potential of Lactobacillus acidophilus (from a commercially available yogurt), Lactobacillus gasseri (P79), Lactobacillus confusus (DSM20196), Streptococcus thermophilus (NCIM 50083), Bifidobacterium breve and Bifidobacterium longum (from human infant stool) to prevent the induction of DNA damage by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 7.5 mg/kg body wt) in colon cells of the rat. Using the new technique of single cell microgel electrophoresis, all investigated strains were antigenotoxic toward MNNG after a single dose of 10(10) viable cells/kg body wt p.o. eight hours before the carcinogen. One-half and one-tenth of this initial dose resulted in a loss of protective activity. High doses of heat-treated L. acidophilus strains were also not antigenotoxic. One mechanism of the preventive effect could be that bacterial metabolites or components are responsible. Accordingly, selected examples were investigated in vitro in colon cells of the rat. Metabolically active L. acidophilus cells, as well as an acetone extract of the culture, prevented MNNG-induced DNA damage. Different cell fractions from L. acidophilus (cytoplasm, cell wall skeleton, cell wall) were devoid of antigenotoxic activity, whereas the peptidoglycan fraction and whole freeze-dried cells were antigenotoxic. As a second carcinogen, 1,2-dimethylhydrazine (DMH) was used. A dose- and time-response study was first performed to assess the effects of DMH in several segments of the gastrointestinal (GI) tract. Exposure for 16 hours to 15 or 25 mg DMH/kg body wt p.o. induced DNA damage in cells of the distal colon of rats, whereas no cytotoxicity was seen. Pretreatment orally with LAB on four consecutive mornings before DMH gavage (8 hours after the last LAB application) revealed that L. acidophilus, L. confusus, L. gasseri, B. longum, and B. breve inhibited the genotoxic effect of DMH. One of four S. thermophilus and one of three Lactobacillus delbrueckeii ssp. bulgaricus strains were also protective. Heat-treated L. acidophilus did not inhibit DMH-induced genotoxicity. A few aliquots of the colon cells were processed immunohistochemically for the presence of the "proliferation cell nuclear antigen" (PCNA). DMH treatment did not increase PCNA, nor was there any modulation by LAB. The effect of L. acidophilus on foreign compound-metabolizing enzymes (Phase I and Phase II) in liver and colon cells of rats revealed only one parameter to be modulated, namely, a two- to three-fold increase in the levels of NADPH-cytochrome P-450 reductase. The meaning of this finding, in terms of possible chemoprevention by LAB, remains unclear. In conclusion, our studies show that most, but not all, LAB tested could strongly inhibit genotoxicity in the GI tract of the rat and that viable LAB organisms are required for the protective effect in vivo. The comet assay technique is a powerful tool to elucidate such in vivo antigenotoxic activities in tumor target tissues.

Vitamin D

1. Blackmore KM, Lesosky M, Barnett H, et al. Vitamin D From Dietary Intake and Sunlight Exposure and the Risk of Hormone-Receptor-Defined Breast Cancer. Am J Epidemiol. 2008 Oct 15; 168(8):915-24.

http://aje.oxfordjournals.org/content/168/8/915.long

*Quick Summary of Study: This epidemiological study investigate the association between vitamin D intake at specific ages and the prevalence of combined estrogen- receptor and progesterone-receptor defined breast cancer in woman living in Ontario Canada.

Abstract

Evidence has emerged for a role of vitamin D in the development of breast cancer, and there is some suggestion that its antiproliferative effect is greater in hormone-receptor-positive cells. Few epidemiologic studies have considered the association between vitamin D and hormone-receptor-defined breast cancer, and the results are conflicting. Considering 759 cases and 1,135 controls from a case-control study (Ontario, Canada, 2003-2005), the authors examined the association between vitamin D intake at specific ages and combined estrogen-receptor- (ER) and progesterone-receptor- (PR) defined breast cancer. While increased intake of vitamin D (from the sun and diet) was most consistently associated with a significantly reduced risk of ER+/PR+ tumors (e.g., odds ratio = 0.76, 95% confidence interval: 0.59, 0.97 for use of cod liver oil during adolescence), comparable nonsignificant associations were found for receptor-negative (ER-/PR-) (odds ratio = 0.74, 95% confidence interval: 0.53, 1.04) and mixed (ER+/PR-) (odds ratio = 0.79, 95% confidence interval: 0.51, 1.22) tumors. This study suggests that vitamin D is associated with a reduced risk of breast cancer regardless of ER/PR status of the tumor. Future studies with a larger number of receptor-negative and mixed tumors are required.

2. Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr. 2004 Dec; 80(6 Suppl):1678S-88S.

http://www.ajcn.org/content/80/6/1678S.long

*Quick Summary of Study: This article explains the essential role that vitamin D has on human health and explains how increasing deficiencies from lack of sun exposure and dietary inadequacies can lead to certain ailments.

Abstract

Most humans depend on sun exposure to satisfy their requirements for vitamin D. Solar ultraviolet B photons are absorbed by 7-dehydrocholesterol in the skin, leading to its transformation to previtamin D3, which is rapidly converted to vitamin D3. Season, latitude, time of day, skin pigmentation, aging, sunscreen use, and glass all influence the cutaneous production of vitamin D3. Once formed, vitamin D3 is metabolized in the liver to 25-hydroxyvitamin D3 and then in the kidney to its biologically active form, 1,25-dihydroxyvitamin D3. Vitamin D deficiency is an unrecognized epidemic among both children and adults in the United States. Vitamin D deficiency not only causes rickets among children but also precipitates and exacerbates osteoporosis among adults and causes the painful bone disease osteomalacia. Vitamin D deficiency has been associated with increased risks of deadly cancers, cardiovascular disease, multiple sclerosis, rheumatoid arthritis, and type 1 diabetes mellitus. Maintaining blood concentrations of 25-hydroxyvitamin D above 80 nmol/L (approximately 30 ng/mL) not only is important for maximizing intestinal calcium absorption but also may be important for providing the extrarenal 1alpha-hydroxylase that is present in most tissues to produce 1,25-dihydroxyvitamin D3. Although chronic excessive exposure to sunlight increases the risk of nonmelanoma skin cancer, the avoidance of all direct sun exposure increases the risk of vitamin D deficiency, which can have serious consequences. Monitoring serum 25-hydroxyvitamin D concentrations yearly should help reveal vitamin D deficiencies. Sensible sun exposure (usually 5-10 min of exposure of the arms and legs or the hands, arms, and face, 2 or 3 times per week) and increased dietary and supplemental vitamin D intakes are reasonable approaches to guarantee vitamin D sufficiency.

3. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008 Apr; 87(4):1080S-6S.

http://www.ajcn.org/content/87/4/1080S.long

*Quick Summary of Study: This article explains the growing concern over vitamin D deficiencies and how these deficiencies are associated with increased risk of several diseases such as osteopenia, autoimmune disorders and certain cancers.

ABSTRACT

Vitamin D deficiency is now recognized as a pandemic. The major cause of vitamin D deficiency is the lack of appreciation that sun exposure in moderation is the major source of vitamin D for most humans. Very few foods naturally contain vitamin D, and foods that are fortified with vitamin D are often inadequate to satisfy either a child's or an adult's vitamin D requirement. Vitamin D deficiency causes rickets in children and will precipitate and exacerbate osteopenia, osteoporosis, and fractures in adults. Vitamin D deficiency has been associated with increased risk of common cancers, autoimmune diseases, hypertension, and infectious diseases. A circulating level of 25-hydroxyvitamin D of >75 nmol/L, or 30 ng/mL, is required to maximize vitamin D's beneficial effects for health. In the absence of adequate sun exposure, at least 800–1000 IU vitamin D3/d may be needed to achieve this in children and adults. Vitamin D2may be equally effective for maintaining circulating concentrations of 25-hydroxyvitamin D when given in physiologic concentrations.

4. Hayes CE, Nashold FE, Spach KM, Pedersen LB. The immunological functions of the vitamin D endocrine system. Cell Mol Biol. 2003; 49(2):277-300. 

http://www.ncbi.nlm.nih.gov/pubmed/12887108?dopt=Abstract

*Quick Summary of Study: This review articles focuses on role that vitamin D plays in the immune system; from the mechanism in which vitamin D may activate certain white blood cells, to its role in regulating inflammation and clearing mycobacterial infections, as well as its role with the endocrine system in establishing self-tolerance and possibly prevention of auto-immune diseases.

Abstract

The discoveries that activated macrophages produce 1alpha25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3), and that immune system cells express the vitamin D receptor (VDR), suggested that the vitamin D endocrine system influences immune system function. In this review, we compare and contrast how 1alpha,25-(OH)2D3 synthesis and degradation is regulated in kidney cells and activated macrophages, summarize data on hormone receptor function and expression in lymphocytes and myeloid lineage cells, and discuss how locally-produced 1alpha,25-(OH)2D3 may activate a negative feed-back loop at sites of inflammation. Studies of immunity in humans and animals lacking VDR function, or lacking vitamin D, are viewed to gain insight into the immunological functions of the vitamin D endocrine system. The strong associations between poor vitamin D nutrition, particular VDR alleles, and susceptibility to chronic mycobacterial infections, together with evidence that 1alpha,25-(OH)2D3 served as a vaccine adjuvant enhancing antibody-mediated immunity, suggest a model wherein high levels of 1alpha,25-(OH)2D3-liganded VDR transcriptional activity may promote the CD4+ T helper 2 (Th2) cell-mediated and mucosal antibody responses to cutaneous antigens in vivo. We also review a diverse and rapidly growing body of epidemiological, climatological, genetic, nutritional and biological evidence indicating that the vitamin D endocrine system functions in the establishment and/or maintenance of immunological self tolerance. Studies done in animal models of multiple sclerosis (MS), insulin-dependent diabetes mellitus (IDDM), inflammatory bowel disease (IBD), and transplantation support a model wherein the 1alpha,25-(OH)2D3 may augment the function of suppressor T cells that maintain self tolerance to organ-specific self antigens. The recent progress in infectious disease, autoimmunity and transplantation has stimulated a gratifying renaissance of interest in the vitamin D endocrine system and its role in immunological health.

5. Lin R, White JH. The pleiotropic actions of vitamin D. Bioessays. 2004; 26(1):21-28.

http://www.ncbi.nlm.nih.gov/pubmed/14696037?dopt=Abstract

Abstract

General knowledge of the role of vitamin D3 in human physiology has been shaped by its discovery as a preventive agent of nutritional rickets, a defect in bone development due to inadequate uptake of dietary calcium. Studies on the function of the hormonal form of vitamin D3, 1alpha,25-dihydroxyvitamin D3, have been greatly accelerated by the molecular cloning and structural analysis of the vitamin D3 receptor, which is a ligand-activated regulator of gene transcription. Molecular genetic techniques including genomics have helped reveal that 1alpha,25-dihydroxyvitamin D3 can control more than calcium homeostasis. It has widespread effects on cellular differentiation and proliferation, and can modulate immune responsiveness, and central nervous system function. Moreover, accumulating epidemiological and molecular evidence suggests that 1alpha,25-dihydroxyvitamin D3 acts as a chemopreventive agent against several malignancies including cancers of the prostate and colon. Here, we survey the most-recent findings and discuss their implications for the potential therapeutic uses of vitamin D analogues.