Mushroom Council Nutrition Research Update.

In the five years since a roundtable of invited scientists charged the industry to discover all it can about mushrooms' nutrient and bioactive composition and role in health promotion and disease prevention, their message is: Research has come a long way, but has a long way to go. Results to date need to be verified by other investigators so that the science is credible and sufficiently robust to support consumer public relations efforts.

Members of the Mushroom Council's Nutrition Research Advisory Panel (Sidebar 1) offered this advice when they met late April in Washington D.C. with several industry funded researchers during the yearly meeting of Experimental Biology, a multidisciplinary meeting that brings together thousands of researchers to present their findings. This article describes some of the latest results of mushroom research projects on immune function and weight management presented during Experimental Biology. In summary:

* Findings about mushrooms and immunity must be considered in the context of the specific cells involved, the specific regulatory function of those cells relative to a target tissue or organ or specific condition. Because of the complexity of the immune system, different varieties of mushrooms may impact immune function in differing ways.

* White button mushrooms may promote innate immunity against viral infections and tumors by enhancing natural killer (NK) cell activity, mainly through increased production of interferon-gamma.

* White button, Maitake and Shiitake mushroom increase defensin production, which may contribute to mushrooms' antimicrobial activity.

* Shiitake, Maitake, Crimini, King Oyster, and White button mushrooms regulate immune cell function both in vitro and in vivo (mouse model) suggesting a possible but need-to-be-tested increased anti-cancer immune response.

* White button mushrooms substituted in meat-based entrees provide a well-accepted, lower calorie alternative to meat without compromising palatability or feelings of satiety.

Mushrooms & Immune Function

(See sidebar 2 for background and definitions)

Mushrooms' proposed anti-tumor, anti-viral and antibacterial properties are thought to be due to the ability to impact immune cell function. Previous studies reported in the literature used mushrooms not commonly eaten in the United States, often involved purified polysaccharide extracts (e.g. beta-glucan) administered through injection or parental routes, and focused primarily on tumor-bearing animals or cancer patients. Because there was little research investigating whole mushrooms' potential impact in healthy subjects, the Mushroom Council funded several studies to investigate mushrooms' role in innate immunity--the body's first line of defense against disease.

Effect of Mushroom Supplementation On Innate Immune Response

Dayong Wu, MD, Ph.D. and Simin Meydani, Ph.D.

USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA

This study investigated the effect of White button mushrooms on indicators of innate and cell mediated immunity in mice, and the effect of in vitro (cell culture) supplementation with White button mushrooms on the maturation and functions of dendritic cells (DC). Mushroom powder (freeze-dried white button mushrooms) added to diets of mice at 0%, 2% (a food portion) and 10% (supplement level) dose-dependently enhanced natural killer (NK) cell activity. The effect of mushrooms on increased NK cell activity is related to higher production of interferon-gamma, a critical cytokine involved in both innate and cell-mediated immunity. Dietary Supplementation with White Button Mushroom Enhances Natural Killer Cell Activity in C57BL/6 Mice, was published in the Journal of Nutrition (2007) Vol. 137, No. 6, pages 1472-77. For abstract, see http://jn.nutrition.org/cgi/content/abstract/137/6/1472

Mushroom supplementation also dose-dependently increased the expression of DC maturation markers and promoted the function of DC in processing and presenting antigen to T cells (cells originating in the thymus gland), functions critical in the body's anti-microbial and anti-tumor defense.

Effects of White Button. Maitake. Shiitake. and Portabella Mushroom Extracts on Intracellular--Defensin by H160 and Thp1 Cells

Solo Kuvidibila, Ph.D., Oklahoma State University, Stillwater, OK and The Research Institute for Children's Hospital, New Orleans, LA.

Mushrooms' effects on defensins have not been previously investigated. Defensins are potent antimicrobial peptides produced by neutrophils and epithelial cells often exposed to pathogens that regulate several immune responses associated with innate and adaptive immunity. The mushroom extracts were prepared by boiling homogenized (crushed) mushrooms for 5, 10, 30, or 60 min. The purpose of boiling was to determine the effects of heat treatment on the loss/recovery of biological activity. Results suggest that mushroom extracts were shown for the first time to increase defensin production by at least 50 percent. Boiling mushrooms increased or decreased defensin production depending on the type of mushroom and cell tested. Additional in vivo studies (in animals) are needed to further substantiate the ability of mushrooms to boost the immune system's defense against infections.

Commonly Consumed Mushrooms Regulate Cytokine Production From Macrophage

Margherita T. Cantorna, Ph.D., Keith Martin, Ph.D., Sanhong Yu, The Pennsylvania State University, University Park, PA

There is little comparative data on whether commonly consumed mushrooms in the United States can beneficially modulate biomarkers of inflammation such as cytokines. Cytokines can enhance immunity but also promote tumor immunity, inflammation, and carcinogenesis if dysregulated. This study investigated whether mushroom powder from Agaricus bisporus (White, Crimini, Portabella), Lentinula edodes (Shiitake), Pleurotus osteratus (Oyster), Pleurotus eryngii (King Oyster), and Grifola frondosa (Maitake), could modulate the immune response using in vitro and in vivo approaches. A macrophage cell line and bone marrow derived macrophage (BMDM) cells from mice were stimulated in vitro to determine the effect of the mushrooms on cytokine profiles.

Results indicate that edible mushrooms show both in vitro and in vivo (when fed to mice) immune regulatory function although the different mushrooms have differing effects on different cytokines. There were, however, no differences between Shiitake, Maitake, Crimini, King Oyster, and White button mushrooms in vitro on macrophage and T cell responses of primary cells from mice. These results suggest a possible, but need-to-be verified, increased anti-cancer immune response associated with eating mushrooms.

Mushrooms & Satiety:

Caloric Compensation. Satiety, and Dietary Satisfaction When Meat Entrees are Substituted with White Button Mushrooms

Lawrence J. Cheskin, MD, Lisa M. Davis, Ph.D., PA-C, Andrea Hanlon-Mitola, Ph.D., Candidate, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD

Obesity is rapidly replacing cigarette smoking as the number one preventable cause of death in the US, and its reach is now worldwide. Current methods of achieving weight control are disappointing. Providing a healthy balance of taste-intensive foods that consumers enjoy eating, such as mushrooms, that can be substituted for higher calorie foods could lower calories and perhaps enhance adherence and diet palatability.

It is important, though, that a careful study of the comparative palatability, satiety, and caloric compensation resulting from mushroom-substituted meals be tested in a controlled fashion to help predict whether mushroom substitutes will fulfill their potential as a means of reducing weight significantly. Previous simulations by Block Dietary Data Systems indicated that for males substituting a 4-ounce grilled portabella mushroom for a hamburger weekly for a year, "Benefits would include the consumption of 18,400 less calories, which could translate to a reduction of 5.3 lbs of body weight as well as a reduction of 2725 g of fat and 13,336 mg of cholesterol." The degree (percent) of caloric compensation from other foods can make or break this important kind of prediction. A level of caloric compensation near zero (poor compensation) would be ideal for weight control, while a level near 100% (perfect compensation) would render the substitution far less valuable for weight control (though it could still prove valuable for reducing dietary fat, especially saturated and trans fats).

This study developed seven easy-to-make test meals (one meal/day for a week) that substituted meat products with White button mushrooms to save at least 100 calories per meal. The final test meals used in the study, however, provided at least 200 calorie savings over the meat meal. The research also studied the palatability, consumer acceptance, and satiating properties of each mushroom-substituted meal using a panel of obese and normal weight subjects. The study tested the percent compensation over a four-day period for the calorie and fat deficit that results when mushroom-substituted meals were consumed compared with unsubstituted meals.

The results suggest that substituting White button mushrooms for traditional meat entrees provides a well-accepted, lower calorie alternative to meat without compromising palatability or feelings of satiety. There were significant reductions in total calories (379), fat and protein with the mushroom entrees. The protein content remained within the RDA range. There was modest compensation (27 percent), which is consistent with other studies on satiety and compensation. With a caloric difference of 379 a day and with compensation at 27 percent, consumers could potentially lose about 29 pounds over a year by substituting mushrooms for meat in one meal each day. Consumed over a longer period of time, entrees made with mushrooms instead of meat may be a useful adjunct for weight control, and may aid in reducing the risk of cardiovascular disease through the reduction in total fat and saturated fat intake. It is important to extend the research to a randomized, controlled clinical trial in a non-laboratory setting to demonstrate longer-term weight control and cardiovascular health benefits.

IMPLICATIONS

This research adds to the growing body of scientific evidence linking mushrooms to overall health, including the maintenance of a healthy immune system and having potential for weight management through substitution for higher calorie/fat ingredients and foods. Additional research is needed to replicate preliminary findings, to investigate effects in different models of immune function, and to determine mechanisms involved.

For example, mushrooms' polysaccharides such as beta-glucan have been investigated and linked to immune function when injected (direct access to the bloodstream) or used in cell-based experiments. However, when fed to animals (and humans), these polysaccharides (as dietary fiber) are not digested and therefore cannot be absorbed through the intestines to have a systemic effect on the immune system or other health outcomes. Therefore, are there other constituents (vitamins, minerals or bioactive compounds) in mushrooms that enhance immunity, or do the polysaccharides exert their effect through the gastrointestinal tract by interacting with gut microorganisms? Research is needed to help answer some of these intriguing questions.

Mary Jo Feeney, MS, RD, FADA

Mushroom Council Nutrition

Research Coordinator

[ILLUSTRATION OMITTED]

RELATED ARTICLE

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MUSHROOM COUNCIL: Nutrition Advisory Panel

Raymond Chang, MD, Medical Director, Meridian Medical Group, New York, NY

Shiuan Chen, Ph.D., Professor and Director, Beckman Research Institute of the City of Hope, Duarte, CA

Johanna Dwyer, D. Sc, RD, Director, Frances Stern Nutrition Center, and Professor, Tufts University, Boston, MA

Clare Hasler, Ph.D., MBA, Executive Director, Robert Mondavi Center for Wine and Food Science, University of California, Davis

John Milner, Ph.D., National Cancer Institute, Washington, DC. Dr. Milner participates on the panel as a scientist not as an official representative of the NCI.

Mark Wach, Ph.D., VP & Director of Research, Sylvan Inc., Kittanning, PA

sidebar 2

The Immune System Background (1)

The immune system provides resistance to or recovery from infection or inflammation and is amazingly complex. The immune system is a network of cells, tissues and organs that work together to defend the body against invading germs, bacteria, viruses and pa[TEXT INCOMPLETE IN ORIGINAL SOURCE]ites. Its job is to keep invading organisms out, or failing that, find and destroy them. The immune system can recognize and remember many different invading organisms and produce secretions and c[TEXT INCOMPLETE IN ORIGINAL SOURCE]s to wipe them out. It uses an elaborate communications network of cells organized into sets and subsets that pass information around. Once immune cells receive notice about an invading organism, th[TEXT INCOMPLETE IN ORIGINAL SOURCE] can undergo changes and produce powerful chemicals that allow the cells to regulate their own growth and activity and direct other cells where needed by releasing chemical messengers.

* Innate or natural immunity is inborn and provides an all-purpose defense system in response to invasion.

* Acquired or adaptive immunity develops when the body is exposed to various antigens (substances or molecules foreign to the body that are recognized by the immune system) and builds a defense that is specific to that antigen

* Dendritic cells link innate and adaptive immune responses and play a predominant role in activation of Natural Killer (NK) cells.

* Lymphocytes are small white blood cells that travel throughout the body using the blood vessels. T lymphocytes, "T Cells," mature in the thymus gland. "B-Cells" come from bone marrow.

* Phagocytes are large white blood cells that ingest microbes, cells or invading organisms.

* Neutrophils are white blood cells and a type of phagocyte.

* Natural killer cells (NK cells) are lymphocytes with granules filled with chemicals that can be used to destroy microorganisms.

* Macrophages are large immune cells found in many organs that devour invading pathogens and stimulate other immune cells.

* Monocytes are large phagocytic white cells that develop into macrophages when entering tissues.

* Cytokines are powerful chemical substances protein in nature secreted by cells that enable the body's cells to communicate with each other and coordinate an immune response. Cytokines include interferons, interleukins, and growth factors.

* Defensins chemically are proteins and include a family of potent antibiotics made within the body by neutrophils and macrophages. Defensins regulate several immune responses associated with innate and adaptive immunity.

Increased cell count and cell activity are ways of measuring enhanced immune function. Since the body has many cells involved in immune function, and since the cells generate in different organs and act in different systems (for example, in the blood stream or in a specific organ, the effect of compounds could differ in their manifestation or enhancement of immune function.

1 Adapted from Understanding the Immune System Fact Sheet. National Institute of Allergy and Infectious Diseases. National Institutes of Health. http://www.niaid.nih.gov/publications/autoimmune.htm Accessed Feb. 1, 2007.