Research Roundtable
by Lori Dahm
Vitamin D and prebiotics take center stage.

This year has witnessed increased interest in the nutritional aspects of dairy, with research focused upon identifying the components within dairy and their nutritional benefits.
The Dairy Council of California and Dairy Field hosted a roundtable discussion on March 28, 2006, in Oakland, Calif., that highlighted two particular aspects of the dairy picture — vitamin D and prebiotics — and their health implications, discussed by two of the industry’s research experts.
Dr. Coni Francis is the scientific affairs manager for GTC Nutrition, a provider of customized nutrition solutions and science-based ingredients to the food industry. Before joining the company, Francis researched glycemia and insulin sensitivity as well as insulin response at Texas Womens’ University and the University of Colorado Health Sciences Center.
Francis currently focuses on researching and communicating the science behind prebiotic fibers and the mechanisms by which they work. She professes a pragmatic point of view, having been in the field of diabetics for more than 30 years, and strongly believes that “today’s consumers are more health-conscious, and although they will look for nutritionally enhanced foods, they will not sacrifice taste or convenience.”
Dr. Charles Stephensen is a research scientist with the U.S. Department of Agriculture Western Human Nutrition Research Center, (WHNRC), and has been at UC-Davis as an adjunct professor in the nutrition department for seven years. The WHNRC has 15 research scientists and four labs that study nutrition and immune function. Stephensen works on immunology and infectious diseases, and particularly on vitamin A and immune function. Vitamins A and D are closely related and have similar mechanisms of action.
Stephensen finds vitamin D very interesting these days with regard to inflammation, immune function, chronic disease and the way it acts at the cellular molecular level. “I developed an interest over the past year in particular on vitamin D and the risk of deficiency in the U.S.,” he says, “and how that may affect people’s resistance to infectious disease or response to immunization or risk of chronic disease.”
The discussion was moderated by Dr. Lori Hoolihan, research specialist for the Dairy Council of California.
Hoolihan: Dr. Francis, let’s start with you. Why don’t you give us a bit of an overview of the basics — what are prebiotics and what are some of the implications or the importance that they have to the dairy industry?
Francis: Prebiotics are nondigestible substances that are passed through the stomach and the small intestine in an intact state. They are then fermented by Bifidiobacteria and Lactobacilli in the large bowel, which in turn creates short-chain fatty acids (SCFA) for positive effects on human health. Our gut is essentially about three pounds of bacteria. Numerous health benefits can be achieved by modulating these bacteria and encouraging the grown of beneficial bacteria.
The intention is to nourish the beneficial bacteria to product SCFAs, which are instrumental in improving health. SCFAs typically produced are acetate, butyrate and proproinate.
The acetate is metabolized in the muscle and the kidney and the heart and the brain. The butyrate is the preferred source of energy from the enterocytes that are in the colon. And also, the butyrate produced is what is thought to reduce the incidence of cancer and lesions in the colon, and is therefore often referred to as offering immune properties in terms of preventing cancer.
Then the proprionate is taken up by the liver, which may suppress the synthesis of cholesterol — potentially reducing cholesterol and offering a positive impact in combating heart disease.
In addition, the SCFAs increase the volume of water and sodium absorption in the colon, so they can provide better digestive health. Prebiotics are an ideal ingredient for dairy applications because they acidify the intestinal luminal environment, thus increasing the absorption of minerals such as and magnesium to improve bone health.
Such benefits cannot be easily achieved by consuming simple food and beverage products because consumers would have to consume approximately 22 bananas, 15 onions or 383 garlic cloves to realize the benefits of offered by certain types of prebiotics.
Hoolihan: Can you talk about some of the more recent research and the biggest areas that are being looked at in terms of prebiotic health benefits?
Francis: Digestive and immune health are the most predominantly studied areas in prebiotics. One reason is that the gut is the largest immune system within the body. About 60 or 65 percent of the immunoglobulins that are secreted in the body end up being secreted into the gut.
An important — but less publicized — benefit of prebiotic fiber is its ability to significantly improve mineral absorption. With one of the prebiotic fibers on the market there is the expression of a calcium binding protein in the large intestine, rather than just in the small intestine. Therefore you have increased mineral absorption.
Current research also indicates that prebiotic fiber may assist in delaying hunger, similar to the viscous fibers on the market. Prebiotics are much easier to incorporate into applications because they are very soluble, and are able to retain water in addition to offering functional benefits such as flavor enhancement and improved texture.
More research is needed on the ability of prebiotics to offer glycemic health and cholesterol and lipid lowering benefits. Yet as research continues and improves, it’s very possible that prebiotic fibers may offer similar heart-health benefits currently being touted by the use of oat and barley fibers.
Hoolihan: Let’s turn to Dr. Charles Stephensen. Why don’t you start by giving us an overview of the vitamin D area and your specific research interests?
Stephensen: One of the important aspects about vitamin D right now is what our dietary intake should be. The last dietary guidelines occurred in 1997. There’s been much research on vitamin D and bone metabolisms, like the prevention of osteoporosis. Higher vitamin D intake is good for maintaining bone health and minimizing bone turnover. That’s why vitamin D aligns with calcium to maintain strong bones and so on. That’s sort of the central role of vitamin D.
There are other functions of vitamin D in the body relating to immune function that are not as well understood. There’s new data that makes nutritionists think that vitamin D may be good for preventing some chronic diseases that are immune mediated, like autoimmune disease or preventing development of cancer because of the effects on cell proliferation. That research is relatively new compared to our knowledge of vitamin D and bone metabolism. There are a lot of questions about what benefits may be realized at levels of intake that are higher than what is needed to prevent deficiency.
In our laboratory we’re actually working on at the cellular molecular role of nutrients like vitamin A and D affecting immune function, particularly T cell development. T cells are those cells in the immune system that help promote a robust response to immunization, like the flu vaccine. In order to promote a good memory response producing antibody and that sort of thing, you need healthy, happy T cells, and vitamin A and vitamin D are important there.
Hoolihan: Vitamin D has traditionally been linked with calcium absorption and, of course, bone health. You mentioned immune function, and we’ve also heard of cancer prevention and more. Which of those do you think have the most promise of being clinically relevant? Do you have any sense for which of those might be considered in the development of the next round of dietary guidelines for D?
Stephensen: Well, the first thing that’s going to be considered is still bone health, because there’s a lot more data now than there was in 1997. The dietary guideline is set so that we take in enough to prevent rickets. But above the level of preventing rickets, there’s biochemical evidence that bone health is improved at higher levels of intake.
Hoolihan: So you think the recommendations will still come back to the research on the bone health?
Stephensen: Primarily, because it’s pretty concrete. There’s a lot of good data there. With regard to the other benefits such as cancer, there are epidemiologic studies showing that more vitamin D or more sun exposure is associated with decreased risk of certain cancers, like prostate cancer in men, also to some extent colon cancer, and also to some extent breast cancer.
Besides bone health and cancer prevention, vitamin D affects the development and function of cells in the immune system. There’s a lot unknown there and there’s a lot of potential benefit.
Vitamin D is of benefit in protection against certain infectious diseases. Several good studies show that vitamin D deficiency is associated with risk of tuberculosis. Recent research published in the past few months shows that one of the key cells that protects against tuberculosis, macrophage, directly responds to vitamin D.
And actually, vitamin D is required for the normal synthesis of a particular antibacterial peptide, a small protein that’s an antibiotic that’s produced by the macrophage. In order for the macrophage to produce that peptide antibiotic, it needs vitamin D. And those peptide antibiotics kill organisms like Mycobacterium tuberculosis. So that’s one example where vitamin D may be key to prevention of an infectious disease.
Multiple sclerosis is an autoimmune disease where the body’s own T cells are reacting against antigens in the central nervous system and basically destroying nerve conduction in the central nervous system. In animal models, several nutrients, including vitamin D, seem to have an anti-inflammatory effect. Thus, vitamin D may have a role in preventing autoimmune diseases like MS by decreasing the inflammation that causes the disease.
While vitamin D helps macrophages produce some antibacterial peptides, a key part of the role of vitamin D in the immune response is that it may help the immune system to regulate itself. So when you’re sort of done with the infection and the pathogenic organism is cleared, the immune system then need to down-regulate itself. And this sort of regulatory role of vitamin D may play that sort of role with regard to helping prevent or diminish severity of diseases like multiple sclerosis in animal models. And there’s epidemiologic data that suggests the better vitamin D status you have early in life, the lower risk of multiple sclerosis later in life.
There’s similar data for juvenile onset diabetes, which is also an autoimmune disease. Better vitamin D status early in life may protect against development of autoimmune diabetes.
Hoolihan: What is the possibility of the vitamin D recommendations being increased in the next few years?
Stephensen: Well, certainly in the vitamin D research community there are many advocates of that, particularly regarding bone health. The bigger potential right now are these other health benefits, like cancer and autoimmune disease, but there’s not enough data yet to convince the dietary guidelines committee of an actual health benefit from the data. But there is data on bone metabolism, which will drive the discussion.
With regard to some of these other health benefits, there was one study published recently on perhaps the most common infectious disease in the U.S. Two-thirds of American adults have gingivitis, a bacterial infection of your gums. This study showed that the higher vitamin D intake you have, the lower your risk of gingivitis and the less severe gingivitis you have. The same antibacterial peptides and regulatory mechanisms that I talked about with regard to tuberculosis and autoimmune disease are at play in your mouth every day affecting development of gingivitis. So that’s an area and an example of how it might have a somewhat common health benefit for a lot of people.
Francis: I think it is kind of interesting that these two things parallel each other. Prebiotic fibers do not provide any food for the bacteria in the mouth, so this ingredient can be used as part of a sweetening mechanism for anti-cariogenic products.
Hoolihan: So D and prebiotics for gingivitis.
Stephensen: In a smoothie preferably.
Hoolihan: A perfect connection.  
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