Health claims make the vital link between a nutrient and a healthy condition for that nutrient. But it is becoming clearer that a single nutrient may be less than effective in promoting health, and that a balance of several nutrients may be required for effectiveness. It appears possible that health claims for a single nutrient may be replaced by a group of nutrients to provide optimum nutrition and further improve healthy conditions. For instance, one of the most abundant minerals on earth, calcium is vital for teeth and bone health. It’s also essential for contraction and relaxation of muscles, blood clotting, and the creation of new cells and body tissues. With concerns about bone health increasing as the country’s population continues to get older, adding calcium to everything from table spreads to orange juice is becoming more and more popular.

When many consumers see the phrase “Now with calcium” on a container, they think the product will improve bone health. But not included in any health claim is that other nutrients, such as vitamins D and K, help the body maximize calcium’s potential, and may be necessary for the calcium to be effective. The way calcium interacts with other nutrients is just one of the nutrient combinations receiving a lot of attention from vitamin and nutrient suppliers.

At least one vitamin supplier has coined a term for these interactions, calling them nutrient clusters. Raimund Hoenes, Roche Vitamins, Marketing Manager, Parsippany, N.J., defined the term nutrient cluster as “nutrients working together for a particular health benefit.”

According to Paul Zimmer, also with Roche, the company has been working for years on the nutrient cluster concept. He feels that the cluster concept represents a paradigm shift from the idea of simple single nutrient fortification to groups of nutrients working together to increase their overall effectiveness. The company believes it is more important to look at the health state and how nutrients interact than to look at nutrients individually.

Combining Nutrients for Effect
Examples of these nutrient clusters and their interactions abound. The challenge for food product developers is combining nutrients so they provide an increased health benefit while remaining compatible and palatable. Bronner and Pansu (1999) describes the role of vitamin D in the absorption of calcium, noting that the amount of calcium absorbed in the intestine depends on habitual calcium intake, which would support addition of calcium to a broader range of foods. The authors note that when intake is low, active transcellular calcium transport in the duodenum is upregulated and a larger proportion of calcium is absorbed by the active process than by the passive paracellular process that prevails in the jejunum and ileum. The researchers found that bioavailability of the calcium source, digestibility, and solubilization play roles under conditions of low calcium intake, but are not too important when calcium intakes are high (e.g. >800 mg/d in people). Vitamin D intake is an important factor, as active calcium transport is dependent on the presence in the intestinal cell of calbindin D9k, the biosynthesis of which is totally vitamin D dependent. Brown (2000) also noted the connection between calcium and vitamins. Others have noted that calcium intestinal uptake is dependent on both vitamins K and D. Getting enough vitamin D can help prevent a number of serious health conditions, including osteoporosis. Vitamin D protects against the preventable bone diseases of rickets, osteomalacia, osteoporosis, and osteopenia. Calcium supplements will not help prevent or treat osteoporosis if your vitamin D level is low. In addition, vitamin K deficiency is linked to osteoporosis because low levels have been found in those with the condition.

Research from the USDA’s Human Nutrition Research Center on Aging also has studied vitamin K and bone health. The research indicates that vitamin K may play a vital role in maintaining bone density. In the mid-1970s, a class of proteins that required vitamin K were discovered in bone. In June 2000, Sarah Booth of the USDA’s Center on Aging published research that found a high correlation between high intake of vitamin K and low risk for hip fracture associated with osteoporosis. However, Booth also pointed out that the mechanism of vitamin K in bone health is not understood. So, the therapeutic value of products based on vitamin K supplementation are still speculative.

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According to research sponsored by Dairy Management, Inc., Rosemont, Ill., food technologists formulating products with significant levels of calcium should first start with foods and ingredients that naturally contain calcium. “When formulating foods, calcium-enriched dairy ingredients are one place to start, “ according to Carolyn Podgurski, dairy ingredients specialist for the Dairy Products Technology Center, Califormia Polytechnic State University, San Luis Obispo, Calif. Podgurski said that research has indicated that calcium found in dairy products may be better absorbed due to the lactose and magnesium they contain.

Another example where nutrient interactions may work better in combination than separately is the antioxidants. As a group, they work together to protect your cells. The carotenes are antioxidants found in vegetables and fruits. Some evidence indicates that foods high in carotenes (such as beta-carotene, lutein, lycopene, and others) might protect against cataract formation.

A specific example is age-related macular degeneration. Age-related macular degeneration is the leading cause of irreversible blindness among Americans ages 65 and older. Parts of the retina and the macula become diseased. As age-related macular degeneration progresses, tiny, fragile blood vessels begin to develop in the retina. These vessels often leak blood and fluid, damaging the retina even further. Research indicates that lutein consumption may play a role in maintaining the health of the eyes.

In addition, some observational studies have indicated that foods high in vitamin E, as well as vitamin E supplements, are associated with a reduced risk of cataracts. Thus, if vitamin E were combined with other antioxidants, the resulting nutrient combination might be helpful in maintaining healthy eyes.

Cardiovascular health is another area in which several nutrients and their interactions may provide increased benefit. Some research indicates that omega-3 fatty acids, vitamin E, and foods rich in antioxidants may provide some heart health benefits.

Omega-3 essential fatty acids, found in fish and some other oils, have been linked in many studies to a lowered risk of heart disease. The omega-3 fatty acids include alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). The omega-3 series may offer a variety of potential therapeutic uses, primarily as part of a heart-protecting diet. Beneficial effects include the possibility of lowering cholesterol and triglyceride levels, reducing the risk of heart disease, and lowering blood pressure.

Vitamin E appears to reduce the risk of cardiovascular disease in several ways. First, it prevents free radical damage to the low-density lipoprotein (LDL) form of cholesterol, blocking one of the earliest steps in the formation of fatty deposits on blood vessel walls. Second, it inhibits the proliferation of smooth muscle cells which would otherwise grow and reduce blood flow in vessels. Finally, it reduces the tendency toward blood clots which can lead to a heart attack.

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Research indicates that diets rich in low-fat dairy foods and rich in antioxidants such as fruits and vegetables may cut heart disease risk. According to information from the National Dairy Council, Rosemont, Ill., the DASH (Dietary Approaches to Stop Hypertension) diet that includes three servings of lowfat dairy foods and 8 to 10 servings of fruits and vegetables, which was shown to help lower blood pressure, may now have another life-saving benefit: protection against heart disease. Published in the American Heart Association’s Circulation, this study indicated that participants on the DASH combination diet saw the greatest reduction in artery-damaging homocysteine compared to the other subjects.

The study’s authors suggest that the increased folate, vitamin B6, and vitamin B12 in the DASH diet may play a role because they work together to reduce the amount of homocysteine in the blood. They noted that while B6 and B12 likely contribute to the DASH diet’s homocysteine-lowering effect, it was only the folate content of the diet that actually predicted the decrease in the amount of homocysteine in the blood.

So along with the omega-3s and vitamin E, the antioxidants and folic acid may play a role in the pathophysiology of coronary disease and stroke. The use of vitamins E, C, or folate supplements may be helpful in preventing myocardial infarction or stroke. Some experts believe that the costs and risks associated with these supplements are low, so recommending vitamin E, folate, and/or vitamin C supplementation may be helpful pending conclusive evidence from clinical trials.

Better knowledge of a diet-cancer relationship may permit a lowering of risk of breast and prostate cancer. This would intensify the potential for greater public health benefits. Experimental and epidemiologic studies including large-scale random tests still leave many unanswered questions. Genenutrient interactions play a key role in an individual’s ability to use anticarcinogenic dietary constituents and to withstand procarcinogens in the diet. A recent example was reported for the genetically controlled metabolic pathway of vitamin D. The pathway includes a vitamin D receptor in intron 8 (Bsml) with polymorphisms associated with increasedprostate cancer risk, a fourfold increase in risk among individuals with one polymorphism and a sixfold reduction in risk among individuals with another, according to Sinha and Caporaso (1999).

Results of current trials in nutrition and cancer prevention for breast and prostate cancer will help formulate goals for future research to gain better understanding of the role of nutrition and gene-nutrient interactions in cancer risk as well as the identification and validation of biomarkers. Cancers, particularly prostate cancer and breast cancer, are on the rise, and the ability to arrest these cancers has given much hope to victims and their relatives. Still, the use of diet to prevent these cancers is widely debated, and practiced as a means of assurance. Beta-carotene supplements may sharply reduce the risk of prostate cancer in men with low beta-carotene blood levels, according to new findings released by researchers at the Harvard Medical School. Meir Stampfer and his colleagues followed the diets, lifestyles, and health of more than 22,000 male doctors in the ongoing Physicians’ Health Study. Stampfer reported his findings May 19, 1997, at the annual meeting of the American Society of Clinical Oncology, held in Denver. Because prostate cancer is the second leading cause of death from cancer in men and the American Cancer Society estimates some 334,500 new cases of prostate cancer will be discovered in this year alone, there is real impetus to alter the diet in order to prevent the disease if possible.

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An earlier study by Harvard University researchers showed that men consuming large quantities of tomatoes, rich in a beta-carotene-related nutrient called lycopene, had only about half the risk of prostate cancer as did men who consumed little of the nutrient. However, lycopene alone doesn’t appear to be the whole answer. Researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Mass. (Johnson et al., 1999) noted that the combination of beta-carotene and lycopene assisted in the absorption of lycopene, although the combination didn’t result in greater uptake of beta-carotene.

Jamison et al. (2001) noted the use of vitamin C and K-3 combinations against prostate cancer, and found the combination to be effective. This work demonstrated that vitamin C showed selective toxicity toward malignant melanoma cells, human leukemia cells, neuroblastoma cells, tumor ascites cells, as well as acute lymphoblastic leukemia, epidermoid carcinoma and fibrosarcoma, with vitamin C acting as a pro-oxidant. Vitamin K-3 (menadione, 2-methyl-1,4-naphthoquinone) is a synthetic derivative of vitamin K-1. It appears to have antitumor activity against liver, cervix, nasopharynx, colon, lung, stomach, breast, leukemia, and lymphoma cell lines, especially in combination with vitamin C.

Of course, the role of phytochemicals, including soy ingredients, bran components, and possibly oligosaccharides are being investigated, and combination of those ingredients awaits fine tuning.

Marketing Nutrient Combinations
After years of closely following and guiding the science going on in the field of nutrient clusters, Roche began to turn its attention to answering the question of how to convey these findings to consumers. The company conducted quantitative studies involving surveys and qualitative studies involving focus groups and found they could divide consumers into different groups with different key drivers, or motivations, Hoenes said.

Roche called the five groups “health benefit platforms.” The first platform, Prevention, includes those who are trying to protect themselves from disease, Hoenes said. A key driver for this group is the desire to achieve the health benefits that result from eating foods or taking supplements that contain the nutrient combination.

The second health benefit platform is Performance. “These are people with Type A personalities,” Hoenes said. “They always want to achieve the best. A key driver for them is the performance benefits, such as immediate energy uptake, being able to perform, as in a marathon, or beating exhaustion.”

The third platform includes mainly mothers and fathers and is called the Nurturing platform. “They’re not thinking so much about themselves, but they’re thinking about their kids,” Hoenes said. “They want them to get a good start in life, a good foundation.” A key driver for this group is child development. The parents want to make sure their children’s brains develop properly, as well as promote healthy immune and other body systems, Hoenes said.

The fourth platform, Appearance, is easily figured out. It involves people who are very appearance oriented; thus, their key driver is concerns about their appearance, he said.

The last platform is Wellness. “These are people who have a holistic approach to life,” Hoenes said. “They try to balance everything in life. They try to feel good on a daily basis.” So their key driver would be to look good and feel good, he said.

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What the company found after studying these different groups is that the best way to market nutrient clusters to consumers is to focus on the benefits, not the ingredients, Hoenes said. Instead of saying, “Now contains vitamins X, Y, and Z,” a product should say “Now contains anti-oxidants,” and then convey the simple message that anti-oxidants help the immune system, he said. “You have to convey the benefits and it has to be simple,” he said. “They were looking for simple messages, like performance. Messages that could be explained in more detail on the side or back panel.”

But companies need to be cautious when conveying the health benefit, Hoenes said. “That’s what they would like to hear, but sometimes it’s difficult because of regulations. We can’t make health claims, so we have to be careful. But you can say a lot, as long as you don’t point to a disease.”

Stating that a product contains ingredients that work together to promote heart health is acceptable, but saying the product cures heart disease obviously is not, he said. But companies also need to be careful not to put too much emphasis on the benefit, he said. Taste still matters more.

“The consumer is not interested in food as medication, because it takes all the fun out of eating,” he said. “They want food to be good for you, but taste is first. Only a very small consumer base is willing to sacrifice taste for a health benefit.”

The product needs to be convenient, Hoenes said. “Consumers won’t change their lifestyles. Food and supplements must fit their lifestyles. If the consumer sits in front of the television the better part of the day, the benefit has to be delivered in a reasonable fashion to the table in front of the television, so in that case, it has to be in snack-type products.”

Older, Wiser, Healthier?
According to some of the preliminary findings of the first published information from the 2000 U.S. Census, Americans are not only increasing their life expectancy from birth, they are also increasing their life expectancy at older ages. The life expectancy of someone aged 60 has increased by 30% in the last 50 years. Seniors are also living healthier and are more active in these extended years. The implications for food product developers have been outlined before, but in the context of nutritional formulation the importance can not be emphasized enough. Products that are aimed at this market will grow in importance. Such products may include those dealing with health issues such as osteoporosis and eye health.

The idea of nutrient clusters also supports the need for varied healthy diets, such as a diet containing the recommended servings of fruits and vegetables. Vitamins are critical to good health, but a completely varied diet that includes plenty of fresh fruits and vegetables, dairy products and grains, as well as proteins and carefully chosen fats is preferred. A limited diet rarely includes the levels of nutrients needed for optimal health.

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One interesting approach to diet management for reducing obesity and chronic disease is the concept called, “The New American Plate” from the American Institute for Cancer Research. They outlined a program that focuses on proportion and portion size. The group believes that based on current nutritional understanding, vegetables, fruits, whole grains, and beans should cover two-thirds on a typical plate and animal-source foods should cover one-third. In a review of the scientific literature on diet and cancer, an expert panel established by the group found 247 studies on the association of vegetables and fruits and cancer prevention. Of those, 78% showed vegetables and fruits to be protective, and none showed a negative effect.

Americans are cooking less than ever. Last year, 44% of weekday meals were prepared in 30 min or less. That’s up from 40% in 1993, according to the NPD Group, Port Washington, N.Y. Since 1995, frozen-food sales have jumped 18%. And every night, 10% fewer food items are prepared than 15 years ago. This may mean that diets are less varied. Prepared food products with a variety or combinations of nutrients will be essential, despite the situation on health claims.

The idea of nutrient clusters may be especially helpful in addressing the interaction between genes and diet and how that interaction can influence the development of diseases. As Don Pszczola points out in the October 2000 issue of Food Technology in an article entitled, “Genes and Diet: The Specialized Role Ingredients May Play,” the emerging discipline called Nutrigenomics studies this interaction. The combination of nutrients in products may be the best method of targeting the treatment of a specific disease, and in enhancing health more completely.

Studies evaluating the multiple effects of dietary deficiencies demonstrate the need for complete diets for optimum growth. Baker (1999) in describing the growth of young chicks showed that methionine, zinc, riboflavin, vitamin B-6, and choline were all necessary to good growth responses. The authors reported the results of studies that used a soy-protein isolate diet that was deficient in methionine, zinc, riboflavin, vitamin B-6, and choline for chick growth and was used to study individual or multiple deficiencies of several of these nutrients. In all cases, adding all three deficient nutrients together resulted in growth responses that were superior to those resulting from supplementation with any pairs of deficient nutrients. In a second assay, single addition of Zn but not of methionine or riboflavin produced a growth response, but the combination of either Zn and Met or Zn and riboflavin resulted in growth responses that were clearly greater than the response shown by zinc alone. Additional assays of individual or multiple deficiencies of choline, riboflavin, and vitamin B-6, and individual additions suggested that choline was first limiting.

We’ve been told to eat a balanced diet, and many of us try hard. Still, the consumption of supplements is on the rise, often as “insurance” against a suboptimal diet. For those who consume supplements, balance is a key there as well, whether the supplement is in a pill, a beverage, or a box that sits on the breakfast table. Optimal health, or in the case of livestock, optimal growth depends on a selection of nutrients to keep growth moving, and while shortage in some doesn’t halt growth, it may slow it. There is much to know about combinations of nutrients, and while there is a great deal of research being done, there is much more to do.

Baker, D.H., Edwards, H.M., Strunk, C.S., Emmert, J.L., Peter, C.M., Mavromichalis, I., and Parr, T.M. 1999. Single vs multiple deficiencies of methionine, zinc, riboflavin, vitamin B-6, and choline elicit surprising growth responses in young chicks. J. Nutr. 129: 2239-2245

Bronner, F and Pansu, D. 1999. Nutritional aspects of calcium absorption. J Nutr. 129: 9-12.

Brown, J. 2000. Calcium intestinal uptake. Am. J. Clin. Nutr. 72:675-676A.

Jamison, J.M., Gilloreaux, J., Taper, H.S., and Summers, J.L. 2001. Evaluation of the in vitro and in vivo antitumor activities of vitamin C and K-3 combinations against human prostate cancer. J Nutr. 131:158S-160S.

Johnson, E.J., Qin, J., Krinsky, N.I., and Russell, R. M. 1997. Ingestion by men of a combined dose of beta carotene and lycopene does not affect the absorption of beta carotene but improves that of lycopene. J. Nutr. 127: 1833-1837.

Sinha R. and Caporaso, N. 1999. Diet, genetic susceptibility, and human cancer etiology. J Nutr. 129: 556S-559S.

Wood, R.J. 2000. Searching for the determinants of intestinal calcium absorption. Am. J. Clin. Nutr. 72: 675-676.