Vitamin and mineral supplement manufacturers are adding more ingredients to multivitamin formulas than ever before. Decades ago, multivitamins mostly contained just vitamins and minerals. But today the word multivitamin is really a misnomer. Most multivitamin products are really multinutrient formulas that provide an assortment of ingredients, including vitamins, minerals, antioxidants, amino acids, and other compounds.
To come up with a successful formula that contains all of these ingredients, today's manufacturers need to ask a lot of questions. For instance: How many ingredients should be included, and in what dosages? What chemical forms of these nutrients work best? And how can all of these compounds fit into a tablet or capsule?
Although there are no simple answers, successful manufacturers have found a number of ways to deal with these questions.
GET ON TARGET
Most manufacturers are of two minds concerning the number of ingredients to be included in a multivitamin formula. On one hand, customers are looking for multivitamins that contain significant quantities of a broad range of nutrients. On the other, customers are looking for multivitamins that address specific health concerns. To fulfill these requirements, multivitamin manufacturers often provide both general and targeted multivitamin formulas.
Marci Clow, RD, product information manager for Rainbow Light (Santa Cruz, CA), stresses that it's important to identify the consumer before determining nutrients and dosage levels for any multivitamin formula.
'At Rainbow Light, we look at the specific audience and then review the entire body of medical research findings pertinent to that population group's particular health concerns,' Clow says. 'Only then can we design a multivitamin that will deliver appropriate, optimal potencies for both immediate and long-term benefits.'
A prenatal supplement, for example, would have different ingredients and nutrient levels than one intended for menopausal women.
'Men, women, older adults, children, and teens all have different health concerns,' Clow says. 'Yet, it's also important to offer high-quality, general formulas for consumers who prefer one product for the whole family.'
THE LEVEL BEST
When it comes to choosing nutrient levels, the recommended dietary allowances (RDAs) and dietary reference intakes (DRIs) are good places to start, says Ram Chaudhari, senior executive vice president and chief scientific officer of Fortitech Inc. (Schenectady, NY).
Unfortunately, the National Academy of Sciences (Washington, DC) has only set RDAs and DRIs for some nutrients, and most of them are vitamins and minerals. For other ingredients, Chaudhari recommends that manufacturers look to clinical research to see what levels are safe and effective.
However, manufacturers should also consider the RDAs and DRIs in a broader context, adds W. H. Leong, vice president of Carotech Inc. (Edison, NJ).
'While it is prudent for a multivitamin to meet the recommendations, you also have to keep up with the research,' Leong says. 'Very often the RDAs are obsolete and don't reflect the latest science.'
The issue of whether or not nutrients should exceed recommended levels is somewhat controversial. Some manufacturers recommend higher levels of ingredients, while others prefer smaller amounts. As a result, consumers are often confused about what levels are appropriate for their needs.
'The paradigm of the 1990s was that supplements were indicated for micronutrients,' says Herbert Woolf, PhD, technical development manager of human nutrition at BASF Corp. (Mount Olive, NJ). 'But there are nutrients now that have a great deal of functionality over the gram level.'
According to John Hathcock, PhD, vice president of scientific and international affairs at the Council for Responsible Nutrition (CRN; Washington, DC), the answer depends on both the particular nutrient and on the consumer's diet. Consumers need to consider whether they are taking a vitamin to meet RDA requirements or to get higher levels of nutrients that provide specific therapeutic benefits.
'If you are concerned about just meeting the RDA, common diets frequently do not provide RDA levels of zinc and copper, and therefore a multivitamin supplement with 100% of these nutrients would fulfill the RDA requirements,' Hathcock says.
However, in other cases, such as when a consumer takes folic acid and vitamins B6 and B12 to reduce homocysteine levels, the amounts of nutrients needed are well above the RDA and might require a B-complex vitamin supplement or a high-potency multivitamin, Hathcock explains.
Conversely, consumers who eat healthy diets that already contain high levels of nutrients may not benefit from greater dosages.
'If someone eats a lot of liver and spinach on a regular basis, then supplements with a higher-than-RDA content of these three B vitamins may not be useful,' Hathcock says. 'Individuals need to be well-informed about their health profile and honest about their diet in order to fully determine their supplement levels.'
'Dosage levels will vary for products designed to deliver certain nutrients for optimal health,' agrees Barry Kaufman, human nutrition product manager at BASF. 'That's why it's important for consumers to consider the ingredients of the product they are using and to check for specific information about usage.'
THE RIGHT STUFF
Although dosage levels are important, manufacturers also need to pay attention to the particular chemical forms of the nutrients they select. Some forms of nutrients may be more potent, absorbable, or bioavailable than others.
'The chemical form of a nutrient is very important when it is added to a multivitamin,' says Larry Robinson, PhD, director of research and development at Zila Nutraceuticals (Prescott, AZ). 'Not only is it essential to understand how vitamins and minerals will interact, but their stability, bioavailability, and nutrient density are also key considerations.'
For instance, if a multivitamin contains a concentrated version of a specific nutrient, it should also have sufficient dissolution and absorption rates, or the vitamin will have little benefit, Robinson says.
'Certain nutrient forms may be easier to absorb than others, and many require conutrients for optimal absorption and utilization,' explains Rainbow Light's Clow. 'A quality product will deliver highly bioavailable nutrient forms along with all of the known conutrients necessary for their absorption.'
Manufacturers also should ensure that the selected nutrients don't interact in ways that undermine the stability of the product by accelerating oxidation, adds Carotech's Leong.
In addition, some nutrients may have certain chemical forms that offer additional advantages when compared with other forms.
Carotech's palm tocotrienol complex, for example, has at least seven unique benefits that aren't found in the regular tocopherol form of vitamin E, Leong says. These benefits range from the ability to reduce total serum cholesterol to the ability to cross the blood-brain barrier.
'Tocotrienol definitely has additional biological advantages over its conventional counterparts,' Leong says.
Similarly, some studies have found that Zila's Ester-C may be more biologically available than other forms of vitamin C; moreover, preliminary studies on the company's new Ester-E ingredient suggest that it may have a different absorption rate than other forms of vitamin E, Robinson says. Zila is developing analytical testing methods for human clinical trials, which are expected to begin later this year at the University of Michigan.
'We anticipate that our human clinical trials will substantiate the existing research,' Robinson says.
MIX IT UP
One of the problems often faced by multivitamin manufacturers is that while product formulas tend to grow, tablets and capsules must remain small. Premixes and excipients can help keep things manageable when a manufacturer plans to use a wide array of ingredients.
'Manufacturers will select a premix when they want to reduce the number of ingredients or simplify their manufacturing process,' says BASF's Kaufman. 'A number of our customers purchase our ingredients from Fortitech, our premix partner.'
Premixes streamline the production process by minimizing the sourcing, testing, and preparation of each supplement ingredient, says Fortitech's Chaudhari. In addition, premixes can also help multivitamin manufacturers by providing nutrient systems that address the needs of specific demographic groups, such as seniors or women.
Excipients, on the other hand, can help solve several problems by ensuring the efficient binding and release of multivitamin components and by helping manufacturers produce smaller tablets.
'Beyond the choice of raw-material components themselves or premixes of these important nutrients, a prudent choice of excipients can ensure efficient production of effective dosage forms,' says Richard Salzstein, PhD, pharmaceutical sales and marketing manager for Hercules's (Wilmington, DE) Aqualon division.
Excipients provide several advantages for formulas with multiple ingredients. For example, excipients help create efficient binding of individual multivitamin components. They can also control the release of ingredients and keep them from interacting with each other. Additionally, they help create smaller tablets.
'Multivitamin tablets are comprised of large numbers of vitamins and minerals,' says Salzstein. 'All of these nutrients must be compacted well into the tablet. Binding of these varied components, to ensure tablet integrity with low friability, allows the nutrients to be delivered in a dosage form that may be easily swallowed.'
Salzstein adds that an efficient binder, such as Aqualon's Klucel Nutra modified cellulose (hydroxypropylcellulose), enables smaller tablet production, requiring lower use levels.
'Smaller tablets can be formulated with low levels of efficient binders, displacing less-efficient, higher-use-level binders,' Salzstein says. 'The advantage of smaller tablets is threefold. First, smaller tablets are easier to swallow. Second, higher-efficiency binding presents the opportunity to include even more nutrients. Third, smaller tablets allow production efficiencies that enable large manufacturing savings.'
Aqualon's Klucel Nutra has been shown to displace volume within a tablet formerly occupied by lower-performing binders, allowing the tablet volume to be reduced by 10-15%, according to Salzstein.
'A tablet that is 10% smaller allows the production of 10% more tablets per batch for a given batch volume,' Salzstein says. 'These efficiencies go directly to the bottom line in terms of savings in production time and quality assurance costs.'
NO SIMPLE SOLUTIONS
While there are a number of strategies that manufacturers can use to build the perfect multivitamin, there are no simple solutions. As the science behind the nutrients used in multivitamins evolves, so do the formulas and the problems that manufacturers encounter.
'If you look at the formulations of multivitamins over the years, they reflect the changing nature of the scientific information that is available,' Kaufman says. 'For example, originally multivitamins had vitamin A but not beta-carotene. As information regarding the benefits of beta-carotene became available, more manufacturers began to formulate it into their products.'
Given the large number of studies under way now on vitamins and other nutrients used in multivitamins, product reformulations are likely to continue. Although the task of building a better multivitamin is never
Building a Better Multivitamin
Saturday, September 25, 2004