In many ways, vitamins and minerals are the dietary supplement category originators. While the market for nutritional products has expanded dramatically over time, the multivitamin/mineral remains the most popular product among supplement users.

Overall, according to experts, minerals in particular are gaining notable attention due to common deficiencies. Calcium tends to be a staple for long-term bone health while zinc is often known as the winter health mineral, present in popular OTC immune support products like Zycam.

On the vitamin side, when one mentions “winter colds,” it’s vitamin C that comes to mind. Eye health? See vitamin A. Energy? Grab some B12. And vitamin D is most often associated with bone health.
Despite the superstar status of these vitamins and minerals, Americans are not obtaining enough of many essential nutrients. According to the Dietary Guidelines for Americans 2015-2020 (Eighth Edition), a publication from the Office of Disease Prevention and Health Promotion, Americans are still not consuming enough vitamins A, C, D and E, minerals like magnesium, calcium, choline, and potassium, and iron in females from adolescence to age 50. Low intake of iron, calcium, and potassium, as well as vitamin D are of high concern, as minimal levels are strongly associated with disease risks.

This data has motivated the FDA to replace the mandatory labeling of vitamins A and C with potassium and vitamin D on nutrition labels. Calcium and iron will remain unchanged, but there is a new daily value (DV) for vitamin C based on scietific consensus. Expect to utilize 90 mg for the DV of vitamin C, an increase of 50% from the former DV of 60 mg. So if the amount in a dietary supplement, food or beverage product is going to remain at 60 mg, labeling must reflect the new DV, about 70%.

“We continue to see a steady upward trend in the dietary supplements market, and vitamins and minerals are leading the way,” commented Tom Druke, marketing director, human nutrition & pharma at Balchem. According to an annual survey commissioned by the Council for Responsible Nutrition (CRN), 77% of adults in the U.S. are using dietary supplements, and 99% of these supplement users said they take vitamins and minerals. This is well above the percentage of supplement users that reported taking specialty supplements, botanicals, or sports nutrition supplements.

CRN’s Consumer Survey on Dietary Supplements 2019 found that vitamins and minerals continue to be the most commonly consumed supplement category, with 76% of Americans having taken these products in the past 12 months.

Broken down into preferences, multivitamin/mineral remained the unequivocal champion at number one with 58%, followed by vitamin D (31%), and vitamin C (28%). Protein was number four, followed by the most popular mineral at the number five spot, calcium (20%). Next was B vitamins/complex at 20%.

“We find it interesting that while the dietary supplement market is constantly seeking innovation, and new ingredient trends, it is the proven, scientifically backed and well-established vitamins and minerals that are most in demand,” said Druke. “Consumers are gaining more understanding of common mineral deficiencies, and the direct impacts these deficiencies can have on general well-being, and long-term health.”

Samantha Ford, director of business development, AIDP, Inc., cited a Nutrition Business Journal report that stated both letter vitamins and minerals were growing at an estimated 5% in 2019, of which vitamins remain the largest segment, reaching 30% of all dietary supplement sales.  Within this scope are several trends, including the growing use of B vitamins as an energy supplement in the beverage space. In addition, vitamin D sales continue to climb from strong consumer awareness, and vitamin K2 has emerged thanks to understanding about its protective benefits and complement to calcium-enriched products.

At Prinova USA, a NAGASE Group Company, vitamin and mineral ingredient formulation sales have seen “unprecedented growth” in recent years, according to Jayesh Chaudhari, senior director of R&D, driven in part by increased demand for fortified food products (e.g., meal replacement, sport nutrition drinks, infant formula, hydration beverages), and supplements like gummies, chews, and shots.

Another reason for the spike in demand, Chaudhari said, is the increased DVs for calcium, potassium, phosphorous, magnesium, manganese, and vitamins C, D, and K as mandated by the FDA.

Magnesium’s Moment
According to Ford, “Magnesium is growing in the mineral space as consumers realize the importance for a variety of health conditions. It is predicted that magnesium sales will surpass calcium in the coming years. Calcium sales have flattened as more novel approaches to bone health have emerged, such as collagen and K2.” 

Validating Ford’s observation about the emergence of magnesium, Ohad Cohen, CEO of mineral specialist Gadot Biochemicals, Ltd., commented, “Magnesium has also been overlooked for quite some time; it was a forgotten mineral. Now magnesium is well on its way to becoming top-of-mind along with calcium, iron, and zinc,” he predicted.

During the past five years, Cohen added, there has been a notable increase in formulators implementing minerals into their products. “This is because consumers are becoming more aware of the importance of mineral intake and the lack of minerals in natural foods due to the use of chelate-forming pesticides that keep minerals bound in the soil in which they grow,” he said.

Magtein Magnesium L-threonate (available from AIDP) is a patented compound discovered by MIT scientists with strong evidence supporting cognitive function and brain health, according to Ford, who added that Magtein is supported by several published studies reporting its mechanism of action and cognitive benefits.

For example, she pointed to a 12-week randomized, double-blind, placebo-controlled human clinical study published in the Journal of Alzheimer’s Disease in 2016. The effect of Magtein on cognitive ability was evaluated in four major domains: executive function, working memory, attention, and episodic memory. Significant improvements were observed in each of these domains and Magtein was shown to reduce brain age by 9 years.

Overall, according to Cohen, more and more science on magnesium is focusing on its actions in specific neurodegenerative states, and the research is showing significant potential for its use in these areas. One study published in Neuron in 2010 suggested that increasing magnesium consumption may be a valuable strategy to enhance cognitive abilities; it also supported the idea that low magnesium levels may impair cognitive function.

Other applications for this up-and-coming mineral include cardiovascular and circulatory health. According to Druke, there are many studies showing a significant correlation between people with low levels of magnesium, either in their diet or in their blood, that demonstrate a higher incidence of heart attack and stroke. There are also studies that connect magnesium with inflammation.

“Magnesium’s value to the heart’s health is crucial,” said Druke, “but it is also crucial to the vitality of all cells, which is why it is the key co-factor in more than 300 metabolic reactions in the body, including protein synthesis, muscle and nerve function, blood glucose control, and blood pressure regulation. Dietary surveys of people in the United States consistently show that intakes of magnesium are lower than recommended amounts.”

A recent study from the National Health Research Institute Database of Taiwan showed that people who consumed magnesium oxide were less likely to develop dementia (Current Medical Research and Opinions, 2018).

Researchers in a review article published in Oxidative Medicine and Cellular Longevity in 2017 documented that magnesium enhances the activity of three important mitochondrial dehydrogenases involved in energy production. Magnesium is also involved in the activation and production of adenosine triphosphate (ATP). “Studies have shown that disruption of the homeostasis of magnesium in the mitochondria leads to lower metabolites from the TCA cycle and lower activity of energy producing dehydrogenases,” Druke explained. “This may cause early fatigue.”

Selenium
Selenium is mostly known as a men’s health mineral, as it has been strongly suggested in numerous studies to protect prostate health.

According to a white paper from Lallemand Bio-Ingredients, not all forms of selenium are the same, and this notion is supported by “abundant preclinical data.” In the Nutritional Prevention of Cancer Trial (NPCT) and the Selenium and Vitamin E Cancer Prevention Trial (SELECT) wherein prostate cancer was the primary endpoint, selenomethionine supplementation was not protective. However, according to the supplier, In the NPCT trial, which used selenium yeast as a supplement, a strong protective effect in the prostate was observed with an 86% prostate cancer risk reduction among men with the lowest concentration of baseline plasma selenium.

And there seems to be more uses for selenium that may soon make it a women’s supplement as well. One recent study (BMC Musculoskeletal Disorders, 2019) examined the association between selenium consumption and prevalence of osteoporosis in 6,267 middle-aged and older men and women in China. After analyzing data, researchers found that those individuals with lower levels of selenium consumption had a higher prevalence of osteoporosis in a dose-dependent manner.

Choline
Sometimes the tail wags the dog; an ingredient can pull consumers into a category, rather than the category pulling consumers to ingredients. According to Druke, choline is a mineral that is helping to drive consumer interest in enhanced cognition in all life stages. Balchem’s VitaCholine salts were the choline source used in a landmark clinical study at Cornell University showing that increased choline intake during pregnancy correlated with improved processing speed in infants (FASEB Journal, 2013). This positive impact on cognition may continue into early childhood; the researchers are currently examining the longer-term benefits of increased maternal choline to these same infants, but now in early childhood.

In addition to the well-established neurodevelopmental benefits of choline, there is emerging research suggesting that there may be neuroprotective benefits, Druke reported. “An exciting new body of animal research at Arizona State University’s Biodesign Institute suggests several novel methods by which choline may mitigate the negative impact of several known risk factors for dementia later in life,” he said.

In an initial study published in Molecular Psychiatry in early 2019, maternal choline intake lowered levels of homocysteine, a pro-oxidant amino acid suspected of contributing to an increased risk of Alzheimer’s Disease. A subsequent study published in Aging Cell in 2019 focused on postnatal choline intake in mice and findings suggest that higher intakes of choline throughout life have a beneficial role in regulating the activity level of microglia, specialized cells that help clean the brain of harmful material. When over-activated, these “cleaner cells” may actually contribute to an increased risk of AD.

Formulation Challenges
Some vitamins and minerals are notoriously persnickety to work with. When choosing the right ingredient, Cohen said the type of formula is very important, whether it’s a solid dose or liquid. Subcategories of solid doses include powders, tablets, capsules, gels, etc. Factors such as solubility, pH, and palatability are very important and different when comparing gluconates to lactates to citrates or other organic salts forms.

“However, the key point is not to compromise on bioavailability,” said Cohen. “GADOT produces citrate-based minerals providing high bioavailability, which is proven by numerous scientific studies. That is why we use our technology to enhance the solubility of, for example, magnesium citrate (GADOMAG, Magnesium Anhydrous), whilst keeping the molecule 100% a citrate. We also micronize our products, encapsulate, or produce tableting grades.”

Formulating with iron in foods, stick packs, chewable tablets, gummies, etc. can be particularly challenging due to the instability of the mineral, combined with its potent and unpleasant flavor, noted Druke. Balchem’s Albion brand of minerals offers proprietary taste-free options for calcium, magnesium, zinc, and iron to remove or limit taste barriers in both supplement production and food fortification. Additionally, through the Balchem Sensory Effects flavor systems and manufacturing innovations, additional customer-specific solutions can be developed.

Other notable minerals also have their fair share of issues; for example, magnesium and iron supplementation can cause gastrointestinal distress, including gas and laxation. And this is where form enhances function.

“Clinical studies have shown less irritation from ingesting minerals as metal chelates, which are compounds where the metal is bonded to nutritionally functional organic compounds such as amino acids,” Druke explained. “These forms provide increased bioavailability of nutrients with greater tolerability compared to other compounds. Albion minerals chelated with amino acids have been shown to have greater bioavailability and utilization in humans. Its ferrous bisglycinate (iron chelated to two glycine molecules), as well as magnesium bisglycinate, have been shown to cause less gastrointestinal distress.”

Some vitamins also seem to have strong personalities. According to Ford, stability is a big challenge for vitamins. AIDP’s proprietary microencapsulation process, enVantec, offers solubility as well as stability for many fat-soluble vitamins, which are generally unstable. 

Cohen agreed, noting, “In general, vitamins are more sensitive than minerals to stress factors that occur during production. Vitamins can lose some activity during processing. Typically, loss in activity is compensated by adding a higher vitamin content than what is required on the label of the final product.”

Minerals are less sensitive than vitamins, Cohen continued, but are also often overdosed in formulas. For example, magnesium oxide is often overdosed in order to compensate for extremely low bioavailability. Another common challenge for formulators to keep in mind is potential nutrient interactions which can have a negative effect on solubility and cause sedimentation. “For these problems, we can look at encapsulation to protect the nutrient or even hide the taste,” he said.

As vitamins and minerals are used in a wide range of products, Chaudhari explained they can pose some technological challenges in terms of performance based on the formulation/end application, such as meal replacement drinks, sports drinks, stick packs, nutrition bars, shots, tablets, chews, and gummies. For liquid shots, solubility and stability of the ingredients are of prime importance.

Simultaneously, acceptable taste and flavor are necessary for the success of the launched product. Under harsh heat treatment, certain sensitive vitamins such as A, B1, and C, can get lost, whereas B12 destabilizes under low pH conditions. Some minerals like iron and copper offer strong metallic taste and trigger unwanted color changes.

“Therefore, in addition to our stabilized form of chromium,” Chaudhari said, “we use chelated forms of iron and copper to minimize off-notes and color change without compromising the bioavailability of the nutrients. In addition, we make and use natural flavor enhancers to overcome the off-notes.”

During processing of the end form, consideration is given to particle morphology and shape, which influence flowability, ease of handling, and processing of the powders, Chaudhari added. “Therefore, particle size management of the ingredients is critical to achieving the desired performance and must be carefully optimized before using in tablets, chews, and stick packs. Because formulations tailored for stick packs require quick dispersion and water solubility, we use water-soluble forms of vitamins and minerals. To enhance the flowability of the mix from the stick pack, we add ‘clean’ flowing agents.”

Gummies pose a different type of challenge. A white or color spot on the gummy is an issue if the formulation doesn’t use the right vitamin/mineral forms. The stability of certain sensitive vitamins such as A and folic acid is another concern when fortifying gummies; therefore, to ensure nutrient claims, Prinova uses a stable form of folic and vitamin A, Chaudhari said.

Brands seeking to make small-serving products such as lozenges, gummies, chews, and tablets, uniform dispersion of the micro-nutrients is a challenge, he added. “The complexity is associated with safety, quality, and efficacy of formulation dosages. We use our validated micro-nutrients trituration of chromium, molybdenum, selenium, and iodine to offer homogenous formulations for such small-serving supplements.”

Another challenge for product developers is ensuring that strict vegans have access to vitamins commonly derived from animals. According to Ford, AIDP offers the only pure vegan vitamin D3, VegD3, which can be used as a 1:1 replacement to animal-based D3. AIDP’s enVantec technology is a gelatin-free encapsulation solution for fat-soluble nutrients. It is Vegan Society approved and there are no supply limitations. “This is the only 100% pure crystal cholecalciferol (vitamin D3) for vegans,” she claimed. 

This is just a glimpse of the activity occurring in the vitamins and minerals category, and it is proof too that the original dietary supplement market segment continues to lead with solid research and manufacturing innovation to fulfill consumers’ self-healthcare goals.