Omega-3 fatty acids are critical nutrients for the developing fetus and the growing child. Published studies attest to the benefits of increasing omega-3 intake levels through dietary practices as well as dietary supplements, especially in pregnant women and in early childhood development. Why? Omega-3 long-chain polyunsaturated fats (PUFA) play major roles in embryonic development that span the gamut of human physiology.

Docosahexaenoic acid (DHA), in particular, is one of the most critical omega-3 fatty acids for fetal development. This is illustrated by the fact that, while concentrations of all fatty acids in maternal blood increase during pregnancy, the concentration of DHA specifically decreases, indicating the growing fetus’s need for DHA. In addition, DHA is one of the few fatty acids that is preferentially transferred to the placenta through the mother’s cord blood.

DHA and other omega-3 fatty acids, including eicosapentaenoic acid (EPA), remain of critical importance after birth, in early childhood and through adolescence. Unfortunately, the majority of DHA and EPA intake comes from the diet, and it has been shown that dietary intake of these essential omega-3s by both young and old remains woefully inadequate. According to National Institutes of Health data, children and teens average about a 40-mg total daily DHA + EPA intake from dietary sources, while adults average about 90 mg.

 This is substantially lower than the 500 mg/day that the Global Organization for EPA and DHA Omega-3 (GOED; Salt Lake City) recommends for health maintenance,

 and does little to fulfill potential daily requirements for these key nutritional factors.

This is concerning, given that ongoing research continues to point to the great need for omega-3 fatty acids for healthy development. Ahead, we highlight some recent studies in the areas of fetal development, childhood growth, and brain development.

Omega-3 fatty acids, in particular DHA, support several aspects of fetal growth. Several, but not all, recent studies indicate that higher intake of omega-3 fatty acids during pregnancy may reduce the incidence of preterm birth and help reduce the likelihood of children being born with low or very low birth weight. Additional research points to the benefits of DHA intake for addressing other areas of fetal development.

A recently conducted analysis led by Susan Carlson from the University of Kansas Medical Center (Kansas City) took data from two clinical studies conducted earlier which assessed other pregnancy-related outcomes in women supplementing with DHA. The University of Kansas researchers performed a secondary analysis on this data looking specifically at the relationship between DHA supplement dosage and the incidence of preterm birth and birth weight in 345 pregnant women.

 In the original studies, healthy pregnant women with singleton pregnancies (no twins, etc.) were assigned to supplement with 600 mg/day of DHA or a corn-and-soybean-oil placebo beginning between week 12 and 20 of gestation until delivery.

Because supplementation compliance was pointed out as an issue of concern in the original studies, the authors looked at the relationship between compliance and the relevant endpoints of preterm delivery and birth weight. They found that the incidence of low and very low birth weight, as well as preterm deliveries, decreased significantly with increased compliance (and therefore greater DHA intake). Upon assessing the data, they determined that a rate of about 50% compliance (or an average intake of 285 mg of DHA/day) reduced preterm birth and reduced low- and very-low-birth-weight rates by nearly half. Increasing the dose of DHA even further (up to 600 mg/day) led to additional declines in preterm birth as well as very-low-birth-weight deliveries.

In another investigation, Annie Penfield-Cyr from Brigham and Women’s Hospital (Boston) led a secondary analysis of data from the Maternal-Fetal Medicine Units Network randomized controlled trial assessing whether supplementation with 2 g of omega-3 fatty acids daily (as 800 mg DHA and 1200 mg EPA) during pregnancy (beginning between weeks 16 and 22) prevented recurrent preterm birth.

While the primary study did not show a benefit of omega-3 supplementation in preventing preterm birth

, this secondary analysis looked at whether the ratio of pro-inflammatory-to-inflammatory fatty acids (omega-6:omega-3 ratio) measured between week 25 and 28 of pregnancy impacted fetal growth parameters. Furthermore, the participants were divided into two subgroups based on their body mass index (BMI) and classified as lean (18.5-24.9 kg/m

). The analysis included 440 pregnant women with a prior history of preterm delivery.

Of the women taking omega-3 supplements during their pregnancy, the researchers found that those classified as obese/overweight with higher omega-6:omega-3 ratios showed impaired fetal growth and shorter gestational length. The babies of these mothers also had a higher incidence of respiratory distress after birth as well as increased hospital stays. These results indicate that higher maternal inflammation (as measured by omega-6:omega-3 ratios during pregnancy) may be a marker of adverse fetal growth outcomes, especially in overweight and obese pregnant women. Because supplementation with omega-3 fatty acids can modify maternal inflammation, it may have a protective effect on fetal growth parameters.

A more recent, large, double-blind, multi-center study performed in Australia and led by Maria Makrides from the South Australian Health and Medical Research Institute (North Terrace, Adelaide, Australia) followed 5,544 pregnancies in which women were asked to supplement with 900 mg of omega-3 fatty acids or placebo daily beginning before 20 weeks of gestation to the end of pregnancy.

 The primary outcome of this study was early preterm delivery.

The results showed that early preterm delivery occurred in 2.0% of the women taking the placebo, while it occurred in 2.2% of those taking omega-3 fatty acids; however, the differences were not statistically significant. On the other hand, a significantly higher percentage of infants born to women taking the omega-3 supplements were very large for gestational age at the time of birth. Given these results, the impact of omega-3 supplementation on preterm birth remains unclear and requires further analysis.

Questions regarding the optimal dose of omega-3s during pregnancy as well as which populations benefit the most remain to be answered. Additionally, the authors of this study mention that previous studies have found that women with the lowest baseline levels of omega-3s are likely to receive the most benefit from supplementation; in the current study, that analysis was not performed, but could very well have resulted in similar findings. It is likely that women with certain baseline risk factors would benefit significantly more than others from omega-3 intake during pregnancy.

Childhood Growth and Healthy Body Composition

Omega-3 intake at a young age and during development has been found to confer significant benefits on several aspects of childhood growth. Research has shown that omega-3s, whether consumed by the mother in pregnancy or by the child during his or her early years, are likely to positively influence body composition and overall growth.

In a recent trial led by Rebecca Vinding from the University of Copenhagen (Copenhagen, Denmark), researchers studying fish oil supplementation during pregnancy and its effects on childhood growth found significant benefits for bone health as well as lean and fat mass.

In the double-blind, placebo-controlled study, researchers followed 736 women and their offspring until age six. The women were asked to supplement with fish oil (2.4 g/day containing 55% EPA and 37% DHA) or an olive oil placebo, from week 24 of pregnancy until one week after birth.

The results indicated that fish oil during pregnancy may have a general and beneficial growth-stimulating effect on the offspring. Significant increases were seen in BMI, weight-to-height ratio, and waist circumference in the offspring between ages 0 and 6 in the fish oil group, but not in the olive oil group; however, it should be noted that these increases did not lead to an increased risk of obesity. Dual-energy x-ray absorptiometry scans (DXA) showed a significantly higher increase in lean mass in the fish oil group versus olive oil, and a higher bone mineral content, revealing that maternal fish oil supplementation led to a proportional increase in lean mass, bone mass, and fat mass.

An additional study explored the impact of maternal DHA supplementation on child body composition at five years of age. Led by Brandon Hidaka from the University of Kansas Medical Center (Kansas City), researchers measured body composition of 154 five-year-old children whose mothers had supplemented with 600 mg of DHA or a placebo during pregnancy.

 The mothers started out with poor DHA status at the beginning of the study and commenced supplementation from before 20 weeks of gestation to birth.

For the present analysis, researchers used air-displacement plethysmography to assess body composition in the children.

 These measurements were compared to three different indicators of DHA status in the mothers. The results of the study showed that maternal red blood cell phospholipid DHA status at delivery was significantly correlated with higher fat-free mass in the children at age five, while the other two measures of DHA status (which included change in maternal blood DHA levels and being a part of the intent-to-treat DHA group) showed a favorable trend for this effect but did not reach statistical significance. The takeaway: overall higher DHA status in mothers during pregnancy had a favorable impact on lean mass in their children at five years of age.

PUFA, and particularly DHA, are known to be important building blocks for brain development. Several studies suggest that supplementation of omega-3 fatty acids either by the mother during pregnancy or by children in their early years may have lasting benefits for brain function and cognition.

Rebecca Lepping and colleagues from University of Kansas Medical Center (Kansas City) conducted a study to evaluate the effect of consuming long-chain-PUFA–fortified infant formula (containing arachidonic acid/ARA and DHA) during the first year of life on brain development at age nine.

In the study, a total of 42 children who consumed formula without long-chain PUFA, or with 0.64% ARA plus three different concentrations of DHA (0.32%, 0.64%, or 0.96%), were then evaluated using various magnetic resonance imaging (MRI) techniques to assess effects on brain structure, function, and metabolism. Following functional MRI analysis, researchers found that children who had consumed long-chain-PUFA–fortified formula during the first year of life had greater brain activation in the anterior cingulate cortex and parietal regions when undergoing the Flanker task (a measure of the brain’s ability to inhibit responses that are inappropriate in a given context), indicating greater inhibition.

Furthermore, resting-state MRI analysis of each of the groups found that those consuming the formula fortified with 0.64% DHA showed greater connectivity between the prefrontal and parietal regions of the brain compared to all other groups. In addition, brain white matter volume in the prefrontal and anterior cingulate cortex increased in the 0.32%- and 0.64%-DHA groups. These results suggest that fortification of formula-fed infants with DHA during their first year of life can have significant lasting benefits for neurological development, including brain structure and function.

Another study looked at the effect on infant brain volumes of a DHA-enriched supplement given to mothers during pregnancy. Led by Enitan Ogundipe from Imperial College of London (London), researchers recruited 300 pregnant women and asked them to consume two capsules of the DHA-based supplement (containing 300 mg DHA, 42 mg EPA, and 8.4 mg ARA per capsule) or a placebo until delivery.

At the end of the study, 86 infants underwent brain MRI scans at an average gestational age of 43 weeks. In female infants, no significant differences in brain volume were noted in the supplement group versus placebo; however, in male infants in the supplement group, DHA led to increased birth length and head circumference as well as increased total brain, cortex, corpus callosum, and whole gray matter volume compared to placebo. The study findings indicate a gender-specific effect of DHA and highlights the need for ensuring optimal DHA status in pregnant women for supporting healthy infant brain development.

The research on omega-3 fats and their ability to positively impact the developing fetus and growing children is clear. Nutritional interventions incorporating these essential and healthy fats can yield significant benefits for childhood growth and development.

Although researchers must continue to tease out issues around dosing as well as identifying population groups that are likely to benefit the most, adding DHA and other omega-3 fatty acids to a child or expecting mother’s daily routine may be a prudent step in ensuring individuals are meeting their need for these critical nutritional factors.

Demmelmair H et al. “Importance of fatty acids in the perinatal period.” 

World Review of Nutrition and Dietetics. 

National Institutes of Health. Omega-3 Fatty Acids: Fact Sheet for Health Professionals. Updated July 9, 2019. Accessed at: 

https://ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional

Global Organization for EPA and DHA Omega-3 Intake Recommendations. Accessed at: 

https://goedomega3.com/intake-recommendations

Carlson SE et al. “Dose-response relationship between docosahexaenoic acid (DHA) intake and lower rates of early preterm birth, low birth weight and very low birth weight.” 

Prostaglandins, Leukotrienes, and Essential Fatty Acids. 

Penfield-Cyr A et al. “Maternal BMI, mid-pregnancy fatty acid concentrations, and perinatal outcomes.” 

Harper M et al. “Omega-3 fatty acid supplementation to prevent recurrent preterm birth: a randomized controlled trial.” 

Makrides M et al. “A randomized trial of prenatal n-3 fatty acid supplementation and preterm delivery.” 

vol. 381, no. 11 (September 12, 2019): 1035-1045	

Vinding RK et al. “Effect of fish oil supplementation in pregnancy on bone, lean, and fat mass at six years: randomised clinical trial.” 

Hidaka BH et al. “Intrauterine DHA exposure and child body composition at 5 y: exploratory analysis of a randomized controlled trial of prenatal DHA supplementation.” 

vol. 107, no. 1 (January 1, 2018): 35-42	

Carlson SE et al. “DHA supplementation and pregnancy outcomes.” 

Lepping RJ et al. “Long-chain polyunsaturated fatty acid supplementation in the first year of life affects brain function, structure, and metabolism at age nine years.” 

Ogundipe E et al. “Randomized controlled trial of brain specific fatty acid supplementation in pregnant women increases brain volumes on MRI scans of their newborn infants.” 

Articles

More evidence that omega-3 fatty acids are critical nutrients for the developing fetus and the growing child.

Omega-3s, infants, and kids: New evidence for healthy mental and physical development

Cardiovascular disease remains the leading cause of death in the United States. Nearly half of all American adults currently have some form of the disease, according to the American Heart Association (AHA). These include coronary heart disease, heart failure, stroke, and high blood pressure.

When these facts are combined with an American public that is growing ever more eager for information about nutrition and exercise and more aware of product labeling and terminology, the result is a consumer base seeking out and researching dietary supplements for improved cardiovascular health.

Members of the scientific and medical communities, however, have yet to reach consensus on the role of dietary supplements in restoring or maintaining cardiovascular health. The reason for this depends on whom you ask; and, by nature, science, medicine, and nutrition are all dynamic areas of study full of complexity. One recent meta-analysis of supplements for cardiovascular health, “Effects of nutritional supplements and dietary interventions on cardiovascular outcomes: an umbrella review and evidence map,” and an associated editorial, “Dispense with supplements for improving heart outcomes,” both published in the August 2019 issue of the 

 garnered quite a bit of attention and reaction from various cardiovascular-health stakeholders.

 The conclusions of the meta-analysis were that reduced salt intake, the use of omega-3 long-chain polyunsaturated fatty acids, and supplementation with folate could reduce the risk of some cardiovascular outcomes in adults. Additionally, “combined calcium plus vitamin D might increase the risk of stroke,” the authors wrote. Limitations of the analysis were “suboptimal quality and certainty of evidence,” they added.

 had some positive findings,” says Andrea Wong, PhD, senior vice president, scientific and regulatory affairs, Council for Responsible Nutrition (CRN; Washington, DC). “It showed omega-3 fatty acids can decrease the risk of heart attack and coronary heart disease. Folic acid can decrease the risk of stroke. But these findings were overshadowed by the accompanying editorial, ‘Dispense with supplements for improving heart outcomes,’ which made very broad and unfounded statements on the whole category of supplements and their effect on heart health. And that really does a disservice to consumers as well as to healthcare providers who are advising their patients.”

Wong goes on to make the point that “heart disease is very complex, and many factors can contribute to its development.” She says it is “unrealistic to expect that making one change, like consuming a dietary supplement, will have a dramatic effect on heart health outcomes.” Supplements can 

 in cardiovascular health, she explains, but consumers also need to practice other healthy habits. She adds that supplements can’t be compared to prescription drugs, and that they are “not meant to replace prescription drugs or dialogue with one’s healthcare provider, so it’s unfortunate that the author of the editorial and others are repeating the same [anti-supplements] message and trying to influence public policy in this area.

His is a blanket statement against supplements in general,” she says. “We can’t apply the drug-research paradigm to nutrition research and expect to have the same type of outcome.”

Matthew Roberts, PhD, chief scientific officer at ChromaDex (Los Angeles), which supplies the nicotinamide riboside ingredient Niagen for heart health, including in its own Tru Niagen supplement, shares Wong’s assertion. “Many attacks on supplements are based on a flawed notion that supplements should be studied like drugs. While supplements are a great tool for supporting and promoting health, they are fundamentally different from drugs and should not be seen as a replacement for them.”

He continues, “Drugs are designed to treat diseases-they function in the body to actively improve a condition and/or reverse symptoms of a disease. Supplements, on the other hand, are exactly that: supplements. They supplement the diet to ensure we are giving our bodies the best nutritional support possible. Through nutrition and healthy habits like exercise and good sleep hygiene, we can support the body’s natural ability to function optimally and stay resilient to stress.”

Omega-3 fatty acids seem to have secured their position among heart-health supplements as one of the leaders. Chris Gearheart, director, member communications and engagement, Global Organization for EPA and DHA Omega-3 (GOED; Salt Lake City), points to three large-scale studies published in the past year-REDUCE-IT

-which have “doubled the number of human subjects studied in the literature on omega-3s and cardiovascular outcomes,” he says. And while not all of those studies met their primary research endpoints, he says, they 

 all show “statistically significant risk reductions in areas like myocardial infarction and coronary heart disease.”

Gearheart explains that there are multiple reasons why some studies show a clear cardiovascular benefit of omega-3s while others do not, including, he says, “the inclusion/exclusion criteria for studies, which are chosen by the authors; the fact that the subjects may be on cardiovascular drugs that are effective, lessening the chance of omega-3s having an additional affect; and, lastly, the lack of baseline level measurement in some studies. If the subjects already have high omega-3 consumption,” he says, “additional omega-3 intake is not as likely to have an impact.” Gearheart adds that GOED is preparing to submit a paper on EPA/DHA and cardiovascular dose response that summarizes the state of the literature in light of this new data, “which we hope to have published this year,” he says.

CRN’s Wong cites a piece published this past September in the 

Journal of the American Heart Association,

 “Marine omega-3 supplementation and cardiovascular disease: an updated meta-analysis of 13 randomized controlled trials involving 127 477 participants,” which, she says, further confirms the supplement’s cardio-friendly attributes.

 The meta-analysis concluded that marine omega-3 supplementation “lowers risk for myocardial infarction, coronary heart disease death, total coronary heart disease, cardiovascular disease death, and total cardiovascular disease, even after exclusion of REDUCE-IT. Risk reductions appeared to be linearly related to marine omega-3 dose,” according to the paper’s authors.

While omega-3s’ cardiovascular benefits are largely (if perhaps grudgingly, by some) accepted in the medical community, the variety and volume of 

 ingredients and supplements with potential for cardiovascular benefits is vast, and study of them is ongoing. What follows is an update on and round-up of some of the most interesting.

“Although scientists first published studies about the molecule nicotinamide riboside (NR) in the 1940s,” says ChromaDex’s Roberts, “its potential to support human health wasn’t uncovered until recently.” And last year, he points out, a study from the University of Colorado Boulder, published in

showed the potential for NR to decrease blood pressure and arterial stiffness.

 “This needs to be replicated,” he says, “but the authors of the study now have two ongoing follow-up clinical trials looking at these cardiovascular endpoints in larger groups of people.” Roberts predicts “lots of exciting research on the horizon” for this ingredient.

A study published in May of this year in 

concluded that glucosamine supplementation in those with osteoarthritis might also be related to lower risk of cardiovascular-disease events.

 In other words, cardiovascular benefits might be a happy side effect.

Jacob Teitelbaum, MD, founder of the “Cures A-Z” app and author of various popular health titles, says that this finding “should not come as a surprise to those who follow the research. Two other large studies with a total of over 330,000 subjects showed similar findings for glucosamine,” he asserts. Teitelbaum is a champion of promoting herbal and other non-pharmaceutical remedies for osteoarthritis pain over the use of NSAIDS, which he says increase the risk of both cardiovascular death and bleeding ulcers. He condones the use of glucosamine and other supplements to treat osteoarthritis pain and laments that marketers of glucosamine can’t cite research findings in support of glucosamine for heart health on their package labels.

“By introducing D-ribose pre- and post-operation in heart surgery, the extensive damage implicated as reperfusion injury”-tissue damage caused when blood supply returns to tissue following a lack of oxygen-“can be reduced or avoided altogether,” says Michael Crabtree, director of scientific affairs, Bioenergy Life Science Inc. (Minneapolis), which markets the Bioenergy Ribose brand of D-ribose. Supplementation with D-ribose is demonstrated to assist in the maintenance and recovery of the elasticity of left-ventricular function, he adds, preserving stroke-volume-the quantity of blood delivered to tissue with each cycle-by maintaining normal energy charge in cardiac cells.

An “important new discovery” on this front, Crabtree says, is that D-ribose helps untrained individuals to adapt to physical exercise.

 “We have also found that D-ribose combined with caffeine increased energy substance and endurance in fatigued mice, as well as in humans.”

A study published in January of this year in 

BMC Complementary and Alternative Medicine 

indicates a positive effect of Arjuna Natural’s (Kerala, India) Tri-Low full-spectrum botanical amla extract 

 on dyslipidemia, a contributor to atherosclerosis.

 The extract, from a fruit widely used in Ayurvedic medicine, has shown “significant potential in reducing total cholesterol and triglyceride levels and stimulating a more favorable balance of lipid ratios,” according to company literature. The company also states that the extract “is the first of its kind standardized with diglycerides of alpha-linolenic acid and polyphenols.”

Harvested from a largely ornamental shrub native to Eastern North America, the aronia berry is rich in polyphenols and is being studied for its potential benefits to cardiovascular health and the microbiome. Eve Landen, media manager, flavor division at Naturex (Avignon, France), part of Givauden (Vernier, Switzerland), points to a recent study published in the 

 that suggests that consumption of both aronia whole-fruit powder and extract of aronia berry (Naturex’s Aronox product) improves endothelial function and modulates the composition of gut microbiota, thereby helping to maintain cardiovascular health.

“Improving endothelial function leads to improvements in blood flow,” Landen says. “A 1% improvement in endothelial function has been shown to correlate with an 8%-12% reduction in CVD risk, according to two recent meta-analyses.”

Supplements aren’t magic bullets or miracle cures, but they are likely to be one of many useful, valuable tools upon which consumers can call for optimal cardiovascular health, along with proper nutrition, exercise, adequate sleep, and high-quality medical care. Rather than “dispensing with” supplements altogether because the science is still in development, the public and the medical establishment alike might perhaps be wise to keep an open mind, and view supplements the way ChromaDex’s Roberts does: as support for the body’s natural ability to function optimally and stay resilient to stress. “Our toolboxes can include supplements, the type and selection of which will depend on one’s health needs and objectives,” he says.

“Heart disease continues to be the leading cause of death of Americans according to the CDC,” adds CRN’s Wong, “and the prevalence is increasing. It’s a huge burden on quality of life, and on individual and family finances. For these reasons, people seem to be taking a more proactive approach to their health. They may not be waiting for a diagnosis, so there’s a lot of interest among consumers in a nutritional way to maintain their heart health.” Along with other healthy lifestyle habits, supplements-thoughtfully selected and appropriately dosed-may be just the thing.

Khan SU et al. “Effects of nutritional supplements and dietary interventions on cardiovascular outcomes: an umbrella review and evidence map.” 

Pandey AC and EJ Topol. “Dispense with supplements for improving heart outcomes.” 

vol. 171, no. 3 (August 2019): 216–217	

Bhatt DL et al. REDUCE-IT Investigators. “Effects of icosapent ethyl on total ischemic events: From REDUCE-IT.” 

Journal of the American College of Cardiology, 

vol. 73, no. 22 (June 11, 2019): 2791-2802	

Manson JE et al., VITAL Research Group. “Marine n-3 fatty acids and prevention of cardiovascular disease and cancer.” 

vol. 380, no. 1 (January 3, 2019): 23-32	

Bavry A et al. “Effects of n-3 fatty acid supplements in diabetes mellitus.” 

 vol. 379, no. 16 (October 18, 2018): 1540-1550	

Hu Y et al. “Marine omega-3 supplementation and cardiovascular disease: an updated meta-analysis of 13 randomized controlled trials involving 127 477 participants.” 

Journal of the American Heart Association, 

vol. 8, no. 19 (October 2019). Published online September 30, 2019.	

Martens CR et al. “Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults.” 

Ma H et al. “Association of habitual glucosamine use with risk of cardiovascular disease: prospective study in UK Biobank.” 

Seifert JG et al. “The influence of D-ribose ingestion and fitness level on performance and recovery.”

 Journal of the International Society of Sports Nutrition. 

Ding Y et al. “Effects of D-ribose on high-energy phosphate metabolism of skeletal muscle tissues of tired mice.” 

World Science and Technology-Modernization of Traditional Chinese Medicine. 

Upadya H et al. “A randomized, double blind, placebo controlled, multicenter clinical trial to assess the efficacy and safety of 

 extract in patients with dyslipidemia.” 

BMC Complementary and Alternative Medicine, 

Istas G et al. “Effects of aronia berry (poly)phenols on vascular function and gut microbiota: a double-blind randomized controlled trial in adult men.” 

vol. 110, no. 2 (August 1, 2019): 316-329

Heart health ingredients bring new science and innovation to market, despite some bad press.

Supplements for heart health: ingredient developments and progress, despite some negative omega-3 headlines

The color of a food or drink makes a big impression when consumers are making a purchasing decision. Artificial colors have long been an important tool for food formulators, but with the push for clean-label products, artificial colors continue to fall out of favor. Natural colors, sourced from food, are growing in popularity, but they still pose some challenges to formulators making clean-label products.

“The main challenges switching to natural colors include stability and cost, and it is not as simple as a 1:1 replacement for artificial,” explains Brian Stuart, color chemist for Gold Coast Ingredients (Commerce, CA). “When using natural colors, the pH, any heat being added, if the product is being exposed to light-all of this has to be taken into account when using natural. Then the cost of natural colors is usually more expensive than artificial colors.”

Because natural colors are sourced from food, their taste may not be neutral and will therefore contribute to the end product. Turmeric and paprika are good examples of ingredients that produce vibrant, natural colors but that also impart flavor. When formulating a product from scratch, this must be taken into account and either intentionally become part of the product’s flavor profile, or else formulators must compensate for the taste.

“This is not often an issue due to the low usage of coloring agents,” says Stuart. “However, if the usage of the coloring agent is high, then it might become necessary to mask any undesired flavor the color gives the product. Masking agents are a great ingredient to mask any off notes put off by natural colorants, which tend to carry an ‘earthy,’ ‘dirt,’ or possibly bitter taste.”

Replacing traditionally used colors with natural colors requires creativity to ensure that the overall flavor profile remains the same. For example, because of Prop 65 regulations in California, many manufacturers are trying to find an alternative to caramel coloring. This is why Sensient (Chicago, IL) recently launched Sienna Colors, a portfolio of brown shades from natural sources that are free from furfuryl alcohol and 4-MEI. Sienna Colors are heat and light stable across a wide pH range.

“If you think about it, caramel may or may not have contributed taste to the product, and if you’re adding different colors, it could affect your taste profile. That’s why the colors and flavors [we offer] are a unique, added-value proposition we have for our customers,” explains Aret Meyer, general manager of savory flavors for Sensient.

If you’ve ever bought paint at a hardware store, you know that the color you choose is actually a blend of many different colors at a specific ratio. Coloring foods can be similar.

“The intensity of the color is dependent on the molecule that acts as the coloring constituent,” explains Stuart. “For example, red beet is a red color, and that specific red color comes from a molecule called betanin. The intensity of the red beet color is determined by the concentration of betanin content. Variation in hue stems from the formulation of blends by adding a variety of natural colors to achieve a new hue, and even small amounts of different additions of colors can make a large difference in terms of a variation of that color-for example, transitioning a light green color to a lime green color.”

The way a color looks may also depend on whether the source material is a powder or liquid. Powders, for instance, can vary in color. “Powders tend to have good-to-okay consistency in terms of shade and hue, but can vary more than liquids due to the fact that it is a natural color. Since the source of the color has several variables, these factors can cause, for example, a blue color to be darker or lighter, but when put into solution would remain consistent in terms of the same color from different batches,” explains Stuart. By contrast, he says, “Liquid colors tend to be consistent in terms of shade and hue since the color is dispersed into a liquid media, which allows for a different color expression than that of powder.”

Using a powder or liquid has different advantages and disadvantages. Powders, for example, can be used in most applications and have a longer shelf life and stability in storage, but liquids tend to be more versatile and easier to work with for measuring out and handling the material. Liquid colors can be more challenging to use in oil-based applications, however.

Considering that these differences are pretty small, powder and liquid forms are mostly interchangeable, says Stuart, and depend on the customer’s preference.

Natural colors, sourced from food, are growing in popularity, but they still pose some challenges to formulators making clean-label products.

Clean-label color challenges

Remember back when you actually had to swallow a tablet or capsule to get dietary supplementation’s nutritional benefits?

Yeah, we can barely remember those days, either. And to the extent that swallowing a vitamin tablet, capsule, or otherwise is now a choice rather than an obligation, we can thank the gummy.

These pudgy, pleasing, and altogether palatable nutrient-delivery vehicles have virtually revolutionized the act of supplementation at the same time that they’ve broadened the base of supplement users. And few appreciate their contribution better than Doug Brown, Americas director, Sirio Pharma (Shantou, China).

“Gummies continue to be a huge deal for the supplements industry,” Brown says. “They’ve added new fuel to the category’s overall growth and clearly signify a strong consumer preference for this fun format.”

So strong is the current consumer preference for vitamin gummies that his company-which has advanced the state of gummy research and development for more than a decade-announced last September the opening of a dedicated new gummy production facility in Ma’anshan, China, a mere 11 years after opening its previous gummy facility.

As far as Brown is concerned, these are wise investments, given the numbers. He cites data from Transparency Market Research predicting 5.2% compound annual growth for gummy vitamins between 2017 and 2025, sending the sector to an estimated value of $4.17 billion.

“The real value of the gummy format,” he says, “is that it provides consumers with a more pleasant choice to address their daily nutritional needs.”

Initially, their appeal aimed mainly at children, who might have been more reluctant-or simply unable-to tolerate more traditional supplement formats. And indeed, Brown says, gummies now account for more than half the children’s vitamin, mineral, and supplement segment’s sales.

“But as it turns out,” he continues, “parents and grandparents soon discovered their ‘inner child’ and have driven strong growth of gummies across the category.” Adults now form the core of gummies’ target audience, he says, and adult-directed supplements are responsible for upwards of 65% of the market.

But gummy supplements don’t just grow on trees. Nor do they come from a candy store-although Brown notes that nutritional gummy manufacturing evolved from the confectionery process.

Fact is, gummy supplements are more difficult to produce and have to clear several formulation and manufacturing hurdles vis-Ã -vis taste, texture, and structural stability.

Consider taste. “Consumer preferences tend toward pleasant fruity flavors with a juicy quality,” Brown observes. Alas, few nutritional ingredients exhibit such profiles. Fortunately for consumers, the fruity, juicy flavors they prize also effectively mask the off flavors of most nutritional ingredients, Brown says. “For the more challenging ingredients, such as B vitamins, minerals, and omega-3s, we’re able to solve issues with our R&D team.” He says his company has built a database of ingredients, flavors, colors, and sweeteners-as well as an inventory of their interactions during manufacturing-to get better leverage over the flavor and formulation challenges.

Texture is another important-and potentially vexing-consideration in gummy formulation. As Brown explains, gummy texture comes mainly from the colloidal base, but in the case of gelatin gummies in particular, some ingredients can compromise the base structure.

Consider calcium, which reduces the gelatin base’s water content. Switching to a plant base, Brown says, resolves the issue.

“To prevent crosslinking from impacting gummy stability and texture,” he continues, “more gelling agent is used to maintain the bond’s strength.”

And opting for micro-ionized forms of some nutritional ingredients, when available, can head off any grittiness in the mouthfeel while at the same time helping to address possible flavor and nutrient-loading issues.

What about those nutritionals themselves: How well does the gummy matrix protect and preserve vulnerable or highly labile nutrients?

“Gummies are an excellent protective medium for most nutritional ingredients,” Brown says. “Absorption is similar to other delivery systems.”

Nevertheless, gummy production involves complex temperature, humidity, and pH conditions that Brown says “require careful stewardship of ingredients.”

Probiotics can suffer especially “as most strains don’t hold up to this type of process,” Brown says. In response, Sirio developed a proprietary probiotic process that ensures their survival and potency in the finished gummy. They’ve even devoted an entire facility to the process, he says.

Finally, manufacturers can’t get into the gummy game without taking clean labeling into account. “Consumers have expressed a clear preference for uncompromising clean, natural ingredients with full transparency,” Brown says.

Thus, his company offers plant-based, low-sugar, and no-sugar versions of its gummies with comparable taste to traditional offerings. “We readily choose natural materials for all aspects of production, so clean label is part of our DNA,” he says.

In fact, he thinks going clean makes gummy production less complicated. Given the dynamic state of the gummy supplement market, that’s good news for all involved.

Transparency Market Research. "Gummy Vitamins Market (Product - Single Vitamin (Biotin, Omega & DHA, Vitamin C, CoQ10, Vitamin D, Melatonin, and High-fiber Formulas) and Multivitamins; Age Group - Children and Adults) Global Industry Analysis, Size, Share, Growth, Trends, and Forecast 2017 - 2025." October 2017. Accessed at: 

www.transparencymarketresearch.com/gummy-vitamins-market.html

Gummy supplements can be difficult to produce and have to clear of several formulation and manufacturing hurdles vis-à-vis taste, texture, and structural stability.

Gummy supplements: Perils and possibilities

The clean-label movement has dominated the past decade, with survey after survey showing that dietary supplement shoppers and the industry alike are moving toward “cleaner” products. Why? Consumers today aspire to a healthier lifestyle-from the environment they live in to what they put in their body-and, for reasons of their own, they associate cleaner labels with healthier products.

 has no official, universally recognized definition, in context it typically refers to products that use all-natural/non-GMO ingredients, transparent supply chains, and inputs that anyone with an eighth-grade education can pronounce. Clean-label products aim to exclude artificial colors, sweeteners, and preservatives, replacing them with natural ingredients that perform the same function.

“In its simplest form, clean label asks three integral questions: 1) Can the consumer pronounce the name of the ingredients or excipients? 2) Does the consumer know where the ingredient comes from? And 3) Does the consumer feel better knowing what they’re consuming?” says Steve Pierce, president of ingredient supplier Ribus (St. Louis), which touts itself as “The Original Clean-Label Company.”

Clean label sets forth a whole new set of targets for everyone in the supply chain to meet-and often, fulfilling those requirements is a lot harder than it sounds. A clean-label supplement must be, or try to be, clean through and through. This includes both active ingredients and their delivery vehicle. And indeed, more consumers are becoming aware of what goes into making the capsules, powders, and tablets they see on store shelves.

Barri Sigvertsen, global innovation marketing manager for Lonza Consumer Health & Nutrition (Morristown, NJ), points out that clean-label ingredients and delivery systems are “symbiotic.”

“They must work together in order to deliver a truly clean-label solution,” Sigvertsen says. “The delivery system is an integral part of the finished product, and so it makes sense to deliver a clean-label ingredient through a clean-label delivery system. The production requirements and challenges are also typically very much aligned; for both components, it is important to check that the raw material sources, vendors, and practices are clean label–compliant to optimize the output and deliver on consumer demands.”

For delivery system providers, performing to clean-label standards means continually expanding the options for supplement makers. We checked in with a few delivery system providers on their latest developments.

For Lonza, Sigvertsen says, “A major part of delivering clean-label solutions is ensuring that the facilities you operate in also adhere to clean-label requirements. As such, we have worked closely with our customers and suppliers to discover new raw material sources that address this need, and deliver our own processes that meet clean-label expectations.”

One of Lonza’s recent efforts is developing natural, food-based colorants for its Vcaps Plus vegetarian capsules. Says Sigvertsen: “Color has long been an important element of the dietary supplements industry, offering an opportunity for brand owners to differentiate and distinguish their products from the competition. The challenge, however, was that in order to create products with stable, long-lasting color, manufacturers were once left with no other option but to turn to artificial colorants, which did not align with consumer preferences.” Lonza’s naturally sourced colors from foods deliver more robust, stable colors with a more sustained performance than was previously possible, she says.

Capsule supplier ACG (Mumbai, India) has introduced its branded ACGcaps H+, a capsule product line that is made without the use of any gelling agents. “These capsules are manufactured with hydroxypropyl methylcellulose (HPMC) and water,” says Justin Kalafat, scientific business development manager for ACG Capsules. Kalafat says that the clean-label feature adds another benefit claim to the HPMC capsules, which already carried vegetarian/vegan, kosher, halal, and GMO-free claims. Kalafat notes that the clean-label shift is simply the next logical outworking of the GMO-free movement.

Kalafat agrees that dietary supplement companies are actively looking into new options for coloring. White capsules that are free from titanium dioxide are also gaining traction and permit brands to make clean-label claims, he says.

Other companies are also introducing their own clean-label alternatives. Susan Freers, technical service manager for specialty ingredients at Grain Processing Corp. (GPC; Muscatine, IA), says that GPC has been making innovations in its delivery system offerings, including its binders, carriers, and film formers.

“We’ve developed a variety of starting formulations for many markets,” Freers says, including makers of softgels, tablets, and capsules. For instance, she says, “we have a full line of identity-preserved, non-GMO maltodextrins, syrup solids, and starches.” GPC’s clean-label delivery systems are also Non-GMO Project Verified.

Excipients are key delivery system components. Pierce says that Ribus offers a “near complete” line of excipients “that offer clean-label alternatives to the industry standards like magnesium stearate (lubricant), silicon dioxide (flow agent), hydroxypropyl cellulose/HPC (binder), and others.” The company is also introducing a new, natural and organic excipient that absorbs oil-such as vitamin oils, omega-3s, or cannabidiol/CBD, for example-and allows oily material to be used in standard capsules, tablets, gummies, or powders. The gummy market, he adds, is now actively cleaning up labels and looking for cleaner ingredients and excipients.

Pullulan, a vegetable-derived, water-soluble polysaccharide used to make capsules, will continue to play an important role in the clean-label movement for years to come. In the U.S., the Organic Trade Association, as well as other industry advocates, have petitioned USDA and the National Organic Program (NOP) to add pullulan to the National List of Allowed and Prohibited Substances-namely, ingredients that are allowed to be used in products labeled as USDA Organic. The effort to add pullulan to the list is significant, considering that there are no other comparable NOP-approved vegetarian alternatives for producing capsules. The National Organic Standards Board has noted that manufacturers would otherwise be forced to use gelatin, which is included on the National List but which does not meet vegetarian, kosher, or halal needs. In 2019, the board voted to add pullulan to the National List. This move is a boon to capsule producers such as Lonza, which makes its Plantcaps vegetarian capsules from pullulan.

Ribus’s Pierce says, “The recent approval of natural pullulan for use in organic capsules-until the organic version [of pullulan] becomes commercialized-is an indicator of the desire to remove synthetics.”

As mentioned, one problem facing brands and formulators is the fact that there is currently no official, universally accepted definition of 

 While some terms in the dietary supplement and functional foods industry, like 

Consumers seeking clean-label products will often turn to the vast number of certification schemes in the market for guidance, including USDA Organic, gluten-free, Non-GMO Project Verified, vegan, and others. Navigating so many certifications can be cumbersome-and may lead to consumer confusion and mistrust-which is why organizations like the Clean Label Project are developing independent certifications specifically for the clean-label audience. Clean Label Project has developed its own certification process for sweeteners, dietary supplements, and other products. It says that it uses a transparent screening process to measure the concentration of toxins, pesticides, residual solvents, and plasticizers in food and supplement products, giving its Purity Award to products that pass its tests.

ACG’s Kalafat says that delivery system manufacturers have little influence over either the definition of 

or the consumer’s perception of the term.

“As a capsule manufacturer, the pure definition of 

 is out of our hands,” Kalafat says. “The basic understanding of the term comes from our current and potential customers. They dictate how we must formulate our capsules to be acceptable in their supply chain. But we’re always keeping up with continual shifts in the industry, and we dictate changes our customers might need to stay ahead.”

Kalafat says that clear and accurate marketing messages are essential to brands that want to capitalize on clean-label delivery systems. Brands and contract manufacturers should avoid making assumptions about the end consumer’s awareness level, he says, and also should ensure that all parties involved in the supply chain have the same understanding of what 

GPC’s Freers says that it’s up to the formulator and the consumer to determine what 

 means to them. She notes, though, that less is often more. “The first thing to be considered when developing a clean-label product is how to create the simplest formula using the fewest possible ingredients,” she says. “Shoppers want to know what they’re consuming, and ingredient labels often determine which products a consumer will purchase.”

Kalafat emphasizes another point: that making a clean-label product can quickly become complicated depending on the number of companies involved in the supply chain.

In the case of a capsule manufacturer selling to a contract manufacturer instead of to a finished-product brand, for instance, all of the parties involved in decision making would need to reach a common agreement on what constitutes a clean-label product. Misunderstandings, Kalafat says, can complicate the plans of finished-product brands that want to make a clean-label claim.

“Finished-product manufacturers desiring clean-label claims might be forced to reformulate their products if they can’t gain clean-label claims for all of the ingredients in a formulation,” he says.

Some suppliers are trying to make it easier for their own customers to find the clean-label solutions they need. An example of this is the Clean Label Alliance, which bands suppliers together to form a “one-stop shop” offering dietary supplement companies guidance and assistance in implementing clean-label practices. Lonza and Ribus were two of the founding members of the alliance.

As consumers increasingly move toward clean-label products, it will become imperative for finished-product brands, contract manufacturers, and delivery system suppliers to communicate on clean-label requirements. Kalafat points to the food and beverage industry as a good example for the supplement industry to follow.

“There are a lot of clean-label products in the food and beverage industry,” he says. “There’s also some crossover, as many products used to make clean-label foods are now being considered for use in dietary supplements. If clean-label food ingredients can replace the standard surfactants and emulsifiers, these could add product value with labeling.”

As demands for clean label get louder alongside growing consumer demand for transparency, brands will be forced to adapt, and the manufacturing supply chain, delivery systems included, will continue adapting with them.

Clean-label demands require that all parties, delivery system manufacturers included, work together.

Dietary supplement delivery systems: The clean-label effect

Meat alternatives are undeniably having a moment. As state-of-the-art plant-based substitutes like Beyond Meat and the Impossible Burger storm grocers, restaurants, and fast-food chains (so it seems per the media coverage they’ve received), there is still a segment of the population skeptical about these products. Here, we look at some of the positive and negative comments.

One of the biggest attributes of plant-based “meats” is that their production is generally more sustainable compared to conventional meat, producing fewer greenhouse gases and using less land and water. However, one of the criticisms leveled at these newer meat analogues is that, although they use plant inputs, the end products are quite processed and contain a long list of ingredients that runs counter to the move toward cleaner labels, fewer and recognizable ingredients, and transparent production. (Playing devil’s advocate: One could also argue back that some foods consumers perceive as healthy are also processed and fortified to some or great extent.)

Here, we look at some of the positive and negative comments.

Nutritional Outlook Vol. 22 No. 9

Omega-3s, infants, and kids: New evidence for healthy mental and physical development

Supplements for heart health: ingredient developments and progress, despite some negative omega-3 headlines

Clean-label color challenges

Gummy supplements: Perils and possibilities

Dietary supplement delivery systems: The clean-label effect

Beyond Meat and Impossible Burger go mainstream as these meat analogues encounter both fans and critics

Meat alternatives technology: Getting better every day

Are whey fractions the next frontier in dairy protein?