New ingredients for immune health


Vitamin C and echinacea are so twentieth century, says Roger Clemens, DrPH, Chief Scientific Officer, HORN, past President, Institute of Food Technologists, and Adjunct Professor, USC School of Pharmacy.

For many in the natural products industry and consumers alike, vitamin C and echinacea are the default dietary interventions to support immune health. They are readily accessible, affordable and commonly recommended by expert sources as valuable contributors to human health. Scrutiny of the science behind them, however, suggests that it is incumbent upon those who develop and recommend immune support products to consumers to take a fresh look at the science.

The same rigour should also be applied to novel dietary interventions to support immune health that are accumulating interest. It is not enough for the research supporting a solution to be statistically significant; it must be clinically relevant as well.

Almost 40% of adults want to understand the role of immune health and how to give it a boost

I had the opportunity to survey the scientific landscape on immune support when called upon to develop an immune health presentation in conjunction with a recent industry conference. It is a timely topic. Consumer interest in immune support is high. Consider that a recent survey among 1,579 adults aged 18+ found that immune health is one of the top three reasons that people took supplements in the past two years.1 Furthermore, the study found that almost 40% of adults want to understand the role of immune health and how to give it a boost. This topic was cited more often than pain relief, weight control and reducing heart risk. In 32 countries, “frequent colds/flu” has evolved into a top-five health issue for consumers.2

This strong interest among consumers is reflected in meaningful sales. US sales and dietary supplements claiming an immune benefit totaled US$2.1bn last year.3 Add US OTC sales of immune products and the total surpasses US$8bn. Meeting this market need with carefully considered solutions is a win-win for the industry and for the health and well-being of consumers.

Whereas mothers of young children have an interest in immune health, they are not the only demographic to consider. Given that immune system function deteriorates as we age — a process known as immunosenescence — we can anticipate that interest in immune health will only grow as a health and wellness topic, particularly as the millions of baby boomers who are in a race against time and are looking for solutions to defend against the effects of ageing.

Immune System Fundamentals

A brief refresher regarding how the immune system works is important before we examine the clinical research behind the various dietary options that support immune health. The immune system defends the body from infections caused by pathogens such as bacteria, viruses and fungi. It protects the body throughout growth and development. The immune system can be broadly segregated into two components: the innate immune system and the adaptive immune system.

The “innate” (meaning: present from birth) part of the immune system is so-called because it has a number of set strategies to rapidly recognise and eliminate potential infections, without needing to be trained to identify them. It includes physical barriers such as skin, as well as phagocytic cells. It does not depend on immunological memory. The adaptive (acquired) immune system develops with time through repeated exposure to antigens. It comprises cell-mediated (T lymphocyte) and humoral (B lymphocyte and immunoglobulins) systems. It attacks specific pathogens or antigens. Unlike the innate immune system, it remembers previous threats and reacts more strongly to subsequent exposures. For example, the bacteria we come in contact with at a young age help prepare our immune system to withstand future similar threats.

Figure 1 illustrates the key developments in the human immune system from birth to age 2 when both the innate and adaptive components are fully developed. At this point, the young child’s immune system is performing as well as that of an adult and will continue to change and mature with time. The lifecycle includes age-related changes in phenotype and alterations of the functionality of the various immune cell populations. Clinically proven and clinically relevant dietary interventions can play a role in helping to improve the effectiveness of the immune system to support the body’s natural defences during each life stage.

Figure 1: Key developments in the human immune system

Figure 1: Key developments in the human immune system

PICO: an Approach to Assessing Evidence Quality

One framework to assess the quality of the scientific evidence is easy to remember by its acronym, PICO.4

  • Patients/population studied: what are the composition, size and alignment of subjects to the research question?
  • Intervention used: what is the functional ingredient, what are its characteristics and what is its intended benefit?
  • Comparison/control group: is there a comparison of results with an appropriate population not ingesting the ingredient?
  • Outcomes: are they appropriate to the research question and are they statistically significant and validated?

Also consider if the results are consistent: do they conflict with or complement outcomes from other studies exploring the same ingredient and intended health benefits? Consistency is another hallmark of a quality research programme.

The Influence of Microbiota

The human body has about seven pounds of microbiota or bacteria on its skin and in its gut. One major role of gut microbiota is to limit intestinal pathogenesis and maintain constitutive low-grade physiological inflammation (state of readiness) and maintain the balance between harmful bacteria and symbiotic micro-organisms, or “good bacteria.” Non-communicable diseases, such as heart disease, diabetes, obesity and even gluten intolerance, may disrupt the homeostasis of the gut bacteria, which can create a proinflammatory shift.

Immunosenescence may in part reflect diminished mucosal tolerance in microbiota, such as creating an overgrowth or slower transit time. Healthy microbiota may play a role in delaying or attenuating immunosenescence and age-related inflammation, such as a decrease in some inflammatory markers.

The balance of antioxidants, which the body produces on a regular basis, and reactive oxygen species that can cause cellular damage play a role in immune system function is a topic of significant investigation and controversy. Diet may make a difference in helping to maintain antioxidant and inflammatory balance, but scientists are still exploring appropriate dosage quantity and frequency, along with the minimum effective dose of a spectrum of potential bioactives.

Dietary antioxidants are not the same as those that our body produces naturally

Dietary antioxidants are not the same as those that our body produces naturally, thus making it difficult to achieve regular and predictable outcomes from an array of possible antioxidant dietary supplements. Several methodologies for measuring antioxidants have been developed, including Total Phenolics, ORAC and CAA, but there has been no agreement regarding which methodology is the best to measure which fruits and vegetables may be the best choices for adding antioxidants to the diet.

Uncertainty surrounding which methodology is best was underscored when the USDA took the step of removing its ORAC Database for Selected Foods owing to mounting evidence that the values indicating antioxidant capacity had no clinical relevance to the effects of specific bioactive compounds, including polyphenols, on human health. USDA noted that there are a number of bioactive compounds theorised to have a role in reducing the risk of developing various chronic diseases. However, the associated metabolic pathways are not completely understood, the clinical relevance of the published research and non-antioxidant underappreciated mechanisms may be responsible.5 Yet, ORAC values continue to be routinely misused by food and dietary supplement manufacturing companies and consumers.

Given the lack of understanding and inconsistencies in clinical outcomes with dietary antioxidants, a diet containing a variety of naturally occurring, antioxidant-rich foods such as fruit, vegetables and tree nuts may be one approach.

Vitamins C and E

Vitamins C and E are thought to protect the body from free radicals that may damage DNA. Normally, the body’s immune system creates free radicals to neutralise viruses and bacteria. Thus, under healthy conditions, the body can manage free radicals through their production or neutralisation. But, if insufficient antioxidants, including those from the diet and others produced by the liver and some types of immune cells are available or there are too many free radicals produced, damage from free radicals can occur. Some ageing models suggest free radicals accumulate during the ageing process, and thus may be important factors to consider in maintaining health and reducing the risk of developing some diseases.6

Vitamin C is commonly associated with helping to reduce the symptoms of the common cold; as it is not made by the human body (although there is some research suggesting that the bodies of lactating mothers may), it is naturally available in many foods and through dietary supplementation. However, a retrospective analysis of 29 studies among subjects using more than 200 mg/d showed no consistent impact on duration or severity of the common cold, with only a possible reduction in symptoms among extreme athletes. Furthermore, in a comparison of 31 studies among those taking 1–2 g/d there was an 18% reduction in duration among children and a 3–12% reduction in duration of the common cold among adults.7 The bottom line? Despite its broad popularity, there is no consistent impact on the severity or duration of cold symptoms from therapeutic administration of vitamin C at pharmacological doses.


The research on echinacea is not definitive either. In one meta-analysis of echinacea usage, 16 clinical trials met the inclusion criteria; 15 of the studies were double-blinded. Comparing an echinacea preparation with a placebo, a significant effect was reported in nine comparisons, there was a positive trend in one study and no differences were shown in six studies.

The echinacea preparations tested differed greatly from study to study, making comparison among the studies difficult. Although there was some evidence to suggest that preparations based on aerial parts of E. purpurea might be effective for early intervention to reduce the symptoms associated with the common colds in adults, the results were inconsistent.

In another meta-analysis in 2007, 14 studies met the inclusion criteria and five studies did not have control groups. Doses varied widely, from 100–900mg/d to 3–6g/d for 7–10 days to 12 weeks.8 The bottom line? Beneficial effects of other echinacea preparations and echinacea used to reduce some cold/flu symptoms might exist, but the clinical data have not demonstrated consistency in outcomes in carefully controlled trials.

In 32 countries, frequent colds and flu are a top-five health issue for consumers

In 32 countries, frequent colds and flu are a top-five health issue for consumers

New Frontiers in Functional Ingredients

With the poor accumulated evidence of these traditional dietary interventions and with recommended dosages all over the map, there is an opportunity to investigate new technologies and explore the science behind them. One option to consider is a yeast beta glucan called Wellmune, which is demonstrated to be stable and GRAS under US FDA guidelines.

With beta glucans, structure matters. Oat beta glucan is a linear structure that helps maintain cholesterol. The Wellmune yeast beta glucan is a branch chain polymer and carbohydrate derived from the cell wall of a proprietary strain of baker’s yeast. Among immune health ingredients, its peer-reviewed clinical research is compelling. This novel ingredient is safe when consumed by diverse populations in the age/stage continuum of life, and appears to naturally prime specific immune cells.

Mechanism of action studies, as well as changes in immune responses, are changing the way researchers think about innate immune function

The ingredient also has a well-understood mechanism of action that is well documented in published, peer-reviewed research. Mechanism of action studies, as well as changes in immune responses, are changing the way researchers think about innate immune function. Wellmune has a body of nine clinical studies that are statistically significant, clinically relevant and consistently demonstrate the positive health benefits of Wellmune on the physical and psychological health of individuals experiencing lifestyle and physical stress that often contribute to frank illness. The studies were conducted among several different populations including firefighters, marathoners, medical students and individuals with high lifestyle stress.

Innovative solutions to meet growing consumer demand for functional foods and beverages with immune health benefits are within reach. Care must be taken when assessing every option to carefully consider the quality, quantity and consistency of research design and clinical results. More rigorous research and more informed decisions at the industry level will ultimately translate into products that will bring greater satisfaction and health to end users.


1. R.J. Blendon, et al., “Users\' Views of Dietary Supplements,” JAMA Intern. Med. 173(1), 74–76. doi:10.1001/2013.jamainternmed.311 (2013).

2. J. Mellentin, “10 Key Trends for 2013,” New Nutrition Business 18(3), 50 (December 2012/January 2013).

3. Ibid.

4. D.L. Sackett, et al., “Evidence-Based Medicine: What it is and What it Isn’t,” BMJ 312(7023), 71–72 (1996).

5A. J.M. Gutteridge and B. Halliwell, “Antioxidants: Molecules, Medicines and Myths,” Biochem. Biophys Res. Commun. 393(4), 561–564 (2010).

5B. M.W. Moyer, “The Myth of Antioxidants,” Scientific American 308, 62– 67 (2013).

6. P.B. Pun, et al., “Ageing in Nematodes: Do Antioxidants Extend Lifespan in Caenorhabditis elegans?” Biogerontology 11(1), 17–30 (2010).

7. R.M. Douglas, et al., “Vitamin C for Preventing and Treating the Common Cold,” Cochrane Database Syst. Rev. 1:CD000980. DOI: 10.1002/14651858.CD000980.pub4 (2013).

8. S.A. Shah, et al., “Evaluation of Echinacea for the Prevention and Treatment of the Common Cold: A Meta-Analysis,” Lancet Infect. Dis. 7, 473–480 (2007).