Immune health and functional dietary supplements

Supplements marketed for “immune health” are popular. However, this label is sometimes confusing. As with other dietary supplements, FDA prohibits marketing of dietary supplements to "diagnose, treat, cure or prevent any disease."¹ Therefore, supplements targeting immune function are usually under the sticker of “immune health.” Immune function is a complicated system, and it is necessary to distinguish between boosting immunity or anti-inflammatory activity. These are different functions and may even have opposite functions. Certain inflammatory responses have positive effects on human health, whereas other inflammatory responses are damaging. Boosting immunity means activating immune cells, which results in the destruction of harmful bacteria. On the other hand, anti-inflammatory activity reduces inflammation.

In addition to widely used vitamin supplements (mainly vitamins C, B6 and E) with well-known effects on the stimulation of immune system, other natural extracts have demonstrated health-improving effects in several clinical studies.  

Immunomodulatory supplements

Supplements containing extracts from echinacea (Echinacea purpurea) are widely used for common colds. Although several clinical trials with echinacea did not demonstrate benefits for treating colds, meta-analysis suggests echinacea may be associated with a small reduction in cold incidence.² The major problem is a difference in the composition of echinacea products due to the use of variable plant material, extraction methods and the addition of other components. On the other hand, a standardized echinacea formulation containing alkamides, cichoric acid and polysaccharides was effective in the symptomatic relief of a common cold.³ Mechanistically, echinacea increased the amount of circulating immune blood cells and suppressed the cold-related increase in superoxide production by neutrophils.³ The proper chemical analysis together with bioassays determining the activity of echinacea in immune cells is necessary for the validation of the health effects of echinacea supplements.

Several clinical studies with beta-glucans from a variety of mushrooms including maitake, oyster, reishi and shiitake demonstrated a stimulation of immune responses. For example, beta-glucans from Pleurotus ostreatus significantly reduced the incidence of upper respiratory tract infections in athletes and increased the number of circulating immune natural killer cells.⁴ Maitake mushroom beta-glucans enhanced the immune response in blood cells in cancer patients.⁵ However, not all mushroom beta-glucans stimulate immune response because different mushrooms contain different beta-glucans. The simplified term, “beta-glucan,” refers to a wide variety of polysaccharides with various chemical structures and activities. Moreover, mushrooms also contain alpha-glucans, and alpha-glucans from Agaricus bisporus demonstrated anti-inflammatory activity in human blood cells.⁶ The activity of mushroom beta-glucans can be assessed for their effectiveness in inducing the production of immune cytokines in blood cells.  

Immunomodulatory properties of probiotic organisms Lactobacillus, Bifidobacterium and Saccharomyces are well documented.⁷ Probiotics may increase nonspecific cellular immune response by activation of immune cells and by the production of cytokines. For example, probiotic consumption significantly increased natural killer cell activity in healthy volunteers.⁸ On the other hand, an enhancement of cognitive function in Alzheimer’s disease patients by probiotic supplementation was probably mediated by the inhibition of neuroinflammation.⁹ Probiotics are usually defined as products that contain viable, non-pathogenic micro-organisms that confer health benefits to the host. However, probiotics might contain dead bacteria and still be active. The effect of probiotics could have dual activity: where live probiotic cells possess an immunomodulating effect, the dead cells could exert anti-inflammatory activity.¹⁰ Cell culture bioassay can distinguish if specific probiotics possess immunomodulatory or anti-inflammatory activity.

Anti-inflammatory supplements

Turmeric (Curcuma longa) extract or purified curcuminoids from Indian spice are mainly marketed for their reduction of pain and inflammation associated with joint health. A clinical study using curcumin demonstrated a significantly decreased pain score in aged patients with knee osteoarthritis (OA).¹¹ Curcumin markedly decreased inflammation after intense exercise.¹² Moreover, curcumin demonstrated anti-inflammatory activity by significant reduction of serum atherosclerotic low-density lipoprotein (LDL) levels in patients with chronic inflammatory lung disease.¹³ Not all curcuminoids are created equal, and the amount of active curcuminoids depend on the turmeric source and extraction procedures. Therefore, cell-based bioassay using immune cells can identify the most biologically active turmeric/curcumin extracts.

Fish oil, containing omega-3 polyunsaturated fatty acids (PUFAs), demonstrated anti-inflammatory activity in several clinical trials. Fish oil supplements reduced joint swelling and pain, and duration of morning stiffness in patients with rheumatoid arthritis (RA).¹⁴ Fish oil supplementation decreased the circulation of inflammatory markers in patients with chronic heart failure associated with cardiovascular disorders.¹⁵ Fish oil is produced globally with different amounts of biologically active omega-3 PUFAs. Since the anti-inflammatory activity of fish oil depends on the amount and ratio of different PUFAs, fish oils must be tested for their activity in specific, cell-based bioassays. 

Ginger (Zingiber officinale) is a popular remedy for relieving nausea and vomiting caused by inflammation. Clinical trials have suggested ginger is an effective nonpharmacological treatment for nausea and vomiting in early pregnancy.¹⁶ Other clinical studies demonstrated ginger prevented nausea and vomiting in chemotherapy patients.¹⁷ Several ingredients with anti-inflammatory activity (gingerol metabolites) were identified in ginger extracts. Therefore, bioassays evaluating the anti-inflammatory activity of ginger extracts in immune cells can validate the effectiveness of these extracts.

Immunomodulatory and anti-inflammatory supplements, mentioned above, are extracts with variable amounts of active constituents. Clinical studies, used for claim substantiations, were performed with specific extracts. However, extracts used in dietary supplements from different manufacturers are diverse. Although chemical analysis of an extract would usually identify the most abundant ingredient(s), the effectiveness of this extract depends on the complete composition of the extract. Moreover, excipients might negatively impact activity of the final product. Therefore, biological testing using specific bioassays are crucial for the validation of supplement effectiveness. These bioassays might independently confirm claim substantiation of the intended effect of a supplement.

DSTest Labs recently evaluated several turmeric/curcumin supplements for their anti-inflammatory activity in a cell culture bioassay. Not surprisingly, some of the turmeric/curcumin products, also from the same manufacturer, had little biological activity, whereas others demonstrated strong efficiency. Moreover, the real anti-inflammatory efficiency of some turmeric/curcumin products did not correspond to the amount of turmeric/curcumin claimed on the supplement label.

In conclusion, only proper testing using specific bioassays will help in the validation of efficient dietary supplements for Immune Health.

For a list of references, email [email protected].

Daniel Sliva, Ph.D., CEO & founder, DSTest Labs, is a senior investigator at Indiana University Health, and an adjunct associate professor at the Indiana University School of Medicine. He has master’s degrees in food and biochemical technology, as well as biochemistry, and a doctoral degree in molecular biology and genetics. Sliva also completed postdoctoral studies at the department of medical nutrition, Karolinska Institute, Sweden, and at the Indiana University School of Medicine, Indianapolis. He founded DSTest Laboratories at Purdue Research Park in 2014 for evaluating and standardizing efficacy of ingredients, nutraceuticals and dietary supplements. In addition to authoring more than 82 peer-reviewed papers and three book chapters, he is an international speaker.