At the beginning of 2020, the world was hit by the novel coronavirus pandemic, which had an impact on individuals’ awareness of health and all levels of society. How to improve the body’s immunity has become the focus of people’s attention. From the popular knowledge of immunization to immune health products, immune health has been pushed into the chair again. Three years on, consumer demand for immunological health products is becoming the “new normal” in the field of nutritional health, whether it is herd natural immunity or vaccine-enhanced immunity. The normalization of outbreaks has prompted consumers to consider a more holistic, long-term approach to maintaining health and immunity.

Immunological health has become the “new normal” with more market segmentation opportunities. In the United States, immune health is not a separate market category but is more associated with colds and flu as a main health direction. According to market data released by Fortune Business Insights, the global immunization health nutrition market is expected to reach $31.5 billion in 2028, growing at a compound annual growth rate of over 6.7%, continuing to be one of the largest categories in the overall dietary supplement market. The global dietary supplement market is expected to exceed $130 billion by 2028.

1. Representative of traditional immunological raw materials

1.1 Vitamin and mineral raw materials

• Vitamin C

Vitamin C is a nutrient widely recognized by consumers, especially the trend of “Morning C and Evening A”.

Efficacy: Vitamin C is essential for healthy immune function and is involved in antibody production and white blood cell activity. When the immune system is stressed, the body’s need for vitamin C increases. Vitamin C is also important for wound healing, collagen production, and increased iron absorption from food.

Main sources: At present, vitamin C in the market mainly comes from natural sources, such as acerola cherry, which has been very popular in the last two years. In addition, other raw materials such as Roxburgh rose, kiwi fruit and berries are expected to become new sources of natural vitamin C.

• Vitamin D

Efficacy: Vitamin D has a variety of physiological functions in the body. It is involved in regulating the immune system and affects certain white blood cells such as monocytes and lymphocytes. An article published in the American Journal of Clinical Pathology in December 2020 indicated that vitamin D deficiency on admission to the hospital was associated with a 3.7-fold increased risk of dying from COVID-19. This finding does not mean that vitamin D prevents or cures COVID-19 or any other disease, but it does point to the importance of optimal vitamin D levels for normal immune function.

Trend: Vitamin D deficiency is a common problem in the world, and it is difficult to meet the body’s vitamin D needs through food alone. A deficiency of vitamin D, which affects calcium absorption and affects bones, teeth, and more, is known to be produced by exposure to sunlight. But without sunscreen, it takes 15 minutes of full sun exposure to meet vitamin D needs, which is unrealistic for most people to rely on.

Market Size: Vitamin D supplement sales grew 47.5% in 2020, according to NBJ Market data. It topped $1 billion for the first time. The rapid growth of the vitamin D market is related to increasing consumer awareness and medical experts’ education on vitamin D during the pandemic.

Vegetarian Source Vitamin D3: Among existing formulations of vitamin D products, D3 is much larger than D2 and is usually derived from animal sources. With the increasing health awareness of consumers and the rapid development of plant-based products, vegetarian sources of D3 are beginning to gain attention in the mainstream market, such as those derived from seaweed.

• Vitamin A

Efficacy: Vitamin A plays a vital role in protecting the body from infection. Vitamin A helps maintain the integrity of surface tissues, including the skin, intestines, and respiratory tract, to strengthen their defenses against potentially invasive microorganisms. Vitamin A deficiency is known to damage the immune system, in part because it plays a key role in the development of certain white blood cells, such as lymphocytes.

Vitamin A was originally known as the “anti-infective vitamin” because it is important for the proper functioning of the immune system. Retinoflavin, A form of vitamin A, is produced by antigen-presenting cells, including macrophages and dendritic cells, and is present at mucosal interfaces and in associated lymph nodes. Retinoflavin appears to act on the dendritic cells themselves to regulate their differentiation, migration, and antigen presentation. In addition, vitamin A is essential for healthy eye function and healthy vision because it is directly involved in photochemical reactions in the retina.

• Vitamin E

Efficacy: It is a fat-soluble vitamin and Vitamin E is also essential for normal immune function. Vitamin E supports a healthy immune response by enhancing antibody response and aiding T and B cell function, which is known for its key role in adaptive immunity. As an antioxidant, this vitamin is especially important for protecting the immune system from damage during oxidative stress and chronic disease.

In addition, vitamin E protects fatty areas of the body, including cell walls and the brain. The brain is 60% fat. Fatty acids in the brain are easily oxidized. When there are high levels of oxidative stress in the brain, it can lead to cognitive decline.

• Zinc

Efficacy: Zinc is an essential trace mineral found in the body that has a variety of roles in supporting cellular metabolism. Zinc is involved in immune function, acting as an antioxidant and supporting the growth and normal function of immune cells, as well as protein and DNA synthesis. Zinc also plays an important role in normal growth and development, it has structural roles in proteins and cell membranes. Since the body can’t store zinc, it’s important to take it regularly.

Market Size: According to market data released by InnovaDatabase, magnesium, calcium, and zinc are the top 3 sales of mineral products in North America. From 2018 to 2021, the compound annual growth rate of zinc products containing zinc elements in North America was 73%, especially with the rapid promotion of the epidemic. North America is also the world’s largest market for mineral supplements, followed by Western Europe and Asia.

1.2 Herbal raw materials

• Elderberry

Market Size: Elderberry is a plant herb with a long history in China. It is the fruit of the elder tree, mainly used to prevent flu, cold, antiviral, etc., which can be traced back to ancient Greece. At present, the health effects of elderberry in improving immunity are relatively recognized in European and American countries, which have a large amount of scientific data and a strong consumer cognition market. A superstar ingredient in the immunization market, elderberry sales grew 69.2 percent in 2020 to a market size of $325 million, according to data.

Main product form： Now, the main forms of elderberry products on the market include powder infusion, liquid drops (syrups), drinks, effervescent tablets, chewable tablets, gummies, capsules, oral liquid, etc. Gummy is the most common and popular dosage form, with audiences ranging from children to elders. The appeal of elderberry products is that they provide immune support from natural sources and they also taste good. More and more consumers are looking for food and drink with functional claims, and the ingredients represented by the elderberry have innate advantages.

• Curcumin

Curcumin is an active compound isolated from the root of the plant Curcumalonga L. It is well known in the nutritional community for its potential anti-inflammatory, antioxidant, and antibacterial properties.

Market Size: According to a market report released by Grand View Research, the global market share is over $58 million in 2020 and is expected to grow at a compound annual growth rate (CAGR) of over 16% from 2020 to 2028. Driving the growth of the curcumin market is clinical research data, and emerging research is expanding the range of curcumin applications and providing more dimensions for brand innovation in natural products.

• Echinacea purpurea

Echinacea purpurea is a Native American plant with over 300 years of application history. Native Americans initially used it to treat coughs, colds, and some lung diseases. Ans were later introduced into Europe and continue to be used today. At present, Echinacea purpurea has become one of the most widely used medicinal plants in Europe and America. It is known as one of the three major anti-cold ingredients.

Ingredient and Efficacy: Echinacea purpurea is rich in various active substances, such as polysaccharides, flavone powder, and caffeic acid ester. The main function of flavonoid powder is antioxidant. At present, it is mainly used for enhancing immunity, antiviral and anti-inflammatory. In 2015, Echinacea purpurea was concluded through clinical analysis that it may reduce the risk of recurrent respiratory infections and their symptoms.

• Andrographis paniculata

Andrographis paniculata is a herbaceous plant that grows throughout Asia. There is a certain history of application in traditional Chinese medicine, and this ingredient is found in common cold medicines in Southeast Asia. Andrographolide is a bitter compound in Andrographis paniculata. Because of its bitter taste, it is called “the king of bitterness”.

Efficacy： Andrographis paniculata can be used to support immune health and symptoms of Respiratory disease. In terms of specific mechanisms, Andrographis paniculata extract can be used as a natural NF-KB inhibitor. By activating NF-KB to stimulate natural defense mechanisms, it increases the production of cytokines such as interference γ and interleukin-2, helping to enhance immunity.

Application： At present, Andrographis paniculata extract suppliers use raw materials in the United States and India, which are also planted locally in India. The main health claims are immune and anti-inflammatory.

1.3 Probiotics and Prebiotics

• Probiotics

Probiotics are a type of active microorganisms that are beneficial to the host by colonizing it in the human body and altering the composition of a certain part of the host’s microbiota. By regulating the immune function of the host mucosa and system, or by regulating the balance of gut microbiota, promoting nutrient absorption, and maintaining intestinal health, single microorganisms or well-defined mixed microorganisms with beneficial health effects are produced.

Efficacy: Probiotics can synthesize digestive enzymes. Together with digestive enzymes synthesized by animals, they participate in the digestion of nutrients in the intestine, stimulate animals to secrete digestive enzymes, reduce the depth of intestinal crypts, increase the height of villi, increase the surface area of the intestine, and promote the absorption of nutrients in the intestine.

• Prebiotics

Prebiotics are nutritional compounds that can selectively stimulate the growth of bifidobacteria and certain lactic acid bacteria in the colon, and have resistance to the effects of the upper digestive system. Some soluble oligosaccharides are well-known prebiotics and have been proven to be beneficial nutritional tools for supporting a healthy colon. In addition, prebiotics also play a role by promoting immune function and resisting potential pathogens.

Market Size: Global Market Insights Market data shows that the market size of prebiotics reached US $3.31 billion in 2015, with a compound annual growth rate of 11.6%. By 2023, the market size will reach US $7.5 billion. Common prebiotics include poly fructose, Galactooligosaccharide, inulin, Stachyose, etc. NBJ Market data shows that the category of prebiotics has been rising steadily in the United States, and the sales volume will be close to $200 million by 2023. Inulin, fructooligosaccharides(FOS), and galactooligosaccharides (GOS) continue to dominate the market, however, the market share among the three is declining from 90% to slightly more than 50%.

• Synbiotics

Synbiotics are a “mixed formulation” of prebiotics and probiotics, serving both functions. It can not only play the role of probiotics but also have the effect of probiotics. Although synbiotics are a mixture of the two, there are strict requirements for adding them to prebiotics: they must promote the colonization of probiotics in the intestine and inhibit the proliferation of harmful bacteria. Common synbiotic preparations include lactic acid bacteria and Lactitol combinations, bifidobacteria and fructooligosaccharides, and bifidobacteria and Galactooligosaccharide.

Market Size: In 2016, Biostime rapidly surpassed prebiotics in total microbial market share and outpaced the sales growth of probiotic dietary supplements. In 2018, for example, U.S. consumers spent $658 million on Biostime, a 16% increase over the previous year. Sales of Biostime formulations are expected to reach $1 billion, while sales of stand-alone probiotic supplements will gradually decline after the pandemic.

2. Potential immunological materials

2.1 Adaptogens

The term adaptogen was first coined by N.V. Lazarev (1947) to refer to a substance that claims to increase “non-specific” resistance to the adverse effects of collective and stress. They are able to activate the innate defense system, increase resistance to stress, enable the organism to adapt to stress, provide anti-fatigue energy, and reduce neuroendocrine-immune system decline associated with aging.

Adaptogens are not a panacea category; some ingredients are stimulating, some calming, and some nourishing. In the traditional medical system, they are rarely used alone, usually in the form of compounding.

• Ashwagandha

Ashwagandha is native to India and North Africa and is one of the most important herbs in Indian medicine. Also known as Indian ginseng, it belongs to the Nightshade family and has a long history of being eaten locally in India. For more than 3,000 years, it has been used to relieve stress, increase energy levels, enhance the body’s immunity, and improve concentration.

Efficacy: Modern scientific research shows that South African eggplant root contains rich phytochemicals, including steroid esters, alkaloids, glycosides, fatty acids, chlorogenic acid, and a variety of amino acids, which have anti-inflammatory, antioxidant, stress relief, enhance immunity, improve memory, improve cognition, anti-cancer and other physiological functions. It acts as an immunomodulator, which alters the immune response by increasing or decreasing immune activity.

• Rhodiola Rosea

Rhodiola rosea is a member of the sedum family, which is native to the Arctic Circle in eastern Siberia. Rhodiola rosea is widely distributed in polar and mountainous regions of Europe and Asia. It grows above elevations of 11,000 to 18,000 feet. Rhodiola rosea was classified as an adaptogen by Soviet scientists because of its effects on a variety of chemical, biological, and physical stressors.

• Ginseng

Panax Ginseng： Ginseng polysaccharide in ginseng can regulate the body’s immune system and maintain its normal physiological function, can significantly promote the natural killer cells, but also improve the killing ability of cells. Ginseng protein can enhance the cellular immunity and immune organ weight of mice, and can also enhance the immune activity of macrophages by enhancing the phagocytosis function of macrophages and releasing immune factors.

Korean Ginseng： Korean red ginseng is unique to South Korea and is also a hot raw material these two years. The study demonstrated through eight weeks of intake testing and subsequent analysis that red ginseng boosts the immune system by increasing T cells, B cells, and WBC, and that it is safe according to the safety assessment of the study, hematologic examination, blood chemistry examination, and urine analysis.

American Ginseng: The chemical composition of American ginseng mainly consists of monosaccharides, polysaccharides, saponins, amino acids, proteins, enzymes, organic acids, and trace elements. In recent years, great progress has been made in the study of American ginseng extract and its application in combination with other Chinese medicines on immune regulation. At present, people mainly focus on the immunopharmacological effects of American ginseng polysaccharide, American ginseng saponin, and American ginseng compound mixture.

Siberian Ginseng: Also known as Siberian ginseng, Acanthopanax Acanthopanax extract can stimulate cellular immunity and is used for a variety of immune-related diseases. Acanthopanax can also significantly improve the ability of cells to produce induced interferon, has a protective effect on leukopenia caused by subcutaneous cyclophosphamide injection, and also has a significant preventive effect on leukopenia.

2.2 Medicinal Mushrooms

Mushrooms began to resonate with health-conscious consumers a few years ago when they exploded in popularity as a key ingredient in adaptogens centered on physical and mental stress management. As consumers began to understand the basic functions of mushrooms, they began to realize that mushrooms have more comprehensive benefits, including blood sugar and immunity support. The outbreak of COVID-19 has prompted an explosion in the use of mushrooms in food and beverages, as well as vitamins and supplements.

Efficacy: The two main factors that mushrooms boost immune function are blocking the glycoprotein hemagglutinin (H) and neuraminidase (N), both of which are involved in the presence of viruses, such as neuraminidase, which enables viral particles to pass through the respiratory mucosa and help spread to infect other cells. Many immune-supporting medicinal mushrooms have been found to inhibit neuraminidase pathways, such as Ganoderma lucidum, grey tree flower, shiitake mushroom, Cordyceps, etc. A recent study on Ganoderma lucidum found triterpene Ganoderic acid T-Q and TR to inhibit neuraminidase in H5N1 and H1N1 virus strains.

• Cordyceps Sinensis

Cordyceps has a double regulatory effect on immune function, which can continuously enhance immunity and improve the body’s ability to resist diseases; It can also play an immunosuppressive role and effectively inhibit rejection after organ transplantation. Experiments have found that cordyceps can stimulate macrophages to produce cytokines, enhance the immune ability of immune cells, and inhibit the lung metastasis of tumor cells after breast cancer surgery.

• Hen of the woods

It is rich in minerals, vitamins, amino acids, and beta-glucans that can be used to balance the inflammatory response, promote healthy cell function, and boost the body’s immune defenses. Specifically, it provides important support to the immune system by helping to activate T cells and influencing appropriate cytokine responses.

2.3 β-glucan

Beta-glucan is a polysaccharide formed by the polymerization of D-glucose. These natural polysaccharides exist on the cell walls of cereals, bacteria, fungi, etc., and can be extracted from yeast, oats, barley, barley, mushrooms, seaweed, etc.

Efficacy: In terms of enhancing immunity, the main health properties of β-glucan include: adaptive immunomodulatory properties, biological response modulators (BRM), activation by immune cells macrophages, and intestinal prebiotic dietary fiber.

2.4 Nigella Damascena

Nigella damascena is an annual herb of the genus nigella in the ranuncualceac family, commonly referred to as Nigella Glanduliferafreyn、Nigella Sativa, and Nigella Damascena. It is found in India, Pakistan, Egypt Central Asia, and other Mediterranean coastal countries, mainly Nigella Sativa. It is grown in China, mainly in the Turpan and Hami areas of Xinjiang. Its seeds are commonly used as medicinal materials, which have the effects of diuresis, promoting blood circulation and detoxification, and tonifying kidneys and the brain.

Efficacy: Used for thousands of years as a spice and food preservative, nigella damascena oil and its active ingredients, including fatty acids, volatile oils, and trace elements, have been shown in studies to have beneficial immunomodulatory properties, enhancing the immune response mediated by T cells and natural killer (NK) cells, which is thought to contribute to its effectiveness. At the same time, it is also rich in unsaturated and essential fatty acids, mainly linoleic acid, followed by oleic acid (Omega-6 and Omega-9, respectively).

Market Size: Nigella damascena is a relatively small raw material, most of the research and development of Nigella damascena is in the form of oil, and the main application direction is beauty and skin care. There are no more than 10 major suppliers of extracts worldwide, some for the sleep market, some for immune health, and some for intestinal health.

3. Others

3.1 Astaxanthin

Astaxanthin is bright red, has very strong coloring, antioxidant capacity, and a variety of biological functions, and has broad application prospects in nutrition and health food, medicine health care, and cosmetics. Rhodophyllum pluvium is a kind of single-celled green algae rich in astaxanthin, which is also a good biological source for natural astaxanthin production in the world.

Efficacy: Scientific research has found that astaxanthin can improve the immune system in several ways. First, astaxanthin has multiple anti-inflammatory effects that can support a healthy immune response. Astaxanthin can directly inhibit the production of inflammatory cytokines, but also by controlling the gene switch NF-B protein that enables the production of inflammatory cytokines. In addition, astaxanthin can also significantly reduce the expression of COX-2 without associated side effects.
Secondly, due to its special chemical structure (13 double bonds), natural astaxanthin is more stable than other antioxidants. Its antioxidant properties may help protect immune cells from excess accumulation of free radicals, while also helping to protect their own antioxidant enzymes. In addition, astaxanthin has a “hydrolipophilic” phospholipid structure that can protect cell membranes and mitochondrial membranes. In addition to energy generation, mitochondria play an important role in immune signal transduction, regulation of immune cell activation, differentiation, and survival.

At present, the main application direction of astaxanthin is still focused on antioxidants, mainly oral beauty, and slightly immature in immune health product development, but with its potential in ATP (adenosine triphosphate), it may be developed in the future in the subcategory of sports people.

3.2 PEA

PEA is an endogenous fatty acid amide, produced in the human body, but also found in animal organs, egg yolks, olive oil, safflower and soy lecithin, peanuts, and other foods. In terms of scientific research, data from more than 350 animal and human studies show that it plays an important role in anti-allergy, analgesia, neuroprotection, anti-influenza, and regulation of immune response. Specifically, the activation of mast cells and spinal glial cells on peripheral and central nervous system neurons plays a role in the development and maintenance of various inflammatory mechanisms in chronic pain states.

Immunomechanism： In terms of improving immunity, PEA acts as an important regulator of inflammatory conditions and a mediator of the interaction between the nervous system and the immune system to enhance the body’s immunity. However, flare-ups of the inflammatory state lead to reduced production of PEA. Therefore, the use of exogenous PEA can supplement endogenous levels and restore its anti-inflammatory and immunomodulatory potential. In addition, PEA has the potential to act as a beneficial endogenous biological mediator, helping to correct the effects of dysbiosis and shaping the immune system.

Market Size: The consumption cognition of the whole market is low. PEA was first sold as a food supplement in 2008, aiming at immunity, exercise recovery, sleep aid, etc. As a fatty acid derivative, PEA has poor absorption and bioavailability in the aqueous medium of the digestive system, so technical intervention is needed to increase bioavailability. The whole product is not rich enough and is concentrated in the North American market.

3.3 DHQ

Known as one of nature’s most powerful antioxidants, dihydroquercetin, also known as theophylline, is a flavonoid found in a variety of foods, including apples and Onions, as well as milk thistle and deciduous pine. Emerging research suggests that DHQ may support immune, respiratory, skin, and cellular health benefits. DHQ’s powerful antioxidant properties also make it a perfect natural alternative to synthetic chemicals for food preservation.

Efficacy: DHQ is a powerful antioxidant, and emerging science suggests that it works by neutralizing free radicals in the body through a healthy inflammatory response, preventing cell damage and thus potentially helping to support immune health. Because it has good antioxidant and anti-inflammatory properties, DHQ may be an ingredient to watch.

Market Size: The efficacy of DHQ has been recognized by a number of national medical institutions, but because of the lack of resources and technical limitations, at present, only the United States, Russia, Japan, and other countries in the world have developed a variety of medicinal food products with DHQ as raw materials, so that it can serve human health.

3.4 Olive Leaf Extract

The Olive leaf is a very old tree, but it also has a strong growth ability of long-lived tree species, the world’s olive tree cultivation of about 500 varieties. Among the many olive tree varieties, Olea europaea varieties are currently the most commercially used in the world, mainly distributed in Mediterranean countries, Greece, Italy, Tunisia, and Spain as the concentrated production.

Olive leaves can be used for feed purposes, but also can be made into tea, the leaves themselves contain a variety of bioactive ingredients, typically oleuropein and olive polyphenols.

Efficacy: Olivin can stimulate the activity of macrophages, on the one hand, promote inflammation in the early stage of inflammation, and kill bacteria and phagocytosis; On the other hand, it inhibits inflammatory response and promotes cell proliferation and collagen deposition in the later stage of inflammation. Studies have also shown that olive oil extract can help support the immune system, as its anti-inflammatory fatty acids play a role in different pathways that activate immune-capable cells.

With the improvement of the awareness of immunological health among consumers of all ages, people pay more attention to immunological health and seek various immunological health products, especially young consumers who are more willing to change their eating habits and lifestyles, and immunity may become a trend with lasting potential.