Zinc is a popular nutrient in winter supplements.  It is an essential nutrient and the second most abundant trace element in the body, after iron ¹.  It is found in every cell in the body and involved in many bodily processes.  It is required by cells from both the innate (general) and adaptive (specialised) immune system ².

The innate immune system is the body’s first line of defence.  When pathogens like infectious bacteria or viruses get into the respiratory tract or gastrointestinal system, the innate immune system responds by sending cells like neutrophils or macrophages to remove the threat.  These cells try to engulf the invading pathogen or create enzymes to destroy it.

The adaptive immune system specifically targets the pathogen and takes over from the innate immune system.  It is often described as the ‘memory’ of our immune system.  Once exposed to a pathogen, the immune system can remember the identity of that pathogen for the future and quickly mount a defence specific to that pathogen.

The role of Zinc in the immune system includes:

• • helping to maintain the integrity of the skin and muscular membranes, preventing pathogen entry into the body.
  • supporting the growth and differentiation of immune cells.
  • supporting the phagocytic activity of monocytes, and help regulate cytokine release.
  • antibody production, particularly IgG and helping the immune system distinguish between “self” and “non-self” ³.

This role has been recognised in an approved European Union health claim for zinc, stating that it “contributes to the normal function of the immune system” and is available to foods that meet defined criteria within the EU ⁴.

Are there Recommended Intakes for Zinc?

Zinc recommendations range from 5 to 11mg per day for adults, varying by each global region ⁵.  In the US, the Institute of Medicine (IOM) recommendations are 11mg per day for men and 8mg per day for women ⁶.  Similarly, the Chinese Nutrition Society Reference intake (RNI) is 12mg per day for adult men and 8.5 mg per day for women⁸.  In Europe, the European Food Safety Authority has established a Population Reference Intake of 9.4 to 16.3mg per day for men with low to higher intakes of dietary phytate and 7.5 to 12.7mg per day for adults women with low to higher intakes of phytate ⁷.

Most people in developed countries get enough zinc through their diet, meaning their immune system isn’t missing the zinc it needs.  For example, in the US around 18% of people do not meet the Estimated Average Requirement (EAR) of zinc per day.  This means most people are not zinc deficient, but  certain people may still benefit from eating more zinc in their diet.

Where can Zinc be Sourced inDietary Sources

Zinc is mostly found in seafood, beef, poultry, beans, nuts, or fortified cereal.  Phytic acid, found in cereals, legumes, and nuts, is known to decrease zinc bioavailability ¹.  Evidence shows that the biofortification of varieties of staple crops may be useful in improving the zinc status of an individual⁵.

Table 1. Zinc content of common foods in the diet ⁹

What Happens with a Zinc Deficiency?

Zinc deficiency is a widespread global health issue, particularly prevalent in low- and middle-income countries.  About 17.3% of the world’s population ¹⁰ is at risk of inadequate zinc intake.  When the body doesn’t have enough zinc, it does not develop a strong immune response.  Zinc deficiency affects many different organs and tissues in the body with signs and symptoms varying by age ⁹.  For example, zinc deficiency can delay growth and cause diarrhoea and alopecia in children, and it can alter cognitive and psychological function in older adults.

Most people in developed countries get enough zinc through their diet but it can affect more vulnerable groups.  For example, the percentage of people in the US that do not meet the  Estimated Average Requirement (EAR) of zinc varies from 16% in households with full food security to 27% in those with very low food security ¹¹.  In Europe, the average intake of zinc is above the recommended amount.  However, certain vulnerable populations may benefit from including more zinc rich foods or supplements in their diet e.g. those on plant-based diets with little animal foods, the elderly ⁵.

Are there Health Risk of Excess Intakes?

Excessive amounts of zinc can cause nausea, dizziness, headaches, gastric distress, vomiting, and loss of appetite and chronic large doses of 50 mg of zinc or more can inhibit copper absorption and reduce immune function ⁹.  Excessive intakes from food sources are unlikely but may occur with excessive supplementation.  The IOM Tolerable Upper Intake Level for zinc is 40mg per day for adults.  EFSA has set the Tolerable Upper Intake Level (UL) for total daily zinc intake from all sources (diet and supplements) at 25mg per day for adults.  This level is based on the reduction of copper status ¹².   Lower limits are recommended for younger groups.

Is Zinc Supplementation Effective?

A 2024 Cochrane review ¹³ based on 34 randomised controlled trials in children and adults (15 prevention, 19 treatment) showed that compared with placebo, taking zinc preventatively may make little to no difference to whether a person catches a cold or to the duration or severity of the cold.   Taking zinc for treatment of an existing cold may reduce the duration but the authors were not confident of the quality of the result which they describe as low to very low.

The most common negative sides effects were irregularities in taste and stomach upset.  A recent review however supports a preventive role of zinc supplementation in reducing the incidence and burden of respiratory infections, particularly in children with recurrent disease and in zinc-deficient populations ¹⁴.

This article was published in March 2020 and updated on March 31, 2026.

Vitamin C is one of the most common nutrients that comes to mind when thinking about immune health.  It is a water-soluble vitamin that serves as a cellular antioxidant, which means it protects cells from reactive oxygen species and cellular damage ¹.  By protecting both skin barriers and immune cells from damage, vitamin C enables them to function properly.  It is required by cells from both the innate (general) and adaptive (specialised) immune system ².

The innate immune system is the body’s first line of defence.  When pathogens like infectious bacteria or viruses get into the respiratory tract or gastrointestinal system, the innate immune system responds by sending cells like neutrophils or macrophages to remove the threat.  These cells try to engulf the invading pathogen or create enzymes to destroy it.

The adaptive immune system specifically targets the pathogen and takes over from the innate immune system. It is often described as the ‘memory’ of the immune system.  Once exposed to a pathogen, the immune system can remember the identity of that pathogen for the future and quickly mount a defence specific to that pathogen.

Vitamin C promotes barrier function, supports the function of neutrophils, monocytes, and macrophages and the activity of NK cells.  It also has a role in the differentiation and function of T cells, especially cytotoxic T cells and in antibody production ¹.  This role has been recognised in an approved European Union health claim for vitamin C, stating that it “contributes to the normal function of the immune system” and is available to foods subject to condition within the EU ³.

Are there Recommended Intakes for Vitamin C?

Global daily vitamin C intake recommendations range from 40 to 110 milligrams per day, depending on region ⁴.  In the US, the Institute of Medicine’s (IoM) recommendations are 90mg per day for men and 75mg per day for women  ⁵.  In the EU, the European Food Safety Authority has established a Population Reference Intake of 110mg per day for adult men and 95mg per day for adult women ⁶.  Similarly, the Chinese Nutrition Society Reference Nutrient intake is 100mg per day for adult men and women ⁷.

What are the Dietary Sources of Vitamin C?

Vitamin C can be found in many fruits and vegetables, such as kiwis, oranges, peppers and broccoli.  The table below shows amounts of vitamin C found in commonly consumed foods.

Source: National Institutes of Health Vitamin C Fact Sheet for Health Professionals ⁸

What Happens with Vitamin C Deficiency?

About 53% of the global population have an inadequate intake of vitamin C ⁹, but the exact number varies depending on global region.  Inadequate intakes were more prevalent in men than women and in areas like South Asia.

Scurvy is a nutritional disorder caused by low vitamin C levels which manifests with varied symptoms affecting multiple organ system due to its role in connective tissue synthesis.  Although it is rarely seen, sporadic cases still occur.  In developed countries, it is mainly diagnosed in the elderly and malnourished individuals and is associated with alcoholism and poor dietary habit s¹⁰.

People who smoke or are exposed to second-hand smoke need more vitamin C in their diets because smoke increases the amount of vitamin C that the body needs to repair damage caused by free radicals ⁵.

Are there and Risks with Excess Intakes of Vitamin C?

In general, vitamin C has low toxicity, and high intakes of vitamin C do not cause serious adverse effects.  However, high doses of vitamin C can lead to diarrhoea, nausea, abdominal cramps, and other gastrointestinal disturbances ⁵.

There are some concerns surrounding high vitamin C intakes, such as the formation of kidney stones and excess iron absorption, but these are not generally considered a risk in healthy individuals. While EFSA did not establish an upper limit, the IoM Tolerable Upper Intake Level for vitamin C ranges from 400 to 2,000mg per day, depending on age ⁵.

What about Vitamin C Supplementation?

There is some evidence that vitamin C doses exceeding recommended daily values could have potential benefit.  A Cochrane review ¹¹ of clinical trials testing vitamin C’s effect on immune health found that regular supplementation (>200mg per day) did not influence how often participants got common colds but reduced the duration of cold symptoms.  A recent meta-analysis ¹² of trials which used doses of Vitamin C above 1g per day found a greater benefit on more severe measures of the common cold.

Severe Acute Respiratory Syndrome Coronavirus 2 , which is a respiratory condition, is marked by significant oxidative stress and an excessive inflammatory response that results in tissue damage of the respiratory system.  For this reason, there has been interest in combining antioxidants like vitamin C with antiviral and anti-inflammatory treatments to improve patient outcomes.  However, a recent review ¹³ suggests that further trials are necessary to determine optimal doses and conditions of use.

This article was first published in May 2022 and updated on March 24, 2026.

Although vitamin A is more frequently associated with vision, it plays multiple roles in supporting the immune system, including:

• • maintaining the integrity of skin and mucosal barriers that protect from pathogen invasion.
  • supporting the innate (general) immune system (e.g. regulating Natural Killer (NK) cell production, supporting phagocytic activity of macrophages).
  • supporting the adaptive (specialised) immune system (e.g. development and differentiation of Th1 and Th2 cells which direct the destruction of invading cells, B cell mediated antibody responses to antigen) ^{1, 2}.

There is an approved European Commission health claim for vitamin A, stating that it “contributes to the normal function of the immune system”, and is available to foods that meet defined criteria within the EU ³.

What are the Recommended Intakes of Vitamin A?

Vitamin A recommendations for adults vary by region:

• • China: the Chinese Nutrition Society Reference Nutrient intake (RNI) is 660mg per day for adult women and 770mg per day for adult men up to 50 years ⁴.
  • Europe: the European Food Safety Authority (EFSA) population reference daily intakes (PRI) are 650 micrograms for women and 750 micrograms for men ⁵.
  • United States: the Institute of Medicine (IOM) recommended dietary allowance (RDA) is 700 micrograms per day for women and 900 micrograms per day for men ⁶.

Where can Vitamin A be Found in the Diet?

Vitamin A in the diet comes from two sources: preformed vitamin A (retinol and retinyl esters) and provitamin A (carotenoids).  Preformed vitamin A is found in foods from animal sources, while provitamin A  are plant pigments that include beta-carotene, alpha-carotene, and beta-cryptoxanthin.  These provitamin A carotenoids are converted into vitamin A in the body, although conversion efficiency shows considerable variation and is influenced by the food source, an individual’s vitamin A levels, and the amount eaten ⁷.

Preformed Vitamin A or retinol is found in animal products mainly including liver, fish and eggs while provitamin A sources are generally found in colourful vegetables like carrots, sweet potato and peppers (See Table 1).

Some countries such as the US routinely add vitamin A to milk and margarine while some ready-to-eat cereals are also voluntarily fortified with vitamin A.  For this reason, it is important to use local information when calculating dietary intakes.

In Western diets, retinol accounts for nearly 65% of total vitamin A intake with carotenoids making up 35% of the total ⁸ but the contribution of carotenoids is higher in countries such as Southeast Asia and Africa where it can make up to 80% of the vitamin A intake ⁹.  Recent data shows that in China, vegetables are the greatest contributor to total vitamin A intakes ¹⁰.

Table 1. Food sources of Dietary Vitamin A ⁷

What are the Effects of Vitamin A Deficiency?

Vitamin A deficiency is a public health problem in more than half of all countries especially those in Africa and South-East Asia ¹¹.  The most severe effects of vitamin A deficiency are seen in young children and pregnant women in low-income countries, ranging from preventable blindness to a weakened ability to fight infections.  Vitamin A deficiency is a double‑edged cycle in which illnesses like diarrhoea and measles further deplete vitamin A levels in the body.

In areas of deficiency, routine vitamin A supplementation is recommended in infants and children up to 5 years of age ¹².  Other strategies include dietary based approaches, biofortification, and food fortification.  Even in developed countries, the importance of vitamin A in the very young is recognised, e.g. it is recommended that children in the UK aged 6 months to 5 years take a vitamin supplement containing vitamins A, C and D every day ¹³.

Are there Risks with Excess Intakes of Vitamin A?

As vitamin A is fat-soluble, it can be stored in the body, particularly the liver and excessive intakes can cause harm.  The US IOM set an upper limit of 3,000mg per day of pre-formed vitamin A for adult men and women including pregnant adults ⁴.  The EFSA have set the same upper limit for adults including women of child-bearing age, pregnant and lactating women and post-menopausal women.  Lower limits are recommended for younger groups ¹⁴.

In terms of the provitamin, beta-carotene, there is no indication that intakes from dietary sources are linked to adverse health effects.  However, smokers have been recommended to avoid consuming food supplements containing beta-carotene, and their use by the general population should be limited to the purpose of meeting vitamin A requirements ¹⁴.

What about Vitamin A Supplementation?

Vitamin A deficiency affects not only the growth and development of children but also increases susceptibility to infectious diseases including respiratory and gastrointestinal infections ⁸.

Across Asia, India and Africa, vitamin A supplementation has been associated with a lower incidence of diarrhoea and measles among children (low quality evidence) while all-cause mortality was also reduced with supplementation (high quality evidence) ¹⁵.

A 2024 Cochrane review showed that vitamin A supplementation did not prevent or reduce the duration of acute upper respiratory infections (URTIs) in children up to seven years of age in low to middle income countries ¹⁶.  However, this was based on a limited number of studies and more research is needed.

The ‘gut microbiota’ refers to the microorganisms (which may include bacteria, fungi and viruses) living in our intestines and they play a vital role in gut health and the management of several gastrointestinal disorders.  The term ‘microbiome’ refers to both microorganisms along with their collective genomes and metabolites (the molecules they produce) ¹.

The composition of gut microbiota can be affected by a wide variety of dietary components including carbohydrates, dietary fibres, fat, polyphenols, plant extracts and by ingredients such as fermented foods, prebiotics, and probiotics ².

What are Probiotics?

Probiotics are defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host” ³.  Usually, this benefit is exerted in the gastrointestinal tract.

Probiotics influence health through non-specific, species-specific, and strain-specific mechanisms.  Non-specific effects—varying across strains and species—include inhibiting pathogenic microbes in the gut, producing bioactive compounds like short-chain fatty acids, and lowering colonic pH.

Species-specific actions may involve vitamin synthesis, strengthening the gut barrier, bile salt metabolism, enzymatic functions, and toxin neutralisation.  Together, these mechanisms can broadly affect human health and disease ⁴.   It is key to remember that the health benefits of probiotics are considered to be strain specific.

For more information on how probiotics work see this section.

How do Probiotics Impact the Immune System?

Immune health is one of the more commonly studied health outcomes of probiotics and the following mechanisms have been proposed ^{4, 5}:

1. Probiotics have been shown to help protect against infection by improving the strength of the intestinal barrier.  This reduces the ability of infectious microbes to enter the body via the gastrointestinal tract.
2. Enhancing phagocytic activity (the process of engulfing and ingesting solid particles, such as bacteria by the cell membrane).
3. Some probiotics, or the products they produce, can interact with immune cells of the human body to influence their effectiveness.  For example, some probiotics can increase the production of cytokines (e.g. Interleukin-1 (IL-1), IL-2, IL-10, IL-12, tumour necrosis factor alpha (TNF-α)) in the intestine.  These cytokines act as chemical messengers to regulate immune responses.

When it comes to researching aspects of immunity, studies often measure the frequency of the common cold, or upper respiratory tract infections (URTIs) and the duration and severity of symptoms among study participants.

A 2022 Cochrane Review ⁵ titled “Probiotics for Preventing Acute Upper Respiratory Tract Infections”, which included 23 randomised controlled trials, found that probiotics were significantly better than placebo or no treatment  for reducing the number and duration of URTIs.  They also reduced the number of participants who used antibiotics for URTIs.  This means that probiotics are likely working with the immune system to have a protective effect against the pathogens that cause URTIs.

Because studies have shown that probiotics may have an impact on upper respiratory tract infections (URTIs), there was significant interest in their potential role during the COVID-19 pandemic.  However, the International Scientific Association for Probiotics and Prebiotics (ISAPP)  stated that no probiotics or prebiotics have been shown to prevent or treat COVID-19 or to inhibit the growth of SARS-CoV-2 ⁶.  In the post-pandemic period, probiotics continue to be studied for their possible role in areas such as vaccine effectiveness and support for individuals experiencing post-COVID-19 syndrome ⁷.

Antibiotics can disturb gastrointestinal microbiota and lead to reduced resistance to pathogens such as Clostridioides difficile and associated diarrhoea (CDAD).  The use of probiotics for the prevention of Clostridioides difficile infection has been researched for many years.  A recent Cochrane meta-analysis concluded that probiotics may be effective for preventing CDAD in those receiving an antibiotic for any reason, suggesting that for every 65 people taking probiotics, one case of CDAD may be prevented ⁸.  Large trials comparing probiotics with placebo in people with a low risk of CDAD are needed.  This will be an interesting area to keep an eye on as the science progresses.

How to Choose a Probiotic

Resources from the International Scientific Association for Probiotics and Prebiotics (ISAPP)

The probiotic marketplace can be confusing for consumers.  See  for some basic information on how to choose a probiotic for healthy people.  There is also useful information about how to read a US and hypothetical European probiotic label.  Here are some basic principles to guide your search:

• • There is no one strain or one dose that is best.  Sometimes lower dose products or products with fewer strains have the best evidence.
  • Any health benefit claim made should be substantiated with a human trial.  The types of claims allowed in the US on foods and dietary supplements are restricted by law.  Contact the manufacturer to get information on what studies have been conducted, or consult Clinical Guide for Probiotic Products Available in the United States ⁹ or the  Guide to Probiotic Products Available in the United Kingdom ¹⁰.
  • One of the biggest challenges in the probiotic market is keeping the probiotic strain alive.  Responsible manufactures go to great lengths to be sure their probiotics retain viability and deliver an efficacious dose through the end of the product’s shelf life.  Unfortunately, not all products on the market are responsibly formulated so consumers should buy products from companies they trust.

Resources for Healthcare Professionals
In addition to resources from ISAPP, in 2023, the  World Gastroenterology Organisation published a resource for professionals working specifically in gastroenterology “WGO Practice Guideline. Probiotics and Prebiotics” ¹¹.

Resources for Researchers
Health benefits of probiotics can be strain-specific and meta-analysis may not represent the ‘gold standard’ for evidence in this area.  This paper identifies common mistakes and offers expert panel recommendations for conducting meta-analysis for probiotic studies ¹².  This perspective literature review describes state-of-the-art tools for harnessing the microbiome for precision health and a corresponding future vision of healthcare ¹³.

This article was first published in April 2020 and updated on March 11, 2026.

Over the past number of years, HMPs have seen a surge in scientific interest, driven by growing awareness of the microbiome’s role in maternal and early-life health and immunity. Recently, the science on HMPs was presented by Kerry Health and Nutrition Institute experts at two industry conferences, ChinaGut in Zhejiang, China, and Growth Asia Summit in Singapore.

ChinaGut 2025

The ChinaGut 2025 conference with the theme of “GUTSY Young, Bright Future “, was held from June 6 – 8, 2025 at the Ningbo International Conference Centre, Zhejiang, China.  This year’s event featured over 30 academic sessions, more than 10 industry-focused sessions, and fourteen key scientific areas including the microbiome, nutrition, digestive system diseases, and immunity.

Dr. Jaume Núñez, Product Manager for Vegetative Probiotics at Kerry, presented the latest scientific research on HMPs as well as providing market trends and consumer insights.  Breast milk is the gold standard of infant nutrition, containing all nutrients required to support a baby’s healthy growth.  However, many mothers lack support or experience difficulties in breastfeeding leading to infants not reaping the benefits of consuming breast milk.

One of the top reasons why women stop breastfeeding is due to mastitis which occurs in approximately 10-20% of mothers who are breastfeeding.  Dr. Núñez highlighted that mastitis is associated with a dysbiosis in the microbiota in breast ducts.  Research findings presented showed the benefits of HMPs supplementation (specifically Lactobacillus) for the prevention and treatment of mastitis, as well as improving infant health.  HMPs are believed to play a role in antimicrobial defence by inhibiting bacterial growth.  Other potential mechanisms of action include increasing the abundance of microbes which produce favourable metabolites, reducing intestinal dysbiosis, and activating the host’s immune response.

A comment from Dr. Núñez:

“Over half of Asian female supplement consumers are seeking alternative solutions to support their pregnancy and breastfeeding journey.  When a mother’s microbiota is transmitted to her baby, this plays a key role in immune system development, allergy and asthma prevention, and nutrient absorption.  Therefore, the addition of HMPs may play an important role for bottle-fed babies.  We need to keep deepening into HMPs mechanisms of action and how they adapt to the different metabolic and immune characteristics of a woman or a child.”

Growth Asia Summit 2025

At the recent Growth Asia Summit 2025 in Singapore in July, two main research topics stood out namely Healthy Ageing, particularly the role of cellular interventions in extending people’s health span versus lifespan, and Women’s Health, with strong focus on nutrition across life stages.  A presentation on HMPs and their positive impact on maternal and infant health was given by Dr Mónica Maria Olivares, RDA Director of Women’s and Infant Health at Kerry.  The audience heard about the fast-growing probiotics market in the Asia Pacific region.

Dr. Olivares followed on by emphasizing the importance of an infant’s first 1,000 days of life, i.e. from conception to two years, for lifelong health.  Similar with what Dr. Núñez discussed in China, one of Dr. Olivares key messages was that breast milk provides essential nutrients and probiotics that nurture an infant’s gut and immunity.

Research documenting the benefits of HMPs such as enhanced infant gut microbiome development and improved resistance to gastrointestinal and respiratory infections was presented.  Different mechanisms, such as the competition with pathogenic bacteria, production of antimicrobial compounds, maturation of the immune system, and improvement of the immune response, have been attributed to the anti-infectious activity of HMPs.

In summary, our understanding on the health benefits of HMPs for mothers and infants continues to evolve.  Further research will give further insights into their health promoting effects and may elucidate the distinct mechanisms of action for specific strains.  Subsequently, this will increase the availability of targeted products to support mothers and infants through breastfeeding.

In Ayurveda, Amla is known to be a potent Rasayana or rejuvenator⁶.  Various parts of the plant are used to treat a range of diseases, but the most important is the fruit, which is small, green, sour-tasting and gooseberry like (Figure 1).  It is also known as one of the oldest and best-known edible fruits in the Indian subcontinent.  It is valued both as a medicine and a tonic for restoring vitality and strength.  Additionally, Amla plays a key role in many complex Ayurvedic formulations⁷, forming an essential ingredient in polyherbal traditional remedies such as Avipattikara Churna, one of the most effective Ayurvedic formulations to manage indigestion and heartburn; or Thriphala Lepam a polyherbal used for millennia to treat inflammation and improve health^7,8.  In TCM, Amla has many functions including clearing heat, cooling blood, digesting food and relieving cough⁹.

Figure 1: Small gooseberry like fruits of Amla (Phyllanthus emblica Linn)

Chemical Components

Amla has been shown to be a font of nutrients and small bioactive chemicals that provide a wide array of health benefits.  It is a rich source of vitamin C which can occur in up to 33%¹, and as reported by Rani (2017) there are high levels of vitamins A (2%), B1 (3%) and B2 (3%), B3(2%), B5 (6%) and B6 (6%), as well as essential minerals such as Magnesium (3%), Manganese (7%), Potassium (4%). Phosphorous (4%), and Zinc (1%)^1,5.  The berry contains a number of phenolic antioxidant compounds including rutin, quercetin, myricetin, ellagic acid, gallic acid, and chlorogenic acid, curcuminoids and complex tannins such as emblicanin, punigluconin, pedunculagin, in addition to the alkaloids Phyllantine, Phyllembein, Phyllantidine².  Many of these metabolites are known to contribute to healing.

Figure 2: Main classes of chemical components in Amla (Phyllanthus emblica Linn).

Pharmacological activities

Pharmacological studies into the bioactivity of Amla fruit and plant extracts support its traditional use in the treatment of inflammation, as an immune enhancer, for antiaging and health promoting effects.  Its seeds have shown promise in treating asthma and bronchitis, while its juice is used for eye care.  Traditional healers have used Amla extracts for wound healing and treating snakebites and scorpion stings^1-5,7.  Some key activities are discussed below.

Amla and Inflammation

Inflammation is the body’s natural response to fight infections like bacteria and viruses, repair tissues, and start the healing process.  However, too much inflammation can cause tissue damage, pain, and reduced function.  Amla fruit extracts have anti-inflammatory compounds, and extracts have shown strong anti-inflammatory effects by blocking two key inflammation-related substances: Nitric Oxide (NO) and COX-2.  NO is an important molecule for immune signalling, but too much of it can cause inflammation, cardiovascular problems, and oxidative stress.  Amla’s anti-inflammatory power comes from its ability to inhibit several inflammation-triggering enzymes, including COX-1, COX-2, and 5-LOX.  By reducing these enzymes, it lowers the production of molecules that cause swelling and pain, making it a promising natural remedy for inflammatory conditions¹⁰.  In a separate study by Li et al (2020), Amla fruit extract has been shown to reduce the production of key the inflammatory substances NO, Tumour Necrosis Factor-alpha (TNF-α), Interleukin-1 beta (IL-1β), and Interleukin-6 (IL-6).  The compounds gallic acid and fisetin have been shown to be responsible for this activity.  Gallic acid is particularly notable, as its presence (over 1.2%) is used as a quality standard for Amla (P. emblica) in traditional Chinese medicine¹¹.

Amla and Cardiovascular Health

Recent scientific literature reveals compelling evidence for amla’s potential to improve cardiovascular health.  Studies have shown that amla can help lower cholesterol (LDL, or “bad” cholesterol), reduce blood pressure due to its high potassium content, and improve blood flow¹².   It also exhibits antioxidant and anti-inflammatory properties that may protect against heart disease¹³.  Some studies suggest that amla may be as effective as certain medications in lowering cholesterol and blood sugar, but without the side effects¹⁴.  While more research is needed to fully understand the mechanisms of action and optimal dosage, the existing findings strongly support amla’s role in promoting cardiovascular health.

Amla and the Immune System

Researchers are increasingly interested in plant-based bioactive compounds that can support immune health.  Amla is such a natural immunomodulator.  In vivo studies have established that at a dose of 250 mg/kg, Amla fruit extracts significantly increase important immune markers such as CD4, CD8, IgM, and IgG in the blood; Amla fruit extract at doses of 100 and 200 mg/kg administered for 19 days showed strong immune responses, including increased antibody levels, white blood cell counts, and better defence against allergens.  These findings support the potential of Amla as an effective natural immunomodulator¹⁵.

Amla as an Antioxidant: Benefits in Diabetes

Current diabetes treatments include insulin and oral medications like sulfonylureas, biguanides, and glinides.  However, these can have side effects, prompting the search for safer alternatives.  Amla has high concentrations of the essential minerals’ chromium, zinc, and copper.  Research studies have shown that chromium, in particular, has shown strong antidiabetic effects, and has been found to improve fat metabolism in diabetic rats, suggesting potential benefits for managing diabetes^3,16.  The antioxidative effects of Amla, and its ability to reduce reactive oxygen species (ROS), can also confer additional health benefits in diseases like diabetes.  Research shows that the ethanolic extract of Amla may help lower blood sugar.  In vivo experiments have shown that administration of extracts of Amla led to a reduction of blood glucose from 380 mg/dL to 166 mg/dL after treatment with 80 mg/kg of the extract.  This study suggests that Amla metabolites, such as tannins, act by blocking digestive enzymes that break down sugars, boosting the storage of glucose, enhancing insulin sensitivity, and preventing harmful sugar-related compounds from forming¹⁷.

Amla and Healthy Ageing

A ground-breaking study by Wu et al. (2022) using the nematode model of Caenorhabditis elegans revealed that polyphenols in Amla fruit have anti-aging effects¹⁸.  These effects were demonstrated by an increase in thermal resistance and a significant reduction in cholinesterase enzymic activity.  The study also found that antioxidant enzyme activity rose significantly. Simultaneously levels of malondialdehyde (MDA), a marker of oxidative stress, dropped by 36.25%.  The fruit’s rich content of antioxidant polyphenols may contribute to these effects.

Beyond healthcare, Amla’s fruit and extracts are widely used in various industries.  They are found in food products, cosmetics, dyes, leather tanning, and it is even used as firewood.  Additionally, its oil has long been valued as a hair tonic, promoting hair growth, and preventing premature greying^7,19.

Conclusion

Amla has well established use as a traditional medicine and food.  It has shown a remarkable array of benefits, from immune system enhancement to its potential as an antidiabetic and health promoting agent.  Extensive research into this powerful plant has unveiled its wide-ranging therapeutic possibilities, sparking interest for future studies and practical applications in medicine and healthcare.  However, most studies have been carried out in laboratory settings or using animal models, which means clinical trials are needed to confirm the efficacy and safety of amla-based treatments for humans.  Another challenge lies in the plant’s diverse chemical composition, which varies depending on geographical and environmental factors. This variation complicates efforts to standardise its use in therapies.  Due to variation in chemical composition, it is best to source quality, standardised extracts and raw material from established producers using validated supply chains.

Deep dive into the world of biotics and the microbiome. This webinar looks to explore the science behind postbiotics, along with the potential role postbiotics can play as a vehicle to meet consumer needs in not only digestive health, but beyond this to other areas of consumer interest, such as immune and cognitive health.

The surge in interest around postbiotics is not just a trend—it’s a response to the incredible body of research and patent filings that have emerged in recent years. With more and more people seeking to age gracefully while staying fit and alert, the connection between different health systems has become more important than ever. Postbiotics, with their unique role in modulating the microbiome, offer a promising avenue to explore these intricate links.

Join key experts in this ever-emerging field as they take you on a journey through the postbiotic continuum, explaining what sets postbiotics apart from other biotics and how they can be harnessed to improve not only gut health but also other critical systems in the body. You’ll hear about the latest studies and findings that are driving this excitement, gaining insights into how postbiotics might benefit you.

Decades later, this observation was noticed again, where vaccinated children in high-mortality areas of West Africa had a significantly lower mortality rate ¹.  In 2012, the mystery behind these observations was finally solved and a new type of immune protection was identified, which is now called trained immunity ².

The understanding of immune memory has been centred around the idea of targeted disease-specific approaches.  The aim of a vaccine is to induce a disease specific memory in your adaptive immune system (memory T and B cells), which then can spring into action if an individual is exposed to that disease.

However, trained immunity research has been ground-breaking within the field of immunology due to its differences in immune memory.  It revealed that cells of the innate immune system also have a kind of memory, although this memory works in a very different way and results in defence against a broad range of threats.

With the discovery of trained immunity, we now know that it is possible to also increase protection against multiple, unrelated diseases.  This important discovery has therefore presented new opportunities to bolster immune defences against a myriad of threats in a non-targeted manner; a new method to protect ourselves from future disease.  Moreover, research has recently shown that it is possible to induce trained immunity through food ³.

How Does Innate Training Occur?

A growing body of research over the past decade has helped identify key mechanisms which explain how innate training occurs. Innate training agents, such as the BCG vaccine ^2,4, and the adenoviral ChAdOx1 nCoV-19 vaccine ⁵ are able to induce trained immunity via metabolic reprogramming and epigenetic modifications ⁶.

Epigenetic Changes – Placing a Bookmark

DNA contains instructions for making proteins, including proteins crucial for launching immune responses.  However, DNA is a very tightly coiled structure where gaining access to the instructions required can take precious time.

Training stimuli, such as the BCG vaccine, in essence creates bookmarks in this instruction manual to be placed on crucial pages for launching immune responses.  This act of “placing the bookmark” is done via epigenetic changes; reversible chemical modifications to the DNA structure that loosen the DNA at certain sites, making the genes/instructions at those sites more easily accessible.

These epigenetic changes are made possible due to altered metabolism within the cell, which provides the materials for these chemical modifications to occur.  Consequently, when a subsequent danger is detected in future, the relevant pages/genes are more easily read, allowing an immune response that is more rapid and potent, compared with non-trained immune cells.  This more potent response is also possible due to metabolic reprogramming.

Placing the bookmark: Innate trainers place bookmarks in the DNA instruction manual; metabolic reprogramming provides the building blocks for chemical modifications (bookmarks) to occur on the DNA – epigenetic changes – resulting in loosened DNA, ready to be read when a new potential danger occurs. Adapted from “Mihai Netea and Niels Riksen at ImmunoMetNet’s Seminar – The double-edged sword of trained immunity” – https://www.youtube.com/watch?v=5AWnp5cEw_4

Metabolic Reprogramming – Meeting Energy Requirements

When an immune cell is activated as part of launching an immune response, processes engage which require a lot of energy and the production of numerous compounds, such as immune messenger signals.  These energy and production demands are met by metabolic machinery.

Innate training stimuli initiate metabolic reprogramming, which not only provides the necessary building blocks for epigenetic changes to occur to the DNA (“placing the bookmark”), but also increases the metabolic machinery available to the cell, to meet future energy and production requirements.  This could be seen as the trained cell building up its energy infrastructure to be better prepared for future challenges.  When a subsequent danger is detected, the innate immune cells can immediately spring into action, as this enhanced metabolic machinery is ready to meet the required energy and production needs, facilitating a rapid and robust immune response ⁷.

Is Trained Immunity Long Lasting?

A hallmark of the adaptive immune response is the induction of long-lived memory cells, which mobilise should a “memorised” danger appear again.  This is the type of memory targeted with a vaccine, to induce long-lived protection.  Trained immunity has also been shown to last for several months, despite innate immune cells not living for very long.

Innate immune cells are replaced regularly, both by cell division and by influx of new cells, coming from hematopoietic stem cells in bone marrow.  These stem cells divide and mature into different types of immune cells, replenishing the body’s immune cells as needed.

The explanation of innate training above has focused on individual innate immune cells coming across training stimuli and thus having a more efficient responses against subsequent dangers.  This type of trained immunity is known as peripheral trained immunity, and is thought to be maintained, at least to a degree, by cell division – where epigenetic modifications (bookmarks) can be passed on to daughter cells ⁸.  Although this is believed to contribute to the longevity of trained immunity, the core component is due to training of hematopoietic stem cells in the bone marrow, as identified by epigenetic changes therein.  This is known as central trained immunity ⁹.

How this training occurs is not fully understood, although certain immune messenger signals have been identified to contribute to this phenomenon.  It has also been postulated that stem cells may be able to detect danger signals, in a similar manner as innate immune cells, possibly leading to similar metabolic and epigenetic outcomes.

Because stem cells divide and become lots of different immune cells, their training can result in altered amounts of certain immune cells, as well as affect their responses.  For instance, central trained immunity induced by BCG vaccination, has been shown to result in a higher number of innate immune cells that are more effective at fighting off infections up to five months post vaccination, due to altered gene expression ¹⁰.

Although studies have shown that innate training can be long lasting, there is an important aspect of this phenomenon that needs to be highlighted: it is reversible.  Epigenetic changes, placing bookmarks at relevant pages, are a core component of trained immunity, which are caused by chemical modification to the DNA.  However, these modifications can be reversed, and the bookmarks consequently removed ^11,12.  This is a highly dynamic feedback system, where the innate immune response is adapting to new information all the time.

Can you Train your Immune Response?

There are numerous substances and challenges that have been shown to cause trained immunity, such as the earlier mentioned BCG and adenovirus COVID-19 vaccines, and more are being discovered all the time.  However, most identified innate trainers need to be either administered by medical staff or occur as the result of an infection/being sick, neither of which is ideal for day-to-day protection.  To both induce and maintain trained immunity, the most desirable approach is something an individual can eat or drink.

Fortunately, research suggests that certain functional/bioactive ingredients found in everyday food, beverages, and dietary supplements may be able to induce and maintain this process of trained immunity.  For instance,  food-safe whole beta glucan particles (WGPs) not only induce trained immunity in isolated innate immune cells (peripheral trained immunity) but also resulted in central trained immunity when ingested by mice ³.  This discovery has opened new dietary possibilities to bolster defences against immune challenges.

In Summary

There is growing enthusiasm in understanding the influence of diet and supplementation on the immune system.  These approaches include the use of probiotics to support balanced gut flora and the inclusion of essential nutrients, such as vitamin C, to maintain regular immune function.  What is exciting about the discovery of trained immunity, and the possibility to induce it through diet, is that it enables next level immune protection.  As discussed herein, it is a recently discovered, natural enhancement of the innate immune defence, enabling the immune system to be at the ready for future challenges.

In the wake of the COVID-19 pandemic, ‘natural’ proactive and immune health solutions have been highlighted as a growing area of consumer interest, with over half of global consumers outlining a willingness to use supplements if they had a greater understanding about the ingredients those supplements contain ⁽¹⁾.  As consumers continue to seek more natural, holistic health solutions and as the area of prevention over cure grows, traditional botanical and herbal ingredients have emerged as a key area of interest ^{(2), (3)}. While botanical extracts have been used in ancient Chinese and India medicine for centuries, this growing popularity has been spurred on by consumer desire for cleaner labels, more sustainable nutrition and ingredients that provide a halo effect ⁽⁴⁾.

Globally, immune support has been outlined by consumers as the number one reason for purchasing healthy lifestyle products ⁽⁵⁾, therefore making it unsurprising that botanical and herbal ingredients that are thought to support immune health have seen a growth spurt over the last number of years. Elderberry is one of the most well-known botanicals that falls under this category, with a compound growth rate of over 25% observed in supplement launches with elderberry over the last 5 years ⁽⁶⁾. With over 50% of global consumers associating elderberry with improving immune health ⁽⁷⁾, we look to explore the origins of the use of elderberry in immune health and the potential mechanism of action which mediates its suggested benefits.

Background & Potential Health Benefits

Elderberry is a plant native to both northern and southern hemisphere sub-tropical areas ⁽⁸⁾. With over 10 species within the genus, research into the structure and function of the species has assessed their effect, if any, on human health ⁽⁹⁾. Sambucus Nigra or black elder is one such species of elderberry commonly used in supplements. Sambucus Nigra has been found to be a natural source of bioactive compounds and therefore have a high antioxidant activity ⁽¹⁰⁾. In addition to the proposed anti-oxidant activity of elderberry, Mlynarczyk et al., 2017 have proposed other potential benefits of the plant and the way in which these are mediated through bioactive compounds (Figure 1) ⁽¹¹⁾.

Figure 1. Proposed Potential Health Benefits of Elderberry ⁽¹¹⁾.

While all parts of the plant (flower, bark, leaf, and fruit) are a rich source of these bioactive compounds, the fruits and flowers of the elderberry plants are the most commonly used components in elderberry extracts ⁽¹²⁾. Extracts can concentrate the flavour, colour, nutritional value and active components of a fruit or plant into a smaller essence while maintaining these desired qualities. The fruit and flowers from black elder have traditionally been used to prevent or reduce the effects of illnesses such as those relating to the respiratory tract, and therefore elderberry and elderberry extract are thought to support immune health.

How is this health benefit modulated?

Elderberry extract has been shown to have antibacterial and antiviral properties in both in-vitro and in-vivo models, further positioning this as an immune modulating ingredient ⁽¹³⁾.

These immune benefits are thought to be modulated through its unique composition, consisting of bioactive compounds such as phenolic compounds like anthocyanins and a variety of vitamins and minerals including vitamin C and Zinc ⁽¹⁰⁾.

These compounds and nutrients have been shown to have antioxidant activity, demonstrating anti-inflammatory, antiviral and immunostimulatory effects in the research. Overall, the research has shown elderberry to reduce the severity or delay the onset of oxidative stress and inflammation mediated chronic health conditions ⁽¹⁴⁾.

In addition to this, clinical studies investigating the effectiveness of elderberry on the common cold and flu have resulted in a reduction in symptoms or reduction in the duration of illness ⁽¹⁵⁾. A study by Tiralongo et. Al., 2016, found elderberry extract supplementation to reduce ‘common cold’ episode days in passengers of long-haul flights. Passengers were given either elderberry extract or placebo, consuming this 10 days before travel until 5 days after arriving at their destination. Those in the placebo group had a duration of 177 cold episode days collectively, versus 57 in the elderberry extract group, while over 580 symptoms were identified across the placebo group on these days versus 327 in the elderberry extract group (Figure 2). On an individual level, this resulted in on average, a 2-day reduction in duration of the cold and decreased symptom load for those supplementing with elderberry extract versus placebo ⁽¹⁴⁾. This is just one study which highlights the potential effects of elderberry in immune health and improving quality of life.

Figure 2. Cold episode days (A) and cold symptom score (B) of participants with a well-defined cold established from Jackson Score ⁽¹⁴⁾.  

While future studies  will be needed to further confirm its efficacy and clarify the way in which elderberry mediates immune benefits, the research has shown, that at a minimum, elderberry is a safe option with the botanical showing no evidence of over stimulating the immune system ⁽¹⁶⁾. In addition to this, organizations such as the German Commission E have approved the flower of Sambucus Nigra for cold and flu ⁽¹⁷⁾, with the European Committee on Herbal Medicinal Products also concluding that Sambucus Nigra can be used in the relief of early symptoms of the common cold ⁽¹⁸⁾.

As consumer interest in more natural, proactive health solutions continues to grow, science-backed, botanical ingredients, such as elderberry have an opportunity to take a further foothold in this market and become the solution of choice when preventing common immune health conditions such as cold and flu.

What is a postbiotic?

A postbiotic is defined as a “preparation of inanimate microorganisms and/or their components that confers a health benefit on the host” by The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics.

This definition was agreed upon by a panel of experts specializing in nutrition, microbial physiology, gastroenterology, paediatrics, food science and microbiology by reviewing existing science, regulations, and commercial use of postbiotics.

What is the difference between probiotics and postbiotics?

The primary difference is that the phrase probiotics refers to live microorganisms, while postbiotics refers to inanimate (inactivated or dead cells) microorganisms or their components. As we learn more about how probiotics work, science has shown that some microorganisms don’t need to be alive to confer a benefit. There might be parts of a microorganism’s cell that interacts with our body (e.g. our immune system), and this part of the cell might be present whether that cell is alive or dead.

The consensus statement from ISAPP proposed that postbiotics may work by interacting with our resident microbiota, modulate immune responses, or interact with our nervous system. It is critical that the microorganism has produced enough of the bioactive molecules that cause these benefits before it is inactivated.

Postbiotics do not need to be alive to confer a benefit, so they are considered stable during industrial processing and storage.

ISAPP has created the infographic below to help clarify the definition of a postbiotic. For more science-based resources on digestive health and the microbiome, you can visit the ISAPP website.

Reaping the benefits of postbiotics in food for humans or animals

• • Postbiotics are inanimate in nature, offering significant advantages for their application in food and feed matrices subject to varying processing conditions, as well as an inherent lower susceptibility to storage conditions
  • Scientific evidence behind postbiotics highlights their ability to increase the host resilience from within by influencing gut function, its microbiota, and the interconnection with the central-nervous system (gut-brain axis)
  • This is an up and coming technology in the ‘biotic’ space with multiple uses in food and feed applications, which will advance significantly in coming years as our scientific knowledge expands into dedicated life-stages and/or need-states

Benefits of postbiotics – where science is today

The research concerning the potential benefits of postbiotics has been focused on gut health, with Lactobacillus-derived postbiotics taking the spotlight.  Postbiotics may act by cellular and molecular mechanisms involving the control of the immune and nervous systems, as suggested by their ability to boost innate immunity, reduce pathogen-induced inflammation and promote the survival of intestinal epithelial cells (Cicenia et al., 2014).  Inactivated Lactobacilli preparations have been capable of reducing pain scores, bloating, and stool frequency in irritable bowel syndrome (IBS) patients (Tarrerias et al., 2011).  Similarly, heat-killed L. acidophilus reduced bowel movements in patients with chronic diarrhoea, even in comparison with the live L. acidophilus-treated group (Xiao et al., 2003), which suggest a significant advantage over any concerns of viability and delivery of a live microbe to the required site of action.

Postbiotics may also play a role in early life interventions.  Healthy toddlers receiving an inactivated L. paracasei fermented cow’s milk preparation showed improved measures of immunity including reduced incidence of common infectious diseases and significant changes in innate and acquired immune biomarkers, such as secretory IgA and defensins (Corsello et al., 2017).  Furthermore, heat-killed L. acidophillus LB plus its culture medium reduced the recovery time of infants with non-rotaviral diarrhoea by 1 day (Liévin-Le Moal et al., 2007).  Thus, postbiotics may represent a feasible intervention to mitigate the incidence and severity of common ailments in children.

How do postbiotics work – are short-chain fatty acids the key?

Provision of postbiotics from L. gasseri through traditional fermented milk beverages also improved stool consistency in healthy individuals with tendency for constipation, with an increase in short-chain fatty acid (SCFA) production (Sawada et al., 2016).  SCFA may play a key role in the functionality of postbiotics, either directly as actives in the postbiotic formulation, or indirectly as metabolites resulting from induced changes in gut microbiota.  SCFA are known to stimulate colonic sodium and fluid absorption, with butyrate showing positive benefits on helping colonocytes grow and repair, enhancing gut barrier function, and mucosal immunity.  Due to the interconnectivity between our gut, brain, and microbiota, postbiotics have also been demonstrated to positively influence measures of anxiety and quality of sleep, as well as enhancing the mood state, of healthy adults (Murata et al., 2018; Nishida et al., 2019).

Postbiotics may also play a role in early life interventions.  Healthy toddlers receiving an inactivated L. paracasei fermented cow’s milk preparation showed improved measures of immunity including reduced incidence of common infectious diseases and significant changes in innate and acquired immune biomarkers, such as secretory IgA and defensins (Corsello et al., 2017).  Furthermore, heat-killed L. acidophillus LB plus its culture medium reduced the recovery time of infants with non-rotaviral diarrhoea by 1 day (Liévin-Le Moal et al., 2007).  Thus, postbiotics may represent a feasible intervention to mitigate the incidence and severity of common ailments in children.

Postbiotics in animal health – a role for improving quality of our food supply

Sustainability and food safety are at the core of our success as a civilization in the centuries to come.  With these aspirations, a robust food supply chain is paramount, and, thus, we need to look beyond our own health to that the animals that constitute/produce our food.

Inactivated Saccharomyces cerevisiae has been shown to reduce Salmonella Enteriditis in commercial laying hens (Gingerich et al., 2021).  This pathogen is responsible for the vast majority of foodborne salmonellosis, and, as such, postbiotics could play a role in reducing foodborne illness by targeting the farming stage of food production.

A Lactic Acid Bacterium derived postbiotic has also shown potential to diminish the severity of gut lesions caused by necrotic enteritis, increasing the liveability and productivity of broilers (Duong et al., 2021).  Postbiotics from L. acidophilus have also been shown to accelerate the development and establishment of microbiome clusters in nursery pigs, which correlated with increases in growth rates (Khafipour et al., 2021).  Overall, there is evidence suggesting that postbiotics can facilitate the production of animals in an effective, safe and sustainable manner.

Looking to the future

The evidence behind the functionality of postbiotics is increasing rapidly.  Nonetheless, in the rather populated functional biotics area, the scientific community is proposing that postbiotics should be characterized by defining the microorganisms in the starting material, identifying the inactivation procedure, and the description and quantification of the final postbiotic composition.  Although this practice has not been fully entrenched yet, much of this information should be at the ready and will only make the case for the use of postbiotics in food and feed applications stronger.