Although certain yeast beta glucans have been recognised as highly efficacious ingredients for immune support for over 20 years, the most recent research exploring the detailed mechanism of action has revealed some surprising findings.  The established scientific thinking from the past 75 years has been that only the adaptive immune system has the capacity to “remember” past experiences with infectious and inflammatory challenges and respond more effectively to them upon a future encounter.  This dogma has now been dismantled with the discovery of trained innate immunity, thanks in large part of the exploration of how specific yeast beta glucans with unique molecular structures support immune health.

Measuring Gene Expression Revolutionises the Quest for Evidence of Innate Immune Training In Vivo

This recent paradigm shift in our understanding of the capabilities of the innate immune system to include trained immunity traces its roots to epidemiologic research in the early 2000’s.  This was followed by a set of human clinical trials published starting in 2009 which provided evidence of the physical health benefit resulting from trained innate immunity ^1-10 .  However, most of the published cellular data revealing trained innate immunity has come from experiments in vitro and pre-clinical models ^11-14, not in human clinical studies.

In the past two years, several clinical reports have now been published describing innate immune training at the cellular level in clinical trials when healthy volunteers consume a particular yeast beta glucan ^15-17.  Previously, the method available to test if the immune system had become trained in human volunteers involved challenging people with physical or lifestyle stressors to provoke an immune response and measuring functional changes that indirectly reflect innate immune training.

The newest publications provide a strong example of direct measurement of innate immune training in humans by measuring changes in gene expression (use) of specific genes that make up cellular innate immune training programs.  They also demonstrate that consumption of a specific yeast beta glucan with a defined molecular structure trains the innate immune system in healthy volunteers and not just laboratory models.  This has revolutionised the study of innate immune training in vivo.  Using the proposed gene expression signature, it seems possible to observe and monitor innate immune training in near real time in healthy people without challenging or unnecessarily stimulating the immune system.

The gene use signature includes genes that are known to have critical roles in the innate immune response to foreign challenges.  Some of these genes code for proteins that are key parts of cellular signalling pathways used by the yeast beta glucan receptor, Dectin-1.  Other genes are part of the innate immune training cellular control program.  Identifying and measuring this signature provides strong evidence that innate immune training occurs in healthy people following daily consumption of a specific yeast beta glucan.  These studies also provide greater insight into how this well characterised yeast beta glucan supports a healthy immune response.  Greater understanding of how this specific type of innate immune training works helps to reassure consumers that this ingredient provides efficacious support for a healthy immune response.

The Importance of Structure–Function Clarity

Although beta glucans are widely recognised, there remains significant confusion in the market about the differences between beta glucan sources such as yeast, cereal, and mushroom.  What sets certain yeast beta glucans apart is their specific molecular structure, including the configuration of (1,3/1,6) linkages and the tertiary conformation that allows them to interact effectively with innate immune receptors like Dectin-1.  These structural features are foundational to whether the body can mount a meaningful trained innate immune response.  By highlighting the importance of well-defined structure–function relationships, this emerging research gives both scientists and product developers a clearer framework for evaluating beta glucan quality.

Consumer and Market Context: Why This Science Matters Now

Over the past several years, consumers have increasingly shifted toward a more proactive and holistic understanding of immune health—one that emphasises everyday resilience, not just seasonal defence.  This shift is reflected in strong ongoing demand for functional foods, beverages, and supplements that provide clinically validated benefits and are grounded in credible mechanisms of action.  As consumers become more discerning, ingredients supported by emerging scientific insights, such as trained innate immunity, stand out as particularly relevant. Yeast beta glucans with well characterised structures and robust clinical substantiation are uniquely positioned to meet these expectations, offering an immune support solution that aligns with how consumers now think about “living well” rather than simply managing illness.

What Does the Future Hold?

Training of the innate immune system has been happening long before we were aware of the concept or understood some of its benefits for our everyday health.  For nearly two decades research has repeatedly shown that daily consumption of a well-studied yeast beta glucan supports immune health, reducing the severity and incidence of symptoms from upper respiratory challenges ^1,2,4,7-10.  Using the recently proposed gene expression signature of a trained innate immune system in healthy people, future research can finetune interventions such as yeast beta glucans to more effectively optimise support for a healthy lifestyle and immune health.

Additionally, by using powerful new data informatics tools coupled with new results from clinical studies, researchers are very likely to uncover new ways that training the innate immune system leads to other benefits to our everyday health and wellness.  We look to the future with great optimism and excitement about what science will teach us about the benefits of training the innate immune system to support our health.

The health and nutrition landscape is evolving rapidly, driven by scientific advances and changing consumer expectations.  In collaboration with KHNI’s extensive network of scientific experts, we identified five health and nutrition megatrends that are reshaping the food and beverage industry.  These trends are influencing innovation in product design, formulation, and reformulation as companies respond to the shifting needs and priorities of consumers.

Understanding these developments is essential for driving innovation and staying aligned with market demands.

To explore some of the most pressing topics, the KHNI’s upcoming webinar will focus on three transformative trends:

1. Food for Health and Longevity
2. Regulations and Reformulation
3. Emerging and New Technologies

Join us on April 30, 2025, for an in-depth discussion of these important themes.  The session will provide insights to help shape the future of food and nutrition while supporting you in navigating evolving consumer expectations, scientific developments, and regulatory landscapes.

Register now to be part of this insightful event and drive the next wave of innovation in health and nutrition.

These guidelines have several roles:

• • To help Americans choose a healthful diet.
  • To advise nutrition standards for a wide variety of federal feeding programmes like the school lunch programme, the Child and Adult Care Food Programme, and the Supplemental Nutrition Programme for Women, Infants and Children (WIC).
  • To support federal and other public health nutrition education programmes.
  • To support food fortification and reformulation efforts by the food industry.

So why have these latest guidelines, published in January 2026, received so much attention?

The New Dietary Guidelines – a Significant Reset?

These 2025-2030 Dietary Guidelines for Americans (DGA’s) ¹ are promoted as the “most significant reset of federal nutrition policy” and highlight the placing of  “real food at the centre of the American diet.”  However, much of the guidance has remained the same with a focus on eating nutrient dense foods, limiting added sugar, and keeping saturated fat intakes below 10% of calorie intakes.

What is different is the emphasis on certain foods and nutrients, the new inverted food pyramid, and how the process was undertaken this time around.  These guidelines are posted on a website including supplemental materials and Grok AI to answer consumers’ questions ².

Key differences in messaging in the 2025-2030 Guidelines:

Here is a quick look at some of the differences in the new guidelines compared to the previous version:

Increased Protein:  Americans have long consumed more protein than earlier dietary recommendations advised.  However, the new dietary guidelines declare an end to the “war on protein” ² and to prioritise protein at every meal.  They substantially increase the suggested intake to 1.2–1.6 g/kg/day for all Americans, rather than recommending increased intakes for specific subpopulations as in the past.  Meat and other animal-based forms of protein are highlighted in the guidance, with an acknowledgement that one can also find protein in other foods like beans, lentils, tofu and nuts.  Previous editions of the DGA’s and other substantial dietary guidance from around the world highlight the importance of using plant-based protein sources for sustainability and health reasons ⁴.  Additionally, meat and animal-based protein tend to be more expensive than plant-based proteins and the costs associated with these changes are a limitation for many Americans.

Saturated Fat-Containing Foods:  These dietary guidelines maintain the previous recommendations to limit saturated fat to less than 10% of calories.  However, these guidelines suggest consuming butter, full-fat dairy products, beef tallow, and eating more meat.  Based on the recommended number of servings for these foods, remaining within the 10% saturated fat limit will be a challenge ⁵.

Define Real Food:  One of the main messages of the 2025-2030 guidelines is to “Eat Real Food”.  These guidelines steer Americans to consume foods like meat, full fat dairy products, fruits, vegetables and whole grains as the real foods, with a strong focus on the meat and dairy product categories.  While there have always been recommendations to consume nutrient-dense foods, these guidelines suggest limiting highly processed foods, implying these do not count as real foods.

Highly processed foods (often referred to as ultra-processed foods (UPF)) are under scrutiny around the world to determine definitions and health effects, but the science is far from settled.  In the guidelines, little guidance is provided on how to make such a substantial change – how to remove highly processed foods from American’s diets and to shift to lower processed foods.

Added Sugars:  The new recommendations are stricter, limiting added sugars to no more than 10g per meal for adults, and no added sugars before the age of 11 years.  They also suggest limiting non-nutritive sweeteners.  The guidelines do include detailed information on identifying added sugar and limits on how much added sugar should be included in snacks.

Sustainability and Equity:  Throughout the world, countries and the Food and Agriculture Organisation of the United Nations (FAO) are focused on integrating the issues of sustainability and equity into their dietary guidance and food policies.  The later scientific committee behind the new DGA’s rejected these priorities in their substantiation documentation, and they are not considered in these new guidelines ⁶.

Reduce Alcohol But How Much?:  As with the previous version of the guidelines, there is a recommendation that drinking less alcohol is better for health.  The difference is that the new DGA’s do not include any specific limits on how many drinks per day should be consumed.

Picture This Pyramid

One of the most visible changes of these dietary guidelines is the launch of a new image of the guidelines – an inverted food pyramid.  The US has not used a food pyramid since 2011 when the USDA switched to MyPlate to make it clearer how much of the plate should be filled with different categories of foods.

This new pyramid (Figure 1) showcases a wide top highlighting meat, cheese, milk, and vegetables; with other proteins, some dairy foods, fats, and fruit in the middle section; and whole grains at the bottom tip.

Figure 1. Dietary Guidelines for Americans 2025-2030 ¹

The number of servings for foods are not listed, nor are the food images shown to scale.  Having whole grains displayed at the bottom tip may lead to consumer confusion as it suggests that very little grains should be eaten.  However, the new guidelines still recommend 2-4 servings of whole grains per day.

Scientific Bodies Weigh In

Several expert public health organisations have responded to the new guidance.  While they are positive about the elements of the DGA’s that align closely with the longstanding dietary guidance, they have also flagged concerns about some of the changes.  These concerns will likely impact on how the guidelines are adopted across the board by healthcare professionals, the public and the food industry alike.

The American Society for Nutrition’s (ASN) statement expressed concern over the change in the established scientific review process.  In 2023, a 20-scientist Dietary Guidelines Advisory Committee (DGAC) was selected, vetted for conflicts of interest, and held public meetings before releasing a comprehensive scientific report in December 2024 with a public comment period ⁷.  Normally, this report would inform the final DGA’s.  However, a new group of nine scientists was contracted to produce The Scientific Foundation for the Dietary Guidelines.  They rejected the results of the DGAC’s report and wrote this new document which was released along with the 2025–2030 Dietary Guidelines in January this year.  ASN believes the change from a rigorous and open process may undermine confidence in the DGAs and nutrition science and contribute to confusion ⁸.

The Academy for Nutrition & Dietetics challenged the guidelines’ emphasis on animal sources of saturated fat, the lack of consideration of diets for people who cannot include dairy and the call for moderation in low calorie non-nutritive sweetener intake in the face of evidence that they are generally considered safe within acceptable intake limits ⁹.

The American Heart Association says it will continue to “encourage consumers to prioritize plant-based proteins, seafood and lean meats and to limit high-fat animal products including red meat, butter, lard and tallow, which are linked to increased cardiovascular risk”  pending any future research ¹⁰.

The World Cancer Research Fund are concerned that the increased emphasis on red meat does not reflect the scientific evidence linking higher intakes of red and processed meat to increased cancer risk ¹¹.

Considerations for Food Industry and Healthcare Professionals

While the new DGAs are still in their early stages, it is possible to begin considering their potential impact.

We know that dietary habits are notoriously resistant to change.  For two decades, the International Food Information Council (IFIC) Food & Health Survey ¹² (an annual survey of 3,000 Americans) has consistently shown that taste dominates food and beverage purchase decisions, followed by price.   These same factors will continue to play a crucial role in shaping the adoption of any new dietary guidance.

It is likely that consumers will encounter more mixed messages from both healthcare professionals and through social media.  The 2025 IFIC Food & Health Survey, showed that eight in ten Americans were confused over what nutrition information to believe in because they felt it changed frequently.  For this reason, it will be important to reassure the public that many elements of the new DGAs remain the same.  This is a key message that can be emphasised by both healthcare professionals and the food industry alike.

Food Industry

• • Food companies will need to decide if they want to make changes to their portfolio based on the new guidance. Some change is already happening – one restaurant chain switched to cooking their fries in beef tallow ¹³.  However, it is early days and having spent years reformulating, food manufacturers may pause before making changes to their products’ recipes considering some of the conflicting evidence.
  • The ambiguity around what defines a ‘highly processed food’ is difficult for product developers who are attempting to innovate or renovate but the DGA’s negative stance on “chemical additives”, added sugars, and non-nutritive sweeteners, may accelerate the clean label trend and lead to shorter ingredient lists.  While this trend creates opportunities for the food industry,  food additives play an important role in food safety, preservation and in reducing food waste which remain priorities.  Fortification with key nutrients often lacking in the US diet should not be abandoned for the sake of a shorter “clean label.”  Companies that successfully balance these competing concerns may gain a competitive advantage.
  • A recent poll found that 1 in 8 U.S. adults are taking GLP-1 medications for weight loss, diabetes, or other conditions ¹⁴. In response, the food industry is focusing on protein-rich, high-fibre, nutrient-dense foods.  Notably, these priorities closely mirror the DGA’s; however, GLP-1 use often requires a more targeted, individualized approach to manage appetite suppression, preserve muscle, and prevent potential nutrient inadequacies that may not be wholly delivered through a focus on real foods alone.

Healthcare Professionals

• • In the social media age, nutrition and dietetic professionals are well used to addressing conflicting advice but should expect growing confusion and challenge from both patients and other healthcare professionals.
  • US federal food programme changes have traditionally followed lengthy rule-making processes, but healthcare professionals engaged in these programs should be ready for faster shifts under the current administration—for example, a recent law allowing whole and 2% milk in schools alongside skim and low-fat options was introduced ¹⁵.

Conclusion

Ultimately, guidance alone does not result in positive dietary changes.  Telling people to eat real foods does not work if they are unaffordable or unavailable.  The real question is whether these DGA’s will be followed by substantive federal action that enables Americans to make these changes in their daily lives.

Funding for educational programs to support healthy eating, reduction of food deserts in communities, cooking classes, reduced prices on food, support for improved food systems, funding for research, and support for farmers to grow the diversity of crops needed are just a few of the actions required to support Americans to change their diets in such a large and profound way.

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.

What is the Role of Vitamin D in Human Health?

Vitamin D, sometimes known as ‘the sunshine vitamin’, is a fat-soluble vitamin important for bone health, muscle function and the immune system ^1-4.  Vitamin D is also being investigated for its role in protecting against some chronic diseases including cardiovascular disease and type-2 diabetes ¹.

Vitamin D exists in two primary forms:

(i) vitamin D2 (ergocalciferol) which is obtained from plant and fungi sources that have been exposed to UV light.

(ii) vitamin D3 (cholecalciferol), found in animal-based products such as fatty fish, eggs and liver ³.

Both forms of vitamin D are biologically inactive when ingested and are absorbed in the small intestine.  They are transported to the liver and converted into 25-hydroxyvitamin D (25(OH)D), also known as calcifediol or calcidiol, followed by conversion in the kidneys into 1,25-dihydroxyvitamin D (1, 25(OH)2D), or calcitriol, which is the biologically active form used by the body (Figure 1) ³.  Studies have shown that vitamin D3 leads to a greater increase of serum 25(OH)D than vitamin D2 ⁵.

The ‘sunshine vitamin’ gets its name from the fact that it is also produced in human skin from 7-dehydrocholesterol when exposed to sunlight or more specifically, UVB rays.

Figure 1. Vitamin D Metabolism.  Image Source: Vitamin D Sources, Metabolism, and Deficiency: Available Compounds and Guidelines for Its Treatment

Functions

Research shows that vitamin D plays a significant role in bone health, muscle health and the immune system:

1. 1. Bone health: Vitamin D is a critical regulator of calcium absorption.  In its active form, 1,25(OH)2D, it interacts with the vitamin D receptor (VDR) in the small intestine resulting in an increase in calcium and phosphate absorption ².  However, calcium homeostasis is primarily regulated to maintain serum calcium within a narrow range for metabolic reasons with the parathyroid gland, bone, intestine, and the kidney working together in this role ⁴.  Chronic vitamin D deficiency that results in an increase in parathyroid hormone leads to increased bone resorption, compromising the structure of the skeleton and increasing the risk of fracture thus vitamin D sufficiency is important to optimise skeletal health ⁴.
   2. Immune health: Vitamin D plays a crucial role in regulating both the innate and adaptive immune responses.  The expression of VDR in many different immune cells has been well demonstrated ⁶.  It modulates the activity of immune cells, such as B cells, T cells, and antigen-presenting cells, and promotes a balanced immune response.  Vitamin D deficiency is associated with an increased risk of hospitalisation for respiratory tract infections ⁷ and supplementation has been shown to boost antigen-specific immunity in older adults with sub-optimal vitamin D status ⁸.  Genetic variation in the VDR genes has also been linked to Vitamin D deficiency and the development of autoimmune disease ⁶.
   3. Muscle function: The identification of a VDR in skeletal muscle cells, along with the strong association between vitamin D deficiency, muscle atrophy, and sarcopenia, suggests an important role in muscle function ⁹.  Proposed mechanisms include modulation of protein synthesis, mitochondrial metabolism, and energy production, which may influence performance.  However, the effects of vitamin D3 supplementation on muscle mass, strength, and physical performance remain debated, with conflicting findings.  Meta-analyses of randomised controlled trials in athletes have not shown conclusive benefits, highlighting the need for further research ^10,11.  In contrast, supplementation has been associated with improved muscle strength in postmenopausal women ¹².  Interpretation of trial results should consider whether populations have insufficient or sufficient vitamin D status and whether any supplementation used has increased 25(OH)D levels sufficiently as these factors may influence outcomes ¹³.
   4. Mental health: Emerging evidence suggests a link between vitamin D and mental health – its neuroprotective properties may contribute to its role in mental wellbeing, reducing neuroinflammation, supporting serotonin synthesis, and improving brain plasticity ¹⁴.  Recent meta-analysis suggests no benefit of supplementation in healthy individuals ¹⁵ but potential effects on depressive symptoms in those with major depressive disorder or with milder, clinically significant depressive symptoms ¹⁴.  However, more high-quality research trials are needed.
   5. Other Potential Roles: Vitamin D has other roles in the body, including modulation of cell growth, neuromuscular function, and glucose metabolism ¹⁶.  Ongoing research is also exploring the potential benefits on other health conditions including heart disease, diabetes, and musculoskeletal diseases like multiple sclerosis ¹⁷.

In European Union countries, approved health claims are available for the role of Vitamin D in supporting a wide range of functions including maintaining normal bones and teeth, muscle and immune function as well as supporting absorption of calcium and phosphorous subject to conditions.  In China, claims relating to the health of bones and teeth, and the absorption and utilisation of calcium and phosphorus are also available for vitamin D containing foods subject to conditions.

Recommended Intakes

In some countries, national dietary reference tables can lag behind updated clinical practice or more recent Vitamin D supplementation policies.

• • United States:  The Institute of Medicine (IOM) Recommended Dietary Allowance (RDA) for vitamin D is 600 IU (15 micrograms) daily for adults aged 19–70 and 800 IU (20 micrograms) daily for adults over 70 years, assuming minimal sun exposure ¹⁸.
  • Europe:  The European Food Safety Authority (EFSA) has set an adequate intake at 15 micrograms per day for healthy individuals over one year of age including pregnant and lactating women to ensure the majority of the population will achieve a serum 25(OH)D concentration near or above the target of 50 nmol/L ¹⁹.
  • China: The Chinese Nutrition Society have set a daily Reference Nutrient intake of 400 IU (10 micrograms) for adults aged 18-50 and 600 IU (20 micrograms) for adults over 50 years ²⁰.

Dietary Sources

Foods rich in vitamin D include oily fish (e.g., salmon, mackerel, and sardines), egg yolks, and offal.  However, sources are limited and there are high levels of inadequacy of vitamin D intake globally ²¹.  In some countries, fortification of staple food (e.g., milk, margarine, cereals) is used to increase vitamin D intake but these policies differ by region and are often voluntary, leading to variable dietary contributions.  For this reason, local food composition data and values should be used when estimating intakes.  For example, milk is frequently quoted as a source of vitamin D but only when vitamin D fortified milk is available.  Liver provides vitamin D but is not widely consumed and is not recommended during pregnancy because of its high vitamin A content ²².  Among plant-based options, mushrooms exposed to sunlight or UV radiation can supply vitamin D2.

Vitamin D – Beyond Food

The level of 25(OH)D in populations varies geographically due to latitude, skin pigmentation, sun exposure, diet, and supplement use.  While endogenous production of vitamin D from sun exposure is also a potential source, recommendations to limit sun exposure to prevent skin cancer and limited sunlight in higher latitudes during winter mean that it cannot be relied upon as a source.

In many countries, vitamin D supplementation is recommended either during winter or throughout the year for more vulnerable populations (e.g. pregnant women, elderly, those with darker skin) ^23-25.  The Endocrine Society also recommend supplementation for children aged 1 to 18 years and those aged 75 years and older as well as pregnant women and those with high-risk prediabetes ²⁶.

Vitamin D Deficiency

The concentration of 25(OH)D in blood serum is currently the main indicator of vitamin D status as it reflects vitamin D produced through both sunlight and from the diet.  There is no universal agreement on the threshold for vitamin D ‘deficiency’.  However, there is widespread acknowledgement of vitamin D deficiency using the most conservative 25(OH)D threshold of < 25/30 nmol/L, in both low- and high-income countries ¹.  Depending on the world region, the prevalence of serum 25(OH)D below this threshold  ranges from ~5 to 18% and 24 to 49% for levels below 50 nmol/L ²¹.

Vitamin D deficiency in toddlers and young adults can cause rickets and slow brain development.  Deficiency in adults causes osteomalacia (brittle bones) increasing susceptibility to fractures.  Confirmed vitamin D deficiency is typically treated with high-dose supplements for a limited number of weeks followed by a maintenance dose ²⁸.

Excess Intakes

It is important to remember that as a fat-soluble vitamin, vitamin D can be stored in the liver and excessive amounts should be avoided.  An upper daily limit of 100 micrograms from all sources has been set in the US by the IOM for those 9+ years ¹⁸ while an upper daily limit of 50 micrograms for children and 100 micrograms for adults has been recommended by the EFSA ²⁷.

In Closing

Ongoing research continues to explore vitamin D’s potential benefits further refining our understanding of its role in human health.  While vitamin D is essential, further research is needed to fully understand its role in various health conditions and to establish clear guidelines for supplementation.

This article was originally published on March 18, 2025, and updated on March 3, 2026.[/vc_column_text][/vc_column][/vc_row]

This healthspan–lifespan gap reflects the global rise in non-communicable diseases (NCDs), including obesity, type 2 diabetes, cardiovascular disease, and neurodegenerative disorders.  These conditions reduce quality of life, increase healthcare expenditures, and limit economic productivity.  The burden of this gap is distributed unevenly across regions, reflecting differences in developmental history, nutritional status, and health system capacity ².

Recent therapeutic advances, particularly GLP-1 receptor agonists (GLP-1 RAs), represent a major breakthrough in the treatment of metabolic disease ³.  However, their effectiveness depends not only on biological efficacy but also on affordability, accessibility, and underlying nutritional conditions.  At the same time, the drivers of disease—and therefore the strategies required for prevention—differ substantially across income settings ⁴.  Nutrition, therefore, occupies a central position at the intersection of treatment, prevention, and economic development.

Drivers of NCDs Across Economic Contexts

A central paradox in global health is that clinical management of major NCDs has become increasingly standardised worldwide, yet the underlying causes of these conditions differ substantially across levels of economic development.  While pharmacological treatments such as GLP-1 RAs act on conserved biological pathways, disease risk is shaped by developmental, nutritional, and environmental exposures that vary across populations ⁵.

In high-income countries, metabolic disease is driven primarily by long-term exposure to unhealthy food environments, sedentary lifestyles, and population ageing.  In middle- and low-income countries, however, metabolic disease risk is strongly influenced by early-life undernutrition, including foetal growth restriction and childhood stunting.  These developmental constraints permanently impair metabolic capacity, increasing vulnerability to obesity, diabetes, and cardiovascular disease later in life ^6,7.

Importantly, early-life undernutrition also impairs cognitive development, physical capacity, and long-term productivity, thereby contributing to intergenerational cycles of poverty, disease, and reduced economic growth.  These differences demonstrate that while treatment mechanisms may be biologically universal, the developmental origins of disease—and, therefore, prevention strategies—must be fundamentally differentiated across economic contexts ⁸.

How Nutrition Shapes Therapeutic Outcomes

Pharmacological treatment of obesity and type 2 diabetes follows broadly similar clinical principles worldwide.  GLP-1 RAs improve metabolic health through appetite regulation, improved insulin sensitivity, and reductions in cardiometabolic risk.  However, treatment effectiveness depends strongly on nutritional status and dietary quality.  GLP-1-induced weight loss frequently includes reductions in lean body mass, particularly in older adults and nutritionally vulnerable populations.  Without adequate protein intake and micronutrient sufficiency, treatment may accelerate sarcopenia and functional decline ⁹.

Although pharmacological treatment is biologically universal, access to both treatment and adequate nutrition vary substantially across income settings ¹⁰.  In high-income countries, access is constrained primarily by cost and lack of insurance coverage.  In middle-income countries, access is limited by both affordability and health system capacity.  In low-income countries, access remains severely restricted due to structural economic constraints, nutrition conditions, and competing health priorities.

How Nutrition Shapes NCD Prevention Across Economic Contexts

In high-income countries, prevention focuses primarily on reducing chronic exposure to unhealthy food environments that promote sustained positive energy balance, obesity, and metabolic dysfunction.  Nutritional prevention strategies emphasise increased consumption of nutrient-dense foods, dietary fibre, and high-quality protein, alongside structural interventions such as food system reform, improved urban design, and promotion of physical activity.  Because early-life undernutrition is uncommon, NCD prevention focuses primarily on mitigating the cumulative effects of excess energy intake and preserving physiological function across the lifespan ¹¹.

In middle-income countries, prevention must address the co-existence of early-life undernutrition and adult overnutrition.  Childhood stunting and foetal growth restriction permanently alter metabolism, body composition, and insulin sensitivity, increasing susceptibility to metabolic disease later in life.  These developmental adaptations result in earlier disease onset and greater disease severity.  NCD prevention, therefore, requires a life-course approach that simultaneously protects early-life nutrition and improves adult dietary quality through increased access to nutrient-dense foods and reduced reliance on foods high in fat, salt and/or sugar ⁵.

In low-income countries, NCD prevention begins with addressing persistent undernutrition and micronutrient deficiencies.  Early-life undernutrition impairs organ development, immune function, and metabolic capacity, increasing vulnerability to chronic disease later in life.  These effects also impair cognitive development and reduce economic productivity.  Prevention strategies must therefore prioritise adequate nutrition during pregnancy, infancy, and childhood, alongside food fortification, supplementation, and improved dietary diversity.  These interventions improve both immediate health outcomes and long-term metabolic resilience ¹².

Affordability Shapes Both Treatment and Prevention

Affordability represents a fundamental determinant of both treatment implementation and prevention effectiveness.  In high-income countries, healthier dietary patterns are often more expensive than unhealthier alternatives, contributing to socioeconomic disparities in disease risk.  In middle-income countries, affordability constraints limit access to both adequate early-life nutrition and healthy adult diets.  In low-income countries, affordability remains the primary barrier to achieving nutritionally adequate diets.  Improving the affordability of nutrient-dense foods represents one of the most cost-effective strategies for reducing disease burden and extending healthspan globally ¹³.

The biological mechanisms underlying metabolic disease and its treatment are broadly universal.  However, treatment effectiveness is constrained by affordability, access, and nutritional infrastructure.  In contrast, prevention strategies must differ fundamentally across income settings due to differences in developmental history, nutritional status, and metabolic capacity.  Nutrition, therefore, serves as both a determinant of treatment effectiveness and a foundational driver of prevention.

Conclusions and Future Perspectives

Closing the global healthspan–lifespan gap requires aligning therapeutic innovation with nutritional equity and affordability.  Pharmacological treatments such as GLP-1 RAs offer unprecedented opportunities to improve metabolic health.  However, their long-term effectiveness depends on access, affordability, and integration with adequate nutritional support.  NCD prevention strategies must address the developmental origins of disease, particularly the long-term effects of early-life undernutrition on metabolic capacity and human capital formation.  Future efforts must integrate pharmacological innovation, nutritional policy, and economic reform to extend healthspan and improve global health outcomes.

Obesity is a complex chronic disease and a major driver of non-communicable diseases, including cardiovascular disease, type 2 diabetes, and several cancers ².  Obesity impacts populations across all countries and globally there are approximately 2.1 billion adults who are overweight or have obesity.  It is forecast that this will substantially rise to around 3.2 billion by 2050 – accounting for almost 60% of the adult population ³.

In their report, two main WHO conditional recommendations are:

• • GLP-1 therapies may be used for long term obesity treatment in adults (excluding pregnant women).
  • Alongside GLP‑1 therapies, structured behavioural interventions—such as healthy eating and increased physical activity—may be offered.

The WHO stresses that obesity cannot be addressed effectively by medications alone.  Their conditional recommendations are part of a strategy that includes regular physical activity, healthy diets, and support from healthcare professionals.  Therefore, three strategic pillars are identified to help combat obesity, in conjunction with GLP-1 therapeutics, namely:

1. Strengthen population level policies to create healthier environments.
2. Protecting high risk individuals with targeted screening and early interventions.
3. Ensuring equitable access to lifelong, person centred care.

The WHO guidance also highlights major challenges including high costs, limited supply, and disparities in global access.  Even with rapid scale up in production, fewer than 10% of people who could benefit from GLP-1 therapies are expected to have access by 2030.

Countries are being urged to establish fair and affordable routes so those with the greatest medical need are prioritised.  The guideance urges global stakeholders to explore strategies such as pooled procurement, tiered pricing, and voluntary licensing to expand availability.

Throughout 2026, the WHO aims to collaborate with key stakeholders to develop a fair, transparent and prioritised framework so those with the greatest need receive treatment first.