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.

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.

Recommended Intakes

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.

Dietary Sources

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

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.

Excess Intakes

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.

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.

• • 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.

Recommended Intakes

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.

Dietary Sources

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

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.

Excess Intakes

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.

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.

Choosing 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.

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.

A wide range of study designs are used in nutrition research, and no single study design can answer every question ².  Understanding the purpose, strengths, and limitations of each approach helps distinguish between stronger and weaker evidence, so the hierarchy of research methods is key to evaluating the quality of evidence.

This article outlines the key study designs used in nutrition research, the types of questions they are best suited to answer, and the strengths and limitations that guide how their findings should be interpreted, based on several resources ^1-5.

Visualising study designs as a pyramid (Figure 1) highlights how evidence strength varies.  Studies at the lower levels of the pyramid tend to offer limited, less practical insights, while those at the top delivering stronger evidence with greater relevance to real world nutrition choices ^3,4.

Figure 1.  The hierarchy of evidence ranks different types of research according to the strength of the conclusions ³.  (Licensed under CC BY 4.0)

Systematic reviews and meta analyses sit at the top of this hierarchy because they provide data across multiple studies to provide more comprehensive conclusions.  Randomised controlled trials and prospective cohort studies typically provide the most robust evidence when examining relationships between dietary exposures and health outcomes.  However, the rapid growth of the field — and the diversity of methods used — can make it challenging for practitioners and consumers to interpret findings and translate them into practice.

Foundational Research: Non-Human Studies

Foundational research — including in vitro studies in cells or tissues and in vivo studies in animal models — plays a critical role in uncovering the biological mechanisms that underpin how nutrients, ingredients, and other food components behave in controlled settings.  These early stage studies provide directional evidence that helps shape hypotheses and supports the rationale for human research.

It is important to note that isolated cells and tissues and animals do not replicate the complexity of human physiology.  Differences in metabolism, exposure levels, and biological responses mean that findings cannot be directly translated to human outcomes.  For instance, a compound that influences cellular metabolism in vitro, for example, may behave very differently within the interconnected systems of the human body.

However, the value of foundational research becomes clear when it is integrated with human data.  For example, while observational research links smoking with cancer, cell studies identify the carcinogenic compounds responsible.  So, when mechanistic evidence aligns with human outcomes, confidence in the overall conclusion(s) is strengthened.

Observational Studies

These studies track large groups of people over time, in real-world settings, to understand how lifestyle behaviours — including dietary patterns — relate to health outcomes.  These studies identify population level patterns and provide potential associations that may warrant further investigation in more controlled study designs.  Observational studies cannot determine cause and effect relationships and, hence, the impact of a single dietary or lifestyle factor.

Common observational designs include prospective cohort studies, case–control studies, and cross sectional studies, each offering different strengths for understanding how diet and lifestyle influence long term health.

Case Control Studies

Case control studies compare people who already have a specific health condition (the cases) with similar individuals who do not (the controls).  Researchers then look back in time to assess whether past exposures — such as dietary habits — differ between the two groups.  For example, comparing fruit and vegetable intake in people with and without heart disease may help identify potential associations with disease risk.

These studies are relatively quick and cost effective, making them especially useful for investigating rare conditions or outcomes that would be difficult to study prospectively.  They can also examine multiple potential risk factors at once and often serve as an important first step in identifying associations that warrant further research.

However, case control studies face several methodological challenges.  Because exposure information is collected retrospectively, they are highly susceptible to recall bias — particularly when individuals with a disease remember past behaviours differently from those without it.  Selection bias, confounding, and reverse causation can also limit the strength of conclusions.  For instance, if higher consumption of non sugar sweeteners is observed among people with obesity, it may reflect dietary changes made after weight gain rather than a causal effect of sweeteners.

Cohort Studies

Cohort studies are observational studies that are either prospective or retrospective, depending on when the data were collected.  In a prospective cohort, participants complete questionnaires and undergo measurements at the start of the study.  On the other hand, with retrospective cohort studies, researchers “look back” to analyse the relationship.

Prospective cohort studies follow large groups of people in real world conditions over many years — sometimes decades — to explore how dietary and lifestyle exposures relate to the development of diseases.  Participants provide information at baseline and at regular intervals on factors such as diet, physical activity, and health status.  Dietary intake is usually self reported, which introduces challenges such as misreporting, difficulty estimating portion sizes, and changes in behaviour over time.

By tracking outcomes over time, researchers can examine patterns and test hypotheses.  Collectively, prospective cohort studies have shaped much of our understanding of how diet and lifestyle influence chronic disease risk, such as cardiovascular disease or osteoporosis.  However, their long duration means they are time and resource intensive.  As with all observational research, these studies can identify associations but cannot establish cause and effect relationships.

Cross Sectional Studies

This type of research provides a snapshot of health behaviours, exposures, and outcomes in a population at a single point in time.  They are typically conducted through surveys or brief assessments that collect information on both potential risk factors and health indicators simultaneously.

However, cross sectional research has important limitations.  Because exposure and outcome are measured at the same moment, it is not possible to determine which came first.  This raises the issue of reverse causality — for example, whether a dietary behaviour contributes to a health outcome or whether the health outcome influences how participants report their diet.  Cross sectional studies can also be affected by selection bias and recall bias, particularly when participants’ awareness of their health status shapes how they report past behaviours.

Despite these constraints, cross sectional studies are cost effective, relatively quick to conduct, and useful for estimating the prevalence of dietary habits, lifestyle behaviours, or health conditions in a population.  They can also highlight potential associations worth exploring in more rigorous study designs.  A typical cross sectional study might compare dietary patterns across countries to explore whether differences in diet align with variations in cardiovascular disease prevalence.

Randomised Controlled Trials (RCTs)

Randomised controlled trials (RCTs) are considered the gold standard for determining cause and effect relationships ^1,2,5.  Participants are recruited and randomly assigned to a control (placebo) group or an intervention group, ensuring the groups are comparable at baseline.  For example, in an RCT examining the Mediterranean diet and cardiovascular risk, the control group might follow a standard low fat diet while the intervention group adopts a Mediterranean pattern ³.  After a defined study period, researchers compare outcomes such as heart attacks or strokes between groups. Because randomisation minimises confounding factors, differences in outcomes can be attributed to the intervention itself.  This is why RCTs provide the strongest evidence for causation rather than correlation. When conducted as double blind trials, neither participants nor researchers know who receives the treatment, further reducing bias and mitigating placebo effects.

Despite their strengths, RCTs come with practical and ethical constraints.  They are expensive, often involve small sample sizes, and may struggle with long term adherence, especially when testing complex dietary patterns.  Ethical considerations limit the ability to test harmful exposures or withhold beneficial treatments.

Systematic Reviews and Meta Analyses

Systematic reviews and meta analyses sit at the top of the evidence hierarchy because they provide a comprehensive overview of existing evidence and can reveal whether findings are consistent across different populations and settings. However, these methods are only as strong as the quality and consistency of the studies they include, and ensuring relevant studies are not missed or intentionally excluded.

However, these methods are only as robust as the quality and consistency of the studies they include, and they rely on thorough, unbiased inclusion of all relevant evidence.

A systematic review uses a structured, transparent process to identify, evaluate, and summarise all relevant research on a specific question. When the included studies are sufficiently similar in design, population, and outcomes, researchers may conduct a meta analysis, which statistically pools results to generate a single, weighted estimate of effect. Larger, well designed studies contribute more heavily to this estimate than smaller or lower quality studies.

Systematic reviews and meta analyses help determine whether scientific findings are consistent, generalisable, and reliable, and they often guide policy decisions, clinical recommendations, and future research priorities.

In Summary

Science is a continuous process.  It can move slowly and often involves uncertainty, yet it remains the most reliable way to build understanding about the world and human health.  Many types of studies contribute to this evidence base, each with its own strengths and limitations, and no single study provides a definitive answer.  Progress happens because researchers continually evaluate and refine one another’s work, identifying opportunities to improve methods and explore new questions.

The therapeutic approach to obesity and type 2 diabetes mellitus (T2DM) is evolving in a similar way to how clinicians use antibiotics: targeting several pathways that often produce stronger and more durable effects than acting on a single pathway.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) laid the foundation, but the complexity of fat mass regulation quickly revealed the limits of one hormonal signal ¹.  This has led to multi-hormonal agents that act simultaneously on glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, amylin, and/or peptide YY (PYY), better replicating the physiological and coordinated post-prandial response.

By engaging these pathways, the new therapies achieve broader and more synergistic metabolic improvements, marking a shift from single target drugs to integrated hormone-based treatment ¹.

GLP-1–Based Therapies

GLP-1 is secreted by intestinal endocrine cells after nutrient ingestion.  It enhances glucose-dependent insulin secretion, slows gastric emptying, reduces appetite, and promotes weight loss ^1–5.  Central nervous system GLP-1 signalling within the hypothalamus and brainstem is central to regulating fat mass ⁶.

Beyond glycaemia, GLP-1 exerts anti-inflammatory, endothelial, and lipid-modulating effects ¹.  Long-acting GLP-1RAs on their own such as semaglutide achieve substantial weight loss and glycaemic improvement, aided by gradual dose escalation strategies that improve tolerability ¹.

Oral semaglutide represents a significant advancement, using SNAC (sodium N-(8-[2-hydroxybenzoyl] amino) caprylate) to overcome gastrointestinal degradation and enable systemic absorption, despite low bioavailability (~1%) and strict fasting administration requirements ⁷.

Further innovations include small-molecule oral GLP-1RAs, such as orforglipron, which activate the GLP-1 receptor (GLP-1R) without peptide structures and offer simpler administration but without the same weight loss range ^1,8-9.

GIP-Related Therapies

GIP is also released by different endocrine cells in the small intestine.  It stimulates insulin secretion during normoglycemia and influences lipid storage, though its metabolic effects are highly context-dependent ¹.

Importantly, both GIP receptor (GIPR) agonism and GIPR antagonism have been shown to reduce body weight; an unexpected therapeutic paradox ¹.  Central GIPR signalling suppresses appetite in rodents, while peripheral GIP actions vary with insulin sensitivity ^1,10.  In humans, exogenous GIP shows limited appetite loss (anorectic) effects, suggesting species-specific physiological differences ¹¹.

GLP-1/GIP Dual Agonists

Dual agonism of the GLP-1R and GIPR aims to capitalise on complementary hormonal effects.  Tirzepatide is the first approved dual GLP-1/GIP agonist and achieves greater weight loss and glycaemic improvement than semaglutide alone, suggesting synergistic incretin modulation ¹².  Additional co-agonists, including SCO-094, VK2735, CT-388, and DR10627, are under development to refine receptor balance and broaden metabolic benefits ¹.

Unimolecular GLP-1RAs/GIPR Antagonists

In contrast to co-agonists, unimolecular agents combining GLP-1R activation with GIPR blockade exploit evidence that GIPR antagonism enhances weight loss by disrupting adipogenic GIP signalling and amplifying GLP-1 driven satiety pathways ¹.

Maridebart cafraglutide (formerly AMG-133) exemplifies this approach by merging GLP-1 agonism with a monoclonal GIPR-blocking antibody.  Monthly dosing produces meaningful body weight reductions (12–16%) and improves glycaemia in people with obesity and T2DM ^1,13.  Pre-clinical work with the GIPR antagonist AT-7687 shows similar synergy when paired with GLP-1RAs ¹.

Oxyntomodulin Physiology and Oxyntomodulin-Based Therapies

Oxyntomodulin (OXM) is also secreted by the endocrine cells in the intestine but does not have a dedicated receptor.  Instead OXM binds to both the glucagon and GLP-1R ¹⁴.  Glucagon as a standalone peptide is secreted by pancreatic alpha-cells.  It increases hepatic glycogenolysis and gluconeogenesis during fasting but also regulates satiety, enhances hepatic β-oxidation, reduces liver fat, and increases energy expenditure ^1,15.

OXM mimics many of these same effects when it binds the glucagon receptors ¹⁴.  These metabolic properties support OXM use within multi-agonist therapies, without the risk of pure glucagon’s inherent hyperglycaemic potential.

OXM analogues (GLP-1/Glucagon Co-agonists)

Co-activation of GLP-1R and glucagon receptors leverages the anorectic and insulinotropic actions of GLP-1 with glucagon-driven increases in energy expenditure.  Survodutide and mazdutide are leading examples.  Survodutide has demonstrated up to 13–15% weight loss, alongside significant improvement in metabolic dysfunction–associated steatohepatitis (MASH) ^1,16-17.  Mazdutide produces dose-dependent weight reduction and glycaemic improvement with good tolerability ¹⁸.

Triple GIP/GLP-1/Glucagon Co-agonists

Retatrutide is a triple agonist that simultaneously activates GLP-1Rs, GIPRs, and glucagon receptors.  This design aims to maximise appetite suppression and thermogenesis.  In phase 2 trials, retatrutide achieved approximately 17–18% weight loss in individuals with obesity without T2DM, surpassing most available pharmacotherapies ^1,19.

Amylin Physiology and Amylin-Based Therapies 

Amylin is co-secreted with insulin and slows gastric emptying, suppresses glucagon, and increases satiety through pathways distinct from other anorectic hormones ^1,20.  Long-acting analogues such as cagrilintide produce clinically significant weight loss ²¹.

Amylin/GLP-1 Dual Agents

CagriSema, a fixed combination of semaglutide and cagrilintide that integrates GLP-1–mediated appetite suppression with amylin driven satiety and gastric emptying effects.  Recent trials show approximately 23% weight loss, exceeding either monotherapy or approaching metabolic surgery efficacy ^1,21.

Peptide YY Physiology and Related Medicines

Peptide YY (PYY) is co-secreted with GLP-1 by endocrine cells in the intestine and converted to its active form PYY 3-36, which acts via Y2 receptors to inhibit neuropeptide Y (NPY) neurons and promote satiety ^1,22.   After bariatric surgery, postprandial PYY, GLP-1, and OXM rises sharply and contributes to improved adipocyte mass regulation.  Early PYY analogues show reduced food intake and modest weight loss in short-term studies ^1,22.

Table 1.  Comparison Table of Novel GLP-1–Based Medications

Conclusion

Together, these advances mark a decisive shift in obesity and T2DM therapeutics from a single pathway modulation toward integrated, multimodal hormone-based interventions.

GLP-1 remains the backbone, but layering complementary signals from GIP, glucagon, amylin, and PYY allows for unprecedented degrees of weight reduction and metabolic restoration, as summarised for comparison in Table 1.

As uni-, dual-, and triple-molecular agents continue to refine receptor balance, the field is rapidly approaching the efficacy once achievable only through metabolic surgery.

The emerging challenge is no longer whether we can produce profound metabolic benefits, but rather how to optimise durability, individualise receptor targeting, and translate these complex pharmacologic innovations into long term clinical decision making.

This therapeutic evolution represents not merely incremental drug development, but a redefinition of how we conceptualise and treat the chronic diseases of obesity and type 2 diabetes.

This year’s event brought together over 1,000 secondary school students from across Ireland, presenting 550 projects spanning artificial intelligence, climate science, mental health research, and sustainable technology.  A panel of 85 judges, including leading academics and industry experts, evaluated projects for their scientific rigour, creativity, and real-world impact.

Among the standout projects was the entry from overall winner, Aoibheann Daly, a fourth-year student at Mercy Secondary School Mounthawk in Kerry.  Aoibheann’s project, GlioScope: Multitask Deep Learning and Causal AI for Glioma & Glioblastoma Profiling, aims to transform brain cancer treatment.  By using standard MRI scans to predict genetic mutations in tumours, her innovation offers a safer, faster alternative to invasive biopsies — potentially improving outcomes for patients worldwide.  Aoibheann will represent Ireland at the European Union Contest for Young Scientists in Germany later this year.

Kerry Sustainable Nutrition Award: A First for YSTE

As a proud silver sponsor of this year’s Stripe YSTE, Kerry introduced the Kerry Sustainable Nutrition Award — the first award of its kind at this long‑standing event.  This award recognises projects that demonstrate scientific innovation in solutions that help maintain good health while ensuring future generations can meet their nutritional needs — without compromising the health of the planet.

The award was presented by Catherine Keogh, Chief Corporate Affairs Officer at Kerry, to Rachel Coughlan, Moate Community School Westmeath, for her innovative project developing a biodegradable chewing gum made sustainably from Irish-grown resources.

Presenting the award, Catherine Keogh remarked: “Rachel truly exemplifies Kerry’s values and our vision for sustainable nutrition.  This award recognises young scientists who are developing innovative, science-led solutions that are better for people, better for society, and better for the planet — reducing environmental impact, improving health outcomes, and ensuring responsible sourcing and production.  The quality, creativity, and ambition on display at this year’s Stripe Young Scientist & Technology Exhibition has been exceptional, reinforcing our belief that Ireland’s future as a global hub for scientific innovation is bright.”

The award was open across multiple scientific categories and age groups, with projects assessed on innovation, scientific rigour, sustainability impact, clarity of communication, and real-world feasibility.  Kerry’s sponsorship and this award align with the company’s Beyond the Horizon sustainability strategy and its vision to reach more than two billion people with sustainable nutrition solutions by 2030.